SAM's Drugs Guide

Self-Assessment Medication’s Guide
Table of content:
Name of the Chapter Page
1. Chapter One: Respiratory system P. 1
2. Chapter Two: Gastro-Intestinal system P. 28
3. Chapter Three: Cardiovascular system P. 60
4. Chapter Four: Central Nervous system P. 111
5. Chapter Five: Infections & Antimicrobials P. 143
6. Chapter Six: Endocrine system and Hormones P. 187
7. Chapter Seven: Obstetrics & Gynecology P. 234
8. Chapter Eight: Genito-Urinary system P. 257
9. Chapter Nine: Pain, Painkillers and Musculoskeletal system P. 276
10. Chapter Ten: Rheumatology & Neurology P. 302
11. Chapter Eleven: Corticosteroids P. 315
12. Chapter Twelve: Ophthalmology (The Eye) P. 322
13. Chapter Thirteen: The Ear, Nose, and Throat (ENT) P. 337
14. Chapter Fourteen: Dermatology P. 348
15. Chapter Fifteen: Blood products and Hematology P. 382
16. Chapter Sixteen: Immunologics & Oncology P. 392
17. Chapter Seventeen: Toxicology P. 417
18. Chapter Eighteen: Miscellaneous Topics: P. 430
First: Smoking Cessation
Second: Anesthetics and related drugs
Third: Appetite Stimulants
Fourth: Obesity and weight reducing agents
Fifth: Vitamins, Mineral and Medical Supplements
Sixth: Medical Dried Milk
19. Index (drug categorization by alphabet)
2015 ‫) لسنة‬2483( ‫رقم اإليداع في دار الكتب والوثائق ببغداد‬

Deposit No. in the House of books and documents in Baghdad (2483)
for the year 2015
RESPIRATORY SYSTEM
Chapter 1: Respiratory System
Part One: Introduction
Part Two:
1.6- Drugs for Cystic Fibrosis
1.1- Bronchodilators and Anti- ➢ Combination Products
Asthmatic Drugs: ➢ Aerosolized Antibiotics
1.1-1. Selective Beta2 agonists
1.1-2. Inhaled corticosteroids
➢ Combination Products
1.1-3. Anti-Muscarinic bronchodilators

➢ Triple Products
1.1-4. Theophylline and Xanthine’s

derivatives
1.1-5. Leukotriene Receptor
Antagonists
1.1-6. Cromoglicate & Nedocromil

1.1-7. Other Asthma Therapies
1.2- Antihistamines
1.2-1. First Generation
1.2-2. Second & Third Generation
1.2-3. Topical Antihistamines
1.2-4. Other Antihistamines
1.3- Cough preparations, Common

Cold and Flu
1.3-1. Topical Sympathomimetics
1.3-2. Common cold & Flu Preparations
1.3-3. Expectorants and Antitussive
1.3-4. Cough medication (Suppositories)
1.3-5. Herbal Mixtures for Cough
1.4- Respiratory Stimulants
1.5- Pulmonary Surfactant

Sam’s Guide: Chapter 1 – Respiratory system
Chapter one: Respiratory System
Part One:
1. Introduction:
➢ The respiratory system consists of the lungs and the air passages, such as the trachea
(windpipe) and bronchi, by which air reaches them; Through the process of inhaling and
exhaling air (breathing) the body obtains the oxygen necessary for survival, and to expel
carbon dioxide, which is the waste product of the basic human biological process.
➢ Air enters the trachea, which branches into two main bronchi, one for each lung. Within the
lungs, the air passes into bronchioles, smaller tubes whose muscular walls may contract or
dilate in response to drugs and nerve signals; The bronchioles open out into tiny, blood-vessel
lined air sacs (alveoli), which allow oxygen to pass into the bloodstream and carbon dioxide
to pass from the bloodstream for expiration.
2. How do we breathe?
➢ Breathing occurs when the contraction or relaxation of muscles around the lungs changes the
total volume of air within the air passages (bronchi, bronchioles) inside the lungs, when the
volume of the lungs changes, the pressure of the air in the lungs changes in accordance with
Boyle's Law, if the pressure is greater in the lungs than outside the lungs, then air rushes out.
If the opposite occurs, then air rushes in; Here is a summary of the process:
o Inspiration occurs when the inspiratory muscles (the diaphragm and the external
intercostal muscles) contract; contraction of the diaphragm (the skeletal muscle below
the lungs) causes an increase in the size of the thoracic cavity, while contraction of the
external intercostal muscles elevates the ribs and sternum; Thus, both muscles cause the
lungs to expand, increasing the volume of their internal air passages, and in response, the
air pressure inside the lungs decreases below that of air outside the body; because gases
move from regions of high pressure to low pressure, air rushes into the lungs.
o Expiration occurs when the diaphragm and external intercostal muscles relax, in
response, the elastic fibers in lung tissue cause the lungs to recoil to their original volume,
the pressure of the air inside the lungs then increases above the air pressure outside the
body, and air rushes out; During high rates of ventilation, expiration is facilitated by
contraction of the expiratory muscles (intercostal muscles and abdominal muscles).
➢ Lung compliance is a measure of the ability of the lungs and thoracic cavity to expand, due to
the elasticity of lung tissue and the low surface tension of the moisture in the lungs (from the
surfactant), the lungs normally have high compliance.
➢ Boyle's Law describes the relationship between the pressure (P) and the volume (V) of a gas.
The law states that if the volume increases, then the pressure must decrease (or vice versa).
This relationship is often written algebraically as PV = constant, or P1V1 = P2V2, both
equations state that the product of the pressure and volume remains the same; (Boyle's Law
applies only when the temperature does not change).
3. Control of Respiration
➢ Respiration is controlled by these areas of the brain that stimulate the contraction of the
diaphragm and the intercostal muscles. These areas, collectively called respiratory centers,
are summarized here:
1. The medullary inspiratory center, located in the medulla oblongata, generates
rhythmic nerve impulses that stimulate contraction of the inspiratory muscles
(diaphragm and external intercostal muscles). Normally, expiration occurs when these
muscles relax, but when breathing is rapid, the inspiratory center facilitates expiration by
stimulating the expiratory muscles (internal intercostal muscles and abdominal muscles).
2. The pheumotaxic area, located in the pons, inhibits the inspiratory center, limiting the
contraction of the inspiratory muscles, and preventing the lungs from overinflating.
3. The apneustic area, also located in the pons, stimulates the inspiratory center,
prolonging the contraction of inspiratory muscles.
Self-Assessment Medications Guide 3.1 ed. Page | 1
➢ The respiratory centers are influenced by stimuli received from the following three groups of
sensory neurons:
1. Central chemoreceptors (nerves of the central nervous system), located in the medulla
oblongata, monitor the chemistry of cerebrospinal fluid. When CO2 from the plasma
enters the cerebrospinal fluid, it forms HCO3– and H+, and the pH of the fluid drops
(becomes more acidic). In response to the decrease in pH, the central chemoreceptors
stimulate the respiratory center to increase the inspiratory rate.
2. Peripheral chemoreceptors (nerves of the peripheral nervous system), located in aortic
bodies in the wall of the aortic arch and in carotid bodies in the walls of the carotid
arteries, monitor the chemistry of the blood. An increase in pH or pCO2, or a decrease in
pO2, causes these receptors to stimulate the respiratory center.
3. Stretch receptors in the walls of bronchi and bronchioles are activated when the lungs
expand to their physical limit. These receptors signal the respiratory center to discontinue
stimulation of the inspiratory muscles, allowing expiration to begin. This response is
called the inflation (Hering‐Breur) reflex.
4. What Can go wrong in the Respiratory tract?

➢ Difficulty in breathing may be due to narrowing of the air passages, from spasm, as in
asthma and bronchitis, or from swelling of the linings of the air passages, as in bronchiolitis
and bronchitis; Breathing difficulties may also be due to an infection of the lung tissue, as in
pneumonia and bronchitis, or to damage to the small air sacs (alveoli) from emphysema or
from inhaled dusts or molds, which cause pneumoconiosis and farmer’s lung.
➢ Smoking and air pollution can affect the respiratory system in many ways, leading to
diseases such as lung cancer and bronchitis.
➢ Sometimes difficulty in breathing may be due to congestion of the lungs from heart
disease, to an inhaled object such as a peanut, or to infection or inflammation of the throat.
➢ Symptoms of breathing difficulties often include a cough and a tight feeling in the chest.
➢ The usual cause of a blocked nose is swelling of the delicate mucous membrane that lines
the nasal passages and excessive production of mucus as a result of inflammation. This may
be caused by an infection (for example, a common cold) or it may be caused by an allergy (for
example, to pollen – a condition known as allergic rhinitis or hay fever). Congestion can also
occur in the sinuses (the air spaces in the skull), resulting in sinusitis.
➢ Coughing is a natural response to irritation of the lungs and air passages, designed to expel
harmful substances from the respiratory tract. Common causes of coughing include infection
of the respiratory tract (for example, bronchitis or pneumonia), inflammation of the airways
caused by asthma, or exposure to certain irritant substances such as smoke or chemical
fumes. Depending on their cause, coughs may be productive – that is, phlegm producing
– or they may be dry. In most cases, coughing is a helpful reaction that assists the body in
ridding itself of excess phlegm and substances that irritate the respiratory system;
suppressing the cough may actually delay recovery. However, repeated bouts of coughing can
be distressing, and may increase irritation of the air passages. In such cases, medication to
ease the cough may be recommended. There are two main groups of cough remedies,
according to whether the cough is productive or dry.
➢ Asthma is a chronic lung disease that is characterized by episodes in which the bronchioles
constrict due to oversensitivity. The attacks are usually, but not always, reversible; asthma is
also known as reversible airways obstruction. About 5 per cent of adults and 10 per cent of
children have the disease. Sometimes the inflammation causing the constriction is due to an
identifiable allergen in the atmosphere, such as house dust mites, but often there is no obvious
trigger. Breathlessness is the main symptom, and wheezing, coughing, and chest tightness are
common. Asthma sufferers often have attacks during the night and wake up with breathing
difficulty. The illness varies in severity, at its most severe, it can even be life threatening.
➢ Chronic Obstructive Pulmonary Disease (COPD) is an umbrella term used to describe
progressive lung diseases including emphysema, chronic bronchitis, and refractory (non-
reversible) asthma. This disease is characterized by increasing breathlessness.
o Damage to the alveoli (air sacs) causes Emphysema. The walls inside the alveoli
disappear, making many small sacs become larger, single sacs. These larger sacs do not
absorb oxygen as well. So, less oxygen is absorbed into the blood; Also, when the alveoli
are damaged, the lungs become stretched out and lose their springiness. The airways
become flabby, and air is trapped in the lungs. It becomes hard to breathe out. This creates
a feeling of shortness of breath.
o Damage to the bronchial tubes causes Chronic Bronchitis. Bronchitis occurs when the
bronchial tubes are irritated and swollen. This causes coughing and shortness of breath.
If mucus comes up with the cough and the cough lasts at least three months for two years
in a row, the bronchitis has become chronic bronchitis; There are hair-like fibers lining
the bronchial tubes of the lungs. These tiny hairs are called cilia. The cilia help move mucus
up the tubes so it can be coughed out. In chronic bronchitis, the tubes have lost their cilia.
This makes it hard to cough up mucus, which causes more coughing. More coughing makes
the tubes more irritated. This creates more mucus. The tubes then become swollen,
making it hard to breathe. Smoking even just a little keeps the cilia from working normally.
Mucus can build up in the lungs. This can cause more damage.
o Refractory (non-reversible) asthma is a type of asthma that does not respond to usual
asthma medications. In an asthma attack, bronchial airways tighten up and swell.
Medications can usually reverse this, opening up the airways and returning them to how
they were before the asthma attack. In refractory asthma, medications cannot reverse the
tightening and swelling of the airways.
5. Spirometry
➢ Spirometry is a common clinical test used to assess how well the lungs work by measuring
how much air they inhale; how much they exhale and how quickly they exhale.
➢ Spirometry is used to diagnose asthma, chronic obstructive pulmonary disease (COPD) and
other conditions that affect breathing; Spirometry may also be used periodically to monitor
the lung condition and check whether a treatment for a chronic lung condition is helping the
patient to breathe better.
➢ Key spirometry measurements include the following:
o Forced vital capacity (FVC): This is the largest amount of air that the patient can
forcefully exhale after breathing in as deeply as he can, a lower than normal FVC reading
(less than 80%) indicates restricted breathing.
o Forced expiratory volume (FEV1): This is how much air the patient can force from his
lungs in one second, this reading helps the doctor to assess the severity of the breathing
problems; lower FEV-1 (less than 80% in 6 seconds) readings indicate significant
breathing obstruction.
o FEV1/FVC ratio: represents the percentage of the lung capacity to exhale in one second.
 Usually used to differentiate between obstructive and restrictive diseases.
 Decreased in obstructive diseases (Asthma, COPD), less than 75%.
 Normal or high in restrictive diseases (Pulmonary Fibrosis).
6. Asthma Vs COPD
Sign Asthma COPD
Cough Usually non-productive; worsen at Usually Productive, and occurs
night and early morning throughout the day
FEV1 Reversible Irreversible
Lung Damage Reversible Irreversible
7. Medications Range and Types:
1. Air entering the lungs passes through narrow tubes called bronchioles, in asthma and
bronchitis the bronchioles become narrower, either as a result of contraction of the muscles
in their walls, or as a result of mucus congestion.
2. This narrowing of the bronchioles obstructs the flow of air into and out of the lungs and
causes breathlessness; Bronchodilators are prescribed to widen the bronchioles and
improve breathing.
3. Drugs with a variety of actions are used to clear the air passages, soothe inflammation, and
reduce the production of mucus:
➢ Decongestants; oral or topical (Phenylephrine, Pseudoephedrine, Xylometazoline)
reduce swelling inside the nose, thereby making it possible to breathe more freely.
➢ If the cause of the congestion is an allergic response, an antihistamine is often
recommended to relieve symptoms or prevent attacks.
➢ Bacterial infections of the respiratory tract are usually treated with antibiotics,
although most respiratory tract infections are viral.
➢ Bronchodilators (Salbutamol, Salmeterol, Terbutaline) are drugs that widen the
bronchi. They are used to prevent and relieve asthma attacks.
➢ Leukotriene antagonists (Montelukast, Zafirlukast) reduce the inflammation and
bronchoconstriction of asthma.
➢ Corticosteroids (Beclomethasone, Budesonide) reduce inflammation in the swollen
inner layers of the airways. They are used to prevent asthma attacks.
➢ Other drugs, such as Sodium Cromoglicate, may be used for treating allergies and
preventing asthma attacks but are not effective once an asthma attack has begun.
➢ Biological therapies (Monoclonal antibodies), used to manage severe asthma
➢ A variety of drugs are used to relieve a cough, depending on the type of cough involved.
Some drugs make it easier to eliminate phlegm (Expectorants or Mucolytics); others
suppress the cough (cough suppressants) by inhibiting the cough reflex.
8. Drug Delivery available for Respiratory tract

A. Inhalation devices:
➢ This route delivers the drug directly to the airways; the dose required is smaller than when given
by mouth and side effects are reduced.
➢ Inhaler devices include pressurized metered-dose inhalers (MDI), breath actuated inhalers
(BAI), and dry powder inhalers (DPI). Many patients can be taught to use a pressurized MDI
effectively but some patients, particularly the elderly and children, find them difficult to use.
Spacer devices can help such patients because they remove the need to co-ordinate actuation with
inhalation, DPI may be useful in adults and children over 5 years who are unwilling or unable to
use a pressurized MDI, breath-actuated inhalers are suitable for adults and older children.
➢ On changing from a pressurized MDI to a DPI dry powder inhaler, patients may notice a lack of
sensation in the mouth and throat previously associated with each actuation, Coughing may also
occur during the change.
➢ Spacer devices remove the need for coordination between actuation of a pressurized MDI and
inhalation. Spacer devices are particularly useful for patients with poor inhalation technique, for
children, for patients requiring high doses of inhaled corticosteroids, for nocturnal asthma, and
for patients prone to candidiasis with inhaled corticosteroids.
B. Nebulizers:
➢ A nebulizer converts a solution of a drug into an aerosol for inhalation. Solutions for nebulization
are available for use in severe acute asthma or COPD
➢ They are administered over 5–10 minutes from a nebulizer usually driven by oxygen in hospital,
Nebulization may be carried out using an undiluted nebulizer solution or it may require dilution
beforehand, the usual diluent is sterile sodium chloride 0.9%.

C. Oral Route
➢ The oral route is used when administration by inhalation is not possible. Systemic side-effects
occur more frequently when a drug is given orally rather than by inhalation.
D. Parenteral Route
➢ Drugs such as β2 agonists, corticosteroids, and aminophylline can be given by injection in acute
severe asthma when administration by nebulization is inadequate or inappropriate.
9. Drugs Available
Drugs used for asthma and/or COPD
Drug classification Examples Route
Bronchodilators β2-agonists Salbutamol, Terbutaline, Systemic,
Formoterol, Salmeterol Inhaled
Antimuscarinic Ipratropium, Tiotropium Inhaled
Xanthines Theophylline, aminophylline Systemic
Corticosteroids Inhaled Beclometasone, Budesonide, ---
Fluticasone
Systemic Prednisolone, Hydrocortisone ---
Leukotriene Receptor Antagonists Montelukast, Zafirlukast Oral
(Leukotriene Modifiers)
Mast Cell Stabilizers Cromolyn sodium Inhaled
Immunosuppresants Omalizumab, S.C inj.
(monoclonal antibodies) Mepolizumab
Reslizumab I.V infusion
Phosphodiesterase type-4 inhibitor Roflumilast Oral
Combination Products
Bronchodilators + Corticosteroids Formoterol + Budesonide Inhaled
Leukotriene Modifiers + Montelukast + Desloratidine Oral
Antihistamines
Drugs used for Cough

Drug classification Examples Route
Decongestants Used topically Oxymetazoline, Xylometazoline Nasal Drops,
Spray
Used orally Phenylephrine, Ephedrine, Oral
Pseudoephedrine
Expectorants Ammonium chloride, Guaifenesin Oral
Mucolytics Carbocysteine, Bromhexine, Oral , Inj.
Ambroxol
Cough Opioid Codeine, Dextromethorphan, Oral
Suppressants Methadone, Pholcodine
Non-Opioid Anti-Histamines Oral , Inj.

Part 2:
1.1-Bronchodilators and Anti-Asthmatic Drugs
1. Administration of drugs by the inhaled route delivers the drug directly to the Airways with
fewer systemic side effects than either the parenteral or oral routes.
2. Commonly inhalation dosage forms available are inhaler, nebulizer, Diskus and turbohaler
(the use of turbohaler is much easier than inhaler).
Teach the Patient

Using a metered dose inhaler (MDI)
1. Remove the cap covering the mouth piece and check that there is no fluff
or dirt in the mouthpiece, then Shake the inhaler.
2. If the inhaler is new or has not been used for some time it will need to be
tested. To test: Hold the inhaler away from body. Press the top of the
aerosol canister once, a fine mist should be puffed into the air. The inhaler
is now ready to use.
3. Tilt head back slightly and Breathe out gently.
4. Place the mouthpiece in the mouth between the teeth (do not bite). Close
lips around the mouthpiece.
5. Start to breathe in slowly through the mouth, at the same time press down on the inhaler to
release the medicine in to the lungs.
6. Hold breath for between 5 and 10 seconds, and then breathe out slowly.
7. If a second dose is required, wait approximately 30 seconds and repeat the process.
8. Replace the cap and if the inhaler is a corticosteroid inhaler, rinse the mouth out with water.
Using a Turbohaler
A Turbohaler is a dry powder inhaler. To load it prior to use:
1. Unscrew the cover and remove it.
2. Hold the Turbohaler upright with one hand and with the other twist
the grip in one direction as far as it will go.
3. Now twist back as far as it will go – a click should be heard, showing
the inhaler is primed and ready for use.
4. Breathe out gently by Placing the mouthpiece between the lips and
breathe in through the mouth as deeply and as hard as possible.
5. Remove the inhaler from the mouth and breathe out slowly.
6. Replace the cover or Repeat the above steps if more than one puff is required.
Using a DISKUS
1. Open your DISKUS and Hold it in the palm of your hand, put the
thumb of your other hand on the thumb grip and push the thumb grip
until it "clicks" into place
2. Slide the lever away from you as far as it will go to get your
medication ready
3. Breathe out away from the device by placing the mouthpiece gently
in your mouth and close your lips around it
5, Breathe in deeply until you have taken a full breath
6. Remove the DISKUS from your mouth
7. Hold your breath for about ten seconds, then breathe out
Always check the number in the dose counter window to see how many
doses are left.

Using a metered dose inhaler

with the aid of a spacer device
1. First assemble the spacer device if necessary as
directed by the manufacturer (with or without a
face mask).
2. Remove the cap from the inhaler and insert the
mouthpiece of the inhaler into the opening at the
end of the spacer.
3. Hold the spacer and inhaler together and
shake.
4. Breathe out.
5. Put the spacer mouthpiece in the mouth and
seal with the lips.
6. Press the inhaler once and then breathe in and
out four or five times.
7. Further doses may be taken waiting a few
seconds between puffs.
8. Separate the spacer and inhaler. Replace the
inhaler cap and store until next dose.
Using an Accuhaler
1. With the Accuhaler mouthpiece facing you, slide the lever
away until it clicks. This will have loaded a dose ready for
inhalation and the Accuhaler will move the dose counter on.
2. Hold the Accuhaler flat and breathe out
away from the inhaler.
3. Seal lips around the Accuhaler mouthpiece and inhale deeply.
4. Remove inhaler from the mouth and hold
breath as long as is comfortable.
5. Slide the thumb grip back towards you to
close the inhaler.
6. For further doses repeat above steps.
Using a Breath actuated inhaler

1. Shake the inhaler.
2. Hold the inhaler upright and open the cap.
3. Breathe out, away from the inhaler.
4. Put the mouthpiece in the mouth, seal lips
around the mouthpiece.
5. Breathe in steadily through the mouthpiece.
6. Hold breath for about ten seconds.
7. Keeping the inhaler upright, close the cap.
8. For further doses repeat the above steps.

1.1.1-Selective Beta2 agonists
1. Beta2-Adrenergic agonists are a class of drugs that act on the beta2-adrenergic receptor,
thereby causing smooth muscle relaxation, resulting in dilation of bronchial passages,
vasodilation in muscle and liver, relaxation of uterine muscle, and release of insulin.
• They are primarily used to treat asthma and chronic pulmonary obstructive disease.
• usually improve breathing within a few minutes of administration.
• Divided into: Short acting, Long acting and Ultra-Long acting
2. Short-acting beta2 agonists (SABAs), (such as Salbutamol or Terbutaline) are considered the
first choice for the treatment of acute asthmatic attack (and other conditions associated with
airways obstruction), Because of their rapid onset of action – within 15 minutes.
• Inhaled SABAs are given ‘as required’ and NOT as Regular treatment.
• Salbutamol may be used by some gynecologist as a uterine relaxant for pregnant
women. (Also is used in the treatment of hyperkalemia).
3. Long-acting beta2 agonists (LABAs), (such as Formoterol and Salmeterol), they are taken
regularly as prophylaxis (usually twice per day) for chronic asthma or chronic obstructive
pulmonary disease (COPD).
• Formoterol is full agonist whereas Salmeterol is partial agonist; therefore, if poor
response to one, try the other, Formoterol has more rapid onset (5 minutes) of action
than Salmeterol (20 minutes)
4. Ultra-Long-acting beta2 agonists (U-LABAs), are a new generation approved on 2011, which
is used once daily. Unfortunately, they are licensed only for the treatment of chronic obstructive
pulmonary disease (COPD), (Not FDA approved for asthma yet)
5. Adverse Effects include tremor, tachycardia, ↑ Risk of hypokalemia & hyperglycemia.
6. They are not recommended during the first 18 months of life because β2 receptors are not
well developed during that age
Scientific name Dosage form Trade name concentration
Short-acting beta2 agonists (SABAs)
Salbutamol * Inhaler Ventolin® , Vental® 100 mcg ( 0.1 mg/puff )
Tab , Syr. Butadin ® 2mg , 2 mg/5 ml
Nebulizing Solu. Aloprol® , Ventolin® 5 mg/1 ml
Inj. 0.5 mg
Levo-Salbutamol * Inhaler Respira ® 50 mcg
Nebulizing Solu. Xopenex ® 1.25 mg/3 ml
Terbutaline Inhaler Bricanyl , Brethaire
® ® 0.2 mg/puff
Tab Brethine ® 2.5 mg , 5 mg
Fenoterol Inhaler Berotec N ® 100 mcg
Pirbuterol Inhaler Maxair Autohaler® 0.2 mg/puff
Long-acting beta2 agonists (LABAs)
Formoterol ** Inhaler Oxis® , Aerolizer® 20 mcg/2 ml
Inhale Powder (cap) Foradil® 12 mcg , 20 mcg
Salmeterol Inhaler Serevent® 25 mcg/puff
Inhale Powder (cap) Serevent Diskus® 50 mcg/inhale
Arformoterol Nebulizing Solu. Brovana ®, Erdotin® 15 mcg/2 ml
Bambuterol Tab Bambec® , Oxeol® 10 mg , 20 mg
Ultra-Long-acting beta2 agonists (U-LABAs)
Indacaterol Cap (inhale Powder) Arcapta Neohaler®, Onbrez® 150 mcg , 300 mcg/cap
Olodaterol Inhaler Striverdi® 2.5 mcg
* Salbutamol is Called Albuterol in USA and Canada (they are the same Drug).
** Levo-Salbutamol is also called Levalbuterol, also Formoterol = Eformoterol.
1.1.2 - Inhaled corticosteroids
1. Corticosteroids are used for the management of reversible and irreversible airways disease. An
inhaled corticosteroid used for 3–4 weeks may help to distinguish asthma from chronic
obstructive pulmonary disease; clear improvement over 3–4 weeks suggests asthma.
• Corticosteroids are used for their anti-inflammatory properties, by suppressing airway
inflammation, they reduce swelling (edema) inside the bronchioles, complementing
relaxation of the walls by the bronchodilators in opening up the tubes.
• Reducing the inflammation also has the effect of reducing the amount of mucus
produced, and this again helps to clear the airways.
2. An inhaled corticosteroid is used regularly for prophylaxis of asthma, but they are ineffective
for acute asthmatic attack.
• For Acute Asthmatic attack (Hydrocortisone Injection) is preferred.
3. Inhaled corticosteroid may cause oral candidiasis (oral fungal infection), hoarseness; and
these side effect can be reduced by rinsing the mouth with water after inhalation of a dose. (4).
4. High doses of inhaled corticosteroids used for prolonged periods can induce adrenal
suppression; Inhaled corticosteroids have been associated with adrenal crisis and coma in
children; excessive doses should be avoided.
• Note that oral and systemic corticosteroids are also used in the treatment of asthma and
COPD, for more information about corticosteroids see chapter 11.
Beclomethasone Inhaler Qvar®, Beclosone®, Becotid® 50 mcg , 100 , 200 , 250 mcg
Budesonide Inhaler , Nebul. Pulmicort® 200 mcg
Inhale Cap Miflonide ® 200 mcg
Fluticasone Aerosol Flixotide® , Flovent® 110 mcg , 100 mcg (Diskus)
Ciclesonide * Inhaler Alvesco® 80 mcg
Flunisolide Aerosol Aerospan® 80 mcg
Mometasone Inhaler Asmanex , Twist-haler
® ® 110 mcg , 220 mcg
Triamcinolone Inhaler Azmacort ® 55 mcg , 100 mcg
Combinations of inhaled corticosteroid and long acting Beta2 agonist
Symbicort®, Inhaler Budesonide + Formoterol (80 mcg + 4.5 mcg),
Foracort ® (Turbohaler) (160 mcg + 4.5 mcg),
Pulmoton® (200 mcg + 6 mcg),
(400 mcg + 12 mcg),
Fostair ® Inhaler Beclomethasone + Formoterol 100 mcg + 6 mcg
Clenil Comp® Inhaler Beclomethasone + Salbutamol 200 mcg + 50 mcg
Dulera® , Zenhale® Inhaler Mometasone + Formoterol (100 mcg + 5 mcg),
(200 mcg + 5 mcg)
Flutiform® Inhaler Fluticasone + Formoterol (125 mcg + 5 mcg),
(250 mcg + 10 mcg)
Seretide Diskus®, Inhalation Fluticasone + Salmeterol (100 mcg + 50 mcg),
Brequal® powder (250 mcg + 50 mcg),
Advair Diskus® (500 mcg + 50 mcg)
Seretide Evohaler®, Inhaler Fluticasone + Salmeterol (50 mcg + 25 mcg),
Rheoran® (125 mcg + 25 mcg)
(250 mcg + 25 mcg)
Breo Ellipta® Inh. powder Fluticasone + Vilanterol 100 mcg + 25 mcg
* Ciclesonide is prodrug activated only in the lung, thus may cause less local or systemic side effects.
** Note that 20-40% of administered dose of the inhaled steroid is systemically absorbed, so you
may see systemic steroid effects if used in high doses and/or long-term.
1.1.3 – Anti-Muscarinic bronchodilators (Ipratropium, and Tiotropium)
1. They are used by inhalation as a bronchodilator in the treatment of asthma and chronic
obstructive pulmonary disease (COPD).
2. They Inhibit action of acetylcholine on bronchial smooth muscle causing bronchodilation.
• They cause this by interfering with nerve signals passed to the muscles through the
autonomic nervous system.
• Because they can stimulate a branch of the autonomic nervous system that controls the heart
rate, they may sometimes cause palpitations and trembling.
3. Inhaled Ipratropium is indicated (as needed); due it has short duration of action 3-5 hours;
or as an adjunctive therapy in severe acute asthma, for short-term relief in mild COPD, and for
COPD exacerbations not completely responsive to β2-agonists alone.
• Ipratropium exhibits anti-secretory properties when applied locally and provides
symptomatic relief of rhinorrhea associated with allergic and other forms of chronic rhinitis.
4. Tiotropium has the advantage of having longer duration of action (24hr) than Ipratropium.
5. They improve lung function and reduces the risk of exacerbation in people with
symptomatic asthma, However, it will not stop an asthma attack already in progress; Because it
has no effect on asthma symptoms when used alone, it is most often paired with a short-acting
β2-adrenergic agonist.
• The use of anticholinergics in combination with short-acting β2-adrenergic agonists has been
shown to reduce hospital admissions in children and adults with acute asthma exacerbations.
6. Adverse Effects: dry mouth, blurred vision, taste disturbance, Urinary retention, difficulty in
passing urine (2); Antimuscarinic bronchodilators should be used with caution in patients with
prostatic hyperplasia, bladder outflow obstruction, and those with angle-closure glaucoma.
7. Revefenacin, a long-acting muscarinic antagonist; that has the advantage of used once daily;
it’s the first and currently the only once-daily, nebulized bronchodilator to be approved by FDA
for the treatment of chronic obstructive pulmonary disease (COPD)
Ipratropium Inhaler Atrovent , Atroaldo , Ipravent 20 mcg
® ® ®
Nebulizing Solu.
Tiotropium Cap (inhale powder) Spiriva® , Tiohaler® 18 mcg
Oxitropium Inhaler Oxivent ® 1.5 mg/ml
Aclidinium Inhaler Tudorza Pressair ® 400 mcg
Glycopyrronium * Cap (inhale powder) Seebri Breezhaler® 50 mcg
Revefenacin Nebulizing Solu. Yupelri ® 175 mcg/3 ml
** Glycopyrronium is also used (orally and by injection) to suppress gastric acid secretion,
and has been used topically and orally to treat hyperhidrosis (condition characterized by
abnormally increased sweating/perspiration); Since it reduces the body's sweating ability, it can
even cause fever, heat stroke in hot environments.
Note1: Combination products for Anti-Muscarinic bronchodilators:

Ipratropium + Salbutamol Inhaler Combivent , Duoneb 20 mcg + 100 mcg
® ®
Nebulizing Solu.
Ipratropium + Fenoterol Inhaler Berodual N® 20 mcg + 100 mcg
Umeclidinium + Vilanterol Inhale powder Anoro Ellipta® 62.5 mcg + 25 mcg
Glycopyrronium+ Indacaterol Inhale powder Ultibro Breezhaler® 50 mcg + 110 mcg
Glycopyrrolate + Formoterol Inhaler Bevespi Aerosphere® 9 mcg + 4.8 mcg
Tiotropium + Olodaterol Inhaler Stiolto Respimat® 2.5 mcg + 2.5 mcg
Note2: Triple products
1. These usually contain a long acting Anti-Muscarinic bronchodilator (LAMA), and a long acting
beta2 agonists (LABA) and an Inhaled corticosteroid (ICS).
2. Triple inhalers have the advantage of convenience and may improve adherence, but there are
risks that the three components may interact chemically in the device, and the fixed doses may
require several dose combinations.
3. They are intended for patients with COPD, including chronic bronchitis and/or emphysema.
4. These combinations improve lung function, health status and reduce exacerbations compared
with ICS/LABA or LAMA monotherapy.
5. Some are taken Once daily; some are taken twice daily.
Triple Products
Scientific name(s) D. Form Trade name Concentrations
Umeclidinium + Vilanterol Inhale powder Trelegy Ellipta® 62.5 mcg + 25 mcg
+ Fluticasone + 100 mcg
Tiotropium + Formoterol Inhaler Triohale® 9 mcg + 6 mcg
+ Ciclesonide + 200 mcg
Cap Triohale Rotacaps® 18 mcg + 12 mcg
(for inhale) + 400 mcg
Glycopyrronium + Formoterol Inhaler Trimbow® 10 mcg + 6 mcg
+ Beclometasone + 100 mcg
Glycopyrronium + Formoterol
+ Budesonide Pending FDA approval (by Novartis)
Glycopyrronium + Indacaterol
+ Mometasone Pending FDA approval (by AstraZeneca)
Note: Nobel Prize in Physiology or Medicine 2019

The 2019 Nobel Prize in Physiology or Medicine awarded to William G. Kaelin Jr, Sir Peter J.
Ratcliffe and Gregg L. Semenza “for their discoveries of how cells sense and adapt to oxygen
availability”. The ability of organisms to respond to changes in oxygen availability is of
fundamental importance to life on earth. Work by the prize-winning scientists has shown that in
animal cells, oxygen availability affects gene expression through oxygen-sensitive post-
translational modification and the subsequent proteasomal degradation of Hypoxia Inducible
Factors. This research laid the foundation for understanding the mechanistic basis for the cellular
response to hypoxia and paved the way for the therapeutic targeting of the response pathway.

1.1.4 - Theophylline (and Xanthine’s derivatives)
1. There are 3 important Xanthine derivatives: (Theophylline, Theobromine and Caffeine).
2. Theophylline is a bronchodilator used in asthma and chronic obstructive pulmonary disease.
• Xanthine drugs are thought to relax the muscle in the bronchioles by a direct effect on the
muscle fibers, their precise action is hypnotized as:
 Inhibit phosphodiesterase enzyme thus increasing cAMP; which leads to relaxation of the
smooth muscles and contraction of the cardiac muscle.
 Blocking Adenosine receptors; causing increased heart rate, and stimulant effect in brain.
3. Theophylline is given by injection as Aminophylline; Aminophylline injection must be given by
very slow intravenous injection (over at least 20 minutes).
4. The use of sustained release formulation of theophylline (Phyllocontine®) is preferred over
ordinary tablet (immediate release tablet) and it is usually given twice daily and the sustained
release tablet should not be splinted or crushed.
• Modified-release theophylline tablet should be taken with or just after food.
5. Adverse Effects: tachycardia, palpitations, insomnia, restlessness, tremor.
• Smoking tobacco and drinking alcohol increase excretion of Xanthines from the body,
reducing their effects, thus Stopping smoking after being stabilized on a xanthine may result
in a rise in blood concentration, and an increased risk of side effects. It is advisable to stop
smoking before starting treatment, also the effects of theophylline may last longer if you have
a viral infection, heart failure, or liver cirrhosis.
6. Have a high Drug-Drug interaction profile.
Theophylline Tab Asmasam® 120 mg
Tab SR Phyllocontine® 225 mg
Cap SR TeoCap® 300 mg
Aminophylline Amp Phyllocontine® 250 mg/10 ml
Dyphylline Tab Lufyllin® , Dilor® 200 mg , 400 mg
Diprophylline Syrup Euphillin® 57 mg/5 ml
Acefylline Tab , Amp Sureptil® 50 mg (tab) , 500 mg (amp)
1.1.5 - Leukotriene Receptor Antagonists

1. Leukotrienes occur naturally in the body, they are chemically related to the prostaglandins, but
are much more potent in producing an inflammatory reaction; they are also much more potent
than histamine at causing bronchoconstriction, thus Leukotrienes seem to play an important
part in asthma; Drugs have been developed that block their receptors (leukotriene receptor
antagonists) and therefore reduce the inflammation and bronchoconstriction of asthma.
2. They are given orally mainly for prophylaxis of asthma. (Not useful in acute asthma).
• Montelukast is Also indicated in exercise-induced bronchospasm and in perennial
allergic rhinitis in children as young as 6 months and for seasonal allergic rhinitis in
children as young as 2 years.
• must be taken on a regular basis, even during symptom-free periods.
3. In addition to ordinary tablet, Montelukast also formulated as Chewable tablet which contain a
lower dose (4 mg) and intended mainly for children.
• The chewable tablet is taken on an empty stomach; this means an hour before food or 2
hours after food.
• Granules may be swallowed or mixed with cold, soft food (or liquid) and taken immediately.
4. Adverse effects: Elevations in serum hepatic enzymes, requiring periodic monitoring and
discontinuation when enzymes exceed three to five times the normal limit.
5. Montelukast and Zafirlukast are Leukotriene receptor antagonists, they block the binding of
leukotriene to its receptors, thus prevent the inflammation process (Leukotriene (LT) B4 and
the cysteinyl leukotrienes, LTC4, LTD4, and LTE4, are products of the 5-lipoxygenase pathway of
arachidonic acid metabolism and part of the inflammatory cascade).
6. Zileuton is a selective and specific inhibitor of 5-lipoxygenase, preventing the formation of both
LTB4 and the cysteinyl leukotrienes.
7. A study was recently published shows a link between leukotriene receptor antagonists and
neuropsychiatric adverse drug reactions (depression, aggression, hyperactivity and
nightmares); especially in pediatrics. (10)
Montelukast Tab Singulair , Monax , Singomed 5 mg , 10 mg
® ® ®
Tab Chew. 5 mg , 4 mg
Oral Granules 4 mg
Pranlukast Oral Granules , Azlaire ® 50 mg , 70 mg , 100 mg
Tab
Zafirlukast Tab Accolate® 20 mg
Zileuton Tab ER Zyflo® , Filmtab® 600 mg
Note: Combination products:

Scientific name D. form
Trade name concentration
Montelukast + Cetirizine Tab
Broncho-Vokast ® (10 mg + 5 mg)
Montelukast + Desloratidine Tab
Aircomb ® (10 mg + 5 mg)
Montelukast + Levocetirizine OnceAir Plus , Bronchorest
Tab ® ®
(10 mg + 5 mg)
Fixdual®
Montelukast + Fexofenadine Tab Lukafen® (10 mg + 120 mg)
Montelukast + Ebastine Tab Ebamont , Ebast-M
® ® (10 mg + 10 mg)
** Desloratidine, Levocetirizine and Ebastine are a 2nd generation antihistamine (see below).
1.1.6 – Cromoglicate and Nedocromil

1. The mode of action of Sodium Cromoglicate (Cromoglycate) and Nedocromil is not
completely understood, but they may be of value in asthma with an allergic basis.
• Cromoglicate and Nedocromil thought to act by stabilizing mast cells in the lungs,
preventing them from releasing histamine, leukotrienes, and other inflammation-causing
chemicals; Indicated for prophylaxis of mild persistent asthma in children and adults.
2. Cromoglicate is also called (Cromoglicic acid, Cromolyn and Cromoglycate).
• Cromoglicate and Nedocromil may also have a role in allergic conjunctivitis; sodium
Cromoglicate is used also in allergic rhinitis.
• Cromoglicate is also used (orally as a capsule) for allergy-related diarrhea; food allergy (in
conjunction with dietary restriction).
• Cromoglicate Capsules maybe swallowed whole or the contents dissolved in hot water and
diluted with cold water before taking, to be taken 30 to 60 minutes before food.
3. Dose frequency is adjusted according to response but is usually 3 to 4 times a day.
4. Side effects include throat irritation, cough, bronchospasm (including paradoxical
bronchospasm), and headache.
Cromoglicate Inhaler Intal® 5 mg per Puff
Cap ®
Gastrocrom® 200 mg
Nedocromil Inhaler Tilade® 2 mg per Puff
1.1.7 – Other Asthma therapies
This section covers all the remaining therapies used in asthma; they are used rarely but still
important because they are the last choice in poor responsive patient to traditional medications.
Roflumilast Tab Daxas , Daliresp
® ® 500 mcg
Omalizumab Amp (S.C inj.) Xolair ® 150 mg/ml
Mepolizumab Amp (S.C inj.) Nucala® 100 mg/ml
Reslizumab Vial (infusion) Cinqair ® 100 mg/10 ml
Benralizumab Prefilled Inj. Fasenra ® 30 mg/ml
Dupilumab Amp (S.C inj.) Dupixent® 300 mg/2 ml
Mg+ Sulphate Amp ---------------- 40 mg/ml , 80 mg/ml
Infusion Solu. ---------------- 1 gm/100 ml , 2 gm/100 ml
Notes:
1. Roflumilast is a drug that acts as a selective long-acting inhibitor of the enzyme PDE-4 with
anti-inflammatory properties; (it was developed from trails on Xanthines)
• It’s approved for severe COPD associated with chronic bronchitis, also approved for
reducing COPD exacerbations, it improves lung functions.
• It’s C.I. in severe immunological disease; severe acute infectious disease; co-administration
with immunosuppressive drugs (except short-term systemic corticosteroids).
2. Omalizumab is a monoclonal antibody that binds to immunoglobulin E (IgE), decreasing its
binding ability to receptors on mast cells and basophils; it is used as additional therapy in
individuals with proven IgE-mediated sensitivity to inhaled allergens, whose severe persistent
allergic asthma cannot be controlled adequately with high dose inhaled corticosteroid together
with a long-acting beta2 agonist.
• Omalizumab should be initiated by physicians in specialist centers experienced in the
treatment of severe persistent asthma. (Given S.C. twice a month), and should be used only
in severe asthma with concurrent allergies.
• Also indicated for chronic idiopathic urticarial.
• Approved only to Use in those ≥ 12 years, Half-life: 26 days.
• In September 2014: FDA Drug Safety Communication announced that Omalizumab Slightly
increased risk of cardiovascular and cerebrovascular serious adverse events, including MI,
unstable angina, TIA, PE/DVT, pulmonary HTN; but no increase in risk of stroke or CV death.
3. Mepolizumab, Reslizumab and Benralizumab are indicated for severe asthma with an
eosinophilic phenotype as add-on maintenance treatment in those above 12 years old.
• It’s an IgG1 Monoclonal antibody, specific for IL-5, it binds IL-5 and thus preventing it for
binding with eosinophils, thus it reduces the eosinophils in blood, tissues and sputum.
• Reduces rate of asthma exacerbations by > 50%.
• Reduces corticosteroid dose by 50%.
4. Magnesium sulfate (administered I.V.) may be useful in some patients because of its modest
ability to cause bronchodilation, it also improves the respiratory muscle strength in
hypomagnesemia patients. It’s also used:
• As an Anti-arrhythmic for the treatment of Torsade’s De Pointes.
• As a Tocolytic to stop preterm labor in Obs/Gyne.
• To prevent seizers associated with pre-eclampsia, and to control seizers with eclampsia.
Note1:
➢ There are several medications available for the treatment of Asthma; are they all the same?
Well; the answer to that question is a little complex; since the choice of drugs depends on the
stage of Asthma or COPD, and wither it’s for acute relief or long-term symptoms control.
Note2: The table below shows a simple guide for choosing anti-asthmatics:
Category Purpose Types
Long-term asthma Taken regularly to control • Inhaled corticosteroids
control medications chronic symptoms and prevent • Leukotriene modifiers
asthma attacks; the most • Long-acting beta agonists
important type of treatment for (LABAs)
most people with asthma • Theophylline
• Combination inhalers
Quick-relief medications Taken as needed for rapid, • Short-acting beta agonists
(rescue medications) short-term relief of symptoms • Ipratropium
used to prevent or treat an • Oral and intravenous
asthma attack corticosteroids (for
serious asthma attacks)
Medications for allergy- Taken regularly or as needed to • Allergy shots
induced asthma reduce the body's sensitivity to (immunotherapy)
a particular allergy-causing • Allergy medications
substance (allergen) (antihistamines)
Biologics Taken with control group to • Omalizumab
stop underlying biological • Mepolizumab
responses causing inflammation • Benralizumab
in the lungs (for Sever Asthma) • Reslizumab
Note3:
Inhaled corticosteroids differ in their potencies, anti-inflammatory effect, and side effects.
➢ The highest inhaled corticosteroid with Relative glucocorticoid receptor binding affinity (or the
highest anti-inflammatory potency) is Fluticasone Furoate, the second in place is
Mometasone, then in third place is Budesonide.
➢ The longest lung retention is with Fluticasone Furoate. (the longest half-life and duration).
➢ Fluticasone Furoate and Mometasone inhalers is given once daily; while other is given twice.
➢ The lowest systemic absorption inhaled corticosteroid is Budesonide.
➢ The lowest side effects profile is Ciclesonide, (it’s a prodrug; activated only in the lungs).
Note4: Salmeterol or Formoterol?

1. The pharmacological evidence for a rapid onset of action of Formoterol (5 min), yet long
duration of effect (12 hours), is supported by several clinical studies; The fast onset of
bronchodilation and high intrinsic activity of Formoterol therefore suggest that it can be used
for relief treatment in patients with asthma if they are concomitantly treated with inhaled
glucocorticoids. (7) (i.e. Formoterol can be used also for acute attack relief).
2. Salmeterol has slightly more prolonged activity (13-14 hours); but slower onset of action
(about 20 minutes); it’s also a partial agonist; which means it causes less side effects than
Formoterol; and has a lower tolerance on the β2-receptors with prolonged use. (8)
3. The real question is Symbicort® or Seretide®?
• Well; it’s for you to decide dear reader; corticosteroid potency or safety; the higher effect or
the least systemic side effects.
Note5: Again; Salmeterol or Formoterol or Tiotropium?

1. In patients with moderate-to-very-severe COPD, Tiotropium is more effective than Salmeterol
in preventing exacerbations. (11)
2. Currently, there is no documentation that Tiotropium is superior to Formoterol or the contrary,
but a combination of them both is more effective than single drugs alone in inducing
bronchodilation and a bronchodilator-mediated symptom benefit in patients suffering from
COPD; although Formoterol has a fast onset and a bronchodilator effect of approximately 12 h,
while Tiotropium has a 24-h bronchodilator effect and is given once daily. (12)
1.2-Antihistamines
1. Their main action is to counter the effects of histamine, one of the chemicals released in the
body when there is an allergic reaction.
2. Histamine is also involved in other body functions, including blood vessel dilation and
constriction, contraction of muscles in the respiratory and gastrointestinal tracts, and the
release of digestive juices in the stomach.
3. The antihistamine drugs described here are also known as H1 blockers because they block the
action of histamine only on certain receptors, known as H1 receptors. Another group of
antihistamines, known as H2 blockers, is used in the treatment of peptic ulcers.
4. Some antihistamines have a significant anticholinergic action; This is used to advantage
in a variety of conditions, but it also accounts for certain undesired side effects.
5. Histamine H1-receptor antagonists bind to H1 receptors without activating them, preventing
histamine binding and action; They are more effective in preventing the histamine response
than in reversing it (4).
• Antihistamines block the action of histamine on H1 receptors; These are found in various
body tissues, particularly the small blood vessels in the skin, nose, and eyes. This helps
prevent the dilation of the vessels, thus reducing the redness, watering, and swelling.
• the anticholinergic action of these drugs contributes to this effect by reducing the
secretions from tear glands and nasal passages.
• Antihistamine drugs pass from the blood into the brain. In the brain, the blocking action of
the antihistamines on histamine activity may produce general sedation and depression of
various brain functions, including the vomiting and coughing mechanisms.
6. Antihistamines are used in the treatment of allergies, nasal allergies (they reduce rhinorrhea
and sneezing), also used to treat urticarial rashes, pruritus, and insect bites and stings.
• Antihistamines are also prescribed for the itching, swelling, and redness of allergic
reactions involving the skin such as dermatitis, and Irritation from chickenpox.
• Antihistamines are often included as an ingredient in cough and cold preparations, when
the anticholinergic effect of drying mucus secretions and their sedative effect on the coughing
mechanism may be helpful.
• Because most antihistamines have a depressant effect on the brain, they are sometimes
used to promote sleep, especially when discomfort from itching is disturbing sleep, the
depressant effect of antihistamines on the brain also extends to the centers that control
nausea and vomiting; thus, effective for preventing and controlling these symptoms (see
Anti-emetics).
The antihistamines may be classified into:
a) Sedating antihistamines: also referred as 1st generation antihistamines older
antihistamines that are associated with troublesome sedative and Antimuscarinic effects.
Examples are (Chlorpheniramine, Clemastine, Cyproheptadine, Ketotifen,
diphenhydramine, and Dimetindene maleate), Drowsiness is a major problem with the
sedating antihistamines and those affected should not drive or operate machinery.
b) Non-sedating antihistamines: also referred as 2nd, are newer antihistamines, they
generally cause little or no drowsiness; Examples are (Cetirizine, Loratadine).
➢ A new classification divides the 2nd generation into a 3rd generation, which
consists only from the active metabolites of the 2nd gen. (ex: Desloratidine,
Levocetirizine, Fexofenadine), which has more efficacy and less side effects.
7. Adverse effects: constipation, dry mouth, Sweating, Blurred vision, Tachycardia.
• In high doses, or in children, some antihistamines can cause excitement, agitation, and
even, in extreme cases, hallucinations and seizures.
8. Antihistamines should be used with caution in patients predisposed to urinary retention and in
those with increased intraocular pressure, hyperthyroidism, and cardiovascular disease.
9. Contraindicated in: Narrow angle Glaucoma, Prostate enlargement, BPH.
10. A new study published on (PubMed) states that: (combining H1 and H2 antagonists in patients
with acute allergic syndromes results in faster improvement from allergy).
(For H2 antagonists see chapter 2, section 3)
1st Generation Antihistamines:
Scientific name D. form Trade name Conc.
Clemastine Tab Tavegyl® 1 mg
Amp Tavegyl , Tavesta
® ® 2 mg
Diphenhydramine Tab Brandyl , Allermine
® ® 25 mg
Amp Allermine ® 10 mg
Syr. Allermine® 10 mg/5 ml
Chlorpheniramine Tab Histadin ® 4 mg
Amp Allergal ® 10 mg/2ml
Syr. Pirafene® 2 mg/5 ml
Pheniramine Tab Avil ® 20 mg
Amp Avil ® 45.5 mg/2 ml
Dexchlorpheniramine Tab Poloramine ® 6 mg
maleate
Doxylamine Tab Unisom®, Sleep Well® 25 mg
. Cyproheptadine Tab Periactin , Ciptadine ,
® ® 4 mg
Cyprodad®, Nebor®
Syr. Cyprodine® , Citadine® 2 mg/5 ml
Ketotifen Tab Zaditin® , Ketofen® 1 mg
Syr. Ketofen , Zylofen
® ® 1 mg / 5 ml
Eye Drop Zaditor , Zyrtec
® ® 0.025%
Hydroxyzine Tab Atarax ® 10 mg , 25 mg
Dimetindene Drop Fenistil® 0.1 gm
Tab 4 mg
Syr. 0.01%
Promethazine Tab Phenadoz ® 25 mg
Syr. 6.25 mg/5 ml
Triprolidine (Found in Combinations Only, As Actifed®)
Carbinoxamine Tab Palgic® , Arbinoxa® 4 mg
Brompheniramine Tab Dimetane® , Respa® 10 mg
Alimemazine Tab Nedeltran®, Panectyl® 10 mg
Syr. 7.5 mg/5 ml
Oxomemazine Syr. Toplexil® , Toxil® 1.65 mg/5 ml
Tab 24 mg
Notes:
1. Diphenhydramine has pronounced sedative properties and may be used as a hypnotic in the
short-term management of insomnia (taken before bedtime).
2. Doxylamine is usually categorized as a sedative/hypnotic agent.
3. Cyproheptadine has been widely used as an appetite stimulant, but in the long-term appears
to have little value in producing weight gain and such use is no longer recommended.
4. Hydroxyzine has strong Anxiolytic effect, with high sedating capacity, it can be abused.
Dimetindene is usually used for pediatrics as antipyretic and sedative, and for allergies, it is safe
for infants from one month and older; (But it’s not recommended to use as sedative).
5. Triprolidine should be given only to children above 6 years old, as approved by the U.S.
Food and Drug Administration (FDA), although some doctors prescribe it to children below 6
years. (educate them about this fact)
6. Alimemazine is also called Trimeprazine (they are the same drug).
7. Oxomemazine is not approved by the U.S.A (FDA), but it is still sold as over the counter
medication in some countries, Oxomemazine has a strong sedative effect – Which may
explain why it’s abused in our markets - (don’t give by hand, ONLY by Rx).
2nd and 3rd Generation Antihistamines:

Scientific name Dosage form Trade name Concentration
Fexofenadine Tab Telfast® , Fexofast® , Fexon® 180 mg , 120 mg
Oral Susp. Allerga® 30 mg/5 ml
Loratadine Tab Claritin®, Tidilor® , 10 mg
Syrup Loratin ® ®
Loratidine , Lortin® 5 mg/5 ml
Cetirizine * Tab Zyrtec® , Cetriz® 5 mg , 10 mg
Syrup , Oral drop Zyrtec® 5 mg/5 ml
Desloratidine Tab Areus® , Clarinex® 5 mg
Syrup 2.5 mg/5 ml
Levocetirizine Tab Xyzal® 5 mg
Oral Solu. 2.5 mg/5 ml
Acrivastine Tab , Cap Semprex® 8 mg
Ebastine Tab Evastin® , Aleva® 10 mg , 20 mg
Syrup 5 mg/5 ml
Bilastine Tab ILaxten® 20 mg
Mizolastine Tab Mizollen® 10 mg
Rupatadine Tab Rupafin® 10 mg
Terfenadine * Tab Seldane® 60 mg
** The safety profile of Fexofenadine is quite favorable, as no cardiovascular or sedative effects have
been shown to occur even when taking 10 times the recommended dose.
** although Cetirizine is a 2nd generation antihistamine; it produces a marked sedation.
** Terfenadine was withdrawn from the markets in the USA due to the risk of disruption of the
electrical rhythms of the heart (cardiac arrhythmia caused by QT interval prolongation).
Comparison of Antihistamines

Note1: which antihistamine is the most potent for allergy?
➢ Levocetirizine and Fexofenadine are the most potent antihistamines in humans in vivo;
Fexofenadine also has the lowest side effects profile in antihistamines group. (9)
Note2: Topical Antihistamine

➢ These are useful for relieving itching that is often associated with sunburns, allergic reactions,
eczema, psoriasis … etc. (for more information see chapter 14, section 9)
Crotamiton Cream/Lotion Eurax® 10%
Calamine Lotion Calamine® 10%
Diphenhydramine Gel Banophen® 1% , 2%
Note3: Other Antihistamines (As Nasal Sprays & Eye drops)

Azelastine Nasal Spray Astelin® , Allergodil® , Rhinolast® 0.1%
Eye Drop Optivar®, Allergodil® 0.05%
Olopatadine Nasal Spray Patanase® 6%
Eye Drop Pataday® , Patanot® , Olopat® 0.1% , 0.2%
Alcaftadine Eye Drop Lastacaft® 0.25%
Bepotastine Eye Drop Bepreve® 1.5%
Emedastine Eye Drop Emadine® 0.05%
Epinastine Eye Drop Elestat® 0.05%
Levocabastine Eye Drop Livostin® 0.05% (0.5 mg/ml)
Nasal Spray 50 mcg/spray
Notes:
1. Intranasal antihistamine rapidly relieves symptoms of seasonal allergic rhinitis. However, patients
should be cautioned about its potential for drowsiness because systemic availability is ∼40%.
Patients may also experience drying effects, headache, and diminished effectiveness over time. (4-5).
2. Ophthalmic antihistamines that can be used for allergic conjunctivitis that is often associated with
allergic rhinitis.
1.3 - Cough preparations, Common Cold and Flu

1. Commonly, cough preparations contain a combination of antitussive or expectorants,
antihistamine, and/or sympathomimetic (for congestion).
2. Lozenges may also be used for cough especially for pregnant women.
3. Some usually contain a combination of Sympathomimetics like pseudoephedrine and
phenylephrine (they reduce nasal congestion) and antihistamine (like Triprolidine) (they
reduce rhinorrhea and sneezing).
➢ Pseudoephedrine in some countries are not available as an OTC; and only given by a
prescription; that is due Pseudoephedrine can be converted chemically (by reduction) to
Methamphetamine.
4. Topical and systemic decongestants are sympathomimetic agents that act on adrenergic
receptors in the nasal mucosa to produce vasoconstriction, shrink swollen mucosa, and improve
ventilation.
5. Prolonged use of topical Sympathomimetics agents (>3–5 days) can result in rhinitis
medicamentosa (which is rebound vasodilation with congestion); Patients with this condition
use more spray more often with less response. Abrupt cessation is an effective treatment, but
rebound congestion may last for several days or weeks; Generally recommended duration for
usage of the topical Sympathomimetics is 3 days.
6. Systemic decongestants should be used with caution in hypertension, hyperthyroidism, and
ischemic heart diseases.
A) Topical Sympathomimetics:
Xylometazoline *4 Nasal Drop / Otrivin Adult®, Triaminic®, 0.1%
Nasal Spray Xylo-mepha®
Nasal Drop/Spray Otrivin Child® 0.05%
Oxymetazoline Nasal Drop Afrin®, Dristan®, Nasordine® 0.05%
Phenylephrine Nasal Spray/Drop NeoSynephrine®, Nazafrine® 0.25% , 0.5%
Naphazoline Nasal Spray/Drop Privine® 0.05%
Tetrahydrozoline Nasal Drop Visine®, Burnil® 0.05% , 0.1%
Propylhexedrine Nasal Spray Benzedrex® 250 mg
Notes:
1. All topical Sympathomimetics are not recommended to use in children below 6 years,
Except for Xylometazoline 0.05% which can be used in children above 2 years old.
2. Younger children (below 2 years) are to use NaCl nasal drops for treatment of decongestion.
3. Adverse effects of topical decongestants are burning, stinging, sneezing, and dryness of the nasal
mucosa.
4. Xylometazoline is also available as a topical cream 1%, indicated for the topical treatment of
persistent facial erythema associated with rosacea in adults.
➢ Xylometazoline can be abused by addicts to obtain the psychoactive effects of inhaled
Xylometazoline; which include excitation and feeling of strength.
5. Topical Sympathomimetics differ in their duration of action as shown in the Table below:
B) Common Cold and Flu:

1. Generally Common Cold and Flu are viral in origin and self-limiting (thus antibiotics have no
role), usually patient will recover within 1 week, Few Cases are due bacterial infection.
2. Mechanism of infection: Once the virus is exposed to the mucosa, it invades the nasal and
bronchial epithelia, causing damage to the ciliated cells. This results in the release of
inflammatory mediators, which in turn leads to inflammation of the tissues lining the nose.
Permeability of capillary cell walls increases, resulting in edema, which is experienced by the
patient as nasal congestion and sneezing. Fluid might drip down the back of the throat, spreading
the virus to the throat and upper chest causing cough and sore throat.
3. All the treatment is given for symptomatic relief ONLY.
Trade name D. form Scientific name(s) Concentration
Actifed® Tab Triprolidine 2.5 mg
Pseudoephedrine 60 mg
Actifed®, Syrup Triprolidine 1.25 mg/5ml
Samafed® (yellow) Pseudoephedrine 30 mg/5ml
Actifed® (red) Syrup Triprolidine + Pseudoephedrine 1.25 mg + 30 mg
(red) Dextromethorphan 10 mg
Actifed® (green) Syrup Triprolidine + Pseudoephedrine 1.25 mg + 30 mg
(green) Guaifenesin 100 mg
Panadol® Night Tab Paracetamol + Diphenhydramine 325 mg + 25 mg
Panadol® Sinus Tab Paracetamol + Pseudoephedrine 500 mg + 30 mg
Panadol® Extra Tab Paracetamol + Caffeine 500 mg + 65 mg
Panadol® Tab Paracetamol + Pseudoephedrine 500 mg + 30 mg
Cold-Flu Chlorpheniramine 2 mg
Panadol® Tab, Paracetamol + Phenylephrine 600 mg + 10 mg
Cold-Flu Lemon Sachet + Vitamin C + 40 mg
Panadol® Tab Paracetamol + Phenylephrine 500 mg + 5 mg
Cold-Flu Day + caffeine + 25 mg
Panadol® Tab Paracetamol + Phenylephrine 250 mg + 5 mg
All in one + Guaifenesin + 100 mg
Coldin® SDI Tab Paracetamol + Promethazine 450 mg + 5 mg
Phenylephrine 5 mg
Syrup Paracetamol + Pseudoephedrine 120 mg + 15 mg
Chlorpheniramine 2 mg
Vitamin C 50 mg
Coldin® Mediphar Cap Paracetamol + Pseudoephedrine 300 mg + 30 mg
+ Pyrilamine + Noscapine + 15 mg + 10 mg
+ Caffeine + 30 mg
Syrup Paracetamol + Pseudoephedrine 120 mg + 15 mg
+ Pyrilamine 6.25 mg
+ Glyceryl Guaiacolate 15 mg
Flu-out® Tab Paracetamol + Chlorpheniramine 350 mg + 2 mg
+ Vitamin C + 100 mg
Flu-cure ® Tab Paracetamol + Chlorpheniramine 400 mg + 2 mg
Stop-cold®
Flu Stop® Elixir Paracetamol + Chlorpheniramine 120 mg + 2 mg
Semprex D® Cap Acrivastine + Pseudoephedrine 8 mg + 60 mg
Grippe stop® Tab Paracetamol + Pseudoephedrine 325 mg + 30 mg
+ Dextromethorphan + 15 mg
Tullin-D® (red), Cap (red), Paracetamol + Pseudoephedrine 325 mg + 30 mg
Congestal® Tab + Dextromethorphan + 10 mg
+ Chlorpheniramine + 2 mg
Tullin-D® (red), Syrup Paracetamol + Pseudoephedrine 160 mg + 15 mg
Congestal® + Dextromethorphan + 7.5 mg
+ Chlorpheniramine + 1 mg
Tullin® Cap Guaifenesin + Pseudoephedrine 100 mg + 30 mg
(blue) (blue) + Dextromethorphan + 10 mg
+ Paracetamol + 250 mg
Dolo-Cold® ** Tab Paracetamol + Chlorpheniramine 500 mg + 2 mg
+ Phenylpropanolamine ** + 12.5 mg
+ Caffeine + Pseudoephedrine + 25 mg + 30 mg
Triaminic® Syrup Pseudoephedrine 15 mg
Dextromethorphan 5 mg
Aspirin-C®, Eff. Tab. Aspirin + Vitamin C 400 mg + 250 mg
Cevamol®
Hayanil® Tab Dexchlorpheniramine + Vit. C +
2 mg + 75 mg +
Dexamethasone 0.25 mg
Co-Aleva® Tab Ebastine + Betamethasone.
10 mg + 500 mcg
Snip® Tab Paracetamol + Pseudoephedrine
325 mg + 15 mg
Salzone® Cap Paracetamol + Phenylephrine
500 mg + 6.1 mg
Clarinase® Tab Loratadine + Pseudoephedrine
5 mg + 120 mg
Xinase®, Clearest® Tab Cetirizine + Pseudoephedrine
5 mg + 120 mg
Orofar® Lozenges Benzoxonium Chloratum 1 mg
Lidocaine + Sorbitol 1 mg + 1 gm
Bebe Col® Syrup Paracetamol + Diphenhydramine (150 mg +1200 mg)/100 ml
Apidon®, Phenadone Syrup Dexamethasone + 10 mg +
Histamed-F® Chlorpheniramine 40 mg
** Phenylpropanolamine has been withdrawn from the markets in USA and Europe, but unfortunately, it’s still
prescribed in our market, it was withdrawn due to the risk of hemorrhagic stroke; spread this fact
C) Expectorants & Antitussive

About Cough:
➢ The cough is a normal reflex to protect the airways, but sometime cough is a symptom of a pathological
disease or a sign for something wrong. To distinguish between the normal cough and the pathological
one you must notice:
1. Sputum color:
a) Mucoid (clear and white) is normally of little consequence and suggests that no infection is present.
b) Yellow, green or brown sputum normally indicates infection.
c) Mucopurulent sputum is generally caused by a viral infection.
d) Hemoptysis can either be rust colored (pneumonia), pink tinged (left ventricular failure) or dark
red (carcinoma).
2. Nature of sputum:
a) Thin and frothy suggests left ventricular failure.
b) Thick, Mucoid to yellow can suggest asthma.
c) Offensive foul-smelling sputum suggests either bronchiectasis or lung abscess.
➢ It’s Very important to ask about the nature of the cough (wet or dry), since each type has its own type
of medication: (5).
• Wet cough (with sputum) → expectorants and mucolytic.
• Dry cough (without sputum) → Cough suppressants (antitussive) + Antihistamines.
➢ If you used an Antitussive for a wet cough → cause congestion → worsen the cough, so be sure of
what you give to your patient.
Note:
A. Expectorants include: (Glyceryl Guaiacolate or Guaifenesin (they are the same drug), Ammonium
Chloride, Carbocysteine, potassium iodide, potassium guaiacolsulfonate).
B. Mucolytics include: (Bromhexine, Ambroxol, Carbocysteine, Acetyl cysteine, Erdosteine)
C. Antitussive include: (Codeine, Dextromethorphan, Butamirate, Benzonatate, Pipazethate, Pholcodine,
Clobutinol, Cloperastine, Oxeladin, Benproperine, Noscapine and Carbetapentane).
Isilin® Syrup Diphenhydramine 0.270 gm/100 ml
Ammonium chloride 2.630 gm/100 ml
Sodium Citrate 0.9 gm/100 ml
Menthol 0.020 gm/100 ml
Histalix® Syrup Diphenhydramine 14 mg
Ammonium chloride 135 mg
Menthol 1.1 mg
Tussilet®, Syrup Glyceryl Guaiacolate 50 mg
Soolan®, Chlorpheniramine 1 mg
Decopect® Phenylephrine 2.5 mg
Tussiram® Syrup Ephedrine 15 mg/10 ml
Phenylephrine 5 mg/10 ml
Chlorpheniramine 2 mg/10 ml
Codeine 8 mg/10 ml
Tussivan® Syrup Ephedrine 5 mg/10 ml
Phenylephrine 5 mg/10 ml
Chlorpheniramine 2 mg/10 ml
Codeine 8 mg/10 ml
Sedilar®, Tussilar® Tab Dextromethorphan 15 mg
Oral Drop
Sedo-pect® Syrup Diphenhydramine 7 mg/5 ml
(children) Sodium Citrate 28.5 mg/5 ml
Menthol 0.55 mg/5 ml
Rhinathiol® Syrup Carbocysteine 5 gm/100 ml (Adult)
2 gm/100 ml (Child)
Rhinathiol Plus® Syrup Carbocysteine + Promethazine (5 gm +0.05 gm)/100 ml
Sedo-pect® Syrup Diphenhydramine + Codeine 14 mg + 5.7 mg
(adult) + Sodium Citrate + Menthol + 57 mg + 1.1 mg (per 5 ml)
Cemo® Syrup Carbinoxamine + Ephedrine HCI 2 mg + 4 mg + 10 mg
(green) + Codeine (per 5 ml)
Cemo® Syrup Carbinoxamine 2 mg/5 ml
(red) Ephedrine HCI 4 mg/5ml
Ammonium chloride 100 mg/5ml
Samilin® Syrup Diphenhydramine 13.5 mg/5 ml
Ammonium chloride 131.5 mg/5 ml
Sodium Citrate 55 mg/5 ml
Menthol 1 mg/5 ml
Sedafen® Syrup Ephedrine 5 mg/5ml
Dextromethorphan 10mg/5ml
Chlorpheniramine 2mg/5 ml
Toxil® Syrup maieate
Dextromethorphan 10 mg/5 ml
Oxomemazine 1.5 mg/5 ml
Solvodin® Syrup Bromhexine HCI 4 mg/5 ml
Bisolvon® Tab Bromhexine 8 mg
Amp Bromhexine 8 mg/2 ml
Mucobrox ® Tab Ambroxol 30 mg
MucoFree®, Mucol® Syrup Ambroxol 15 mg/5 ml , 30 mg/5 ml
Mucinex® Tab Guaifenesin 600 mg
Tusscapine® Syrup Noscapine 15 mg/5 ml
Selgon® Tab Pipazethate 20 mg
Drop 40 mg/ml
Paxeladine® Cap, Oxeladine citrate 40 mg (cap)
Syrup 2 mg/5 ml (syrup)
Mucosolvan®, Tab, Cap Acetyl cysteine * -----------------
Mucomyst® Susp.
Mucotec® Cap, Erdosteine 150 mg, 300 mg (cap)
Susp. 175 mg/5 ml (Susp.)
Transpulmin® Syrup Pipazethate + Glyceryl Guaiacolate 10 mg + 25 mg
+ Isothipendyl + Liquorice extract + 2 mg + 50 mg
Codilar® Syrup Phenylephrine + 4 mg +
Dextromethorphan + 10 mg +
Bronkovet® Syrup Salbutamol 2 mg
Bromhexine HCI + Guaifenesin 4 mg + 50 mg
All-Vent®, Syrup Terbutaline + Bromhexine + 1.25 mg + 4 mg +
Bro-zedex® Guaifenesin + Menthol 50 mg + 2.5 mg (per 5 ml)
Brovensin® Syrup Terbutaline + Bromhexine + 2.5 mg + 8 mg +
Guaifenesin 100 mg (per 10 ml)
Farcosolvin® , Cap, Ambroxol + Theophylline + (30mg+100mg+60mg) Cap
Trisolvin® Syrup Guaifenesin (15mg+30mg+50mg)/5 ml
Ultrasolv® Tab, Guaiphenesin + Carbocysteine + (225mg+375mg+5mg) Tab
Syrup Oxomemazine (100mg+125mg+2mg)/5 ml
Bronchophane® Syrup Guaifenesin + Ephedrine + 50 mg + 7.5 mg +
Diphenhydramine + 5 mg +
Dextromethorphan 4.58 mg (per 5 ml)
Mucovent® Cap Acetyl cysteine + Ambroxol 200 mg + 30 mg
Mucophylline® Syrup Bromhexine + Acefylline (4 mg + 100 mg)/5 ml
Octovent® Syrup Guaifenesin + Salbutamol (50 mg + 2 mg)/5 ml
Achee® Tab Paracetamol + Bromhexine 450 mg + 8 mg
Chlorpheniramine + Guaifenesin 2 mg + 100 mg
Bronquium®, Elixir Glyceryl Guaiacolate 0.6 gm/100 ml
Exidil® Theophylline 1 gm/100 ml
Noradran® Syrup Guaifenesin + Diphenhydramine 25 mg + 5 mg
+ Dihydroxypropyltheophylline + 50 mg
+ Ephedrine + 7.5 mg (per 5 ml)
Sinecode®, Tab, Butamirate 50 mg (tab)
Dricod® Syrup, 0.15% (syrup)
Oral Drops 5 mg/ml (drop)
Antitussive Notes:
1. Codeine is also used as an analgesic; it suppresses cough for about 6 hours.
2. Dextromethorphan is best to be avoided in asthma, as it causes release of histamine, thus
worsening the asthmatic attack.
➢ It’s free from addictive properties; but at high doses it may cause hallucinations.
3. Butamirate has the advantage of causing bronchodilation; so, it can be used in asthmatics.
➢ Can be used safely in infants as drops.
4. Noscapine (an alkaloid); has a mild analgesic effect.
5. Clobutinol can prolong the QT interval; thus, was withdrawn from several markets.
6. Cloperastine has both antitussive and antihistamine properties.
7. Oxeladin is the most potent antitussive available, and has a high selectivity for cough center.
8. Pipazethate also has a bronchodilation effect.
Mucolytic Notes:
1. All Mucolytic agents should be used with caution it patients with peptic ulcer.
2. Acetyl Cysteine or N-acetylcysteine (NAC), a mucolytic with an anti-inflammatory and anti-
oxidant effect; it decreases thickness (viscosity) of the mucus secretion in the lungs.
➢ It’s also used I.V. or orally to treat Paracetamol overdose and toxicity.
➢ it’s also given to treat infertility (decreasing sperm viscosity thus enhancing its motility).
3. Ambroxol Improve mucous flow and transport (Muco-kinetic effect); it’s the active metabolite
of Bromhexine.
4. Erdosteine has an anti-oxidant effect.
5. Carbocysteine has both Mucolytic and Expectorant effect; also has an anti-oxidant effect and
anti-inflammatory effect; with mucoregulator properties.
Expectorants Notes:
1. Guaifenesin has a muscle relaxant effect and anticonvulsant properties.
2. Guaifenesin increases the analgesic effect of paracetamol and NSAIDs; and also increases the
sedative effect of alcohol, Hypnotics and Anxiolytics.
Note: American College of Chest Physicians (ACCP) Recommendations

Drugs recommended in the 2016 ACCP guidelines
for the treatment of acute and subacute cough
Drug or Cough Acute Post infectious Pertussis
Drug class associated with bronchitis cough (whooping
common cold cough)
Central-acting Not Recommended Recommended if both Not
antitussives recommended inhaled ipratropium and recommended
(prescription) inhaled corticosteroids
are ineffective
Antihistamine/ Recommended Not recommended Not recommended Not
Decongestants recommended
Inhaled Recommended Not recommended First-line therapy Not
Ipratropium recommended
Naproxen * Recommended Not recommended Not recommended Not
recommended
Inhaled Not Not recommended Recommended if Not
corticosteroids recommended inhaled ipratropium is recommended
not effective
β2 Agonist Not Recommended Not recommended Not
bronchodilators recommended only when recommended
wheezing
accompanies the
cough
Antibiotics Not Not recommended Recommended only if Macrolide
recommended associated with antibiotics
bacterial sinusitis recommended
early in the
course of
infection (first
few weeks)
* Naproxen was the only NSAID recommended in the guidelines for treatment of cough associated with colds
because it was the only NSAID studied in this setting.
D) Cough medications as Suppositories
These are usually given for infants and Childs.
Trade name Dosage form Scientific name(s) concentration
Selgon® Supp. Pipazethate 10 mg
Eucaphol® Supp. Guaifenesin + Pholcodine 30 mg + 5 mg
+ Camphor + Eucalyptus + 50 mg + 100 mg
Rectoplexil® Supp. Oxomemazine + Paracetamol 3.3 mg + 66.6 mg
+ Guaifenesin + Na+ benzoate + 66.6 mg + 66.6 mg
Prosban® , Liblab® Supp. Dried Ivy leaf extract ----------------------
Minophylline® Supp. Theophylline 125 mg , 250 mg
E) Herbal mixtures for Cough

Herbal preparation usually contains one or more of these herbs: Guava, Tilia, Thyme, Fennel,
Licorice, Anise oil, Peppermint, Ginger, Honey, Ivy Leaves and Camphor.
➢ Zexuf® Syrup contains (Glycyrrhiza Glabra) which can raise the blood pressure, so try
avoiding that herbal mixture in the high-risk group (cardiac patients).
➢ GeloMyrtol is used for acute and chronic bronchitis, and sinusitis.
Trade name D. form Scientific name concentration
Zecuf ® Syrup, Lozenges Herbal preparation -----------
Melrosum® Syrup Thyme fluid extract 15gm/100 ml
Bronchicum® Elixir Thyme fluid extract 5 gm/100 ml
Primula root fluid extract 2.5 gm/100 ml
GeloMyrtol Forte® Cap Eucalyptus oil + Lemon oil 300 mg per cap
+ Myrtle oil + sweet orange oil
Balsam® Syrup Herbal preparation -----------
Apdyl-H® Syrup Herbal preparation -----------
Mucosal® Syrup Thyme + Grindelia + Honey 130 ml
Ribosan® Syrup Ribwort herb soft extract 100 ml
Ivypect® Syrup Dried Ivy extract + Honey 100 ml
Thymepect® Syrup Thyme fluid extract + Honey 100 ml
+ Elderberry juice
Liblab®, Prosban® Syrup, Lozenges Dried Ivy leaf extract 35 mg/5 ml
Meritus® Syrup Honey, Lemon, Strawberry -----------
The difference between the Expectorant and Mucolytic:
• Expectorant works to increase the Bronchial Glands Secretions, this means more impulsively
secretion of the Watery Secretions and therefore the intensity and extent of (phlegm) is decreased
in the bronchial tubes; thus, it becomes easier exit through coughing.
• Mucolytic Work to dissolve the mucus by the fragmentation of the bonds that bind them and thus
diminish their density and ensure easy exit of (phlegm) either by coughing or is absorbed through
the body and take it out through the other body secretions.
1.4 – Respiratory Stimulants

1. They are used in intensive care settings to stimulate the respiratory rate in patients with respiratory
failure. Also, may be useful for treating respiratory depression that caused by certain drugs.
2. Respiratory stimulants can also be harmful in respiratory failure since they stimulate non respiratory as
well as respiratory muscles. They should only be given under expert supervision in hospital and must be
combined with active physiotherapy.
Doxapram Vial (solu.) Dopram® 20 mg/ml (400 mg/20 ml)
Caffeine Vial (solu.) Vivarin® , Cafcit®, Cafirate® 20 mg/ml (3 ml vial)
Almitrine Tab Duxil® 30 mg
1.5 – Pulmonary Surfactant
1. Pulmonary surfactants are used in the management of respiratory distress syndrome (hyaline
membrane disease) in neonates and preterm neonates. They may also be given prophylactically to
preterm neonates at risk of developing the syndrome; They act by reducing surface tension, thus act
to increase pulmonary compliance and prevent atelectasis (collapse of the lung) at the end of
expiration, and to facilitate recruitment of collapsed airways.
2. Pulmonary surfactants have been associated with intracranial hemorrhage. Bradycardia, pulmonary
hemorrhage.
Beractant Intra-tracheal Susp. Survanta , Alveofact
® ® 25 mg/ml
Calfactant Intra-tracheal Susp. Infasurf ® 3 ml , 6 ml
Lucinactant Intra-tracheal Susp. Surfaxin® 8.5 ml/Vial
Poractant Alfa Intra-tracheal Susp. Curosurf ® 8 mg/ml (1.5 ml , 3 ml)
1.6 – Drugs for Cystic Fibrosis

1. Cystic fibrosis (CF), also known as mucoviscidosis, is an autosomal recessive genetic disorder that
affects mostly the lungs, Difficulty in breathing is the most serious symptom and results from frequent
lung infections.
2. The main signs and symptoms of cystic fibrosis are salty tasting skin, poor growth and poor weight
gain despite normal food intake, accumulation of thick sticky mucus, frequent chest infections, and
coughing or shortness of breath.
3. Treatment options include: Bronchodilators, Hypertonic saline (It hydrates the airway mucus
secretions and facilitates mucociliary function), Dornase Alfa (Enzyme that cleaves extracellular
DNA, which results in decreased viscosity of mucus), and aerosolized antibiotics such as
Tobramycin (TOBI®)
Dornase Alfa Inhale Solu. Pulmozyme® 1 mg/ml (2.5 ml)
Ivacaftor Tab Kalydeco® 150 mg
Nintedanib Cap Ofev® 100 mg , 150 mg
Pirfenidone Cap Esbriet® 267 mg
Tab Pirfenex® 200 mg
Combination Product
Lumacaftor + Ivacaftor Tab Orkambi® 200 mg + 125 mg
Aerosolized Antibiotics
Tobramycin Inhale Solu. TOBI® 300 mg/5 ml (amp)
Aztreonam Inhale Solu. Cayston® 75 mg/vial
Colistimethate Inhale Powder Colistin® 1 million IU
References
1- Sean C. Sweetman, Martindale: The Complete Drug Reference, 38th Edition
2- Lexi-comp: Drug information handbook, 2022 Ed.
3- Mary Anne koda-kimble, Applied Therapeutics: The clinical use of drugs, 11th Ed.
4- Joseph T. DiPiro, Robert L. Pharmacotherapy: A Pathophysiologic Approach, 11th Ed.
5- Comprehensive Pharmacy Review for NAPLEX 8 th Ed.
6- Community Pharmacy: Symptoms, Diagnosis and Treatment, By Paul Rutter, 2017 4th ed.
7- https://www.ncbi.nlm.nih.gov/pubmed/11534896
8- https://www.atsjournals.org/doi/abs/10.1164/ajrccm.160.1.9901063
9- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667286/
10- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625152/
11- https://www.nejm.org/doi/full/10.1056/NEJMoa1008378
GASTROINTESTINAL SYSTEM
Chapter 2: Gastrointestinal System
Part One: Introduction 2.9 - Drugs for Inflammatory bowel

disease - (IBD) (ulcerative colitis
Part Two:
and Crohn’s disease)
2.1 – Antacids a. Amino-salicylates
b. Some Corticosteroids
2.2 – Anti-Ulcer (Acid suppression) c. Some Immunosuppressant’s
drugs
A) Proton Pump Inhibitors 2.10- Products for flatulence and
B) H2 Receptor Antagonists abdominal gases
➢ Some combination products of PPIs a. For Adults
and H2Ras b. For Infants and children
C) Other agents that suppress
gastric acid secretion 2.11 - Enzymes preparation for
D) Other GI ulcers related drugs digestion support
2.12 – Gallstone solubilizing
2.3 – Laxatives agents
a. Stimulant Laxative
b. Bulk Forming Laxative 2.13 – Drugs for Hepatic (liver)
c. Stool Softeners detoxification
d. Osmotic Laxative
2.14 – Drugs for food allergy
e. Guanylate Cyclase-C agonists
f. Peripheral acting μ-opioid antagonist
g. Other drugs used for Constipation 2.17 - Preparations for anal and
rectal disorders (hemorrhoids)
2.4 – Bowel Cleansing Preparations
2.5 – Anti-Diarrheals
a. Anti-Motility drugs
b. Adsorbents
c. Other agents used for diarrhea
2.6 – Antispasmodics
a. Anticholinergics
b. Other antispasmodics
c. Combination products for IBS
d. Herbal Combination products for IBS
2.7 - Anti-Emetics and Prokinetics
2.8 – Drugs for the treatment of

Hiccups
Sam’s Guide: Chapter 2 – GIT
Chapter Two: Gastro-intestinal System
Part One:
1. Introduction:
➢ The gastrointestinal tract, also known as the digestive or alimentary tract, is the pathway
through which food passes as it is processed to enable the nutrients it contains to be absorbed
for use by the body.
➢ It consists of the mouth, esophagus, stomach, duodenum, small intestine, large intestine
(including the colon and rectum), and anus. In addition, a number of other organs are involved
in the digestion of food: the salivary glands in the mouth, the liver, pancreas, and gallbladder.
These organs, together with the gastrointestinal tract, form the digestive system.
➢ The digestive system breaks down the large, complex chemicals – proteins, carbohydrates, and
fats – present in the food we eat into simpler molecules that can be used by the body.
• The stomach holds food and passes it into the intestine. The lining of the stomach releases
gastric juice that partly digests food. The stomach wall continuously produces thick mucus
that forms a protective coating.
• The duodenum is the tube that connects the stomach to the intestine. Its lining may be
damaged by excess acid from the stomach.
• The pancreas produces enzymes that digest proteins, fats, and carbohydrates into simpler
substances; pancreatic juices neutralize the acidity of the food passing from the stomach.
• The gallbladder stores bile, which is produced by the liver, and releases it into the
duodenum. Bile assists the digestion of fats by reducing them to smaller units that are more
easily acted upon by digestive enzymes.
• The small intestine is a long tube in which food is broken down by digestive juices from
the gallbladder and pancreas. The mucous lining of the small intestine consists of tiny,
finger-like projections called villi that provide a large surface area through which the
products of digestion are absorbed into the bloodstream.
• The large intestine receives both undigested food and indigestible material from the
small intestine. Water and mineral salts pass through the lining into the bloodstream.
When a sufficient mass of undigested material, together with some of the body’s waste
products, has accumulated, it is expelled from the body as feces.
➢ Food is propelled through the gastrointestinal tract by rhythmic waves of muscular
contraction called peristalsis; Muscle contraction in the gastrointestinal tract is controlled by
the autonomic nervous system and is therefore easily disrupted by drugs that either stimulate
or inhibit the activity of the autonomic nervous system; Excessive peristaltic action may
cause diarrhea, and constipation may result from slowed peristalsis.
2. What Can go wrong in the Gastrointestinal tract?

➢ Inflammation of the lining of the stomach or intestine (gastroenteritis) is usually the result
of an infection or parasitic infestation.
➢ Damage may also occur through the inappropriate production of digestive juices, leading to
minor complaints like acidity and major disorders like peptic ulcers.
➢ The lining of the intestine can be damaged by abnormal functioning of the immune system IBD
(inflammatory bowel disease).
➢ The rectum and anus can become painful and irritated by damage to the lining, tears in the
skin at the opening of the anus (anal fissure), or enlarged veins (hemorrhoids).
➢ Constipation, diarrhea, and irritable bowel syndrome (IBS) are the most frequently
experienced gastrointestinal complaints, and they usually occur when something disrupts the
normal muscle contractions that propel food residue through the bowel.

➢ Many drugs for gastrointestinal disorders are taken by mouth and act directly on the
digestive tract without first entering the bloodstream; Such drugs include certain
antibiotics and other drugs used to treat infestations.
➢ Some antacids for peptic ulcers and excess stomach acidity, and the bulk-forming agents for
constipation and diarrhea, also pass through the system unabsorbed.
➢ However, for many disorders, drugs with a systemic effect are required, including antiulcer
drugs, opioid antidiarrheal drugs, and some of the drugs for inflammatory bowel disease.
➢ Medications available include:

Drug classification Examples
Antacids Aluminium hydroxide, Calcium carbonate
Antifoaming agents (anti flatulence) Dimeticone, Simethicone
Anti-ulcer drugs Proton pump inhibitors Esomeprazole, Lansoprazole, Omeprazole
H2 blockers Cimetidine, Famotidine
Others Sucralfate, Misoprostol
Antidiarrheal drugs Opioid related Co-phenotrope, Loperamide
Adsorbents Kaolin
Laxatives Stimulant laxative Bisacodyl
Bulk-forming laxative Ispaghula
Lubricants Liquid paraffin
Osmotic laxative Lactulose
Antispasmodic drugs Hyoscine, Otilonium
Drugs for irritable bowel syndrome Mebeverine
Anti-Emetics and Prokinetics Metoclopramide, Domperidone
Drugs for inflammatory bowel disease Mesalamine, Sulfasalazine
Drug treatment for gallstones Ursodeoxycholic acid
Drugs for Hepatic detoxification Milk Thistle
Drug treatment for pancreatic disorders Amylase, Lipase, Pancreatin, Protease
Drugs for rectal and anal disorders Combination products (cream, Oint. , gel)

Part Two:
2.1 Antacids
➢ Digestive juices in the stomach contain acid and enzymes that break down food before it passes
into the intestine. The wall of the stomach is normally protected from the action of digestive acid
by a layer of mucus that is constantly secreted by the stomach lining. Problems arise when the
stomach lining is damaged or too much acid is produced and eats away at the mucous layer.
➢ Excess acid that leads to discomfort, commonly referred to as indigestion, may result from
anxiety, overeating or eating certain foods, coffee, alcohol, or smoking; Some drugs, (aspirin
and non-steroidal anti-inflammatory drugs), can irritate the stomach lining and cause ulcers.
1. Antacids are basic compounds that neutralize hydrochloric acid in the gastric secretions; and
thus, relieve pain; They are simple chemical compounds that are mildly alkaline and some also
act as chemical buffers. Their chalky taste is often disguised with flavorings.
• They are used in the symptomatic management of gastrointestinal disorders associated with
gastric hyperacidity such as dyspepsia, gastro-esophageal reflux disease (GERD), and
peptic ulcer disease.
• By neutralizing stomach acid, antacids prevent inflammation, relieve pain, and allow the
mucous layer and lining to mend. When used in the treatment of ulcers, they prevent acid
from attacking damaged stomach lining and so allow the ulcer to heal.
2. Antacids are best given when symptoms occur (when required) or are expected, usually
between meals and at bedtime, their duration of action is short (about 30 minutes on an empty
stomach), but duration of action can be extended to 3 hours when given with or within 1 hour
after a meal.
3. Types of antacids: they are divided according to their base component as:
• Aluminium compounds: These drugs have a prolonged action and are widely used,
especially for indigestion and dyspepsia. They may cause constipation, but this is often
countered by combining this type of antacid with one containing magnesium.
Aluminium compounds can interfere with the absorption of phosphate from the diet,
causing muscle weakness and bone damage if taken in high doses over a long period. A high
blood level of Aluminium in people with kidney failure, may cause a dementia-like illness.
• Magnesium compounds Like the Aluminium compounds, these have a prolonged action. In
large doses magnesium compounds can cause diarrhea, and in people who have impaired
kidney function, a high blood magnesium level may build up, causing weakness,
lethargy, and drowsiness.
• Sodium bicarbonate: This antacid act quickly, but its effect soon passes. It reacts with
stomach acids to produce gas, which may cause bloating and belching. Sodium bicarbonate is
not advised for people with heart or kidney disease, because it can lead to
accumulation of water (edema) in the legs and lungs or serious changes in the acid-base
balance of the blood.
• Combined preparations Antacids may be combined with other substances called alginates
and antifoaming agents. Alginates are intended to float on the contents of the stomach
and produce a neutralizing layer to subdue acid that can otherwise rise into the
esophagus, causing heartburn. Antifoaming agents are used to relieve flatulence. In some
preparations, a local anesthetic is combined with the antacid to relieve discomfort in
esophagitis; but the value of these additives is not proved.
4. Antacid suspensions are more effective and work more quickly than tablets (of the same type
and quantity) the suspension is better due it acts faster and covers more area.
5. Patient should be instructed to chew the tablets thoroughly followed by a full glass of water to
ensure maximum therapeutic effect.
6. It might be appropriate for the patient to have both; tablet antacid may be taken during a day
at the work while suspension is taken at home.
7. Interactions: Antacids can affect the absorption of a number of drugs (via chelation and
adsorption) and the majority of these interactions are easily overcome by leaving a minimum
gap of (1-2) hours between the doses of each drug; Also, Antacids increase the PH of the
stomach, thus cause a premature release of enteric coated tablets or granules in the stomach
rather than the intestine.
8. Side effects of antacids
A. AL-containing antacids tend to be constipating, Mg-containing antacids tend
to cause osmotic diarrhea and are useful in patients who are slightly constipated.
Thus, combination products of AL and Mg salts cause minimum bowel
disturbances.
B. Antacids containing sod. Bicarbonate should be avoided in patients if sodium
intake should be restricted (e.g. in patient with CHF, hypertension).
9. Other drugs that may be combined with antacid formulations include Simethicone, which acts
as a defoaming agent to reduce excess gas in the stomach, and alginates, which form a gel or
foam on the surface of the stomach contents thereby impeding reflux and protecting the
esophageal mucosa from acid attack.
Trade name Dosage form Scientific name Concentration
Rennie® Tab Ca+ carbonate , Mg+ carbonate 680 mg + 80 mg
Syrup Ca+ carbonate , Mg+ carbonate (680 mg + 80 mg)/5 ml
Citrogram® Susp. Tartaric acid 26.5%
Citric acid 14.5%
Na bicarbonate 59%
Stomacol® Susp. AL(OH)3 , Mg(OH)2 (225mg + 195mg)/5ml
Maalus®, Malox® Tab , Susp. AL(OH)3 400 mg/10 ml
Moxal® Mg(OH)2 200mg/10 ml
Moxal PLus®, Tab , Susp. AL(OH)3 + Mg(OH)2 (225mg+200mg+25mg)
Acilox Plus® + Simethicone
Gaviscon® Tab , Susp. Na alginate, Ca+ Carbonate ----------------
Sodium hydrogen carbonate
Actonorm® Powder, Atropine , Peppermint Oil , 0.1 mg + 0.5 mg,
(Susp.) Mg Carbonate, Mg Trisilicate, 381.4 mg + 50 mg
Ca+ Carbonate, Na Bicarbonate, 145 mg + 373 mg
AL(OH)3 50 mg
Gel AL(OH)3 + Mg(OH)2 + Dimeticone 220mg + 200mg + 25 mg
Extra Notes about Antacids:
1. Small amounts of Aluminum and Magnesium are absorbed systemically and have the potential
to accumulate in patients with renal insufficiency and lead to toxicity, thus magnesium-
containing antacids should be avoided in patients with a creatinine clearance less than 30mL/
minute, and chronic use of aluminum-containing antacids in patients with renal failure should be
avoided.
2. High-dose regimens of Ca+ (4–8 g/day) in combination with alkalinizing agents (Na bicarbonate)
can produce the milk-alkali syndrome (i.e., hypercalcemic nephropathy with alkalosis).
3. Na bicarbonate should not be used for long periods of time (especially in the renal impaired
patient) because systemic alkalosis can result from the accumulation of bicarbonate.
Additionally, the high sodium content (274 mg sodium/g sodium bicarbonate) has been
associated with sodium retention and may pose a problem in patients with hypertension, ascites,
severe renal dysfunction, or heart failure.
4. Antacids may interfere with the absorption of many orally administered drugs (digoxin,
phenytoin, isoniazid, ketoconazole, Itraconazole, iron preparations) that require an acidic
environment for dissolution and absorption.
5. Antacids containing calcium, aluminum, or magnesium can bind to concomitantly administered
drugs and interfere with the absorption of drugs that are susceptible to complexation.
➢ Tetracyclines and the fluoroquinolones are susceptible to this interaction, as they bind to
divalent and trivalent cations. The bioavailability of ciprofloxacin is reduced by more than
50% when concomitantly administered with an antacid, because aluminum and magnesium
ions chelate with the antibiotic to form an insoluble and inactive complex. The administration
of ciprofloxacin 2 hours before an antacid increases ciprofloxacin bioavailability more than
when administered 2 hours after the antacid.
2.2- Anti-Ulcer (Acid suppression) drugs

➢ Normally, the linings of the esophagus, stomach, and duodenum are protected from the irritant
action of stomach acids or bile by a thin covering layer of mucus. If this is damaged, or if large
amounts of stomach acid are formed, the underlying tissue may become eroded, causing a peptic
ulcer (break in the gut lining).
➢ An ulcer often leads to abdominal pain, vomiting, and changes in appetite; the most
common type of ulcer occurs just beyond the stomach, in the duodenum.
➢ An organism found in almost all patients who have peptic ulcers, Helicobacter pylori, is believed
to be the main causative agent of peptic ulcers.
➢ The symptoms caused by ulcers may be relieved by an antacid, but healing is slow. The usual
treatment is with an anti-ulcer drug, such as a PPI, H2 blocker, sucralfate and bismuth.
A. Proton pump inhibitors (PPIs)

1. PPIs are the most potent inhibitors of gastric acid secretion and include Omeprazole,
Lansoprazole, Rabeprazole, Pantoprazole, and Esomeprazole.
• PPI suppresses gastric acid secretion by inhibition of the H+/K+-ATPase in the gastric
parietal cell; they inhibit 90-98% of 24-hour acid secretion.
2. PPIs are used for the treatments of gastric and duodenal ulcers; they are also used in
combination with Antibacterials for the eradication of Helicobacter pylori (a bacterium
that is common cause of ulcer); PPIs can be used for the treatment of dyspepsia and gastro-
esophageal reflux disease (GERD), they are also used for the prevention and treatment of
NSAID-associated ulcers.
3. A PPI can be used to reduce the degradation of pancreatic enzyme supplements in patients
with cystic fibrosis; They can also be used to control excessive secretion of gastric acid in
Zollinger–Ellison syndrome; high doses are often required
4. They are most effective when taken 30 to 60 minutes before meals; The once daily dose usually
given in the morning before meals, while twice daily dose given morning and night before meals.
5. Various PPI dosage forms and formulations exist and include the enteric-coated granules
contained in gelatin capsules (omeprazole, esomeprazole, and lansoprazole), and delayed
release enteric-coated tablets (Rabeprazole, Pantoprazole) the enteric coating prevents
degradation of the drug in stomach acid.
6. Adverse effects are usually few, but may include nausea, abdominal pain, constipation,
flatulence and diarrhea.
a. Hypergastrinemia occurs in 5-10% of long-time omeprazole users, Development of
hypergastrinemic state predisposes the patient to rebound hyper-secretion of gastric acid
following discontinuation of therapy.
b. PPIs have been associated with an increased risk of infections (pneumonias, enteric
infections) possibly owing to the ability of the microorganism’s ability to survive in a less
acidic environment. However, data suggest that they rarely lead to illness.
c. PPIs have been associated with interstitial nephritis, but this is an extremely rare finding.
(Only with high doses and long-term use > 3 years).
7. Prolonged therapy with agents that suppress gastric acid, such as the PPIs and H2 antagonists:
a. May result in low vitamin B12, because acid is required for its absorption in a complex with
intrinsic factor .
b. Also, will result in Low Iron Absorption → lead to Anemias.
c. Also, will result in Hypomagnesemia.
d. Another problem is the potential for incomplete absorption of calcium carbonate products.
An effective option would be to use calcium citrate as a source of calcium for patients
taking prolonged acid-suppressing medications, because the absorption of the citrate
salt is not affected by gastric pH.
e. Thus, long term therapies may Cause Neuropathies (Due to low vitamin B12) and increase risk
of fractures (Due ↓ in Ca+), to avoid → give supplements of B12 and Ca+.
8. A dosage reduction is not required in patients with renal insufficiency, but is recommended for
patients with severe hepatic impairment.
9. The US Food and Drug Administration (FDA) issued a labeling change for Clopidogrel and a safety
warning recommending providers to avoid the co-administration of (omeprazole,
omeprazole/sodium bicarbonate, or esomeprazole) with Clopidogrel.
a. This is because of the hypothesis that states: PPIs attenuates (decrease) the antiplatelet
effects of Clopidogrel and potentially increases the risk of cardiovascular effects.
b. Solutions include: (double Clopidogrel dose to 150 mg, separate the two drugs by at
least 8-12 hours, and switching to Pantoprazole).
c. There is no strong evidence to suggest switching from one PPI to another or that separating
the timing of doses has any clear benefit on reducing the effect of interaction.
d. FDA and AGA then published a statement notifying that this interaction is of a LOW
SIGNIFICANCE, and there is no need to alter or change the medications accordingly. (8)
10. A study was published stated that long term PPI is associated with Cancer, below some
explanations and available data:
a. There is no clinical evidence to suggest that long-term (>10 years) therapy progresses
to a higher grade of hyperplasia or gastric ECL carcinoid.
b. There is evidence to suggest a relationship between elevated serum gastrin concentrations
and ECL hyperplasia as a result of the PPIs’ profound ability to inhibit gastric acid secretion.
It has been hypothesized that this can progress to gastric carcinoid tumors (a precursor of
gastric cancer).
c. Bacterial overgrowth (secondary to PPI treatment) has been hypothesized to increase the
risk of gastric cancer, because bacteria in the stomach responsible for conversion of dietary
nitrates to nitrites can flourish at a higher pH and increase the development of N-
nitrosamines (a carcinogenic by-product).
11. Co-administration of other acid-suppressing agent with PPIs (such as H2-receptor
antagonists or Anticholinergics) will diminish the efficacy of the PPIs
a. Some patients when treated with PPIs will have nocturnal acid breakthrough, those patients
will benefit from the addition of H2-receptor antagonists at night to PPI regimen
b. (Nocturnal acid breakthrough is Presence of at least 60 continuous minutes of intragastric pH
less than 4 during the night, in patients taking a PPI twice daily before meals.
12. Some says all PPIs are the same; well that’s not quite true, they differ in their onset of action, and
in their safety profile regarding drug-drug interactions.
• The fastest acting PPI is Rabeprazole, it acts within few minutes (about 5 to 8 min), and hence
its named Rapi-prazole (from Rapid).
• The safest PPI regarding D-D interactions is Pantoprazole.
• The only PPIs that can be takin without regarding the food are Rabeprazole and
Pantoprazole, (can be taken before or after meal); Nexium® dosage form formulation does so.
• The highest affinity for H+/K+-ATPase pump PPI is Esomeprazole.
• The highest PPI with relative potency is Rabeprazole, then in 2nd place Esomeprazole.
13. PPIs (especially Rabeprazole), lowers serum TSH levels; thus, may be beneficial in patients with
hyperthyroidism, but PPIs should be added to the list of medications affecting the level of thyroid
hormone in patients with hypothyroidism treated with Levothyroxine replacement; those Patients
may need adjustment of their Levothyroxine dose. (7)
14. Regimen for the eradication of Helicobacter Pylori usually composed of proton pump inhibitor
(PPI), Clarithromycin, and either Amoxicillin or Metronidazole for 10–14 days; this regimen is
called (triple therapy) (4), other regimens are mentioned below.
• In penicillin-allergic patients, metronidazole is substituted for amoxicillin.
• Some Guidelines switch Metronidazole in H. Pylori eradication therapy with Levofloxacin.
Available H. Pylori Eradication Regimens (8)
Regimen Drugs and doses
Clarithromycin PPI (standard or double dose) BID + amoxicillin 1000 mg BID or
Triple metronidazole 500 mg TID + clarithromycin 500 mg BID for 10-14 days
Bismuth Quadruple PPI (standard dose) BID + Bismuth subsalicylate 300 mg QID or Bismuth
subcitrate 120-300 mg QID + metronidazole 250 QID or 500 mg TID-QID
+ tetracycline 500 mg QID d + PPI BID x 10-14 days
Concomitant PPI (standard dose) BID + clarithromycin 500 mg BID + amoxicillin 1000
mg BID + metronidazole or Tinidazole 500 mg BID for 10-14 days
Sequential PPI (standard dose) BID + amoxicillin 1000 mg BID for 5–7 days; then
PPI BID + clarithromycin 500 mg BID + metronidazole or Tinidazole 500
mg BID for 5–7 days
Hybrid PPI (standard dose) BID + amoxicillin 1000 mg BID for 7 days; then PPI
BID + amoxicillin 1 g BID + clarithromycin 500 mg BID + metronidazole
or Tinidazole 500 mg BID for 7 days
Levofloxacin triple PPI (standard dose) BID + levofloxacin 500 mg daily + amoxicillin 1000
mg BID for 10–14 days
Levofloxacin PPI (standard or double dose) BID + amoxicillin 1000 mg BID for 5-7
sequential days; then PPI BID + amoxicillin 1000 mg BID + levofloxacin 500 mg daily
+ metronidazole or Tinidazole 500 mg BID for 5-7 days
LOAD PPI (double dose) daily + levofloxacin 250 mg daily + metronidazole or
Tinidazole 500 mg BID + doxycycline 100 mg daily
15. Available Diagnostic tests for H. pylori infection include:
a) Serologic tests: Detect immunoglobulin (Ig) G to H. pylori in the serum by enzyme-linked
immunosorbent assay; it Cannot distinguish between active infection and past exposure. Because
antibodies persist for long periods after eradication, cannot use to test for eradication after
treatment.
b) Urea breath test: detects the exhalation of radiolabeled CO2 after the ingestion of 13C- or 14C-
radiolabeled urea. H. pylori hydrolysis of the radiolabeled urea results in CO2 production; It is used
to make a diagnosis and to test for eradication.
Recent use of antibiotics or PPIs can cause false-negative results in up to 40% of patients. Patients
should discontinue antisecretory agents or antibiotics at least 2 weeks before UBT testing or wait
4 weeks after treatment has ended before having the UBT performed.
c) Stool antigen tests: are polyclonal or monoclonal antibody tests that detect the presence of H.
pylori in stool; They can be used to make a diagnosis and to confirm eradication.
Recent use of bismuth, antibiotics, or PPIs can also cause false-negative results. Patients should
discontinue antisecretory agents or antibiotics at least 2 weeks before stool antigen testing or wait
4 weeks after treatment has ended before having the stool antigen test performed.
d) Rapid urease tests: detect the presence of ammonia (NH3) in a sample generated by H. pylori
urease activity, False-negative results can be caused by a partly treated infection, GI bleeding,
achlorhydria, or use of PPIs, H2RAs, or bismuth. Patients should discontinue antisecretory agents
for at least 1 week before the test is performed.
PPIs products
Scientific name D. form Trade name Concentration
Esomeprazole Cap Nexium® , Es-omperal® 20 mg , 40 mg
Vial Nexium® 40 mg
Sachet Nexium® 10 mg
Tab Esofag® 20 mg
Lansoprazole Cap Lanzor® , Lancid®, Monolitum® 15 mg , 30 mg
Oro Disp. Tab 15 mg
Sachet 15 mg
Dexlansoprazole Cap Dexilant® , Kapidex® 30 mg , 60 mg
Tab EC Retard Delaxise® 30 mg
Omeprazole Cap , Vial Losec® , Gasic®, Asiloc® Aprazole® , 20 mg , 40 mg
Lomac® , Emilok®
Rabeprazole Tab Aciphex® , Pariete® , Rabezole® 10 mg , 20 mg
Tab Ozo® 20 mg
Pantoprazole Tab Counterlac® , Protonix® , Pantium® 20 mg , 40 mg
Vial Protofix® 40 mg
Tenatoprazole Cap Acidlock® 20 mg , 40 mg
ILaprazole Cap , Tab Noltec® , Adiza® 5 mg , 10 mg , 20 mg
B. Histamine-2 Receptor Antagonists (H2RAs)

1. H2RAs include Cimetidine, Ranitidine, Famotidine, and Nizatidine.
2. H2RAs are competitive antagonists of histamine at the parietal cell's H2 receptor; they suppress
the normal secretion of acid by parietal cells and the meal-stimulated secretion of acid, they
accomplish this by two mechanisms:
➢ Histamine released by ECL cells in the stomach is blocked from binding on parietal cell H 2
receptors, which stimulate acid secretion.
➢ Other substances that promote acid secretion (such as gastrin and acetylcholine) have a
reduced effect on parietal cells when the H2 receptors are blocked.
3. H2RAs are used for the treatments of gastric and duodenal ulcers. They can be used for the
treatment of dyspepsia and gastro-esophageal reflux disease.
➢ Ranitidine when given by I.V. route should be diluted with 10 ml DW and given over at
least 10 minutes, because rapid I.V. injection may cause tachycardia or bradycardia and
can be complicated to cause even cardiac arrest and death, this is due to H2 antagonism in
coronary smooth muscles and cholinesterase inhibition.
4. Tolerance to the anti-secretory effect 0f H2RAs may develop after several days of regularly
scheduled (continuous) use but can be avoided by taking the H2RA only when needed.
5. Bioavailability is lower for Cimetidine, Famotidine, and Ranitidine because they are absorbed
incompletely and undergo first-pass metabolism resulting in 40% to 65% bioavailability; but the
bioavailability of Nizatidine is considered near 100% because this agent does not undergo first-
pass metabolism.
6. Hepatic metabolism is the principal pathway for the elimination of cimetidine, famotidine, and
ranitidine, whereas renal excretion is the major route for elimination of Nizatidine.
7. Cimetidine inhibits several CYP450 isoenzymes, resulting in numerous drug interactions
(e.g., theophylline, warfarin, and Clopidogrel); Avoidance of the combination or a reduction in the
dosage of these drugs may be required; Also switching to PPI would be reasonable, Ranitidine
has less potential for hepatic CYP450 drug interactions, while famotidine and Nizatidine do
not interact with drugs metabolized by the hepatic CYP450 pathway.
8. Cimetidine has a weak anti-androgenic effect, it also increases prolactin levels and may cause
Gynecomastia and Impotence in men; these effects are usually reversible.
➢ Cimetidine also can cause confusion in the elderly.
➢ Some Dermatologists uses Cimetidine for Hormonal Acne Due its Anti-Androgenic effect.
9. They are rarely used these days, most physicians and pharmacists prefer PPIs, because PPIs
are superior to H2RAs in reducing gastric acid secretion and mucosal healing, although
Ranitidine can be used as on need basis (due it acts within few minutes).
➢ People who suffer from infrequent heartburn may take either antacids or H2RAs for
treatment. The latter offer several advantages over antacids, including longer duration of
action (6–10 hrs. vs 1–2 hrs. for antacids), greater efficacy, and ability to be used
prophylactically before meals to reduce the chance of heartburn occurring.
10. Lafutidine, a new type of H2RAs, has a unique mechanism of action:
a) Activates calcitonin gene-related peptide, resulting in the stimulation of nitric oxide (NO)
and regulation of gastric mucosal blood flow.
b) Increases somatostatin levels; thus, resulting in less gastric acid secretion.
c) Causes the stomach lining to generate more mucin.
d) Inhibits neutrophil activation; thus, preventing injury from inflammation.
e) blocks the attachment of Helicobacter pylori to gastric cells.
11. A 31-study review found that overall risk of pneumonia is about 1 in 4 higher among H2RAs
users; named (Use of acid-suppressive drugs and risk of pneumonia: a systematic review and
meta-analysis) and published on pubmed.
H2RAs products
Cimetidine form
Tab Tagmet® 200 mg , 400 mg
Amp Tagmet® , Tagadin® 200 mg
Ranitidine Tab Zantac® , Peptacid® , Histac® 150 mg , 300 mg
Sachet Rani® , Aciloc® 75 mg , 150 mg
Amp Rantidine® 150 mg
Famotidine Tab Ulceran® , Famosam® 20 mg , 40 mg
Tab Pepcid® 20 mg
Nizatidine Cap Axid® 150 mg , 300 mg
Roxatidine Cap Roxit® , Roxane® , Roxagen® 75 mg , 150 mg
Lafutidine Tab Stogar® , Lafaxid® 10 mg
Combination products of some PPIs and H2RAs
Scientific name(s) D. form Trade name concentration
Omeprazole + Na Bicarbonate Cap Zegerid®, Aprazole pls® 20 mg + 100 mg
Omeprazole + Aspirin * Cap Asp Plus® 20 mg + 81 mg
Omeprazole + Ketoprofen * Cap Axorid® (20 mg + 100 or 200 mg)
Esomeprazole + Naproxen * Tab Vimovo® 20 mg + 500 mg
Esomeprazole + Meloxicam * Tab Rumonal Pro® 20 mg + 15 mg
Omeprazole + Domperidone Tab Aprazole D® 40 mg + 10 mg
Rabeprazole + Domperidone Tab Dorafem® 20 mg + 10 mg
Pantoprazole + Domperidone Tab Ripane® 40 mg + 30 mg
Pantoprazole + Ranitidine Tab RaniPan® 40 mg + 150 mg
Famotidine + Ibuprofen * Tab Duexis® 26.6 mg + 800 mg
Famotidine + Mg(OH)2 Chew. Tab Gastroprotect® 10 mg + 165 mg
+ Ca+ Carbonate + 800 mg
* Those are NSAIDs (anti-inflammatory) for more info see chapter 9.
** Domperidone is an anti-emetic and prokinetic (see below section 8).
C. Other agents that suppress gastric acid secretion:
These are anticholinergics, works by blocking the activity of (acetylcholine) in the body, which
decreases secretions of gastric acid. (They are also used to treat extra salivation and doodling;
some is used as pre-anesthetic medication to dry up the mucosal secretions).
Glycopyrrolate * Tab Cuvposa , Robinul
® ® 1 mg , 2 mg
Inj. Solu Glycopyrronium® 0.2 mg/ml
Mepenzolate Tab Cantil ® 25 mg
Pirenzepine ** Tab Gastrozepin 25 mg
Methscopolamine Tab Pamine® 2.5 mg , 5 mg
Notes:
1. Glycopyrrolate has been used topically and orally to treat hyperhidrosis (condition characterized
by abnormally increased sweating/perspiration). Since it reduces the body's sweating ability, it can
even cause fever and heat stroke in hot environments.
➢ It’s also called (Glycopyrronium) as a scientific name; It’s also used as an inhaler for the
treatment of Asthma (see chapter 1, section 1.3).
2. Pirenzepine is an M1 selective antagonist, is used in the treatment of peptic ulcers, as it reduces
gastric acid secretion and reduces muscle spasm.
D. Other GI ulcers related drugs:

Bismuth subcitrate * Tab Bismul®, Bismuth Arya® 120 mg
Bismuth subcitrate Cap Pylera® 140 mg + 125 mg
+ Tetracycline + Metronidazole + 125 mg
Omeprazole + Amoxicillin Cap DR Talicia® 10 mg + 250 mg
+ Rifabutin + 12.5 mg
Rebamipide Tab Mucosta® , Rebagen® 100 mg
Charcoal (antidote) Tab Eucarbon® 250 mg
Sucralfate Tab Ulcifat®, Antepsin® 1 gm
Misoprostol Tab Cytotec® 200 mcg
Notes:
1. Bismuth subcitrate is a chelating agent, has an antibacterial effect and an anti-inflammatory
effect; with possible antidiarrheal effect (due to chelating).
➢ May cause black discoloration of the tongue and stool.
2. Pylera® is mainly given for H. Pylori eradication; and usually with a PPI.
➢ Taken as 3 capsules every 6 hours (12 cap/day) for 10 days with PPI twice a day.
3. Talicia® is specifically indicated for the treatment of H. pylori infection in adults.
➢ Taken as 4 capsules every 8 hours (12 cap/day) for 14 days
4. Rebamipide is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of
gastritis; It works by enhancing mucosal defense, scavenging free radicals, and temporarily activating
genes encoding cyclooxygenase-2 (act by increasing effects of gastric mucosal prostaglandin E2 and
protective effect of gastric mucosa; It also increases gastric mucus and blood flow in gastric mucosa).
5. Sucralfate provides a direct mucosal barrier; modulates pepsin, mucus activity, bicarbonate
secretion, and tissue growth repair, also it forms ulcer-adherent complex, thus protect the ulcer from
acids, bile salts and allows it to heal.
➢ It requires an acidic pH for activation; thus, PPIs and H2RAs may reduce its effect.
➢ Useful in the prevention of stress ulcers; but it does not prevent NSAIDs induced ulcers.
6. Misoprostol is a prostaglandin analogue, which is used to inhibit gastric acid secretion and protect
gastric mucosa, it is also used for pregnancy termination and may be abused to induce illegal
abortions, its effects are dose dependent including Cervical dilation.
2.3- Laxatives (Constipation drugs)
1. Constipation refers to bowel movements that are infrequent or hard to pass, the stool is often
hard and dry; Other symptoms may include abdominal pain, bloating, and feeling as if one has
not completely passed the bowel movement.
➢ Another definition is a symptom-based disorder defined as unsatisfactory defecation and is
characterized by infrequent stools, difficult stool passage, or both.
2. Complications from constipation may include Hemorrhoids, anal fissure or fecal impaction,
the normal frequency of bowel movements in adults is between three per day and three per
week; Babies often have three to four bowel movements per day while young children typically
have two to three per day.
➢ Certain drugs may be constipating: for example, opioid analgesics, tricyclic
antidepressants, and antacids containing aluminium.
➢ Some diseases, such as hypothyroidism (an underactive thyroid gland), and Parkinson
disease can also lead to constipation.
➢ Reduced fiber and water intake also causes constipation.
Notes:
1. Laxatives promote defecation and are used in the treatment of constipation and for bowel
evacuation before investigational procedures such as endoscopy.
2. Before prescribing laxatives, it is important to be sure that the patient is constipated and that the
constipation is not secondary to an underlying undiagnosed complaint.
➢ Danger signs include: Symptoms for more than 1–2 weeks despite treatment, Considerable
pain or cramping, Presence of fever, Blood in the stool, Sudden Weight loss, Paraplegia,
quadriplegia (if one of those signs is present directly refer to a doctor).
3. Non pharmacological treatment of constipation includes:
a) Increasing fluid intake to 6–8 glasses of water per day, although minimal evidence to support
efficacy if dehydration is not present,
b) Increase dietary fiber to 20–30 g/day.
c) Incorporate or increase exercise to 3–5 days/week.
4. Type of laxative:
Type of laxative Example(s) Approximate
onset of action
1-Stimulant laxative Senna , Bisacodyl , Sodium Picosulfate, and Oral: 6-12 hr.
Glycerin (supp.) , Castor Oil Rectal: 0.5-1 hr.
2-Bulk-forming laxative Methylcellulose , Bran , Sterculia 1-3 days
and Ispaghula Husk (Metamucil ) ®
3-Lubricant (stool softeners) Liquid paraffin 6-8 hours

4-Osmotic laxative Lactulose , Sorbitol 1-2 days
5-Saline Osmotic laxatives Magnesium citrate, magnesium hydroxide, 15 min to 3 hrs.
sodium phosphate
6-Guanylate Cyclase-C agonist Linaclotide, Plecanatide 1 – 6 days
7-Peripheral acting μ-opioid Methylnaltrexone, Naloxegol, Alvimopan Within 4 hrs.
antagonist (PAMORAs)
5. Product selection guidelines

Patient Preferred laxative
1- Pregnant women Bulk-forming laxative or Lactulose may be used.
2- Breast-feeding mother Bulk-forming laxative
3- Children and infants Glycerin(supp.) , Lactulose
4- Advanced age (elderly) Bulk-forming laxative, Also Lactulose, Glycerin (supp.) are safe.

A- Stimulant laxatives:
1. Stimulants cause the bowel muscles to contract, increasing the speed at which fecal matter
goes through the intestine.
2. Prolonged use may result in loss of colonic smooth muscle tone; Stimulant laxatives should
therefore be used for only short periods of a few days.
3. Bisacodyl tablet is enteric-coated; therefore, it should be swallowed whole and should not
be taken within one hour of antacid or milk as this will lead to dissolution of the coating
and release of the drug into the stomach and cause gastric irritation.
4. Usual Doses: Senna tab and Bisacodyl 5 mg tab: Adult dose: usually 2 tablets (usually take
at night to produce the effect next morning). While the dose of supp. Is one supp. (usually in
the morning), Glycerin suppositories: The patient should expect to have bowel movement
quickly (within one hour).
5. Senna may color the urine yellowish-brown at acid pH, and red at alkaline pH
6. Castor Oil is also given to ease the delivery of pregnant women. (C.I in early Pregnancy due
it causes uterine contractions → dislodging of the fetus)
B- Bulk-forming laxative:
1. Bulk-forming laxatives relieve constipation by increasing stool mass which stimulates
peristalsis; the laxative effect can take several days to develop.
2. Bulk-forming laxative preparations should not be taken immediately before going to bed,
because there may be a risk of esophageal blockage if the patient lies down directly after
taking them, also they can cause gas and bloating
3. When recommending the use of a bulk laxative, the pharmacist should advise that an
increase in fluid intake would be necessary; (they require water to be effective).
4. Methylcellulose, Ispaghula, and Sterculia are useful in patients who cannot tolerate bran.
Also, Methylcellulose also acts as a Stool softener.
C- Stool Softener (Liquid paraffin): its use declined nowadays due to many disadvantages.
these preparations make bowel movements softer and easier to pass without increasing their
bulk, but prolonged use can interfere with the absorption of some essential vitamins.
D- Osmotic laxatives: (3) these include Lactulose, Macrogols and Magnesium Salts
they act by keeping water in the bowel, and thereby make the bowel movements softer; This
also increases the bulk of the feces and enables them to be passed more easily.
1. About lactulose:
a. It can be taken by all age groups, and can be safely used in pregnancy.
b. It is intensely sweet in taste (but it is safe for diabetic patients).
c. Adult laxative dose: 15 ml twice daily, Child dose: 2.5 – 5 ml twice daily.
d. It discourages the proliferation of ammonia-producing organisms. It is therefore useful
in the treatment of hepatic encephalopathy (in patients with liver cirrhosis).
2. About Macrogols (Movicol®):
a. Adult and Child dose 1-3 sachets daily
b. Safe in pregnancy
E- Guanylate Cyclase-C agonists: This type of laxative changes stool consistency.

by increasing the amount of water into the GI lumen and increases gastrointestinal
movement, they include (Linaclotide, Plecanatide); which are both C.I. in children below 6
years old, and best to be avoided in patients below 17 years old.
a. Linaclotide is indicated for the treatment of irritable bowel syndrome with constipation
(IBS-C) and chronic idiopathic constipation (CIC).
b. Plecanatide is approved for chronic idiopathic constipation (CIC) only.
F- Peripheral acting μ-opioid antagonist (PAMORAs):
1. These are used to reverse adverse effects caused by chronic use of opioids; interacting with
receptors outside the central nervous system (CNS), mainly those located in the
gastrointestinal tract; PAMORAs are designed to specifically inhibit certain opioid receptors in
the gastrointestinal tract and with limited ability to cross the blood-brain barrier; thus PAMORAs
do not affect the analgesic effects of opioids within the central nervous system.
➢ PAMORAs are used in the treatment of opioid-induced bowel dysfunction (OIBD) or
opioid-induced constipation (OIC), a potential adverse effect caused by chronic opioid use.
PAMORAs act on the three pathophysiological mechanisms of this adverse effect: They act
on gut motility, gut secretion and sphincter function.
2. They include:
a. Methylnaltrexone: approved for Opioid Induced Constipation (IOC) in palliative care
patients and for OIC in adult patients with non-cancer pain, when response to laxatives has
not been sufficient.
b. Naloxegol: indicated for (IOC) in adults with chronic non-cancer pain, contraindicated with
use of strong CYP3A4 inhibitors or in patients with obstruction.
c. Alvimopan: indicated for postoperative ileus after bowel resection with primary
anastomosis; long-term use associated with myocardial infarction.
d. Naldemedine: Opioid antagonist with binding affinities for mu-, delta-, and kappa-opioid
receptors; it is a derivative of naltrexone to which a side chain has been added that
increases the molecular weight and the polar surface area, thereby reducing its ability to cross
the blood-brain barrier. It is indicated for (OIC) in adults with non-cancer pain.
General Notes:
• Tap water enemas may be used to treat simple constipation. The administration of 200 mL of
water by enema to an adult often results in a bowel movement within 1.5 hours.
• Soapsuds are no longer recommended in enemas because their use may result in proctitis or
colitis.
• Whole-bowel irrigation with PEG−electrolyte lavage solution has become popular for colon
cleansing before diagnostic procedures or colorectal operations.
• Saline cathartics are composed of relatively poorly absorbed ions such as magnesium, sulfate,
phosphate, and citrate, which produce their effects primarily by osmotic action to retain fluid
in the GI tract. These agents may be given orally or rectally.
A) Stimulant laxative
Bisacodyl EC Tab Dulcolax® 5 mg
Supp. Dulcolax®, Laxamid® 5 mg, 10 mg
Glycerin (or) Glycerol Supp. Glycerol® 400 mg, 700 mg
Enema Baby Enema® 2.25 gm
Glycerin + Gelatin Supp. Glycerin® (1.4 gm + 0.32 gm),
(0.7 gm + 0.32 gm)
Senna Extract Tab Senade® 13.5 mg
Sennosides Chocolated Tab Exlax® 15 mg
Na+ Picosulfate Cap Dulco-lax Pico® 2.5 mg
Drops PicoLax® 7.5 mg/ml (15 ml)
Elixir 5 mg/5 ml
Docusate Na+ Cap Dioctyl® 100 mg
Enema Norgalax® 120 mg
Castor oil Emulsion Castor oil® 60 ml

B) Bulk-forming laxative drug
Methylcellulose Powder, Methylcellulose®, 500 mg
Tab Celevac®
Ispaghula husk Powder (Sachets) Fybogel®, Ispagel® 3.5 gm/sachet
Sterculia Granules Normacol® 62%
Sterculia + Frangula Granules Normacol Plus® 62% + 8%
* Bulk Laxatives are useful in controlling diarrhea associated with diverticular disease.
Combination products: Stimulant Laxative + Bulk Laxative

Ispaghula husk + Plantago ovate Granules Agiolax® ---------------
+ Senna
Ispaghula husk + Senna Granules Manevac® 54.2% +
Castor Oil + Glycerol + Gelatin Cap Castolax® 12.4%
1000 mg cap
* Ispaghula is a Bulk Laxative,
* Senna is a stimulant Laxative.
C) Stool Softeners (No Longer Recommended)
D) Osmotic laxative drugs

Lactulose Oral Solu. , Duphalac® 10 gm/15 ml
Rectal Solu.
Lactulose + Inulin Oral Solu. Peristil® 200 ml solu.
+ Fructo-oligosaccharide *
Lactitol + Fiber Oral Solu. Lactofibre® (2.5 gm + 3 gm) Per 10 ml
Macrogol (PEG) + Powder for oral Movicol® 13.125 gm +
Na Chloride + Solution 350.7 mg +
Na Bicarbonate + 178.5 mg +
K Chloride 46.6 mg
Sorbitol Solu. Irragate ® 3 gm/100 ml (3%)
* Fructo-oligosaccharides and Inulin promote the natural balance of the intestinal bacterial flora.
E) Guanylate Cyclase-C agonists:

Linaclotide Cap Linzess®, Constella® 145 mcg , 290 mcg
Plecanatide Tab Trulance® 3 mg
F) Peripheral acting μ-opioid antagonist (PAMORAs):

Alvimopan Cap Entereg® 12 mg
Naloxegol Tab Movantik® 12.5 mg , 25 mg
Naldemedine Tab Symproic® 0.2 mg
Methylnaltrexone Inj. Solu. Relistor® 8 mg/0.4 ml
Tab 150 mg
G) Other drugs used for constipation (2)
Lubiprostone Cap Amitiza ® 8 mcg , 24 mcg
Tegaserod (Tegaseride) Cap , Inj. Solu. Zelnorm ® ---------------
Renzapride Tab Renzapride ® 1 mg , 2 mg , 4 mg
Prucalopride Tab Resolor®, Resotran® 1 mg , 2 mg
Tenapanor Tab Ibsrela® 50 mg
Notes:
1. Lubiprostone is a chloride channel activator that acts locally on the gut to accelerate
genitourinary transit time and delay gastric emptying. It is approved for chronic idiopathic
constipation and constipation predominant IBS in adults.
a. results in intestinal fluid secretion; can reduce bloating and abdominal pain.
b. dose is 24 mcg twice daily for constipation and 8 mcg twice daily for IBS-C.
c. need negative pregnancy test before use.
2. Tegaseride (or Tegaserod) is used for treatment of women who have irritable bowel syndrome
(IBS) with constipation, But it was withdrawn from the U.S. market on 2007, due to a higher
chance of heart attack, stroke, and worsening chest pain that can become a heart attack.
3. Renzapride is a gastroprokinetic agent and antiemetic which acts as a full 5-HT4 full agonist
and 5-HT3 antagonist, it’s used for the treatment of constipation-predominant irritable bowel
syndrome (IBS-C). It is also potentially effective for irritable bowel syndrome with alternating
stool pattern (IBS-A).
4. Prucalopride is a selective, high affinity 5-HT4 receptor agonist, which targets the impaired
motility associated with chronic constipation, thus normalizing bowel movements.
a. Elicits GI prokinetic actions that stimulates colonic peristalsis.
b. indicated for chronic constipation only when other Rx fails.
2.4– Bowel Cleansing Preparations

1. Bowel cleansing preparations are used before colonic surgery, colonoscopy, or radiological
examination to ensure the bowel is free of solid contents, they are not treatments for
constipation.
2. Bowel cleansing preparations should be used with caution in patients with fluid and electrolyte
disturbances. Renal function should be measured before starting treatment in patients at risk of
fluid and electrolyte disturbances; Bowel cleansing preparations should be used with caution in
colitis (avoid if acute severe colitis), in children, in the elderly, or in those who are debilitated.
3. To use Bowel Cleansers: Empty the content of the sachet into 1 Liter of water and stir until the
powder is completely dissolved, then drink 1 glassful of the solution every 10 minutes until all
the solution has been consumed. Repeat the step with each sachet as instructed.
Scientific name D. form Trade name concentration
Macrogol + Na Sulfate Sachets Klean-Prep®, 59 gm + 5.685 gm
+ Na+ Bicarbonate + NaCL + KCL Coloclean®, Fortrans® +1.68 gm +1.46 gm + 743 mg
Macrogol + Na Sulfate Sachets Moviprep® 100 gm + 7.5 gm
+ NaCL + KCL 2.691 gm + 1.015 gm
Mg+ Carbonate + Citric acid Sachets Citramag® 11.57 gm + 17.79 gm
Na+ Picosulfate + Mg+ Citrate Sachets Picolax®, CitraFleet® 10 mg/sachet
Na+ Picosulfate + Mg+ Oxide Sachets Picoprep® 10 mg + 3.5 gm
+ Citric acid + 12 gm
Monosodium phosphate Tab Colokit® 1102 mg
+ Anhydrous disodium phosphate + 398 mg
2.5- Anti-Diarrheals
1. Diarrhea is an increase in the fluidity and frequency (more than 3 per day) of bowel
movements. In some cases, diarrhea protects the body from harmful substances in the intestine
by hastening their removal.
➢ The most common causes of diarrhea are viral infection, food poisoning, and parasites, but
it also occurs as a symptom of other illnesses; also, it can be a side effect of some drugs.
➢ Diarrhea may also be caused by anxiety.
➢ Danger signs include: Immunocompromised, Presence of fever, Blood in the stool, Sudden
Weight loss, suspected invasive infection.
o if one of those signs is present directly refer to a doctor.
2. The main aim in the management of acute diarrhea is the correction of fluid and electrolyte
depletion with rehydration therapy; this is especially important in infants and young
children and anti-Diarrheals are not generally recommended for this age group.
➢ Zinc supplements have been shown to reduce the incidence, intensity, or duration of
acute diarrhea in children, the WHO/UNICEF recommend that children with acute diarrhea
also receive zinc (10 mg of elemental zinc/day for infants younger than 6 months; 20 mg of
elemental zinc/day for older infants and children) for 10 to 14 days.
➢ Probiotics (Lactobacillus species) have been shown to decrease the duration of infectious
and antibiotic-induced diarrhea (AAD) in adults and children; these actions due to
Competition with pathogenic organisms, production of antimicrobial substances, and
enhancement of immune response.
1- Anti-motility drugs (opioid related) [Loperamide, (Diphenoxylate + Atropine)]

These decrease the intestinal muscles propulsive activity so that fecal matter passes more
slowly through the bowel, avoid if suspected invasive infection.
➢ Loperamide is pregnancy category B.
A) Anti-motility drugs are not recommended for acute diarrhea in young children, in the UK, both
Diphenoxylate and Loperamide are not licensed for children under 4 years of age, in the
USA, Loperamide is not recommended for children under the age of 2 years.
Adult doses: * Loperamide: initially 2 tablets followed by 1 tablet after each loose stool;
(16 mg/day maximum).
* Diphenoxylate + Atropine: 4 tablets initially followed by 2 tablets every 6 hours.
B) Codeine is used as an anti-motility drug for the treatment of acute diarrhea, it’s given as 30 mg
3-4 times per day. (Codeine is also an analgesic and an antitussive).
2- Adsorbents (pectin + kaolin)

These absorb water and irritants in the bowel, resulting in larger, firmer stools at less frequent
intervals.
➢ Kaolin is a clay-like powder believed to work by attracting and holding onto the
bacteria or germ that may be causing the diarrhea.
➢ Kaolin has been used for years in combination with pectin for diarrhea; However, in April
2003, the U.S. (FDA) found that there wasn't enough scientific support for kaolin's use
in treating diarrhea. Since April 2004, drug manufacturers have not been allowed to put
kaolin in diarrhea medicine.
➢ Adsorbents such as kaolin are not recommended for acute diarrheas.
➢ Kaolin can form insoluble complexes with some drugs in the gastrointestinal tract and reduce
their absorption; oral doses should not be taken at the same time.
➢ Bulk-forming Laxatives, such as Ispaghula, methylcellulose, and Sterculia (section 3) are
useful in controlling diarrhea associated with diverticular disease.
3- Oral rehydration solution (ORS)
1. A premixed solution or sachets of powder for
reconstitution are available; these contain sodium
as chloride and bicarbonate, glucose and potassium
2. Only water should be used to make the solution
and that boiled and cooled water should be used
for children < 1 year.
3. Stability of the ORS after reconstitution: After
reconstitution, any unused solution should be
discarded after 1 hour of preparation unless it
stored in refrigerator where it may be kept for 24
hours.
4. Dose of ORS: See table →
A) Anti-Motility drugs
Diphenoxylate + Atropine Tab
1 Lomotil® , Entero stop® 2.5 mg/0.025 mg
Loperamide 2 Tab Vacontil® , Diarrhea stop® 2 mg
Cap Imodium® 2 mg
Syrup Imodium® 1 mg/5 ml
Loperamide + Simethicone Caplet
3 Imodium plus® 2 mg + 125 mg
Difenoxin + Atropine Tab Motofen® 1 mg/0.025 mg
Opium tincture Oral Liquid Paregoric® 2 mg/5 mL
Notes:
1. Atropine is added in sub-therapeutic quantity to discourage deliberate overdose of
Diphenoxylate, Difenoxin (opioids)
2. The FDA issued a warning about Loperamide in 2016 = (in high doses, it can cause serious heart
problems – including abnormal heart rhythm - that can lead to death).
3. Simethicone is an anti-Flatulence.
4. Opium tincture contain morphine → inhibit GI motility, used in Acute diarrhea, Chronic orphan
diarrhea, it should not be used in diarrhea due to poisoning
B) Adsorbents
Kaolin + pectin Susp. Pectokal , Pecta
® ® 1 gm + 0.02 gm
Polycarbophil * Tab Mitrolan , Equalactin
® ® 625 mg
Chewable Tab 625 mg
Diosmectite ** Sachets Smecta ® 3 gm
Tannate Gelatin ** Cap Tasectan ® 500 mg
Sachets 250 mg
Attapulgite Tab Diasorb ® 600 mg
Oral Liquid K-Pek ® 750 mg/15 ml
* Polycarbophil is also a bulk producing laxative that restores normal moisture levels in
intestine
** Tannate acts mechanically by protecting inflamed intestinal mucosa, due its ability to form a
protective, protein-based mucoadhesive film which forms a complex with the mucoproteins
responsible for local inflammation and promotes their precipitation and elimination in the feces.
** Diosmectite is an activated natural Aluminosilicate clay consisting of a double Aluminium
and Magnesium silicate.
C) Other drugs used for Diarrhea
Bismuth subsalicylate Tab Kaopectate , Pepto B 262 mg , 525 mg
® ®
Oral Susp. 262 mg/15 ml , 525 mg/15 ml

Lactase Oral drops Lactaid® 1,250 units/4 drops
Lactobacillus acidophilus Tab, cap Vitalatic B®, Lactol® -------------------------
+ Lactobacillus bulgaricus Drops Enterolactis ®
Lactobacillus Species Sachet Biolact® 5 billion unit + 10 mg zinc

+ Zinc Sulphate + Inulin
Octreotide Inj. Solu. Sandostatin® 0.1 mg/ml , 0.5/ml , 1mg/ml
Alosetron Tab Lotronex ® 0.5 mg , 1 mg
Racecadotril Cap Hidrasec ® 100 mg
Granules 10 mg/sachet , 30 mg/sachet
Crofelemer Tab Fulyzaq® 125 mg
Eluxadoline Tab Viberzi® 75 mg , 100 mg
Telotristat Tab Xermelo® 250 mg
Notes:
1. Bismuth has Antimicrobial + anti-inflammatory effect, while subsalicylate has the anti-secretory
effect, generally it’s used in the treatment of diarrhea associated with H. pylori infections, and
often used for treatment or prevention of (traveler’s diarrhea).
➢ It also binds toxins in the intestinal tract, may cause Stool discoloration.
➢ avoid in salicylate allergy, age <12 years, and in pregnancy.
2. Lactase is an enzyme that digests lactose (the naturally occurring sugar in milk), used for Diarrhea
due to the Lactose Intolerance.
3. Lactobacillus preparation is intended to replace colonic micro normal flora; This supposedly
restores intestinal functions and suppresses the growth of pathogenic microorganisms, generally
used to normalize GIT in Irritable Bowel Syndrome (IBS).
4. Octreotide, a synthetic octapeptide analogue of endogenous somatostatin, it blocks the release of
serotonin and other active peptides and is effective in controlling diarrhea and flushing.
➢ Used for managing diarrhea associated with carcinoid tumors.
➢ Used in HIV-associated diarrhea.
➢ Also is given as an infusion for management of acute hemorrhage from esophageal varices
in liver cirrhosis on the basis that it reduces portal venous pressure.
➢ Used in the treatment of refractory hypoglycemia in neonates and sulphonyl urea induced
hypoglycemia in adults.
➢ associated with adverse effects such as Hyperglycemia, gallstone formation (cholelithiasis),
nausea, and abdominal pain.
5. Alosetron is a 5-HT3 antagonist used for the management of severe diarrhea-predominant irritable
bowel syndrome (IBS) in women only, it was withdrawn from the market in 2000 owing to the
occurrence of serious life-threatening gastrointestinal adverse effects (colonic ischemia), but was
reintroduced in 2002 with availability and use restricted.
6. Racecadotril reduce intestinal motility and has an anti-secretory effect.
➢ It is an oral enkephalinase inhibitor for use in the treatment of acute diarrhea; it acts by
preventing the degradation of endogenous enkephalins.
➢ Racecadotril reduces hypersecretion of water and electrolytes into the intestinal lumen;
thus, reducing the incidence and duration of acute diarrhea and reduces diarrhea-associated
symptoms, also results in significant reductions in stool output.
7. Crofelemer is indicated for non-infectious diarrhea in adult patients with HIV, AIDS who are
receiving antiretroviral therapy.
8. Eluxadoline is μ-opioid receptor agonist, it is indicated for diarrhea-predominant irritable bowel
syndrome (IBS-D).
2.6- Antispasmodics
1. Used for smooth muscle contraction, especially in tubular organs of the gastrointestinal tract, the
effect is to prevent spasms of the stomach, intestine or urinary bladder.
2. Anticholinergic/antispasmodic agents inhibit the action of acetylcholine; they stop the
transmission of parasympathetic nerve impulses → lessens the spasms of smooth muscle.
A) Antimuscarinics (Hyoscine butyl-bromide)
1. Used for symptomatic relief of gastro-intestinal disorders due to smooth muscle spasm.
2. Antimuscarinics are contraindicated in patients with prostatic enlargement, glaucoma.
3. They should be used with caution in the elderly.
B) Other antispasmodics (Mebeverine, Alverine, Drotaverine) are used to relieve pain in
irritable bowel syndrome; They have no anticholinergic side effects.
A) Antimuscarinics/Anticholinergics:
Atropine Tab Atreza® 0.4 mg , 0.6 mg
Hyoscine butyl bromide Amp Buscopan® , Scopinal® 10 mg/2 ml
Tab Buscopan®, Spasmosam® 10 mg
Scopolamine Metho-nitrate Syr. Kimidal® 0.12 gm/5 ml
Prifinium Bromide Tab Riabal® 30 mg
Amp Riabal® 15 mg/2 ml
Syrup Riabal® 7.5 mg/5 ml
Otilonium Bromide Tab Spasmomen® 40 mg
Tiemonium methyl-sulfate Tab , Supp. Visceralgine® 50 mg (tab) , 20 mg (supp)
Oral Syrup Spasmofree® 10 mg/5 ml
Amp 5 mg/2 ml
Propantheline bromide Tab Pro-Banthine® 15 mg
Dicyclomine * Tab , Cap Bentyl® , Spasmorest® 20 mg (Tab) , 10 mg (Cap)
* Dicyclomine = Dicycloverine, they are the same drug.
B) Other antispasmodics
Mebeverine HCL Tab Duspatalin®, Colospasmine® 135 mg
Meva® , Antispasmin® , Mevir®
Cap Duspatalin Retard® , ColoFac MR® 200 mg
Alverine Cap Spasmonal® 60 mg
Cap Spasmonal Forte® 120 mg
Peppermint Oil Cap Mintec® , Colpermin® 0.2 ml/Cap , 200mg
Pinaverium Tab Dicetel® , Eldicet® 50 mg , 100 mg
Drotaverine Tab Dot®, Dotarin®, Dover®, Doverin® 40 mg , 80 mg
Trimebutine Tab , Susp. Debridat® 100 mg
Phloroglucinol Tab Spasfon® 80 mg
+ Trimethylphloroglucinol + 80 mg
1. Peppermint Oil causes heartburn, it can worsen GERD, but can improve symptoms in IBS.
2. Drotaverine is also prescribed for patients with renal colic as a muscle relaxant, as well as for
pregnant women to accelerate labor.
3. Trimebutine is a regulator of digestive motility, it has a spasmolytic effect.
4. Spasfon® is used in treatment of spasmodic pain of the intestines, biliary tract, bladder or uterus.
a. It Provide relief from irritable bowel syndrome; preventing or treating bladder spasm after
transurethral resection of the prostate.
b. Phloroglucinol is not widely used because it also used in making explosives.
Combination Products of Mebeverine
Mebeverine + Sulpiride * Coated Tab Colona ® 100 mg + 25 mg
Mebeverine + Sulpiride Tab Coloprid , IB-Lax
® ® 135 mg + 25 mg
+ Simethicone + 180 mg
Mebeverine + Simethicone Tab PrXicol® 135 mg + 40 mg
+ Escitalopram * + 10 mg
Mebeverine + Dimethicone Tab Coloverin D® 135 mg + 40 mg
Mebeverine + Ispaghula Granules Fybogel Plus® (135 mg + 3.5 gm)/sachet
1. Sulpiride is an anti-psychotic; it has a sedative effect, it may have a role in IBS, but it causes
extrapyramidal side effects (involuntary movements of the face lips and tongue); thus its use is
unjustified and not preferred for long term use; (For more info see chapter 4, section 2).
2. Simethicone, Dimethicone are an anti-flatulence drug.
3. Escitalopram is an antidepressant (SSRIs), see chapter 4 for more info.
4. Ispaghula is a bulk forming Laxative.
Notes for Irritable Bowel Syndrome (IBS):

1. Antispasmodics may be combined with benzodiazepine (Librax®) or a phenothiazine (Stelabid®) and
used for gastrointestinal disorders associated with or due to anxiety; and for irritable bowel
syndrome (IBS); Also, they may be combined with analgesics.
2. Tricyclic antidepressants (TCAs) as (Amitriptyline) and Selective serotonin reuptake inhibitors
(SSRIs) as (Fluoxetine, Escitalopram) are used for IBS (used at sub-therapeutic doses); they
increase pain threshold in the guts and delay gastric emptying time, and decrease stool frequency.
➢ TCAs have anti-pain and gut-slowing qualities, and seem to do this by acting on the
neurotransmitter’s serotonin and norepinephrine; This slowing down of gut motility makes the
TCAs better suited for the treatment of diarrhea-predominant IBS (IBS-D); while the lack of a
constipating effect makes the SSRIs a better choice for those who suffer from constipation
predominant IBS (IBS-C); For more info on antidepressants see chapter 4.
3. Some guidelines support the use of Probiotics for the treatment of IBS.
Combination products for IBS
Trade names Scientific name D. form Concentration
Librax® Chlordiazepoxide + Clidinum bromide Tab 5 mg + 2.5 mg
Coloverin A® Chlordiazepoxide + Mebeverine Tab 5 mg + 135 mg
Stelabid® Trifluoperazine + Isopropamide Tab 1 mg + 5 mg
Meteospasmyl® Alverine + Simethicone Cap 60 mg + 300 mg
Dicetel Duo® Pinaverium + Dimethicone Tab 100 mg + 300 mg
Colo-Tri® Trimebutine + Simethicone Tab 200 mg + 80 mg
Buscopan Plus®, Hyoscine butyl bromide + Paracetamol Tab 10 mg + 500 mg
Spazmotek Plus®
Riabal-Co® Clidinum bromide + Paracetamol Tab 5 mg + 325 mg
Panvoxan® Pantoprazole + Simethicone + Levosulpiride Tab 40mg+ 80mg + 25mg
Donnatal® Atropine + Hyoscyamine + Scopolamine Tab, ---------------------
+ Phenobarbital Cap
Bellamine® * Belladonna + Ergotamine + Phenobarbital Elixir
Tab ---------------------
* Bellamine® is also used to treat symptoms of menopause including hot flashes, sweating, anxiety, and trouble
sleeping. (It’s contraindicated in pregnancy).
Herbal Combinations for IBS
Trade names Scientific name D. form Concentration
ProIBS® Fructose + Aloe Barbadensis extract Sachet ----------
+ Vit. C + Vit. B2 + Inulin
Biocolin® Curcumin + Fennel oil Cap 42 mg + 25 mg
2.7– Anti-Emetics and Prokinetics
A) Vomiting is a reflex action for getting rid of harmful substances, but it may also be a symptom
of disease; Vomiting and nausea are often caused by a digestive tract infection, travel
sickness, pregnancy, or vertigo (a balance disorder involving the inner ear), they can also
occur as a side effect of some drugs, especially those used for cancer, radiation therapy, or
general anesthesia.
B) Nausea and vomiting occur when the vomiting center in the brain is stimulated by signals from
three places in the body: the digestive tract, the part of the inner ear controlling balance, and the
brain itself via thoughts and emotions and via its chemoreceptor trigger zone, which responds
to harmful substances in the blood.
➢ Anti-emetic drugs may act at one or more of these places.
➢ Some help the stomach to empty its contents into the intestine.
➢ A combination may be used that works at different sites and has an additive effect.
C) Stimuli for nausea are processed through several major anatomic areas, each of which has
various receptors associated with input to the medullary vomiting center:
a) Visceral stimuli: Mediated through dopamine and serotonin receptors; Major stimuli
include: Gastric irritants, Non-gastric stimuli (peritonitis, intestinal or biliary distension,
pancreatitis, gastroparesis), Abdominal radiation, Chemotherapeutic agents, Pharyngeal
stimulation.
b) Chemoreceptor trigger zone: Mediated by dopamine (D2), serotonin, and some
histamine (H1) and muscarinic (M1) and substance P/neurokinin 1; major stimuli
include: Medications (Opiates, dopamine agonists, digoxin, chemotherapeutic agents,
macrolides, general anesthetics), Metabolic disturbances (uremia, diabetic ketoacidosis,
hypercalcemia, hypoxemia), Bacterial toxins, Radiation therapy.
c) Vestibular labyrinths: Mediated through H1 and M1; Major stimuli include: Motion
sickness, Labyrinth infection.
d) Cerebral cortex: Receptor involvement not well characterized; noxious odors, visions, and
tastes.
1. Antiemetics should be prescribed only when the cause of vomiting is known because
otherwise, they may delay diagnosis, particularly in children, they are unnecessary and
sometimes harmful when the cause can be treated, such as in diabetic ketoacidosis, or in digoxin
or antiepileptic overdose.
2. They include: (Prochlorperazine, Metoclopramide, Domperidone and Cinnarizine ), which
all can be used to treat or prevent nausea and vomiting.
3. Cinnarizine is an antihistamine. Used to prevent motion sickness where the dose is taken two
hours before travel, also used to relief the symptoms of inner ear disorders such as Meniere's
disease (sensations of ringing or other noise in the ears).
➢ It acts by preventing Ca+ ions from entering the cells, thus preventing the smooth muscle
of the arteries from contraction, thereby increasing the blood supply to the brain and
extremities = relief Nausea and vertigo.
4. Metoclopramide sometimes causes a seizure-like reaction (Tardive dyskinesia) which is
characterized by the eye lid blinking and muscle rigidity.
➢ So, in patients under 20 years: the dose of Metoclopramide should be determined on the
basis of body-weight (0.1 mg/kg/dose) to avoid dystonic reaction.
➢ Should not be given more than 5 days, and its C.I in children below 1 year.
➢ Should be used with caution in patients with heart disease and Liver cirrhosis, because it
may lead to fluid accumulation by causing an increase in serum aldosterone.
➢ Also, should be used with caution in patients with epilepsy (increase convulsions
frequency).
➢ Metoclopramide is the only anti-emetic that has been specifically studied in the treatment
of renal colic, in 2 double-blinded studies; Metoclopramide provided pain relief
equivalent to narcotic analgesics in addition to relieving nausea.
5. Prochlorperazine is a dopamine (D2) receptor antagonist that belongs to the phenothiazine
class of antipsychotic agents that are used for the antiemetic treatment of nausea and vertigo. It
is also a highly potent typical antipsychotic, 10–20 times more potent than chlorpromazine. It
is also used to treat migraine headaches.
➢ May cause dry mouth, blurred vision, or difficulty in passing urine
6. Domperidone has the advantage over metoclopramide and the Prochlorperazine of being less
likely to cause central effects such as dystonic reactions (tetanus-like reaction) because it does
not readily cross the blood-brain barrier, it also improves upper GIT motility.
➢ Domperidone is not approved by the FDA, it’s approved in EMA and MHRA only.
➢ Domperidone I.V formulation was withdrawn from the markets in 2006 due cases of
cardiac arrest, arrhythmias and sudden death; oral formulation may cause the same
cardiac problems in patient over 60 years old if given more than 30 mg/day.
➢ The max recommended dose is 30 mg per day for 7 days only.
➢ With the recommendation of avoidance in patients with cardiac diseases.
➢ Avoid co-administration with drugs that prolong QT interval (Azithromycin, Ciprofloxacin)
due increased risk of cardiovascular side effects.
a) Anti-emetics and also Gastric Motility Stimulant (Prokinetics)

Metoclopramide Tab Placil®, Meclodin® 5 mg , 10 mg
Drop Meclodin® 4 mg/1 ml
Syrup Meclopram® 5 mg/5ml
Amp Placil® , Metamide® 10 mg/2 ml
Domperidone * Tab Motilium® , Motinorm® 10 mg
Supp. Motilium® 10 mg , 30 mg , 60 mg
Oral Susp. Domby® 200 ml
b) Gastric Motility Stimulant (Prokinetics)

1. They enhance gastrointestinal motility by increasing the frequency of contractions in the small
intestine or making them stronger, but without disrupting their rhythm.
2. They are used to relieve gastrointestinal symptoms such as abdominal discomfort, bloating,
constipation, heart burn, nausea, and vomiting.
Mosapride Tab Fluxopride ® 5 mg
Cisapride Tab Prepulsid , Propulsid
® ® 10 mg , 20 mg
Itopride Tab Ganaton ® 50 mg
Prucalopride Tab Resotran ® 1 mg , 2 mg
c) Other Anti Emetics

Scientific name Dosage form Trade name Conc.
Cinnarizine * Tab , Cap Stugeron® 25 mg , 75 mg
Prochlorperazine ** Tab Stemetil® , Compazine® 5 mg , 10 mg
Amp Promotil®, Stemetil® 12.5 mg/1 ml
Meclizine * Tab Antivert ® 25 mg , 50 mg
Vitamin B6 (Pyridoxine) Tab , Amp ---------- 40 mg
Meclizine + B6 * Tab Navidox , Navidoxine
® ® 25 mg + 50 mg
Cinnarizine + Domperidone Tab Vertigun ® 20 mg + 15 mg
* Safe in pregnancy, the most used antiemetic in pregnancy is (Meclizine + B6).
* Note: also see (Chapter 4, Section 6) for more details on the Drugs that are used in
nausea/vomiting and vertigo.
2.8- Drugs for the treatment of Hiccups
1. A hiccup is an involuntary contraction (myoclonic jerk) of the diaphragm that may repeat
several times per minute, in medicine, it is known as synchronous diaphragmatic flutter (SDF),
or Singultus.
2. Hiccups, in general, resolves itself without intervention, although many home remedies are
often used to attempt to shorten the duration, Medical treatment is occasionally necessary in
cases of chronic hiccups.
3. A simple treatment involves increasing the partial pressure of CO2 and inhibiting diaphragm
activity by holding one’s breath or rebreathing into a paper bag, or by scaring the patient
suddenly.
4. Various medications have been used to cure hiccups; Chlorpromazine appears to be the drug
of choice, Haloperidol and Metoclopramide have been used successfully.
➢ Chlorpromazine is an antipsychotic, used for intractable hiccups 25-50 mg orally every
8 hours, if the hiccups still persist after 3 days of oral treatment; administer 25 mg I.M.
every 4 hours. (For more info see chapter 4, section 2 for more info).
➢ Haloperidol is useful in treatment of irregular spasmodic movements of muscles, 2-5mg
I.M. followed by 1-4 mg tid orally for two days may be equally effective with less potential
for side effects. (For more info see chapter 4, section 2 for more info).
➢ Metoclopramide 10 mg I.V. or I.M. followed by a maintenance regimen of 10 to 20 mg qid
for 10 days. (See the previous section for more info).
5. Several anticonvulsant agents (phenytoin, Valproic acid, and carbamazepine) have effectively
treated intractable hiccups in typical anticonvulsant doses. Gabapentin has been effective in
patients with central nervous system (CNS) lesions and in some other groups.
6. Of the anesthetic agents, ketamine has been the most successful; Baclofen is particularly useful
in patients for whom other agents are contraindicated, Other reportedly beneficial agents include
muscle relaxants (Orphenadrine).
Chlorpromazine Tab Largactil®, Thorazine® 50 mg , 100 mg , 200 mg
Amp 25 mg/5 ml , 25 mg/ml
Haloperidol Tab Haldol®, Peridol® 0.5 mg , 1 mg , 2 mg , 5 mg
Amp Haldol Lactate® 5 mg/ml
2.9- Drugs for Inflammatory bowel disease IBD

(ulcerative colitis and Crohn’s disease)
1. Inflammatory bowel disease (IBD) is the term used for disorders in which inflammation of the
intestinal wall causes recurrent attacks of abdominal pain, general feelings of ill-health, and
frequently diarrhea, with blood and mucus present in the feces, Loss of appetite and poor
absorption of food may often result in weight loss.
2. There are two main types of IBD: Crohn’s disease and ulcerative colitis.
➢ In Crohn’s disease (also called regional enteritis), any part of the digestive tract may become
inflamed, although the small intestine is the most commonly affected site.
➢ In ulcerative colitis, it is the large intestine (colon) that becomes inflamed and ulcerated,
often producing blood-stained diarrhea.
3. The exact cause of these disorders is not known, although stress-related, dietary, infectious, and
genetic factors may all be important.
➢ The exact cause of continuing inflammation of the GI mucosa is unknown, but it is thought
that the inflammation is secondary to an antigen-driven response; Contributing factors
include: Defects in the intestinal epithelial barrier and immune system.
4. Establishing a proper diet and a less stressful lifestyle may help to alleviate these conditions, Bed
rest during attacks is also advisable, However, these simple measures alone do not usually relieve
or prevent attacks, and drug treatment is often necessary.
➢ Note: Smoking worsens Crohn’s disease; but Smoking is associated with improvement
in Ulcerative Colitis symptoms, (who says smoking has no advantages?).
5. Clinical Features of Inflammatory Bowel Disease:
Clinical Findings Crohn Disease Ulcerative Colitis
Bowel involvement May be anywhere from Confined to rectum and colon
mouth to anus (66% of Terminal ileal involvement
cases located in ileum) (backwash ileitis) in a minority of
patients
Perianal involvement Yes Unlikely
Depth of ulceration May extend to submucosa Superficial
or deeper
Continuous inflammation Rarely, a patchy, Very common
“cobblestone” appearance
Histology Transmural lesions, Nontransmural, crypt abscesses
granulomas
Fistula, perforation, or Yes No
strictures
Development of toxic No Yes
mega colon
Malabsorption or Yes, often vitamin Rare
malnutrition deficiencies; possible
growth retardation in
children
Risk factor for colorectal Uncommon Yes
cancer
Pseudo polyps Fairly uncommon Common
6. Three types of drug are used to treat IBD: Aminosalicylates anti-inflammatory drugs
(sulfasalazine), corticosteroids, Immunosuppresants (including Monoclonal antibodies).
Nutritional supplements (used especially for Crohn’s disease) and antidiarrheal drugs may also
be used. Surgery to remove damaged areas of the intestine may be needed in severe cases.
➢ Drugs cannot cure inflammatory bowel disease, but treatment is needed, not only to
control symptoms, but also to prevent complications, especially severe anemia and
perforation of the intestinal wall.
➢ Aminosalicylates are used to treat acute attacks of ulcerative colitis and Crohn’s disease, and
they may be continued as maintenance therapy.
➢ People who have severe bowel inflammation are usually prescribed a course of
corticosteroids, particularly during a sudden flare-up.
➢ Once the disease is under control, an immunosuppressant may be given to prevent a relapse.
7. Corticosteroids and sulfasalazine damp down the inflammatory process, allowing the
damaged tissue to recover; They act in different ways to prevent migration of white blood cells
into the bowel wall, which may be responsible in part for the inflammation of the bowel.
➢ Taken to treat attacks, these drugs relieve symptoms within a few days, and general health
improves gradually over a period of a few weeks.
➢ Aminosalicylates usually provide long term relief from the symptoms of IBD.
➢ Treatment with an immunosuppressant drug may take several months before the
condition improves; and regular blood tests to monitor possible drug side effects are often
required.
A. Aminosalicylates (Mesalamine, and Sulfasalazine)
1. Sulfasalazine combines Sulfapyridine (antibiotic) and Mesalamine (5-aminosalicylic acid – an
anti-inflammatory) in the same molecule, Sulfasalazine is given orally. Sulfapyridine is
believed to be responsible for many of the adverse reactions of sulfasalazine; Mesalamine
alone can be used.
➢ Sulfasalazine is cleaved by colonic bacteria to the active portion (5-aminosalicylate)
Sulfapyridine; Avoid in patients with a sulfa allergy.
➢ Dosed 4–6 gm/day for induction and 2–4 gm/day for maintenance; titrated from 500 mg once
or twice daily to avoid adverse effects.
➢ Sulfasalazine is often associated with either dose-related or idiosyncratic adverse drug
effects, or Dose-related side effects usually include GI disturbances such as nausea, vomiting,
diarrhea, or anorexia, but they may also include headache and arthralgia.
2. Patients receiving sulfasalazine should receive oral folic acid supplementation, as
sulfasalazine inhibits folic acid absorption.
➢ Patient should avoid direct sun light, because it increases sun light sensitivity.
➢ It may cause urine discoloration to brown orange color.
➢ May lead to temporary sperms malformation in men, thus preventing conception.
3. Mesalamine can be used as an enema or suppository for the treatment of proctitis or given
orally in slow-release formulations that deliver it to the small intestine and colon.
➢ Mesalamine formulations are coated tablets or granules, they should not be crushed or
chewed.
➢ Mesalamine it safe to use for patients with sulfonamide allergies.
➢ May impose a lower frequency of adverse effects compared with sulfasalazine.
4. Enemas or suppositories should be administered in the evening; They are given rectally,
particularly when disease affects the sigmoid colon and rectum.
5. Other Aminosalicylates available:
a) Olsalazine: The Dimer of 5-aminosalicylic acid, converted to Mesalamine by the intestinal
flora, associated with secretory diarrhea in up to 25% of patients.
b) Balsalazide: contains 2 molecules of Mesalamine attached together; link is broken by the
intestinal flora to give 2 molecules.
6. Sulfasalazine is also used for rheumatoid arthritis (it is one of the Disease-Modifying
Antirheumatic Drugs).
B. Other drugs may be used for the Inflammatory bowel disease (IBD) include corticosteroids (see
Chapter 11), immunosuppressant’s (see Chapter 10)
Sulfasalazine EC Tab Salazopyrin® 500 mg
Supp. 500 mg
Mesalamine EC Tab Pentasa® , Mesacol® 500 mg
EC Tab Asacol® 400 mg , 800 mg
Tab Mezavant XL® 1.2 gm
Supp. Asacol® 1000 mg
Enema Pentasa® , Salofalk® 1 gm , 2 gm , 4 gm
Olsalazine * Cap Dipentum® 250 mg
Balsalazide * Cap Colazal® , Colazide® 750 mg
Tab Giazo® 1.1 gm
Some of the Corticosteroids that have a role in IBD:
➢ Corticosteroids work quickly to suppress inflammation during acute flares.
➢ They have no role in maintenance therapy; however, more than 50% of patients with
severe disease may become steroid-dependent.
Budesonide * Cap Budenofalk® 3 mg
Granules 9 mg
Enema Entocort® 2 mg/100 ml
Hydrocortisone Tab Cortef® 10 mg
Vial 100 mg
Rectal Foam Colifoam® 10%
Methylprednisolone Tab Medrol® 4 mg
Vial DepoMedrol® 40 mg , 80 mg
Vial SoluMedrol® 250 mg , 500 mg , 1000 mg
Prednisolone Tab Cortancyl® 5 mg , 20 mg
Rectal Foam Predsol® 20 mg
Enema 20 mg/100 ml
* Budesonide is about 15-fold more potent than prednisone; with minimal systemic adverse effects
compared with other corticosteroids.
Some FDA approved Immunosuppressant for IBD

➢ Immunomodulators such as Mercaptopurine, azathioprine, or methotrexate are
Indicated only for maintenance therapy; because of long onset of action (3–15 months).
• Use can result in a steroid-sparing effect.
➢ Infliximab (monoclonal antibody against TNFα), is contraindicated in New York Heart
Association (NYHA) class III/IV heart failure; do not exceed 5-mg/kg dose in other patients
with chronic heart failure.
• Since it’s a Chimeric monoclonal antibody; it may cause Antibody induction, up to
50% of patients may develop antinuclear antibodies; 19% may develop anti-double-
stranded DNA antibodies.
• May cause reactivation of latent infections (bacterial, including disseminated
tuberculosis, fungal, sepsis and hepatitis); do not give to patients with active infections.
➢ Adalimumab (Fully humanized antibody to TNFα), therefore, theoretically, no development
of antibodies as in with Infliximab.
• Higher efficacy compared to Infliximab; with Complete remission rates at week 4
range from 21% to 54%; Efficacy rates for maintenance therapy are 56%–79% at week
4 and 36%–46% at week 56.
• The adverse effect profile of Adalimumab is similar to that of Infliximab, except for the
development of antibodies to Adalimumab.
Methotrexate Tab Trexall®, MTX® 2.5 mg
Vial (Solu.) 50 mg
Azathioprine Tab Imuran® 50 mg , 75 mg , 100 mg
Inj. Powder 100 mg/Vial
Mercaptopurine Tab 6-MP® , Puri-nethol® 50 mg
Cyclosporine Cap Sandimmune® , Gengraf® 25 mg , 50 mg , 100 mg
Inj. Solu. 50 mg/ml
Infliximab Inj. Powder Remicade® 100 mg/vial
Adalimumab Prefilled Inj. Humira® 40 mg/0.8 ml
Certolizumab Inj. Powder Cimzia® 200 mg/vial
Natalizumab Inj. Solu. Tysabri® 300 mg/15 ml
Golimumab Prefilled Inj. Simponi® 50 mg/0.5 ml
Vedolizumab Inj. Powder Entyvio® 300 mg/vial
2.10- Products for flatulence and abdominal gases
A- Gas in the digestive system is part of the normal process of digestion. Getting rid of excess gas, either
by Burping or passing gas (farting), also is normal; Gas pain may occur if gas is trapped or not
moving well through the digestive system.
➢ An increase in gas or gas pain may result from eating foods that are more likely to produce gas;
Often, relatively simple changes in eating habits can lessen bothersome gas.
➢ some digestive system disorders, such as irritable bowel syndrome or celiac disease, may cause
(in addition to other signs and symptoms) an increase in gas or gas pain.
B- Also Burping is normal, particularly during or right after a meal; Most people pass gas up to 20 times
a day. Therefore, while having gas may be inconvenient or embarrassing, burping and passing gas
are rarely by themselves a sign of a medical problem.
C- Gas in the stomach is primarily caused by swallowing air during eating or drinking, also Gas forms in
the large intestine (colon) when bacteria ferment carbohydrates — fiber, some starches and some
sugars — that aren't digested in the small intestine. Bacteria also consume some of that gas, but the
remaining gas is released when passing gas from the anus.
D- Several products are available for flatulence and abdominal gases; these products usually contain
Simethicone (or Dimethicone), Dill oil, Fennel Oil, Alpha-galactosidase, Lactase, Activated
Charcoal and Probiotics.
Notes:
1. Simethicone is an anti-foaming agent that decreases the surface tension of gas bubbles, causing
them to combine into larger bubbles in the stomach that can be passed more easily.
• Simethicone does not reduce or prevent the formation of gas in the digestive tract,
rather, it increases the rate at which it exits the body;
• It is not absorbed by the body into the bloodstream, and thus is considered safe.
2. Fennel essential oil can help to clear the bowels, relieve constipation, and get rid of gas and bloating,
Dill oil (the essential ingredient for gripe water); is given to babies to relieve flatulence and colic.
3. Alpha-galactosidase is an enzyme used for the prevention of flatulence and bloating attributed to a
variety of grains, cereals, nuts, and vegetables containing the sugars raffinose, stachyose, verbascose.
4. Lactase helps to digest the sugar in dairy products (lactose); this reduces gas symptoms if the patient
is lactose intolerant.
5. Probiotics is used to help kill the bad bacteria and add good bacteria to the digestive tract, thus
helping in normalizing the gas production rate.
a) For Adults
Dimicone® Chew Tab, Cap Dimethicone 40 mg
Disflatyl® Tab Simethicone + Silicon Dioxide 40 mg + 2 mg
Ovol® Cap Simethicone 180 mg
Mestil Forte® Tab Simethicone 80 mg
Gazclear® Tab Simethicone + Charcoal 50 mg + 300 mg
Meteospasmyl® Cap Simethicone + Alverine 300 mg + 60 mg
lactaid® Tab , chew tab Lactase enzyme 9,000 units
Gas enzyme® Chew Tab Alpha-galactosidase 300 units
Carminex® Syrup Herbal Preparation ----------------------
Eucarbon® Tab Senna + Rhubarb + Charcoal 105 mg + 25 mg
+ Sulphur sublimated +180 mg + 50
+ Peppermint oil + Fennel oil + 20 mg
Flatulence® Sachets Simethicone + Anise extract 80 mg + 5 mg
+ Mint extract + 5 mg
Aeris® Cap Charcoal + Fennel oil 315 mg + 140 mg
+ Lemon Balm + Green Aniseed + 90 mg + 3.6 mg
b) For infants and Children
Disflatyl® drop Simethicone 40 mg / 30 ml
Infasooth® drop Simethicone 40 mg / 50 ml
Ovol®, Baby Cone® drop Simethicone 40 mg / 15 ml
Colic EZ® drop Simethicone + (40 mg + 0.005 ml
Dill oil + Fennel Oil + 0.0007 ml)/1 ml
Happy baby® drop Chamomile dry extract 50 mg
+ Lemon balm + 10 mg
+ Fennel oil + 0.2 mg
Spastal®, * drop Pipenzolate + 4 mg
Babytal® Phenobarbitone 6 mg
Stop Colic® cream Cumin oil + Vaseline 5% (50 ml cream)
Notes:
1. Pipenzolate is an Antimuscarinic; It binds to muscarinic acetylcholine receptors as an
antagonist therefore preventing acetylcholine from binding to the receptors.
• Inhibition of Acetylcholine produces relaxation of smooth muscles of gastrointestinal
tract and genitourinary tract and reduces the painful spasm and cramp.
• It does not produce CNS effects and free from atropine-like side effects.
2. Spastal® is not recommended anymore in any guideline; because it contains phenobarbital,
which has been associated with brain atrophy when used in infants as the new studies have
stated. (2-4); Phenobarbital is added to potentiate the spasmolytic action of Pipenzolate, also to
sedate the child, and to relieve anxiety which usually associates colic.
3. Cumin oil helps to facilitate digestion and elimination of gas pains; its applied by massage into
the baby’s abdomen 2-3 times a day, used for babies older than 5 weeks.
2.11- Drugs for pancreatic disorders (Enzymes for digestion support)

1. The pancreas releases certain enzymes into the small intestine that are necessary for digestion
of a range of foods. If the release of pancreatic enzymes is impaired (by chronic pancreatitis or
cystic fibrosis), enzyme replacement therapy may be necessary.
➢ They do not cure the underlying disorder, but it restores normal digestion.
➢ should be taken just before or with meals, and usually take effect immediately.
➢ Sometimes, the doctor will probably advise patients to eat a diet that is high in protein and
carbohydrates and low in fat.
➢ Pancreatin, is a protein composed of (amylase, Lipase and protease) – enzymes in which
they respectively digest carbohydrates, fats and proteins.
• Pancreatin is extracted from pig pancreas
• Treatment must be continued indefinitely as long as the pancreatic disorder persists.
➢ Other products contain Cellulase, Lactase, Maltase and other lytic enzymes.
Creon® Cap Pancreatine 150 mg , 400 mg
Spasmo-Canulase® Bitab (multi layers) Digestive Enzymes --------------------
Trizyme® Tab Digestive Enzymes --------------------
Combizyme® Tab Digestive Enzymes --------------------
Digest Support® Tab Digestive Enzymes --------------------
2.12- Gallstone solubilizing agents
1. The formation of gallstones is the most common disorder of the gallbladder, which is the storage
and concentrating unit for bile, a digestive juice produced by the liver.
➢ During digestion, bile passes from the gallbladder via the bile duct into the small intestine,
where it assists in the digestion of fats.
➢ Bile is composed of several ingredients, including bile acids, bile salts, and bile pigments; It
also has a significant amount of cholesterol, which is dissolved in bile acid.
➢ If the amount of cholesterol in the bile increases, or if the amount of bile acid is reduced, a
proportion of the cholesterol cannot remain dissolved, and under certain circumstances this
excess accumulates in the gallbladder as gallstones.
2. Gallstones may be present in the gallbladder for years without causing symptoms;
However, if they become lodged in the bile duct, they cause pain and block the flow of bile.
➢ If the bile accumulates in the blood, it may cause an attack of jaundice, or the gallbladder may
become infected and inflamed.
3. Drug treatment with Ursodeoxycholic acid is only effective against stones made
principally of cholesterol (some contain other substances), and even these take many months
to dissolve.
➢ Therefore, surgery and ultrasound have become widely used, especially the use of
laparoscopic (keyhole) surgery; Surgery and ultrasound treatments are always used to
remove stones blocking the bile duct.
4. Ursodeoxycholic acid is a substance that is naturally present in bile; It acts on chemical

processes in the liver to regulate the amount of cholesterol in the blood by controlling the
amount that passes into the bile.
➢ Once the cholesterol level in the bile is reduced, the bile acids are able to start dissolving the
stones in the gallbladder.
➢ To achieve maximum effect, Ursodeoxycholic acid treatment usually needs to be
accompanied by adherence to a low cholesterol, high-fiber diet.
➢ Even after successful treatment with drugs, gallstones often recur when the drug is stopped;
In some cases, drug treatment and dietary restrictions may be continued even after the
gallstones have dissolved, to prevent a recurrence.
➢ Although it reduces cholesterol in the gallbladder, it increases the level of cholesterol
in the blood because it reduces its excretion in the bile; thus, caution should be advised in
patients with cardiovascular risk or with atherosclerosis.
5. Ursodeoxycholic acid is also used in primary biliary cirrhosis; it slows disease progression,
and usually combined with Fenofibrate for better results in cirrhosis.
• Also indicated for Cholestatic liver disease, Alcoholic and non-alcoholic fatty liver.
• Sometimes combined with Silymarin (antioxidant and liver detoxifying agent), for the
management of some liver diseases.
6. Other drug options: Terpene mixtures (Rawachol®) are used for prevention only.

Ursodiol Cap Urso® , Ursoflor® , Actigall® 300 mg
Tab Urso 250® 250 mg
Tab Urso Forte® 500 mg
Chenodiol Tab Chenodal® 250 mg
Terpene mixtures Cap Rawachol® ----------
* Ursodiol = Ursodeoxycholic Acid, they are the same drug.
* Chenodiol = Chenodeoxycholic Acid, they are the same drug.
2.13– Drugs for Hepatic (liver) detoxification
1. The liver represents the human body’s primary filtration system, one of the largest and most
important human organs; in addition to storing and releasing energy from foods, it acts by
converting toxins into waste products, cleansing the blood, and metabolizing nutrients and
medications to provide the body with some of its most important proteins.
2. There are a lot of products in our markets with names like “Liver Guard,” “Liver Rescue,” and
“Liver Detox” that claims they can get the liver in top shape — and help patients to feel better in
the process, but unfortunately; few ingredients have been shown to have positive results in
hepatic disease in studies, these include:
❖ Milk Thistle: has been shown to decrease liver inflammation.
❖ Turmeric Extract: has been shown to protect against liver injury.
❖ Artichoke leaf: antioxidant, it may help liver cells regenerate.
❖ Dandelion root: used to treat liver ailments
❖ S-adenosyl-L-methionine (SAMe): antioxidant, used in alcohol liver disease.
❖ Silymarin: antioxidant – the active metabolite of milk thistle, works by reducing the
turnover of membrane phospholipids and stabilizes the cell membranes of hepatocytes.
3. But also, there have not been adequate clinical trial data in humans to recommend the routine
use of these natural compounds for prevention.
Trade name D. form Scientific names concentration
Simal® Tab Milk Thistle + Curcuma Rhizomes 90 mg + 70 mg
+ Artichoke + Liquorice + 90 + 50 mg
Legalon Forte® Cap Milk Thistle extract 173 mg
Bilirel® Tab Artichoke + Milk Thistle + L-Methionine 900 mg Comb.
+ Fumitory + L-Glutathione
ElixirSame® Tab S-Adenosyl L-Methionine 200 mg
+ Folic acid + Vitamin B12 + 200 mcg + 2.5 mcg
2.14– Drugs for food allergy

1. Food allergy is an immune system reaction that occurs soon after eating a certain food, even a
tiny amount of the allergy-causing food can trigger signs and symptoms such as digestive
problems, hives or swollen airways. In some people, a food allergy can cause severe symptoms
or even a life-threatening reaction known as anaphylaxis.
2. Allergy with classical symptoms of vomiting, colic and diarrhea caused by specific foods such as
shellfish should be managed by strict avoidance.
3. The condition should be distinguished from symptoms of occasional food intolerance in those
with irritable bowel syndrome.
4. Sodium Cromoglicate may be helpful as an adjunct to dietary avoidance.
5. For a minor allergic reaction, over-the-counter or prescribed antihistamines may help reduce
symptoms. These drugs can be taken after exposure to an allergy-causing food to help relieve
itching or hives. However, antihistamines can't treat a severe allergic reaction.
6. For a severe allergic reaction, you may need an emergency inj. of epinephrine, this device is a
combined syringe and concealed needle that injects single dose of medication when pressed.
For antihistamines see chapter 1, section 2
Na Cromoglicate
+ Cap Nalcrom® 100 mg
Epinephrine Prefilled Inj. EpiPen® , Twinject® 0.15 mg/0.15 ml
Auvi-Q® 0.3 mg/0.3 ml
2.15- Preparations for anal and rectal disorders (Hemorrhoids)
1. The most common disorder of the rectum (the last part of the large intestine) and anus (the
opening from the rectum) is hemorrhoids, commonly known as piles; They occur when
hemorrhoidal veins become swollen or irritated, often due to prolonged local pressure such
as that caused by a pregnancy or a job requiring long hours of sitting.
➢ Hemorrhoids may cause irritation and pain, especially on defecation, and are aggravated
by constipation and straining during defecation.
➢ In some cases, hemorrhoids may bleed, and occasionally clots form in the swollen veins,
leading to severe pain, a condition called thrombosed hemorrhoids.
➢ Other common disorders include anal fissure (painful cracks in the anus) and pruritus ani
(itching around the anus).
2. Preparations for relief of hemorrhoids and anal discomfort fall into three main groups:
❖ Drugs act locally to relieve inflammation and irritation.
❖ Drugs which reduces pain by relieving anal pressure and increasing blood flow.
❖ Drugs that relieve constipation, which contributes to the formation and discomfort from
hemorrhoids and anal fissures.
3. These products are usually formulated as ointments and creams or suppositories.
• Ointments and creams can be used for internal and external hemorrhoids while
suppositories are used for internal hemorrhoids, however both are usually given twice
daily (morning and evening) and after each bowel movement.
• When used intra-rectally, the ointment may be inserted using an applicator or finger but the
applicator is preferred because it can reach an area where the finger cannot reach. The
applicator should be lubricated by the ointment before insertion.
• Locally acting treatments often contain a soothing agent with antiseptic, astringent, or
vasoconstrictor properties, such ingredients include zinc oxide, bismuth, hamamelis
(witch hazel), and Peru balsam.
• Some of these also include a mild local anesthetic such as lidocaine.
• Some contain a corticosteroid to relieve inflammation around the anus.
➢ Steroid-containing agents should not be used for more than 14 days, as they may
cause thinning of the skin
• May include a barrier substance such as Petroleum jelly or Zinc oxide and a
vasoconstrictor such as Epinephrine.
• Some products contain Calcium Channel blockers (Amlodipine or Nifedipine) or Glyceryl
tri-nitrate; these are added due their topical effect as vasodilators, although they are used
off-label to treat hemorrhoids
4. There is a new tech. that uses cryotherapy (ice therapy) for immediate relief of pain, itching,
inflammation, and bleeding of hemorrhoids, these devices usually contains a formulated cooling
liquid which when dispensed cause a controlled degree of cold directly to the internal rectal
tissue, this cooling action causes the blood vessels in the affected area to shrink, which in turn
soothes the swollen tissue, reducing bleeding, pain and itching.
➢ An example of such devices is Anurex®, usually used twice daily.
5. Neither of these treatments above can shrink large hemorrhoids, although they may provide
relief while anal fissures heal naturally.
➢ Severe, persistently painful hemorrhoids that continue to be troublesome in spite of these
measures may need to be removed surgically or, more commonly, by banding. This is a
procedure in which a small rubber band is applied tightly to a hemorrhoid, thereby blocking
off its blood supply; the hemorrhoid will eventually wither away.

Trade name Dosage form. Scientific name Concentration
Procto-Glyvenol® Cream , Supp. Tribenosid + Lidocaine 5 gm + 2 gm
Faktu® Supp. Policresulen* + Cinchocaine 100 mg + 2.5 mg
Hirudoid® Cream , Oint. Mucopolysaccharide + 0.3 gm
Heparinoid 25,000 U
Proctoheal® Oint. , cream, Lidocaine + Fluocinolone 20 mg + 0.1 mg
Supp.
H-Formula® Cream , Supp. Shark liver oil + Phenylephrine 3% + 0.25%
+ Dibucaine + 1%
Proctosedyl® Oint. Cinchocaine HCL + 5 mg
Hydrocortisone + 5 mg
Framycetin Sulphate + 11.89 mg
Aesculin 10 mg
Proctosedyl bd® Cream Lignocaine + Phenylephrine 2.5% + 0.1%
+ Beclomethasone + 0.025%
Procto-Venart® Oint. Ruscogenins + Prednisolone + 0.8 gm + 0.15 gm
Cinchocaine + Menthol + 0.5 gm + 0.2 gm
+ Zinc oxide +10 gm
Anugesic HC®, Cream , Supp. Benzyl benzoate + 1.2% +
Anusol HC® Bismuth Oxide + Pramocaine 0.86% + 1%
Zinc Oxide + Hydrocortisone 12.35% + 0.5%
Xyloproct® Oint. Lidocaine + Hydrocortisone 5% + 0.275%
+ Zinc Oxide + 18%
+ Aluminum acetate + 3.5%
Daflon®, Pelethrocin® Tablet (Diosmin + Hesperidin)** 500 mg
Pelethrocin® Cream (Diosmin + Hesperidin)** 2% (50 gm tube)
Pilex® Cream , Tab Herbal preparation -------------
--
Rectogesic®, Myovin® Rectal Gel Glyceryl tri-nitrate 4 mg/gm (2%)
ANO Bliss® Cream Nifedipine + Lidocaine 0.3% + 1.5%
CremaGel® Gel Diltiazem 2%
* Policresulen is a topical hemostatic and antiseptic.
** Daflon® and Pelethrocin® are a micronized purified flavonoid fraction containing (90%
Diosmin and 10% Flavonoids) expressed as Hesperidin, it is a veno-tonic (it increases venous
tone) and a vasculoprotector (it increases resistance in small blood vessels). It is recommended
for treating venous circulation disorders (swollen legs, pain, restless legs) and for treating
acute hemorrhoid attack.
References
1- Sean C. Sweetman. Martindale: The Complete Drug Reference, 38th Edition
2- Lexi-comp, Drug information handbook, 2022Ed.
3- Joseph T. DiPiro, Robert L. Pharmacotherapy: A Pathophysiologic Approach, 11th Edition.
4- Mary Anne koda-kimble (ed.), Applied Therapeutics: The clinical use of drugs, 11th ed.
5- Handbook of Nonprescription Drugs: An Interactive Approach to Self-Care, 17th Edition.
6- Comprehensive Pharmacy Review for NAPLEX 8th Ed.
8- ACCP Updates in Therapeutics® 2021: Pharmacotherapy Preparatory Review

CARDIOVASCULAR SYSTEM
Chapter Three: Cardiovascular System
Part One: Introduction 3.15 - Lipid-regulating drugs (Anti-
Lipemic agents)
Part Two: a. Statins
3.1 – Diuretics b. Fibrates
a. Loop Diuretics c. Bile acid Sequestrants
b. Thiazide Diuretics d. Injectable Anti-Lipemic drugs
c. K+ sparing Diuretics e. Other Anti-Lipemic drugs
d. Osmotic Diuretics f. Anti-Lipemic Combos
e. Carbonic anhydrase inhibitors
f. Combination Diuretics products 3.16 - Drugs used to prevent Abnormal
Blood Clotting
3.2 – Angiotensin converting enzyme a. Antiplatelet drugs
inhibitors (ACEI) b. Anticoagulants
c. Thrombolytic drugs (Fibrinolytics)
3.3 - Angiotensin II receptor antagonists
(A2RAs or ARBs) 3.17 – Drugs used to Prevent Bleeding
(anti-Fibrinolytics)
3.4 – Direct Renin inhibitor
3.18 – Drugs that raise low blood
3.5 – Neprilysin inhibitors
pressure (Anti-Hypotensive)
3.6- Beta-adrenoceptor blocking drugs
3.19 - Volume Expanders (I.V. Fluids)
(Beta-Blockers)
a. Crystalloids
3.7 - Calcium-channel blockers (CCBs) b. Colloids
3.20 – Positive Inotropics
3.8 - Fixed-dose Combination Products
a. Two fixed products 3.21 – Drugs for Pulmonary
b. Three (triple) dose combination Hypertension
products 3.22 - Miscellaneous cardiovascular
3.9 - Centrally acting (α) agonists drugs
Vasodilators
3.10 - α-adeno receptor antagonists
3.11 - Drugs for Pheochromocytoma
3.12 - Nitrates, Vasodilators and Anti-
Anginal Drugs:
a. Nitrates
b. Other Anti-Anginal drugs
c. Other Central Vasodilators
d. Peripheral Vasodilators
3.13 - Emergency Antihypertensives
3.14 - Anti-Arrhythmic Drugs
Sam’s Guide: Chapter 3 – Cardiovascular
Chapter Three: Cardiovascular System
Part One:
1. Introduction:
➢ The blood transports oxygen, nutrients, and heat, contains chemical messages in the form of
drugs and hormones, and carries away waste products for excretion by the kidneys; Blood is
pumped by the heart to and from the lungs, and then in a separate circuit to the rest of the body,
including the brain, digestive organs, muscles, kidneys, and skin.
➢ The heart is a pump with four chambers – two atria and two ventricles. The atrium and ventricle
on the left side pump oxygenated blood to the body, while those on the right pump deoxygenated
blood to the lungs; Backflow of blood is stopped by one-way valves at the chamber exits.
➢ Arteries carry blood away from the heart; Their muscle walls are elastic, contracting and dilating
in response to nerve signals.
➢ Veins carry blood back to the heart; Their walls are thinner and less elastic than those of arteries.
2. What Can go wrong in the Cardiovascular system

➢ The efficiency of the circulation may be impaired by weakening of the pumping action of the heart
(heart failure) or by irregularity of the heart rate (arrhythmia).
➢ The blood vessels may be narrowed and clogged by fatty deposits (atherosclerosis).
➢ reduced blood supply to the brain and the extremities (peripheral vascular disease), or
reduced to the heart muscle (coronary heart disease), causing (Angina).
➢ Cardiovascular disorders that can be complicated by the formation of clots that may block a
blood vessel; a clot in the arteries supplying the heart muscle is known as coronary thrombosis;
a clot in an artery inside the brain is the most frequent cause of (stroke).
➢ abnormal high blood pressure (hypertension), in which the pressure of circulating blood on the
vessel walls is increased for many reasons, or abnormal low blood pressure (hypotension).

Because people suffering from heart disease often have more than one problem, several drugs
may be prescribed at once.
➢ Many drugs act directly on the heart to alter the rate and rhythm of the heartbeat; These are
known as anti-arrhythmics and include Beta blockers (BBs), Calcium channel blockers
(CCBs), and Digoxin.
➢ Other drugs affect the diameter of the blood vessels, either by dilating them (vasodilators);
such as Angiotensin-converting enzyme inhibitors (ACEIs), Angiotensin II receptor
blockers (ARBs), or other direct vasodilators - to improve blood flow and reduce blood
pressure
➢ drugs affecting the diameter of the blood vessels by constricting them (vasoconstrictors).
➢ Diuretics (used in the treatment of hypertension and heart failure) increase the body’s
excretion of salt and water.
➢ Lipid-lowering drugs reduce blood cholesterol levels, thereby minimizing the risk of
atherosclerosis.
➢ Drugs to reduce blood clotting are administered if there is a risk of abnormal blood clots
forming in the heart, veins, or arteries, Drugs that increase clotting are given when the
body’s natural clotting mechanism is defective.
➢ Drugs that increase the heart rate and contractility (used in emergencies).
➢ Drugs for pulmonary hypertension.
➢ Drugs that increase the blood volume (IV solution - plasma expanders).

4. What is Blood Pressure BP
1. Blood pressure is the force exerted by the blood against the artery walls. Two measurements are
taken: one indicates force while the heart’s ventricles are contracting (systolic pressure); This
reading is a higher figure than the other one, which measures the blood pressure during ventricle
relaxation (diastolic pressure).
2. Blood pressure varies among individuals and normally increases with age. If a person’s blood
pressure is higher than normal on at least three separate occasions, a doctor may diagnose
the condition as hypertension.
3. Although hypertension does not usually cause any symptoms, severely raised blood pressure
may produce headaches, palpitations, and general feelings of ill-health; It is important to reduce
high blood pressure because it can have serious consequences, including stroke, heart
attack, heart failure, and kidney damage.
4. Certain groups are particularly at risk from high blood pressure; These risk groups include
diabetics, smokers, people with pre-existing heart damage, and those whose blood contains a
high level of fat.
5. Blood pressure depends not only on the force with which the heart pumps blood, but also on the
diameter of blood vessels and volume of blood in circulation: blood pressure is increased
either if the vessels are narrow or the volume of blood is high.
6. Antihypertensive drugs lower blood pressure either by dilating the blood vessels or by reducing
blood volume; Each type of antihypertensive acts in a different way to lower blood pressure:
• Centrally acting drugs act on the mechanism in the brain that controls the diameter of the
blood vessels.
• Beta blockers reduce the force of the heartbeat.
• Diuretics act on the kidneys to reduce blood volume.
• ACE inhibitors act on enzymes in the blood to dilate blood vessels.
• Vasodilators and calcium channel blockers act on the arterial wall muscles to prevent
constriction.
• Alpha blockers block nerve signals that trigger constriction of blood vessels.
5. How Does the Body Control Blood Pressure

1. Changes in blood pressure are routinely made in order to direct appropriate amounts of oxygen
and nutrients to specific parts of the body. For example, when exercise demands additional
supplies of oxygen to skeletal muscles, blood delivery to these muscles increases, while blood
delivery to the digestive organs decreases. Adjustments in blood pressure are also required when
forces are applied to the body, such as when starting or stopping in an elevator.
A) Blood pressure can be adjusted by producing changes in the following variables:
1. Cardiac output: which can be altered by changing stroke volume or heart rate.
2. Resistance to blood flow in the blood vessels: it is most often altered by changing the
diameter of the vessels (vasodilation or vasoconstriction); Changes in blood viscosity
(its ability to flow) or in the length of the blood vessels (which increases with weight gain)
can also alter resistance to blood flow.
B) The following mechanisms help regulate blood pressure:
1. The cardiovascular center provides a rapid, neural mechanism for the regulation of blood
pressure by managing cardiac output or by adjusting blood vessel diameter, Located in the
medulla oblongata of the brain stem.
➢ The cardiac center stimulates cardiac output by increasing heart rate and
contractility; These nerve impulses are transmitted over sympathetic cardiac nerves.
➢ The cardiac center inhibits cardiac output by decreasing heart rate. These nerve
impulses are transmitted over parasympathetic vagus nerves.
➢ The vasomotor center regulates blood vessel diameter; Nerve impulses transmitted
over sympathetic motor neurons called vasomotor nerves innervate smooth muscles in
arterioles throughout the body to maintain vasomotor tone, a steady state of
vasoconstriction appropriate to the region.
➢ The cardiovascular center receives information about the state of the body through the
following sources:
a. Baroreceptors: are sensory neurons that monitor arterial blood pressure, major
baroreceptors are located in the carotid sinus (an enlarged area of the carotid artery
just above its separation from the aorta), the aortic arch, and the right atrium.
b. Chemoreceptors: are sensory neurons that monitor levels of (CO2 and O2); These
neurons alert the cardiovascular center when levels of O2 drop or levels of CO2 rise
(which result in a drop in pH), Chemoreceptors are found in carotid bodies and aortic
bodies located near the carotid sinus and aortic arch.
c. Higher brain regions, such as the cerebral cortex, hypothalamus, and limbic system,
signal the cardiovascular center when conditions (stress, fight‐or‐flight response, hot
or cold temperature) require adjustments to the blood pressure.
2. The kidneys provide a hormonal mechanism for the regulation of blood pressure by
managing blood volume.
➢ The renin‐angiotensin‐aldosterone system of the kidneys regulates blood volume; In
response to rising blood pressure, the juxtaglomerular cells in the kidneys secrete renin
into the blood; Renin converts the plasma protein angiotensinogen to angiotensin I,
which in turn is converted to angiotensin II by enzymes from the lungs. Angiotensin II
activates two mechanisms that raise blood pressure:
a. Angiotensin II constricts blood vessels throughout the body (raising blood
pressure by increasing resistance to blood flow). Constricted blood vessels reduce
the amount of blood delivered to the kidneys, which decreases the kidneys' potential
to excrete water (raising blood pressure by increasing blood volume).
b. Angiotensin II stimulates the adrenal cortex to secrete aldosterone, a hormone
that reduces urine output by increasing retention of H2O and Na+ by the kidneys
(raising blood pressure by increasing blood volume).
C) Various substances influence blood pressure; Some important examples follow:
1) Epinephrine and norepinephrine, hormones secreted by the adrenal medulla, raise
blood pressure by increasing heart rate and the contractility of the heart muscles and by
causing vasoconstriction of arteries and veins. These hormones are secreted as part of the
fight‐or‐flight response.
2) Antidiuretic hormone (ADH), a hormone produced by the hypothalamus and released
by the posterior pituitary, raises blood pressure by stimulating the kidneys to retain H2O
(raising blood pressure by increasing blood volume).
3) Atrial natriuretic peptide (ANP), a hormone secreted by the atria of the heart, lowers
blood pressure by causing vasodilation and by stimulating the kidneys to excrete more
water and Na+ (lowering blood pressure by reducing blood volume).
4) Nitric oxide (NO), secreted by endothelial cells, causes vasodilation.
5) Nicotine in tobacco raises blood pressure by stimulating sympathetic neurons to increase
vasoconstriction and by stimulating the adrenal medulla to increase secretion of
epinephrine and norepinephrine.
6) Alcohol lowers blood pressure by inhibiting the vasomotor center (causing
vasodilation) and by inhibiting the release of Antidiuretic hormone (ADH); (increasing
H2O output, which decreases blood volume).
➢ Cheeeeeeeeeers!

Part Two:
3.1-Diuretics
➢ The kidney normal filtration process takes water, salts (mainly potassium and sodium), and
waste products out of the bloodstream, most of the salts and water are returned to the
bloodstream, but some are expelled from the body with the waste products in the urine.
• Diuretics interfere with this filtration process by reducing the amounts of sodium and water
taken back into the bloodstream, thus increasing the volume of urine produced.
• Modifying the filtration process in this way means that the water content of the blood is
reduced; less water in the blood causes excess water present in the tissues to be drawn out
and eliminated in urine.
• Thus; Diuretic drugs help to turn excess body water into urine, and as the urine is
expelled, the tissues become less water-swollen (less edema) and the heart action improves
because it has to pump a smaller volume of blood.
➢ There are several classes of diuretic, each of which has different uses, modes of action, and
effects; But all diuretics act on the kidneys, the organs that govern the water in the body.
➢ Diuretics are most commonly used in the treatment of high blood pressure
(hypertension); By removing a larger amount of water than usual from the bloodstream, the
kidneys reduce the total volume of blood circulating; This drop in volume causes a reduction of
the pressure within the blood vessels, Diuretics are also widely used to treat heart failure in
which the heart’s pumping mechanism has become weak; they do that remove fluid that has
accumulated in the tissues and lungs; The resulting drop in blood volume reduces the work of
the heart.
➢ Other conditions for which diuretics are often prescribed include nephrotic syndrome (a kidney
disorder that causes edema), liver cirrhosis (in which fluid may accumulate in the abdominal
cavity), and premenstrual syndrome (when hormonal activity can lead to fluid retention and
bloating), and Less commonly, diuretics are used to treat glaucoma and Ménière’s disease.
1. They are not the 1st line of therapy in Comorbid Hypertension; so don’t use them instantly
for any HT case, they may increase the blood viscosity and lead to decrease perfusion and blood
supply, which may lead to serious deteriorations.
2. The principal groups of diuretics are as follows.
Diuretic type examples
Thiazide and related diuretics Hydrochlorothiazide, Chlorthalidone
Loop Diuretics Furosemide, Bumetanide
Potassium (K )-sparing diuretics
+ Amiloride
Aldosterone antagonist Spironolactone
Carbonic anhydrase inhibitors Acetazolamide (mainly for glaucoma)
Osmotic diuretics Mannitol (to ↓ intracranial pressure)
3. Diuretics are effective in lowering BP by 10-15 mm Hg in most patients.

4. Diuretics ideally should be dosed in the morning if given once daily and in the morning and
afternoon if dosed twice daily to minimize the risk of night-time diuresis.
5. Thiazide and loop diuretics can cause hypokalemia while K-sparing diuretics can cause
retention of potassium and therefore, they are given with thiazide or loop diuretics to minimize
hypokalemia.
➢ Hypokalemia can cause confusion, weakness, and trigger abnormal heart rhythms
(especially in people taking digitalis drugs).
➢ Potassium supplements or a diet that is rich in potassium (containing plenty of fresh fruits
and vegetables) may be helpful.
6. Spironolactone has an anti-androgenic property, therefore:
A. It causes side effects like Gynecomastia and impotence in men.
B. It has been used for its anti-androgenic properties in some cases of Acne and for women
with Hirsutism.
7. Loop and thiazide diuretic may cause Sulphur allergies in some patients, so in Patient with
Sulpha allergies switch to (Ethacrynic acid), which don’t cause (S) allergies.
➢ For a synergistic effect, combine Loop diuretic with (Metolazone).
8. Thiazide diuretic cause Hyperuricemia (raise blood levels of uric acid), thus they are not
recommended in Patient with Gout, they may trigger Acute Gout Attacks.
9. Loop diuretics increase the Ca2+ content of urine, whereas thiazide diuretics decrease it.
10. Because they do not alter disease progression or prolong survival in patients with heart
failure, diuretics are not required for HF patients without fluid retention.
a) Loop Diuretics
The loop diuretics are the drugs of choice for reducing the acute pulmonary edema of heart
failure; Because of their rapid onset of action.
➢ Act at the ascending limb of the loop of Henle in the kidney.
➢ They are also useful in treating hypercalcemia and hyperkalemia.
➢ a loop diuretic can be added to antihypertensive treatment to achieve better control of
blood pressure in those with resistant hypertension, or in patients with impaired renal
function or heart failure.
➢ Large doses given into a vein may disturb hearing or cause a temporary hear loss.
➢ Loop diuretics produce a more potent diuresis, but a smaller decrease in peripheral
vascular resistance (PVR), and less vasodilation than thiazide diuretics.
➢ The loop diuretics are more potent than thiazides, and retain their effectiveness in renal
insufficiency; Thus, in most patients with HF, loop diuretics are preferred.
• Loop diuretics usually have a "ceiling" effect where there is a maximum level of dosage
where further increase in dosage will not increase the clinical effect of the drug.
➢ I.V Furosemide doses greater than 50 mg given by intravenous infusion only. Give
continuously in sodium chloride 0.9%; glucose solutions are unsuitable.
• Intravenous dose of furosemide is twice as potent as the oral route.
➢ Torsemide has longer half-life (12-16 hours) when compared to Furosemide (6-8 hours);
Also, Torsemide has a more rapid oral absorption (1 hour) than Furosemide (2-3 hours).
➢ A dose of 40 mg of furosemide is equivalent to 20 mg of Torsemide and 1 mg bumetanide.
• Thus, Bumetanide is 40 times more potent than Furosemide.
Furosemide Tab Lasix® , Lasimex® 40 mg
Tab 500 mg
Amp Lasix® 20 mg/2 ml
Oral Solu. Lasidex® 10 mg/ml
Bumetanide Tab Burinex® 1 mg
Amp 500 mcg/ml
Torsemide Tab Torem® , Demadex® 5 mg , 10 mg , 20 mg
Toras-Denk®
Tab PR Sutril Neo® 5 mg , 10 mg
Solu. For Inj. 10 mg/ml
Ethacrynic acid Tab Edecrin® 25 mg
Azosemide Tab , Amp Azoselic® , Daitalic® 40 mg , 80 mg (amp = 20 mg)
Piretanide Tab Arelix® , Eurelix® 3 mg , 6 mg
Tripamide Tab Normonal® 15 mg
b) Thiazide Diuretics and Thiazide-Like Diuretics
1. Thiazides and related compounds are moderately potent diuretics; they inhibit sodium
reabsorption at the beginning of the distal convoluted tubule, they act within 1 to 2 hours of
oral administration and most have a duration of action of 12 to 24 hours; they are usually
administered early in the day so that the diuresis does not interfere with sleep.
➢ Thiazides lose their effectiveness when creatinine clearance decreases to less than 30
mL/minute; thus, Not recommended for patients with a CrCl less than 30 mL/minute
because of reduced efficacy.
➢ Metolazone is an exception in that its activity may be preserved in these patients.
➢ Chlorthalidone, a thiazide-related compound, has a longer duration of action than the
thiazides and may be given on alternate days to control edema.
➢ Xipamide and Indapamide are chemically related to Chlortalidone.
2. Indapamide is claimed to lower blood pressure with less metabolic disturbances, particularly
less aggravation of diabetes mellitus; (thus its preferred by endocrinologists for the Rx of HT).
➢ Lowers systolic blood pressure 54% more than HCTZ.
➢ It has a direct vasodilation effect (Ca+2 channel blocker effect).
➢ In a study pairing an ACEI (perindopril) with Indapamide as the diuretic in
hypertensive diabetic persons, the relative risks of diabetic micro- and macro-vascular
disease were reduced in the ACEI-Indapamide combination by 9%, cardiovascular
mortality by 18%, and all-cause mortality by 14%. (8)
3. Thiazides have the unique ability to produce hyperosmolar urine, they can substitute for
antidiuretic hormone in the treatment of nephrogenic diabetes insipidus; the urine volume
of such individuals may drop from 11 L/day to about 3 L/day when treated with these drugs.
4. Thiazides also lower urinary calcium excretion, making them useful in preventing calcium-
oxalate containing kidney stones; This effect is associated with positive calcium balance and is
associated with an increase in bone mineral density and reductions in fracture rates attributable
to osteoporosis.
5. By a poorly understood mechanism, thiazides directly stimulate osteoblast differentiation
and bone mineral formation, further slowing the course of osteoporosis.
Chlorthalidone * Tab Hygroton® , Thalitone® 50 mg
Chlorothiazide Tab Diuril® 250 mg , 500 mg
I.V. Solu. 500 mg/vial
Hydrochlorothiazide Tab , Cap HydroDiuril®, Microzide®, Esidrix® 12.5 mg , 25 mg
Indapamide Tab Natrilix®, Diurex® 1.25 mg , 2.5 mg
Xipamide Tab Diurexan® 20 mg
Clopamide Tab Hypoten®, Brinaldix® 20 mg
Metolazone Tab Zaroxolyn®, Metenix® , Mykrox® 2.5 mg , 5 mg
Cyclopenthiazide Tab Navidrex® 5 mg
Bendroflumethiazide ** Tab Aprinox® , Urizide® , Naturetin® 2.5 mg , 5 mg
Hydroflumethiazide Tab Saluron® 50 mg
Methyclothiazide Tab Enduron® 5 mg
Polythiazide Tab Renese® 1 mg , 2 mg , 4 mg
Trichlormethiazide Tab Naqua® 2 mg , 4 mg
Quinethazone Tab Hydromox® 50 mg
* Chlorthalidone = Chlortalidone, they are the same drug.
** Bendroflumethiazide = Bendrofluazide, they are the same drug.

Comparison between Loop diuretics and Thiazides
c) K+ sparing Diuretics
1. On their own are weak diuretics, they cause retention of potassium and are therefore given with
thiazide or loop diuretics as a more effective alternative to potassium supplements.
2. Administration of a potassium sparing diuretic to a patient receiving an ACE inhibitor or an
angiotensin-II receptor antagonist can also cause severe hyperkalemia.
3. Eplerenone and Spironolactone are also an Aldosterone Antagonists, they are used in the
treatment of primary hyperaldosteronism.
4. Spironolactone is also used in the treatment of Ascites in cirrhosis of the liver, it frequently
causes gastric upsets and can cause peptic ulcers.
➢ Furosemide can be used as an adjunct with Spironolactone in Ascites.
➢ Low doses of spironolactone are beneficial in moderate to severe heart failure.
➢ It’s also acts as anti-androgen that is employed for reducing elevated or unwanted
androgen activity in the body.
➢ Thus, it’s used off-label in the treatment of Hirsutism in females, and hormonal Acne.
➢ Also used to treat hyperandrogenism in polycystic ovary syndrome (PCOS).
5. Eplerenone is a selective aldosterone antagonist, adverse effects such as Gynecomastia and
vaginal bleeding seem to be less likely in patients who take Eplerenone than in those who take
spironolactone.
➢ Clinical trials demonstrated that Eplerenone has antihypertensive activity that is additive
with that of either an ACEIs or ARBs alone.
➢ In diabetic hypertensive patients with microalbuminuria, adding Eplerenone to ACEIs
therapy reduces proteinuria more than using the ACRIs alone, independent of effects on
Blood Pressure.
Non-Aldosterone Antagonists (epithelial channel blockers)
Amiloride Tab Midamor® 5 mg
Triamterene Cap Dyrenium ® 50 mg , 100 mg
Aldosterone Antagonists
Eplerenone Tab Inspra® 25 mg , 50 mg
Spironolactone Tab Aldacton ® 25 mg , 50 mg , 100 mg
d) Osmotic Diuretics
Mannitol is used to decrease (↓) intraocular pressure, and in the treatment of cerebral
edema, it’s also used to force diuresis in Anuria/Oliguria.
➢ Used for Preservation of perioperative renal function in patients undergoing major
vascular and cardiac surgery and in those with jaundice.
➢ Used for Promotion of urinary excretion of toxic materials.
➢ Also used as Mucolytic by inhalation route for the treatment of Bronchiectasis in patient
suffering from Cystic Fibrosis.
➢ In concentrations of 15% or greater, mannitol may crystallize when exposed to low
temperatures. Do not use a mannitol solution containing crystals. If such crystallization
occurs, the recommended procedure for resolubilization is to heat the mannitol in a dry heat
cabinet to 70 °C for flexible plastic containers with the overwrap intact or to 80 °C for glass
containers with vigorous shaking; the use of a water bath is not recommended.
Other Osmotic Diuretics include: Glycerin, Isosorbide and Urea. (Rarely used these days).
Scientific name Dosage form Trade Name Conc.
Mannitol Inj. Solu. (infusion) Osmitrol® 5% , 10% , 20% , 25%
Isosorbide Oral Solu. Ismotic® (45%) 100 gm/220 mL
Glycerin Oral Solu. Osmoglyn® (50%) 0.6 mg/ml
e) Carbonic anhydrase inhibitors (CAIs)

1. Carbonic anhydrase inhibitors are weak diuretics; they are mainly used to treat Glaucoma;
(See chapter 12)
2. Acetazolamide inhibits carbonic anhydrase, an enzyme which is responsible for the small
amount of active Na+ reabsorption in the proximal tubule in exchange for H+ secretion into the
tubule.
➢ Used with other medications to treat high pressure inside the eye due to certain types of
Glaucoma; It works by decreasing the production of fluid inside the eye.
➢ It is also used as an anticonvulsant to control certain seizures in the treatment of epilepsy.
➢ It is also sometimes used to prevent or lessen some effects in mountain climbers who
climb to high altitudes; it can decrease headache, tiredness, nausea, dizziness, and shortness
of breath that can occur when climbing quickly to high altitudes
➢ Used for urine alkalizing to enhance renal secretion of uric acid and cysteine.
Oral CAIs
Scientific name D. form Trade name Conc. Indication
Acetazolamide Tab Cidamex® 250 mg Glaucoma, Drug-induced edema,
Cap ER Diamox Sequels® 500 mg CHF edema, Mountain Sickness
Methazolamide Tab Neptazane® 25 mg , 50 mg Glaucoma , Altitude Sickness
CAIs as Eye Drops
Dorzolamide Eye drop Trusopt® , Xola® 2% Ocular hypertension (only)
Brinzolamide Eye drop Azopt® 1% Ocular hypertension +
Open-angle Glaucoma
Dorzolamide + Eye drop Cosopt® , Xolamol® 0.5/2% Open-angle Glaucoma (only)
Timolol *
* Timolol is a Beta blocker, used topically to treat Glaucoma
** For other combination products see chapter 12, section 1.

F) Combination Diuretics products:
➢ These products usually contain a Thiazide/Loop diuretic plus a Potassium sparing diuretic,
this combination cause a balance in potassium levels.
➢ It is preferable to prescribe thiazides and potassium-sparing diuretics separately, the use of fixed
combinations may be justified if compliance is a problem.
Trade name Dosage Scientific name concentration
form Loop Diuretic + K sparing Diuretic
Lasilacton® Tab Furosemide + Spironolactone 40 mg + 100 mg
Frusene® Tab Furosemide + Triamterene 40 mg + 50 mg
Frumil® Tab Furosemide + Amiloride 40 mg/5 mg , 80 mg/10 mg
Buriplus® Tab Bumetanide + Amiloride 1 mg + 5 mg
Thiazide Diuretic + K sparing Diuretic
Navispare® Tab Cyclopenthiazide + Amiloride 2.5 mg + 2.5 mg
Moduretic® Tab Hydrochlorothiazide + Amiloride 50 mg + 5 mg
Aldactazide® Tab Hydrochlorothiazide + Spironolactone 25 mg/25 mg , 25 mg/50 mg
Dyazide® Tab Hydrochlorothiazide + Triamterene 50 mg + 25 mg
Maxzide® Cap Hydrochlorothiazide + Triamterene 50 mg + 75 mg
Kalspare® Tab Chlorthalidone + Triamterene 50 mg + 50 mg
Epitens® Tab Xipamide + Triamterene 10 mg + 30 mg
3.2-Angiotensin-converting enzyme inhibitors (ACEIs)

1. Examples include (Captopril, Enalapril, Lisinopril and Ramipril).
2. They Inhibit the conversion of angiotensin I to angiotensin II (a powerful vasoconstrictor),
also prevent the degradation of bradykinin (a vasodilator) thus Causing vasodilatation, and
they decrease aldosterone secretion; (thus inhibiting the reduction in urine volume and the
raise in blood pressure due to increased blood volume).
• The main uses of ACE inhibitors are in the management of heart failure, hypertension, and
myocardial infarction, also they are used for the prevention and treatment of diabetic
nephropathy.
• Can provide nephroprotection and reduced CV risk when used in diabetic patients.
• It may take several weeks before the full antihypertensive effects of ACEIs are seen.
• In Heart Failure; They Decreased mortality (about 25%–50% relative risk reduction
compared with placebo depending on severity of HF)
3. Pronounced hypotension may occur at the start of therapy with ACEIs (first dose hypotension)
(1). Therefore:
A- The first dose should preferably be given at bedtime.

B- Starting dose should be low then increased gradually.
4. All ACEIs (except Captopril and Lisinopril) undergo hepatic conversion to active
metabolites, so these agents may be preferred in patients with severe hepatic impairment.
5. Renal function and electrolytes should be checked before starting ACEIs (or increasing the
dose) and monitored during treatment; Patients with an increase in serum creatinine of greater
than 30% should have their ACEI therapy temporarily discontinued.

6. Adverse effects include persistent dry cough, Angioedema (swelling of the face, lips and
tongue), and hyperkalemia.
a. If dry cough is annoying to the Patient → Switch to ARBs.
b. A new study suggests that iron supplementation may be a simple solution to the
persistent dry cough associated with the use of ACEIs
c. Angioedema is treated with an antihistamine, if no response occurs then stop the ACEI.
➢ Sever angioedema is treated with norepinephrine S.C. inj. (EpiPen®).
d. They are contraindicated in pregnancy (teratogenic).
Enalapril * Tab Renitec , Vasotec , Korandil
® ® ® 5 mg , 10 mg , 20 mg
Lisinopril * Tab Zestril®, Privinil®,Lisnop®, Omace® 5 mg , 10 mg , 20 mg
Captopril Tab Capoten , Aceprotin , Captophen
® ® ® 25 mg , 50 mg
Ramipril Tab , Cap Altace , Tritace , Rampil
® ® ® 2.5 mg , 5 mg , 10 mg
Imidapril Tab Tanatril , Hipertene
® ® 2.5 mg , 5 mg , 10 mg
Delapril Tab Delaket ® 15 mg , 30 mg
Benazepril Tab Lotensin ® 5 , 10 , 20 , 40 mg
Fosinopril ** Tab Monopril ® 10 , 20 , 40 mg
Cilazapril Tab Vascace ® 5 mg
Moexipril Tab Perdix , Univasc
® ® 7.5 mg , 15 mg
Perindopril Tab Aceon ® 2 mg , 4 mg , 8 mg
Tab Coversyl ® 2.5 mg , 5 mg , 10 mg
Quinapril Tab Accupril , Accupro
® ® 5 mg , 10 mg , 20 mg
Trandolapril Tab Gopten , Mavik
® ® 1 mg , 2 mg , 4 mg
Zofenopril Tab Zofecard , Zocardis
® ® 15 mg
* Enalapril is a pro-drug which is converted into Enalaprilat.
* Lisinopril is given once daily without regard to meal (not effected by food).
** Fosinopril is the only ACEI that is eliminated from both kidney and liver.
Note:
➢ So many ACEIs are available in the markets; which one is better than others?
Well; the answer to that question is complicated, as each drug has some advantages over others,
and that’s the beauty of pharmacology and pharmacotherapy. So; below some studies that shows
some of the main differences in ACEIs.
A) Comparison of the Efficacy and Safety of Different ACEIs in Patients with Chronic Heart
Failure; a meta-analysis of ACEIs in patients with heart failure showed that:
1) Enalapril might be the best option when considering factors such as increased ejection
fraction, stroke volume, and decreased mean arterial pressure. However, Enalapril was
associated with the highest incidence of cough, gastrointestinal discomfort, and greater
deterioration in renal function.
2) Trandolapril ranked first in reducing systolic and diastolic blood pressure.
3) Ramipril was associated with the lowest incidence of all-cause mortality.
4) Lisinopril was the least effective in lowering systolic and diastolic blood pressure and was
associated with the highest incidence of all-cause mortality.
B) Regarding Perindopril: has a sustained 24 h antihypertensive activity with once-daily
dosing, it was able to reverse arterial remodeling in hypertensive patients; also, trials have
shown that reversal of abnormal endothelial function. (9)
➢ In a study pairing an ACEI (Perindopril) with Indapamide as the diuretic in hypertensive
diabetic persons, the relative risks of diabetic micro- and macro-vascular disease were
reduced in the ACEI-Indapamide combination by 9%, cardiovascular mortality by 18%, and
all-cause mortality by 14%. (8)
3.3-Angiotensin II receptor antagonists (A2RAs or ARBs)
1. Examples include (Candesartan, Telmisartan, losartan and valsartan), (Sartans).
2. They act as vasodilators; They block the binding of angiotensin II to the AT1 receptor,
thereby inhibiting the effects of angiotensin II; Their main uses are in the management of heart
failure, hypertension, diabetic nephropathy and myocardial infarction.
➢ As ACEIs; they Decrease HF-related hospitalizations and decrease death from CV causes.
3. Unlike ACE inhibitors they do not inhibit the breakdown of bradykinin; thus, they are less
likely to cause the persistent dry cough which can complicate ACEIs therapy; They are a
useful alternative for patients who have to discontinue an ACEI because of persistent cough.
4. Contraindicated in pregnancy (teratogenic).
5. ARBs have differing potencies in relation to blood pressure control, with statistically differing
effects at the maximal doses. When used in clinical practice, the particular agent used may vary
based on the degree of response required.
6. Some of these drugs have a Uricosuric Effect (increase uric acid secretion in urine); such as
Losartan.
7. ARBs are slightly more effective than ACEIs in preventing angiotensin II vasoconstriction due
the last can be generated from angiotensin I by non-ACE enzyme (such as chymase); Thus, ARBs
are slightly better Antihypertensives than ACEIs.
Candesartan Tab Atacand®, Blopress®, Amias® 8 mg , 16 mg
Losartan Tab Cozaar® , Losanet® , Angizar® 25 mg , 50 mg
Telmisartan Tab Micardis® 20 mg , 40 mg , 80 mg
Valsartan Cap Diovan®, Tareg® , Univan® , Arbiten® 80 mg , 160 mg
Irbesartan Tab Avapro® , Approvel® , Gezlan® 75 mg , 150 mg , 300 mg
Olmesartan Tab Benicar® , Olmetec® 5 mg , 20 mg
Fimasartan Tab Kanarb® 60 mg , 120 mg
Eprosartan Tab Teveten® 400 mg , 600 mg
Azilsartan Tab Edarbi® 40 mg , 80 mg
Note1:
We all know that Antagonizing angiotensin II will lower the high blood pressure; but what if we
triggered it and used Agonism instead??? The answer is below:
➢ Recently the US (FDA) has approved angiotensin II injection for intravenous infusion
to increase blood pressure in adults with septic shock or other distributive shock.
synthetic human Injectable Giapreza ® 2.5 mg/ml,
angiotensin II Solu. 5 mg/2 ml
Note2:
Again; so many ARBs are available in the markets; are they all the same? Here some Key elements
➢ Losartan: - The only medicine in its class proven to lower the chance of stroke.
- Only ARB that has been shown to reduce serum uric acid levels.
- Only ARB approved by the FDA for treating nephropathy in patients with T2DM.
➢ Valsartan: - First ARB to receive approval in Heart Failure
- Reverses ventricular remodeling and Improves survival outcome in HF.
➢ Telmisartan: - Highly selective inhibition of the angiotensin II receptor 1 (AT1)
- Has the longest plasma half-life and largest volume of distribution of any ARBs.
- Powerful 24-hour action, curbing the morning surge in blood pressure
- Has PPAR-gamma activity and hence improves Insulin sensitivity
➢ Olmesartan: - Significant mean double-digit blood pressure (BP) reductions vs baseline at
the starting dose, only once daily dose.
Note3: Anti-inflammatory effects of Olmesartan
o EUTOPIA study, stated that Treatment with Olmesartan significantly reduces biochemical
markers of (vascular) inflammation in patients with essential hypertension by as early as
week 6 of therapy; These anti-inflammatory properties may have beneficial cardiovascular
effects in addition to their BP lowering action.
Note4: AT 1 affinity
o The specific AT1 affinity relates to how specifically attracted the medicine is for the correct
receptor, in which Valsartan has the highest affinity (20,000 folds), and Losartan has the
Lowest affinity (1000-fold).
Valsartan > Olmesartan (12,500) > Candesartan > Irbesartan (8500) > Telmisartan > Losartan
o Although; Olmesartan and Telmisartan are faster than older ARBs in Blood Pressure reduction
at 1 and 2 weeks.
Note5: Monotherapy at Starting doses achieving goal BP*

Drug Olmesartan Telmisartan Irbesartan Losartan Valsartan
Daily Dose 20 mg/d 40 mg/d 150 mg/d 50 mg/d 80 mg/d
BP reduction 33% 32% 26% 16% 14%
* a retrospective analysis; note also that combination products have the similar results.
Note6: ACEIs or ARBs in DM?
A) A recent meta-analysis (Cheng et al 2014) concluded that:
➢ ACEIs and ARBs differentially affect the risk of all-cause mortality, CV deaths and CV
events patients with diabetes.
➢ ACEIs reduce the risk of mortality, myocardial infarction and heart failure, while
ARBs do not affect risk of mortality and major CV events.
➢ ARBs therapy did reduce the risk of heart failure.
➢ No effect on stroke was seen with either treatment.
➢ Based on these data, ACEIs should be considered first-line treatment in patients with
diabetes mellitus, to reduce mortality and morbidity, and not ARBs.
➢ This study questions the ‘alternative’ status of ARBs in diabetics.
B) Although; Telmisartan and Olmesartan: May increase insulin sensitivity (activate PPAR
Gamma), May decrease systemic inflammation (decrease CRP).
C) The Spanish researchers found that taking (ARBs or ACEIs or BBs) at bedtime rather than waiting
until morning may cut the risk of developing type 2 diabetes by more than half. (18)
Note7: FDA approvals

1) Valsartan and Candesartan - FDA approved for heart failure, to reduce cardiovascular
mortality in clinically stable patients with left ventricular failure, left ventricular dysfunction
following myocardial infarction.
2) Irbesartan - FDA approved for diabetic nephropathy.
3) Losartan - FDA approved for stroke prophylaxis
Note8: Bed time is the best time to take blood pressure medication
o People with high blood pressure who take all their ARBs or ACEIs or BBs at bedtime have better
controlled blood pressure and a significantly lower risk of death or illness caused by heart or
blood vessel problems, compared to those who take their medication in the morning. (17)
Note9: Combination Products of ACEIs and ARBs:
o Products incorporating an ACEIs/ARBs with a thiazide diuretic or a calcium-channel blocker are
available for the management of hypertension. Use of these combination products should be
reserved for patients whose blood pressure has not responded adequately to a single
antihypertensive drug.
➢ For combination with diuretics see next page.
➢ For combination with other drugs see section 8 below (2 fixed products).
Diuretics and ACE inhibitors Combos: Diuretics and ARBs Combos:

• Hydrochlorothiazide—captopril (Capozide®) HCTZ—losartan (Hyzaar®), (Angizar-H)®
• Hydrochlorothiazide—benazepril (Lotensin HCT®) Hydrochlorothiazide—Irbesartan (Avalide)®
• Hydrochlorothiazide—Lisinopril (Prinzide)®, Hydrochlorothiazide—valsartan (Co-Diovan)®
(Zestoretic)® Hydrochlorothiazide—Telmisartan (Micardis plus)®
• Hydrochlorothiazide—Enalapril (Vaseretic®) Hydrochlorothiazide—candesartan (Atacand plus)®
• Hydrochlorothiazide—Fosinopril Hydrochlorothiazide—Eprosartan (Teveten HCT)®
• Hydrochlorothiazide—Moexipril (Uniretic®) Hydrochlorothiazide—Olmesartan (Benicar HCT)®
Chlorthalidone—Azilsartan (Edarbyclor) ®
3.4- Direct Renin inhibitor

1. These drugs inhibit the first and rate-limiting step of the renin–angiotensin–aldosterone
system (RAAS), namely the conversion of angiotensinogen to angiotensin I; This leads to a
totality in absence of Angiotensin II based on the rationale that renin only acts to inhibit this step
unlike Angiotensin Converting Enzyme which is also involved in other biochemical reactions.
2. The first drug in this class was Aliskiren, which received a marketing approval in 2007; As of
January 2012, it is the only renin inhibitor on the market.
➢ It can also be combined other Antihypertensives.
➢ Aliskiren is an alternative therapy because of lack of long-term studies evaluating CV
event reduction and its significant cost.
➢ Aliskiren can cause diarrhea, especially at higher doses.
➢ Aliskiren can also cause cough and angioedema, but probably less often than ACEIs.
➢ Aliskiren is contraindicated during pregnancy.
Aliskiren Tab Rasilez® , Tekturna® 150 mg , 300 mg
Aliskiren + Amlodipine Tab Tekamlo® 150 mg/5mg , 150 mg/10mg
Aliskiren + Valsartan Tab Valturna® 150 mg/160 mg
3.5- Neprilysin inhibitors

1. Neprilysin is responsible for the degradation of atrial and brain natriuretic peptide, thus a
Neprilysin inhibitor act by increasing levels of natriuretic peptides; resulting in varied
effects including increased diuresis, natriuresis, and vasodilation.
2. Sacubitril is a Neprilysin inhibitor, it’s indicated in combination with Valsartan for the
treatment of chronic Heart failure in patient with reduced ejection fraction (reduce risk of
Cardiovascular death by 20% and reduce hospitalization rate by 21%).
3. Sacubitril/Valsartan Combo decreased all-cause mortality (16% relative risk reduction) and CV
death (20% relative risk reduction) compared with Enalapril monotherapy.
➢ Although a study published recently; showed that Sacubitril/valsartan did not result in a
Significant lower rate of hospitalizations for heart failure and death from cardiovascular
causes among patients with heart failure and an ejection fraction of 45% or higher. (16)
➢ This study shows that Sacubitril/Valsartan Combo is useful only in heart failure with low
ejection fraction.
4. Because of the risk of angioedema, patients should not start taking Sacubitril within 36 hours
of taking their last ACEI dose.
5. Omapatrilat: also, a Neprilysin inhibitor (as well as an ACEI and aminopeptidase P inhibitor),
was studied in both hypertension and HF, but terminated because of an unacceptable
incidence of angioedema (3-fold increased risk of angioedema as compared with Enalapril).
Sacubitril + Valsartan Tab Entresto ® (24 mg + 26 mg), (49 mg + 51 mg),
(97 mg + 103 mg)
3.6-Beta-adrenoceptor blocking drugs (Beta-Blockers)
a. Beta blockers are drugs that interrupt the transmission of stimuli through beta receptors of
the body; and since the actions that they block originate in the adrenal glands they are called beta
adrenergic blocking agents.
b. There are 3 types of beta receptor in the body: beta1, beta2, beta3; Beta1 receptors are located
mainly in the heart muscle; Beta2 receptors in the airways and blood vessels; Beta3 are
located on adipocytes and are thought to be involved with fatty acid metabolism,
Cardioselective drugs act mainly on beta1 receptors: non-Cardioselective drugs on all types.
c. By occupying the beta receptors, in different parts of the body, beta blockers nullify the
stimulating action of norepinephrine (noradrenaline), the main “fight or flight” hormone;
and as a result, they reduce the force and speed of the heart beat and prevent the dilation
of the blood vessels surrounding the brain and leading to the extremities, as a summery:
➢ In Heart: Slowing of the heart rate and reduction of the force of the heart beat reduces the
workload of the heart (means that less oxygen is required), thus helping to prevent angina
and abnormal heart rhythms; This action may worsen heart failure, however.
➢ In Lungs: Constriction of the airways, thus may provoke breathlessness in asthmatic patients
or those with chronic bronchitis.
➢ In Brain: Dilation of the blood vessels that surround the brain is inhibited, thereby
preventing migraine.
➢ In Blood vessels: causing constriction, thus may cause coldness of the hands and feet and
erectile dysfunction.
➢ In Eye: Beta blocker eye drops reduce fluid production, lowering pressure inside the eye.
➢ In Muscles: Muscle tremor caused by anxiety or over activity of the thyroid gland is reduced.
d. They lower Blood pressure due to reduction in the rate and force at which the heart pumps
blood around the body.
1. Examples include (Atenolol, Bisoprolol, Carvedilol, Metoprolol, and Propranolol).
2. Beta blockers are used in the management of:
a. Cardiovascular disorders such as hypertension, angina pectoris, cardiac
arrhythmias, myocardial infarction, and some of them are used for heart failure.
b. They are also given to control symptoms of sympathetic over activity, anxiety states,
hyperthyroidism (in which all condition has a hypersecretion of norepinephrine).
c. Used in the prophylaxis of migraine, (Propranolol).
d. Some Beta blockers used as eye drops (Timolol) to reduce raised intra-ocular pressure
in Glaucoma.
3. Bisoprolol, Carvedilol, Metoprolol (Succinate) and Nebivolol are the beta-blockers that are
used to treat heart failure (other beta- blockers are contraindicated in heart failure). (4-5)
➢ When used in HF they decrease mortality (about 35%), and decreased hospitalizations
(about 25%) compared with placebo.
➢ Should be initiated only when HF symptoms are stable and patients are euvolemic.
➢ higher β-blocker doses are associated with greater mortality reduction; Therefore, if
hypotension alone is the problem, try reducing the ACEI (or another antihypertensive) first.
4. Esmolol is a relatively Cardioselective beta-blocker with a very short duration of action, used
intravenously for the short-term treatment of supraventricular arrhythmias.
5. Sotalol is a non-Cardioselective beta-blocker with additional class III anti-arrhythmic activity,
that is used for prophylaxis and treatment in ventricular & supraventricular arrhythmias.
6. When used for heart failure or Hypertension, β-blockers should be started in very low doses with
slow upward dose titration every one or two weeks (start low, go slow) example:
Carvedilol start with 3.125 mg 6.25 mg 12.5 mg 25 mg
7. Beta-blockers can precipitate bronchospasm and should therefore usually be avoided in
patients with a history of asthma, or use Cardioselective Beta blockers.
8. Beta-blockers can affect carbohydrate metabolism, causing hypoglycemia or hyperglycemia
in patients with or without diabetes; they can also interfere with metabolic and autonomic
responses to hypoglycemia, thereby masking symptoms, such as tachycardia.
9. Beta-blockers, especially when combined with a thiazide diuretic, should be avoided for the
routine treatment of uncomplicated hypertension in patients with diabetes or in those at
high risk of developing diabetes.
10. Abrupt cessation of β-blocker therapy should be avoided (abrupt discontinuation of β-
blockers may be associated with tachycardia, in addition to increased BP). For these reasons, it
is always prudent to taper the dose gradually over 1 to 2 weeks before discontinuation.
11. At higher doses, β1 selectivity is lost.
12. Some Beta Blockers Properties:
A. Water solubility: the major β-selective agents can be remembered by the mnemonic
PAANTS = (Pindolol, Atenolol, Acebutolol, Nadolol, Timolol, and Sotalol). Water soluble
agents tend to be renal excreted (thus C.I. in renal failure), have longer half-lives, are less
able to cross the blood brain barrier and are less likely to cause CNS side effects, others
are lipid soluble which can cause nightmares (cross blood brain barrier).
B. Intrinsic sympathomimetic activity (ISA, partial agonist activity) represents the capacity
of beta-blockers to stimulate as well as to block adrenergic receptors. (Oxprenolol, Pindolol,
Acebutolol, Carteolol, Mepindolol and Celiprolol) have intrinsic sympathomimetic
activity; they tend to cause less bradycardia than the other beta-blockers and may also
cause less coldness of the extremities.
C. Vasodilation effect: (Labetalol, Celiprolol, Carvedilol, and Nebivolol) are beta-blockers
that have an arteriolar vasodilation action, by different mechanisms, and thus lower
peripheral resistance.
D. Membrane stabilizing activity: or local Anesthetic activity (Acebutolol, Betaxolol,
Pindolol and Propranolol) due their ability to block Na+ channels.
E. Anti-Oxidant effect: (Carvedilol and Nebivolol) only.
F. Calcium Channel Blocking effect: (Carvedilol, Betaxolol and Bevantolol)
13. The β-blockers decrease libido and cause impotence, Drug-induced sexual dysfunction can
severely reduce patient compliance, Beta-blockers are also associated with fatigue, coldness
of the extremities (may be less common with those with ISA, see above), and sleep
disturbances with nightmares (may be less common with the water-soluble beta-blockers, see
notes above).
14. Obviously, BBs are not the same, below some more interesting facts:
A) A new classification divides BBs into three different generations, the 1st generation being
non-selective, the 2nd generation being beta1-selective (Cardioselective), and the 3rd generation
showing additional vasodilating effects.
B) Some BBs exert additional properties independent of beta-receptors:
1) Propranolol, its D-enantiomer inhibits the conversion of Thyroxin (T4) to
Triiodothyronine (T3), whereas only the L-enantiomer shows beta-blocking effects.
2) Nebivolol, the drug with the highest beta1-selectivity, it causes NO-derived vasodilation,
this vasodilating effect has clinical relevance since it has been shown that the beta-blocking
potency of 5 mg Nebivolol is comparable to that of 25 mg Atenolol, whereas the blood
pressure lowering effect of 5 mg Nebivolol is comparable to that of 100 mg Atenolol. (10)
➢ Nebivolol decreases the incidence of new onset diabetes compared to placebo. (11)
➢ Nebivolol does not decrease nocturnal melatonin release (cause less sleeplessness).
➢ Plasma concentrations of Nebivolol do not increase during exercise.
3) Carvedilol, has an additional blocking effects on adrenergic alpha1-receptors; Thus, this
drug exerts an additional effect independent of beta-blockade that, on the one hand,
increases its blood pressure lowering effect and, on the other hand, may decrease
potential side effects resulting from beta-blockade since the decrease of blood pressure
caused by alpha-blockade may cause a refractory increase of sympathetic tone, thus reducing
beta-blocking (side) effects such as bradycardia, bronchial constriction, impotence, and
metabolic side effects.
➢ Carvedilol shows a favorable metabolic effect such as an increase of the insulin
sensitivity index and a decrease in triglyceride plasma concentrations. (12)
➢ Carvedilol does not reduce nocturnal melatonin release (cause less sleeplessness).
➢ Carvedilol shows an increase in heart rate in healthy subjects with the administration
of increasing doses of the drug, thus being a unique finding in the class of beta-blockers
that increasing doses may cause increasing heart rates. (13,14)
4) Bisoprolol, has the lowest drug-drug interaction profile compared with other BBs, thus,
making it a very good option when the patient has many medications.
➢ Comes in 2nd place in Beta1-selectivity, after Nebivolol.
➢ Bisoprolol inhibits renin secretion by about 65%.
Cardio-Selective β blockers
Atenolol Tab Tenormin® , Novaten® ,Vascoten® 25 mg , 50 mg , 100 mg
Amp Tenormin ® 0.5 mg/ml (10 ml amp)
Bisoprolol Tab Concor cor , Zebeta
® ® 1.25 mg , 2.5 , 5 , 10 mg
Metoprolol Tab Hypopresor® , Lopress® 50 mg , 100 mg , 200 mg
(Tartrate) * Amp Betaloc® 1 mg/ml (5 ml amp)
Metoprolol Tab Betaloc® , Toprol XR® 50 mg , 100 mg , 200 mg
(Succinate) * MetoHexal® 23.75 mg , 50 mg , 100 mg
Nebivolol Tab Bystolic® , Nebilet® 2.5 mg , 5 mg , 10 mg
Landiolol Amp Onoact® 50 mg/amp
Tilisolol Tab Selecal® 10 mg , 20 mg
Non-Cardio-Selective β blockers
Propranolol Tab Inderal® , Becardin® 10 mg , 40 mg
Cap Innopran® 80 mg , 120 mg , 160 mg
Amp Inderal® 1 mg/1 ml
Nadolol Tab Corgard® 40 mg , 80 mg
Mixed α and β blockers
Carvedilol Tab Dilatrend® , Coreg® 3.125 mg , 6.25 mg ,
12.5 mg , 25 mg
Cap Coreg CR ® 10 mg , 20 mg ,
40 mg , 80 mg
Bucindolol Tab Gencaro ® 50 mg
Labetalol Tab Trandate® , Lobet® 50 , 100 , 200 , 400 mg
Inj. Amp Trandate ® 5 mg /ml (20 ml amp)
Cardio-selective β blockers with Intrinsic sympathomimetic activity (ISA)
Acebutolol Cap Sectral® 100 mg , 200 mg , 400 mg
Pindolol Tab Visken® 5 mg , 10 mg , 15 mg
Celiprolol Tab Celectol® 200 mg , 400 mg
Penbutolol ======
Tab Levatol® 20 mg , 40 mg
Oxprenolol ====
Tab Trasicor ® 20 mg , 40 , 80 , 160 mg

Other β blockers
Betaxolol Tab Kerlone® 10 mg , 20 mg
Esmolol Inj. Brevibloc ® 10 mg/ml (10 ml vial)
Sotalol Tab Sotacor ® 20 mg , 40 mg , 80 mg
Timolol Tab Betim ® 10 mg
β blockers: Dosage Form As Drops
Betaxolol Eye drop Betoptic® 0.5% , 0.25%
Timolol Eye drop Timolol® , Ophtamolol® , Timoptof® 0.5% , 0.25%
Carteolol Eye drop Ocupress® , Carteol® 1% , 2%
Levobunolol Eye drop Betagan ® 0.5% , 0.25%
Metipranolol Eye drop Optipranol® 0.3%
* Metoprolol Succinate is an extended-release medication, and Metoprolol Tartrate is an

immediate-release medication.
Diuretics and Beta-Blockers Combos:
➢ For combination with diuretics ↦ • Bendroflumethiazide—Nadolol (Corzide®)
• Chlorthalidone—atenolol (Tenoretic®)
For combination with other drugs see
• Hydrochlorothiazide—propranolol (Inderide®)
section 8 below (2 fixed products) • Hydrochlorothiazide—metoprolol (Lopressor HCT®)
• Hydrochlorothiazide—bisoprolol (Ziac®)
3.7- Calcium-channel blockers (CCBs)

o They dilate blood vessels by relaxing the muscle layer in the blood vessel walls and heart
(they does this by blocking the entry of calcium into the cells of the heart and blood
vessels), thus prevents constriction (as Vasodilators); Blood is more easily pumped through the
dilated vessels; this reduces the strain on the heart, they also improve blood flow and thus the
oxygen supply.
1. CCBs include:
A. Dihydropyridine (DHP) CCBs (ex: Amlodipine, Nifedipine): They have a greater
selectivity for vascular smooth muscle than for cardiac muscles and therefore their main
effect is vasodilatation; (They don’t dilate veins).
B. Non-Dihydropyridine CCBs (ex: Diltiazem and Verapamil): They have selectivity for
both Cardiac and vascular smooth muscle.
2. The main use of CCBs is in the management of Angina Pectoris and Hypertension (both types
of CCBs); some are also used in cardiac arrhythmias (non-Dihydropyridine CCBs).
➢ All CCBs are valuable in angina associated with coronary vasospasm.
➢ Some CCBs are used as Tocolytics to delay preterm delivery (Nifedipine), See chapter 7
➢ Some CCBs are used Topically to treat Hemorrhoids, see chapter 2; section 15.
3. Nifedipine is a short acting; therefore, it is commonly formulated as sustained release (SR)
formulation (long acting dosage form).
➢ Nifedipine is also indicated for Raynaud’s syndrome, postponement of premature labor,
and hiccup in palliative care.
4. Nimodipine is related to Nifedipine but the smooth muscle relaxant effect preferentially acts on
cerebral arteries; It’s approved in the prevention and treatment of vascular spasm following
aneurysmal subarachnoid hemorrhage.
5. When using CCBs (especially Dihydropyridine CCBs); a Dose-dependent peripheral
vasodilatation occurs, leading to pedal edema, ankle edema (swelling), dizziness,
headache, eye pain, and facial flushing.
➢ The peripheral edema can be reduced by combining with an ACEI or an ARB.
➢ Edema may respond only partially to diuretics.
6. Ankle edema is a troublesome side effects, more than 69% of patients may discontinue their
CCBs therapy due ankle edema; so, is there a CCB without that side effect?
➢ Unfortunately, No … But the risk of peripheral edema with Lipophilic Dihydropyridine
(DHP) CCBs was 57% lower than with traditional DHP CCBs.
• Lipophilic DHP CCBs include: (Manidipine, Lacidipine, Lercanidipine, Nicardipine).
➢ Also, the Incidence of peripheral edema in patients on DHPs was 12.3% compared with
3.1% with non-DHPs (Diltiazem, Verapamil).
7. Chronic use of CCBs can lead to gum hyperplasia.
8. Dihydropyridine CCBs can worsen proteinuria in patients with nephropathy.
9. Verapamil and Diltiazem should be avoided in heart failure because they may further depress
cardiac function and cause clinically significant deterioration.
➢ Verapamil is used also as prophylaxis of cluster headache and prevention of Migraine.
➢ Verapamil can prevent diabetes and enhance β-cell survival and function; (inhibits
thioredoxin-interacting protein, that leads to the death of the pancreatic beta cell). (19)
➢ Diltiazem has a less negative inotropic effect than Verapamil and significant myocardial
depression occurs rarely.
➢ Diltiazem and Verapamil are useful in diastolic HF (HF with preserved ejection fraction).
➢ For supraventricular tachycardia (PSVT), Diltiazem appears to be as effective as
Verapamil in treating re-entrant supraventricular tachycardia.
➢ Diltiazem is also indicated for Atrial fibrillation or Atrial flutter; The initial bolus should
be 0.25 mg/kg, intravenous (IV).
Dihydropyridine CCBs
Amlodipine Tab Istin® , Amlong® , Amady® 2.5 mg , 5 mg , 10 mg
Cap Norvasc ® 5 mg
Nifedipine Tab Adalat , Epilat , Adakate
® ® ® 10 mg , 20 mg
Tab Ex R Procardia , Adalat XL
® ® 30 mg , 60 mg , 90 mg
Nimodipine * Tab Nimotop® 30 mg
Vial Nimotop ® 200 mcg
Manidipine Tab Artedil ® 10 mg , 20 mg
Nisoldipine Tab Sular® 8.5 mg , 17 mg , 34 mg
Clevidipine Infusion Solu. Cleviprex ® 0.5 mg/ml
Isradipine Tab Prescal® , DynaCirc® 2.5 mg
Lacidipine Tab Motens , Lacipil
® ® 2 mg , 4 mg
Lercanidipine * Tab Zanidip , Lercadip
® ® 10 mg , 20 mg
Felodipine Tab , Tab XR Plendil® , Cabren® 2.5 mg , 5 mg , 10 mg
Nicardipine Cap Cardene ® 20 mg , 30 mg
Nitrendipine Tab Baypress , Cardif
® ® 10 mg , 20 mg
Non-Dihydropyridine CCBs
Diltiazem Cap SR Mono-Tildiem® 200 mg , 300 mg
Tab Tildia®, Progor®, Altiazem®, 60 mg , 90 mg , 120 mg
Verapamil Tab Zilden ® ®
Danistole , Calan® , Isoptin® 40 mg , 80 mg
Cap SR Verapress , Univer
® ® 120 mg , 180 mg , 240 mg
Gallopamil ** Tab , Cap Procorum ® 50 mg
Fendiline Tab , Cap Sensit , Difmecor
® ® 50 mg , 75 mg , 100 mg
* Nimodipine can pass the blood-brain barrier and is used to prevent cerebral vasospasm.
* Lercanidipine prevents renal damage induced by angiotensin II and demonstrates anti-inflammatory,
antioxidant, and anti-atherogenic properties through an increasing bioavailability of endothelial nitric
oxide; its displays a renal protection with a significant decrease of microalbuminuria and improvement
of creatinine clearance.
** Gallopamil is an analog of Verapamil.
3.8 - Fixed-dose Combination Products
A) Two fixed products:
Several fixed-dose combination products are available; their use can reduce the number of
tablets or capsules taken by patients. This has been demonstrated to improve adherence
compared with using two separate single-drug products. Improved adherence may increase
the likelihood of achieving goal BP values.
Diuretics + ACEIs
Delapride® Tab Indapamide + Delapril 2.5 mg/15 mg , 2.5 mg/30 mg
Coversyl Plus® Tab Indapamide + Perindopril 1.25 mg/5 mg , 2.5 mg/10 mg
CCBs + ACEIs
Coveram®, Prestalia® Tab Amlodipine + Perindopril 5mg/5mg , 5mg/10mg, 10mg/10mg
Lotrel®, Amlobenz® Tab Amlodipine + Benazepril 5mg/10mg , 10mg/20mg
Hipril-A® Tab Amlodipine + Lisinopril 5mg/10mg
Eneas® Tab Nitrendipine + Enalapril 10mg/20mg
Lexxel® Tab Felodipine + Enalapril 5mg/5mg
Triapin® Tab Felodipine + Ramipril 2.5mg/2.5mg , 5mg/5mg
Vivace® Tab Manidipine + Delapril 10 mg/30 mg
Tarka® Tab Verapamil + Trandolapril 180mg/2mg , 240mg/2mg
CCBs + ARBs
Exforge® Tab Amlodipine + Valsartan 5 mg/80 mg , 5mg/160mg ,
10mg/160mg
Twynsta® Tab Amlodipine + Telmisartan 5mg/40mg , 10mg/40mg
Azor® , Sevikar® , Tab Amlodipine + Olmesartan 5mg/20mg , 10mg/20mg
Vocado® 10mg/40mg
CCBs + BBs
Amlong-A® Tab Amlodipine + Atenolol 5mg/50mg
Tenif® , Beta-Adalat® Cap Nifedipine + Atenolol 20mg/50mg
Logimax® Tab Felodipine + Metoprolol 5 mg/47.5 mg , 10 mg/95 mg
ARBs + BBs
Byvalson® Tab Valsartan + Nebivolol 80mg/5mg
B) Three Fixed-dose combination products (Triple products)

Exforge HCT® Tab Amlodipine + Valsartan + (5 mg/160 mg/12.5),
Hydrochlorothiazide (10 mg/160 mg/12.5 mg),
(5 mg/160 mg/25 mg),
(10 mg/160 mg/25 mg)
Tribenzor®, Tab Amlodipine + Olmesartan + (5 mg/20 mg/12.5 mg),
Sevikar HCT®, Hydrochlorothiazide (5 mg/40 mg/25 mg)
Vocado HCT® (10 mg/40 mg/25 mg)
Triplixam®, Tab Amlodipine + Perindopril + (5 mg + 5 mg + 1.25 mg),
Coveram Plus® Indapamide (10 mg + 5 mg + 1.25 mg),
(10 mg + 10 mg + 1.25 mg)
Amturnide® Tab Amlodipine + Aliskiren + 5mg/10mg/12.5 mg ,
Hydrochlorothiazide 10mg/20mg/25 mg

3.9 - Centrally acting (α) agonists Vasodilators:
1. They have been used in the past as alternatives to initial Antihypertensives, their use in mild-to-
moderate hypertension has been reduced, and they are used today in Emergency Hypertension or in
Hypertension Crisis.
2. Methyldopa is commonly used in pregnancy associated Hypertension.
➢ Methyldopa has dual mechanisms, first its converted into a false transmitter in the CNS, leading
to central α2 agonism, causing a decrease in norepinephrine and renin and ↓ BP; also, it acts as a
competitive inhibitor of dopa-decarboxylase (that converts L-dopa to dopamine).
➢ Common side effects of Methyldopa include orthostatic hypotension, fluid accumulation (in the
absence of a diuretic), and rebound hypertension on abrupt withdrawal; Sedation is a
common finding upon initiating therapy and when increasing doses; Fever and other flu-like
symptoms occasionally occur.
3. Minoxidil should be reserved for the treatment of severe hypertension resistant to other drugs.
Vasodilatation is accompanied by increased cardiac output and tachycardia and the patients develop
fluid retention; For this reason, the addition of a beta-blocker and a diuretic (usually furosemide, in
high dosage) are mandatory.
➢ Minoxidil is being less used these days as an emergency antihypertensive.
➢ Its cause Hypertrichosis (increased hair growth) as a side effect, thus it’s used topically to
reverse hair fall and boldness. (see dermatology chapter for more info).
4. Clonidine does not decrease renal blood flow or glomerular filtration and, therefore, is useful in the
treatment of hypertension complicated by renal disease.
➢ Also Used for prevention of recurrent migraine and prevention of vascular headache.
➢ Clonidine has the disadvantage that sudden withdrawal of treatment may cause severe
rebound hypertension, (causing a life-threatening hypertensive crisis).
5. Hydralazine is used to treat moderately severe hypertension; it is almost always administered in
combination with a β-blocker, such as Propranolol, Metoprolol, or Atenolol (to balance the reflex
tachycardia) and a diuretic (to decrease sodium retention).
➢ Hydralazine infusion is used for hypertensive emergencies (including during pregnancy).
➢ Hydralazine in combination with nitrate is also used for heart failure (patients who cannot
tolerate an ACEI or ARB, or in whom they are contra-indicated, may be given Isosorbide dinitrate
(ISDN) with hydralazine; The combination may be considered in addition to standard therapy with
an ACEI and a β-blocker in patients who continue to remain symptomatic.
➢ A lupus-like syndrome can occur with high dosage (usually occurs as sudden weight loss,
arthritis, and un-explained pain), it is reversible on discontinuation of the drug.
6. Moxonidine is licensed for mild to moderate essential hypertension; It may have a role when
thiazides, calcium-channel blockers, ACEIs, and beta-blockers are not appropriate or have failed to
control blood pressure.
7. Nitroprusside cause excessive plasma concentration of the Cyanide (because its molecule contains
CN); causing tachycardia, sweating, hyperventilation, arrhythmias, metabolic acidosis.
Hydralazine Tab Apresoline® 25 mg , 50 mg
Inj. Apresoline® 20 mg/1ml
Methyldopa Tab Aldomet® 250 mg , 500 mg
Nitroprusside Na+ Vial Nipride®, Nitropress® 50 mg
Clonidine Tab Catapress®, Duraclon® 0.1 mg , 0.2 mg , 0.3 mg
Inj. Solu. 100 mcg/ 1ml
Minoxidil Tab Loniten® 5 mg , 10 mg
Moxonidine Tab Physiotens®, Cynt® 200 mcg , 400 mcg
Guanfacine * Tab Tenex®, Intuniv® 1 mg , 2 mg , 3 mg , 4 mg
* Guanfacine is commonly mistaken with Guaifenesin (expectorant), so be careful.
* Guanfacine in Extended release tab (Intuniv®) is approved for the treatment of attention-deficit
hyperactivity disorder (ADHD) in people ages 6–17 years, also used as an Anxiolytic.
Combination products of Centrally acting (α) agonists Vasodilators
Methyldopa + Tab Aldomet Plus® (250 mg + 15 mg),
Hydrochlorothiazide (250 mg + 25 mg)
Clonidine + Chlorthalidone Tab Clorpres® , Combipres® (0.1 mg + 15 mg),
(0.3 mg + 15 mg)
Hydralazine + Cap Apresazide® (25 mg + 25 mg),
Hydrochlorothiazide (50 mg + 50 mg)
Hydralazine + Tab BiDil® 37.5 mg
Isosorbide dinitrate + 20 mg
3.10- selective α1 adeno receptor antagonists

1. They act by blocking nerve signals that trigger constriction of blood vessels; Only Prazosin,
terazosin, Doxazosin are FDA approved to treat hypertension; this group of drugs is available
for hypertensive patients who have not responded to initial antihypertensive therapy.
➢ Prazosin, terazosin and Doxazosin have α-blocking and vasodilator properties.
➢ Prazosin cause slight improvement in symptoms of Raynaud's disease.
➢ Prazosin is used in treating patients with posttraumatic stress disorder (PTSD)
induced nightmares due to its ability to block the effects of norepinephrine.
2. Others are used for the treatment of Benign Prostate Hyperplasia (BPH).
3. These drugs cause only minimal changes in cardiac output, renal blood flow, and glomerular
filtration rate; Thus, long-term tachycardia does not occur, but salt and water retention does.
4. Concomitant use of a β-blocker may be necessary to blunt the short-term effect of reflex
tachycardia.
5. First-dose phenomenon with α1 adeno receptor antagonists: A syncopal episode may occur
within 30 to 90 minutes of the first dose; similarly associated are postural hypotension, nausea,
dizziness, headache, palpitations, and sweating. To minimize these effects, the first dose should
be limited to a small dose (1 mg) and administered just before bedtime.
6. Yohimbine, a selective α2 receptor blocker, it increases norepinephrine; thus, raises blood
pressure and heart rate; its medically used for general sexual problems in both men and
women, arouse sexual excitement, for erectile dysfunction (ED), sexual problems caused by
selective-serotonin reuptake inhibitors (SSRIs).
➢ It acts by increasing blood flow and nerve impulses to the penis or vagina.
Doxazosin Tab Cardura® , Cardosyr® 1 mg , 2 mg , 4 mg
Tab MR Cardura XL® 8 mg
Prazosin Tab Minipress® , Hypovase® , Prazo® 1 mg , 2 mg , 5 mg
Prazosin + Polythiazide Cap Minizide® 1 mg/0.5 mg , 2 mg/0.5 mg
Terazosin Tab Hytrin® 1 mg , 2 mg , 5 mg , 10 mg
Alfuzosin Tab Xatral® 2.5 mg , 5 mg , 10 mg
Tamsulosin * Cap Flomax® , Omnic® 0.4 mg
Silodosin Cap Rapaflo® , Urorec® 4 mg , 8 mg
Indoramin Tab Doralese® 25 mg
α2 receptor blocker
Yohimbine Cap Aphrodien® 2.5 mg , 6 mg , 10 mg
* Tamsulosin: α1-blocker with greater selectivity for prostate muscle, has been used in the treatment of
benign prostatic hyperplasia. It is also used to dilate the ureter and helps to pass kidney stones. (it may ↓
outlet resistance and ↓ leak point pressures in patient with neurogenic bladder (2)
** See chapter 8 for benign prostatic hyperplasia.
3.11 – Drugs for Pheochromocytoma (non-selective α blockers)
1. Pheochromocytoma (PCC) is a neuroendocrine tumor of the medulla of the adrenal glands
(originating in the chromaffin cells), or extra-adrenal chromaffin tissue that failed to involute
after birth and secretes high amounts of catecholamine’s, mostly norepinephrine, plus
epinephrine to a lesser extent; Sign and symptoms include: Elevated heart rate, Palpitations,
Anxiety (resembling that of a panic attack), Diaphoresis (excessive sweating), and Headaches.
➢ Long-term management of Pheochromocytoma involves surgery; However, surgery should
not take place until there is adequate blockade of both alpha and beta-adrenoceptors; the
optimal choice of drug therapy remains unclear. Alpha-blockers are used in the short-term
management of hypertensive episodes in Pheochromocytoma.
➢ Once alpha blockade is established, tachycardia can be controlled by the cautious addition of
a beta-blocker (a cardio selective beta-blocker is preferred).
2. Phenoxybenzamine is a very powerful alpha-blocker (non-selective irreversible), its
effective in the management of Pheochromocytoma but it has many side-effects.
➢ Also indicated for Bladder Management Micturition disorders.
3. Phentolamine is a short-acting alpha-blocker (non-selective) used mainly during surgery of
Pheochromocytoma, also used for hypertensive emergencies, hypertensive crisis.
➢ Used for Erectile Dysfunction by intracavernous injection (a direct inj. To the penis!).
Phenoxybenzamine Cap , Inj. Solu. Dibenzyline® 10 mg (cap) , 50 mg/ml (inj.)
Phentolamine Inj. Solu. Regitine® , Oraverse® 10 mg/ml
Metyrosine Cap Demser® 250 mg
Tolazoline Inj. Solu. Priscoline®, Tolazil® 100 mg/ml
4.12- Nitrates, Vasodilators and Anti-Anginal Drugs:

a. Angina is chest pain produced when insufficient oxygen reaches the heart muscle; This is
usually caused by a narrowing of the blood vessels (coronary arteries) that carry blood and
oxygen to the heart muscle, in the most common type of angina (classic angina), pain usually
occurs during physical exertion or emotional stress. In variant angina, pain may also occur at rest.
➢ In classic angina, the narrowing of the coronary arteries results from deposits of fat, known
as atheroma, on the walls of the arteries. In the variant type, however, angina is caused by
contraction (spasm) of the muscle fibers in the artery walls.
b. Frequent episodes of angina can be disabling and, if left untreated, can lead to an increased risk
of a heart attack; Drugs can both relieve angina attacks and reduce their frequency, people
who suffer only occasional episodes are usually prescribed a rapid acting drug to take at the first
signs of an attack, or before an activity that is known to bring on an attack (Glyceryl trinitrate).
➢ Nitrates dilate blood vessels by relaxing the muscle layer in the blood vessel walls
c. If attacks become more frequent or more severe, regular preventative treatment may be advised.
Beta blockers, long-acting nitrates, and calcium channel blockers are used as regular medication
to prevent attacks; Drugs can often control angina for many years, but they cannot cure the
disorder. When severe angina cannot be controlled by drugs, then surgery to increase the blood
flow to the heart may be recommended.
Notes:
1. Nitrates are peripheral and coronary vasodilators used in the management of angina
pectoris, heart failure, and myocardial infarction (1).
2. Sublingual (or aerosol spray) of glyceryl trinitrate (GTN) are used to provide rapid
symptomatic relief of acute Anginal attack while and transdermal patches of glyceryl
trinitrate are used the long-term prophylaxis of angina.
3. Other Nitrate available are: Isosorbide Dinitrate (ISDN) and Isosorbide Mononitrate (ISMN)
which are commonly given by oral route.
• Isosorbide Dinitrate ISDN needs to be dosed three times a day.
• ISMN has longer duration than ISDN: The advantage of ISMN is twice daily dosing (or once
daily with sustained release products) which mean better compliance.
• Isosorbide dinitrate (ISDN) and Isosorbide Mononitrate (ISMN) are most commonly
prescribed for long-term prevention (prophylaxis) of angina episodes.
4. Nitrate can cause headache that is usually transient, typically lasting several days to few weeks.
Patients can use simple analgesics (as Paracetamol) when required to control any headaches.
5. Nitrates should not be used within 24 hours of taking Sildenafil or Vardenafil or within 48
hours of taking Tadalafil because of the potential for life-threatening hypotension; This may
cause death.
6. Nitrate tolerance is a major problem with the long-term use of nitroglycerin and long-acting
nitrates; Several agents such as ACEIs, N-Acetyl Cysteine (NAC), L-Methionine and diuretics
have been shown to reverse nitrate tolerance by increasing the availability of sulfhydryl
radicals; However, practical considerations suggest that less frequent administration (8 to 12
hrs. of nitrate-free intervals) is effective without introducing additional agents, (Free period is
usually at night).
➢ Carvedilol and Nebivolol (BBs with antioxidant + vasodilator effects) may reduce nitrate
tolerance.
7. Patient education about using sublingual glyceryl trinitrate:
A. In the event of an acute attack, patients should be instructed to sit or lie down, place the dose
(spray or tablet) under the tongue, and not swallow the tablet. Relief of pain should occur
within 5 minutes; If the pain persists or is unimproved 5 minutes after the first dose of GTN,
the patient should call an ambulance transport as they may be experiencing an MI; If patient
needs more than one tablet, he can take a maximum of three tablets in 15 minutes.
B. SL nitrates can also be used to prevent acute episodes if given 2 to 5 minutes prior to activities
known to produce angina; protection can last for up to 30 minutes.
C. The tablets should be dispensed in the original, unopened manufacturer ‘s container and
stored in the original brown bottle.
D. The bottle should be stored in a cool, dry place, but not refrigerated. The bottle should be
closed tightly after each opening.
E. GTN tablets should be supplied in glass containers of not more than 100 tablets closed with a
foil-lined cap, and containing no cotton wool wadding; they are discarded after 8weeks of use.
F. Expiration dating should be monitored closely, and tablets should be replaced immediately if
they are exposed to excessive light, heat, moisture, or air.
8. Sometimes glyceryl trinitrate GTN is used topically as a cream/gel for the treatment of
Hemorrhoids, due its vasodilator effect, for more details see chapter 2, section 15.
A) Nitrates:
Glyceryl trinitrate Sublingual Tab Angiseed® , Nitrostat® 0.5 mg
Patch Nitroderm® 10 mg , 20 mg
Infusion Tridil® , Nitrobid® 25 mg , 50 mg /250ml
Sublingual Spray Glytrin® 0.4 mg/puff
Isosorbide mono nitrate Tab Isosorbide mono nitrate® 10 mg , 20 mg , 40 mg
Tab Imdur® 60 mg
Isosorbide di nitrate Tab Isosorbide di nitrate® 10 mg , 20 mg , 40 mg
Sublingual Spray Angitak® 12.5 mg/puff
Inj. (amp) Isoket® 1 mg/ml (10 ml)

B) Other Anti-Anginal drugs:
These include: Ranolazine, Nicorandil, Trimetazidine and Ivabradine; each one has a special
feature and many advantages compared with traditional antianginals:
1. Ranolazine inhibits the late phase of the sodium current (late INa) improving the oxygen
supply-and-demand equation (2), is an anti-ischemic agent; Has an advantage over traditional
antianginal agents that it has no negative effect on heart rate and BP, which makes it useful in
patients in need of further antianginal therapy (who remain symptomatic while on standard
angina pharmacotherapy) but who have marginal BP or heart rates preventing titration of
conventional antianginal agents.
2. Nicorandil is a vasodilator (K Channel Activator); has both arterial and venous vasodilating
properties and is licensed for the prevention and long-term treatment of angina; Nicorandil
may produce additional symptomatic benefit in combination with other antianginal drugs.
3. Trimetazidine acts as fatty acid oxidation inhibitor, thus shifting to glucose oxidation →
stimulates glucose utilization → ATP production with less oxygen consumption ,,,,, It’s also used
as anti-vertigo and in tinnitus. (2), C.I. in Parkinson disease and renal failure.
4. Ivabradine is a pure heart rate lowering agent, acting by selective and specific inhibition of
the cardiac pacemaker If current that controls the spontaneous diastolic depolarization in the
sinus node and regulates heart rate, indicated in Symptomatic treatment of chronic stable
angina pectoris, and in chronic heart failure. (2) Decrease CV death for HF by 18%.
➢ It is licensed for the treatment of angina in patients who are in normal sinus rhythm in
combination with a β-blocker, or when β-blockers are contraindicated or not tolerated.
➢ licensed for mild to severe stable chronic heart failure (in combination with a β-blocker
unless contra-indicated or not tolerated), in patients who are in sinus rhythm.
➢ If there is no improvement within 3 months; Ivabradine should be discontinued.
Ranolazine Tab Ranexa® 500 mg , 750 mg , 1000 mg
Tab PR 375 mg , 500 mg
Nicorandil Tab Ikorel®, Dancor®, Sigmart® 10 mg , 20 mg
Trimetazidine Tab , Tab MR Vastrel® , Tricardia® 30 mg , 35 mg
Menthol + Sub-Lingual Validol® 60 mg
Menthyl isovalerate * Tab
Ivabradine Tab Procoralan®, Corlanor® 5 mg , 7.5 mg
* Validol® produces a sedative effect, at sublingual administration the effect is produced in 5 minutes
and 70 % of the preparation is released in 3 minutes; used in cases of heart disease, angina, motion
sick-ness, nausea, vomiting when seasick or airsick, hysteria, nervousness, headaches from taking
nitrates.
C) Other Central Vasodilators:

These include: Molsidomine, Isoxsuprine.
1. Molsidomine is a long acting vasodilating drug, its metabolized in the liver to the active
metabolite linsidomine, which is the compound that releases nitric oxide (NO) upon decay as
the actual vasodilating compound; thus, relaxing the smooth muscles of blood vessels.
➢ used for the prevention and long-term treatment of stable and unstable angina
pectoris, with or without left heart failure; also used to treat angina in the context of an
acute myocardial infarction; Also has a role in pulmonary hypertension.
2. Isoxsuprine is also a beta-adrenergic agonist that causes direct relaxation of uterine and
vascular smooth muscle, used also for treatment of premature labor (Tocolytic).
Molsidomine Cap Corvasal® 2 mg , 4 mg
Isoxsuprine Tab Duvilane® 10 mg
D) Peripheral Vasodilators and Vasoprotective agents:
Peripheral vascular disease can be either occlusive (intermittent claudication) in which
occlusion of the peripheral arteries is caused by atherosclerosis, or vasospastic (Raynaud’s
syndrome), treatment option includes: Cilostazol, Pentoxifylline and Vincamine.
1. Cilostazol is a vasodilator and an anti-platelet; licensed for use in intermittent claudication
to improve walking, also used for secondary stroke prevention.
➢ Cilostazol and its metabolites are inhibitors of phosphodiesterase III; As a result, cyclic
AMP is increased leading to reversible inhibition of platelet aggregation, vasodilation, and
inhibition of vascular smooth muscle cell proliferation.
➢ Based on the American College of Chest Physicians (ACCP) guidelines for antithrombotic
therapy, Cilostazol is an effective and recommended alternative antithrombotic to
either aspirin or Clopidogrel in a dual antiplatelet regimen when allergy or drug
intolerance to either agent occurs in patients who have undergone elective PCI with bare
metal or drug-eluting stent placement.
➢ Based on the American College of Chest Physicians (ACCP) guidelines for antithrombotic
therapy, Cilostazol is an effective and recommended alternative antithrombotic in
patients with a history of non-cardio embolic ischemic stroke or TIA.
➢ Also used in the Prevention of stent thrombosis and restenosis after coronary stent
placement (adjunct with aspirin and Clopidogrel).
2. Pentoxifylline (also called Oxpentifylline); a xanthine derivative; improves blood flow by
decreasing blood viscosity and increasing RBC Flexibility; thus, increasing oxygen supply.
➢ Has been shown to increase leukocyte deformability and to inhibit neutrophil
adhesion and activation;
➢ Tissue oxygen levels have been shown to be significantly increased by therapeutic
doses of Pentoxifylline in patients with peripheral arterial disease.
➢ Uses include improving psychopathological symptoms in patients with cerebrovascular
insufficiency, in diabetic angiopathies, transient ischemic attacks, leg ulcers, sickle cell
anemia’s, strokes, Raynaud phenomenon and in male infertility (enhance sperms quality).
3. Vincamine; an Alkaloid found in the leaves of (Vinca minor); it’s a Peripheral Vasodilator that
acts by increasing cerebral blood circulation, also it’s considered as a Nootropic agent; is
used for the treatment, control, prevention, and improvement of Cerebrovascular disorders
and Hypertension; in Europe its indicated for the treatment of primary degenerative and
vascular dementia.
➢ Vinpocetine (Caventona® AMS) is a synthetic derivative of Vincamine.
Cilostazol Tab Pletal® 50 mg , 100 mg
Inositol Nicotinate Tab Hexopal® 500 mg , 750 mg
Moxisylyte Tab Opilon® 40 mg
Naftidrofuryl Cap Praxilene® 100 mg , 200 mg
Pentoxifylline Tab Trental® 400 mg
Calcium Dobesilate Cap Doxium® 500 mg
Vincamine Cap SR Oxybral® 30 mg
Amp ® 15 mg/2 ml
Oxerutins Cap Paroven® 250 mg
Trimetazidine Tab MR Vastrel® , Tricardia® 30 mg , 35 mg
Notes
1. Moxisylyte = Thymoxamine, they are the same drug.
2. Doxium® is an exclusive Vasoprotective used is Chronic Venous Insufficiency, In
Hemorrhoids and in Diabetic Retinopathy.

Guide-Line of Hypertension Treatment lines (4)
** Mild Pregnancy hypertension
is usually treated acutely with
(labetalol) to prevent maternal
cerebrovascular complications.
** Avoid ACEIs, ARBs and
Aliskiren because these drugs
may cause fetal injury or death.
** Nitroprusside is C.I. in the
later stages of pregnancy due to
possible fetal cyanide poisoning if
used for more than 4 hours.
3.13 – Emergency Antihypertensive drugs:

Nicardipine Infusion Cardene® 20 mg/200 ml , 40 mg/200 ml
Inj. Solu. 2.5 mg/ml
Nitroprusside Na+ Vial Nipride®, Nitropress® 50 mg
Inj. Solu. 25 mg/ml
Fenoldopam Inj. Solu. Corlopam® 10 mg/ml
Nitroglycerin Inj. Solu. NTG® , Tridil® 400 mcg/ml
Hydralazine Inj. Solu. Apresoline® 20 mg/1ml
Labetalol Inj. Solu. Trandate® 5 mg /ml
Enalaprilat Inj. Solu. Epaned® , Vasotec® 1.25 mg/ml , 2.5 mg/ml
Trimetaphan Inj. Solu. Arfonad® 25 mg , 50 mg
Esmolol Inj. Solu. Brevibloc® 10 mg/ml , 20 mg/ml
Phentolamine Vial Regitine® , Oraverse® 5 mg , 0.4 mg/1.7 ml
3.14 - Anti-Arrhythmic Drugs:

1. The heart contains two upper and two lower chambers, which are known as the atria and
ventricles. The pumping actions of these two sets of chambers are normally coordinated by
electrical impulses that originate in the heart’s pacemaker and then travel along conducting
pathways so that the heart beats with a regular rhythm.
➢ If this coordination breaks down, the heart will beat abnormally, either irregularly or faster
or slower than usual; The general term for abnormal heart rhythm is arrhythmia.
➢ Arrhythmias may occur as a result of a birth defect, coronary heart disease, or other less
common heart disorders, a variety of more general conditions, including over-activity of the
thyroid gland, and certain drugs, such as caffeine and anticholinergic drugs, can also disturb
heart rhythm.
2. Arrhythmias can be divided into two groups: Tachycardias (as atrial fibrillation), in which the
heart rate is faster than normal; and Bradycardias (as heart block), in which the rate is slower.
3. Minor disturbances of heart rhythm are common and do not usually require drug treatment.
However, if the heart’s pumping action is seriously affected, the circulation of blood throughout
the body may become inefficient, and drug treatment may be necessary.
4. Drugs may be taken to treat individual attacks of arrhythmia, or they may be taken on a regular
basis to prevent or control abnormal heart rhythms; The particular drug prescribed depends
on the type of arrhythmia to be treated, but because people differ in their response, it may be
necessary to try several in order to find the most effective one; When the arrhythmia is
sudden and severe, it is necessary to inject a drug immediately to restore normal heart function.
➢ The heart pumping action is governed by electrical impulses under the control of the
sympathetic nervous system; These signals pass through the heart muscle, causing the two
pairs of chambers – the atria and ventricles – to contract in turn.
➢ All anti-arrhythmic drugs alter the conduction of electrical signals in the heart;
However, each drug or drug group has a different effect on the sequence of events controlling
the pumping action:
• Some block the transmission of signals to the heart (beta blockers).
• Some affect the way in which signals are conducted within the heart (digitalis).
• Others affect the response of the heart muscle to the signals received (calcium
channel blockers, Disopyramide, and Procainamide).
➢ They don’t cure arrhythmia; they usually reduce the frequency and the severity.
➢ They may further disrupt heart rhythm, and therefore they are used only when the likely
benefit outweighs the risks.
➢ Anti-Arrhythmics may cause arrhythmias itself if used improperly, most of them is called
pro-arrhythmic.
➢ Should be initiated in the hospital (minimum of 3-day stay) so that QTc interval, serum
electrolytes, and renal function can be monitored.
Common types of Arrhythmias:
A) Atrial fibrillation: in this type of arrhythmia, the atria contract irregularly at such a high rate
that the ventricles cannot keep pace. The condition is treated with digoxin, verapamil,
amiodarone, or a beta blocker.
B) Ventricular tachycardia: This condition arises from abnormal electrical activity in the
ventricles that causes the ventricles to contract rapidly. Treatment with Disopyramide,
procainamide, or amiodarone may be effective, although implanted defibrillators are replacing
drug treatment for this condition.
C) Supraventricular tachycardia: This condition occurs when extra electrical impulses arise in the
pacemaker or atria, stimulating the ventricles into contracting rapidly. Attacks may disappear on
their own without treatment, drugs used: adenosine, digoxin, verapamil, or propranolol.
D) Heart block: When impulses are not conducted from the atria to the ventricles, the ventricles
start to beat at a slower rate. Some cases of heart block do not require treatment. For more severe
heart block accompanied by dizziness/fainting, the fitting of an artificial pacemaker is necessary.
Notes about Anti-Arrhythmics:

1. Atropine is used for bradycardia and AV nodal blockade; In patients with hemodynamically
unstable or unresponsive to atropine, epinephrine or dopamine may be administered.
2. Adenosine is the drug of choice for pharmacologic termination of paroxysmal
supraventricular tachycardia (PSVT).
3. Hemodynamically stable torsade de pointes is often treated with I.V magnesium.
4. Hemodynamically unstable PSVT, ventricular tachycardia, atrial fibrillation, torsade de pointes,
or ventricular fibrillation (already hemodynamically unstable) should be terminated
immediately using direct current cardioversion (DCC).
5. Flecainide and Propafenone can be considered first-line therapies for patients without
structural heart disease; Propafenone displays independent nonselective β-blocking
properties (which may cause bronchospasm, thus its best be avoided in patients with asthma);
both drugs are Contraindicated in patients with structural heart disease (including CHD,
HF, left ventricular hypertrophy, and valvular heart disease).
6. Sotalol is also a Beta Blocker (non-selective), used for ventricular and supraventricular
arrhythmias (2), Contraindicated in patients with uncontrolled HF; CrCl less than 40 mL/minute;
QTc interval greater than 450 milliseconds; and second- or third-degree AV block.
7. Amiodarone is the most commonly used antiarrhythmic agent; It is used for rate and rhythm
control of atrial fibrillation and to treat and prevent ventricular arrhythmias.
➢ Reserved for patients with life-threatening arrhythmias due to its substantial toxicity.
➢ Contains an Iodine moiety that contributes to its thyroid toxicity.
➢ Patients should be monitored routinely for the possible development of hepatic dysfunction,
thyroid disorders (hyperthyroidism, hypothyroidism), and photosensitivity.
➢ Because of the possibility of phototoxic reactions, patients taking amiodarone should be
advised to shield the skin from light during treatment and for several months after
discontinuing amiodarone.
➢ Oral loading dose required (400 mg 2 or 3 times per day for 2 weeks and then 400 mg/day
for 4 weeks, followed by a 200-mg/day maintenance dose); and Achieving a loading dose of
10 gm is desirable.
➢ Has a very Long half-life of about 60 days.
8. Dronedarone: An Amiodarone analog; lacking the iodine moiety that contributes to the thyroid
toxicity of amiodarone, but may result in acute kidney injury, that reversible on discontinuation.
9. Digoxin is a cardiac glycoside that increases the force of myocardial contraction (so used for
Heart Failure HF) and reduces conductivity within the atrioventricular (AV) node (so used
for atrial fibrillation or flutter) (2), its Half-life is about 36 hours.
➢ Digoxin does not improve survival in patients with HF; but does provide symptomatic
benefits only; (digoxin is added for patients who remain symptomatic despite an optimal HF
regimen consisting of an ACEI or ARB, β-blocker, and diuretic.
➢ Digoxin is also prescribed routinely in patients with HF and concurrent atrial fibrillation (AF)
to slow ventricular rate regardless of HF symptoms.
➢ Loading dose of digoxin (Rapid digitalization) is usually given for atrial fibrillation or
flutter; (half of the total loading dose administered as the first dose, with the remaining
portion divided and administered every 6–8 hours initially).
A) Class I (Na+ Channel Blockers)
Disopyramide ( Ia ) Cap , Cap ER Norpace , Rythmodan
® ® 100 mg , 150 mg
Procainamide ( Ia ) Tab Pronestyl , Procan
® ® 250 mg , 500 mg
Quinidine ( Ia ) * Tab Quinidex®, Quinacard® 200 mg , 300 mg
Lidocaine ( Ib ) ** Inj. Solu. Xylocaine , Lidopen
® ® 10 mg/ml
Mexiletine ( Ib ) Cap Mexitil® 150 mg , 200 mg
Flecainide ( Ic ) Tab Tambocor ® 50 mg , 100 mg
Propafenone ( Ic ) Tab , Cap Rythmol , Rythmonorm 150 mg (tab) , 225 mg (cap)
® ®
* Quinidine is also anti-malarial.

** Lidocaine is also a Local anesthetic used as Ointment and Cream for topical use.
B) Class II (Beta Blockers)

Only (Esmolol, Metoprolol, propranolol, Acebutolol) is FDA approved as Anti-Arrhythmic.
Scientific name D. form Trade name Cone.
Inj. Inderal ® 1 mg/1 ml
Metoprolol Tab Betaloc , Hypopresor
® ® 50 mg , 100 mg
Inj. Lopress®®
Betaloc 1 mg/1 ml
Esmolol Inj. Solu. Brevibloc ® 10 mg/1 ml , 20 mg/1 ml
Acebutolol cap Sectral ® 200 mg , 400 mg
C) Class III (K+ Channel Blockers)
Amiodarone Tab Codaron® 100 mg , 200 mg
Inj. Solu. Codaron® , Nexterone® 50 mg/ml
Sotalol Tab Betapace® 80 mg , 120 mg , 160 mg
Inj. Solu. Sorine® 15 mg/ml
Dronedarone Tab Multaq® 400 mg
Ibutilide Inj. Solu. Corvert® 0.1 mg/ml
Dofetilide Cap Tikosyn® 125 mcg , 250 mcg , 500 mcg
Vernakalant * Inj. Solu. Brinavess® 500 mg/25 ml
* Vernakalant blocks atrial potassium channels, thereby prolonging repolarization; It differs from typical
class III agents by blocking a certain type of potassium channel, the cardiac transient outward potassium
current, with increased potency as the heart rate increases; This means that it is more effective at high
heart rates, while other class III agents tend to lose effectiveness under these circumstances; It also
slightly blocks the hERG potassium channel, leading to a prolonged QT interval.
D) Class IV (Ca+ Channel Blockers)

Only (Diltiazem, Verapamil) is FDA approved as Anti-Arrhythmic. (See Above)
E) Other Anti-Arrhythmics
Adenosine Inj. Solu. Adenocard® 3 mg/ml
Digoxin Tab Lanoxin® 0.125 mg , 0.25 mg
Elixir 0.05 mg/ml
Inj. Solu. 0.1 mg/ml , 0.25 mg/ml
Digitoxin * Tab Digitoxin® 100 mcg
* Digitoxin has a long half-life, about 7 days.
Note: too much antiarrhythmics?? Don’t worry;

The following table summarize the effects of antiarrhythmic drugs:
Class Agent Physiological effect Result on ECG
Class I parameters
(Na channel Blockers)
IA (intermediate) Quinidine ↓ Conduction velocity, ↑ QRS complex,
Disopyramide ↑ refractory period ↑ QT interval
Procainamide
IB (fast) Lidocaine ↓ Conduction velocity, ↓ QT interval
Mexiletine ↓ refractory period
IC (Slow) Flecainide ↓ Conduction velocity ↑ QRS complex
Propafenone (highly decrease),
∅ refractory period
Class II (BBs) Metoprolol ↓ Conduction velocity, ↓ HR
Esmolol ↑ refractory period ↑ PR interval
Atenolol
Class III Amiodarone ∅ Conduction velocity, ↑ QT interval
(K channel Blockers) Dronedarone ↑ refractory period
Dofetilide (highly increase)
Ibutilide
Class IV Diltiazem ↓ Conduction velocity, ↓ HR
(Ca channel Blockers) Verapamil ↑ refractory period ↑ PR interval
Class V Digoxin ↓ Conduction velocity, ↑ PR interval
Digitoxin ↑ refractory period
Adenosine
** ∅ = no effect, ↓ = decrease, ↑ = increase.
3.15 - Lipid-regulating drugs (Anti-Lipemic agents)
1. Cholesterol and triglycerides are two of the major fats in the blood; One or both may be raised,
influencing the choice of lipid-lowering drug.
➢ Cholesterol is essential for making a number of critical hormones, including the stress hormone
cortisol; Cholesterol is also used to make the sex hormones testosterone, progesterone, and
estrogen; The liver also uses cholesterol to make bile, a fluid that plays a vital role in the
processing and digestion of fats; the body also needs cholesterol to make vitamin D, as in the
presence of sunlight, cholesterol is converted into vitamin D.
• High Cholesterol may contribute to hardening of the arteries or thickening of the artery walls
(arteriosclerosis); which increases the risk of stroke, heart attack and heart disease.
➢ Triglycerides (TG): when we eat, the body converts any calories it doesn't need to use right away
into triglycerides; The triglycerides are stored in your fat cells. Later, hormones release
triglycerides for energy between meals.
• High levels of TGs can increase the risk of heart disease; heart attack or stroke (due to
atherosclerosis).
• Extremely high TGs can also cause acute inflammation of the pancreas (pancreatitis).
2. The normal level of cholesterol in the blood is less than 200 mg/dl.
3. The normal level of TG is less than 150 mg/dl.
4. There is a common notion that the restricted diet for cholesterol-rich foods and the sport is the
foundation and starting point in the treatment of high blood cholesterol; the truth of this information
is correct, but inaccurate due to the amount of cholesterol reaching into the body daily is distributed
as follows:
➢ 80% is made endogenously in the liver without being related to food intake and 20% is of
the incoming food; Therefore, effective treatment and principal of the high blood cholesterol in
the case of increase for the limit of 240 is essentially pharmacological and especially with group
Statins, and accompanied by a diet
➢ The diet itself needs 6-12 month to take effect and lower cholesterol, and that's a lot
especially for patients who have other risk factors, diet is useful in patients who are still in the
borderline cholesterol control.
5. Cholesterol and Triglycerides (TG) are transported from the liver to blood stream and vice versa
through a carrier called Lipoproteins, which are divided into 4 types according to their actions:
a. Chylomicrons carry triglycerides from the intestines to the liver, to skeletal muscle, and to the
adipose tissue (for storage).
b. Very-low-density lipoproteins (VLDL) carry (newly synthesized) triglycerides from the liver to
the adipose tissue (for storage).
c. Low-density lipoproteins (LDL) carry 3,000 to 6,000 fat molecules (phospholipids, cholesterol,
triglycerides) around the body; LDL particles are referred to as "bad" lipoprotein because their
increase correlate with atherosclerosis progression.
d. High-density lipoproteins (HDL) collect fat molecules (phospholipids, cholesterol,
triglycerides) from the body's cells/tissues, and take it back to the liver to get metabolized and
broken down; HDLs are referred to as "good" lipoprotein because higher concentrations
correlate with low rates of atherosclerosis progression and/or regression.
6. When treating high levels of lipids, it’s important to focus on two parameters: LDL-C and HDL-C as:
• Each 1% reduction in LDL-C equals a 1% reduction in CHD risk.
• Each 1% increase in HDL-C reduces CHD risk by 1-3%.
7. Lipid regulating drugs are used to modify blood lipid concentrations in the management of
hyperlipidemias and for the reduction of cardiovascular risk, The principal groups of lipid
regulating drugs are:
a. Statins like (Atorvastatin, Rosuvastatin, and Simvastatin)
b. Fibrates like Gemfibrozil and Fenofibrate.
c. Bile acid Sequestrants like Colesevelam and Colestipol.
d. Others like Ezetimibe, Omega 3 Fatty Acids.
A) Regarding Statins:
1. They act by inhibiting HMG CoA reductase, the rate-limiting step in cholesterol synthesis.
2. Statins are more effective than other lipid-regulating drugs at lowering LDL-cholesterol
concentration but they are less effective than the fibrates in reducing triglyceride
concentration.
3. They reduce LDL-C by (24–60%); reduce TG by (7–30%); raise HDL-C by (5–15%).
4. Cholesterol synthesis in the liver peaks during the early morning (midnight to 3 am), thus most
of statins should be taken in at night.
➢ An exception for that are Rosuvastatin, Atorvastatin; which both have long half-lives that
allows them to be administered any time a day and still overs the HMG peak time;
(Rosuvastatin 19 – 24 hrs., Atorvastatin 11 – 14 hrs.).
➢ Simvastatin is used topically for accelerating wound healing in diabetes by enhancing
angiogenesis and lymph-angiogenesis (off-label use), it’s also has a neuroprotective
function and thus it’s preferred by neurologists.
➢ Atorvastatin is a Lipid-soluble statin, and it’s preferred in patients with renal failure.
➢ Rosuvastatin is a Water-soluble statin, preferably avoided in End stage renal disease.
5. The most common adverse effects reported include muscle pain and weakness (myalgia),
headache, GI symptoms, including dyspepsia, flatus, constipation, and abdominal pain, and skin
rashes; These symptoms are usually mild and often dissipate with continued therapy.
➢ Co-Q10 supplementations are sometimes used to treat statin-associated myopathy.
6. Some studies claim that Statins (Atorvastatin, Rosuvastatin) can be given every other day,
or 3 or 2 times weekly, and once weekly for Rosuvastatin.
➢ This is supported by the fact that it takes several weeks for cholesterol levels to return to
baseline after treatment with statins is stopped, Rosuvastatin with a 19-hr. half-life and
Atorvastatin with an 11–14 hr. half-life, are particularly useful for this approach.
➢ Review of studies comparing alternate-day dosing with daily dosing of statins indicates that
the magnitude of LDL cholesterol reduction with alternate-day dosing is nearly the same, with
obvious cost savings and less side effects specially muscle aches and myalgia.
➢ Relative LDL-C-Lowering Efficacy of Statins
Note that Rosuvastatin has the highest LDL lowering effect.

Atorvastatin Tab Lipitor® , Avas® , Astatin® 10 , 20 , 40 , 80 mg
Simvastatin Tab Zocor® , Simvas® , Simvor® 10 , 20 , 40 , 80 mg
Fluvastatin Cap Lescol® 20 mg , 40 mg
Tab (MR) Lescol XL® 80 mg
Lovastatin Tab Mevacor® , Atloprev® 10 , 20 , 40 mg
Pravastatin Tab Pravachol®, Lipostat® 10 , 20 , 40 , 80 mg
Pitavastatin Tab Livalo® 1 mg , 2 mg , 4 mg
Rosuvastatin Tab Crestor® , Stage®, Rosogard® 10 mg , 20 mg , 40 mg
B) Regarding Fibrates:
1. Fibrate reduces the rate of lipogenesis in the liver, thus lowering TG and cholesterol levels.
• mainly used for the treatment of hypertriglyceridemia (hyper TG).
• Recommendations for fibrate use were not included in the 2016 ACC guideline.
• When initiation therapy with Fibrates; evaluate renal status at baseline, within 3 months after
initiation, and every 6 months thereafter.
• Due to a rare paradoxical decrease in HDL-C seen in some patients on Fenofibrate, the FDA
recommended that the HDL-C levels be checked within the first few months after initiation of
fibrate therapy; If a severely depressed HDL-C level is detected, fibrate therapy should be
withdrawn, and the HDL-C level monitored until it has returned to baseline.
• Fibrates Use has been associated with PE (pulmonary Embolism) and DVT (deep vein
thrombosis); Use with caution in patients with risk factors for VTE.
2. They lower LDL-C by 5–20% (with normal TG); but may raise LDL-C with very high TG levels.
3. They Lower TG by 20–50%; and raise HDL-C by 10–20%.
4. Fibrates may cause Dyspepsia, and because these drugs increase biliary cholesterol excretion,
they lead to the formation of gallstones (Lithiasis).
• Thus C.I. in pre-existing gallbladder disease.
• Also C.I. in Severe renal or hepatic disease.
5. Increased risk of myopathy and rhabdomyolysis when co-administered with statins; Risk
is greater with gemfibrozil than with Fenofibrate.
6. Bezafibrate and Fenofibrate are given with or just after food; while Gemfibrozil is given 30 to
60 minutes before food.
Gemfibrozil Tab Lopid® 600 mg
Fenofibrate Tab , Cap Tricor®, Lipofen®, Lipanthyl® 145mg (tab) , 200mg (cap)
Tab Supralip® 160 mg
Bezafibrate Tab Bezalip® 200 mg , 400 mg
Ciprofibrate Tab Ciprofib® 100 mg
C) Bile acid Sequestrants (binders)

1. Bile salts contain a large amount of cholesterol and are normally released into the bowel to aid
digestion before being reabsorbed into the blood; so, drugs that bind to bile salts reduce
cholesterol levels by blocking their reabsorption, allowing them to be lost from the body.
2. Bile acid Sequestrants are anion exchange resins that bind negatively charged bile acids and
bile salts in the small intestine; the resin/bile acid complex is excreted in feces, thus preventing
the bile acids from returning to the liver by the entero-hepatic circulation.
➢ Lowering the bile acid concentration causes hepatocytes to ↑ conversion of cholesterol to
bile acids, resulting in a replenished supply of these compounds → the intracellular
cholesterol concentration decreases.
➢ Bile acid Sequestrants interfere with the absorption of fat-soluble vitamins; supplements
of vitamins A, D, K, and folic acid may be required when treatment is prolonged.
➢ Adverse effects include: GI distress, constipation.
3. They reduce LDL-C by 15–27%, and raise HDL-C by 3–5%, but may increase TG
concentrations; (thus C.I. with raised TG concentrations especially greater than 400 mg/dl).
➢ Colesevelam is FDA approved for use in type 2 diabetes to improve glycemic control.
➢ Cholestyramine is used for pruritus associated with partial biliary obstruction and
primary biliary cirrhosis, it also used for diarrhea associated with Crohn’s disease, ileal
resection vagotomy, diabetic vagal neuropathy, and radiation.
Colesevelam Tab , Cap WelChol , Cholestagel
® ® 625 mg
Colestipol Tab , Granules Colestid ® 1 gm (tab) , 5 gm (granules)
Cholestyramine Powder for Susp. Questran®, Prevalite® 4 gm/sachet
D) Injectable Anti-Lipemic drugs:

These include Evolocumab, Alirocumab and Mipomersen.
1. Evolocumab and Alirocumab are both PCSK9 Inhibitors; Monoclonal antibodies that inhibit a
protein called PCSK9, thus increasing cholesterol clearance from the liver.
➢ Lower LDL-C by an additional 45–68% when combined with statin therapy;
Evolocumab reduces CV events when added to statin therapy.
➢ Both administered by SC inj. Every 2 weeks, or at a double dose each month.
➢ Adverse effects: Injection-site reactions, respiratory infections.
2. Mipomersen is an Oligonucleotide inhibitor, which targets the messenger RNA for Apo-
lipoprotein B-100 → inhibit VLDL & LDL synthesis, it lowers LDL-C by about 25%.
➢ administered by SC inj. Once weekly; should only be prescribed in the context of a risk
management plan by specialist.
➢ The drug has a black box warning about the risk of liver damage; specifically, it can
cause elevations in the levels of transaminases and causes fatty liver disease.
Mipomersen S.C. Inj. Kynamro ® 200 mg/ml
Alirocumab S.C. Inj. Praluent ® 75 mg/ml , 150 mg/ml
Evolocumab S.C. Inj. Repatha® 140 mg/ml
E) Other Anti-Lipemic drugs: (2)

These include: Ezetimibe, Omega 3 Fatty acids, Lomitapide and Niacin (vitamin B3).
1. Ezetimibe selectively inhibits absorption of dietary and biliary cholesterol from the small
intestine; may be used alone or in combination with a statin or Fenofibrate along with diet for
the management of dyslipidemia, specifically to lower LDL-C.
➢ It lowers LDL-C by 18–20%; Can raise HDL-C by 1–5%; lowers TG by 5–10%.
➢ In combination with a statin, it demonstrates an additive effect, enhancing LDL-C lowering
by an additional 10% to 20%.
2. Omega 3 Fatty acids, Contains Eicosapentaenoic acid (EPA) and Docosahexaenoic acid
(DHA), which differs from the traditional fish oil.
➢ Mainly used for reduction of TG; it acts by reduction of hepatic production of VLDLs;
with a possible reduction in hepatic synthesis of TG; and increased hepatic β-oxidation.
➢ A safer option compared with Fibrates.
➢ Lowers TG by 26–45%, and raises HDL-C by 5–14%.
➢ But may raise LDL-C up to 45% when TG concentrations are very High.
➢ Effective Dose: 2–4 gm/day as a single dose or in two divided doses.
3. Omega-3 carboxylic acids are derived from fish oil and are a purified mixture of the
polyunsaturated free fatty acids Docosahexaenoic acid (DHA) and Eicosapentaenoic acid
(EPA); used in addition to changes in diet to reduce triglyceride levels in adults.
➢ Lowers TG 20-35%, and raises HDL-C by 5%
➢ But may raise LDL-C up to 25% when TG concentrations are very High.
➢ Effective Dose: 2–4 gm/day as a single dose or in two divided doses.
➢ Following the recommendation from an independent Data Monitoring Committee,
AstraZeneca has decided to close the Phase III STRENGTH trial for Epanova (omega-3
carboxylic acids) due to its low likelihood of demonstrating a benefit to patients with
mixed dyslipidemia (MDL) who are at increased risk of cardiovascular (CV) disease.
4. Lomitapide, a Selective microsomal TG protein inhibitor; directly bind and inhibit
Microsomal Triglyceride Transfer protein (MTP), thus preventing Apo-B Lipoprotein Assembly
→ inhibit synthesis of Chylomicrons and VLDL.
➢ Lowers LDL-C by about 45%, but has a high profile in GIT side effects (hepatotoxic).
➢ Should be given only under the supervision of a specialist.
➢ C.I in pregnancy and moderate liver impairment.
5. Niacin (vitamin B3), inhibits mobilization of free fatty acids from peripheral adipose tissue to
the liver and reduces synthesis of TG, VLDL, and LDL-C
➢ It lowers LDL-C by 5–25%; lowers TG by 20–50%; and raises HDL-C by 15–35%.
➢ its value as anti-Lipemic is limited by its side-effects, especially vasodilatation.
➢ Can cause an intense cutaneous flush and pruritus; Administration of aspirin prior to
taking niacin decreases the flush.
6. Bempedoic acid is a non-statin, targeted therapy that is designed to primarily work in the liver
to inhibit cholesterol biosynthesis.
➢ Inhibits adenosine triphosphate citrate lyase (ACL); an enzyme two steps upstream from
HMG-CoA reductase, along the cholesterol biosynthesis pathway.
➢ By inhibiting ACL, Bempedoic acid reduces cholesterol synthesis, resulting in LDL
receptor upregulation and increased clearance of LDL from the bloodstream
➢ In a study, it reduced LDL cholesterol by about 20 mg/dl compared to placebo and had no
more side effects than placebo.
➢ Regardless of other lipid lowering therapy, fixed dose Bempedoic acid + Ezetimibe combo
lowered LDL-C levels by a 36-38% when compared with placebo, versus 23% for
ezetimibe alone and 17% for Bempedoic acid alone. (EAS 2019).
Niacin (Vit. B3) Tab Niaspan , Niacor
® ® Various conc.
Acipimox Cap Olbetam ® 250 mg
Ezetimibe Tab Ezetrol® , Zetia® , Zetex® 10 mg
Omega 3 Fatty Acids Cap Lovaza , Omacor
® ® 1 gm
Omega 3 Carboxylic acids Cap Epanova ® 1 gm
Icosapent ** Cap Vascepa ® 1 gm
Lomitapide Cap Juxtapid® 5 mg , 10 , 20 , 40 , 60 mg
Bempedoic acid Tab Bempo ® 180 mg
** Icosapent is an Eicosapentaenoic acid (ethyl ester) an Omega Fatty acid, which ↓ VLDL-TG
synthesis, ↓ lipogenesis in liver, ↑ plasma lipoprotein lipase activity.
F) Anti-Lipemic Combos:
Inegy®, Vytorin®, Tab Ezetimibe + Simvastatin 10mg/20mg , 10mg/40 mg
AlkorPlus®
Liptruzet® Tab Ezetimibe + Atorvastatin 10mg/20mg , 10mg/40 mg
Rosuzet® Tab Ezetimibe + Rosuvastatin 10mg/10mg , 10mg/20 mg
Bempoplus® Tab Ezetimibe + Bempedoic acid 10mg/180mg
Advicor® Tab Lovastatin + Niacin 20mg/500mg
Simcor® Tab Simvastatin + Niacin 20mg/500mg
Lipikind F®, Tab Fenofibrate + Atorvastatin 160mg/10mg ,
Statring plus® 160mg/20mg
Rosulip F® Tab Fenofibrate + Rosuvastatin 145mg/10mg , 145mg/20mg
Lipid Free® Tab Fenofibrate + Rosuvastatin 160 mg/40 mg
Pravafen® Cap Fenofibrate + Pravastatin 160mg/40mg

3.16 - Drugs used to prevent Abnormal Blood Clotting
a. Blood clots normally form only as a response to injury, in some people, however, there is a
tendency for clots to form in the blood vessels without apparent cause; Disturbed blood flow
occurring as a result of the presence of fatty deposits (atheroma) inside the blood vessels
increases the risk of the formation of this type of abnormal clot (or thrombus); In addition, a
portion of a blood clot (known as an embolus) formed in response to injury or surgery may
sometimes break off and be removed in the bloodstream.
➢ The likelihood of this happening is increased by long periods of little or no activity.
➢ When an abnormal clot forms, there is a risk that it may become lodged in a blood vessel,
thereby blocking the blood supply to a vital organ such as the brain or heart.
b. There are Three main types of drugs are used to prevent and disperse clots: Antiplatelet drugs,
Anticoagulants, and Thrombolytics.
1. Antiplatelet Drugs
o Taken regularly by people with a tendency to form clots in the fast-flowing blood of the heart and
arteries, these drugs are also given to prevent clots from forming after heart surgery (such
as PCI); They reduce the tendency of platelets to stick together when blood flow is disrupted.
o The most widely used antiplatelet drug is Aspirin, which has an antiplatelet action even when
given in much lower doses than would be necessary to reduce pain; Other antiplatelet drugs are
Clopidogrel and dipyridamole.
2. Anticoagulants
o They help to maintain normal blood flow in people at risk from clot formation; They can either
prevent the formation of blood clots in the veins or stabilize an existing clot so that it does
not break away and become a circulation-stopping embolism.
o All anticoagulants reduce the activity of certain blood clotting factors, but each drug’s mode of
action differs. These medicines do not dissolve clots that have already formed, however: these
are treated with thrombolytic drugs.
o Anticoagulants fall into two groups: those that are given by intravenous injection and act
immediately, and those that are given by mouth and take effect after a few days.
A. Injectable Anticoagulants: such as Heparin, the most widely used drug of this type and it
is used mainly in hospital during or after surgery. It is also given during kidney dialysis to
prevent clots from forming in the dialysis equipment. Because heparin cannot be taken by
mouth, it is less suitable for long term treatment in the home, other Injectable
Anticoagulants include Enoxaparin, Dalteparin.
B. Oral Anticoagulants: such as Warfarin, the most widely used of the oral anticoagulants.
These drugs are mainly prescribed to prevent the formation of clots in veins and in the
chambers of the heart (they are less likely to prevent clot formation in arteries). Oral
anticoagulants may be given following injury or surgery (in particular, heart valve
replacement) when there is a high risk of embolism.
o Oral Anticoagulants are also given long-term as preventative treatment to people at risk of
strokes. A common problem with these drugs is that over dosage may lead to bleeding from the
nose or gums, or in the urinary tract. For this reason, the dosage needs to be carefully calculated;
regular blood tests are performed to ensure that the clotting mechanism is correctly adjusted,
although this is not necessary with new oral anticoagulants such as Dabigatran and
Rivaroxaban; The action of oral anticoagulants may be affected by many other drugs, and it may
therefore be necessary to alter the dosage of anticoagulant when other drugs also need to be
given. In particular, no anticoagulant should be taken together with aspirin except on the
direction of a doctor.
3. Thrombolytics
o Also known as Fibrinolytics, these drugs are used to dissolve clots that have already formed.
They are usually given in hospital intravenously to clear a blocked blood vessel (in coronary
thrombosis, for example); The sooner they are given after the start of symptoms, the more
likely they are to reduce the size and severity of a heart attack.
o Thrombolytic drugs may be given either intravenously or directly into the blocked blood vessel;
The main Thrombolytics are Streptokinase and Alteplase, which act by increasing the blood
level of plasmin, the enzyme that breaks down fibrin, when given promptly, Alteplase appears
to be tolerated better than streptokinase.
o The most common problems with these drugs are increased susceptibility to bleeding and
bruising, and allergic reactions to streptokinase, such as rashes or breathing difficulty. Once
streptokinase has been given, patients are given a card indicating this, because further treatment
with the same drug may be less effective and an alternative (such as Alteplase) used instead.
First: Antiplatelet drugs

➢ It is important to distinguish between thrombi and emboli; a clot that adheres to a vessel
wall is called a “thrombus,” whereas an intravascular clot that floats in the blood is termed an
“embolus.” Thus, a detached thrombus becomes an embolus.
o Both thrombi and emboli are dangerous, because they may occlude blood vessels and
deprive tissues of oxygen and nutrients.
o Arterial thrombosis usually consists of a platelet- rich clot, venous thrombosis
typically involves a clot that is rich in fibrin, with fewer platelets than arterial clots.
1. Antiplatelet drugs reduce platelet aggregation and are used to prevent further
thromboembolic events in patients at risk (ex: patients who have suffered myocardial
infarction, ischemic stroke or transient ischemic attacks, or unstable angina), and for primary
prevention of a thromboembolic event in patients at risk.
2. They Also inhibit thrombus formation in the arterial circulation, because in faster-flowing
vessels, thrombi are composed mainly of platelets with little fibrin.
3. The most commonly used Antiplatelet drugs are aspirin (at low dose) and Clopidogrel and less
commonly is Dipyridamole.
a. Clopidogrel may be given as an alternative to aspirin (in patients who cannot take aspirin),
Clopidogrel may be given in combination with aspirin in some conditions like myocardial
infarction for synergistic effect.
b. Aspirin tablet commonly formulated as enteric coated tablet to decrease GIT irritation.
c. Pregnant women who are at high risk of developing preeclampsia, or if they have had
hypertension during a previous pregnancy; these women are advised to take aspirin once
daily (unlicensed indication) from week 12 of pregnancy until the baby is born.
d. Owing to an association with Reye’s syndrome, aspirin-containing preparations should not
be given to children under 16 years, unless specifically indicated, as for Kawasaki disease.
4. Types of Antiplatelet (According to mechanism of Action)

a) Aspirin (inhibition of COX-1 → decreased thromboxane A2 synthesis)
b) Clopidogrel, Ticlopidine, Ticagrelor and Prasugrel (inhibit the activation of the GP
IIb/IIIa receptors required for platelets to bind to fibrinogen & to each other)
c) Eptifibatide and Tirofiban (blocking the GP IIb/IIIa receptor)
d) Abciximab (monoclonal antibody which blocks GP IIb/IIIa receptor)
e) Dipyridamole (coronary vasodilator, increases intracellular levels of cAMP by inhibiting
cyclic nucleotide phosphodiesterase, resulting in ↓ thromboxane A2 synthesis)
f) Cilostazol (vasodilator, inhibit phosphodiesterase type III, which prevents the degradation
of cAMP, thereby increasing levels of cAMP)
g) Anagrelide (inhibit phosphodiesterase type III)
Scientific name Dosage Trade name concentration
Aspirin form
Tab , EC Tab ( Various ) 75 , 81 , 100 , 300 mg
P2Y12 antagonists (Thienopyridines)
Clopidogrel Tab Plavix® 75 mg , 300 mg
Ticlopidine Tab Ticlid® 250 mg
Ticagrelor Tab Brilinta , Brillique
® ® 90 mg
Cangrelor Inj. Solu. Kengreal ® 50 mg/vial
Prasugrel Tab Effient® 5 mg , 10 mg
Glycoprotein IIb/IIIa inhibitors
Eptifibatide Inj. Solu. Integrilin® 2 mg/ml (10 ml vial)
Infusion 750 mcg (100 ml vial)
Tirofiban Inj. Solu. Aggrastat ® 50 mcg/ml
Abciximab Inj. Solu. ReoPro ® 2 mg/ml (5 ml vial)
Other antiplatelets
Dipyridamole Tab Procardin® , Persantin® 25 mg , 50 mg , 75 mg
Cap MR Persantin ® 200 mg
Inj. Solu. Persantine ® 5 mg/ml
Cilostazol Tab Pletal ® 50 mg , 100 mg
Vorapaxar Tab Zontivity ® 2.08 mg
Atopaxar Pending FDA approval
Anagrelide Cap Agrylin ® 0.5 mg , 1 mg
Notes:
1. All antiplatelet drugs can cause prolonged bleeding for which there is no antidote.
2. About P2Y12 antagonists:
a. Ticagrelor is more potent (more effective) than Clopidogrel, same potent as Prasugrel but
with less side effects (Ticagrelor have less bleeding tendency than Prasugrel).
b. Prasugrel is more potent than Clopidogrel, but Prasugrel is only indicated for PCI.
c. Ticlopidine is associated with neutropenia that requires frequent monitoring of the CBC
during the first 3 months of use.
d. Clopidogrel is given once daily (300 mg LD, 75 mg MD), Prasugrel is given once daily (60
mg LD, 10 mg MD) and Ticagrelor is given twice daily (180 mg LD, 90 mg MD).
e. In a study published by JAMA, Ticagrelor was found to have a bactericidal activity against
all gram-positive strains tested, including drug-resistant strains MRSE, MRSA. (15)
3. Glycoprotein IIb/IIIa inhibitors are indicated for the prevention of cardiac ischemic
complications in patients undergoing PCI only.
a. Abciximab has a high potential for bleeding, especially if used with anticoagulants,
Abciximab is expensive, limiting its use in some settings.
b. Eptifibatide, Tirofiban are only available as IV formulations because oral preparations of
these GP IIb/IIIa blockers are too toxic. The major adverse effect of both drugs is bleeding.
4. Dipyridamole causes vasodilation when given at high doses for a short time.
a. has been shown to lower pulmonary hypertension without significant drop of systemic blood
pressure, also has been shown to increase myocardial perfusion and left ventricular function
in patients with ischemic cardiomyopathy.
b. It can be used for myocardial stress testing as an alternative to exercise-induced stress
methods such as treadmills.
c. A combination of dipyridamole and aspirin is FDA-approved for the secondary prevention of
stroke; However, it is not licensed as monotherapy for stroke prophylaxis.
5. Anagrelide is also used to treat essential Thrombocytosis and Thrombocythemia.
a. It also has been used in the treatment of chronic myeloid leukemia.
6. Cilostazol is an oral antiplatelet agent that also has vasodilating activity; It is FDA approved
to reduce the symptoms of intermittent claudication.
a. It is also used in the treatment of Buerger disease (the recurring progressive
inflammation and thrombosis (clotting) of small and medium arteries and veins of the hands
and feet), vascular sclerosis complicating diabetes mellitus, and used for the improvement
of symptoms in patients with chronic cerebral ischemia.
b. Cilostazol is contraindicated in patients with congestive heart failure of any severity,
and it should be used cautiously in patients with a history of any cardiac disease.
c. Based on the American College of Chest Physicians (ACCP) guidelines for antithrombotic
therapy, Cilostazol is an effective and recommended alternative antithrombotic to
either aspirin or Clopidogrel in a dual antiplatelet regimen when allergy or drug
intolerance to either agent occurs in patients who have undergone elective PCI with bare
metal or drug-eluting stent placement.
d. Based on the American College of Chest Physicians (ACCP) guidelines for antithrombotic
therapy, Cilostazol is an effective and recommended alternative antithrombotic in
patients with a history of non-cardio embolic ischemic stroke or TIA.
e. Also used in the Prevention of stent thrombosis and restenosis after coronary stent
placement (adjunct with aspirin and Clopidogrel).
Anti-platelet combinations:
Aggrenox® Cap ER Aspirin + Dipyridamole 25 mg + 200 mg
Dospin®, Cugrel-A® Tab Aspirin + Clopidogrel 75 mg + 75 mg
Dospin-A®, Tab, Aspirin + Clopidogrel (75mg+75mg+10mg) Dospin-A
Atormac Gold® Cap + Atorvastatin (75mg+75mg+20mg) Atromac G
Cargrel® Cap Aspirin + Clopidogrel 150 mg + 75 mg
Notes:
1. In trials in which a regimen of Dipyridamole plus aspirin was compared with aspirin alone,
Dipyridamole provided no additional beneficial effect (Antithrombotic Trialists’ Collaboration,
2002)
2. A recent study comparing this combination with Clopidogrel for secondary prevention in patients
with stroke or transient ischemic attacks showed no advantage of Dipyridamole plus aspirin.
Second: Anticoagulants
1. Anticoagulants are used in the treatment and prophylaxis of thromboembolic disorders, or
extension of an existing thrombus in the slower-moving venous side of the circulation in the
slower-moving venous side of the circulation, where the thrombus consists of a fibrin web
enmeshed with platelets and red cells.
2. Anticoagulants are of less use in preventing thrombus formation in arteries, for in faster-
flowing vessels thrombi are composed mainly of platelets with little fibrin.
3. Anticoagulants available:
a) Injectable Anticoagulants:
• Unfractionated heparin
• Low-molecular-weight heparins (LMWHs) (Enoxaparin, Dalteparin, Tinzaparin)
• Fondaparinux
• Direct thrombin inhibitors (Lepirudin, Bivalirudin, Argatroban, Desirudin)
b) Oral anticoagulants (as Warfarin), and direct acting as: (Dabigatran, Rivaroxaban).
4. Anticoagulants can cause bleeding; therefore, their anticoagulant effects must be monitored by
laboratory test to avoid excessive bleeding:
A. Warfarin is monitored by a test called international normalized ratio INR.
B. Unfractionated heparin is monitored by a test called activated partial
thromboplastin time (APTT).
5. Heparin and LMWHs are the anti-coagulants of choice for treating pregnant women with
prosthetic heart valves or venous thromboembolism, because these agents do not cross the
placenta (due to their large size and negative charge).
6. Regarding Warfarin:
➢ it inhibits the production of vitamin K–dependent clotting factors
➢ it has no effect on circulating coagulation factors that have been previously formed,
and its therapeutic antithrombotic activity is delayed for 5 to 7 days
➢ In patients with acute VTE, a rapid-acting anticoagulant (UFH, LMWH, or Fondaparinux)
should be overlapped with warfarin for a minimum of 5 days and until the INR is
greater than 2 and stable.
➢ Hemorrhagic complications ranging from mild to severe and life-threatening can occur
at anybody site; The GI tract and nose are the most frequent sites of bleeding.
➢ Intracranial hemorrhage is the most serious complication and often results in
permanent disability and death.
➢ Because of the large number of foods–drug and drug–drug interactions with warfarin,
close monitoring and additional INR determinations may be indicated whenever other
medications are initiated, or discontinued, or an alteration in consumption of vitamin K–
containing foods is noted
➢ Vitamin K is the antidote of Warfarin.
7. Regarding Heparin (unfractionated Heparin UFH):
➢ UFH can be administered via the intravenous (IV) or subcutaneous (SC) route.
➢ Drug of choice for using in pregnant women (don’t cross the placenta).
➢ dose in MI (60 mg/kg LD, 12 mg/kg MD) and in DVT (80 mg/kg LD, 18 mg/kg MD).
➢ adverse effects include: Hypersensitivity reactions (chills, fever), Thrombocytopenia,
Long-term UFH has been reported to cause alopecia, priapism, hyperkalemia, and
osteoporosis
➢ Heparin-induced thrombocytopenia (HIT) is a serious immune-mediated problem that
requires immediate intervention (discontinue heparin and initiate alternative
anticoagulation with a parenteral direct thrombin inhibitor)
➢ UFH can be used in those at high risk of bleeding because its effect can be terminated
rapidly by stopping the infusion (because it’s short acting).
o If major bleeding occurs, discontinue UFH and give I.V. protamine sulfate.
8. Regarding LMWHs:
➢ Advantages of LMWHs over UFH include: predictable anticoagulation dose response,
improved SC bioavailability, dose-independent clearance, longer biologic half-life, lower
incidence of thrombocytopenia, and less need for routine laboratory monitoring (4)
➢ LMWHs can be easily administered in the outpatient setting, thus enabling the
treatment of VTE at home
➢ Because LMWH anticoagulant response is predictable when given by SC injection, routine
laboratory monitoring is unnecessary.
➢ As with other anticoagulants, bleeding is the most common adverse effect of LMWH
therapy, but major bleeding may be less common than with UFH; If major bleeding
occurs, administer protamine sulfate IV, although it cannot neutralize the anticoagulant
effect completely
➢ Thrombocytopenia can occur with LMWHs, but the incidence of HIT is three times
lower than with UFH
➢ Enoxaparin LD is 30 mg I.V bolus, normal dose is 1 mg/kg every 12 hours.
o Enoxaparin 1 mg = 100 IU.
o Enoxaparin maybe administered via inhalation route for the prevention of
exercise-induced Bronchoconstriction.
➢ Tinzaparin was withdrawn from the USA markets due to the presence of particulate
matter found in the injection solution, also due to poor sales. It also increases the risk of
death in patients over 70 years old with renal disease.
9. Regarding Direct Oral Anticoagulants:
➢ These currently include two categories: direct thrombin (factor IIa) inhibitor (DTI)
(Dabigatran) and direct Xa inhibitors (Rivaroxaban, Apixaban, and Edoxaban).
➢ As compared to warfarin, these oral anticoagulants have a more rapid onset, shorter
half-life, wider therapeutic window, and more predictable pharmacokinetics.
o These features allow for sole oral therapy without the need for an overlapping
parenteral agent (with the exception of Edoxaban for VTE), no need for titration
or dose adjustments in patients with normal renal function, and no need for
routine monitoring.
➢ Compared to warfarin, they have a lower risk of intracranial hemorrhage.
➢ Issues of concern include the lack of antidotes, and risk of thrombosis due to missed doses.
➢ Dabigatran dose is dependent on CrCl:
o CrCl greater than 30 mL/minute: 150 mg twice daily
o CrCl 15–30 mL/minute: 75 mg twice daily.
o Dabigatran has the highest half-life (17 hour), and the only direct oral
anticoagulant that is dialyzable.
o Idarucizumab is a monoclonal antibody fragment used to reverse Dabigatran
anticoagulation.
➢ Rivaroxaban dose is also dependent on CrCl: once daily dosing
o CrCl greater than 50 mL/minute: 20 mg/day with evening meal.
o CrCl 15–50 mL/minute: 15 mg/day with evening meal.
o Also, the dose is regarded to the indication as follows:
▪ DVT prophylaxis for Knee replacement 10 mg/day for 12 days.
▪ DVT prophylaxis for Hip replacement 10 mg/day for 35 days.
▪ Non valvular AF 20 mg/day
▪ DVT or PE treatment 15mg twice for 21 days, then 20 mg/day.
▪ Reduction risk of recurrence of DVT, PE 10 mg/day.
▪ Reduction risk of major cardiovascular events 2.5 mg twice + Aspirin.
➢ Apixaban is dosed 5 mg twice daily unless: In patients with at least two of the following
characteristics: (age 80 years or older, body weight of 60 kg or less, or SCr of 1.5 mg/dl or
greater) the recommended dose is 2.5 mg twice daily.
10. Regarding Parenteral direct thrombin inhibitors:
➢ injectable DTIs include: Lepirudin, Bivalirudin, Argatroban, and Desirudin.
➢ Parenteral DTIs are considered the drugs of choice for the treatment of VTE in patients
with a diagnosis or history of HIT.
➢ Used with caution in patients with renal insufficiency as no antidote exists.
11. Regarding Parenteral Xa inhibitor (Fondaparinux):
➢ Selectively inhibits only Factor Xa, do not increase PT and PTT.
➢ synthetically derived with no variable biologic activity.
➢ safe and effective alternative to LMWH for treatment of VTE. It is also being approved for
prevention of VTE following orthopedic or abdominal surgery
➢ Patients receiving Fondaparinux do not require routine coagulation testing.
➢ FDA warning: Fondaparinux should not be used in the setting of lumbar puncture or
spinal cord surgery, due to risk of epidural or spinal hematomas.
Oral Anticoagulants
Warfarin Tab Coumadin®, Marevan® 1 mg , 2 mg , 3 mg , 4 mg , 5 mg
Vial (powder) Jantoven® 5 mg/vial
Acenocoumarol Tab Sinthrome® 1 mg
Phenindione Tab Phedone®, Dindevan® 10 mg , 25 mg , 50 mg
Dabigatran Cap Pradaxa® 75 mg , 110 mg , 150 mg
Apixaban Tab Eliquis® 2.5 mg , 5 mg
Rivaroxaban Tab Xarelto® 10 mg , 15 mg , 20 mg
Edoxaban Tab Savaysa® , Lixiana® 15 mg , 30 mg , 60 mg
Betrixaban Cap Bevyxxa® 40 mg , 80 mg
Vorapaxar Tab Zontivity® 2 mg
Injectable Anticoagulants
Unfractionated Inj. Solu. Heparin®, Poliparin® 1000 IU/ml , 2500 IU/ml ,
Heparin 5000 IU/ml
LMW Heparins
Enoxaparin Prefilled Syringe Lovenox®, Clexan® 2000 IU , 4000 IU , 6000 IU
Multidose Vial 100 mg/ml (3 ml vial)
Dalteparin Prefilled Syringe Fragmin® 2500 IU , 5000 IU , 7500 IU
Inj. Solu. 10,000 IU/ml , 25,000 IU/ml
Tinzaparin * Multidose Vial Innohep® 20,000 IU/2ml , 40,000 IU/2ml
Prefilled Syringe 3500 IU , 7000 IU , 10,000 IU
Bemiparin Inj. Solu. Ivor®, Hibor® 1000 IU/ml , 5000 IU/ml
Nadroparin Inj. Solu. Fraxiparine® 9500 IU/ml , 19,000 IU/ml
Ardeparin Prefilled Syringe Normiflo® 5000 IU , 10,000 IU
Reviparin Prefilled Syringe Clivarine® 1432 IU , 3436 IU
Multidose Vial 34,356 IU
Injectable Direct Thrombin Inhibitors
Lepirudin Vial (powder) Refludan® 50 mg/vial
Desirudin Inj. Solu. Iprivask® 15 mg/vial
Bivalirudin Vial (powder) Angiomax® , Angiox® 250 mg/vial
Argatroban Inj. Solu. Acova®, Exembol® 100 mg/ml (2.5 ml vial)
Selective Factor Xa inhibitors
Fondaparinux Prefilled Syringe Arixtra® 2.5 mg , 5 mg , 7.5 mg , 10 mg
Idraparinux Prefilled Syringe Idra® 2.5 mg
Idrabiotaparinux Prefilled Syringe -------------- -------------
Other Anticoagulants
Danaparoid Inj. Solu. Orgaran® 1250 IU/ml (0.6 ml amp)
Epoprostenol Infusion Flolan® 500 mcg/vial
Sulodexide Cap , Amp Vessel Due F® 250 LSU (cap) , 600 LSU (amp)
Notes:
1. Danaparoid is a Heparinoid used for prophylaxis of deep-vein thrombosis in patients undergoing general
or orthopedic surgery, it also has a role in patients who develop heparin-induced
thrombocytopenia.
2. Epoprostenol (prostacyclin) can be given to inhibit platelet aggregation during renal dialysis when
heparins are unsuitable or contra-indicated. It is also licensed for the treatment of primary pulmonary
hypertension resistant to other treatments (see section 20)
3. Sulodexide is an Anticoagulant, Antiplatelet and a Fibrinolytic.
Notes:
1. Protamine sulfate is used to treat over-dosage of unfractionated or LMWH (only partially
reverses the effects of LMWHs); The long half-life of LMWH should be taken into
consideration when determining the dose of protamine sulfate; the effects of LMWH can persist
for up to 24 hours.
➢ Dosed as 1-1.5 mg per each 100 units of Heparin.
➢ Dosed as 0.5-1 mg per each 100 units of LMWHs.
➢ Excessive doses of protamine can have an anticoagulant effect.
2. Idarucizumab is a monoclonal antibody fragment used to reverse Dabigatran anticoagulation.
➢ Dosed as 5 gm infused I.V. either as a bolus or separated 2.5 gm vials
3. Andexanet Alfa is specifically indicated for patients treated with Rivaroxaban and Apixaban,
when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.
➢ Administer as an intravenous (IV) bolus, with a target rate of 30 mg/min, followed by
continuous infusion for up to 120 minutes.
Protamine Sulfate Inj. Solu. Protamine® 10 mg/ml (10 ml amp)
Idarucizumab Inj. Solu. Praxbind® 2.5 gm/50 ml vial
Andexanet Alfa Vial AndexXa® 100 mg/vial
Third: Thrombolytic drugs (Fibrinolytics)

1. Acute thromboembolic disease in selected patients (usually in emergency State) may be treated
by the administration of agents that activate the conversion of plasminogen to plasmin, a serine
protease that hydrolyzes fibrin and, thus, dissolves clots.
2. The thrombolytic agents do not distinguish between the fibrin of an unwanted thrombus and the
fibrin of a beneficial hemostatic plug; Thus, hemorrhage is a major side effect .
3. Thrombolytic drugs are indicated for any patient with acute myocardial infarction, Trials
have shown that the benefit is greatest in those with ECG changes that include ST segment
elevation (especially in anterior infarction) and in patients with bundle branch block.
a. Alteplase, streptokinase, and Urokinase can be used for other thromboembolic
disorders such as deep-vein thrombosis and pulmonary embolism (massive emboli).
b. Alteplase is also used for acute ischemic stroke.
c. Urokinase is also licensed to restore the patency of occluded intravenous catheters and
cannulas blocked with fibrin clots.
4. Alteplase should be given within 6–12 hours of MI symptom onset, Reteplase and
Streptokinase within 12 hours of symptom onset, but ideally all should be given within 1
hour; use after 12 hours requires specialist advice; Tenecteplase should be given as early as
possible and usually within 6 hours of symptom onset
➢ Alteplase may cause Angioedema.
5. Practice guidelines indicate that a more fibrin-specific agent (Alteplase, Reteplase, or
Tenecteplase) is preferred over the non–fibrin-specific agent streptokinase, because
Fibrin-specific agents open a greater percentage of infarct arteries, which results in smaller
infarcts and lower mortality, doses are given as below:
➢ Streptokinase: 1.5 MU IV over 60 min.
➢ Alteplase: 15 mg IV bolus followed by 0.75 mg/kg IV over 30 min (max 50 mg) followed
by 0.5 mg/kg (max 35 mg) over 60 min (maximum total dose = 100 mg).
➢ Reteplase: 10 units IV x 2, 30 min apart.
➢ Tenecteplase: according to weight, less than 60 kg (<132 lbs.) = 30 mg IV bolus
60 - 69.9 kg (132–153 lbs.) = 35 mg IV bolus
70 - 79.9 kg (154–176 lbs.) = 40 mg IV bolus
6. Intra-Cranial Hemorrhage (ICH) and major bleeding are the most serious side effects. The risk
of ICH is higher with fibrin-specific agents than with streptokinase; However, the risk of systemic
bleeding other than ICH is higher with streptokinase than fibrin-specific agents.
7. Defibrotide is indicated for the treatment of severe hepatic veno-occlusive disease (only).
8. Relative and Absolute contraindications of Thrombolytics:

Alteplase Powder for Inj. Activase® , Actilyse® , TPA® 2 mg , 50 mg , 100 mg
Reteplase Powder for Inj. Retavase®, Rapilysin® 10.4 units
Tenecteplase Powder for Inj. ®
Metalyse ® , TNKase® 40 mg , 50 mg
Streptokinase * Powder for Inj. Streptase®, Kabikinase® 25 mg
Anistreplase Powder for Inj. Eminase® 30 units
Defibrotide Solu. For infusion Defitelio®, Noravid® 80 mg/ml
Urokinase ** Powder for Inj. Abbokinase® , Kinlytic® 10,000 units
Syner-KINASE® 25,000 units
* Streptokinase is a foreign protein and it is an antigenic. Rashes, fever, and anaphylaxis occur.
** Urokinase is produced naturally in the body by the kidneys. Therapeutic Urokinase is isolated from
human kidney cells and has low antigenicity.
3.17 - Drugs used to Prevent Bleeding (anti-Fibrinolytics)

a. When bleeding occurs as a result of injury or surgery, the body normally acts swiftly to stem the
flow by sealing the breaks in the blood vessels; This occurs in two stages; first when cells called
platelets accumulate as a plug at the opening in the blood vessel wall, and then when these
platelets produce chemicals that activate clotting factors in the blood to form a protein (fibrin).
b. Vitamin K plays an important role in this process; An enzyme in the blood called plasmin ensures
that clots are broken down when the injury has been repaired.
➢ If the blood does not clot, there is a danger of excessive blood loss.
c. It is sometimes useful to promote blood clotting in non-hemophiliacs when bleeding is difficult
to stop (for example, following surgery); In such cases, blood clots are sometimes stabilized by
reducing the action of plasmin with an anti-fibrinolytic (or hemostatic) drug like Tranexamic
acid; this is also occasionally given to hemophiliacs before minor surgery as tooth extraction.
1. Tranexamic acid and Aminocaproic acid: They are used to prevent bleeding or to treat bleeding
as (bleeding associated with menorrhagia); excessive menstrual bleeding, given 3 times daily.
a) Tranexamic acid is 10x times more potent than Aminocaproic acid).
b) Tranexamic acid is used in hereditary angioedema, epistaxis, and in thrombolytic overdose.
c) In 2010, the CRASH-2 trial showed that Tranexamic acid safely reduces mortality in bleeding
trauma patients.
d) It also reduces rates of mortality and urgent surgery in patients with upper GI hemorrhage.
e) Also used successfully to control bleeding in pregnancy (category B).
2. Aprotinin may cause fatal anaphylactic or anaphylactic reactions (including kidney
dysfunction); The drug was temporarily withdrawn worldwide in 2007 after studies suggested
that its use increased the risk of complications or death, In February 2012 the European
Medicines Agency (EMA) scientific committee reverted its previous standpoint regarding
Aprotinin, and has recommended that the suspension be lifted.
a) In cardiac surgery with a high risk of significant blood loss, Aprotinin significantly reduced
bleeding, mortality and hospital stay; Beneficial effects were also reported in high-risk
orthopedic surgery; In liver transplantation, initial reports of benefit were overshadowed by
concerns about toxicity.
3. Etamsylate is a hemostatic drug, it acts by increasing capillary endothelial resistance and

promoting platelet adhesion; indicated for Prophylaxis and control of hemorrhages from small
blood vessels, neonatal intra-ventricular hemorrhage capillary bleeding of different etiology,
including: menorrhagia, hematuria, epistaxis, prevention of periventricular hemorrhages in
prematurely born children.
➢ It is also possible that Etamsylate would reduce reperfusion hemorrhage in ischemic areas
of the brain, preventing secondary damage.
Note: A tendency to bleed may also occur with deficiency of vitamin K, which is required for
the production of several blood clotting factors. Vitamin K is absorbed from the intestine in fats,
but some diseases of the small intestine or pancreas cause fat to be poorly absorbed; As a result,
the level of vitamin K in the circulation is low, causing impaired blood clotting.
➢ A similar problem sometimes occurs in newborn babies due to absence of vitamin K (because
Vit. K cannot reach the baby while its still in the uterus, and in his first days of life the baby
cannot produce Vit. K because there are no bacteria present in his intestine yet); causing
hemorrhagic disease of the newborn; thus, all newborn infants are routinely given Vit. K.
➢ Injections of Phytomenadione, a vitamin K preparation, are used to restore levels to normal.
➢ I.V. administration of Vit. K should be very slowly, not exceeding 1 mg/minute, severe
hypersensitivity reaction (including anaphylactic shock and deaths) have been reported
following rapid I.V. administration.
Anti-Fibrinolytics
Tranexamic acid Amp Exacyl® , Lysteda® 100 mg , 50 mg
Tab Cyklokapron® 500 mg , 650 mg
Aminocaproic acid Tab Amicar® , Cyclo-C® 500 mg
Aprotinin Inj. Solu. Trasylol® 10 million IU/ml
Etamsylate Tab , Amp Dicynone® 250 mg
Vitamin K products
Phytomenadione Amp Konakion MM® 10 mg/1 ml
(Vit K1) * Amp Konakion MM Pediatric® 2 mg/0.2 ml
* Can be taken orally, by I.M. injection or I.V. route.

3.18- Drugs that raise low blood pressure (Anti-Hypotensive)
1. The causes of low blood pressure can range from dehydration to serious medical or surgical
disorders (ex: heart failure, diabetes or hypothyroidism), Low blood pressure is treatable, but it's
important to find out what's causing it so that it can be properly treated.
• Low blood pressure that either doesn't cause signs or symptoms or causes only mild
symptoms, such as brief episodes of dizziness when standing, rarely requires treatment.
• When low blood pressure is caused by medications, treatment usually involves changing the
dose of the medication or stopping it entirely.
2. Here are several ways to increase low blood pressure:
a. Use more salt: Sodium can raise blood pressure, sometimes dramatically. For people with
low blood pressure, that can be a good thing.
b. Drink more water: Fluids increase blood volume and help prevent dehydration, both of
which are important in treating hypotension.
c. Morning dose of Caffeine, as in coffee, Tea or tablet form.
d. Medications: Several medications, either used alone or together, can be used to treat low
blood pressure that occurs when you stand up (orthostatic hypotension).
3. Commonly we have four medications:
a. Fludrocortisone: is a Corticosteroid intended for use as a mineralocorticoid only, it causes
Na+/water retention; thus, increasing blood pressure.
➢ It is also used to replace the missing hormone aldosterone in various forms of adrenal
insufficiency such as Addison's disease and the classic salt wasting form of congenital
adrenal hyperplasia; Usual dose is 1 tab daily (0.1 mg once).
➢ Used with caution in Diabetes, Congestive Heart Failure and Glaucoma
b. Etilefrine (cardiac stimulant); it is a direct-acting a sympathomimetic agent stimulating
both α and β receptors; but it has a high affinity for α receptors.
➢ Tablet and drops dosed 3 times daily, while the MR dosage form is given once daily.
c. Midodrine: works by restricting the ability of blood vessels to expand (α1 agonist), which
raises blood pressure, it also acts on β receptors and has a positive inotropic action.
➢ The usual dose is 1 tablet (10 mg) every 8 hours (3 times daily).
➢ Also indicated for the treatment of stress incontinence (off-label).
d. Droxidopa is approved at Jan. 2014 for Neurogenic Orthostatic Hypotension; it acts as a
prodrug to the neurotransmitter norepinephrine (noradrenaline).
➢ Unlike norepinephrine, Droxidopa is capable of crossing the protective blood–brain
barrier (BBB).
➢ Also used for Intradialytic hypotension (IDH) or hemodialysis-induced hypotension.
4. Other drugs act by raising blood pressure in different mechanisms, they are used in chronic
hypotension, and in emergency cases when blood pressure drops to a critical point.
➢ These include (Epinephrine, Norepinephrine, Dopamine and Dobutamine).
Etilefrine Tab Effortil , Vascon
® ® 5 mg
Tab MR Vascon MR® 25 mg
Drop 7.5 mg/ml
Midodrine Tab Orvaten® , Gutron® , ProAmatine® 2.5 mg , 5 mg , 10 mg
Fludrocortisone Tab Florinef® 0.1 mg
Heptaminol * Tab Corasore ® 150 mg
Droxidopa Cap Northera ® 100 mg , 200 mg , 300 mg
* Heptaminol has a +ve inotropic effect, also has a mild peripheral vasoconstrictor effect.

3.19-Volume Expanders (I.V. Fluids)
1. When blood is lost; the greatest immediate need is to stop further blood loss. The second greatest
need is replacing the lost volume. By This way the remaining red blood cells can still oxygenate
body tissue.
2. Normal human blood has a significant excess oxygen transport capability, only used in cases of
great physical exertion. Provided blood volume is maintained by volume expanders.
3. There are two main types of volume expanders: crystalloids and colloids.
A. Crystalloids: The most commonly used crystalloid fluid is Normal Saline (N/S), a solution of
sodium chloride at 0.9% concentration, which is close to the concentration in the blood
(isotonic). Ringer's lactate or Ringer's acetate is another isotonic solution often used for large-
volume fluid replacement. A solution of 5% dextrose in water, sometimes called D5W, is often
used instead if the patient is at risk for having low blood sugar or high sodium. The choice of
fluids may also depend on the chemical properties of the medications being given. (4)
Solution Contains [Na+](mmol/L) [Cl](mmol/L) [Glucose](mmol/L)

D5W 5% Dextrose 0 0 278
2/3 D & 1/3 S 3.3% Dextrose 51 51 185
+ 0.3% saline
Half-normal 0.45% NaCl 77 77 0
saline
Normal saline 0.9% NaCl 154 154 0
Ringer's Lactated 130 109 0
lactate Ringer
D5NS 5% Dextrose + 154 154 278
Normal Saline
Notes about Crystalloids:
1. Lactated Ringer solution may be preferred because it is unlikely to cause the hyperchloremic
metabolic acidosis seen with infusion of large amounts of normal saline.
o One liter of lactated Ringer's solution contains: 130 mEq of sodium ion = 130 mmol/L, 109
mEq of chloride ion = 109 mmol/L, 28 mEq of lactate = 28 mmol/L, 4 mEq of potassium
ion = 4 mmol/L, 3 mEq of calcium ion = 1.5 mmol/L
2. Ringer Solution is a standard isotonic solution 6.5 g NaCl, 0.42 g KCL, 0.25 g CaCl2 and 1 mole of
sodium bicarbonate is dissolved in one liter of distilled water.
3. Crystalloids are administered at a rate of 500 to 2,000 mL/hour, depending on the severity of the
deficit, degree of ongoing fluid loss, and tolerance to infusion volume.
4. Advantages of crystalloids include rapidity and ease of administration, compatibility with most
drugs, absence of serum sickness, and low cost.
5. The primary disadvantage is the large volume necessary to replace or augment intravascular
volume. Approximately 4 L of normal saline must be infused to replace 1 L of blood loss. In
addition, dilution of colloid oncotic pressure leading to pulmonary edema is more likely to follow
crystalloid than colloid resuscitation.
6. Best Selection of Crystalloids:
• If the patient has high BP → choose Glucose water D5W.
• If the patient has High blood Glucose level → choose Normal Saline 0.9% NaCl.
• If the patient has Hepatic Coma (this will lead to 2ndry hyperaldosteronism with salt and
water retention) thus → Avoid Normal Saline 0.9% NaCl.
• If the patient has Gastroenteritis → choose Ringer Solution or Lactated Ringer, to
replenish Electrolyte Loss.
B. Colloids: Colloids preserve a high colloid osmotic pressure in the blood, they are larger
molecular weight solutions (>30,000 Daltons) that have been recommended for use in
conjunction with or as replacements for crystalloid solutions. They Include (Albumin, starch,
dextran, Hetastarch, Succinylated gelatin).
Albumin (I.V.) Inj. Solu. Bumibate® , Flexbumine® 5% , 25%
Dextran Inj. Solu. Rheomacrodex® , Gentran® 6% , 10%
Hetastarch Inj. Solu. Hespan® , Hextend® 6%
Succinylated gelatin Infusion Solu. Gelofusine® 4%
Notes about Colloids:
1. The theoretical advantage of colloids is their prolonged intravascular retention time
compared with crystalloid solutions. Isotonic crystalloid solutions have substantial interstitial
distribution within minutes of IV administration, but colloids remain in the intravascular space
for hours or days, depending on factors such as capillary permeability.
2. The 5% albumin solution is relatively iso-oncotic, whereas 25% albumin is hyperoncotic and
tends to pull fluid into the compartment containing the albumin molecules.
o The current evidence-based indications for plasma expansion with human albumin in
patients with cirrhosis are the treatment of hepatorenal syndrome, the prevention of
circulatory dysfunction which follows therapeutic paracentesis, and the prevention of
circulatory dysfunction and hepatorenal syndrome in patients with spontaneous bacterial
peritonitis.
3. Hetastarch may cause elevations in serum amylase concentrations but does not cause
pancreatitis.
4. Adverse effects of colloids are generally extensions of their pharmacologic activity (e.g.,
fluid overload and dilutional coagulopathy). Albumin and dextran may be associated with
anaphylactic reactions or anaphylaxis. Bleeding may occur in certain patients receiving
Hetastarch and dextran.
3.20 - Positive Inotropics

o These increase myocardial contractility, and are used to support cardiac function in conditions
such as decompensated congestive heart failure, Shock (hypovolemic shock, cardiogenic shock,
and septic shock), myocardial infarction, cardiomyopathy, etc.
Scientific nameDosage form Trade name concentration
Dopamine Inj. Solu. Intropin ® 40 mg/ml & 80 mg/ml
Dobutamine Inj. Solu. Dobutrex® 12.5 mg/ml
Dopexamine Solu. for infusion Dopacard ® 50 mg/5ml
Epinephrine Inj. Solu. EpiPen , Adrenalin
® ® 0.1 mg/ml & 1 mg/ml
Isoproterenol Inj. Solu. Isuprel® 0.2 mg/ml
Aerosol 0.131 mg/inhale
Norepinephrine Inj. Solu. , amp Levophed , Noradrenalin
® ® 1 mg/ml , (4 mg/4 ml amp)
Phenylephrine Inj. Solu. Neo-Synephrine ® 10 mg/ml
Milrinone Inj. Solu. Primacor ® 1 mg/ml
Inamrinone ** Inj. Solu. Inocor® 5 mg/ml
Enoximone Inj. Solu. Perfan ® 5mg/ml (20 ml)
** was named (Amrinone), but changed in 2000 to prevent confusion with Amiodarone.

Notes About positive Inotropics:
A) For easy memorization remember:
➢ Epinephrine: acts on (α1, α2, β1, β2).
➢ Norepinephrine: acts on (α1, α2, β1).
➢ Isoproterenol: acts on (β1, β2).
➢ Dopamine: acts on (α1, β1) and dopaminergic receptors.
➢ Dobutamine: acts specifically on (β1), with very mild activity on (β2, α1)
➢ Phenylephrine: acts only on (α1)
B) Specific notes:
1. Dopamine is the drug of choice for cardiogenic and septic shock and is given by continuous
infusion. It raises the blood pressure by stimulating the β1 receptors on the heart to increase
cardiac output and α1 receptors on blood vessels to increase total peripheral resistance. In
addition, it enhances perfusion to the kidney and splanchnic areas; increased blood flow
to the kidney enhances the glomerular filtration rate and causes sodium diuresis.
➢ Low dose increases renal blood flow, intermediate dose has a beta effect, higher
doses has an alpha effect.
2. Dobutamine is primarily a selective β1-agonist with mild β2 and vascular α1 activity, resulting
in strong positive inotropic activity without concomitant vasoconstriction. Increases cardiac
output and does not significantly elevate oxygen demands of the myocardium, a major
advantage over other sympathomimetic drugs.
➢ It Has a short plasma half-life.
3. Epinephrine is the primary drug used in the emergency treatment of any condition of the
respiratory tract when bronchoconstriction has resulted in diminished respiratory exchange.
Thus, in treatment of acute asthma and anaphylactic shock, epinephrine is the drug of
choice.
➢ Epinephrine is the drug of choice for the treatment of Type I hypersensitivity reactions
in response to allergens
➢ Local anesthetic solutions usually contain 1:100,000 parts epinephrine to increase the
duration of the local anesthesia.
4. Norepinephrine is a combined α- and β-agonist, but it primarily produces vasoconstriction.
5. Phenylephrine is a pure α1 -agonist and is thought to increase BP through vasoconstriction. It
may also increase contractility and CO.
➢ Phenylephrine may be beneficial in septic shock because of its selective α-Agonism,
vascular effects, rapid onset, and short duration.
➢ Phenylephrine may be a useful alternative in patients who cannot tolerate the
tachycardia or tachy-dysrhythmias with use of dopamine or norepinephrine.
3.21 – Drugs for Pulmonary Hypertension
1. Pulmonary hypertension (PH) is an increase of blood pressure in the pulmonary artery, pulmonary
vein, or pulmonary capillaries, leading to shortness of breath, dizziness, fainting, leg swelling and
other symptoms.
2. Capillaries become narrowed, blocked or destroyed, this makes it harder for blood to flow through
the lungs, and raises pressure within lung arteries, as the pressure builds, the heart right ventricle
must work harder to pump blood through the lungs, eventually causing the heart muscle to weaken
and eventually fail), Pulmonary hypertension can be a severe disease with a markedly decreased
exercise tolerance and heart failure.
3. Pulmonary hypertension isn't curable, treatments available can help lessen symptoms and
improve quality of life; Treatment options include: high dose Ca+ channel blockers (ex:
amlodipine up to 20 mg daily) with loop diuretics, PDE-5 Inhibitors, Endothelin Antagonists
and Prostacyclin Analogs.
➢ PDE-5 Inhibitors is not recommended in patients with either of two rare diseases often associated
with PH: pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.
Endothelin Antagonists
Ambrisentan Tab Letairis® 5 mg , 10 mg
Bosentan Tab Tracleer®, Bosentas® 62.5 mg , 125 mg
Macitentan Tab Opsumit® 10 mg
Sitaxentan Tab Thelin® 100 mg
Prostacyclin Analogs
Epoprostenol Inj. powder Flolan® , Veletri® 0.5 mg , 1.5 mg (per vial)
ILoprost Amp Ventavis® 10 mcg/ml , 20 mcg/ml
Beraprost Tab Dorner® , Berasil® 20 mcg
Treprostinil Tab Orenitram® 0.125 mg , 0.25 mg , 1 mg
Inj. Solu Remodulin® 1 mg , 2.5 mg , 5 mg (per 1ml)
Inhale Solu. Tyvaso® 600 mcg/ml
Selexipaq Tab Uptravi® 200 , 400 , 800 , 1200 mcg
PDE-5 Inhibitors
Sildenafil Tab Viagra®, Kamagra® 25 mg , 50 mg , 100 mg
Inj. Solu. Revatio® 10 mg/12.5 ml
Tadalafil Tab Cialis® 5 mg , 10 mg , 20 mg
Guanylate Cyclase Stimulator
Riociguat Tab Adempas® 0.5 mg , 1 mg , 2 mg
Notes:
1. Endothelin receptor antagonists reverse the effect of Endothelin, a substance in the walls of blood
vessels that causes them to narrow.
a. Patients using Bosentan, Ambrisentan needs monthly liver monitoring, because these drugs
can cause severe damage the liver.
b. Pfizer withdrew Sitaxentan (Thelin®) worldwide because of fatal liver complications.
2. Prostacyclins are Blood vessel dilators (vasodilators), they are unstable, and therefore have to
be kept on ice during administration. Since they have a half-life of 3 to 5 minutes, the infusion has to
be continuous (24/7), and interruption can be fatal.
a. Treprostinil (Remodulin®) can be given intravenously (IV) or subcutaneously (SC), but the
subcutaneous form can be very painful.
b. The inhaled form of Treprostinil has the advantage of selective deposition in the lungs with
less systemic side effects; however, coughing and throat irritation commonly occur.
3. Sildenafil and Tadalafil works by opening the blood vessels in the lungs to allow blood to flow
through more easily, also used for Erectile Dysfunction. (see chapter 8, section 5)
a. Tadalafil is also indicated for the treatment of signs and symptoms of BPH.
3.22 - Miscellaneous cardiovascular drugs
Scientific name Category D. form Trade name concentration
Nesiritide Natriuretic Analogue Inj. Solu. Natrecor® 1.5 mg/vial
Urapidil Antihypertensive Cap Uradil® 30 mg , 60 mg , 90 mg
Guanethidine Antihypertensive Amp Ismelin® 10 mg/ml
Levosimendan Calcium Sensitizer Inj. Solu. Simdax® 2.5 mg/ml (5 ml vial)
Amyl Nitrite (nitrate) Vasodilator Amp (Solu.) ---------- 0.3 ml
Papaverine Vessels Relaxant Cap Para Time® 150 mg
Inj. Pavabid® 30 mg/mL
Gel TriMix® 2%
Reserpine Antipsychotic + Tab Serpasil® 0.1 mg , 0.25 mg
Antihypertensive
Deserpidine Antihypertensive Tab Canescine® 0.25 mg , 0.5 mg
Mecamylamine Antihypertensive Tab Vecamyl® 2.5 mg
Strange Combinations
Reserpine + Polythiazide Tab Renese-R® 0.25 mg + 2 mg
Reserpine + Hydrochlorothiazide Tab Ser-Ap-Es® 0.25 mg + 25 mg
+ Hydralazine Relazide® + 25 mg
Deserpidine + Methyclothiazide Tab Enduronyl® 0.5 mg + 5 mg
Notes:
1. Nesiritide works to facilitate cardiovascular fluid homeostasis through counter-regulation of the renin-
angiotensin-aldosterone system, stimulating cyclic guanosine monophosphate, leading to smooth muscle
cell relaxation. Nesiritide is beneficial for acute decompensated congestive heart failure.
➢ That’s due the fact that Nesiritide is a balanced vasodilator that acts on arteries to decrease systemic
vascular resistance and thereby lowers left ventricular afterload, and acts on veins to increase venous
capacitance and thereby lowers left and right heart failing pressures.
2. Urapidil is a sympatholytic antihypertensive drug, it acts as an α-1 receptor antagonist, it is currently
not approved by the U.S. FDA, but it is available in Europe.
➢ Reduces blood pressure without altering heart rate.
➢ the antihypertensive efficacy of Urapidil was lower than that of hydrochlorothiazide in some trials.
➢ Urapidil does not elicit reflex tachycardia, and this may be related to its weak β1-adrenoceptor
antagonist activity
3. Guanethidine is an antihypertensive drug that reduces the release of catecholamines, such as
norepinephrine, thus gradually decreasing BP and HR; also, Intravenous nerve block (Bier block) using
Guanethidine has been used to treat chronic pain caused by complex regional pain syndrome.
4. Levosimendan is indicated for the short-term treatment of acutely decompensated severe chronic
heart failure (ADHF) in situations where conventional therapy is not sufficient, and in cases where
inotropic support is considered appropriate.
➢ It enhances myocardial contractility without increasing oxygen requirements, and causes
coronary and systemic vasodilation.
➢ Levosimendan has shown preliminary positive effects in a range of conditions requiring inotropic
support, including right ventricular failure, cardiogenic shock, septic shock.
5. Papaverine, an alkaloid; it’s used to improve blood flow in patients with circulation problems.
➢ It works by relaxing the blood vessels so that blood can flow more easily to the heart and through
the body, its FDA approved for the treatment of Arterial spasms.
➢ Papaverine is also an antiarrhythmic medication that treats certain abnormal heartbeats
(ventricular arrhythmias); It works by blocking the abnormal electrical activity in the heart so a
normal heart beat can return; It may help the heart beat better by increasing blood flow to the heart.
➢ Some also uses it for Erectile Dysfunctions as an intracavernous inj. (direct inj. To the penis!).
• It should not be injected into the penis; This practice has resulted in painful or prolonged erection
that may require surgery to correct; A topical gel is also available for Erectile Dysfunction
treatment, which is safer and more efficient than the injectable dosage form.
6. Amyl Nitrate, by inhalation of crushed amp its used for the relief of Acute Angina; (the amp is crushed
and its contents is poured into a gauze and placed in front of patient’s mouth).
➢ Used also in Cyanide poisoning; (see chapter 17 for more details).
➢ It is abused to enhance sexual experience or to experience a general sense of sexual pleasure and
Euphoria (feeling instant multiple orgasms); known locally as Poppers; (The effects are felt within 30
seconds of taking the drug, and last for around 2-3 minutes), they also cause a warming sensation,
feelings of excitement and relaxation of involuntary muscles, especially the anal and vaginal sphincter.
o Taking the drug in this way is not safe; it can cause irregular and rapid heart rhythms and result
in a syndrome called "sudden sniffing death, they also cause temporary or permanent vision loss.
7. Reserpine is used to treat high blood pressure, also used to treat severe agitation in patients with
severe mental disorders.
➢ It works by slowing the activity of the nervous system (via depletion of tissue store of catecholamines
as norepinephrine, dopamine), causing heart beat to slow and the blood vessels to relax.
➢ Has a high side effect profile; thus, used only in emergency HT these days.
8. Deserpidine, an alkaloid; a competitive inhibitor of the angiotensin converting enzyme (ACE); it is
related to Reserpine.
9. Mecamylamine is a potent, oral antihypertensive agent and ganglion blocker, and is a secondary amine.
it is indicated for the management of moderately severe to severe essential hypertension and in
uncomplicated cases of malignant hypertension.
References
3- Mary Anne koda-kimble (ed.), Applied Therapeutics: The clinical use of drugs, 11th Ed.
5- Comprehensive Pharmacy Review for NAPLEX 8th Ed.
6- Journal of the American Society of Nephrology. 18 (9): 2509–16.
7- Lawrence A. Trissel. Handbook on injectable drugs - 15th ed. 2009.
8- Levy BL, Taddei S. Vascular legacy beyond blood pressure control. Curr. Med. Res. Opin. 2018
9- European Heart Journal Supplements (2007) 9 (Supplement E), E10–E19
10- Cockroft JR et al. Nebivolol vasodilates human forearm vasculature: Evidence for an L-arginine/NO-
dependent mechanism. J Pharmacol Exp Ther 1995; 274: 1067-1071
11- Agabiti Rosei E, Rizzoni D. Metabolic profile of nebivolol, a beta-adrenoceptor antagonist with unique
characteristics. Drugs 2007; 67: 1091-1107
12- iugliano D, Acampora R, Marfella R, de Rosa N, Ziccardi P, Ragone R, de Angelis L, d'Onofrio F.
Metabolic and cardiovascular effects of carvedilol and atenolol in non-insulin-dependent diabetes mellitus
and hypertension – a randomized, controlled trial. Ann Intern Med 1997; 126: 955-959
13- Koshucharova G, Zweiker R, Maier R, Lercher P, Stepan V, Klein W, Stoschitzky K. Different beta-
blocking effects of carvedilol and bisoprolol in humans. J Clin Basic Cardiol 2001; 4: 53-56
14- Stoschitzky K, Koshucharova G, Zweiker R, Maier R, Watzinger N, Fruhwald FM, Klein W. Differing
beta-blocking effects of carvedilol and metoprolol. Eur J Heart Failure 2001; 3: 343-349 (Impact 2,122)
15- https://jamanetwork.com/journals/jamacardiology/fullarticle/2732487
17- https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehz754/5602478
18- https://www.webmd.com/diabetes/news/20150923

CENTRAL NERVOUS SYSTEM
Chapter Four: Central Nervous System
Part Two:
4.1 - Hypnotics and Anxiolytics 4.9 - Nootropics
a. Benzodiazepines
b. Barbiturates 4.10 - Herbals and Supplements for
c. Other Sedative/Hypnotics and Cognitive function
Anxiolytics
4.2 - Antipsychotic drugs

a. The older agents (typical or
conventional antipsychotics)
b. Atypical antipsychotics (the
Newer Generation)
c. Antipsychotic Depot Inj.
4.3 - Anti-Depressant drugs

a. selective serotonin re-uptake
inhibitors (SSRIs)
b. TCAs and related drugs
c. Serotonin Norepinephrine
Reuptake Inhibitors (SNRIs)
d. Atypical Antidepressants
e. Monoamine Oxidase Inhibitors
(MAOIs)
f. Other Antidepressant drugs
g. Psychotherapeutic combos
4.4 – Anti-epileptic drugs (AEDs)
4.5 - Drugs used in Parkinsonism
4.6 - Drugs used in Nausea and

Vertigo
a. 5HT3-receptor antagonists
b. Butyrophenones
c. Cannabinoids
d. Miscellaneous agents
4.7 - Drugs for Dementia (Anti-

Alzheimer)
4.8- CNS Stimulants

Sam’s Guide: Chapter 4 – CNS
Chapter Four: Central nervous system
Part one:
1. Introduction:
1. The human brain contains more than 100 billion nerve cells (neurons); These nerve cells receive
electrochemical impulses from everywhere in the body, they interpret these impulses and send
responsive signals back to various glands and muscles, the brain functions continuously as a
switchboard for the human communications system; at the same time, it serves as the seat of
emotions and mood, of memory, personality, and thoughts.
2. Extending from the brain is an additional, large rod-shaped cluster of nerve cells that forms the
spinal cord; Together, these two elements comprise the central nervous system.
3. Radiating from the central nervous system is the peripheral nervous system, which has three
parts. One branches off the spinal cord and extends to skin and muscles throughout the body,
another, in the head, links the brain to the eyes, ears, nose, and taste buds, the third is a semi-
independent network called the autonomic, or involuntary, nervous system.
➢ This is the part of the nervous system that controls unconscious body functions such as
breathing, digestion, and glandular activity.
➢ Signals traverse the nervous system by electrical and chemical means; Electrical impulses
carry signals from one end of a neuron to the other, and to cross the gap between neurons,
chemical neurotransmitters are released from one cell to bind on to the receptor sites of
nearby cells; Excitatory transmitters stimulate action; inhibitory transmitters reduce it.
4. The autonomic, or involuntary, nervous system governs the actions of the muscles of the
organs and glands; such vital functions as heart beat and digestion continue without conscious
direction, whether we are awake or asleep, the autonomic nervous system is divided into two
parts, the effects of one generally balancing those of the other:
a) The sympathetic nervous system: has an excitatory effect, it widens the airways to the
lungs, increases the heart rate, and increases the flow of blood to the arms and legs.
b) The parasympathetic system: by contrast, has an opposing effect, it slows the heart rate,
narrows the large airways, and redirects blood from the limbs to the gut.
5. Although the functional pace of most organs results from the interplay between the two systems,
the muscles in the blood vessel walls respond only to the signals of the sympathetic
nervous system; whether a vessel is dilated or constricted is determined by the relative
stimulation of two sets of receptor sites: alpha sites and beta sites.
➢ Blood vessels in the skin: These are constricted by stimulation of alpha receptors by the
sympathetic; the parasympathetic has no effect on them.
➢ The Heart: The rate and strength of the heart are increased by the sympathetic and reduced
by the parasympathetic.
➢ The pupils: These are dilated by the sympathetic and constricted by the parasympathetic.
➢ The airways: The bronchial muscles are relaxed and widened by the sympathetic and
contracted and narrowed by the parasympathetic.
➢ Intestines: The activity of the intestinal wall muscles is reduced by the sympathetic and
increased by the parasympathetic.
6. The parasympathetic nervous system depends on the neurotransmitter Acetylcholine to
transmit signals from one cell to another; The sympathetic nervous system relies on
epinephrine (adrenaline) and norepinephrine (noradrenaline) for the transmission.
7. The drugs described in this chapter don’t eliminate or cure nervous system disorders; Their
function is to correct or modify the communication of the signals that traverse the nervous
system, by doing so they can relieve symptoms or restore normal functioning and behavior; in
some cases, as anxiety and insomnia, drugs are used to lower the level of activity in the brain, in
other disorders (as depression) drugs are given to encourage the opposite effect, increasing the
level of activity.
8. Drugs that act on the nervous system are also used for conditions that outwardly have nothing
to do with nervous system disorders; such as Vomiting, for example, may be treated with drugs
that directly affect the vomiting center in the brain or block stimulatory nerve signals to the
vomiting center.
➢ The drugs that stimulate the sympathetic nervous system are called Adrenergics (or
Sympathomimetics); They either promote the release of epinephrine (adrenaline) and
norepinephrine (noradrenaline) or mimic their effects.
➢ Drugs that interfere with the action of the sympathetic nervous system are called
Sympatholytics, as Alpha blockers act on alpha receptors; beta blockers act on beta receptors.
➢ Drugs that stimulate the parasympathetic nervous system are called Cholinergics (or
Parasympathomimetics).
➢ Drugs that oppose the action of parasympathetic are called Anticholinergics (or
Parasympatholytics).
2. What Can go wrong in the Central Nervous system

1. Disorders of the brain and nervous system may manifest as illnesses that show themselves as
physical impairments, such as epilepsy or strokes, or mental and emotional impairments (for
example, schizophrenia and depression).
➢ Illnesses causing physical impairments can result from different types of disorder of the brain
and nervous system.
➢ Death of nerve cells resulting from poor circulation can result in paralysis, while electrical
disturbances of certain nerve cells cause the seizures or epilepsy.
➢ Temporary changes in blood circulation within and around the brain are associated with
migraine headache.
➢ Parkinson’s disease is caused by a lack of dopamine, a neurotransmitter that is produced by
specialized brain cells.
➢ The causes of disorders that trigger mental and emotional impairment are not known, but
these illnesses are thought to result from the defective functioning of nerve cells and
neurotransmitters.
2. Note: Most of the CNS drugs (like antipsychotics, antidepressant, antiepileptics, anxiolytics,
hypnotics, and opioid analgesics) can cause drowsiness, thereby affecting the ability to drive
and operate hazardous machinery and patients should be warned about this.
(Remember: the drugs in this chapter has high potentials for abuse → give ONLY by Rx).

4.1-Hypnotics and Anxiolytics
1. Difficulty in getting to sleep or staying asleep (insomnia) has many causes, most people have
sleepless nights from time to time, usually due to a temporary worry or discomfort from a minor
illness, Persistent sleeplessness can be caused by psychological problems including anxiety or
depression, or the pain and discomfort of a physical disorder.
➢ A certain amount of stress can be beneficial, providing a stimulus to action; But too much will
often result in anxiety, which might be described as fear or apprehension not caused by any
real danger or harm.
➢ Clinically, anxiety arises when the balance of certain chemicals in the brain is disturbed,
the fearful feelings increase brain activity, stimulating the sympathetic nervous system and
often triggering physical symptoms, for example, breathlessness, shaking, palpitations,
digestive distress, and headaches.
2. For occasional sleeplessness, simple, common remedies to promote relaxation, such as taking a
warm bath or a hot milk drink before bedtime, are usually the best treatment.
3. Sleeping drugs (also known as hypnotics) are normally prescribed only when these self-help
remedies have failed, and when lack of sleep is beginning to affect general health.
➢ They are used to re-establish the habit of sleeping, and should be used in the smallest dose
and for the shortest possible time (not more than three weeks).
➢ It is best not to use Hypnotics every night.
➢ Do not use alcohol to get to sleep; as it can cause disturbed sleep and insomnia; alcoholics
when taken properly might act as mild tranquilizers.
4. Most sleeping drugs promote sleep by depressing brain function; They interfere with chemical
activity in the brain and nervous system by reducing communication between nerve cells, this
leads to reduced brain activity, allowing you to fall asleep more easily.
➢ Because the sleep induced by drugs is not the same as normal sleep, many people find that
they do not feel as well rested by it as by a night of natural sleep; This is the result of
suppressed brain activity.
➢ Hypnotics become less effective after the first few nights and there may be a temptation
to increase the dose.
➢ When Hypnotics are suddenly withdrawn, anxiety, seizures, and hallucinations sometimes
occur; Sleeplessness will recur and may lead to a temptation to use sleeping drugs again.
5. Anti-anxiety drugs (also known as anxiolytics or minor tranquillizers) are prescribed for
short-term relief of severe anxiety and nervousness caused by psychological problems; they also
used in hospitals to calm and relax people undergoing uncomfortable medical procedures.
Notes:
1. Hypnotics are used for patients with insomnia, while anxiolytics are used for anxiety.
2. Prescribing of these drugs is widespread but dependence and tolerance occur; This may lead
to difficulty in withdrawing the drug.
3. Hypnotics and anxiolytics should be reserved for short courses to alleviate acute conditions
after causal factors have been established.
4. Benzodiazepines are the most commonly used anxiolytics and hypnotics; The most commonly
Benzodiazepines available are: (Alprazolam, Chlordiazepoxide, Diazepam, and Lorazepam).
➢ Mechanism of Action: depress activity in the part of the brain that controls emotion by
promoting the action of the neurotransmitter gamma-aminobutyric acid (GABA), which binds
to neurons, blocking transmission of electrical impulses and thereby reducing
communication between brain cells; Benzodiazepines increase the inhibitory effect of
GABA on brain cells, preventing the excessive brain activity that causes anxiety.

➢ Short-acting or intermediate acting hypnotics
(Alprazolam) are preferable in patients with sleep
onset insomnia, when sedation the following day is
undesirable, or when prescribing for elderly patients.
➢ Long-acting hypnotics (Diazepam) are indicated in
patients with poor sleep maintenance (ex: early
morning waking) that causes daytime effects, when an
anxiolytic effect is needed during the day, or when
sedation the following day is acceptable.
5. Benzodiazepines are used as anxiolytics, hypnotics,
management of alcohol withdrawal, anticonvulsants,
skeletal muscle relaxants, conscious sedation, surgical
adjuncts such as Perioperative anxiolysis/sedation, and
induction and maintenance of anesthesia.
➢ Anxiolytic benzodiazepine treatment should be
limited to the lowest possible dose for the shortest
possible time.
6. Side effects of Benzodiazepines include drowsiness, dizziness, ataxia, CNS depression,
psychomotor impairment, confusion, cognitive impairment, aggression.
➢ Withdrawal of a benzodiazepine should be gradual because abrupt withdrawal may
produce confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens
➢ There is a risk of neonatal withdrawal symptoms when benzodiazepines are used during
pregnancy; Avoid regular use and use only if there is a clear indication such as seizure
control, High doses administered during late pregnancy or labor may cause neonatal
hypothermia, hypotonia, and respiratory depression.
7. Barbiturates have been less used these days due they are associated with very severe
withdrawal symptoms; Foremost is their ability to cause coma.
➢ The long-acting barbiturate (Phenobarbital) is still sometimes of value in epilepsy (see
section 4) but its use as a sedative is unjustified; Phenobarbital has been regarded as the
drug of choice for treatment of young children with seizures; However, phenobarbital
can depress cognitive performance in children, and the drug should be used cautiously.
➢ Thiopental is still used these days to induce anesthesia.
8. Beta-blockers do not affect psychological symptoms of anxiety, such as worry, tension, and fear,
but they do reduce autonomic symptoms, such as palpitation and Shaking (tremor).
➢ They block the action of a chemical transmitter called norepinephrine (noradrenaline) in the
body, thus reducing the physical symptoms of anxiety.
➢ commonly prescribed for people who feel excessively anxious in certain situations, such as
interviews or public appearances.
➢ The most common beta blocker given as anxiolytic is propranolol.
A) Benzodiazepines (BZD)
Short acting BZDs
Triazolam Tab Halcion® 0.125 mg , 0.25 mg
Midazolam Tab Versed®, Dormicum® 7.5 mg
Nasal spray Nayzilam® 5 mg
Inj. (Amp) 1 mg/ml , 5 mg/ml
Oxazepam Cap Serax® , Comedormir® 10 mg , 15 mg , 30 mg
Brotizolam Tab Lendormin® 0.25 mg
Loprazolam Tab Havlane®, Dormonoct® 1 mg
Lormetazepam Tab Dormagen® 0.5 mg , 1 mg
Intermediate acting BZDs
Alprazolam Tab Xanax® , Niravam® 0.25 mg , 0.5 mg , 1 mg , 2 mg
Oral Susp. 0.75 mg/ml
Lorazepam Tab Ativan® 0.5 mg , 1 mg , 2 mg
Inj. 2 mg/ml , 4 mg/ml
Clonazepam Tab Rivotril® , Klonopin® 0.5 mg , 1 mg , 2 mg
Oral Drops Rivotril® 2.5 mg/5 ml (10 ml drop)
Estazolam Tab ProSom® 1 mg , 2 mg
Temazepam Cap Restoril® 7.5 mg , 10 mg , 15 mg
Nitrazepam Tab , Susp. Mogadon® 5 mg (tab) , 2.5 mg/5 ml (Susp)
Long acting BZDs
Chlordiazepoxide Tab , Cap Librium® 5 mg , 10 mg
Diazepam Tab Valium® , Diastat®, Dialar® 2 mg , 5 mg , 10 mg
Oral Solu. 1 mg/1ml , 5 mg/1ml
Inj. 5 mg/1ml
Nasal Spray Valtoco® 5 mg , 10 mg , 15 mg , 20 mg
Bromazepam Tab Lexotanil® , Calmepam® doses.
1.5 mg , 3 mg , 6 mg
Flurazepam Cap Dalmane® , Somnol® 15 mg , 30 mg
Quazepam Tab Doral® 7.5 mg , 15 mg
Clorazepate Tab Tranxene® 7.5 mg , 15 mg
Clobazam Tab Ofni® , Frisium® 10 mg , 20 mg
1. Diazepam is useful in the treatment of skeletal muscle spasms, as in muscle strain, and in treating
spasticity from degenerative disorders, such as multiple sclerosis and cerebral palsy
➢ Also, some gynecologists give it as a Uterine relaxant to ease delivery in labor, this is not (FDA)
approved, but some studies support this off-label use
➢ Also, some uses it as antihypertensive, this is also NOT (FDA) approved.
2. Only 5 BZD are FDA approved as sedative-Hypnotics; Quazepam, Flurazepam, Temazepam, Estazolam
and Triazolam; because they are rapidly absorbed and produce CNS sedation more quickly
3. Clonazepam, Lorazepam are usually used as anticonvulsant.
4. Diazepam, Clorazepate, Chlordiazepoxide, and Flurazepam have active metabolites with very long
half-lives, and cumulative effects occur with chronic administration.
5. Flumazenil is a benzodiazepine antagonist that can be used to treat benzodiazepine overdose; it has a
short half-life and continuous monitoring is required.
Flumazenil Inj. Romazicon® 0.1 mg/ml
B) Barbiturates
Phenobarbital Tab Luminal® 15 mg , 30 mg
Elixir , Amp 20 mg/5 ml , 30 mg/ml (Amp)
Primidone * Tab Mysoline® , Liskantin® 50 mg , 250 mg
Oral Susp. Liskantin Saft® 125 mg/5 ml (250 ml)
Amobarbital Inj. Powder Amytal® 500 mg
Pentobarbital Inj. Solu. Nembutal® 50 mg/ml
Secobarbital Cap Seconal® 100 mg
Butabarbital Tab Butisol® 30 mg & 50 mg
Thiopental ** Inj. Powder Pentothal® , Trapanal® -------------------------
* Primidone is a pro-drug, which is metabolized into Phenobarbital, phenylethylmalonamide, which
both have an antiepileptic action.
** Thiopental Along with Pancuronium bromide and potassium chloride, is used in 34 states of the
USA to execute prisoners by lethal injection, (Cause death without pain; like you’re going to sleep).
C) Other Sedative/Hypnotics and Anxiolytics
Chloral hydrate Cap , Oral Solu. Somnote® , Noctec® 500 mg , 500 mg/5 ml
Etifoxine Cap Stresam® 50 mg
Eszopiclone Tab Lunesta® 1 mg , 2 mg
Tofisopam Tab Grandaxin®, Sériel® 50 mg
Ramelteon Tab Rozerem® 8 mg
Zaleplon Cap Sonata® , Siesta® 5 mg , 10 mg
Zopiclone Tab Zimovane® , Imovane® 3.75 mg , 7.5 mg
Zolpidem Tab Stilnox® , Ambien® 5 mg , 10 mg
Sub-lingual Tab Intermezzo® , Edluar® 1.75 , 3.5 , 5 , 10 mg
Meprobamate Tab Miltown® , Equanil® 200 mg , 400 mg
Buspirone Tab Buspar® 10 mg , 30 mg
Sodium Oxybate Oral Solu. Xyrem® 500 mg/ml
Suvorexant Tab Belsomra® 5 mg , 10 mg , 20 mg
Melatonin Tab Meloset® , Circadin® 2 mg , 3 mg
Tab SR , Cap 5 mg , 10 mg
Oral Drops 3 mg/1 ml
Notes: (2-9)
1. Chloral hydrate is used in pediatrics for sedation before procedures, (Usually in 10% syrup).
➢ Onset of action 30-60 min, while duration 7-11 hours.
➢ There is no convincing evidence that it is particularly useful in the elderly.
2. Etifoxine has an anxiolytic activity and has a mild sedative effect.
3. Tofisopam is only an Anxiolytic, does not have anticonvulsant, sedative, skeletal muscle
relaxant effects.
4. Ramelteon is a selective agonist at the MT1 and MT2 subtypes of melatonin receptors.
Stimulation of MT1 and MT2 receptors by melatonin in the SCN is able to induce and promote
sleep and is thought to maintain the circadian rhythm underlying the normal sleep–wake cycle.
➢ Thus, Ramelteon is indicated for the treatment of insomnia in which falling asleep is
the primary complaint. (Note that Ramelteon increase prolactin levels).
5. Zaleplon, Zolpidem and Zopiclone are sometimes referred to as Z-drugs, they act at the
benzodiazepine receptor; they are not licensed for long-term use, although; dependence has been
reported in some patients.
➢ Zolpidem and Zopiclone have a short duration of action; Zaleplon is very short acting.
➢ They have no anticonvulsant or muscle-relaxing properties; It shows few withdrawal
effects and exhibits minimal rebound insomnia and little tolerance occurs in prolonged use.
6. Eszopiclone (isomer of Zopiclone), has the advantage that its FDA approved for long-term
treatment of insomnia, (unlike other hypnotics which are only used for short terms).
7. Buspirone is different from other anti-anxiety drugs; it binds mainly to serotonin receptors
and does not cause drowsiness; Its effect is not felt for at least 2 weeks after treatment has begun.
8. European Medicines Agency (EMA) has recommended (Jan. 2012) the suspension of all
marketing for Meprobamate because the risks, particularly of serious CNS side-effects, outweigh
the benefits.
9. Sodium Oxybate is a central nervous system depressant that is licensed for the treatment of
narcolepsy with cataplexy.
10. Suvorexant exerts its therapeutic effect in insomnia through antagonism of orexin receptors;
The orexin neuropeptide signaling system is a central promoter of wakefulness.
11. Melatonin is the hormone produced by the pineal gland; it regulates sleep cycles.
➢ Licensed for the short-term treatment of insomnia in adults.
➢ Also licensed for the prevention of Cluster headaches, Migraine headache.
4.2-Antipsychotic drugs (for treatment of schizophrenia)
1. Psychosis is a term used to describe mental disorders that prevent the sufferer from thinking
clearly, recognizing reality, and acting rationally, these disorders include schizophrenia and
bipolar disorder (manic depression).
2. The precise causes of these disorders are unknown, although a number of factors, including
stress, heredity, and brain injury, may be involved, Temporary psychosis can also arise as a result
of alcohol withdrawal or the abuse of mind-altering drugs.
3. It is thought that some forms of mental illness are caused by an increase in communication
between brain cells due to over-activity of an excitatory chemical called dopamine, this may
disturb normal thought processes and produce abnormal behavior; Dopamine combines with
receptors on the brain cells.
➢ Antipsychotic drugs reduce the transmission of nerve signals by binding to these receptors,
thereby making the brain cells less sensitive to dopamine.
➢ Some newer antipsychotic drugs, such as clozapine, risperidone, and sertindole, also bind
to receptors for the chemical serotonin (block serotonin-2 receptors.)
➢ Because antipsychotics depress the action of dopamine, they can disturb its balance
with another chemical in the brain, Acetylcholine; (increase its concentrations), if an
imbalance occurs, extrapyramidal side effects (EPSE) may appear. These include
restlessness, disorders of movement, and parkinsonism.
➢ Antipsychotics may block the action of noradrenaline, another neurotransmitter in the
brain; This lowers the blood pressure, especially when standing up, causing dizziness, it may
also prevent ejaculation causing an Erectile Dysfunction.
➢ Antipsychotic drugs (also called major tranquillizers or neuroleptics) do not cure the
disorder, but they do help to control symptoms.
➢ Some antipsychotic drugs also have a powerful action against nausea and vomiting, and are
therefore sometimes used as premedication before a person has surgery.
4. Because antipsychotic drugs can have permanent as well as temporary side effects, the
minimum necessary dosage is used; This minimum dose is found by starting with a low dose
and increasing it until the symptoms are controlled.
➢ Sudden withdrawal after more than a few weeks can cause nausea, sweating, headache, and
restlessness; Therefore, the dose is reduced gradually when treatment needs to be stopped.
➢ The most serious long-term risk of anti-psychotic treatment is a disorder known as tardive
dyskinesia, which may develop after one to five years; it consists of repeated jerking
movements of the mouth, tongue, and face, and sometimes of the hands and feet
o The condition is less common with the newer antipsychotics (atypical
antipsychotics) than the older drugs (typical antipsychotics).
Notes:
1. There is a little difference in efficacy between each of the antipsychotic drugs (other than
clozapine), and response and tolerability to each antipsychotic drug varies. There is no first-
line antipsychotic drug which is suitable for all patients.
2. Choice of antipsychotic medication is influenced by the patient’s medication history, the
degree of sedation required (although tolerance to this usually develops), and consideration of
individual patient factors such as risk of extrapyramidal side-effects, weight gain, impaired
glucose tolerance, QT-interval prolongation, or the presence of negative symptoms.
3. Long-acting depot injections antipsychotic are used for maintenance therapy especially
when compliance with oral treatment is unreliable. Depot antipsychotics are administered by
deep intramuscular injection at intervals of 1 to 4 weeks
4. All antipsychotics carry a black box warning against use in older adults with dementia;
First Generation Antipsychotics may have a higher mortality rate than Second Generation
Antipsychotics when used in older adults with dementia.
First: The older agents (typical or conventional antipsychotics).
1. They can also be classed by chemical structure (phenothiazine and non-phenothiazine).
2. Examples include: haloperidol, Fluphenazine, chlorpromazine, and Thioridazine.
3. The typical antipsychotic drugs act predominantly by blocking dopamine D2 receptors in the
brain; They are not selective for any of the four dopamine pathways in the brain and so can
cause a range of side-effects, particularly extrapyramidal symptoms (EPS) and elevated
prolactin levels.
➢ Typical antipsychotics have a large side effect profile; they may cause Neurological side
effects (Tardive dyskinesia, Dystonia, Parkinsonism), Drowsiness and sedation,
Anticholinergic side effects, and sexual dysfunction.
4. Extrapyramidal symptoms (EPS) consist of:
a. Parkinsonian symptoms (including tremor), which may occur more commonly in adults.
b. Dystonia (abnormal face and body movements) and dyskinesia, which occur more
commonly in children or young adults.
c. Akathisia (restlessness), which characteristically occurs after large initial doses and may
resemble an exacerbation of the condition being treated.
d. Tardive dyskinesia (rhythmic, involuntary movements of tongue, face, and jaw), which
usually develops on long-term therapy or with high dosage, also may occur after
withdrawal of the drug.
5. The likelihood of certain adverse effects occurring is directly related to the potency of the
antipsychotic; It is a relationship where the higher potency agents (lower mg dose), bind more
tightly to the dopamine D2 receptors; The higher the potency the more likely the agent is to
cause neurological side effects. The lower the potency the more likely the agent is to cause
the non-neurological side effects.
6. Must be avoided in patients with history of Parkinson’s disease, convulsive disorders, severe
Cardiac disease, narrow angle glaucoma, or previous neuroleptic malignant disorder.
7. Electrocardiographic (ECG) changes occur with 1st Gen. antipsychotics; QTc prolongation
can predispose the patient to ventricular arrhythmias, including torsade’s de pointes syndrome.
➢ The risk appears highest with chlorpromazine, haloperidol, and Thioridazine.
8. Venous thromboembolism (VTE): Three case-control studies and a retrospective study suggest
an increased risk of VTE in patients taking antipsychotics. The risk may be higher in older adults
and women. The risk appears greatest within the first 3 months of therapy.
Chlorpromazine form
Tab Largactil , Thorazine
® ® 50 mg , 100 mg , 200 mg
Amp 25 mg/5 ml , 25 mg/ml
Prochlorperazine Tab Stemetil® , Compazine® 5 mg , 10 mg
Amp Promotil ® 12.5 mg/1 ml
Fluphenazine Tab Modicate , Prolixin
® ® 2.5 mg , 5 mg , 10 mg
Elixir 2.5 mg/5 ml
Amp Modicate HCL® 2.5 mg/ml
Depot Inj. Modicate Deconate ® 25 mg/ml
Perphenazine Tab Fentazin ® 2 mg , 4 mg
Promazine Tab ProMaz® 25 mg , 50 mg
Sulpride Tab Dogmatil ® 200 mg , 400 mg , 500 mg
Haloperidol Tab Haldol , Peridol
® ® 0.5 mg , 1 mg , 2 mg , 5 mg
Oral Solu. Dozic® 5mg/5 ml
Depot Inj. Haldol Deconate® 50 mg/ml , 100 mg/ml
Pimozide Tab Orap ® 1 mg , 2 mg , 4 mg
Mesoridazine Tab Serentil ® 25 mg , 100 mg
Levomepromazine Tab Nozinan® 25 mg
Amp 25 mg/ml (1 ml amp)
Pericyazine Tab Perzyst® 2.5 mg , 10 mg
Cap Neuleptil® 5 mg , 10 mg , 20 mg
Oral Drops Neuleptil® 4% , 10%
Thiothixene Cap Navane® 1 mg , 2 mg , 5 mg
Loxapine Cap Loxitane® 5 mg , 10 mg , 25 mg
Inhaler Adasuve® 10 mg (single use Inhaler)
Thioridazine Tab Mellaril®, Sonapax®, Ridazin® 10 mg , 25 mg
Trifluoperazine Tab Stelazine® 1 mg , 2 mg , 5 mg
Flupenthixol Tab Depixol® 3 mg
Amp Fluanxol® , Depixol® 50 mg/0.5 ml
Amp depot Fluanxol Depot® 100 mg/2 ml
Zuclopenthixol Tab Clopixol® 2 mg , 10 mg , 25 mg
Amp Clopixol Acuphase® 50 mg/ml (1 ml amp)
Amp depot Clopixol Depot® 200 mg/ml
Benperidol Tab Anguil® 2.5 mg
Notes:
1. concerning Chlorpromazine (Largactil®):
a. It is used in the alleviation of intractable hiccup, (usually 12.5 mg once).
b. It is widely abused in our market by some addicts.
2. Prochlorperazine is usually used as antiemetic.
3. Haloperidol is used for Treatment of severe nausea and emesis in postoperative and palliative
care, also for Treatment of intractable hiccups, hyperactivity, and aggression.
4. Fluphenazine causes Euphoria, thus abused by some addicts.
5. Loxapine is indicated for acute treatment of agitation associated with schizophrenia or bipolar
disorder in adults.
6. Thioridazine was withdrawn worldwide in 2005 Due to concerns about cardio-toxicity and
retinopathy at high doses this drug.
7. Trifluoperazine comes with Isopropamide (anticholinergic) in a combination Known as
Stelabid® for the treatment of irritable bowel syndrome (IBS).
8. Both Flupenthixol and Zuclopenthixol are long-acting injection given once in every two or
three weeks, (although they are not approved to use in USA).
9. Flupenthixol comes with Melitracen (a tricyclic antidepressant) in combination Known as
Deanxit® It is designed as antidepressant combo for short term usage only, it’s banned in USA,
the UK, Ireland, Canada, Japan, and Australia due association with potentially serious
neurological side effects; And it’s still used in our market for IBS!
10. Valbenazine, was (FDA) approved on April 11, 2017, as the first drug to carry an indication
for tardive dyskinesia; reversibly and selectively inhibits the vesicular monoamine transporter
2 (VMAT2); Valbenazine thus regulates the packaging of dopamine and other monoamines in
the neuronal cytoplasm into vesicles for storage and release into synapses, decreasing the
amount of dopamine released, which in turn results in fewer postsynaptic dopamine
receptors and less dyskinetic movement.

Valbenazine form
Cap Ingrezza® 40 mg , 80 mg

Second: Atypical antipsychotics (the Newer Generation)
1. Newer antipsychotics such as clozapine, Risperidone, Olanzapine and Quetiapine are often
referred to as atypical antipsychotics because of their reduced tendency to cause the
extrapyramidal side-effects (EPS), (1) (better tolerated than other antipsychotic drugs).
➢ Has the ability to block serotonin-2 receptors is present; This property may improve
activity for the negative symptoms of schizophrenia and reduce the risk of EPS; This may
also be related to their efficacy in mood disorders.
2. But still have the Drowsiness and sedation, Anticholinergic side effects, Cause Prolactin
elevation and sexual dysfunction.
➢ Aripiprazole; unlike other antipsychotic drugs, lowers prolactin.
➢ All antipsychotics lowers the seizure threshold.
3. Major additional side effect: association with weight gain, development of type 2 diabetes
and dyslipidemia, precipitation of DKA have also been reported.
4. Also; Electrocardiographic (ECG) changes occur with 2nd Gen. antipsychotics; QTc
prolongation can predispose the patient to ventricular arrhythmias, including torsade’s de
pointes syndrome; (Clozapine, Ziprasidone, and iloperidone appear to have the highest risk).
Clozapine Tab Clozaril , Leponex , Zaponex 50 mg , 100 mg , 200 mg
® ® ®
Oral Susp. Versacloz® 50 mg/ml

Risperidone Tab Risperdal® , Rison® 0.5 mg , 1 mg , 2 mg , 4 mg
Oro Desp. tab 1 mg , 2 mg , 3 mg , 4 mg
Oral Solu. 1 mg/ml
Olanzapine Tab Zyprexa , Olan , Olapex
® ® ® 2.5 mg , 5 mg , 10 mg
Oro Desp. tab 2.5 mg , 5 mg , 10 mg
Inj. (I.M.) 10 mg
Quetiapine Tab Seroquel , Xeroquel , Serex
® ® ® 25 mg , 100 mg , 200 mg
Tab XR Seroquel XR® 50 mg , 200 mg , 300 mg
Aripiprazole Tab Abilify , Lemidal
® ® 2 mg , 5 mg , 10 mg
Oral Solu. 1 mg/ml
Inj. (I.M.) Aristada ® 7.5 mg/ml (1.3 ml amp)
Brexpiprazole Tab Rexutii® 0.25 , 0.5 , 1 , 2 , 4 mg
Amisulpride Tab Solian® 50 mg , 100 mg , 200 mg
Paliperidone Tab Invega® 3 mg , 6 mg , 9 mg
Asenapine Subling. Tab Saphris® 2.5 mg , 5 mg , 10 mg
Lurasidone Tab Latuda® 20 mg , 40 mg , 80 mg
Cariprazine Cap Vraylar® 1.5 mg , 3 mg , 6 mg
Pimavanserin Tab Nuplazid® 17 mg
Iloperidone Tab Fanapt® 1 mg , 2 mg , 4 mg , 6 mg
Sertindole Tab Serdolect®, Serlect® 4 mg , 16 mg , 20 mg
Ziprasidone Cap Geodon® , Zeldox® 20 mg , 40 mg , 60 mg , 80 mg
Inj. powder 20 mg
Notes:
1. Clozapine can cause agranulocytosis; Periodic monitoring of blood counts is a MUST.
➢ FDA Black box warning: May cause seizures, Myocarditis, and respiratory arrest.
2. Olanzapine: This drug is structurally similar to clozapine and has a similar pharmacologic
profile, but unlike clozapine, it has not been associated with agranulocytosis.
➢ Olanzapine carries the highest risk of diabetes.
➢ It Comes with Fluoxetine (SSRI) in combo (Symbyax®) for treatment-resistant depression.
3. Risperidone: This drug is a potent dopamine D2 antagonist and a serotonin-2 antagonist; It
has limited anticholinergic activity, at doses of up to 6 mg/day, the incidence of EPS has been no
higher than with placebo in clinical studies.
➢ Risperidone, the first drug approved for children with autism and the most widely
used, improves some children’s behavior, effectively treats the explosive and aggressive
behavior that can accompany autism.
➢ Off-label uses include treatment of other symptoms of autistic disorder, including
aggression, self-injurious behavior, hyperactivity, and inattention.
➢ Risperidone has shown promise in treating therapy-resistant obsessive–compulsive
disorder, when serotonin reuptake inhibitors are not sufficient.
4. Paliperidone: is the active metabolite of Risperidone; Its pharmacologic profile is similar to
that of the parent drug.
➢ Invega® is an extended release formulation of Paliperidone that uses the OROS extended
release system to allow for once-daily dosing.
5. Aripiprazole is also used as an add-on treatment in major depressive disorder, tic disorders and
irritability associated with autism.
➢ Aripiprazole; unlike other antipsychotic drugs, lowers prolactin.
➢ Aripiprazole has the lowest risk in most forms of EPS, including tardive dyskinesia.
➢ Also available in a once monthly dosage form (Abilify Maintena®).
6. Quetiapine: it has in addition to antagonism at the D2 and serotonin-2 receptors, it has a high
affinity for histamine-1 receptors
➢ Quetiapine offers a low incidence of EPS; For this reason, it is often used for psychosis
associated with Parkinson disease.
➢ Quetiapine does not decrease agitation among people with Alzheimer's; Quetiapine
worsens intellectual functioning in the elderly with dementia and therefore is not
recommended.
➢ Used as tranquilizer for major Depressive disorder.
➢ Used (off-label) as 25 mg at bed time for insomnia.
7. Pimavanserin is indicated only for Parkinson Disease Psychosis.
8. Ziprasidone is also used off-label for depression, bipolar maintenance, mood disorders, anxiety,
aggression, dementia, attention deficit hyperactivity disorder, obsessive compulsive disorder,
autism, and post-traumatic stress disorder.
Third: Antipsychotic Depot Injections

1- There is no clear-cut division in the use of the conventional antipsychotics, but Zuclopenthixol
may be suitable for the treatment of agitated or aggressive patients whereas Flupenthixol can
cause over-excitement in such patients.
2- Zuclopenthixol Decanoate may be more effective in preventing relapses than other
conventional antipsychotic depot preparations.
3- The incidence of extrapyramidal reactions is similar for the conventional antipsychotics.
Flupenthixol Decanoate Inj. oily Depixol® 20 mg/ml , 100 mg/ml , 200 mg/ml
Zuclopenthixol Decanoate Inj. oily Clopixol® 200 mg/ml , 500 mg/ml
Fluphenazine Decanoate Inj. oily Modecate® 25 mg/ml , 100 mg/ml
Haloperidol Decanoate Inj. oily Haldol® 25 mg/ml , 50 mg/ml
Olanzapine Embonate Vial (powder) ZypAdhera® 210 mg , 300 mg , 405 mg (per vial)
Paliperidone Palmitate Prefilled inj. Xeplion® 50 mg , 75 mg , 100 mg , 150 mg
Pipotiazine Palmitate Inj. oily Piportil® 50 mg/ml
Risperidone Vial (powder) Risperdal Consta® 25 mg , 50 mg (per vial)
4.3 - Anti-Depressant drugs
1. Normally, the brain cells release sufficient quantities of certain chemicals (known as
neurotransmitters such as serotonin and dopamine) in the brain to stimulate neighboring cells,
the neurotransmitters are constantly reabsorbed into the brain cells, where they are broken
down by an enzyme called monoamine oxidase.
2. Depression is thought to be caused by a reduction in the level of neurotransmitters in the brain.
➢ Antidepressants raise the levels of these neurotransmitters.
➢ Available Antidepressant classes include:
Class of Antidepressant Example(s)
1. Selective serotonin reuptake Citalopram, Escitalopram, Fluoxetine, Fluvoxamine,
inhibitors (SSRIs) Paroxetine, Sertraline
2. Tricyclic antidepressants (TCAs) Amitriptyline, Desipramine, Dosulepin, Doxepin,
and tetracyclic antidepressants Lofepramine, Imipramine, Nortriptyline, Mianserin
(tetracyclic), Trimipramine
3. Norepinephrine and dopamine Bupropion
reuptake inhibitor (NDRI)
4. Mixed serotonergic effects Nefazodone, Trazodone, Vilazodone, Vortioxetine
(Mixed 5-HT)
5. Serotonin and α2-adrenergic Mirtazapine
antagonist
6. Monoamine oxidase inhibitors Phenelzine, Selegiline, Tranylcypromine
(MAOIs)
7. Melatonin receptor agonist Agomelatine
8. Noradrenaline reuptake Reboxetine
inhibitors
9. Serotonin and noradrenaline re- Duloxetine, Venlafaxine
uptake inhibitors.
Notes:
1. Antidepressant drugs are effective for treating moderate to severe depression associated with
psychomotor and physiological changes such as loss of appetite and sleep disturbance;
improvement in sleep is usually the first benefit of therapy.
2. The major classes of antidepressant drugs available include: the tricyclic and related
antidepressants (TCAs), the selective serotonin re-uptake inhibitors (SSRIs), the serotonin
norepinephrine re-uptake inhibitors (SNRIs), and the monoamine oxidase inhibitors (MAOIs).
3. There is little to choose between the different classes of antidepressant drugs in terms of efficacy,
so choice should be based on the individual patient’s requirements, including the presence of
concomitant disease, existing therapy, suicide risk, and previous response to antidepressant
therapy.
a. There may be an interval of 2 weeks before the antidepressant action takes place.
b. Electroconvulsive treatment may be required in severe depression when delay is
hazardous or intolerable.
c. During the first few weeks of treatment, there is an increased potential for agitation,
anxiety, and suicidal ideation.
4. Patients should be reviewed every 1–2 weeks at the start of antidepressant treatment, And the
treatment should be continued for at least 4 weeks (6 weeks in the elderly) before considering
whether to switch antidepressant due to lack of efficacy.
a. In cases of partial response, continue for a further 2–4 weeks (elderly patients may take
longer to respond).
b. Following remission, antidepressant treatment should be continued at the same dose
for at least 6 months (about 12 months in the elderly).
A) The selective serotonin re-uptake inhibitors (SSRIs)
1. SSRIs include: Citalopram, Escitalopram, Fluoxetine, Paroxetine, and Sertraline.
➢ These selectively inhibit the reuptake of serotonin into the presynaptic neuron and
desensitize the presynaptic serotonin auto-receptor, resulting in increased serotonin
concentrations.
2. SSRIs are generally chosen as first-line antidepressants because of their safety in overdose
and improved tolerability compared with earlier agents; The SSRIs produce fewer sedative,
anticholinergic, and cardiovascular adverse effects than the TCAs and are less likely to cause
weight gain than the TCAs.
a. In patients with unstable angina or who have had a recent myocardial infarction, sertraline
has been shown to be safe.
b. All these medications are given at night, Except Fluoxetine; which is given at morning,
due it has a Cognitive stimulant effect.
3. Important: In the treatment of depression the usual initial dose of Fluoxetine is 20 mg once
daily; US product information recommends giving this dose in the morning.
4. Some SSRIs are also used as part of the management of generalized anxiety disorder, obsessive-
compulsive disorder, panic disorders, some are useful in neuropathic pain management,
Fluoxetine is also used in the treatment of premenstrual syndrome.
5. The most common adverse effects associated with this class of agents include GI complaints,
insomnia, restlessness, headache, and sexual dysfunction.
➢ Sertraline is used off-label in the treatment of premature ejaculation (due its side effect).
6. Co-administration of monoamine oxidase inhibitors (MAOI) is CONTRAINDICATED, Due
Potential for producing a potentially lethal serotonin syndrome (characterized by nausea,
vomiting, flushing, agitation, hyperthermia, diaphoresis, tachycardia, autonomic instability,
tremor, hyperreflexia, myoclonus, and rigidity) and that is due to dangerously high levels of
brain serotonin.
7. The antidepressant effects of SSRIs may not appear until 3 to 6 weeks after initiation of
treatment, (Never stop them abruptly).
8. To minimize occurrence of discontinuation syndromes, all antidepressants should be slowly
tapered (25% dose reduction per week), rather than abruptly discontinued.
9. Within days of abrupt cessation, patients may suffer from dizziness, nausea, fatigue, muscle
aches, chills, anxiety, and irritability, while not dangerous, discontinuation side effects can be
distressing and uncomfortable, often lasting 1-2 weeks.
10. SSRIs appear to increase the risk of bleeding; Several mechanisms have been proposed,
including the inhibition of serotonin activation of platelets, case-control and cohort studies also
suggest an increased incidence of both vertebral and non-vertebral bone fractures.
Hyponatremia is a potential adverse effect, particularly in older adults.
Fluoxetine Cap Prozac® 20 mg , 40 mg
Cap DR Sarafem® 90 mg
Paroxetine Tab Seroxat® , Paxil® , Pexeva® 10 mg , 20 mg , 40 mg
Cap Seroxat CR® 30 mg
Sertraline Tab Zoloft® , Lustra® 50 mg , 100 mg
Citalopram Tab Celexa® , Cipramil® 10 mg , 20 mg , 40 mg
Escitalopram Tab Lexapro®, Cipralex® 5 mg , 10 mg , 20 mg
Fluvoxamine Tab Luvox® , Faverin® 25 mg , 50 mg , 100 mg
Cap ER 100 mg , 150 mg
Dapoxetine Tab Priligy®, Longus®, Joypox® 30 mg , 60 mg

Notes:
1. Fluoxetine differs from the other members of the class in two respects; First, it has a much longer
half-life (50 hours) and is available as a sustained-release preparation allowing once-
weekly dosing; Second, it has Cognitive stimulant effect, useful in patients with somnolence.
2. Paroxetine and Fluvoxamine are generally more sedating than activating, and they may be
useful in patients who have difficulty sleeping; Conversely, patients who are fatigued or
complaining of excessive somnolence may benefit from one of the more activating
antidepressants, such as fluoxetine or sertraline.
➢ Fluvoxamine is indicated only for obsessive-compulsive disorder (OCD).
➢ Paroxetine have also a delayed release formulation capsules that is given once weekly.
3. Escitalopram is the pure S-enantiomer of citalopram.
➢ Used for Insomnia due to depression or due to panic disorder.
➢ Used for vasomotor symptoms associated with Menopause.
4. About Sertraline:
a. Food increases its absorption.
b. Safe to use in patients with unstable angina or myocardial infarction.
5. Dapoxetine is the first compound developed specially for the treatment of premature
ejaculation (PE) in men 18–64 years old, although it was rejected by the FDA in 2011
B) TCAs and related antidepressants

1. Examples are Amitriptyline, Clomipramine, and Imipramine.
➢ They act by blocking serotonin and norepinephrine re-uptake.
2. TCAs are strong antidepressants, but their use has diminished because of the availability of
equally effective therapies that are safer on overdose and better tolerated.
a. Some tricyclic antidepressants (TCAs) are used in the management of panic and other
anxiety disorders, as (Doxepin), other are useful in migraine prophylaxis.
b. Some TCAs have a role in some forms of neuralgia (neuropathic pain), as (Amitriptyline).
c. Also, some used in nocturnal enuresis in children, as (Imipramine).
3. TCAs have α-adrenergic blockade, antihistaminic effects, and anticholinergic effects, which lead
to orthostasis, sedation, and anticholinergic side effects, respectively.
➢ They also lead to cardio toxic effects (Life-threatening arrhythmias).
➢ These drugs are not recommended in patients with cardiac disease or seizure disorders.
4. Tricyclic antidepressant drugs have Antimuscarinic activity, and therefore caution is needed
in patients with prostatic hypertrophy, chronic constipation, increased intra-ocular pressure,
urinary retention, or those with a susceptibility to angle-closure glaucoma.
5. TCAs cause Sexual dysfunction, as evidenced by Erectile dysfunction in men and Anorgasmia
in women; although some of them are used for premature Ejaculation in men.
6. TCAs and related antidepressants should be withdrawn slowly, because of dangerous
withdrawal symptoms such as influenza-like symptoms (chills, myalgia, sweating, headache, and
nausea), insomnia and vivid dreams.
Amitriptyline Tab Deprezole®, Elavil® , Levate® 10 mg , 25 mg , 50 mg
Tab Tryptizole® 75 mg
Nortriptyline Tab Allegron® 10 mg , 25 mg
Amoxapine Tab Asendin® 10 mg , 25 mg
Imipramine Tab , Cap Tofranil® 10 mg , 25 mg & 75 mg (Cap)
Clomipramine Tab , Cap Anafranil® , Anafranil SR® 25 mg , 50 mg & 75 mg (SR)
Desipramine Tab Norpramin® 10 mg , 25 mg , 50 mg
Lofepramine Tab Feprapax® 70 mg
Protriptyline Tab Vivactil® 5 mg , 10 mg
Trimipramine Cap Surmontil® , Trimip® 25 mg , 50 mg
Dosulepin * Tab , Cap Prothiaden® 25 mg , 75 mg
Doxepin Tab , Cap Sinequan® , Sinepin® 10 mg , 25 mg , 50 mg
Related antidepressants
Maprotiline Tab Ludiomil® 25 mg , 50 mg , 75 mg
Mianserin Tab Miarin ® 10 mg , 30 mg
Trazodone Tab , Cap Molipaxin , Desyrel , Oleptro 50 mg , 100 mg , 150 mg
® ® ®
1. Imipramine has been used to control bed-wetting in children (older than age 6 years) by causing
contraction of the internal sphincter of the bladder. At present, it is used cautiously because of the
inducement of cardiac arrhythmias and other serious cardiovascular problems.
2. Amitriptyline, have been used to treat migraine headache and chronic pain syndromes (for example,
neuropathic pain) in a number of conditions for which the cause of the pain is unclear.
3. Dosulepin = Dothiepin, they are the same drug.
4. Doxepin can be used to treat insomnia.
5. Maprotiline have antidepressant, sedative, anxiolytic, and sympathomimetic activities.
6. Trazodone also has antianxiety (anxiolytic/hypnotic) effects, also used for Erectile Dysfunction.
o Has a strange side effect (causing priapism; a painful erection that lasts more than 4 hrs.).
C) Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

1. They act by blocking the reuptake of norepinephrine and serotonin; Unlike TCAs, they have low
or negligible effects at other receptors that cause anticholinergic or antihistaminic adverse
effects; Examples include: Duloxetine, Venlafaxine, Desvenlafaxine.
2. They are effective in treating depression in patients in whom SSRIs are ineffective, also
depression is often accompanied by chronic painful symptoms, such as backache and muscle
aches, against which SSRIs are also relatively ineffective. This pain is, in part, modulated by
serotonin and norepinephrine pathways in the CNS, Both SNRIs and TCAs, with their dual
actions of inhibiting serotonin and norepinephrine reuptake, are sometimes effective in relieving
physical symptoms of neuropathic pain such as diabetic peripheral neuropathy.
3. Duloxetine is also used in the treatment of generalized anxiety disorder, treatment of diabetic
peripheral neuropathic, and the treatment of moderate to severe stress urinary incontinence
in women, also indicated for the treatment of Fibromyalgia.
➢ Recommended as a first line agent for the treatment of chemotherapy-induced neuropathy by
the American Society of Clinical Oncology.
➢ On November 4, 2010, the FDA approved Duloxetine to treat chronic musculoskeletal pain,
including discomfort from osteoarthritis and chronic lower back pain.
➢ Deceased appetite/weight loss is considered a common side effect of Duloxetine, with about
10% of users reporting one or both of these side effects.
4. Venlafaxine is a pure SNRI; it lacks the sedative and Antimuscarinic effects of the tricyclic
antidepressants, but treatment with venlafaxine is associated with a higher risk of withdrawal
effects compared with other antidepressants.
Duloxetine Cap , Cap CR Cymbalta ® 30 mg , 60 mg
Reboxetine Tab Edronax ® 4 mg
Venlafaxine Tab Effexor ® 25 mg , 50 mg
Cap Effexor XR® 75 mg , 150 mg
Desvenlafaxine Tab Pristiq , Khedezla
® ® 50 mg , 100 mg
Milnacipran * Tab Savella ® 12.5 mg , 25 mg , 50 mg
levoMilnacipran Cap Fetzima ® 20 mg , 40 mg , 80 mg
* Milnacipran is used in the clinical treatment of fibromyalgia.
D) Atypical Antidepressants
1. The atypical antidepressants are a mixed group of agents that have action at several different
sites, this group includes bupropion, mirtazapine, Nefazodone and trazodone.
2. They are not any more efficacious than the TCAs or SSRIs, but their side effect profiles are
different.
Bupropion Tab Wellbutrin , Zyban
® ® 75 mg , 100 mg , 150 mg
Mirtazapine Tab Remeron® 7.5 mg , 15 mg , 30 mg
Nefazodone Tab Serzone ® 50 mg , 100 mg , 150 mg
Trazodone Tab Molipaxin , Desyrel , Oleptro
® ® ® 50 mg , 100 mg , 150 mg
Notes:
1. Bupropion (weak norepinephrine-dopamine reuptake inhibitor); it is also used in smoking
cessation, it assists in decreasing the craving and attenuating the withdrawal symptoms for
nicotine in tobacco users trying to quit smoking; Its use should be avoided in patients at risk for
seizures (lowers seizure threshold); or who have eating disorders (such as bulimia).
2. Mirtazapine (antagonist of presynaptic α2-autoreceptors and heteroreceptorsis); markedly
sedating, due its potent antihistaminic activity, but it does not cause the Antimuscarinic side
effects of the TCAs, or interfere with sexual functioning, as do the SSRIs.
➢ It also blocks 5-HT2 and 5-HT3 receptors; also, it’s a Potent H1 antagonist
➢ It can cause an increased appetite, and weight gain.
3. Nefazodone sale was discontinued in 2003 in some countries due to the rare incidence of
hepatotoxicity (liver damage), could lead to the need for a liver transplant, or even death.
4. Trazodone (both 5-HT2 serotonin antagonist and serotonin reuptake inhibitor); it has
antianxiety (anxiolytic/hypnotic) effects, also used for erectile dysfunction.
➢ May cause marked sedation, Priapism (painful erection), and orthostatic hypotension.
5. Both Nefazodone and Trazodone have mild to moderate α1-receptor antagonism contributing
to orthostasis and dizziness side effects.
E) Monoamine Oxidase Inhibitors (MAOIs)

1. Monoamine Oxidase (MAO) in the neurons acts as a safety valve to oxidatively deaminate and
inactivate any excess neurotransmitters (as Norepinephrine, Dopamine and Serotonin).
2. MAOIs acts by blocking the enzyme responsible for the breakdown of these neurotransmitters;
There are two forms of this enzyme (MAO-A and MAO-B), and drugs can block one or both of
them; either reversibly or irreversibly causing accumulation of neurotransmitters within the
presynaptic neuron, leading to leakage into the synaptic space.
3. Their use these days are limited due to:
a. The Severe and often unpredictable side effects
b. The drug-food interaction (usually Tyramine) and drug-drug interactions (complicated
dietary restrictions required of patients taking them.).
4. Tyramine (found in aged cheese, preserved meats, Soya bean); causes the release of large
amounts of stored catecholamines from nerve terminals, resulting in what is termed a
“hypertensive crisis,” with signs and symptoms such as occipital headache, stiff neck,
tachycardia, nausea, hypertension, cardiac arrhythmias, seizures, and stroke.
➢ Patients must be educated to avoid Tyramine containing foods.
5. MAOIs and SSRIs should not be co-administered due to the risk of the life-threatening
serotonin syndrome. Both types of drugs require washout periods of at least 2 weeks before
the other type is administered.
6. Combination of MAOIs and bupropion can produce seizures.
7. They are contraindicated in pregnancy.
Isocarboxazid Tab Marplan® 10 mg
Phenelzine Tab Nardil® 15 mg
Selegiline * Tab , Cap Eldepryl® 1.25 mg (Tab) , 5 mg (Cap)
Patch Emsam® 6 mg , 9 mg , 12 mg / 24 hr.
Tranylcypromine Tab Parnate® 10 mg
Moclobemide ** Tab Manerix® 150 mg , 300 mg
Safinamide Tab Xadago® 50 mg , 100 mg
* Selegiline is also used for the treatment of early-stage Parkinson's disease, and senile dementia.
** Moclobemide is indicated for major depression and social anxiety disorder; it is reported to act by
reversible inhibition of monoamine oxidase type A (it is therefore termed a RIMA). It should be
reserved as a second-line treatment.
F) Other Antidepressants/Psychoanaleptics drugs:
Melatonin Tab , Oral drops Meloset® , Circadin® 2 mg , 3 mg , 5 mg , 10 mg
Agomelatine Tab Valdoxan®, Thymanax® 25 mg
Tianeptine Tab Stablon® 12.5 mg
Reboxetine Tab Edronax® , Norebox® 4 mg
Esketamine Nasal Spray Pravato® 28 mg/device
Vilazodone Tab Viibryd® 10 mg , 20 mg , 40 mg
Vortioxetine Tab Brintellix®, Trintellix® 5 mg , 10 mg , 15 mg
1. Melatonin is the hormone produced by the pineal gland; it regulates sleep cycles.
➢ Licensed for the short-term treatment of insomnia in adults.
➢ Also licensed for the prevention of Cluster headaches, Migraine headache.
2. Agomelatine is a melatonergic agonist (MT1 and MT2 receptors) and 5-HT2C antagonist, it has no effect
on monoamine uptake and has no affinity for adrenergic, histaminergic, cholinergic, dopaminergic and
BZD receptors, indicated in Treatment of major depressive episodes.
3. Tianeptine is used mainly in the treatment of major depressive disorder, although it may also be used to
treat anxiety, asthma, and irritable bowel syndrome.
➢ It has antidepressant and anxiolytic effects with a relative lack of sedative, anticholinergic, and
cardiovascular side effects, but it can induce euphoria.
Used in Parkinson's disease, post-traumatic stress disorder; also effective for asthma
➢ Effective in men with depression and erectile dysfunction, also has anticonvulsant and analgesic
effects (useful in treating pain due to fibromyalgia), for attention-deficit hyperactivity disorder.
4. Reboxetine is a norepinephrine reuptake inhibitor (NRI); used in the treatment of major depression,
although it has also been used off-label for panic disorder and attention deficit hyperactivity disorder.
5. Esketamine is indicated for treatment-resistant depression.
6. Vortioxetine, Vilazodone (both 5-HT1A agonist and serotonin reuptake inhibitor); are indicated to treat
adults with major depressive disorder.
G) Psychotherapeutic combos:
These combos are usually given in some cases that require additive therapy, or in severe cases that doesn’t
response to single agent therapy; All given for a short time ONLY.
Amitriptyline + Perphenazine Tab Etrafon®, Triptafen® 10mg/2mg , 25mg/2mg
Amitriptyline + Chlordiazepoxide Tab Limbitrol® 12.5mg/5mg , 25mg/10mg
Nortriptyline + Fluphenazine Tab Movital® 10 mg + 0.5 mg
Fluoxetine + Olanzapine Cap Symbyax® 25mg/3mg , 25mg/6mg
Alprazolam + Melatonin Tab Destres® 0.25 mg + 3 mg
Flupenthixol + Melitracen * Tab Deanxit® 0.5 mg/10 mg
* (Flupenthixol + Melitracen) Deanxit®, It’s designed for short term usage only, it’s banned in USA, the UK,
Ireland, Canada, Japan, and Australia due association with potentially serious neurological side effects, and
it’s still used in our market for IBS!
4.4 – Anti-epileptic drugs (AEDs)
1. Electrical signals from nerve cells in the brain are normally finely coordinated to produce smooth
movements of the arms and legs, but these signals can become irregular and chaotic, and trigger
the disorderly muscular activity and mental changes that are characteristic of a seizure (also
called a fit or convulsion).
➢ In an epileptic seizure, uncontrolled electrical activity starts in one part of the brain and
spreads to other parts, causing uncontrolled stimulation of brain cells.
➢ Most of the anticonvulsants have an inhibitory effect on brain cells and damp down electrical
activity, preventing the excessive build-up that causes epileptic seizures.
2. The most common cause of seizures is epilepsy, which occurs as a result of brain disease or injury.
In epileptics, a seizure may be triggered by an outside stimulus such as a flashing light, seizures
can also result from the toxic effects of certain drugs and, in young children; seizures may be
caused by a high temperature; there are several types of Epilepsy:
a) Generalized epilepsy: In this form of epilepsy, there is widespread disturbance of electrical
activity in the brain, and loss of consciousness occurs at the outset, in its simplest form, a
momentary loss of consciousness occurs during which the sufferer may stare into space, this is
called an absence seizure, and mainly affects children; Seizures do not occur, another form of
generalized epilepsy causes a brief jerk of a limb (myoclonus).
b) Tonic-Clonic (grand mal) seizure, which is characterized by loss of consciousness and seizures
that may last for a few minutes.
c) Partial (focal) epilepsy: This type of epilepsy is caused by an electrical disturbance in only one
part of the brain. The result is a disturbance of function, such as an abnormal sensation or
movement of a limb, without loss of consciousness. Known as a simple partial seizure, this may
precede a more serious attack associated with loss of consciousness (complex partial seizure),
which may in turn progress to a generalized convulsive seizure.
d) Status epilepticus: Repeated attacks without full recovery between, or a single attack lasting
more than 10 minutes, occur in this form of epilepsy; Emergency treatment is required.
Notes:
1. Example of some antiepileptic drugs available: Carbamazepine, Gabapentin, Lamotrigine,
Levetiracetam, Phenytoin, Pregabalin, Topiramate and Valproate.
Other examples include Benzodiazepines as (Diazepam, Lorazepam, and Clonazepam), and
Barbiturates as (Phenobarbital, Primidone) → see above section 1.
➢ AEDs suppress seizures; but do NOT CURE epilepsy.
➢ Other indications for some AEDs are: neuropathic pain, migraine prophylaxis, trigeminal
neuralgia, bipolar disorder, and anxiety disorder
2. The choice of an AED depends on the seizure type, potential for drug interactions and side
effects, cost and physician familiarity with the drug.
➢ If one drug is not effective, a different one will be tried.
➢ Occasionally, it is necessary to take a combination of drugs.
3. Usually, therapy is initiated at low dose and gradually increased over 3 or 4 weeks to an
effective dose.
4. Adverse effects of AEDs: Two types of adverse effects occur with AEDs, dose-related and
idiosyncratic:
a. For many AEDs, common dose-related adverse effects include sedation, ataxia, and
diplopia (If a patient has a job that requires mental alertness, it is best to choose an AED that
is less likely to cause sedation (lamotrigine).
b. Idiosyncratic adverse effects will almost always result in the AED being discontinued. Rash,
hepatotoxicity, and hematologic toxicities are the most common idiosyncratic reactions seen
with AEDs.
5. Antiepileptic hypersensitivity syndrome is a rare but potentially fatal syndrome associated
with some antiepileptic drugs (carbamazepine, Lacosamide, lamotrigine, oxcarbazepine,
phenobarbital, phenytoin, Primidone, and Rufinamide); rarely cross-sensitivity occurs between
some of these antiepileptic drugs.
a. The symptoms usually start between 1 and 8 weeks of exposure; fever, rash, and
lymphadenopathy are most commonly seen.
b. Other systemic signs include liver dysfunction, hematological, renal, and pulmonary
abnormalities, vasculitis, and multi-organ failure.
6. One chronic adverse effect that is of concern is osteoporosis; Carbamazepine, phenytoin,
Phenobarbital, and valproate have all been shown to decrease bone mineral density, even after
only 6 months of treatment; Patients taking these drugs for longer than 6 months should
take supplemental calcium and vitamin D (8).
7. Sexual dysfunction was reported in 30%–60% of patient with epilepsy.
➢ Sexual dysfunction has been reported with carbamazepine, phenobarbital, phenytoin,
Pregabalin, Topiramate, and Zonisamide.
➢ But Improved sexual functioning has been reported with lamotrigine and oxcarbazepine.
8. Regarding suicide with AEDs, the ones most associated with depression and suicidality are
Levetiracetam, Perampanel, phenobarbital, Primidone, Tiagabine, Topiramate, and Vigabatrin.
➢ Thus; When starting or switching AEDs, patients should be advised to report any changes
in mood and suicidal ideation.
9. AEDs are associated with many different drug interactions:
a. Phenobarbital, phenytoin, and carbamazepine are potent inducers of various CYP-450
isoenzymes, increasing the clearance of other drugs metabolized through these pathways.
b. Valproic acid inhibits many hepatic enzyme systems.
c. Felbamate and Topiramate can act as inducers with some isoforms and inhibitors with
others.
10. A febrile seizure (fever fit or febrile convulsion) is an epileptic seizure associated with a high
body temperature but without any serious underlying health issue. They most commonly occur
in children between the ages of 6 months and 5 years. Most seizures are less than five minutes in
duration and the child is completely back to normal within 16 minutes of the event.
a. Antipyretic medication (Paracetamol) is commonly used (rectally or I.V.) to reduce
fever and prevent further convulsions.
b. Some physicians prefer to use Diazepam (amp.) rectally.
Carbamazepine Tab Tegretol , Taver , Tegral 200 mg
® ® ®
Tab ER Tegretol CR® 200 mg , 400 mg

Oral Susp. 100 mg/5 ml
Supp. 125 mg , 250 mg
Eslicarbazepine Tab Zebinix , Aptiom
® ® 200 mg , 400 mg , 800 mg
Oxcarbazepine Tab Trileptal ® 150 mg , 300 mg , 600 mg
Valproic acid Cap Depakene , Depacon
® ® 125 mg , 250 mg , 500 mg
Syrup 250 mg/5 ml
Inj. 100 mg/ml
Divalproex Tab Depakote® 250 mg , 500 mg
Stiripentol Cap Diacomit 250 mg , 500 mg
Ethosuximide Cap Zarontin , Petnidan
® ® 250 mg
Syrup Meside ® 250 mg/5 ml
Ezogabine Tab Potiga® 200 mg , 300 mg , 400 mg
Retigabine Tab Trobalt® 100 mg , 200 mg , 300 mg
Tiagabine Tab Gabitril® 2 mg , 4 mg , 12 mg
Rufinamide Tab Inovelon®, Banzel® 100 mg , 200 mg , 400 mg
Felbamate Tab Felbatol® 400 mg , 600 mg
Lamotrigine Tab Lamictal® 25 mg , 50 mg , 100 mg
Brivaracetam Tab Briviact® 10 , 25 , 50 , 75 mg , 100 mg
Levetiracetam Tab Keppra®, EPIXX® 250 mg , 500 mg , 750 mg
Oral Solu. 100 mg/ml
Infusion Solu. 100 mg/ml (5 ml vial)
Phenytoin Tab , Cap Epanutin® 100 mg , 200 mg
Inj. (Amp) 50 mg/ml
Fosphenytoin Inj. (Amp) Cerebyx® 50 mg/ml
Lacosamide Tab Vimpat® 100 mg , 150 mg , 200 mg
Infusion Solu. 10 mg/ml (200 mg vial)
Methsuximide Cap Celontin® 150 mg , 300 mg
Topiramate Tab Topamax® 25 mg , 50 mg , 100 mg
Vigabatrin Tab Sabril® 500 mg
Zonisamide Cap Zonegran® 25 mg , 50 mg , 100 mg
Gabapentin Cap Neurontin® , Gabamed® 100 mg , 300 mg , 400 mg
Tab 600 mg , 800 mg
Pregabalin Cap Lyrica® 50 mg , 75 mg , 150 mg
Cap SR 200 mg , 225 mg , 300 mg
Perampanel * Tab Fycompa® 2 mg , 4 mg , 8 mg , 12 mg
Cannabidiol ** Oral Solu. Epidiolex® 100 mg/ml
Cenobamate Tab Xcopri® 25 , 50 , 100 , 150 , 200 mg
* Perampanel is an AMPA antagonist, uses as adjunctive therapy for treatment of partial-onset seizures
with/without secondary generalized seizures, has risks for serious neuro-psychiatric events.
** Cannabidiol is approved by (FDA) for treatment of epilepsy associated with Lennox–Gastaut syndrome
or Dravet syndrome in patients 2 years of age and older.
Notes:
1. Carbamazepine is also mood-stabilizing drug used primarily in the treatment of epilepsy and
bipolar disorder, as well as trigeminal neuralgia; It is also used off-label for a variety of
indications, including attention-deficit hyperactivity disorder (ADHD), (Carbamazepine
Stabilizes inactivated state of sodium channels, thereby making neurons less excitable).
➢ Can cause hyponatremia, Aplastic anemia
➢ Can cause Folate deficiency, thus give folic acid as supplementation with it.
➢ It may cause an increase in seizures.
2. Valproic acid is also mood-stabilizing and also used to treat migraine headaches.
3. Divalproex consists of a compound of sodium valproate and Valproic acid in a 1:1 molar
relationship in an enteric coated form.
4. Lamotrigine is one of a small number of FDA-approved therapies for seizures associated with
Lennox-Gastaut syndrome, also seems to act as an effective mood stabilizer.
5. Levetiracetam has potential benefits for other psychiatric and neurologic conditions such as
Tourette syndrome, autism, bipolar disorder and anxiety disorder, as well as Alzheimer's disease,
However, its most serious adverse effects are behavioral (aggression, agitation, anger,
anxiety, apathy, depersonalization, hostility, hyperkinesis, irritability, nervousness, neurosis, and
personality disorder) and its benefit-risk ratio in these conditions is not well understood.
6. Phenytoin is very old anticonvulsant, may cause gingival hyperplasia (cause the gums to grow
over the teeth), this side effect led Phenytoin to be used topically for wound healing.
➢ See chapter 14, section 21 for more info.
➢ Phenytoin should not be given I.M. as it causes tissue necrosis, given only as I.V infusion.
➢ Fosphenytoin is a pro drug, that is converted to Phenytoin; it can be given as I.M. inj.
7. Topiramate is used to treat epilepsy in children and adults, for seizures associated with
Lennox-Gastaut syndrome, this drug is also widely used to treat migraines due to the effect
it has on the blood vessels in the brain; It is used as a preventative for atypical migraine and
Cluster headaches, also used for alcoholism, smoking cessation and in combination with
phentermine for weight loss.
➢ Maintain adequate fluid intake due to kidney stone risk with Topiramate.
➢ Monitor closely for decreased sweating and increased body temperature.
8. Vigabatrin is an antiepileptic drug that inhibits the catabolism of gamma-amino butyric acid
(GABA) by irreversibly inhibiting GABA transaminase; It is an analog of GABA, but it is not a
receptor agonist.
➢ Only used for refractory complex partial seizures and infantile spasms.
➢ Causes permanent vision loss in infants, children, and adults and includes
progressive and permanent bilateral concentric visual field constriction in >30% of
patients and ranges in severity from mild to severe, including tunnel vision to within 10
degrees of visual fixation, and can result in disability
➢ May damage the central retina and decrease visual acuity.
➢ Vision loss onset is unpredictable and can occur within weeks of starting treatment, or
sooner, or at any time during treatment (even after months or years), and possibly after
Vigabatrin is discontinued
➢ Vision testing is required at baseline and then at least every 3 months (unless patient
is formally exempt), but cannot reliably prevent vision damage.
➢ The retinal toxicity of Vigabatrin can be attributed to a taurine depletion.
9. Ethosuximide is useful only for absence seizures.
10. Lamotrigine occasionally causes Rash; and thus, must be titrated slowly to avoid a rash.
➢ when adding Lamotrigine to Valproic acid; the dose of Lamotrigine should be reduced or
titrated to avoid the skin rashes, which is very serious and may progress to a life-
threatening reaction.
➢ Estrogen-containing oral contraceptives increase lamotrigine clearance; therefore, twice
the amount of lamotrigine may be necessary.
11. Lacosamide may cause PR interval prolongation or first-degree atrioventricular block;
thus, its preferred not to use in patients with cardiac problems.
➢ Has euphoretic effect; a Controlled substance schedule V.
12. Zonisamide is also indicated for Weight Loss, maintain fluid intake due to risk of kidney stone
formation, discontinue treatment if significant sustained increase in creatinine occurs.
➢ Combination with Topiramate or Acetazolamide increase the risk of metabolic acidosis.
13. Gabapentin is a GABA analogue; structurally related to neurotransmitter GABA, but has no effect
on GABA binding, uptake, or degradation; mechanism for analgesic and anticonvulsant
activity unknown.
➢ Used to relieve neuropathic pain; may help with menopausal symptoms, effective treatment
for migraine prophylaxis [unlicensed]; Helps with itching due to renal failure, known as
uremic pruritus, useful anxiety with bipolar disorder and restless leg syndrome.
14. Pregabalin is a GABA analogue, appears to be as effective as Gabapentin for neuropathic pain;
but costs more; Used in:
➢ Diabetic Peripheral Neuropathic, Post-herpetic Neuralgia, Neuropathic Pain with Spinal Cord
Injury, Fibromyalgia, perioperative pain; It appears to have anxiolytic effects similar to
benzodiazepines, and is licensed for the treatment of generalized anxiety disorder.
4.5-Drugs used in Parkinsonism
1. In Parkinson’s disease, the progressive degeneration of pigmented neurons in the substantia nigra
leads to a deficiency of the neurotransmitter dopamine, the resulting neurochemical
imbalance in the basal ganglia causes the characteristic signs and symptoms of the illness.
➢ Parkinsonism is caused by an imbalance of chemicals in the brain; the effect of
acetylcholine is increased by a reduction in the action of dopamine.
➢ Drugs to treat Parkinsonism restore the balance between dopamine and acetylcholine;
They fall into two main groups: those that reduce the effect of acetylcholine and those that
boost the effect of dopamine.
2. The primary objective of drug therapy is to enhance dopaminergic activity within the
damaged areas of the basal ganglia, and this is achieved in various ways (see table below).
3. Currently available drugs offer temporary relief from the symptoms of the disorder, but they
do not arrest or reverse the neuronal degeneration caused by the disease.
➢ That’s due the degeneration of brain cells in Parkinson’s disease cannot be halted.
4. No treatment has been unequivocally shown to prevent progression of Parkinson disease;
therefore, treatment is based on symptoms.
5. In patients who need the initiation of dopaminergic treatment, either levodopa or a dopamine
agonist can be used. The choice depends on the relative impact of improving motor disability
(better with levodopa) compared with the lessening of motor complications (better with
dopamine agonists) for each individual patient.
Notes:
1. Ergot-derived dopamine-receptor agonists (bromocriptine, cabergoline, and pergolide), have
been associated with pulmonary, retroperitoneal, and pericardial fibrotic reactions.
2. Apomorphine is a potent dopamine-receptor agonist that is sometimes helpful in advanced
disease for patients experiencing unpredictable ‘off’ periods with levodopa treatment.

Dopamine agonists
Bromocriptine Tab Parlodel® , Cycloset® 2.5 mg , 5 mg , 10 mg
Cabergoline Tab Dostinex® , Cabaser® 0.5 mg , 1 mg
Ropinirole Tab Requip® 0.5 mg , 1 mg , 2 mg
Tab MR Requip XL® 4 mg , 8 mg
Pramipexole Tab , Mirapex®, Sifrol®, Pexola® 0.125 mg , 0.25 mg , 0.5 mg
Tab ER Mirapex ER® 1 mg , 1.5 mg , 3 mg
Tab PR Motorax® 0.52 mg , 1.05 mg , 2.1 mg
Pergolide Tab Pergo® 50 mcg , 250 mcg
Rotigotine Skin patch Neupro® 1 mg , 2 , 4 , 8 mg (per 24 hr.)
Apomorphine Inj. APO-go® 10 mg/ml
Levodopa derivatives
Levodopa + Tab Sinemet®, Isicom® (100 mg + 25 mg) Sinamet®,
Carbidopa Parcopa® (250 mg + 25 mg) Isicom®,
Tab MR Caramet CR® 200 mg + 50 mg
Intestinal Duodopa® 20 mg + 5 mg
Gel *
Levodopa + Tab , Cap Madopar® (50 mg + 12.5 mg),
Benserazide (100 mg + 25 mg)
Levodopa + Carbidopa Tab Stalevo®, (150 mg + 37.5 mg + 200 mg)
+ Entacapone Corbilta® (100 mg + 25 mg + 200 mg)
Monoamine-oxidase-B inhibitors
Selegiline * Tab , Cap Eldepryl® , Jumex® 1.25 mg (Tab), 5 mg (tab, Cap)
Rasagiline Tab Azilect® 0.5 mg , 1 mg
Safinamide Tab Xadago® 50 mg , 100 mg
Catechol-O-methyl transferase (COMT) inhibitors
Entacapone Tab Comtan® , Comtess® 200 mg
Tolcapone Tab Tasmar® 100 mg
Antimuscarinics
Benztropine Tab Cogentin® 0.5 mg , 1 mg , 2 mg
Inj. Solu. 1 mg/ml
Benzhexol (or) Tab, Parkizol®, Trihex® 2 mg , 5 mg (Tab)
Trihexyphenidyl Elixir Artane® 0.4 mg (Elixir)
Procyclidine Tab Kemadrin® , Arpicolin® 5 mg
Other drugs
Biperiden Tab Akineton®, Dekinet® 2 mg
Piribedil Tab Trivastal® 50 mg
Amantadine Tab , Cap Symmetrel® 100 mg
* Selegiline = Deprenyl, they are the same drug.
Notes:
1. Levodopa is a metabolic precursor of Dopamine; it restores dopaminergic neurotransmission
in the corpus striatum by enhancing the synthesis of dopamine.
Dopamine itself does not cross the blood-brain barrier, but Levodopa is actively transported
into the CNS and is converted to dopamine in the brain.
a. It Has a short half-life (1-2 hours), and should be taken on empty stomach.
b. It causes a brownish urine and saliva.
2. Carbidopa and Benserazide, are Dopa-decarboxylase inhibitor, they diminish the
metabolism of levodopa in the gastrointestinal tract and peripheral tissues, thereby increasing
the availability of levodopa to the CNS; Also, they lower the dose of levodopa needed by 4 to
5-fold and thus decreases the severity of side effects from peripherally formed dopamine.
a. Side effects of this combination include: Anorexia, nausea, and vomiting occur because
of stimulation of the chemoreceptor trigger zone of the medulla
➢ (Don’t give B6 for the treatment of vomiting in this case, B6 increases the
peripheral breakdown of levodopa and diminishes its effectiveness, thus use
another antiemetic).
b. Other side effects: Visual and auditory hallucinations, Tachycardia, Hypotension.
c. Benserazide is not approved for use in the US.
d. These combinations are also used for the treatment of restless legs syndrome.
3. Levodopa derivatives has a wearing-off effect; (wearing off occurs when patients experience
recurrence of symptoms before the next dose of medication).
➢ Possible options to solve such problem include: the drug needs to be given more
frequently, or the addition of the COMT inhibitor Entacapone, or the MAO-B inhibitor
Rasagiline, or a dopamine agonist (ex: Pramipexole, Ropinirole)
4. Another complication of Levodopa derivatives therapy is dyskinesia (an involuntary chorea
form movement (too much movement); involving the neck, trunk, and extremities lower and
upper; Possible options to solve such problem include: The use of lower individual doses of
L-dopa (with an increase in dosage frequency) or addition of Amantadine (3).
5. Monoamine-Oxidase-B inhibitors are used in conjunction with levodopa to reduce (end-of-
dose) deterioration in advanced Parkinson’s disease.
a. Selegiline is metabolized to Methamphetamine and Amphetamine, which have
stimulating properties that may produce insomnia and restlessness.
b. Rasagiline is an irreversible and selective inhibitor of brain monoamine oxidase Type-
B, has 5 times the potency of Selegiline.
➢ It’s not metabolized into Methamphetamine and Amphetamine.
➢ Ciprofloxacin can double the concentration of Rasagiline (through CYP1A2).
6. COMT inhibitors prevent the peripheral breakdown of levodopa, by inhibiting Catechol-O-
methyl transferase, allowing more levodopa to reach the brain.
a. Used only in conjunction with carbidopa/L-dopa; (not used as monotherapy).
b. Tolcapone is associated with fulminating hepatic necrosis, therefore; it should be used
along with appropriate hepatic function monitoring.
c. Entacapone does not exhibit the above liver toxicity and has largely replaced Tolcapone.
d. Both are not affected by food.
e. Entacapone may cause urine discoloration.
7. Both Bromocriptine and Cabergoline are dopamine receptor agonist on D2 receptors. Both
have a direct inhibitory effect on pituitary lactotroph (prolactin) cells, thereby inhibiting
prolactin release → used in Hyperprolactinemia.
a. With Bromocriptine in patients with peripheral vascular disease, a worsening of the
vasospasm occurs, and in patients with peptic ulcer, there is a worsening of the ulcer.
Also, it has the potential to cause pulmonary and retroperitoneal fibrosis.
b. Bromocriptine is also FDA approved for the treatment of Diabetics type 2 (DM).
c. Cabergoline have a high affinity for D2 receptors, more than Bromocriptine.
d. Bromocriptine and Cabergoline are sometimes used as a lactation suppressant, and
this is not (FDA) approved.
e. Cabergoline has been found to raise a man's chances of sustaining multiple orgasms
during sex, (enhance Erection and libido), But don’t try this at home, it’s not (FDA)
approved.
8. Amantadine which is an (antiviral) was accidentally discovered that it has an anti-
Parkinsonism action.
a. Amantadine has been found to have antidyskinesia effects.
b. It’s no longer recommended for treatment of influenza in the USA.
c. It is also used for post-herpetic neuralgia.
d. If dopamine release is already at a maximum; then Amantadine has no effect.
e. It May cause restlessness, agitation, confusion, and hallucinations, and, at high doses, it
may induce acute toxic psychosis. Orthostatic hypotension, urinary retention, peripheral
edema, and dry mouth.
9. Piribedil is an antiparkinsonian agent and Piperazine derivative which acts as a D2 and D3
receptor agonist. It also has α2-adrenergic antagonist properties.
a. Also used in the treatment of pathological cognitive deficits in the elderly (impaired
attention, motivation, memory, etc.)
b. Used as adjunctive treatment of intermittent claudication due to peripheral vascular
disease (PVD) of the lower limbs, it also showed a positive effect in restless legs syndrome.
10. Antimuscarinic drugs exert their anti-Parkinsonian action by reducing the effects of the relative
central cholinergic excess that occurs as a result of dopamine deficiency; Antimuscarinic drugs
can be useful in drug induced Parkinsonism, but they are generally not used in idiopathic
Parkinson’s disease because they are less effective than dopaminergic drugs and they are
associated with cognitive impairment.
a. Benzhexol in a high dose have a direct central inhibition effect on the cerebral motor
centers, it’s abused due to a short acting mood-elevating and euphoretic effect. (It’s
called by the local addicts “the miracle tab”, “abu-Tabrah”).
b. Procyclidine overdose can cause sleeplessness that can last up to or more than 24
hours, it also has a euphoretic effect (abused by many addicts).
4.6-Drugs used in Nausea and Vertigo

1. Antiemetics should be prescribed only when the cause of vomiting is known because
otherwise, they may delay diagnosis, particularly in children; Antiemetics are
unnecessary and sometimes harmful when the cause can be treated, such as in diabetic
ketoacidosis, or in digoxin or antiepileptic overdose.
2. See also Anti-Emetics in chapter 2; (The drugs mentioned in this section acts on the vomiting
trigger zone (deactivates the vomiting center) in the brain, they are used mainly for drug-induced
emesis or chemotherapy induced emesis).
3. 5HT3-receptor antagonists (like Ondansetron) are of value in the management of nausea and
vomiting in patients receiving cytotoxics and in postoperative N/V.
4. Dexamethasone has antiemetic effects and it is used in vomiting associated with cancer
chemotherapy, it can be used alone or with metoclopramide, Prochlorperazine, lorazepam, or a
5HT3 antagonist.
5. Antihistamines are also used as Antiemetics, especially those with anticholinergic effect,
as (diphenhydramine, Doxylamine, hydroxyzine, meclizine, Cyclizine, promethazine).
➢ Scopolamine, meclizine, Cyclizine, are very useful in motion sickness but are ineffective
against substances that act directly on the chemoreceptor trigger zone.
6. Droperidol and Haloperidol act by blocking dopamine receptors. They are moderately effective
Antiemetics. (Haloperidol is also used as antipsychotics)
7. Lorazepam and Alprazolam has a low antiemetic effect.

8. Aprepitant belongs to a new family of antiemetic agents. It targets the neurokinin receptor in
the brain and blocks the actions of the natural substance. It is only indicated for highly or
moderately emetogenic chemotherapy regimens.
9. Betahistine is an analogue of histamine and is licensed for vertigo tinnitus, and hearing loss
associated with Meniere’s disease; (Meniere’s disease is a disorder of the inner ear that can
affect hearing and balance to a varying degree. It is characterized by episodes of vertigo, low-
pitched tinnitus, and hearing loss).
➢ Betahistine dilates the blood vessels within the inner ear which can relieve pressure from
excess fluid and act on the smooth muscle.
A) 5HT3-receptor antagonists
Ondansetron Tab Zofran® , Zuplenz® 4 mg , 8 mg
Oral Solu. No-Vomit® 4 mg/5 ml
Inj. Solu. (Amp) 2 mg/ml
Supp. 16 mg
Palonosetron Inj. Solu. Aloxi® 50 mcg/ml
Cap 500 mcg
Dolasetron Tab Anzemet® 50 mg , 100 mg
Inj. Solu. 20 mg/ml
Granisetron Tab Granisol® , Kytril® 1 mg
Patch Sancuso® 3 mg (each 24 hours)
Inj. Solu. , Amp Kytril® , Grani-Denk® 0.1 mg/ml , 1 mg/ml
Notes:
1. 5HT3-receptor antagonists are not effective against motion sickness.
2. Ondansetron is used off-label to treat morning sickness and hyperemesis gravidarum of pregnancy.
(Pregnancy risk factor = B); Ondansetron may have value in the treatment of schizophrenia, also useful
in treating antipsychotic-induced tardive dyskinesia in people with schizophrenia.
B) Butyrophenones
Haloperidol form
Tab Haldol® , Peridol® 0.5 mg & 1 mg & 2 mg & 5 mg
Depot Inj. Haldol Deconate® 50 mg/ml & 100 mg/ml
Droperidol Inj. Solu. Inapsine® , Droleptan® , Dridol® 2.5 mg/ml
C) Cannabinoids
Dronabinol * Cap Marinol® 2.5 mg , 5 mg , 10 mg
Nabilone Cap Cesamet® 1 mg
* Dronabinol is also used to treat loss of appetite, treat weight loss and the 1st drug approved for the
treatment of sleep Apnea.
D) Miscellaneous agents
Aprepitant Cap Emend® 40 mg , 80 mg , 125 mg
Inj. Powder 150 mg/vial
Fosaprepitant * Inj. Powder Ivemend® 150 mg/vial
Rolapitant Tab Varubi® 90 mg
Trimethobenzamide Cap Tigan® 300 mg
Betahistine Tab Betaserc® 8 mg , 16 mg
* Fosaprepitant is a pro-drug of Aprepitant.
* Rolapitant is FDA approved for the prevention of chemotherapy-related N/V.
4.7- Drugs for Dementia (Anti-Alzheimer)
1. In Dementia, there is a deterioration memory, judgment, language and communication.
Alzheimer’s disease is the most common cause of dementia and accounts for over half of
all patients; about one-third of dementia cases are due to vascular disease.
➢ Dementia can be sudden and irreversible, due to a stroke or head injury.
➢ It can also develop gradually and may be a feature of disorders such as poor circulation
in the brain, multiple sclerosis and Alzheimer’s disease.
2. In healthy people, Acetylcholinesterase (an enzyme in the brain) breaks down the
neurotransmitter Acetylcholine, balancing its levels and limiting its effects; In Alzheimer’s
disease, there is a deficiency of acetylcholine.
➢ So, we use a group of drugs called Acetylcholinesterase inhibitors; that blocks the
action of the enzyme acetylcholinesterase, raising brain levels of Acetylcholine, and
thus increasing alertness and slowing the rate of deterioration.
➢ Donepezil, Galantamine, Tacrine and Rivastigmine are the main (central)
Acetylcholinesterase inhibitors; All have produced modest improvement in mild to
moderate disease state.
3. Acetylcholinesterase inhibitors can cause unwanted cholinergic side-effects, including:
(nausea, diarrhea, vomiting, anorexia, tremors, bradycardia, and muscle cramps), all of which are
predicted by the actions of the drugs to enhance cholinergic neurotransmission, unlike the
others, Tacrine is associated with hepatotoxicity.
➢ Thus; drug treatment is started at a low dose and increased gradually to minimize
side effects and any improvements should begin to appear in about three weeks.
➢ Assessment is repeated at six-monthly intervals to decide if the treatment is beneficial.
4. Rivastigmine is a unique cholinesterase inhibitor with both Acetylcholinesterase and
Butyrylcholinesterase inhibitory activity.
➢ Butyrylcholinesterase, also known as pseudocholinesterase; is a nonspecific
cholinesterase enzyme, which is similar in activity to Acetylcholinesterase.
➢ Thus; Rivastigmine is more potent and more effective than Donepezil in Dementia.
➢ But the incidence of adverse events is generally lower for Donepezil and higher for
Rivastigmine, (thus some doctors prefer to use Rivastigmine Patch).
5. There is increasing evidence that memory loss and dementia in Alzheimer's disease are related
to malfunctioning of the signals that pass messages between the nerve cells in the brain, in
particular, there is evidence that excessive activity of a natural body chemical called glutamate
contributes to the symptoms of Alzheimer's and the progression of this disease.
➢ Glutamate acts on receptors called NMDA receptors that are found on nerve cells in the
brain, these receptors and nerve cells are involved in transmitting nerve messages in the
brain that are important in learning and memory; Glutamate can damage the nerve
cells by excessively stimulating the NMDA receptors.
6. Memantine works by blocking the NMDA receptors in the brain; This blocks the excessive
activity of glutamate, but still allows the normal activation of these receptors that occurs when
the brain forms a memory.
➢ Memantine may improve brain functioning in Alzheimer's disease, and may also block
the glutamate activity that could cause further damage to the brain cells.
➢ Its licensed for treating moderate to severe Alzheimer’s disease.
➢ Memantine is often given in combination with an AChE inhibitor,
➢ Side effects include: confusion, agitation, and restlessness.
7. Other herbal treatments include:
a) Gingko Biloba: was not effective in prevention or treatment in randomized controlled trials.
b) Citicoline: may improve cognitive impairment, especially of vascular origin; it serves as
choline source in the metabolic pathways for biosynthesis of Acetylcholine; (for more details see
section 9, Nootropics).
8. Summary of treatment guideline recommendations of the American Psychiatric Association,
American College of Physicians, and American Academy of Family Physicians, 2007–2008:
a. Initiate an AChE inhibitor in patients with mild to moderate Alzheimer Disease.
b. No evidence one agent is superior to others
c. Titrate to recommended maintenance dose as tolerated.
d. Increase to maximum dose if tolerated and maintenance dose no longer effective, but
clinically meaningful improvement unlikely
e. In moderate to severe disease, may use an AChE inhibitor, Memantine, or both as a
combination; but Slight or no benefit with combination therapy in systematic reviews.
f. Studies find no benefit of Memantine in mild Alzheimer Disease.
Donepezil Tab Aricept® 5 mg , 10 mg
Galantamine Tab , Tab ER Razadyne® , Reminyl® 4 mg , 8 mg , 12 mg
Rivastigmine Cap Exelon® 1.5 mg , 3 mg , 6 mg
Skin Patch 9.5 mg (each 24 hr.)
Tacrine Cap Cognex® 10 mg , 20 mg , 30 mg
Memantine * Tab Ebixa® , Namenda® , Demax® 5 mg , 10 mg
Cap ER 7 mg , 14 mg , 21 mg
Oral Solu. 2 mg/ml
Memantine + Tab Namzaric® , Carrier Plus® (20 mg + 5 mg) ,
Donepezil (20 mg + 10 mg)
* Memantine was used first as an anti-diabetic agent at its discovery.
4.8- CNS Stimulants

1. A person’s state of mental alertness varies throughout the day and is under the control of
chemicals in the brain, some of which are depressant, causing drowsiness, and others that are
stimulant, heightening awareness.
2. It is thought that an increase in the activity of the depressant chemicals may be responsible for a
condition called Narcolepsy, which is a tendency to fall asleep during the day for no obvious
reason; In this case, the nervous system stimulants are administered to increase wakefulness.
➢ These drugs include the amphetamines (usually dexamphetamine), the related drug
methylphenidate, and Modafinil.
➢ Amphetamines are used less often these days because of the risk of dependence.
3. A common home remedy for increasing alertness is caffeine, a mild stimulant that is present in
coffee, tea, and cola and Red-bull
4. The level of wakefulness is controlled by a part of the brain stem called the reticular activating
system (RAS); Activity in this area depends on the balance between chemicals, some of which are
excitatory (including norepinephrine), and some inhibitory, such as gamma aminobutyric acid
(GABA).
5. This Section describes a group of drugs that act primarily to stimulate the central nervous system
(CNS); The psychomotor stimulants, cause excitement and euphoria, decrease feelings of fatigue
and increase motor activity; As a group the CNS stimulants have diverse clinical uses and are
important as drugs of abuse. (This group is widely abused by addicts).
6. Stimulants are used both individually and clinically for therapeutic purposes in the treatment
of a number of indications, including the following:
1. To counteract lethargy and fatigue throughout the day while at work or while doing other
activities.
2. To reduce sleepiness and to keep the person awake when necessary, as well as to treat
narcolepsy.
3. To decrease appetite and promote weight loss, as well as to treat obesity.
4. Occasionally, they are also used off label to treat clinical depression, more particularly, non-
typical depression and treatment-resistant depression.
5. To improve concentration and focus while at work or school, especially for those with
attentional disorders such as ADHD (attention deficit hyperactivity disorder).
➢ It seems a weird and strange to use a CNS stimulant to treat a hyperactivity
disorder (ADHD); but stimulants in ADHD cause a negative response (i.e. decrease
abnormal hyperactivity).
6. To treat Autism in children (although safer options are available, as Risperidone and
Aripiprazole, which are FDA approved for Autism).
Armrodafinil form
Tab Nuvigil ® 50 mg , 150 mg
Atomoxetine Cap Strattera ® 10 mg , 25 mg , 40 mg , 60 mg
Caffeine Comes in Combination in analgesics, pain killers, stimulant combination
Dexmethylphenidate
Tab Focalin® 2.5 mg , 5 mg , 10 mg
Cap Focalin XR® 15 mg , 20 mg , 25 mg
Dextroamphetamin Tab , Cap Dexedrine , Liquadd
® ® 5 mg , 10 mg
e
Diethylpropion Tab Tenuate ® 25 mg , 75 mg
lisdexamfetamine Cap Vyvanse® , Elvanse® 20 mg , 30 mg , 40 mg , 50 mg
Methamphetamine Tab Desoxyn® 5 mg
Methylphenidate Tab Ritalin , Concerta
® ® 5 mg , 10 mg , 20 mg
Cap Ritalin SR ® 20 mg , 30 mg , 40 mg
Skin Patch Metadate ® --------------------
Oral Solu. 5 mg/5 ml
Modafinil Tab Provigil , Modalert
® ® 100 mg , 200 mg
Phendimetrazine Tab , Cap Bontril ® 35 mg (tab) , 105 mg (cap)
Phentermine Tab , Cap Adipex P , Suprenza
® ® 15 mg , 30 mg
4.9- Nootropics
1. These drugs improve mental functions such as cognition, memory, attention, and concentration,
they enhance attentional control and memory, and Nootropics are cognitive enhancers that
are neuroprotective.
Cerebrolysin Amp , Vial Cerebrolysin ® 1 ml , 5 , 10 , 30 ml
Piracetam Tab Nootropil® 800 mg , 1200 mg
Oral Solution
Vincamine Cap Oxybral® 30 mg
Vinpocetine Cap Cavintona , Cavintona Advanced 10 mg , 20 mg
® ®
Idebenone Tab Geniceral® 30 mg , 45 mg

Meclofenoxate Amp , Vial Lucidril®, Luciforte® 250 mg , 500 mg
Sulbutiamine Tab Arcalion® 200 mg
Citicoline Tab Lira ® 500 mg
Inj. (Amp) Somazina ® 500 mg , 1000 mg
Oral Solution Somazina , Trausan , Citoneurox 100 mg/ml
® ® ®
Sachets 1000 mg/10 ml

Citicoline + B6 + B12 Sachets Brain Food ® 250mg + 1.4mg + 2mcg
Pyritinol Oral Solution Encephabol® 100 ml
Tab 100 mg , 200 mg
Notes:
1. Cerebrolysin, a peptide preparation produced from purified pig brain proteins; it mimics the
effects of endogenous neurotrophic factors and activates components of the endogenous defense
system within the nervous tissue.
➢ Indicated for patients suffering from dementia, stroke, and traumatic brain injury.
2. Piracetam, a derivative of the neurotransmitter (GABA), has neuroprotective and
anticonvulsant properties, and improves neuroplasticity. At a vascular level, it appears to
reduce erythrocyte adhesion to vascular endothelium, hinder vasospasm, and facilitate
microcirculation; This diverse range of physiological effects is consistent with its use in a range
of clinical indications, its efficacy is documented in cognitive disorders and dementia, vertigo,
cortical myoclonus, dyslexia, and sickle cell anemia; Although it’s still not FDA approved.
3. Vincamine is a Peripheral Vasodilator that acts by increasing cerebral blood circulation.
➢ Vinpocetine is a synthetic derivative of Vincamine; may lead to improved attention,
focus, and memory.
4. Idebenone is indicated for the Treatment of mild and moderate cognitive alterations in patients
with Alzheimer or vascular dementia.
5. Sulbutiamine is a synthetic derivative of thiamine (Vit. B1), it is used to treat symptoms of
weakness or fatigue, it is also sold as a dietary supplement; it may enhance memory, focus, mood
and Endurance.
6. Meclofenoxate is a cholinergic nootropic used as a dietary supplement and drug in the
treatment of symptoms of senile dementia and Alzheimer's disease.
a. In elderly patients, Meclofenoxate has been found clinically to improve memory, have a
mentally stimulating effect, and improve general cognition.
b. Also increases cellular membrane phospholipids.
7. Citicoline supplements help improve focus and mental energy and may possibly be useful in the
treatment of attention deficit disorder.
a. it inhibits apoptosis associated with cerebral ischemia and several models of
neurodegeneration, it is able to potentiate neuroplasticity and is a natural precursor of
phospholipid synthesis, chiefly phosphatidylcholine or rather serves as choline source in
the metabolic pathways for biosynthesis of acetylcholine.
b. used for treatment in cases of head trauma, stroke, neurodegenerative disease
c. Improves visual function in patients with glaucoma, amblyopia, and non-arteritic
ischemic optic neuropathy.
d. Citicoline reduces oxidative stress; it also prevents excessive inflammatory response in
the brain by inhibiting the release of free fatty acids and decreasing blood–brain barrier
breakdown.
8. Pyritinol is semi-natural water-soluble analog of vitamin B6 (Pyridoxine), it is approved for
"symptomatic treatment of chronically impaired brain function in dementia syndromes
and for supportive treatment of sequelae of craniocerebral trauma.

4.10- Herbals and Supplements for Cognitive function
This section describes the herbals and supplements that is used for the enhancement of
cognition, memory and brain boost; many of them are also Nootropics.
1. Ginkgo Biloba has been repeatedly evaluated for its ability to reduce anxiety, stress and other
symptoms associated with Alzheimer’s disease and cognitive decline associated with aging.
➢ It cannot be concluded that Ginkgo treats Alzheimer’s and other forms of dementia, but it
might help in some cases; The chances of it helping seem to increase when used alongside
conventional treatment; also, Some research shows that Ginkgo may improve mental
performance in healthy people, but the data is inconsistent.
➢ Ginkgo may improve symptoms of sexual dysfunction due to its impact on blood flow.
However, research has not proven it to be effective.
2. Ginseng may improve thinking processes and cognition; although its well-known for its
effectiveness in the treatment of erectile dysfunction.
3. 5-Hydroxytryptophan (5-HTP) is an amino acid that the body naturally produces; it’s used by
the body to produce serotonin, a chemical messenger that sends signals between the nerve cells
(Low serotonin levels are associated with depression, anxiety, sleep disorders, weight gain and
other health problems), thus increasing the body’s production of serotonin may have various
benefits including cognitive ones.
4. L-Arginine which enhances blood circulation, by increasing the amount of nitric oxide in the
body, they stimulate blood vessels to become larger (thus also used by bodybuilders); This
improves blood flow, and increasing blood supply to the brain, which could help in cognition.
5. Coenzyme Q10 (CoQ10) has been shown to protect brain cells from oxidative damage and
reduce the action of harmful compounds that can lead to brain disease.
6. Lecithin is used for treating memory disorders such as dementia and Alzheimer’s disease; its
converted into acetylcholine, a substance that transmits nerve impulses.
7. Alpha-Lipoic acid (ALA) is a synthetic version of Lipoic acid, which helps cells make energy. It
has antioxidant properties and may reduce inflammation.
➢ It may protect brain cells from conditions such as stroke, multiple sclerosis, and
Alzheimer's disease; Preclinical studies also indicate that ALA or a combination of ALA
and regular exercise may improve certain aspects of learning and memory; However, no
clinical studies suggest that ALA can prevent dementia or improve cognition.
8. St John's Wort, or called (Hypericum perforatum) may counteract stress-induced memory
impairment; it’s also considered an antidepressant and anti-anxiety agent, it effects multiple
neurotransmitters in a non-competitive synergistic manner, and may have nootropic potential.
➢ It has a high drug-drug interaction profile; thus, France has banned the use of St. John's
Wort in products. In other countries it is only available with a prescription.
Trade name D. form Scientific name(s) concentration

Neuro-All® Tab Ginkgo Biloba + Vit. B1 + Vit. B6 + Vit. B12 50mg + 200mg + 50mg + 1mg
Ginkgo Ceutica® Tab Ginkgo Biloba + Ginseng 80 mg + 150 mg
Neurozan® Tab Ginkgo Biloba + 5-HTP + L-Arginine 120 mg + 20 mg + 40 mg
+ L-Glutamine + L-Glutathione + 10 mg + 5 mg
+ Co-Q10 + Phosphatidylcholine + 10 mg + 10 mg
+ Phosphatidylserine + Beta-carotene + 10 mg + 2 mg
+ Vitamin D + Vitamin E + Vitamin C + 25 mcg + 36 mg + 80 mg
+ Vit.B1 + Vit.B2 + Vit.B3 + Vit.B6 + Vit.B12 + 25mg+3mg+32mg+10mg
+ Folic Acid + Pantothenic acid + 400 mcg + 36 mg
+ Minerals

Active Memory® Cap Lecithin + Vit. E + Folic acid 1000 mg + 30 mg + 400 mcg
+ Vit. B1 + Vit. B2 + Vit. B6 + Vit. B12 + 4.2mg+4.8mg+4.8mg+6mcg
+ Niacin + 27 mg
Mentat® Syrup Herbal combination 100 ml
Neurobooster® Cap Coenzyme Q10 + Alpha-Lipoic Acid 1000 mg blend
+ Acetyl-L-Carnitine (per 2 caps)
Memo Up® Oral Ginkgo Biloba + Gotu Kola 60 ml blend
Drop + Eleutherococcus Senticosus
+ Foti root extract
Think-Rite® Cap Ginkgo Biloba + Acetyl-L-Carnitine 50 mg + 50 mg
+ Phosphatidylserine Complex + 125 mg
+ St. John’s Wort + Bacopin + 250 mg + 100 mg
+ L-Glutamine + Vinpocetine + 150 mg + 2 mg
+ DMAE Bitartrate + 50 mg
Memo-B® Oral Fructoplant of blueberry berries 2.4 gm (per 20 ml)
Solu. + Brewer's yeast + Royal jelly + 200 mg + 100 mg
+ Schisandra berries dry extract + 200 mg
+ Astragalus root dry extract + 200 mg
+ Vit. B1 + Vit. B3 + Vit. B6 + CoQ10 + 1.7mg + 24mg + 2mg +10mg
Speak® Cap D-alpha Tocopherol 500 IU
+ Gamma Tocopherol + Vitamin K + 200 mg + 2.3 mg
+ Eicosapentaenoic Acid (EPA) + 725 mg
+ Docosahexaenoic Acid (DHA) + 275 mg
+ Gamma-linolenic acid + 60 mg
References
1- Sean C. Sweetman. Martindale: The Complete Drug Reference, 38th Edition.
3- Russell J Greene, Norman D Harris. Pathology and Therapeutics for Pharmacists: A basis for clinical
pharmacy practice third edition, 2012 by pharmaceutical press.
7- Canadian pharmacists association, Therapeutic choices. 2014.
8- Marie A. Chisholm-Burns, Pharmacotherapy Principles & Practice Copyright © 2014
9- Comprehensive Pharmacy Review for NAPLEX 8th Ed
INFECTIONS
Chapter Five: Infections
Part One: Introduction 5.4- Anthelmintics (drugs used
Part Two: for worms)
5.1- Antibacterial drugs 5.5- Antiprotozoal drugs
1. Penicillins
1. Amebicides
2. Cephalosporins
2. Drugs for Toxoplasmosis
3. Carbapenems
3. Drugs for Leishmaniasis
4. Other Beta-lactams
4. Drugs for Trypanosomiasis
5. Tetracyclines
5. Drugs for Balantidiasis and
6. Aminoglycosides
Cryptosporidiosis
7. Macrolides
6. Drugs for Pneumocystis
8. Quinolones
Pneumonia
9. Urinary tract Antiseptics
7. Drugs for Trichomoniasis
10. Lincosamides
8. Drugs for Malaria
11. Sulfonamides, Trimethoprim
12. Antimycobacterials (anti-TB)
13. Drugs used to treat Leprosy
14. Metronidazole, Tinidazole and
their relatives
15. Other Antibacterials:
a. Glycopeptides
b. Quinupristin/Dalfopristin
c. Tedizolid
d. Linezolid
e. Nifuroxazide
f. Rifaximin
g. Chloramphenicol
h. Thiophenicol, Colistimethate,
Lefamulin, Daptomycin
16. Topical antibiotics
5.2- Antifungal drugs
1. Systemic antifungals
2. Topical antifungals
3. Vaginal Antifungals
5.3- Antiviral drugs
1. Herpes simplex and varicella–
zoster infections
2. Cytomegalovirus (CMV) infection
3. Influenza Virus infection
4. Viral Hepatitis infections
5. Respiratory syncytial virus
6. human immunodeficiency virus
(HIV)
Sam’s Guide: Chapter 5 – Infections
Chapter Five: Infections
Part One:
1. Introduction:
1. The human body provides a suitable environment for the growth of many types of microorganism
(MO), including bacteria, viruses, fungi, yeasts, and protozoa; It may also become the host for
animal parasites such as insects, worms, and flukes.
2. Microorganisms (microbes) exist all around us (in the air we breathe, on the mucous membranes
of our mouth and nose, on our skin, and in our intestines – but we are protected, most of the time,
by our immunological defences); microbes can be transmitted from person to person in many
ways: direct contact, inhalation of infected air, and consumption of contaminated food or water.
3. Not all microorganisms cause disease; many types of bacteria exist on the skin surface or in
the bowel without causing ill effects
➢ Normally, the immune system protects the body from infection; Invading microbes are
killed before they can multiply in sufficient numbers to cause serious disease.
2. Types of Infecting Organism

A) Bacterium: consists of a single cell with a protective wall, some bacteria are aerobic (requiring
oxygen) and are therefore more likely to infect surface areas such as the skin or respiratory tract,
Others are anaerobic and multiply in oxygen-free surroundings, as the bowel or deep wounds.
➢ Bacteria can cause symptoms of disease in two principal ways: by releasing toxins that
harm body cells and by provoking an inflammatory response in the infected tissues.
B) Viruses: are smaller than bacteria and consist simply of a core of genetic material surrounded
by a protein coat; it can multiply only in a living cell, by using the host tissue’s replicating material.
C) Fungi: group of living organisms which are classified in their own kingdom; This means they are
not animals, plants, or bacteria. Unlike bacteria, which have simple prokaryotic cells, fungi have
complex eukaryotic cells like animals and plants.
➢ In humans, fungal infections occur when an invading fungus takes over an area of the body
and is too much for the immune system to handle.
D) Protozoa: are single-celled parasites and are slightly bigger than bacteria, many protozoa live in
the human intestine and are harmless; other types cause malaria, sleeping sickness, dysentery.
E) Parasites: Invasion by parasites that live on the body (as lice) or in the body (as tapeworms) is
known as infestation, it’s associated with tropical climates, poor standards of hygiene.
3. What can go wrong

1. Infectious diseases occur when the body is invaded by microbes, this may be caused by the body
having little or no natural immunity to the invading organism, or the number of invading
microbes being too great for the body’s immune system to overcome.
2. Serious infections can occur when the immune system does not function properly or when a
disease weakens or destroys the immune system, as occurs in patients taking high doses of
corticosteroids or Immunosuppresants.
➢ Some parts of the human body are more susceptible to infection than others; respiratory
tract infections are relatively common, whereas bone and muscle infections are rare.
➢ Some symptoms are the result of damage to body tissues by the infection, or by toxins
released by the microbes. In other cases, the symptoms result from the body’s defence
mechanisms.
➢ Most bacterial and viral infections cause fever; Bacterial infections may also result in
inflammation and pus in the affected area.
5.1-Antibacterial drugs
1. Before selecting an antibacterial you must first consider two factors: the patient and the
known or likely causative organism.
2. Factors related to the patient which must be considered include history of allergy, renal and
hepatic function, susceptibility to infection (whether immunocompromised), ability to tolerate
drugs by mouth, severity of illness, ethnic origin, age, whether taking other medication and, if
female, whether pregnant, breast-feeding or taking an oral contraceptive.
3. Before starting any anti-infective therapy, the following precepts should be considered:
➢ Viral infections should not be treated with Antibacterials, however, Antibacterials may be
used to treat secondary bacterial infection (e.g. bacterial pneumonia secondary to influenza).
➢ Samples should be taken for culture and sensitivity testing; ‘blind’ antibacterial prescribing
for unexplained pyrexia usually leads to further difficulty in establishing the diagnosis.
➢ Knowledge of prevalent organisms and their current sensitivity is of great help in choosing
an antibacterial before bacteriological confirmation is available. Generally, narrow-
spectrum Antibacterials are preferred to broad-spectrum Antibacterials unless there is
a clear clinical indication (e.g. life-threatening sepsis).
➢ The dose of an antibacterial varies according to a number of factors including age, weight,
hepatic function, renal function, and severity of infection.
➢ The prescribing of the ‘standard’ dose in serious infections may result in failure of treatment
or even death of the patient; therefore, it is important to prescribe a dose appropriate to
the condition.
➢ An inadequate dose may also increase the likelihood of antibacterial resistance, On the
other hand, for an antibacterial with a narrow margin between the toxic and therapeutic dose
(e.g. an aminoglycoside) it is also important to avoid an excessive dose and the concentration
of the drug in the plasma may need to be monitored.
➢ The route of administration of an antibacterial often depends on the severity of the infection,
Life-threatening infections require intravenous therapy, Antibacterials that are well
absorbed may be given by mouth even for some serious infections, Parenteral administration
is also appropriate when the oral route cannot be used (e.g. because of vomiting) or if
absorption is inadequate.
➢ Whenever possible, painful intramuscular injections should be avoided in children.
➢ Duration of therapy depends on the nature of the infection and the response to treatment,
Courses should not be unduly prolonged because they encourage resistance, they may
lead to side-effects and they are costly. However, in certain infections such as tuberculosis or
osteomyelitis it may be necessary to treat for prolonged periods. Conversely a single dose of
an antibacterial may cure uncomplicated urinary-tract infections.
➢ The prescription for an antibacterial should specify the duration of treatment or the date
when treatment is to be reviewed.
4. There is a term called (superinfection) that is generally defined as a second infection
superimposed on an earlier one, especially by a different microbial agent that is resistant to the
treatment used against the first infection, an example of this is the overgrowth of endogenous
Clostridium difficile which occurs following treatment with a broad-spectrum antibiotic.
➢ In virology, the definition is slightly different: Superinfection is the process by which a cell
that has previously been infected by one virus gets co-infected with a different strain of the
virus, or another virus, at a later point in time, Viral superinfections may be resistant to the
antiviral drug or drugs that were being used to treat the original infection. Viral
superinfections may also be less susceptible to the host's immune response.
• Classes of Antibiotics include: Penicillins (First introduced in the 1940s), Cephalosporins,

Carbapenems, Macrolides, Tetracyclines, Aminoglycosides, Lincosamides, Quinolones and
Sulfonamides.
The table below shows common drugs in each class of antibiotic used to treat infections in
different parts of the body. (It is not intended as a guide to prescribing.)

5.1.1- Penicillins (Bactericidal antibiotics)
1. The Penicillins are bactericidal and act by interfering with bacterial cell wall synthesis, they
diffuse well into body tissues and fluids, but penetration into the cerebrospinal fluid is poor
except when the meninges are inflamed, they are classified as:
Penicillin groups Examples
1 Natural penicillin’s Benzyl penicillin and Phenoxymethylpenicillin
2 Penicillinase-resistant penicillin’s Flucloxacillin, Cloxacillin
3 Broad-spectrum penicillin’s Amoxicillin, Ampicillin
4 Antipseudomonal penicillin’s Piperacillin, Ticarcillin
2. The most important side-effect of the penicillin’s is hypersensitivity which causes rashes and
anaphylaxis and can be fatal, other includes: diarrhea and headache.
How to do Penicillin Allergy skin Test
Dissolve 1 vial of penicillin (Amoxicillin or Ampicillin) in 5 ml of Distal water for injection, then
take 10 units from the vial (by insulin syringe) and complete the volume to 100 units by Distal
water, then inject 10 units only as intradermal injection, Then wait and observe for about 15 –
30 minutes, a skin reaction will conform that the patient has a Penicillin allergy.
3. Ampicillin, Flucloxacillin and Cloxacillin must be given on an empty stomach (1 hr. before food
or 2 hrs. after food) while Amoxicillin maybe taken without regard to meal.
4. Co-Amoxiclave consists of amoxicillin with the beta-lactamase inhibitor (clavulanic acid);
Clavulanic acid inactivates beta-lactamases, making the combination active against beta-
lactamase-producing bacteria that are resistant to Amoxicillin.
5. Various combinations between (Amoxicillin and Clavulanic acid) are presents:
Combinations (mg) Dosage form Notes
156 (125 +31) , 312 (250 + 62) suspension
457 (400 + 57) , 642.9 (600 + 42.9) suspension Given twice daily (every 12 hours)
375 (250 + 125) , 625 (500 + 125) Tablet
1000 (875 +125) Tablet Given twice daily (every 12 hours)
600 (500 + 100) , 1200 (1000 + 200) Injection For intravenous injection only
Comes in many trade names, include: (Augmentin®, Augmenta®, Cloclav®, Co-Amox®, etc.)
6. For the eradication of H. pylori (a bacterium that causes ulcer), Amoxicillin is given with
Clarithromycin and a proton pump inhibitor; usual doses of amoxicillin for the eradication of
H. pylori is 1 g twice daily; (for more details see chapter 2, section 2, PPIs).
Procaine benzyl penicillin Vial Procaine benzyl 0.4 , 0.6 , 0.8 , 1.2 mega gram
Amoxicillin penicillin ®
Cap , Vial Amoxil , Neomox ® 250 mg , 500 mg , 1000 mg
Susp. Neomox , Glomox
® ® 250 mg/5 ml , 125 mg/5 ml
Sachets Amoxil Sachets SF ® 3 gm per sachet
Amoxicillin + Flucloxacillin Cap Flumox® 250 mg , 500 mg
Amoxicillin + Sulbactam Vial BiomoxSalb ® (0.5 gm + 0.25 gm)
Ampicillin + Cloxacillin Cap Ampiclox ® 250 mg + 250 mg
Vial Ampiclox ® 250 mg + 250 mg
Ampicillin + Sulbactam Vial Unasyn , BioSalb
® ® (0.5gm+0.25gm), (1gm+0.5gm)
Ampicillin Susp. Ampicillin ® 250 mg/5 ml
Ampicillin Cap Ampicillin ® 250 mg , 500 mg
Piperacillin + Tazobactam Vial Tazocin , Tazopip
® ® 2.25 gm , 4.5 gm
Ticarcillin + Clavulanic acid Vial Timentin ® 3.2 gm
Flucloxacillin Cap Fluxa ® 500 mg
** Ampicillins (including Amoxicillin) when mixed with water has stability of 1 hour ONLY, thus
discard any solution remaining in the vial after 1 hour.
5.1.2- Cephalosporins (Bactericidal antibiotics)
The pharmacology of the Cephalosporins is similar to that of the Penicillins, Cephalosporins
penetrate the cerebrospinal fluid poorly unless the meninges are inflamed.
1. Classification
Cephalo Groups Examples
1 First-generation Cephalexin and Cefadroxil
2 Second -generation Cefuroxime
3 Third-generation Cefotaxime, Ceftazidime, ceftriaxone, Cefpodoxime
4 Fourth-generation Cefepime
5 Fifth -generation Ceftraroline
2. In general, the activity against gram negative bacteria is increase and the activity against gram
positive bacteria is decrease when we move from first to third generation Cephalosporins.
3. Some important properties for specific agents:
Drug Properties
Ceftriaxone It has a long half-life (may be given once daily), safe in hepatic failure.
Cefotaxime Safe in renal failure.
Ceftazidime Has good activity against pseudomonas, safe in renal and hepatic failure
Cefixime Oral third Marketed generation cephalosporin (in fact it’s a 2nd gen.)
Cefpodoxime Oral third-generation cephalosporin (must be given after food).
4. The principal side-effect of the Cephalosporins is hypersensitivity and about 0.5–6.5% of
penicillin-sensitive patients will also be allergic to the Cephalosporins, other includes:
diarrhea and headache and arrhythmias.
Patients with a history of immediate hypersensitivity to penicillin should not receive a
cephalosporin (relative contraindication).
➢ Antibiotic-associated colitis may occur with the use of broad-spectrum Cephalosporins,
particularly second and third-generation Cephalosporins.
5. IMPORTANT: regarding Cefotaxime, and Ceftriaxone:
When given by an intravenous injection these drugs should be given over at least 2–4 minutes
(arrhythmias following rapid injection reported); There have been cases of death recorded
due to the rapid I.V. inj. of Cefotaxime, and Ceftriaxone.
➢ A newer recommendation states that (Cefotaxime, Ceftriaxone) must be given in at
least 100 mL I.V. infusion ONLY; although 10 ml is sometimes enough.
➢ Some new studies found that Ceftriaxone causes PARF (pediatric acute renal failure), by
forming urine stone that precipitate in the renal tubules causing PARF.
➢ Ceftriaxone is contraindicated in babies below 28 days because it can displace bilirubin
leading to bilirubin encephalopathy in these patients.
➢ Ceftriaxone when mixed with water has stability of 24 hr., while Cefotaxime has a 12 hr.
➢ Ceftriaxone, Cefoperazone are metabolized by liver, so they are used safely in renal
failure, while Cefotaxime is metabolized by kidney, so it’s used safely in liver failure.
➢ It’s a fatal mistake to combine ceftriaxone with Ca+ containing fluids in the same IV
route, high risk of fatal particulate precipitation in lungs and kidneys, separate by at least
48 hr., or use alternatives as Cefotaxime, Cefoperazone. (Does not cause precipitations).
1st Generation Cephalosporins
Cephalexin Cap Keflex® , Cephalonin® 250 mg & 500 mg
Susp. Acaflex® 250 mg/5 ml
Cefadroxil Tab Cefadrox®, Duricef® 1000 mg
Cefalothin Vial Keflen® 1 gm
Cefazolin Vial Cefazo® 0.5 gm , 1 gm
2nd
Generation Cephalosporins
Cefaclor Cap Ceclor® , Cloracef Forte® 250 mg & 500 mg
Susp. Cloracef ® 250 mg/5 ml , 375 mg/5 ml
Cefotetan Vial Cefotetan ® 1 gm , 2 gm
Cefoxitin Vial Cefoxitin ® 1 gm , 2 gm
Cefprozil Tab Cefzil ® 250 mg & 500 mg
Susp. 250 mg/5 ml , 125 mg/5 ml
Cefuroxime Tab Zinnat , Zamor , Zinacef
® ® ® 250 mg , 500 mg
Susp. 250 mg/5 ml , 125 mg/5 ml
Inj. Powder Ceftin ® 225 mg , 750 mg , 1.5 gm
** Cefuroxime is the only cephalosporin that can be given both orally and as injection, other Cephalosporins are
either given orally OR as injection. (One route only).
3rd Generation Cephalosporins
Cefotaxime Vial Claforan® , Cefotac® 0.25 gm , 0.5 gm , 1 gm
Ceftriaxone Vial Rocephin , Mesporin , Novocef 0.25 gm , 0.5 gm , 1 gm
® ® ®
Ceftriaxone + Vial Philbacxone® 1 gm +

Sulbactam 0.5 gm
Ceftazidime Vial Fortaz® , Tazicef®, Tottizim® 0.5 gm , 1 gm
Ceftazidime + Vail Avycaz® 2 gm/0.5 gm
Avibactam
Cefoperazone Vial Cefobid®, Ceprazo®, Magnamycin® 0.25 gm , 0.5 gm , 1 gm
Cefoperazone + Vial Cef Novo® , Cefortal® , Cefobid S® (1 gm + 0.5 gm) &
Sulbactam (1 gm + 1 gm) & (2 gm + 1gm)
Ceftizoxime Vial Cefizox ® 0.5 gm , 1 gm
Cefdinir * Cap Omnicef ® 300 mg
Cefditoren Tab Spectracef® 200 mg , 400 mg
Ceftibuten Cap Cedax ® 400 mg
Cefixime * Cap Suprax , Cefix
® ® 200 mg , 400 mg
Susp. 100 mg/5 ml , 200 mg/5 ml
Granules 50 mg/Sachet
Cefpodoxime Tab Orelox , Vantin , Zakon , Infex
® ® ® ® 100 mg , 200 mg
Susp. Cefpodox ® 50 mg/5 ml , 100 mg/5 ml
Cefpodoxime + Tab, Infex Plus ® (200 mg + 125 mg) Tab
Clavulanic Acid Susp. (100 mg + 62.5)/5 ml Susp
4 Generation Cephalosporins
th
Cefepime Infusion Maxipime® , Maxcef® , Cepimax® 1 gm/50 ml , 2 gm/100 ml

Vial 0.5 gm , 1 gm , 2 gm
Cefpirome Vial Cefrom , Keiten , Broact
® ® ® 1 gm , 2 gm
Cefluprenam Infusion --------------------- 1 gm/50 ml
Cefozopran Infusion --------------------- 1 gm/50 ml
Cefquinome Infusion --------------------- 1 gm/50 ml
5 Generation Cephalosporins
th
Ceftraroline Vial Teflaro®, Zinforo® 400 mg , 600 mg

Ceftobiprole Infusion Zevtera ® 500 mg
Cefiderocol Vial Fetroja® 1 gm
Ceftolozane + Vial Zerbaxa ® 1 gm/0.5 gm
Tazobactam
* Both Cefixime (Suprax®) and Cefdinir (Omnicef®) are considered as a 2nd generation cephalosporin (by their
chemical structure), but are intentionally marketed as a 3rd generation cephalosporin, mainly to increase their sells.
5.1.3- Carbapenems (Bactericidal antibiotics)
1. The Carbapenems are beta-lactam Antibacterials with a broad-spectrum of activity which
includes many Gram positive and Gram-negative bacteria, and anaerobes.
➢ Imipenem and Meropenem have good activity against Pseudomonas aeruginosa, the
Carbapenems are not active against methicillin-resistant Staphylococcus aureus and
Enterococcus faecium.
2. Imipenem is partially inactivated in the kidney by enzymatic activity and is therefore
administered in combination with Cilastatin, a specific enzyme inhibitor, which blocks its
renal metabolism. (Cilastatin is not required with the others, because these are not sensitive
to renal enzyme; which is dipeptidase).
3. Most physicians prescribe Meropenem 500 mg or 1 gm every 12 hours; and that’s wrong; its
half-life is only 1 hour and its serum level will totally disappear after 5-7 hour; thus, it should
be given every 8 hours; (Meropenem dose should not exceed 2 gm every 8 hr.).
➢ Imipenem is given twice daily or 4 times a day according to the severity.
➢ Ertapenem is given 1 gm once daily.
4. Side-effects of Carbapenems are similar to those of other beta-lactam antibiotics; neurotoxicity
has been observed at very high dosage, in renal failure, or in patients with CNS disease.
➢ High levels of Imipenem may provoke seizures, but Meropenem is possibly less
likely to do so, Doripenem has not demonstrated any potential to cause seizures.
➢ Patients who are allergic to penicillin or Cephalosporins may suffer cross-sensitivity
reactions during Carbapenems therapy.
Imipenem + Cilastatin Vial Primaxin , Tenam
® ® (250 mg + 250) , (500 mg + 500 mg)
Imipenem + Cilastatin Vial Recarbrio ® 500 mg + 500 mg
+ Relebactam * + 250 mg
Meropenem Vial Meronem®, Merrem® 500 mg , 1 gm
Doripenem Vial Doribax® 500 mg
Tebipenem Vial Orapenem ® 500 mg , 1 gm
Ertapenem Vial Invanz® 1 gm
Meropenem Vial Vabomere ® 1 gm +
+ Vaborbactam * 1 gm
* Relebactam and Vaborbactam are β-lactamase inhibitors.
5.1.4- Other Beta-lactams Antibacterials
These include: Aztreonam and Pivmecillinam
1- Aztreonam is a monocyclic beta-lactam (monobactam) antibiotic with an antibacterial spectrum
limited to Gram-negative aerobic bacteria including Pseudomonas aeruginosa, Neisseria
meningitides, and Hemophilus influenza; it should not be used alone for ‘blind’ treatment
since it is not active against Gram-positive organisms.
➢ It resembles the aminoglycosides in its efficacy against many gram-negative
organisms but does not cause nephrotoxicity or ototoxicity.
➢ Other advantages of this drug include its ability to preserve the body’s normal gram-
positive and anaerobic flora, activity against many gentamicin-resistant organisms,
and lack of cross-allergenicity with penicillin.
2- Pivmecillinam has significant activity against many Gram-negative bacteria including
Escherichia coli, Klebsiella, Enterobacter, and salmonellae; It is not active against
Pseudomonas aeruginosa or enterococci.
Pivmecillinam Tab Selexid® 200 mg
Aztreonam Vial Azactam® 1 gm , 2 gm
Inhaler powder Cayston® 75 mg/vial
5.1.5- Tetracyclines (Bacteriostatic antibiotics)
Tetracyclines are a group of broad-spectrum antibiotics whose general usefulness has been
reduced with the onset of antibiotic resistance. Despite this, they remain the treatment of choice
for some specific indications.
1. Important: Oral administration:
A- Tetracyclines must be given on an empty stomach (This means an hour before food or 2
hours after food) while Doxycycline is given during meals.
B- Capsules and tablets should be swallowed whole with plenty of fluid while sitting or
standing; (because they may cause esophageal irritation).
2. Deposition of tetracycline’s in growing bone and teeth (by binding to calcium) causes
staining, thus they are contraindicated in children under 12 years, or to pregnant or breast-
feeding women.
3. Other side effects include: dysphagia, and esophageal irritation, GI disturbance, dizziness,
nausea and vomiting, photo-toxicity (they increase the risk of sunburn under exposure to light
from the sun or other sources).
4. About Doxycycline:
➢ Doxycycline has longer duration than tetracycline and may be given once or twice daily.
➢ Common indications for doxycycline include: genital Chlamydia, acne, and in
brucellosis (in combination with rifampicin).
➢ Also given in the treatment of recurrent Aphthous ulceration, or as an adjunct to
gingival scaling and root planning for periodontitis.
➢ Also used for Lyme disease.
➢ It is used in prophylaxis against malaria, it should not be used alone for initial treatment
of malaria, even when the parasite is doxycycline-sensitive.
5. Minocycline have immunomodulatory, anti-inflammatory, or chondroprotective effects;
thought to be a potent inhibitor of metalloproteinase, which are active in rheumatoid arthritis
joint destruction, thus; it’s used off-label in the treatment of Rheumatoid Arthritis.
6. Tigecycline is a glycylcycline antibacterial structurally related to the Tetracyclines; side
effects similar to those of the Tetracyclines can potentially occur, Tigecycline is active against
Gram-positive and Gram-negative bacteria including tetracycline-resistant organisms.
Tetracycline * Cap Hostacycline® , Sumycin® , 250 mg , 500 mg
Samacycline®
Doxycycline Cap , Tab Vibramycin® , Doxidar® 100 mg
MR Cap Efracea® 40 mg
Demeclocycline Tab Declomycin® 150 mg , 300 mg
Lymecycline Cap Tetralysal® 408 mg
Minocycline Cap , Tab Dynacin® , Minocin® 50 mg , 100 mg
MR Cap Minocin MR® 100 mg
Vial Solodyn® 100 mg
Oxytetracycline Tab Oxymycin®, Terramycin® 250 mg
Tigecycline Vial (I.V.) Tygacil ® 50 mg
Eravacycline Vial Xerava ® 50 mg
Omadacycline ** Tab , Vial Nuzyra® 150 mg (tab), 100 mg (vial)
Sarecycline ** Tab Seysara ® 60 mg , 100 mg , 150 mg
* Tetracycline is also available as skin cream, eye ointment.
** Omadacycline is a new broad-spectrum antibiotic; its FDA approved for the treatment of
community-acquired bacterial pneumonia and acute skin and skin structure infections.
** Sarecycline is approved by the FDA for the treatment of moderate to severe acne vulgaris.
5.1.6- Aminoglycosides (Bactericidal antibiotics)
1. These include: Amikacin, gentamicin, neomycin, streptomycin, and tobramycin.
2. The aminoglycosides are not absorbed from the gut and must therefore be given by injection
for systemic infections (1). Except for Neomycin which is given orally for local effect.
➢ Neomycin is too toxic for parenteral administration and can only be used for
infections of the skin or mucous membranes or to reduce the bacterial population of the
colon prior to bowel surgery or in hepatic failure.
3. The important side-effects are ototoxicity, and nephrotoxicity; They are dose related; Their
relative ototoxicity is as follows:
Streptomycin = kanamycin > Amikacin > gentamicin > tobramycin > Netilmicin.
➢ Gentamicin and streptomycin cause primarily vestibular damage (manifested by
tinnitus, vertigo, and ataxia). Such damage may be bilateral and irreversible.
➢ Amikacin, kanamycin, and neomycin cause mainly auditory damage (hearing loss).
➢ Tobramycin can result in both vestibular and auditory damage.
➢ Ototoxicity and nephrotoxicity occur most commonly in the elderly.
4. Streptomycin is used mainly for tuberculosis (2nd line drug) and for brucellosis.
5. The aminoglycosides synergize (increased effect dramatically) with the β-lactam antibiotics
(Penicillins, Cephalosporins, Carbapenems), because of the latter’s action on cell wall
synthesis, which enhances diffusion of the aminoglycosides into the bacteria.
6. Whenever possible; treatment should not exceed 7 days with aminoglycosides.
7. Once daily administration of aminoglycosides is more convenient, provides adequate serum
concentrations, and in many cases has largely superseded multiple daily dose regimens (given in
2–3 divided doses during the 24 hours).
8. Aminoglycosides may impair neuromuscular transmission, thus:
➢ C.I. in patients with myasthenia gravis.
➢ Large doses given during surgery have been responsible for a transient myasthenic
syndrome in patients with normal neuromuscular function.
9. Aminoglycoside should be avoided in patients with a creatinine clearance less than 20 mL/Min,
also dosage adjustment is needed in patients with renal disease.
10. There is an increased risk of auditory or vestibular nerve damage in the infant when
Aminoglycosides are used in the second and third trimesters of pregnancy.
Gentamicin Amp Garamycin®, Cidomycin® 80 mg/2 ml , 20 mg/2 ml
Amikacin Vial (Solu.) Amikin® 100 mg/2 ml , 500 mg/2 ml
Neomycin Tab , Powder Myciguent® , Mycifradin® 500 mg
Streptomycin Vial (powder) Streptomycin® 1 gm
Tobramycin Inj. Solu. Nebcin® 10 mg/ml , 40 mg/ml
Inhalation Sol. Bramitob®, Tobi® 75 mg/ml , 60 mg/ml
Kanamycin Inj. Solu. Kantrex® 500 mg/2 ml
Netilmicin Amp Netromycin® 10 mg , 25 mg , 50 mg
Plazomicin Vial (Solu.) Zemdri® 500 mg/10 ml
Notes:
1. Gentamicin is also found as skin cream/ointment, Eye drop/ointment.
2. Neomycin is also found in combination of skin creams/Oint., Ear drops/Oint., Eye drops.
• Neomycin is not absorbed into the blood stream; it’s usually used with lactulose in
the treatment of hepatic encephalopathy.
3. Tobramycin is also found as eye drop or in combination of eye drops.
5.1.7- Macrolides (Bacteriostatic antibiotics)
1. The Macrolides have an antibacterial spectrum that is similar but not identical to that of
penicillin; these include Erythromycin, Azithromycin and Clarithromycin, they are the 1st
choice as an alternative to penicillin in individuals allergic to β-lactam antibiotics.
2. About Erythromycin: it is given 4 times daily.
➢ Has a prokinetic effect, it improves gastric emptying and symptoms from delayed gastric
emptying.
➢ I.V. administration is associated with a high incidence of thrombophlebitis; however, the
incidence of thrombophlebitis reported with I.V. administration of Azithromycin is less than
1%; Erythromycin can cause fatal levels of digoxin, Terfenadine, and theophylline leading to
QT prolongation and sudden death. (3)
3. About Azithromycin: it’s given once daily.
➢ Azithromycin is slightly less activity than erythromycin against Gram-positive bacteria,
but enhanced activity against some Gram-negative organisms.
➢ It has a long half-life, and once daily dosage is recommended.
➢ Azithromycin capsules must be given on an empty stomach (an hour before food or 2 hours
after food) while Azithromycin tablet and Susp. are given without regard to meal.
➢ Can cause irregular heart activity and result in a fatal heart rhythm (QT prolongation);
it’s already been banned in some countries especially for pediatrics.
4. About Clarithromycin: it’s given twice per day.
➢ Clarithromycin has slightly greater activity than the parent compound.
➢ Clarithromycin is one of the components of triple therapy for eradication of H. Pylori (a
bacterium that cause ulcer).
➢ Co-administration with Cabergoline is C.I.; its causes severe Vasospasm.
5. Side effects of Macrolides include: Epigastric distress, Cholestatic jaundice, Ototoxicity,
(Transient deafness)
➢ Macrolides should be used with caution in patients with a predisposition to QT interval
prolongation (including electrolyte disturbances and concomitant use of drugs that prolong
the QT interval). (also see notes below)
➢ Macrolides may aggravate myasthenia gravis.
Azithromycin Tab , Cap Zithromax , Zithrocan
® ® 250 mg , 500 mg
Susp. Azi-Once , Azro
® ® 100 mg/5 ml
Inj. Powder 500 mg
Clarithromycin Tab Biaxin ® 500 mg
Susp. 125 mg/5 ml , 250 mg/5 ml
Erythromycin * Tab E-Mycin ® 200 mg , 250 mg , 500 mg
Susp. Erythrodar ® 125 mg/5 ml , 200 mg/5 ml
Inj. Powder 500 mg , 1 gm
Telithromycin Tab Ketek® 400 mg
Roxithromycin Tab Roxithin , Biaxsig
® ® 150 mg , 300 mg
Miocamycin Tab, Susp. Miocamen ® 600 mg (tab), 200 mg/5 ml
Josamycin Tab Josaxin 500 mg
Spiramycin Tab Rovamycin , Rovac
® ® 1.5 & 3 million I.U
Cap 250 mg , 500 mg , 1 gm
Inj. 500 mg , 1 gm
Supp. 250 mg , 500 mg
Fidaxomicin Tab Dificid® 200
Troleandomycin Cap Tao , Triocetin
® ® 250 mg , 500 mg
* Erythromycin is also formulated as skin gel/cream, mainly used for acne.
** Fidaxomicin is related to Macrolides (Macrocycles), it’s bactericidal against C. Difficile.
Extra Notes:
1. Roxithromycin is not available in the USA, but available in Australia, Europe; it possesses an
antimalarial activity, and currently undergoing clinical trials for the treatment of male-
pattern hair loss.
2. Spiramycin is still considered as an experimental drug in the USA, but can sometimes be
obtained by special permission from the FDA for toxoplasmosis in the first trimester of
pregnancy, however it has been used in Europe since the year 2000, where it is mostly
marketed to dentists for mouth infections.
• Spiramycin comes with Metronidazole in a combination known as Rodogyl® tab, which
contains (Metronidazole 125 mg; Spiramycin 750,000 I.U.).
3. Fidaxomicin is non-systemic, meaning it is minimally absorbed into the bloodstream, it has
demonstrated selective eradication of pathogenic Clostridium Difficile with minimal
disruption to the multiple species of bacteria that make up the normal, healthy intestinal flora.
5.1.8- Quinolones (Bactericidal antibiotics)

1. These include Nalidixic acid, Norfloxacin, Ciprofloxacin, Gatifloxacin, Ofloxacin,
Levofloxacin, Moxifloxacin.
2. About Nalidixic acid:
➢ It is used mainly in the treatment of lower urinary-tract infections in pediatrics, (but it
should be avoided in infants less than 3 months old).
➢ Withdrawn from USA and no longer used there.
3. About Ciprofloxacin: given twice daily
➢ It is the drug of choice for Typhoid fever.
➢ Should not be taken with Dairy products (interfere with the absorption).
4. Norfloxacin should be taken on an empty stomach.
5. About Levofloxacin: given once daily
➢ Cause a rare but serious adverse reaction such as spontaneous tendon ruptures and
irreversible peripheral neuropathy.
➢ Contraindicated in patients with epilepsy or other seizure disorders; as it’s a GABA
antagonist which cause imbalance between stimulation/inhibition, thus cause convulsions.
6. About Moxifloxacin: given once daily
➢ It has been associated with QT interval prolongation and life-threatening hepatotoxicity.
➢ Not active against Pseudomonas Aeruginosa or Methicillin-resistant Staphylococcus
Aureus (MRSA).
7. Disadvantage of the quinolones:
a) Cause acute hemolytic anemia when taken by individuals with Glucose 6-phosphate
dehydrogenase (G6PD) deficiency, or any hemolytic anemia (thalassemia).
b) Cause Glycemic reactions including hypoglycemia (within 3 days) and hyperglycemia
(Within 4-10 days) can occur in ~1% of patients on oral hypoglycemic or insulin.
c) Concurrent use with (NSAIDs) may increase the risk of CNS stimulation (seizures).
d) May produce prolonged QT interval (cause accumulation of K inside the cardiac muscles)
when administered with antiarrhythmic agents; (Gemifloxacin, Moxifloxacin) should be
avoided in patients with known prolongation of the QTC interval, with uncorrected
hypocalcemia, or who are receiving class IA or class III antiarrhythmic drugs.
8. They are generally not recommended for use in children under 18 years, adolescents, and
pregnant or breast-feeding women because of their propensity to cause joint erosions and
dwarfism, Although FDA has licensed ciprofloxacin in ages below 18 ONLY in: Complicated
urinary tract infections (UTI), Pyelonephritis and Post-exposure treatment for inhalation
anthrax.
1 generation Fluoroquinolones
st
Nalidixic acid Cap Neggram® , Naldexin® 500 mg

Susp. Negramon ® 300 mg/5 ml
Norfloxacin Tab Noroxin® , Utenor® 400 mg
nd
Ciprofloxacin Tab Cipro® , Ciprodar® 250 mg , 500 mg , 750 mg

Tab ER Bactiflox® 500 mg , 1000 mg
Infusion Solu. 200 mg , 400 mg
Ofloxacin Tab Floxin ® 200 mg , 300 mg , 400 mg
Lomefloxacin Tab Maxaquine , Okacin
® ® 400 mg
rd
Levofloxacin Tab Levaquin® , Tavacin® 250 mg , 500 mg , 750 mg

Inj. Solu. Tavanic ® 500 mg/20 ml , 750 mg/30 ml
Sparfloxacin Tab Zagam ® 100 mg , 200 mg , 400 mg
Grepafloxacin Tab Raxar ® 200 mg
th
Moxifloxacin Tab Avelox® , Maxim® , Moxai® 400 mg

Inj. Solu. Avelox® 400 mg/250 ml
Gemifloxacin Tab Factive ® 320 mg
Trovafloxacin Tab Trovan , Turvel
® ® 100 mg , 200 mg
Gatifloxacin Tab Tequin ® 200 mg , 400 mg
Inj. Solu. 400 mg/40 ml
Delafloxacin Tab , Vial Baxdela ® 450 mg (tab) , 300 mg (vial)
Extra Notes:
1. Gatifloxacin has been associated with a higher incidence of dysglycemia, it was withdrawn
from the Markets in March 2006 due it can cause life threatening side effects including serious
diabetes, hallucinations, liver damage and purpura, Gatifloxacin is currently available only as an
ophthalmic solution.
2. Lomefloxacin Brand Company discontinued its manufacturer in 2008, due it forms a
magnesium chelate with itself during long shelf storage; The chelate is formed between the 2-
carbonyl groups of two separate Lomefloxacin molecules, (It destroys itself), But generic
formulas are still available.
3. Sparfloxacin is limited in use due it has a controversial safety profile, as (Prolonged QT interval,
Torsade’s de pointes, Seizures); it is no longer available in the USA.
4. Grepafloxacin was withdrawn worldwide from markets in 1999, due to its side effect of
lengthening the QT interval, leading to cardiac events and sudden death.
5. Delafloxacin was approved by FDA in 2017 used to treat acute skin and skin structure infections.
Some Quinolones are formulated as ophthalmic solutions as:
Ciprofloxacin Eye drop/Oint. Ciprodar® , Ciloxan® 0.3% (both)
Ofloxacin Eye drop Ocuflox® 0.3%
Norfloxacin Eye drop Chibroxin®, Apiflox® 0.3%
Lomefloxacin Eye drop Okacin® 0.3%
Levofloxacin Eye drop Iquix® , Quixin® , Vefloxin® 0.5%
Moxifloxacin Eye drop/Oint. Vigamox®, Moxeza®, Moxicip® 0.5%
Besifloxacin Eye drop Basivance® 0.6% (5 ml)
Gatifloxacin Eye drop Zymar® , Tequin® , Zymaxid® 0.3% , 0.5%
5.1.9- Urinary Tract Antiseptics (Nitrofurantoin, Methenamine, Fosfomycin)
These agents tend to concentrate in the renal tubules and bladder, these agents exert local
antibacterial effects; most do not achieve blood levels high enough to treat systemic infections.
1. Nitrofurantoin (bacteriostatic) is used in the treatment and prophylaxis urinary-tract
infections (UTI), not recommended for the treatment of pyelonephritis and prostatitis.
a. It is given orally, 2 or 3 times daily, with food or milk.
b. Any prophylactic dose of antibiotic for UTI should be given at bedtime.
c. May cause a brownish discoloration of the urine.
d. Should not be taken with an Alkaline effervescent (which is usually given to treat kidney
stones); due its only active in acidic environment.
e. Has Pregnancy Category B (safe), it’s one of the few drugs commonly used in pregnancy
to treat UTIs, but Contraindicated in pregnancy at term or ≥ 38 weeks pregnant due to
the potential risk of hemolytic anemia in the newborn.
f. Also contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency
(G6PD) or any type of hemolytic anemia because of risk of intravascular hemolysis
resulting in more severe anemia.
2. Methenamine (bactericidal) decomposes at an acidic pH of 5.5 or less in the urine, thus
producing formaldehyde, which acts locally and is toxic to most bacteria.
a. Urea-splitting bacteria that alkalinize the urine, such as Proteus species, are usually
resistant its action; thus; used to treat lower UTIs but is not effective in upper UTIs.
b. Contraindicated with Sulfonamides (co-trimoxazole).
3. Fosfomycin (bactericidal) used only for UTI and prostatitis, pregnancy Category (B).
a. It’s used (off-label) in combination with tobramycin to treat lung infections in patients
with cystic fibrosis; It’s not recommended for children and pediatrics.
b. Dosed as 3 gm once for uncomplicated UTI, and 3 gm every 2 days for 3 doses in
complicated UTI, and 3 gm every 3 days for 21 days in prostatitis.
Nitrofurantoin Cap Macrobid® , Uvamin® 50 mg , 75 mg , 100 mg
Oral Susp. Furadantin®, Urodantin® 25 mg/5 ml
Methenamine Tab Hiprex® , Urex® 500 mg , 1 gm
Fosfomycin Sachets Monurol® , Berny® 3 gm
5.1.10-Lincosamides (Lincomycin and Clindamycin) (Bacteriostatic)

1. Active against Gram-positive cocci, and also against many anaerobes, the main indication for
the use of Lincosamides is now in the treatment of severe anaerobic infections.
2. Clindamycin is much better absorbed from the GIT than Lincomycin, they both penetrate
well into bone and have been used successfully in osteomyelitis.
➢ Clindamycin also exhibits some activity against parasitic protozoa, and has been used in
toxoplasmosis and malaria.
3. The capsules should be taken with a glass of water.
4. Clindamycin have also been used topically in the treatment of acne vulgaris.
5. Patients should discontinue immediately and contact doctor if diarrhea develops,
(Lincosamides are reported to produce diarrhea, in some patient’s severe antibiotic-associated
or pseudomembranous colitis may develop during therapy or up to several weeks after it, and
has proved fatal).
Lincomycin Cap Lincocin® , Lincodar® 250 mg , 500 mg
Vial (Solu.) 300 mg/2 ml , 600 mg/2 ml
Clindamycin Cap Cleocin® , Clindamycin® 75 mg , 150 mg
Inj. Solu. (Amp) 150 mg/ml (600 mg/4 ml)
Vag. Cream/Supp. Clindamax® 2% (cream) , 100 mg (Supp.)
5.1.11- Sulfonamides and Trimethoprim (Bacteriostatic)
1. Sulfamethoxazole and Trimethoprim are used in combination (as co-trimoxazole) because of
their synergistic activity; Trimethoprim is also used alone particularly in the treatment of
infections of the urinary and respiratory tracts.
➢ A report showed increase sudden death in patients over 60 years who is taking Co-
trimoxazole with ARBs or ACEIs; so, avoid this combination always.
2. Sulfamethoxazole is from a family called (Sulfonamides) or the Sulpha drugs, the same family
of sulfasalazine that is used for the IBD, Sulfonamides are inhibitors of folate synthesis.
3. This group should not be given to infants below 6 weeks of age because of the risk of
kernicterus, also Should not be given to pregnant at term or nursing Mother (it passes
throw the placenta and excreted in the milk)
➢ They Cause kernicterus; because sulfa drugs displace bilirubin from binding sites on
serum albumin, the bilirubin is then free to pass into the CNS, because the baby’s blood
brain barrier is not fully developed
4. This group should be avoided by people with G6PD deficiency or any type of hemolytic
anemia, causes blood dyscrasias, Granulocytopenia and thrombocytopenia.
5. Other side effects include: Crystalluria and hematuria that possibly leading to urinary tract
obstruction; (Adequate fluid intake and urine alkalization can prevent or minimize this risk),
also cause Hypersensitivity reactions (rashes, angioedema, and Stevens-Johnson syndrome).
A) Sulfonamides
Mafenide * Cream, Topical Solu. Sulfamylon ® --------------
Silver sulfadiazine Cream Silvadene ® 1%
*
Sulfisoxazole Tab , Susp Gantrisin ® 500 mg , 500 mg/ml
Sulfadiazine ** Tab Lantrisul , Neotrizine 500 mg
® ®
Sulfadoxine Tab Sulfaxine® 500 mg

Sulfasalazine See chapter 2 , Section 9 , Drugs for IBD
* Mafenide and Silver sulfadiazine are usually used in burns treatment as topical antibiotics.
** Sulfadiazine is also used for the treatment of toxoplasmosis.
B) Folate reduction inhibitors (Trimethoprim, Pyrimethamine)

Trimethoprim Tab ------------ 100 mg
Pyrimethamine * Tab Daraprim® 25 mg
* Pyrimethamine is also an anti-malarial; mainly is used for the treatment of toxoplasmosis, it
also comes in combination with Sulfadoxine.
C) Combinations
Sulfamethoxazole + Tab Bactrim®, Septrim®, Cotrim® (80 mg + 400 mg) &
Trimethoprim (160 mg + 800 mg)
Oral Solu. (80 mg + 400 mg)/5 ml
Sulfisoxazole + Oral Susp. Pediazole ® (600 mg + 200 mg)/5 ml
Erythromycin
Pyrimethamine + Tab Fansidar® 25 mg + 500 mg
Sulfadoxine
* Fansidar® it is no longer recommended as a routine preventative, but only to treat serious
malaria infections or to prevent them in areas where other drugs may not work; it’s also given for
the treatment of Toxoplasmosis.
5.1.12- Antimycobacterials (drugs used for Tuberculosis)
1. Tuberculosis is an infectious bacterial disease acquired by inhaling the tuberculosis bacilli
that are present in the spray of a sneeze or cough from an actively infected person, it may
also, rarely, be acquired from infected unpasteurized cow’s milk; The disease usually starts in a
lung and takes one of two forms: primary or reactivated infection.
➢ In 90-95% of those with a primary infection, the body’s immune system suppresses the
infection but does not kill the bacilli, they remain alive but dormant and may cause the
reactivated form of the disease, after they are reactivated, the tuberculosis bacilli may
spread via the lymphatic system and bloodstream throughout the body.
2. Tuberculosis is treated in two phases: an initial phase using 4 drugs and a continuation phase
using 2 drugs:
➢ Initial Phase: The treatment of choice for the initial phase is the daily use of Isoniazid,
Rifampicin, Pyrazinamide and Ethambutol, these drugs should be continued for 2
months.
➢ Continuation phase: treatment is continued for a further 4 months with Isoniazid and
Rifampicin, Longer treatment duration is necessary for meningitis, HIV patients.
3. For Latent Infection:
1. Isoniazid 300 mg daily in adults is the preferred treatment generally given for 9 months
2. Rifampicin 600 mg daily for 4 months, can be used when isoniazid resistance is suspected
or when the patient cannot tolerate isoniazid.
3. Rifabutin 300 mg daily, may be substituted for rifampin for patients at high risk of drug
interactions.
4. Special Populations:
➢ TB Meningitis: Isoniazid, Pyrazinamide, Ethionamide, and Cycloserine penetrate the
cerebrospinal fluid readily, patients with CNS TB are often treated for longer periods (9–12
months). With the addition of Dexamethasone injection (used for three days only).
➢ Extra pulmonary TB: Can be treated with same regimens but typically treated for 9 months.
➢ Children TB: Extend treatment to 9 months; Pediatric doses of drugs should be used.
➢ Pregnant Women: The usual treatment of pregnant women is Isoniazid, Rifampicin and
Ethambutol for 9 months.
5. Common TB medications:
Drug Usual dose per day Common side effect
Isoniazid 300 mg Hepatitis, Peripheral neuritis, psychotic episodes,
vertigo
Rifampicin 600 mg Flu-like symptoms, acute renal failure, shock
Ethambutol According to Kg: Optic neuritis, red/green color blindness, Peripheral
800 mg (40–55 kg) neuritis and thrombocytopenia.
1,200 mg (56–75 kg) And uric acid retention.
1,600 mg (76–90 kg)
Pyrazinamide According to Kg: hepatotoxicity including fever, anorexia,
1,000 mg (40–55 kg) hepatomegaly, splenomegaly, jaundice
1,500 mg (56–75 kg) And uric acid retention.
2,000 mg (76–90 kg)
1. Rifampicin (also Called Rifampin in USA) is used mainly for Tuberculosis (in combination with
other Antituberculosis drugs) and in Brucellosis (in combination with Doxycycline for 6
weeks), also used for Leprosy.
➢ It must be taken 30 to 60 minutes before food.
➢ Rifampicin causes a harmless orange-red discoloration of the urine, feces, sweat,
saliva, sputum, tears, and other body fluids.
2. Isoniazid is a synthetic analog of pyridoxine, a common side effect of Isoniazid is Peripheral
neuritis (manifesting as paresthesias of the hands and feet), appears to be due to a relative
pyridoxine deficiency, most of the toxic reactions are corrected by supplementation of 25 to 50
mg per day of Pyridoxine (vitamin B6).
1st line treatment drugs
Rifampicin Cap Rifadin® , Rimactane® 150 mg , 300 mg
Inj. Powder 600 mg
Isoniazid Tab Nydrazid® 50 mg , 100 mg
Inj. Solu. 25 mg/ml , 100 mg/ml
Ethambutol Tab Myambutol® 100 mg , 400 mg
Pyrazinamide Tab Zinamide® 500 mg
Rifabutin Cap Mycobutin® 150 mg
Rifapentine Tab Priftin® 150 mg
2nd line treatment drugs
Amino salicylic acid Granules Paser® 4 gm/packet
Capreomycin Inj. Powder Capastat® 1 gm/vial
Clofazimine Cap Lamprene® 50 mg
Cycloserine Cap Seromycin® 250 mg
Ethionamide Tab Trecator® 250 mg
Bedaquiline Tab Sirturo® 100 mg
Pretomanid Tab ------------- 200 mg
Extra Notes:
1. Aminoglycosides, Fluoroquinolones, Macrolides maybe used as 2ndary line treatments.
2. Rifampin, Rifabutin, and Rifapentine are all considered to be (Rifamycins), a group of structurally
similar macrocyclic antibiotics, which are first-line drugs for tuberculosis.
3. Capreomycin Adverse effects include nephrotoxicity and 8th cranial auditory vestibular nerve
toxicity; this drug should not be given with streptomycin or other drugs that may damage the
auditory vestibular nerve. Patients on this drug will often require audiology tests.
4. Clofazimine has a marked anti-inflammatory effect and is given to control the leprosy.
5. Cycloserine is also being tested as an adjuvant to exposure therapy for anxiety disorders (e.g.
phobias), depression, obsessive-compulsive disorder and schizophrenia, it has been experimentally
used for treatment of Gaucher's disease.
6. Bedaquiline (approved 2013) is indicated for the multidrug-resistant TB in adults 18 years and
older when other alterations are not available.
a. Bedaquiline has a black-box warning for arrhythmias, as it may induce long QT syndrome
by blocking the hERG channel.
Combination products for Tuberculosis:

Rifamate® Cap Rifampicin + Isoniazid 300 mg + 150 mg
Bunex®, Coxrid® Tab Ethambutol + Isoniazid 400 mg + 150 mg
Rifater® Tab Rifampicin + Isoniazid + 120 mg + 50 mg +
Pyrazinamide 300 mg
Bunex E®, Tab Ethambutol + Isoniazid + 275 mg + 75 mg +
Actuate 3® Rifampicin 150 mg
Zucox 4® Tab Ethambutol + Isoniazid + 275 mg + 75 mg +
Actuate 4® Pyrazinamide + Rifampicin 400 mg + 150 mg
* Combination products increase patient complaints, but it’s usually costs more than each
individual drug alone combined with another.
Tuberculosis Prevention
A vaccine prepared from an artificially weakened strain of cattle tuberculosis bacteria can provide
immunity from tuberculosis by provoking the development of natural resistance to the disease.
➢ The BCG (Bacille Calmette-Guérin) vaccine is a form of tuberculosis bacillus that provokes
the body’s immune response but does not cause the illness because it is not infectious.
➢ The vaccine is usually injected into the upper arm; A small pustule usually appears 6 to 12
weeks later, by which time the person can be considered immune.
5.1.13- Drugs used to treat Leprosy

1. Leprosy (Called in the USA: Hansen’s disease) is primarily a granulomatous disease of the
peripheral nerves and mucosa of the upper respiratory tract; skin lesions are the primary
external sign, (Caused by Mycobacterium leprae).
2. If left untreated, leprosy can be progressive, causing permanent damage to the skin, nerves, limbs
and eyes, leprosy does not cause body parts to fall off, although they can become numb or
diseased as a result of secondary infections; these occur as a result of the body's defenses being
compromised by the primary disease.
3. Secondary infections, in turn, can result in tissue loss causing fingers and toes to become
shortened and deformed, as cartilage is absorbed into the body.
4. The World Health Organization (WHO) recommends the triple-drug regimen of Dapsone
(bacteriostatic), Clofazimine (bactericidal), and Rifampin for 6 to 24 months.
Dapsone Tab Dapsone® 25 mg , 100 mg
Topical Gel Aczone® 5%, 7.5% (30, 60 gm tube)
Clofazimine Cap Lamprene® 50 mg
Rifampicin Cap Rifadin® 150 mg , 300 mg
Inj. Powder 600 mg
Notes:
1. Dapsone causes hemolysis, especially in patients with (G6PD) or in any other type of
hemolytic anemia, also causes Methemoglobinemia and peripheral neuropathy.
a. Dapsone is the drug of choice for treating leprosy.
b. Dapsone Topical Gel is used for the treatment of Acne.
c. Maybe used for the treatment of toxoplasmosis.
d. Dapsone may develop erythema nodosum leprosum (a serious and severe skin
complication of leprosy); The latter is treated with corticosteroids or thalidomide.
2. Clofazimine has an anti-inflammatory activity; thus, erythema nodosum leprosum does not
develop, but Patients may develop a red-brown discoloration of the skin.
a. Urine, sweat, and other body fluids may be discolored.
b. Should be taken with food only.
Clinical Tip
Increasing bacterial resistance against current antibiotics and lack of new molecules to combat
bacterial resistance are key challenges to global health. There is, therefore, a continuing need to
develop new antibiotics. Teixobactin, a cyclic undecapeptide, displays excellent antibacterial
activities against a range of pathogenic bacteria, such as methicillin-resistant Staphylococcus aureus
(MRSA) and Mycobacterium tuberculosis. Interestingly, it operates by multiple modes of actions and
is bactericidal toward S. aureus without detectable resistance; This unique combination of wide
Gram-positive activity coupled with its inability to elicit resistance make it a very attractive molecule
for antimicrobial therapeutic development.

5.1.14- Metronidazole, Tinidazole and relatives (Bactericidal)
1. They are active against anaerobic bacteria and protozoa (Entamoeba histolytica, Giardia
lamblia); Tinidazole is similar to metronidazole but has a longer duration of action.
➢ Metronidazole when used orally is effective for the treatment of Clostridium difficile
infection.
➢ Topical metronidazole is used in the treatment of Acne and Rosacea.
➢ It also (topically) reduces the odor produced by anaerobic bacteria in fungating tumors.
2. Metronidazole and Tinidazole tablets are taken with or after food.
• They can produce nausea and an unpleasant metallic taste.
• The patient may experience headaches if used metronidazole or Tinidazole for the
first time, (you may give Paracetamol for this case).
• Metronidazole and Tinidazole are contraindicated in the 1st trimester of
pregnancy, after that it’s OK to use them.
• Not recommended for nursing mother.
• Tinidazole may be given as a single dose of 2 gm (4 tablets) for some infections
including (Amebiasis, Giardiasis, Trichomoniasis and Bacterial Vaginosis).
• In clinical studies; Tinidazole is more effective than Metronidazole.
3. Secnidazole offers the advantage of once daily dose, (its half-life is 19-27 hours).
➢ Drug of choice for patients with hepatic Amebiasis.
➢ Can be used for Amebiasis, Giardiasis, Trichomoniasis and Bacterial Vaginosis; with less risk
of drug resistance
4. Ornidazole offers the advantages of both once daily dose, and a higher efficacy against
anaerobic bacterium; although it’s not FDA approved yet.
➢ In Europe it’s used to treat infections of the stomach, intestine, urinary tract and genital area,
also used to prevent possible infections during a surgical procedure.
➢ It has also been investigated for use in Crohn's disease after bowel resection.
5. When given with alcohol, metronidazole and Tinidazole may provoke a disulfiram-like
reaction (occurs as abdominal cramps, nausea, vomiting, severe headache, psychotic reaction,
nervousness, flushing of the skin, tachycardia and shortness of breath).
• This is actually used clinically to treat alcohol addiction; they give metronidazole to the
addict, and each time he drinks alcohol he will have a disulfiram-like reaction, without
knowing that metronidazole did this to him; he is then forced to stop drinking or he will suffer
this painful sensation over and over again each time he drinks.
Metronidazole Tab Flagyl®, Flazole® 250 mg , 500 mg
Syrup Flagyl® 200 mg/5 ml
Infusion Solu. 500 mg/100 ml
Mouth Gel Metrogyl® ------------
Vaginal Gel Vandazole® 0.75% (37.5 mg)
Va
Vaginal Supp. 500 mg , 1 gm
Tinidazole Tab Fasigyn®, Tindamax® 500 mg
Secnidazole Tab Flagentyl®, Sindose® 500 mg
Oral Granules Solosec® 2 gm
Ornidazole Tab Avrazor® , Borneral® 500 mg
Oral Susp. Ornida® 125 mg/5 ml
Vaginal Supp. Ornidaz® 500 mg
Gel 10 mg
Combination Products:
Tinidazole + Norfloxacin Cap Tinidol plus® 600 mg + 400 mg
Secnidazole + Itraconazole Cap Sporasec® , Itrasec® 166.6 mg + 33.3 mg
Secnidazole + Albendazole Tab C Cobistal® , Prothelmint® 1 gm (2 tabs) + 200 mg (2 tabs)
Secnidazole + Fluconazole Tab Gynflu® 500 mg + 37.5 mg
Tab Gynflu D® 1000 mg + 75 mg
Ornidazole + Ofloxacin Tab Bactorax OZ® , Chekmet® 500 mg + 200 mg
Susp. (125 mg + 50 mg)/5 ml
Ornidazole + Ciprofloxacin Tab Orcipol® , Repixol® 500 mg + 500 mg
Ornidazole + Levofloxacin Tab Lebact-O® 500 mg + 200 mg
Ornidazole + Gatifloxacin Tab Diragyl® 500 mg + 200 mg
Susp. Asoget OZ® 30 ml , 60 ml
Ornidazole + Cefixime Tab Cefit-OZ® 500 mg + 200 mg
5.1.15-Other Antibacterials (3-4)

A) Glycopeptides: (Bactericidal)
These include: Vancomycin, Telavancin, Dalbavancin, Oritavancin and Teicoplanin: which
are active against aerobic and anaerobic Gram-positive bacteria including multi-resistant
staphylococci.
• Vancomycin is not absorbed after oral administration. (not active against Gram -ve)
a. It has a long duration of action and can therefore be given every 12 hours.
b. Vancomycin given by mouth for 10–14 days is effective in the treatment of
Clostridium difficile infection.
c. Side effects of Vancomycin include: fever, chills, and/or phlebitis at the infusion
site. Flushing (“red man syndrome”) and shock result from histamine release
associated with a rapid infusion.
d. If an infusion-related reaction occurs, slow the infusion rate to administer
Vancomycin over 2 hours, increase the dilution volume, and/or pre-treat with an
antihistamine 1 hour prior to administration.
• Telavancin cause taste disturbances, nausea, vomiting, insomnia, and foamy urine.
a. Causes Nephrotoxicity: New onset or worsening renal impairment has occurred;
monitor renal function in all patients
b. Avoided in pregnancy, it showed teratogenic effects in animal studies.
• Teicoplanin is indicated in potentially serious Gram-positive infections.
a. Given once daily, has a very long half-life (45-70 hrs.)
b. Associated with a lower incidence of nephrotoxicity than vancomycin.
c. Causes Thrombocytopenia.
d. Teicoplanin should not be used during pregnancy.
• Dalbavancin is given by 2-dose regimen of 1000 mg I.V. followed 1 week later by 500 mg
I.V. (should be infused I.V. over 30 min.), Oritavancin is given as a single 1200 mg dose
administered I.V. over 3 hours; both have a very long half-life (about 6-11 days), which
supports once weekly I.V. dosing (single or double dose only).
Vancomycin Vial (powder) Vancocin® 500 mg , 1 gm
Telavancin Vial (powder) Vibativ® 250 mg , 750 mg
Teicoplanin Vial (powder) Targocid® 200 mg , 400 mg
Dalbavancin Vial (powder) Dalvance®, Xydalba® 500 mg
Oritavancin Vial (powder) Orbactiv® 400 mg
B) Quinupristin/Dalfopristin: mixture of two streptogramins in a ratio of 30% to 70%, they
synergistically interrupt protein synthesis; The combination drug is (bactericidal) and has a long
post-antibiotic effect, mixed and administered only in 5% D5W solution, insoluble in NS 0.9%.
• Adverse effects include: Arthralgia and myalgia, Hyperbilirubinemia.
• Mild to life-threatening pseudomembranous colitis has been reported.
Quinupristin + Inj. powder Synercid® (150 mg + 350 mg)/10 ml
Dalfopristin
C) Tedizolid: it’s an oxazolidinone-class antibiotic, used for the treatment of acute bacterial skin and
skin structure infections, it is 4-16-fold more potent against staphylococci and enterococci compared
to Linezolid (see below).
➢ The recommended dosage for treatment is 200 mg once daily for six days.
Tedizolid Tab Sivextro® 200 mg
Vial (powder) 200 mg/vial
D) Linezolid: used for the treatment of serious infections caused by Gram-positive bacteria that are
resistant to several other antibiotics, it’s also used to treat tuberculosis.
• Linezolid is bacteriostatic against Enterococci and Staphylococci, and bactericidal
against Streptococci.
• Common adverse effects of short-term use include headache, diarrhea, and nausea.
Long-term use, however, has been associated with serious adverse effects; linezolid can
cause bone marrow suppression and low platelet counts, particularly when used for
more than two weeks; Irreversible peripheral neuropathies and optic neuritis
(causing blindness) is associated with greater than 28 days of use.
• Inhibit MAO activity, and can precipitate serotonin syndrome in patients concomitantly
taking SSRIs, the condition was reversible when the drug was suspended.
Linezolid Tab Zyvox® 600 mg
Infusion Solu. 2 mg/ml
E) Nifuroxazide: oral nitrofuran antibiotic, used to treat colitis and diarrhea; has a spectrum which
covers: Shigella, Escherichia coli, Salmonella, Staphylococci, Klebsiella, Yersinia.
Nifuroxazide Cap Ercefuryl® , Diax® 200mg
Oral Susp. Diax® , Antinal® 220 mg/5 ml
F) Rifaximin: is used in the treatment of traveler’s diarrhea, Irritable bowel syndrome, and
used for the prophylaxis of hepatic encephalopathy.
• Maybe combined with Lactulose for hepatic encephalopathy.
• Also used for irritable bowel syndrome (IBS) diarrhea predominant type.
• Can be taken with or without food.
Rifaximin Tab Xifaxan® , ColiDur® 200 mg , 550 mg
G) Chloramphenicol, Thiophenicol, Colistimethate, Lefamulin and Daptomycin:

• Daptomycin is bactericidal, inactivated by pulmonary surfactants; thus, it should never be
used in the treatment of pneumonia.
a. Activity similar to Vancomycin.
b. Side effects include: constipation, nausea, headache, myalgias and insomnia.
c. Discontinue Statins when giving Daptomycin (it causes myopathy, rhabdomyolysis).
• Chloramphenicol (bacteriostatic) is active against a wide range of gram-positive and
gram-negative organisms. However, because of its toxicity, its use is restricted to life-
threatening infections for which no alternatives exist.
a. Causes bone marrow suppression, Hemolytic anemia, Aplastic anemia.
b. Causes Gray baby syndrome when given to newborn infants (leads to poor
feeding, depressed breathing, cardiovascular collapse, cyanosis).
c. It’s used these days only as topical preparations as eye drop/Oint.
• Thiophenicol (bacteriostatic) is Chloramphenicol analog that have an advantage of not
causing Aplastic anemia, some drug references consider it as a veterinary antibiotic,
but it’s approved for human use in Italy and Argentina.
• Colistimethate has bactericidal activity against aerobic gram-negative micro-
organisms; it is particularly indicated when the infection is caused by sensitive strains of
Pseudomonas aeruginosa; either by I.V. injection or by inhalation of the powder in the
vial content.
• Lefamulin (bactericidal), approved in 10/2019 by the FDA; it is used to treat adults with
community-acquired bacterial pneumonia.
Daptomycin Vial (powder) Cubicin® 500 mg
Chloramphenicol * Cap Biomicin® 250 mg
Inj. (vial) Chloromycetin® 1000 mg
Eye drop/Oint. Phenicol® , Optrex® 1%
Thiophenicol Inj. (vial) Thiophenicol® 750 mg
Colistimethate Inj. (I.V. or Inhale) Xylistin® 1 million IU
Lefamulin Tab Xenleta® 600 mg
I.V. Solu. 150 mg/15 ml
* The Manufacture of oral chloramphenicol was stopped in the USA in 1991.
5.1.16- Topical antibiotics

These include:
1. Fusidic acid: (bacteriostatic), the only indication for their use is in infections caused by
penicillin-resistant staphylococci; It’s also used in the treatment of burns.
a. Occasionally used as a treatment for acne.
b. Comes in combination with hydrocortisone or betamethasone.
2. Bacitracin: (bacteriostatic), used only for the prevention of superficial skin infections caused by
the susceptible bacteria. (Not substantially absorbed from intact or denuded skin, wounds, or
mucous membranes).
3. Mupirocin: used for furuncle, impetigo, open wounds, do not apply to eyes; do not apply topical
to mucous membranes.
4. Nadifloxacin is a topical fluoroquinolone antibiotic for the treatment of acne vulgaris; It is
also used to treat bacterial skin infections, it also showed potent antibacterial activity against
methicillin-resistant Staphylococcus aureus (MRSA).
5. Mafenide and Silver sulfadiazine (see Sulfonamides above); Usually used for burns.
6. Retapamulin: for treatment of bacterial skin infections such as impetigo
7. Fusafungine: for the treatment of nasal and throat infection; It also possesses anti-
inflammatory properties.
8. Retapamulin was approved by the FDA for the treatment of bacterial skin infections such as
impetigo in adults and children older than nine months.
Fusidic acid Cream/Oint. Fucidin , Fucine ,
® ® 2%
Fucibact®
Eye Oint./Drop Fucithalmic® 1% (5 mg/Tube)
Bacitracin Oint. / Powder Baciquent ® 500 Unit/gm
Nadifloxacin Cream Nadixa , Magnis
® ® 1%
Mupirocin Cream/Oint. Bactroban®, Avoban® 2%
Mafenide Cream, Topical Solu. Sulfamylon® --------------
Silver Sulfadiazine Cream Silvadene® 1%
Retapamulin Oint. Altabax ® 1% (5 gm , 10 gm Tubes)
Ozenoxacin Cream Xepi ® 1%
Fusafungine Oro/nasal Spray Locabiotal , Bioparox
® ® 1% (500 mcg)
Retapamulin Oint. Altabax 1%
Note1: Combination products of some topical Antibacterials:

Scientific name(s) D. Form Trade name concentration
Fusidic acid + Cream Fucibet® , 2% + 0.1% (15 gm tube)
Betamethasone Fucibact B®
Fusidic acid + Cream Fucidin H® 2% + 1% (15 gm tube)
Hydrocortisone
Polymyxin B + Bacitracin Cream/Oint Polysporin® (10,000 unit + 500 unit) per gm
Neomycin + Polymyxin B + Cream, TAO® (3.5 mg + 5,000 unit + 400 unit)
Bacitracin Oint. Per 1 gm
Neomycin + Polymyxin B + Oint. TriBiozene® (3.5 mg + 10,000 unit + 500 unit
Bacitracin + Pramoxine + 10 mg ) per 1 gm
Note2: Other Antibacterials that can be formulated as skin products include:

• Erythromycin, Gentamycin, Neomycin, Tetracycline, Clindamycin, Metronidazole and Dapsone.

5.2-Antifungal drugs
a. The most common fungal infections are caused by the tinea group, these include tinea pedis
(athlete’s foot), tinea cruris (jock itch) tinea corporis (ringworm), and tinea capitis (scalp
ringworm).
➢ They are spread by direct or indirect contact with infected humans or animals.
b. Problems may also result from the proliferation of a fungus normally present in the body; the
most common example is excessive growth of candida, a yeast that causes thrush infection of the
mouth, vagina, bowel; It can infect other organs if spread through the body via the bloodstream.
➢ Overgrowth of candida may occur in people taking antibiotics or oral contraceptives, in
pregnant women, or in those with diabetes or immune system disorders.
1. Antifungals are classified as:
A) Systemic antifungals: as (Amphotericin B, Griseofulvin, Fluconazole, Itraconazole).
B) Topical antifungals: as (Tolnaftate, Sertaconazole, Ciclopirox).
C) Vaginal antifungal: as (Miconazole, Terconazole, Tioconazole).
2. Or they can be classified on their pharmacological structure as:
Class Examples
Echinocandin antifungals Nidulafungin, Caspofungin, Micafungin,
Polyene antifungals Amphotericin B, Nystatin.
Triazole antifungals Fluconazole, Itraconazole, Posaconazole, Voriconazole
Others Flucytosine, Griseofulvin
3. The table below shows some indications for some antifungals:
4. Some systemic antifungals are also available as topical products, also systemic antifungals maybe
used for vaginal infections.
5. Fluconazole is used 150 mg as a single oral dose for vaginal candidiasis, while for recurrent
vulvovaginal candidiasis: Initially 150 mg every 72 hours for 3 doses, then 150 mg once weekly
for 6 months.
6. Itraconazole, Fluconazole and ketoconazole must be given after food.
7. The use of ketoconazole may be restricted from the oral use due to the risk of
hepatotoxicity (reported very rarely); also ketoconazole has anti-androgenic effects causing
Gynecomastia, decreased libido, impotence, oligospermia, and decreased testosterone
levels in men, and menstrual irregularities in women, result from the blocking of Androgen
and adrenal steroid synthesis, leading to decreased testosterone and cortisol production.
➢ Ketoconazole is topically effective for treatment of seborrheic dermatitis and dandruff.
➢ 2% Ketoconazole shampoo was found to improve hair density and the size and
proportion of anagen follicles in androgenetic alopecia (AGA) and used in combination with
finasteride, to have an additive effect for AGA.
A) Systemic antifungals:
Amphotericin B Vial (powder) Ambisome® 50 mg
Flucytosine Cap Ancobon® , 5-FC® 250 mg , 500 mg
Caspofungin Inj. powder Cancidas® 50 mg , 70 mg
Anidulafungin Inj. powder Eraxis ® 50 mg
Micafungin Inj. powder Mycamine ® 50 mg , 100 mg
Fluconazole * Cap Diflucan ® 150 mg
Inj. Solu. 2 mg/ml
Itraconazole * Cap Sporanox , Inox , Omnel
® ® ® 100 mg
Ketoconazole * Tab Nizoral , Ketonaz
® ® 200 mg
Shampoo Nizoral shampoo ® 1% , 2%
Posaconazole * Tab Noxafil ® 100 mg
Oral Susp. 40 mg/ml (105 ml)
Voriconazole * Tab Vfend , Voricona-Denk
® ® 50 mg , 200 mg
Inj. powder 200 mg
Isavuconazole * Cap Cresemba ® 100 mg
(Isavuconazonium) Vial (powder) 200 mg
Terbinafine Tab Lamisil , Lamifin , Terbisil 250 mg
® ® ®
Griseofulvin Tab Grifulvin® 500 mg , 750 mg

Nystatin Tab Mycostatin ® 500,000 Units
Oral Susp. 100,000 Units
Oral Drop 100,000 Units
* Items are called Azoles.
** Voriconazole is 300 times more potent than Ketoconazole, it’s also very high in price.
Itraconazole + Secnidazole Cap Sporasec® , Itrasec® 33.3 mg + 166.6 mg
Fluconazole + Secnidazole Tab Gynflu® 37.5 mg + 500 mg
Gynflu D® 75 mg + 1000 mg
Fluconazole + Tinidazole Tab Azostat® 150 mg + 1 gm
Notes:
1. Amphotericin B (Fungistatic, Fungicidal) depending on the type of organism; it is the drug of
choice for the treatment of life-threatening systemic mycoses.
a. Act by decreasing Ergosterol content of the fungal membrane.
b. Amphotericin B has a low therapeutic index, causes: (Fever and chills, renal impairment,
Hypotension, Anemia, Neurologic effects, Thrombophlebitis), which all can be reduced by
formulating Amphotericin B as Lipid soluble formula.
➢ Premedication with a corticosteroid or an antipyretic help to prevent Fever & chills.
➢ A shock-like fall in blood pressure accompanied by hypokalemia may occur, requiring
potassium supplementation.
➢ Adding heparin to the infusion can alleviate thrombophlebitis.
c. Amphotericin B is also used in the treatment of the protozoal infection Leishmaniasis.
d. Can be used as a Topical preparation to eradicate cutaneous and mucocutaneous
candidiasis.
e. Amphotericin B parenteral use should be mixed only in dextrose 5% in water (D5W) and
should be protected from light.
f. Sometimes used in combination with Flucytosine (5-FC) for synergistic effect.
2. Flucytosine (5-FC) causes reversible neutropenia, thrombocytopenia, and dose-related bone
marrow depression, reversible hepatic dysfunction, gastrointestinal disturbances.
➢ Used in combination with Amphotericin B (it increases cell permeability, allowing more
Flucytosine to penetrate the cell, thus leading to a synergistic effect).
3. Echinocandins which include (Caspofungin, Anidulafungin, and Micafungin) interfere with
the synthesis of the fungal cell wall by inhibiting the synthesis of β (1, 3)-D-glucan, leading to lysis
and cell death, available for IV administration once daily; Micafungin does not require a
loading dose, others do.
a. Caspofungin is the first approved member of the Echinocandins class of antifungal drugs.
b. Anidulafungin significantly differs from other antifungals in that it undergoes chemical
degradation to inactive forms at body pH and temperature; Because it does not rely on
enzymatic degradation or hepatic or renal excretion, the drug is safe to use in patients with
any degree of hepatic or renal impairment.
c. Echinocandin antifungals are only active against Aspergillus spp. and Candida spp.
4. Azoles Include: (Fluconazole, Itraconazole, ketoconazole, Voriconazole, Posaconazole) all
are Fungistatic. (They disrupt fungal membrane structure and function, which inhibits fungal
cell growth); All are teratogenic, and should not be used in pregnancy.
a. Fluconazole may rarely cause serious liver disease.
b. To increase efficacy of Fluconazole for topical fungal infections; the patient should be advised
to sweat (do exercise); due the fact that Fluconazole is concentrated in the sweat.
c. Itraconazole has a -ve inotropic effect; should not be taken by patients with evidence of
ventricular dysfunction, such as congestive heart failure (CHF) or a history of CHF.
d. Voriconazole is associated with visual and auditory hallucinations, (blurred vision).
e. Posaconazole (approved 2008) must be administered with a high fat meal.
f. All Azoles must be taken after food.
5. Griseofulvin is contra-indicated in pregnancy, and women should not become pregnant
during, or within 1 month of stopping therapy; Also, men should avoid fathering a child
during and for at least 6 months after administration.
a. Griseofulvin is a fungistatic; it is effective in Tinea infections of the skin, hair, and nails
(including athlete’s foot, jock itch, and ringworm).
b. Absorption of Griseofulvin from the GIT is enhanced by reducing the particle size or when
given with a fatty meal (should be given with or after meals).
c. It possesses a vasodilator activity and may be used in Raynaud disease, and also it may be
used to treat gout.
6. Nystatin is used for oral, oropharyngeal, and perioral infections by local application in the
mouth; (will be discussed later in chapter 13), and it may be given orally for the treatment of
intestinal candidiasis.
a. Nystatin is not absorbed orally (or poorly absorbed), and act by direct contact to the fungal cells,
thus its preferred in pediatric patients and in neonates.
b. Nystatin comes in combination with many skin products/vaginal products.
B) Topical antifungals:
Duration of therapy is dependent on the site of the infection and may extend to a number of
months; (2 to 8 weeks for infections of the hair and skin, up to 6 months for infections of the
fingernails, and 12 months or more for infections of the toe nails).
1. Miconazole is also used for oral, oropharyngeal, and perioral infections by local application in
the mouth, Topical Miconazole is highly effective in vulvovaginal candidiasis, ringworm, and
other skin infections, and it has some activity against Gram positive bacteria.
2. Clotrimazole is an Azole antifungal agent
➢ The cream, lotion, or solution is used to treat dermatophytoses, superficial mycoses, and
cutaneous candidiasis.
➢ Intravaginal dosage forms are useful in treating vulvovaginal candidiasis.
➢ The lozenges, which are administered five times per day, are useful in treating oropharyngeal
candidiasis.
3. Terbinafine (Fungicidal) is indicated is used to treat dermatophytoses, superficial mycoses,
and cutaneous candidiasis, it’s also used to treat fungal infections of the toe nails and fingernails.
4. Sertaconazole, an imidazole topical antifungal; has a low antibacterial activity, and moderate
anti-inflammatory and antipruritic effects.
➢ It has a Significantly lower relapse rate than other antifungal drugs.
5. Amphotericin B is available as a 3% cream or lotion or an oral suspension that is not absorbed
through the GI tract, (usually prepared in the pharmacy).
➢ Used for oropharyngeal candidiasis, cutaneous and mucocutaneous candida infections, or
as a local irrigant for the bladder and intrapleural or intraperitoneal areas.
6. Gentian violet is a dye that possesses the ability to kill fungi, yeasts, and some gram-positive
bacteria, may cause irritation or sensitivity reactions or possibly ulceration of the mucous
membranes, if the solution is swallowed, esophagitis, laryngitis, or tracheitis may occur.
Butenafine Cream Lotrimin®, Mentax® 1%
Ciclopirox Cream, Lotion, Loprox®, Penlac® 0.77%
Gel
Shampoo 1%
Nail Lacquer 8%
Clotrimazole Cream, Lotion Canesten® , Gynomizole® , 1%
Lozenges Mycelex® 10 mg
Econazole Cream Gyno-Pevaryl® , Ecostatin®, 1%
Spectazole®
Efinaconazole Cream, Topical Solu. Topazole®, Jublia® 10%
Gel, Nail Lacquer
Amorolfine Nail Lacquer Loceryl® 5% (50 mg/ml)
Ketoconazole Cream, Gel, Foam Nizoral® , Ketonaz® 2%
Shampoo 1% , 2%
Luliconazole Cream Luzu® , Lulican® 1%
Miconazole Cream Desenex®, Fungoid®, Daktarin® 2%
Naftifine Cream, Gel Naftin® 1% , 2%
Nystatin Cream, Oint Pediaderm®, Mycostatin® 100,000 Units/gm
Oxiconazole Cream, Lotion Oxistat®, Tinox® 1%
Sertaconazole Cream Ertaczo®, Dermofix®, Onabet® 2%
Topical Spray 2% (15 ml)
Shampoo 20 mg/gm
Eberconazole Cream Ebernet® 1%
Sulconazole Cream, Lotion Exelderm® 1%
Isoconazole Cream Travocort® , Travogen® 1%
Tioconazole Cream Trosyd® 1%
Butoconazole Cream Gynazole-1® 2%
Terconazole Cream Terazole® , Zazole® 0.4% , 0.8%
Terbinafine Cream, Lotion Lamisil®, Lamifin®, Terbisil® 1%
Tolnaftate Cream, Powder, Solu. Tinactin®, Aftate®, Tolnalin® 1%
Bifonazole Cream Mycospor® 1%
Tavaborole Topical Solu. Kerydin® 0.5% (43.5 mg/ml)
Efinaconazole Topical Solu. Jublia® 10%
C) Vaginal Antifungals
1. Duration of therapy ranges from short courses of 1 to 14 days according to the preparation used;
treatment can be repeated if initial course fails to control symptoms or if symptoms recur, all
internal preparations should be administered at night.
➢ this give the drug time to be absorbed, and eliminate the possibility of accidental
loss which is more likely to occur if the person is mobile or moving.
2. Vaginal Antifungal preparations may damage birth-control devices such as condoms and
diaphragms, leading to inadequate protection. Consider alternative methods of birth control.
Clotrimazole Vag. Cream Canestene®, Gyne-Mycelex® 1% , 2%
Vag. Tab Canestene® 100 mg , 200 mg
Butoconazole Vag. Cream Femstat® 2%
Fenticonazole Vag. Cream Gynoxin® 2%
Vag. Cap 200 mg , 600 mg
Miconazole * Vag. Cream Gyno-Daktarin®, Mycoheal® 2% , 4%
Vag. Supp. Gyno-Mikazole® 200 mg , 400 mg
Nystatin * Vag. Tab Monicure ® 100,000 Units
Terconazole Vag. Cream/Supp. Terazole ® 0.4% , 0.8%
Tioconazole Vag. Oint. Vagistat®, Topazole V® 6.5%
Vag. Cream Topzole V ® 2% (20 gm cream)
Sertaconazole Vag. Cap Dermofix Ovule® 2%
Econazole Vag. Supp. Ecorex ® 150 mg
* Miconazole and Nystatin comes in many combination products of vaginal creams and Supps.
Note: See also Chapter 7, section 2, for more details on vaginal infections and
Gynecological combinations.
Clinical Tip
Some antibiotics have a non-antibacterial use; such as:
• Erythromycin (as prokinetic) in Gastroparesis.
• Isoniazid in Multiple Sclerosis.
• Rifampicin in Cholestatic Jaundice.
• Rifaximin in IBS (irritable bowel syndrome).
• Dapsone gel in Acne

5.3-Antiviral drugs
First: Herpes Simplex and Varicella–Zoster infections
1. Herpes viruses (HSV) are associated with a broad spectrum of diseases, for example, cold sores,
viral encephalitis, and genital infections, drugs that are effective against these viruses exert their
actions during the acute phase of viral infections and are without effect during the latent phase,
except for Foscarnet and Fomivirsen.
a. Herpes infection has 2 serotypes, HSV-1 usually affects the mouth, lips and the eye, other
areas of the skin may also be infected, especially in immunodeficiency, Genital infection is
most often associated with HSV-2 and also HSV-1.
b. Varicella-zoster infection (Chickenpox) is more severe in adolescents and adults than in
children; antiviral treatment started within 24 hours of the onset of rash may reduce the
duration and severity of symptoms.
➢ Treatment also include antipyretics, calamine lotion and antihistamines.
c. In herpes zoster (shingles) systemic antiviral treatment can reduce the severity and
duration of pain, reduce complications, and reduce viral shedding.
➢ Accompanied by Chronic pain which persists after the rash has healed (Post herpetic
neuralgia) requires specific management (usually given Gabapentin or Pregabalin).
2. The most common Antiviral drug used for Herpes simplex and varicella–zoster infections is
Acyclovir, usually given 5 times daily (every 4 hours for 5 times).
➢ Acyclovir is active against herpes viruses but does not eradicate them.
➢ Topical Acyclovir is applied directly on herpes lesions in recurrent herpes labialis (cold
sores); it is not recommended for use on genital herpes lesions due to poor efficacy.
➢ Acyclovir IV administration may cause dose-dependent renal impairment, crystalline
nephropathy, neurological effects (e.g., lethargy, confusion, tremors, agitation, seizures,
coma), hypotension, rash, itching, and phlebitis at the injection site.
Second: Cytomegalovirus (CMV) infection
CMV infections are frequently associated with the salivary glands causing flu-like symptoms,
CMV infection is typically unnoticed in healthy people, but can be life-threatening for the
immunocompromised, such as HIV-infected, organ transplant recipients, newborn infants.
➢ Symptomatic CMV disease can affect almost every organ of the body, resulting in fever of
unknown origin, pneumonia, hepatitis, encephalitis, myelitis, colitis, uveitis, retinitis, and
neuropathy; In patients with HIV infection, CMV involves the entire GI tract. Retinitis is the
most common manifestation of CMV disease in patients who are HIV positive.
Antivirals for Herpes simplex, Varicella Zoster and Herpes Zoster
Acyclovir Tab Zovirax , Veramed
® ® 200 mg , 400 mg , 800 mg
Susp. 200 mg/5 ml
Vial (powder) 250 mg , 500 mg , 1 gm
Cream/Oint. Sitavig® 5%
Eye Oint 1%
Famciclovir Tab Famvir ® 125 mg , 250 mg , 500 mg
Penciclovir Cream Fenlips , Denavir
® ® 10 mg/gm (2 gm tube)
Docosanol Cream Abreva® 10%
Tromantadine Gel Viru-Merz ® 1% (5 gm tube)
Trifluridine Eye Drop Viroptic ® 1% (7.5 ml drop)
Valacyclovir Tab Valterx® 500 mg , 1 gm
Inosine Pranobex Tab Imunovir ® 500 mg
Tecovirimat * Cap Tpoxx ® 200 mg
* Tecovirimat is indicated for the treatment of human smallpox disease caused by Variola virus.
Antivirals for CMV
Ganciclovir Cap Cytovene®, Cymevene® 250 mg , 500 mg
Vial (I.V.) Cymevene® 500 mg
Eye gel Zirgan® , Vitrasert® 0.15% (5 gm)
Cidofovir Inj. Solu. Vistide® 75 mg/ml
Foscarnet sodium Inj. Solu. Foscavir® 24 mg/ml (250 ml vial)
Fomivirsen Intravitreal inj. Vitravene® 6.6 mg
Letermovir Tab Prevymis® 240 mg , 480 mg
Valganciclovir Tab Valcyte® 450 mg
Oral solution 250 mg/5 ml
1. Cidofovir is used for the treatment (but not the cure) of CMV retinitis.
a. Causes acute renal failure leading to dialysis or death.
b. It is carcinogenic and teratogenic.
2. Ganciclovir is related to Acyclovir but it is more active against cytomegalovirus (CMV); it is also much
more toxic (myelosuppression) than Acyclovir.
➢ It has a black box warning concerning increased potential for neutropenia, anemia, and
thrombocytopenia; It is also teratogenic, carcinogenic, and mutagenic, Adverse effects commonly
include: fever, rash, and GI disturbances; Phlebitis, pain may occur at the site of infusion.
Third: Influenza Virus infections:
Influenza is one of the most common infectious diseases, is a highly contagious airborne disease
that occurs in seasonal epidemics and manifests as an acute febrile illness with variable degrees
of systemic symptoms, ranging from mild fatigue to respiratory failure and death.
➢ Onset of illness can occur suddenly over the course of a day, or it can progress more slowly
over the course of several days. Typical signs and symptoms include the following (Cough,
Fever, Sore throat, Myalgias, severe fatigue and weakness, Tachycardia, Red-watery eyes).
➢ There are 3 antiviral drugs are approved for chemoprophylaxis and treatment of influenza:
Oseltamivir, Zanamivir and Peramivir.
➢ Amantadine can be used for Influenza, but it’s not recommended these days, (it’s used mainly
as an anti-Parkinson’s), Rimantadine is active against Influenza A only.
Antivirals for Influenza
Oseltamivir Cap Tamiflu® 30 mg , 45 mg , 75 mg
Susp. 75 mg/5 ml
Zanamivir Inhale Powder Relenza® 5 mg (20 Units)
Peramivir I.V. Solu. Rapivab® 200 mg/20 ml
Laninamivir Inhale Powder Inavir 20 mg , 40 mg (single inhale)
Baloxavir Marboxil Tab Xofluza® 40 mg , 80 mg
Amantadine Tab , cap Symmetrel® 100 mg
Rimantadine Tab Rymanta® 100 mg
1. Oseltamivir is active against both Influenza A and B; It is one of the preferred agents for use against the
2009 H1N1 strain of influenza.
a. It is also approved for the prophylaxis of influenza infections in patients 1 year of age and older, BUT
the influenza virus vaccine is still the gold standard for prophylaxis.
b. The most common adverse effects are nausea and vomiting, delirium; Some recent studies showed that
there is no difference between Oseltamivir and Placebo in the management of Influenza.
2. Zanamivir is used for prevention or treatment of Avian and Swine (H1N1) influenza; the use of Zanamivir
is not recommended in patients with a history of asthma or chronic obstructive pulmonary disease, owing
to the risk of bronchospasm and acute decline in lung function.
3. Baloxavir, is an antiviral medication for treatment of influenza A and influenza B, has an advantage that
it is taken as a single dose by mouth; it targets the endonuclease function of the viral PA polymerase
subunit and prevents the transcription of viral mRNA.
Forth: Viral Hepatitis:
Viral hepatitis is liver inflammation due to a viral infection; it may present in acute (recent infection,
relatively rapid onset) or chronic forms. The most common causes of viral hepatitis are the five
unrelated hepatotropic viruses (A, B, C, D and E).
A. Hepatitis A:
HAV infection usually produces a self-limited disease and acute viral infection, with a low fatality rate,
and confers lifelong immunity, it’s primarily occurs through transmission by the fecal-oral route,
person-to-person, or by ingestion of contaminated food or water.
➢ HAV does not lead to chronic infections.
➢ Management of HAV infection is primarily supportive, Steroid use is not recommended.
➢ Two inactivated virus vaccines are currently licensed by FDA (Havrix® and Vaqta®).
➢ A single dose of IG of 0.02 mL/kg is given I.M. for post-exposure prophylaxis or short term (≤5
months) pre-exposure prophylaxis. For lengthy stays, a single dose of 0.06 mL/kg is used, HAV
vaccine may also be given with IG.
B. Hepatitis B:
HBV is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma, Transmission of
HBV occurs sexually, parenterally, and parentally.
➢ Two products are available for prevention of HBV infection: HBV vaccine; which provides active
immunity, and HBV Ig; which provides temporary passive immunity.
➢ Drug therapy is used to suppress viral replication by immune mediating or antiviral effects:
Interferon-α2b (IFN-α2b), Lamivudine, Telbivudine, Adefovir, Entecavir, Pegylated IFN-
α2a (PEG-IFN), and Tenofovir.
➢ Treatment for a minimum of 12 months is associated with greater sustained virologic response
rates than treatment for 4 to 6 months.
➢ Conventional IFN therapy has been virtually replaced with PEG-IFN, because of the ease of
administration (once-weekly injections), fewer side effects, and improved efficacy.
➢ Lamivudine (100 mg daily given orally) in combination with PEG-IFN resulted in greater HBV
DNA suppression.
C. Hepatitis C:
1. HCV is the most common blood-borne pathogen, it’s a lethal infection leading to chronicity and
carcinogenicity with no available product for prevention and prophylaxis yet.
➢ During the initial infection people often have mild or no symptoms, occasionally a fever, dark
urine, abdominal pain, and yellow tinged skin occurs.
➢ Over many years however, it often leads to liver disease and occasionally cirrhosis, in some
cases, those with cirrhosis will develop complications such as liver failure, liver cancer, or
dilated blood vessels in the esophagus and stomach.
2. HCV is most often acquired through injection drug use, may occur by sexual contact; hemodialysis; or
perinatal exposure.
➢ An estimated 20% of patients with chronic HCV infection will develop cirrhosis, and half of
those patients will progress to decompensated cirrhosis or hepatocellular carcinoma.
➢ The current standard of care for chronic HCV patients is combination therapy of a once-
weekly injection of PEG-IFN and a daily oral dose of Ribavirin.
➢ Ribavirin adverse effects include hemolytic anemia (black box warning) and GI upset,
Ribavirin is teratogenic; its use is contraindicated in pregnancy.
➢ PEG-IFN monotherapy can cure recent HCV infection in about 90% of the patients.
3. There is a new generation of drugs - direct acting antiviral (DAA)- approved for HCV that have a
cure rate up to 95%, although their price is high, include: (Sofosbuvir, Ledipasvir, Velpatasvir).
➢ Their initial recommended treatment depends on the type of hepatitis C virus (HCV
genotype) and whether or not a person has cirrhosis.
➢ The treatment regimen is 12 weeks of therapy.
➢ Treatment during the first six months is the most effective period.
➢ Adverse effects with these treatments were common, with half of people getting flu like
symptoms and a third experiencing emotional problems.
4. Successful treatment does not give any protection against another hepatitis C infection;
the patient can still catch it again and get re-infected.
➢ Usually cure rate is about 95%, but if the treatment does not work, it may be repeated,
extended, or a different combination of medicines may be tried.
5. Note: The recommended treatment regimen in HCV depends upon the genotype as below:
Drug Combination Regimen Indication(s)
1. Sofosbuvir + Ledipasvir Genotype 1, 4, 5, 6 infection
(with or without ribavirin)
2. Sofosbuvir + Velpatasvir All 6 genotypes
3. Sofosbuvir + Daclatasvir Genotype 1, 3, 4 infection
4. Sofosbuvir + Simeprevir Genotype 1, 4 infection
5. Sofosbuvir + Velpatasvir + Voxilaprevir All 6 genotypes
6. Ombitasvir + Paritaprevir + Ritonavir Genotype 1 infection only
+ Dasabuvir (with or without ribavirin)
7. Ombitasvir + Paritaprevir + Ritonavir Genotype 4 infection only
(with ribavirin)
8. Grazoprevir + Elbasvir Genotypes 1, 4 infection
9. Glecaprevir + Pibrentasvir All 6 genotypes
Drugs Available for Hepatitis

Adefovir dipivoxil Tab Hepsera® 10 mg
Ribavirin Tab , Cap Rebetol® , Virazole® 200 mg , 400 mg , 600 mg
Inhale Solu. 6 gm per vial
Entecavir Tab Baraclude® 0.5 mg , 1 mg
Telbivudine Tab Sebivo® , Tyzeka® 600 mg
Lamivudine Tab Zeffix® , Epivir® 100 mg , 150 mg , 300 mg
Boceprevir Cap Victrelis® 200 mg
Sofosbuvir Tab Sovaldi® 400 mg
Telaprevir Tab Incivo® 375 mg
Tenofovir Tab Viread® 150 mg , 200 mg , 300 mg
Simeprevir Cap Olysio® 150 mg
Daclatasvir Tab Daklinza® 30 mg , 60 mg
Combination Products (Double products)

Sofosbuvir + Ledipasvir Tab Harvoni®, Ledifos ® 400 mg + 90 mg
Hetrosofir Plus®
Sofosbuvir + Velpatasvir Tab Epclusa®, Velasof® 400 mg + 100 mg
Sofosbuvir + Simeprevir Tab Olysova® 400 mg + 150 mg
Sofosbuvir + Daclatasvir Tab Sovodak® 400 mg + 60 mg
Elbasvir + Grazoprevir Tab Zepatier® 50 mg + 100 mg
Glecaprevir + Pibrentasvir Tab Mavyret® 100 mg + 40 mg
Combination Products (Triple & Quadrant products)
Sofosbuvir + Tab Vosevi® 400 mg +
Velpatasvir + 100 mg +
Voxilaprevir 100 mg
Ombitasvir + Tab Technivie® , Qurevo® 12.5 mg +
Paritaprevir + 75 mg +
Ritonavir 50 mg
Ombitasvir + Tab Veikira XR®, 8.33 mg +
Paritaprevir + Viekira Pak® 50 mg +
Ritonavir + 33.33 mg +
Dasabuvir 200 mg
Pegylated interferons
Peg-Interferon Vial Pegasys® 180 mcg/ml (single use)
Alfa-2a Prefilled Inj. 180 mcg/0.5 ml (single use)
Peg-Interferon Alfa- Inj. Powder Sylatron® 444 mcg/vial , 888 mcg/vial
2b Prefilled Inj. PEG Intron® 80 mcg , 120 mcg , 180 mcg
D. Hepatitis D:
HDV is transmitted through percutaneous or mucosal contact with infectious blood, it is an
incomplete virus that requires the helper function of HBV to replicate and only occurs in people
infected with HBV.
➢ There is no vaccine for HDV.
➢ Treatment by Pegylated Interferon-Alfa.
E. Hepatitis E:
HEV is spread by the fecal–oral route, HEV usually results in a self-limited, acute illness.
➢ Hepatitis E usually resolves on its own, treatment is supportive (rest, fluids).
Fifth: Respiratory syncytial virus (RSV)

1. it’s a common respiratory virus that usually causes mild, cold-like symptoms, most people
recover in a week or two, but RSV can be serious, especially for infants and older adults.
➢ RSV is the most common cause of bronchiolitis, pneumonia, and middle ear infections
in children younger than 1 year of age.
➢ The virus can spread through both direct and indirect contact with secretions from people
with the infection.
2. Ribavirin is licensed for administration by inhalation for the treatment of severe bronchiolitis
caused by the respiratory syncytial virus (RSV) in infants, especially when they have other
serious diseases.
3. Palivizumab is a monoclonal antibody licensed for preventing serious lower respiratory-tract
disease caused by respiratory syncytial virus in children at high risk of the disease (e.g. those
with chronic lung disease, congenital heart disease)
Palivizumab Inj. powder Synagis® 100 mg/ml
Ribavirin Tab , Cap Rebetol® , Virazole® 200 mg , 400 mg , 600 mg
Inhale Solu. 6 gm per vial

Sixth: human immunodeficiency virus (HIV)
a. The disease AIDS (acquired immune deficiency syndrome) is caused by infection with the
human immunodeficiency virus (HIV), this virus invades certain cells of the immune system,
particularly the white blood cells called T-helper lymphocytes (or CD4 cells), which normally
activate other immune cells to fight infection.
b. HIV kills T-helper lymphocytes, so that the body cannot fight the virus or subsequent infections,
in recent years the number of drugs to treat HIV has increased considerably, as well as knowledge
about how best to use them in combination.
➢ Current treatment for HIV is not a curative, but it can keep HIV under control very
effectively and prevent it from spreading to others.
➢ Although, several cases around the world had a 100% cure form HIV (google it).
1. Drugs that act directly against HIV are called antiretrovirals; the most common groups work by
interfering with enzymes vital for virus replication.
a) The first group inhibit an enzyme called reverse transcriptase, they are divided according
to their chemical structure into nucleoside inhibitors, and non-nucleoside inhibitors.
o Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) are analogs of the
naturally occurring deoxynucleotides needed to synthesize the viral DNA, and they
compete with them for incorporation into the growing viral DNA chain (NRTIs act as a
chain terminators).
o Non-nucleoside reverse transcriptase inhibitors (NNRTIs) binds directly at an
allosteric hydrophobic site adjacent to the active site, inducing a conformational change
that results in enzyme inhibition and blocks viral dependent DNA polymerase activity;
unlike the NRTIs, NNRTIs neither compete with nucleoside triphosphate nor require
phosphorylation to be active.
b) The second group interfere with an enzyme called protease (protease inhibitors).
o They prevent viral replication by selectively binding to viral protease and blocking
proteolytic cleavage of protein precursors that are necessary for the production of viral
particles.
c) Entry, or fusion, inhibitors, interfere with the entry of the virus into the cell.
o HIV attachment to the host cell entails binding of the viral envelope glycoprotein complex
to the cellular receptor CD4, this binding induces conformational changes that enable
access to the chemokine receptors CCR5, chemokine receptor binding induces further
conformational changes leading to fusion of the viral envelope with the host cell
membrane and subsequent entry of the viral core into the cellular cytoplasm.
d) Integrase inhibitors prevents the virus from injecting its genetic material into cell nucleus.
o Also called Integrase strand transfer inhibitors (INSTIs), works by inhibiting the insertion
of viral DNA into the host cell DNA.
e) Other drugs to target the receptor sites the virus relies on for entry into cells; Chemokine co-
receptor antagonists (CCR5 antagonists).
2. Antiretrovirals are much more effective in combination, treatment usually starts with two
nucleoside transcriptase inhibitors plus a non-nucleoside drug or protease inhibitor.
3. The regimens of choice contain Tenofovir and Emtricitabine combined with either:
➢ (Efavirenz) or (Ritonavir + Atazanavir) or (Ritonavir + Darunavir) or (Raltegravir).
4. Alternative regimens contain Abacavir and Lamivudine combined with either:
➢ (Lopinavir + Ritonavir) or (Ritonavir + Fosamprenavir) or (Nevirapine) or (Rilpivirine).
5. New York state department of health AIDS institute (NYSDOH AI) recommends:
➢ Tenofovir + (Emtricitabine or Lamivudine) + (Raltegravir or Dolutegravir)

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
Abacavir Tab Ziagen® 300 mg
Lamivudine Tab Epivir , Zeffix
® ® 100 mg , 150 mg , 300 mg
Zidovudine Tab Retrovir ® 300 mg
Cap 100 mg
Inj. Solu. 10 mg/ml
Emtricitabine Cap Emtriva ® 200 mg
Zalcitabine Tab Hivid ® 0.375 mg , 0.750 mg
Tenofovir (fumarate) Tab Viread ® 150 mg , 300 mg
Tenofovir (alafenamide) Tab Vemlidy® 25 mg
Didanosine Cap Videx® 125 mg , 250 mg , 400 mg
Stavudine Cap Zerit® 15 mg , 20 mg , 30 mg
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Efavirenz Tab Sustiva® 600 mg
Cap 200 mg
Doravirine Tab Pifeltro 100 mg
Etravirine Tab Intelence® 100 mg , 200 mg
Nevirapine Tab, Tab ER Viramune® 200 mg , 400 mg (ER tab)
Rilpivirine Tab Edurant® 25 mg
Delavirdine Tab Rescriptor® 100 mg , 200 mg
Protease inhibitors
Ritonavir Tab , Cap Norvir® 100 mg
Atazanavir Cap Reyataz ® 100 mg , 200 mg , 300 mg
Darunavir Tab Prezista ® 400 mg , 600 mg , 800 mg
Amprenavir Cap Agenerase ® 50 mg , 150 mg
Oral Solu. 15 mg/ml (240 ml solu.)
Fosamprenavir Tab Lexiva ® 700 mg
Tipranavir Cap Aptivus ® 250 mg
Nelfinavir Tab Viracept ® 250 mg , 625 mg
Indinavir Cap Crixivan ® 200 mg , 400 mg
Saquinavir Tab Invirase ® 500 mg
Entry inhibitors (Fusion inhibitors)
Enfuvirtide Inj. powder Fuzeon® 90 mg/ml
Ibalizumab Inj. Solu. Trogarzo ® 200 mg/1.33 ml
Integrase inhibitors
Dolutegravir Tab Tivicay® 50 mg
Elvitegravir Tab Vitekta ® 150 mg
Raltegravir Tab Isentress ® 400 mg , 600 mg
Bictegravir Tab Bikta ® 50 mg
Cabotegravir (pending FDA approval)
Chemokine co-receptor antagonists (CCR5 antagonists)
Maraviroc Tab Selzentry® 150 mg , 300 mg

Double Combination Products
Abacavir + Lamivudine Tab Epzicom® 600 mg + 300 mg
Lamivudine + Zidovudine Tab Combivir® 150 mg + 300 mg
Lamivudine + Raltegravir Tab Dutrebis® 150 mg + 300 mg
Lamivudine + Tenofovir Tab Cimdue® , Temixys® 300 mg + 300 mg
Emtricitabine + Tenofovir Tab Truvada® , Descovy® 200 mg + 300 mg
Dolutegravir + Rilpivirine Tab Juluca® 50 mg + 25 mg
Dolutegravir + Lamivudine Tab Dovato® 50 mg + 300 mg
Atazanavir + Cobicistat * Tab Evotaz® 300 mg + 150 mg
Darunavir + Cobicistat * Tab Prezcobix® 800 mg + 150 mg
Lopinavir + Ritonavir Tab Kaletra® 200 mg + 50 mg
Triple Combination Products

Abacavir + Lamivudine + Zidovudine Tab Trizivir® 300 mg + 150 mg + 300 mg
Abacavir + Dolutegravir Tab Triumeq® 600 mg + 50 mg
+ Lamivudine + 300 mg
Efavirenz + Emtricitabine + Tenofovir Tab Atripla® 200 mg + 600 mg + 300 mg
Efavirenz + Lamivudine + Tenofovir Tab Symfi® 600 mg + 300 mg + 300 mg
Doravirine + Lamivudine + Tenofovir Tab Delstrigo® 100 mg + 300 mg + 300 mg
Emtricitabine + Rilpivirine Tab Complera®, 200 mg + 25 mg
+ Tenofovir Odefsey® + 300 mg
Bictegravir + Emtricitabine Tab Biktarvy® 50 mg + 200 mg
+ Tenofovir + 25 mg
Quadruple Combination Products

Darunavir + Cobicistat * Tab Symtuza® 800 mg + 150 mg
+ Emtricitabine + Tenofovir + 200 mg + 10 mg
Elvitegravir + Cobicistat * Tab Stribild®, Genvoya® 150 mg + 150 mg
+ Emtricitabine + Tenofovir + 200 mg + 10 mg
* Cobicistat is a CYP3A inhibitor, its added as a pharmacokinetic enhancer for other HIV treatments.
** Tenofovir and Lamivudine are also used in the treatment of hepatitis B virus.

5.4- Anthelmintics (drugs used for worms)
1. Anthelmintics are drugs that are used to eliminate the many types of worm (helminths) that can
enter the body and live there as parasites, producing a general weakness in some cases and serious
harm in others, most species spend part of their life cycle in another animal, and the infestation is
often passed on to humans in food contaminated with the eggs or larvae; in some cases, such as
hookworm, larvae enter the body through the skin; Larvae or adult worm may attach themselves to
the intestinal wall and feed on the bowel contents; others feed off the intestinal blood supply, causing
anemia, worms can also infest the bloodstream or lodge in the muscles or internal organs.
➢ Body’s natural defences against infection are not effective against most worm infestations.
➢ Doctors may recommend anthelmintic treatment for the whole family to prevent reinfection.
➢ If worms have invaded tissues and formed cysts, they may have to be removed surgically.
➢ Laxatives are given with some Anthelmintics to hasten expulsion of worms from the bowel.
Types of infestation
1. Threadworm (enterobiasis): The most common worm infection in Iraq, especially among young
children, the worm lives in the intestine but travels to the anus at night to lay eggs, causing itching;
scratching leaves eggs on the fingers, usually under the fingernails; sucking the fingers or eating food
with unwashed hands often transfers these eggs to the mouth, keeping the nails short; good hygiene,
including washing the hands after using the toilet and before each meal; and an early morning bath
to remove the eggs are important in eradicating the infection.
➢ Drugs of choice: Mebendazole, all members of the household should be treated
simultaneously.
2. Common roundworm (ascariasis): The most common worm infection worldwide, it is transmitted
to humans in contaminated raw food or in soil, the worms are large, and they infect the intestine,
which can be blocked by dense clusters of them.
➢ Drugs of choice: Levamisole, Mebendazole
3. Tropical threadworm (strongyloidiasis): Occurs in the tropical areas; The larvae from
contaminated soil penetrate the skin, pass into the lungs, are swallowed, and pass into the gut.
➢ Drugs of choice: Albendazole, Tiabendazole, Ivermectin
4. Whipworm (trichuriasis): Mainly occurs in tropical areas of the world as a result of eating
contaminated raw vegetables, the worms infest the intestines
➢ Drug of choice: Mebendazole
5. Hookworm (uncinariasis): Mainly found in tropical areas, the worm larvae penetrate the skin and
pass via the lymphatic system and bloodstream to the lungs; They then travel up the airways, are
swallowed, and attach to the intestinal wall, where they feed off the intestinal blood supply.
➢ Drug of choice: Mebendazole
6. Pork roundworm (trichinosis): Transmitted in infected undercooked pork; Initially, the worms
lodge in the intestines, but larvae may invade muscle to form cysts that are often resistant to drug
treatment and may require surgery.
➢ Drugs of choice: Mebendazole, Tiabendazole
7. Toxocariasis (visceral larva migrans): Usually occurs as a result of eating soil or eating with fingers
contaminated with dog or cat feces, the eggs hatch in the intestine and may travel to the lungs, liver,
kidney, brain, and eyes; Treatment is not always effective.
➢ Drugs of choice: Mebendazole, Tiabendazole, Diethylcarbamazine
8. Creeping eruption (cutaneous larva migrans): Mainly occurs in tropical areas and coastal areas as
a result of skin contact with larvae from cat and dog feces, Infestation is usually confined to the skin.
➢ Drugs of choice: Tiabendazole, Ivermectin, Albendazole
9. Filariasis (including onchocerciasis and loiasis): Occurs in tropical areas only, it may affect the
lymphatic system, blood, eyes, and skin; Infection by this group of worms is spread by the bites of
insects that are carriers of worm larvae or eggs.
➢ Drugs of choice: Diethylcarbamazine, Ivermectin, Moxidectin.
10. Flukes, Sheep liver fluke (fascioliasis): Infestation usually results from eating watercress grown in
contaminated water, it mainly affects the liver and biliary tract, other flukes only found abroad may
infect the lungs, intestines, or blood; Drug of choice: Praziquantel, Triclabendazole.
11. Tapeworms (including beef, pork, fish, and dwarf tapeworms): Depending on the type, worms
may be carried by cattle, pigs, or fish and transmitted to humans in undercooked meat, most types
affect the intestines; Larvae tapeworm may form cysts in muscle and other tissues.
➢ Drugs of choice: Niclosamide, Praziquantel
12. Hydatid disease (echinococciasis): The eggs are transmitted in dog feces, and the larvae may form
cysts over many years, commonly in the liver; Surgery is the usual treatment for cysts.
➢ Drug of choice: Albendazole
13. Bilharzia (schistosomiasis): Occurs in polluted water in tropical areas; The larvae may be
swallowed or penetrate the skin and once inside the body, they migrate to the liver; adult worms live
in the bladder; Drug of choice: Praziquantel
Notes:
1. The most common Anthelmintic drugs available are Mebendazole and Albendazole.
2. For the treatment of Pinworms (Enterobius vermicularis):
a. Mebendazole is the drug of choice for treating threadworm infection in patients of all ages
over 2 years, it is given as a single dose of 100 mg; as reinfection is very common, a second
dose (100 mg) should be given after 2 weeks.
b. Albendazole maybe also given as a single dose of 400 mg; as reinfection is very common, a
second dose (400 mg) should be given after 2 weeks.
3. In the treatment of Echinococcosis (hydatid disease), Albendazole is given orally with meals
in a dose of 400 mg twice daily for 28 days, the 28-day course may be repeated after 14 days
without treatment (treatment may need to continue for months or years).
4. Mebendazole is effective against Ascaris Lumbricoides and is generally considered to be the
drug of choice; the usual dose is 100 mg twice daily for 3 days.
Mebendazole Tab Vermox ® 100 mg
Oral Susp. 2% (20 mg/ml) , 30 ml
Albendazole Tab Zental , Albenza
® ® 200 mg , 400 mg
Levamisole Tab Katrex® 40 mg
Tiabendazole Tab, Susp. Mintezol ® 500 mg (tab) , 500 mg/5 ml
Flubendazole Tab, Susp. Fluvermal , Flub
® ® 100 mg , (20 mg/ml)
Pyrantel pamoate Cap Pin Rid ® 180 mg
Oral Susp. Pin X® 250 mg/5 ml
Diethylcarbamazine Tab Hetrazan ® 200 mg , 400 mg
citrate
Niclosamide Tab Yomesan , Niclon
® ® 500 mg
Ivermectin Tab Scav®, Gmtcin® 6 mg , 12 mg
Moxidectin Tab ------------ 2 mg
Praziquantel Tab Biltricide ® 600 mg
Triclabendazole Tab Egaten® 250 mg
1. About Mebendazole: (3)
a. contraindicated in pregnant women, also Myelosuppression (neutropenia and
thrombocytopenia) can occur with high doses as in (40 to 50 mg/kg/day).
b. Several studies show Mebendazole exhibits potent antitumor properties, it significantly
inhibited cancer cell growth, migration and metastatic formation of adrenocortical carcinoma,
both in vitro and in vivo.
c. From December 2011, it is no longer available from any manufacturer in the USA, and no reason
was given publicly for this discontinuation.
2. About Albendazole: (3)
a. contraindicated in pregnant women
b. should be administered with a fatty meal to achieve optimal absorption
c. Side effects include: Hepatotoxicity, which occurs in 16% of patients; liver function tests every
2 weeks are recommended while taking Albendazole.
3. Tiabendazole (or Thiabendazole – they are the same drug); is used to treat roundworm hookworm
and Toxocariasis.
4. Pyrantel causes a spastic paralysis of the helminth, (not death).
5. Diethylcarbamazine is used for the treatment of Bancroft’s Filariasis, onchocerciasis, ascariasis and
loiasis, but has severe allergic phenomena in conjunction with a skin rash.
6. Ivermectin is often favored over Diethylcarbamazine due to its less severe adverse effects.
a. It’s the drug of choice for the treatment of onchocerciasis (river blindness).
b. Contraindicated in patients with meningitis and in pregnancy.
c. It can be used in Scabies (taken as two doses, 200µg/kg/dose, one week apart)
7. Moxidectin, was once used only in animals, but FDA approved its use for Onchocerciasis (river
blindness) in humans, dosed 8 mg (4 tabs) as a single dose.
8. Praziquantel may impair activities that require mental alertness.
a. Treatment of ocular cysticercosis (in the eye) is contraindicated because parasite destruction
within the eyes may cause irreparable lesions.
5.5- Antiprotozoal drugs

Protozoa are single-celled organisms that are present in soil and water, they may be transmitted
to or between humans via contaminated food or water, sexual contact, or insect bites.
➢ There are many types of protozoal infection, each of which causes a different disease,
depending on the organism involved; Trichomoniasis, Toxoplasmosis, Cryptosporidium,
Giardiasis, and Pneumocystis Pneumonia are the most common protozoal infections.
First: Amebicides (for the treatment of Amebiasis and Giardiasis)

➢ Amebiasis (caused by Entameba histolytica), or Amebic dysentery, is an infection of the
bowel (and sometimes the liver and other organs), usually transmitted in contaminated food
or water; Its major symptom is violent, sometimes bloody diarrhea, treatment is with
Diloxanide, Metronidazole, or Tinidazole.
➢ Giardiasis (caused by Giardia lamblia), or Lambliasis, affects the bowel and is usually
transmitted in contaminated food or water; but it may also be spread by some types of sexual
contact, its major symptoms are generalized ill-health, diarrhea, flatulence, and abdominal
pain, treatment is with Mepacrine, metronidazole, or Tinidazole.
1. Amebicides include: Metronidazole, Tinidazole (discussed previously in section1 part14),

Diloxanide Furoate, Iodoquinol, Nitazoxanide, Paromomycin, Quinacrine (Mepacrine).
2. Diloxanide Furoate is a luminal Amebicide acting principally in the bowel lumen and is used
in the treatment of intestinal Amebiasis.
a. Diloxanide is considered second-line agent.
b. It is given alone in the treatment of asymptomatic cyst passers (patients with E. histolytica
cysts in the feces)
c. Diloxanide is not effective as single-agent therapy for extra intestinal Amebiasis.
d. Given with an Amebicide that acts in the tissues, such as metronidazole, in patients with
invasive Amebiasis (1, 2) and the usual course is of 10 days.
e. Flatulence is the most common adverse effect during treatment with Diloxanide Furoate
Diloxanide Furoate Tab Furamide® 250 mg , 500 mg
Iodoquinol Tab Yodoxin® 210 mg , 650 mg
Nitazoxanide Tab Alinia® 500 mg
Susp. Nanazoxid® 100 mg/5 ml
Paromomycin Cap Humatin® 250 mg
Quinacrine Or Mepacrine Tab Calbiochem ® 100 mg
Furazolidone Tab Furoxone® , Furazol® 100 mg
Susp. Furazon® 50 mg/15 ml
Notes:
1. Iodoquinol may produce optic neuritis or atrophy or peripheral neuropathy with high-dose,
long-term use.
2. Nitazoxanide may cause abdominal pain, diarrhea, vomiting, headache, flatulence, fever, eye
discoloration, rhinitis, and discolored urine
3. Paromomycin is an aminoglycoside antibiotic indicated for acute and chronic intestinal
Amebiasis; it is not useful for extra-intestinal Amebiasis because it is not absorbed.
a. It is also effective against enteric bacteria Salmonella and Shigella.
b. Paromomycin may cause nausea, cramping, and diarrhea at high doses (≥ 3g/day).
c. Inadvertent absorption through ulcerative bowel lesions may result in ototoxicity or renal
damage
4. Quinacrine (also called Mepacrine – they are the same drug) should be administered with
extreme caution in patients with psoriasis because it may cause exacerbation of this disease.
5. Furazolidone is also used to treat diarrhea and enteritis caused by bacteria or protozoan
infections, it has been used to treat traveler's diarrhea, cholera and bacteremic salmonellosis.
Combination products:
Diloxanide Furoate Tab Dilazole® , Di-Nidazole® (250 mg + 200 mg),
+ Metronidazole (500 mg + 400 mg)
Susp. (125 mg + 100 mg) per 5 ml
Diloxanide Furoate + Tab Tinidafyl plus® (250 mg + 300 mg)
Tinidazole
Second: Drugs for Toxoplasmosis

Toxoplasmosis (caused by Toxoplasma gondii), is usually spread via cat feces or by eating
undercooked meat, although usually symptomless, toxoplasmosis may cause generalized ill-
health, mild fever, and eye inflammation.
➢ Treatment is usually with Pyrimethamine with Sulfadiazine, or with azithromycin,
clarithromycin, or clindamycin/Spiramycin (during pregnancy).
1. Congenital toxoplasmosis is not a problem in women who have Toxoplasma antibody before
conception, but if toxoplasmosis is acquired in pregnancy, it may transfer to the baby,
transplacental infection may lead to severe disease in the fetus.
2. The medications prescribed for acute toxoplasmosis are:

a) Pyrimethamine — an antimalarial medication.
b) Sulfadiazine — an antibiotic used in combination with Pyrimethamine
• Combination therapy is usually given with folic acid supplements to reduce the
incidence of thrombocytopenia.
• Combination therapy is most useful in the setting of HIV.
c) Clindamycin. (see above, section 1, part 9)
d) Spiramycin — an antibiotic used for pregnant women to prevent the infection of their
children (reduce the risk of transmission of maternal infection to the fetus) (1).
e) Atovaquone — an antimalarial that has been used to kill Toxoplasma cysts inside AIDS
patients, (Clindamycin in combination with Atovaquone, seemed to optimally kill cysts).
f) Dapsone — anti-Leprosy drug. (see above, section 1, part 12)
3. Other antibiotics, such as minocycline, have seen some use as a salvage therapy.
4. In people with latent toxoplasmosis, the cysts are immune to these treatments, as the
antibiotics do not reach the bradyzoites in sufficient concentration, thus it’s preferable to use
Atovaquone.
Pyrimethamine Tab Daraprim® 25 mg
Sulfadiazine Tab Lantrisul® , Neotrizine® 500 mg
Spiramycin Tab Rovamycin® 1.5 & 3 million I.U
Cap 250 mg , 500 mg , 1 gm
Inj. 500 mg , 1 gm
Supp. 250 mg , 500 mg
Atovaquone Tab Mepron® 250 mg
Notes:
1. Pyrimethamine is contraindicated in Megaloblastic anemia (it is classified as a folic acid
antagonist; It works by inhibiting folic acid metabolism and therefore the making of DNA).
➢ It was previously used for malaria but is no longer recommended due to resistance.
➢ It’s also used with Dapsone as a second-line option to prevent Pneumocystis jirovecii
pneumonia
2. Spiramycin is still considered an experimental drug in the USA, but can sometimes be
obtained by special permission from the FDA for toxoplasmosis in the first trimester of
pregnancy, however it has been used in Europe since the year 2000, where it is mostly
marketed to dentists for mouth infections.
3. Atovaquone oral absorption significantly increases when administered with food (especially a
high-fat meal), it is also used for:
a. For pneumocystis pneumonia (PCP), or pneumocystosis, Caused by P. jirovecii.
b. For babesia (protozoan parasites of the blood that causes a hemolytic disease), it is often
used in conjunction with oral azithromycin.
Scientific name(s) Dosage form Trade name concentration
Pyrimethamine + Tab Fansidar® 25 mg + 500 mg
Sulfadoxine
Spiramycin + Tab Rodogyl® 750,000 I.U. +
Metronidazole 125 mg
Atovaquone + Tab Malarone® 250 mg + 100 mg
Proguanil

Third: Drugs for Leishmaniasis (Leishmaniacides)
Leishmaniasis (caused by Leishmania), or called Kala-azar, is a mainly tropical and subtropical
disease caused by organisms spread through sand fly bites, it affects the mucous membranes of
the mouth, nose, and throat and may, in its severe form, invade organs such as the liver.
1- There are three types of Leishmaniasis: cutaneous, mucocutaneous, and visceral.
a) Cutaneous is the most common form of Leishmaniasis; which causes skin ulcers.
b) Mucocutaneous Leishmaniasis causes ulcers in skin, mouth and nose.
c) Visceral is a severe form in which the parasites migrate to the vital organs; causing skin
ulcers, fever, low red blood cells and enlarged spleen and liver.
2- Drugs for Leishmaniasis include:
a) Sodium Stibogluconate; is used for visceral Leishmaniasis (kala-azar) and for extensive
Cutaneous Leishmaniasis; it is given by injection (usually I.M) 20mg/kg/day for 28 days
in visceral Leishmaniasis and for 20 days in cutaneous infection.
➢ I.V injections must be given slowly over 5 minutes (to reduce risk of local thrombosis)
and stopped if coughing or substernal pain occur; Injection should be filtered
immediately before administration using a filter of 5 microns or less.
➢ Serious side effect may include an irregular heartbeat or pancreatitis
b) Meglumine antimoniate is a pentavalent antimony compound with properties similar to
sodium stibogluconate; it should not be used in people with significant heart, liver, or
kidney problems.
c) Miltefosine, it should not be used in the pregnancy or in the case of children below 2
years of age.
d) Pentamidine and Amphotericin B is also used as backup agents in the treatment of
Leishmaniasis, Allopurinol has also been reported to be effective.
Scientific name D. Form Trade name concentration
Sodium Stibogluconate Inj. Solu. Pentostam® 100 mg Sb/ml
Meglumine Antimoniate Inj. Solu. (amp) Glucantim® 1.5 gm/5 ml
Miltefosine Cap Impavido® , Miltex® 50 mg
Pentamidine Inj. Powder Pentam® 300 mg
Inhale Powder NebuPent® 300 mg
Notes:
1. Miltefosine was originally developed as an antineoplastic (and licensed for topical use), then it
was used as an antiprotozoal drug.
a. Has antifungal activity, especially against metronidazole-resistant variants of
Trichomonas vaginalis, (a sexually transmitted protozoal disease).
b. It is also under investigation as a potential therapy against HIV infection.
c. Has exhibited teratogenicity, and should not be administered to pregnant women,
adequate methods of contraception are advised during therapy and for 5 months after.
2. Pentamidine is active against a variety of protozoal infections, including:

a. For Trypanosomiasis.
b. For pneumocystis pneumonia (PCP), or pneumocystosis, Caused by P. jirovecii.
c. For babesia (protozoan parasites of the blood that causes a hemolytic disease).
Side effects of Pentamidine include: Nephrotoxicity, bronchospasm, and cough are produced
by intravenous or inhaled Pentamidine; severe hypotension may occur after a parenteral dose,
cardiorespiratory arrest can occur after a single rapid infusion of the drug.
➢ Hypoglycemia may occur with initial administration of drug via the IV, IM, or inhalational
route. After the patient has been on the drug for a period, hyperglycemia will result. The effect
of the drug may actually induce a reversible insulin-dependent diabetes mellitus.
Fourth: Drugs for Trypanosomiasis
1- There are two types of Trypanosomiasis:
a) African Trypanosomiasis (or called sleeping sickness), is spread by the tsetse fly and
causes fever, swollen glands, and drowsiness; the parasite invades the CNS, causing an
inflammation of the brain and spinal cord that produces the characteristic lethargy and
eventually, continuous sleep.
➢ Sleeping sickness is treated with Pentamidine, Suramin, Eflornithine, or Melarsoprol.
b) South American Trypanosomiasis (or called Chagas disease) is spread by assassin bugs
and causes inflammation, enlargement of internal organs, and infection of the brain, it is
caused by T. Cruzi
➢ Chagas disease is treated with Primaquine or Nifurtimox.
Benznidazole Tab Radanil® , Rochagan® 100 mg
Melarsoprol Inj. Solu. (I.V) Arsobal® 180 mg/5 mL
Nifurtimox Tab Lampit® 30 mg , 120 mg
Primaquine Tab Primaquine® 26.3 mg
Pentamidine Inj. Powder Pentam® 300 mg
Inhale Powder NebuPent® 300 mg
Suramin Inj. Powder Germanin® 1 gm (to get 100 mg/ml)
Eflornithine Inj. Solu. Ornidyl® 200 mg/ml
Notes:
1. Melarsoprol is a toxic organic compound of arsenic, it is a highly dangerous treatment which is
only administered by injection under the supervision of a physician, as it can produce similar
effects as arsenic poisoning, it is known to cause a range of side effects including convulsions,
fever, loss of consciousness, rashes, bloody stools, nausea, and vomiting. It is fatal in and of itself
in around 8% of cases.
2. Pentamidine is discussed in details above.
3. Suramin adverse reactions include shock and loss of consciousness; acute urticaria; and
neurologic problems, including paresthesia, photophobia, palpebral edema (edema of the
eyelids), and hyperesthesia of the hands and feet.
4. Eflornithine causes Myelosuppression, Seizures occur in about 8% of treated patients.
➢ Available as a topical product for the treatment of Hirsutism.
Fifth: Drugs for Balantidiasis and Cryptosporidiosis

A) Balantidiasis (caused by Balantidium coli) is an infection of the bowel, specifically the colon,
that is usually transmitted through contact with infected pigs. Possible symptoms include
diarrhea and abdominal pain.
➢ Treatment of the infection is with tetracycline, metronidazole, Tinidazole or
diodohydroxyquinoline.
B) Cryptosporidiosis (caused by Cryptosporidium) affects the bowel (and occasionally the

respiratory tract and bile ducts); Cryptosporidiosis is spread through contaminated food or
water or by contact with animals or other humans, symptoms include severe diarrhea and
abdominal pain.
➢ there are no specific drugs to treat it, but Paromomycin, azithromycin, or Eflornithine may be
effective.

Sixth: Drugs for Pneumocystis Pneumonia
Caused by (Pneumocystis jirovecii), it is a potentially fatal lung infection usually affecting only
people with reduced resistance to infection, symptoms include fever, cough, breathlessness, and
chest pain; Treatment is with drugs such as Atovaquone, co-trimoxazole, Pentamidine, and
Dapsone with trimethoprim.
Seventh: Drugs for Trichomoniasis

Caused by (Trichomonas vaginalis); which most often affects the vagina, causing irritation and
an offensive discharge, also can cause infection in men, it may occur in the urethra; It is usually
sexually transmitted and Treatment is with Metronidazole or Tinidazole.
Eighth: Drugs for Malaria (Antimalarial Drugs)

1. Malaria is an acute infectious disease caused by four species of the protozoal genus Plasmodium.
The parasite is transmitted to humans through the bite of a female Anopheles mosquito, which
thrives in humid, swampy areas.
➢ Transferred to humans in the saliva of the female mosquito as she penetrates (“bites”) the
skin, the malaria parasite enters the bloodstream and settles in the liver, where it multiplies
asexually; then following its stay in the liver, the parasite (or plasmodium) enters another
phase of its life cycle, circulating in the bloodstream, penetrating and destroying red blood
cells, and reproducing again.
➢ If the plasmodia, then transfer back to a female Anopheles mosquito via another “bite”, they
breed sexually, and are again ready to start a human infection.
2. Malaria is a Disease that is characterized by persistent high fever, orthostatic hypotension, and
massive erythrocytosis (an abnormal elevation in the number of red blood cells accompanied by
swollen, reddish limbs), which can lead to capillary obstruction and death.
3. Major and common antimalarial drugs include: Chloroquine, Hydroxychloroquine,
Primaquine, Pyrimethamine, Quinine, and Mefloquine, in addition to combination brands.
➢ They can be classified as follows:
Available Antimalarials
Drugs used for malaria prophylaxis Drugs used for treatment of malaria
1- Atovaquone + Proguanil 1- Artesunate
2- Chloroquine phosphate 2- Artemether + Lumefantrine
3- Doxycycline 3- Atovaquone + Proguanil
4- Hydroxychloroquine 4- Chloroquine
5- Mefloquine 5- Clindamycin, Doxycycline
6- Primaquine 6- Hydroxychloroquine
7- Sulfadoxine + Pyrimethamine 7- Mefloquine
8- Primaquine
9- Quinidine
10- Quinine

Chloroquine Tab Aralen® 250 mg , 500 mg
Hydroxychloroquine Tab Plaquenil® 200 mg
Primaquine Tab Primaquine® 26.3 mg
Amodiaquine Tab ADQ 200 mg
Halofantrine Tab Halfan 250 mg
Pyrimethamine Tab Daraprim® 25 mg
Quinine Cap Qualaquin® 324 mg
Mefloquine Tab Lariam® 250 mg
Tafenoquine Tab Krintafel® , Arakoda® 150 mg , 100 mg
Artemisinin Tab , Cap ------------ 200 mg
Other Antimalarial (rarely used)

Artemether Tab Artenam® 50 mg
Inj. Solu. 100 mg/ml
Artesunate Inj. Powder Artesunate® 60 mg/vial
Atovaquone Tab Mepron® 250 mg
Proguanil Tab Paludrine® 200 mg
Quinidine * Tab Quinidex® 200 mg , 300 mg
Oral Syrup Quinaglute® 10 mg/ml
* Quinidine is also an anti-arrhythmic.
Combination Products for Malaria:

Pyrimethamine + Sulfadoxine Tab Fansidar® 25 mg + 500 mg
Piperaquine + Dihydroartemisinin Tab Demoque® 320 mg + 40 mg
Atovaquone + Proguanil Tab Malarone® 250 mg + 100 mg
Artemether + Lumefantrine Tab Coartem® 20 mg + 120 mg
Artesunate + Amodiaquine Tab Camoquin® 200 mg + 600 mg
Artesunate + Mefloquine Tab Artequin® (600 mg + 750 mg) Adult,
(300 mg + 375 mg) Child
Sulfamethoxypyrazine Tab Asu-Denk® 500 mg
+ Artesunate + 200 mg
+ Pyrimethamine + 25 mg
References
1- BNF 82.
2- Sean C. Sweetman, Martindale: The Complete Drug Reference, 38th Edition.
5- ACCP Updates in infectious diseases 2020

ENDOCRINE SYSTEM
Chapter Six: Endocrine System
Part Two:
6.1- Diabetes Mellitus 6.4- Posterior pituitary hormones
1. Oral Antidiabetics 1. Vasopressin, Desmopressin and
2. Insulin’s Oxytocin
3. Other anti-diabetic agents 2. Vasopressin related drugs:
Terlipressin, Conivaptan, Tolvaptan
4. Hypoglycemia
5. Hyperglycemic Emergencies
6.5– Other pituitary hormones
1. Growth Hormone (GH) and its
analogs
6.2- Thyroid and anti-Thyroid 2. GH inhibiting hormone and its
drugs analogs (Octreotide and relatives)
1. Thyroid hormones 3. Prolactin, Bromocriptine and
2. Anti-thyroid drugs Cabergoline
6.3- Sex hormones 6.6- Drugs for Adrenal Gland

1. Female Sex Hormones
Disorders
a. Estrogens
1. Hypersecretory cortisol diseases
b. Selective Estrogen Receptor (Cushing syndrome)
Modulators (SERMs) 2. Hyperaldosteronism
c. Estrogen receptor Antagonists 3. Hyposecretory adrenal disorders
d. Anti-Estrogens
e. Progestogens
➢ Progestogens and Estrogens 6.7- Bone disorders (Osteoporosis,
Combinations for CC Osteomalacia)
➢ Progestogens and Estrogens a. Bisphosphonates
Combinations for HRT b. Calcium Metabolism Modifiers
f. Anti-Progestins and c. Vitamin D Analogs
Prostaglandins
6.8- Calcimimetics
6.3- Sex hormones
2. Male Sex Hormones 6.9- Other Endocrine drugs
a. Androgens
b. Anabolic steroids 6.10- Rare Drugs used in Rare
c. Anti-Androgens Metabolic Disorders
3. Gonadotropins
a. Gonadotropin-releasing hormone
(GnRH) Analogs
b. Gonadotropin-releasing hormone
(GnRH) Antagonists
Sam’s Guide: Chapter 6 – Endocrine
Chapter Six: Endocrine system and Hormones
Introduction:
1. The endocrine system is a collection of glands located throughout the body that produce
hormones and release them into the bloodstream. Each endocrine gland produces one or more
hormones, each of which governs a particular body function, including growth and repair of
tissues, sexual development and reproductive function, and the body’s response to stress.
➢ The pituitary gland produces hormones that regulate growth, and sexual and reproductive
development, and also stimulate other endocrine glands.
➢ The thyroid gland regulates metabolism; Hyperthyroidism or hypothyroidism may occur if
the thyroid does not function well.
➢ The adrenal glands produce hormones that regulate the body’s mineral and water content
and reduce inflammation.
➢ The pancreas produces insulin to regulate blood glucose levels, and glucagon, which helps
the liver and muscles to store glucose.
➢ The kidneys produce a hormone, erythropoietin, needed for red blood cell production;
Patients with kidney failure lack this hormone and become anemic; they may be given
Epoetin, a synthetic version of the hormone.
➢ The ovaries (in women) secrete estrogen and progesterone, responsible for female sexual
and physical development.
➢ The testes (in men) produce testosterone, which controls the development of male sexual
and physical characteristics.
2. Most hormones are released continuously from birth, but the amount produced fluctuates with
the body’s needs, others are produced mainly at certain times – for example, growth hormone is
released mainly during childhood and adolescence, while Sex hormones are produced by the
testes and ovaries from puberty onwards.
3. Many endocrine glands release their hormones in response to triggering hormones produced by
the pituitary gland, this gland releases a variety of pituitary hormones, each of which, in turn,
stimulates the appropriate endocrine gland to produce its hormone.
4. A feedback system usually regulates blood hormone levels: if the blood level rises too high, the
pituitary responds by reducing the amount of stimulating hormone produced, thereby allowing
the blood hormone level to return to normal.
Endocrine disorders, usually

resulting in too much or too
little of a particular
hormone, have a variety of
causes. Some are congenital
in origin; others may be
caused by autoimmune
disease (including some
forms of diabetes mellitus),
malignant or benign tumors,
injury, or certain drugs.

Note1: A Partial Listing of the Endocrine Glands
Note2: Conversion of Pre hormones into Biologically Active Derivatives

6.1- Diabetes Mellitus
1. The body obtains most of its energy from glucose, a simple form of sugar made in the intestine
from the breakdown of starch and other sugars; Insulin, one of the hormones produced in the
pancreas, enables body tissues to take up glucose from the blood, either to use it for energy or to
store it.
➢ In diabetes mellitus, there is either a complete lack of insulin or too little is produced, this
results in reduced uptake of glucose by the tissues and therefore the glucose level in the blood
rises abnormally, a high blood glucose level is known medically as hyperglycemia.
➢ If diabetes is left untreated, the continuous high blood glucose levels damage various parts of
the body, the major problems are caused by reducing the flow of blood, and this can result in
heart attacks, blindness, kidney failure, reduced circulation in the legs, and even gangrene.
2. There are two main types of diabetes mellitus:
a) Type 1 (insulin-dependent) diabetes, usually appears in young people, with 50 per cent of
cases occurring around the time of puberty.
➢ The insulin-secreting cells in the pancreas are gradually destroyed, due to either an
autoimmune condition (where the body recognizes its pancreas as “foreign” and tries to
eliminate it) or a childhood viral infection.
➢ The decline in insulin production is slow, the condition often appears suddenly, brought on
by periods of stress (as infection, puberty) when the body’s insulin requirements are high.
➢ Symptoms of Type 1 diabetes include extreme thirst, increased urination, lethargy, and
weight loss. This type of diabetes is fatal if it is left untreated.
➢ In Type 1 diabetes, insulin treatment is the only treatment option. It has to be continued for
the rest of the patient’s life.
b) Type 2 diabetes, formerly known as non-insulin-dependent diabetes mellitus (NIDDM), or
maturity-onset diabetes, tends to appear at an older age (usually over 40, although it has become
increasingly common in younger age groups) and to come on much more gradually – there may
be a delay in its diagnosis for several years because of the gradual onset of symptoms.
➢ In this type of diabetes, the levels of insulin in the blood are usually high; but, the cells of the
body are resistant to the effects of insulin and have a reduced glucose uptake despite the high
insulin levels, this results in hyperglycemia.
➢ Obesity is the most common cause of Type 2 diabetes.
3. In both types of diabetes, an alteration in diet is vital, a healthy diet consisting of a low fat, high-
fiber, low simple sugar (cakes, sweets) and high complex sugar (pasta, rice, potatoes) intake is
advised, in Type 2 diabetes, a reduction in weight alone may be sufficient to lower the body’s
energy requirements and restore blood glucose to normal levels, if an alteration in diet fails, oral
antidiabetic drugs are prescribed; Insulin may need to be given to people with Type 2 diabetes if
the treatments fail, or in pregnancy, during severe illness, and before the patient undergoes any
surgery requiring a general anesthetic.
4. Normal Value of Blood glucose for a fasting person is from 70 – 110 mg/dl, if the value came at
border line (near the 110 ± 5) → preform another test to conform DM, either the 2-hour OGTT, or
the HbA1C.
5. The American Diabetic Society considers the patient a Diabetic if:
1. Fasting blood glucose ≥ 126 mg/dl (regardless of symptoms)
2. Random Blood glucose ≥ 200 mg/dl (with presence of the classic DM symptoms)
3. HbA1C ≥ 6.5%
6. Patients with type 2 Diabetes should be treated to achieve an HbA1C between 7% and 8%, rather
than the old recommendation 6.5% to 7%.

First: Oral Antidiabetics: (they are given for type II diabetes).
1- Classification and administration with respect to food:
Groups Example(s) Administration
1 Sulphonylureas Glibenclamide, Glimepiride With food
2 Biguanides Metformin Take with or just after food
3 Dipeptidyl peptidase-4 Sitagliptin, Saxagliptin, Without regard to meal
inhibitors (DPP-4) Vildagliptin
4 Thiozolidinediones Pioglitazone, Rosiglitazone Without regard to meal
5 Meglitinides Nateglinide, Repaglinide Within 30 minutes before meals,
if a meal is skipped, the
medication should be skipped
6 Alpha-Glucosidase Acarbose, Miglitol Tablets should be chewed with
inhibitor first mouthful of food or
swallowed whole with a little
liquid immediately before food.
7 (SGLT2) Sodium glucose Dapagliflozin, Canagliflozin Taken in the morning once daily
transporter 2 inhibitors with or without food
2- Adverse effects:
a) Sulfonylureas and Meglitinides: hypoglycemia and weight gain (about 2 kg).
b) Thiozolidinediones: Weight gain (increase S.C. fat or cause fluid retention), osteopenia,
increase risk of myocardial infarction and death from cardiovascular causes.
c) Metformin: GIT disturbances (anorexia, nausea, vomiting, diarrhea); and weight loss
• To minimize GI side effects, metformin should be initiated at 500 mg once or twice daily, to be
taken with food, followed by weekly or biweekly increases in increments of 500 mg daily);
Hypoglycemia is rare with a Biguanides given alone, although it may occur if other
contributing factors or drugs are present.
d) Dipeptidylpeptidase-4 inhibitors (DPP-4): increased risk of infection, Pancreatitis, severe and
disabling joint pain.
e) Sodium glucose transporter 2 (SGLT2) inhibitors: increase (generally mild) urinary tract
infections and cause genital Mycotic (fungal) infections.
Biguanides
Metformin Tab Glucophage®, Siofor®, Riomet® 500 mg , 850 mg , 1000 mg
Tab XR 500 mg , 750 mg , 1000 mg
Efferv. Tab Metfull ® 500 mg
Phenformin Tab Both withdrawn from markets due toxicity, mainly due to the
Buformin Tab lactic acidosis.
Sulfonylureas
Glibenclamide, Or Tab Daonil® , Diabeta® , Glynase® 5 mg
(Glyburide in USA)
Glimepiride Tab Amaryl®, Glemax®, Glucophen® 1 mg , 2 , 3 , 4 mg , 6 mg
Gliclazide Tab Diamicron® 30 mg , 60 mg
Glipizide Tab Minidiab®, Minodiab® 5 mg , 10 mg
Gliquidone Tab Glurenorm® 30 mg
Glibornuride Tab Glutril® 25 mg , 100 mg
Glyclopyramide Tab Deamelin-S® 250 mg
Meglitinides
Repaglinide Tab Novonorm® , Prandin® 0.5 mg , 1 mg , 2 mg
Nateglinide Tab Starlix® 60 mg , 120 mg
Mitiglinide Tab Glufast® 10 mg
Thiozolidinediones
Pioglitazone Tab Actos®, Glustin® 15 mg , 30 mg , 45 mg
Rosiglitazone Tab Avandia® 2 mg , 4 mg , 8 mg
Lobeglitazone Tab Duvie® 0.5 mg
Glitazars or (Dual PPAR agonists)
Saroglitazar Tab Lipaglyn® 2 mg , 4 mg
Dipeptidyl peptidase-4 inhibitors (DPP-4)
Dosage form
Sitagliptin Tab Januvia® 50 mg , 100 mg
Trade name
Saxagliptin Tab Onglyza® 2.5 mg , 5 mg
Concentration
Vildagliptin Tab Galvus®, Zomelis® 50 mg
Alogliptin Tab Nesina® 12.5 mg , 25 mg
Linagliptin Tab Tradjenta® 5 mg
Gemigliptin Tab Zemiglo® 50 mg
Anagliptin Tab Suiny® 100 mg
Teneligliptin Tab Tenelia® 20 mg
Trelagliptin Tab Zafatek® 50 mg , 100 mg
Omarigliptin Tab Marizev® 12.5 mg , 25 mg
Evogliptin Tab Suganon® 5 mg
Gosogliptin Tab SatRx® 20 mg , 30 mg
Alpha-glucosidase inhibitor
Acarbose Tab Precose®, Glucobay® 25 mg , 50 mg , 100 mg
Miglitol Tab Glyset® 25 mg , 50 mg , 100 mg
Voglibose Tab Voglib® 0.2 mg , 0.3 mg
Sodium glucose transporter 2 (SGLT2) inhibitors
Dapagliflozin Tab Farxiga®, Forxiga®, Divinus® 5 mg , 10 mg
Canagliflozin Tab Invokana® 100 mg , 300 mg
Empagliflozin Tab Jardiance ® 10 mg , 25 mg
Ertugliflozin Tab Steglatro ® 5 mg , 15 mg
Ipragliflozin Tab Suglat ® 25 mg , 50 mg
Tofogliflozin Tab Apleway ® 20 mg
Sotagliflozin Pending FDA approval
Notes:
1. About Metformin:
a. Metformin is the first line of therapy for type 2 DM; it exerts its effect mainly by decreasing
gluconeogenesis and by increasing peripheral utilization of glucose.
b. It causes a 1%–2% HbA1C reduction; recommended to start metformin at diagnosis of DM.
c. The sustained-release preparation of metformin will last 24 hours if given with the evening
meal; Sustained-release preparations have fewer GI side effects; Metformin may be used for
the glycemic management of Type 1 DM, (it reduces the needed doses of insulin).
d. Not associated with weight gain, thus it is preferred in obese patients.
e. Metformin is used for the symptomatic management of polycystic ovary syndrome
[PCOS] → Metformin helps to normalize menstrual cycle (increasing the rate of spontaneous
ovulation) Due Its ability to lower insulin resistance in these women with PCOS can result
in ovulation and, therefore, possibly pregnancy.
f. It is sometimes used to reduce weight, this is not FDA approved, and in fact FDA rejected
this indication in 2009 due to the risk of insulin resistance in normal patients, and thus
increases the risk of DM in those patients.
g. A new study found that Metformin targets Oncogene to prevent Prostate Cancer.
h. May improve hirsutism (1).
(Rarely used to treat hirsutism).
i. Metformin is contraindicated in diabetic patients with renal disease (serum creatinine
levels over 150 mmol/L or 1.7 mg/dL), and in those with diabetic ketoacidosis;
Accumulation can contribute to toxicity (lactic acidosis) in patients with renal dysfunction.
j. It should be discontinued in cases of acute myocardial infarction, exacerbation of
congestive heart failure, and severe infection.
k. Metformin should be used with caution in patients older than age 80 years and in those with
a history of congestive heart failure or alcohol abuse.
l. Long-term use may interfere with vitamin B12 absorption, (cause Neuropathies)
m. Metformin interacts with the I.V. Contrast used in the Catheterization, and may lead to
acute renal failure, the patient should stop using Metformin before 2 days from the
operation and 2 days after.
2. Sulfonylureas act mainly by augmenting insulin secretion (Bind to receptors on pancreatic β-
cells causing stimulation of insulin secretion); thus, thy are effective only when some residual
pancreatic beta-cell activity is present.
a. They also reduce hepatic glucose production and increase peripheral insulin sensitivity.
b. First-generation sulfonylureas (withdrawn from the markets) have been associated
with thrombocytopenia, agranulocytosis, hemolytic anemia, hyponatremia, SIADH, and
disulfiram-like reactions; The three agents in this class include: Tolbutamide (Orinase®),
Tolazamide (Tolinase®), and Chlorpropamide (Diabinese®).
c. Second generation include: Glimepiride, Gliclazide, Glipizide and Glibenclamide;
d. all should be avoided in patient with sulfa or sulfur allergy.
e. All 2nd Gen. Sulfonylureas are equally effective in lowering blood glucose when
administered in equipotent doses; On average, the A1C will fall by 1.5% to 2% with FPG
reductions of 60 to 70 mg/dL.
3. Meglitinides (Nateglinide, Repaglinide = FDA approved; Mitiglinide = Japan) lower glucose
by stimulating pancreatic insulin secretion, but insulin release is glucose dependent and
diminishes at low blood glucose concentrations.
a. They should not be combined with Sulfonylureas, because they have the same mechanism
of action and also because of the increased risk of hypoglycemia.
b. Cause severe hypoglycemia in patients who are also taking the lipid-lowering drug
(Gemfibrozil), and concurrent use is contraindicated.
c. The average reduction in A1C is ∼0.8% to 1.5%.
d. They are most effective on postprandial glucose excursions
4. Thiozolidinediones or TZDs (Pioglitazone, Rosiglitazone = FDA approved; Lobeglitazone =
Korea & Japan); they act by increasing expression of genes responsible for glucose metabolism,
resulting in improved insulin sensitivity.
a. TZDs act by activating PPARs (peroxisome proliferator-activated receptors), a group of
nuclear receptors, specific for PPARγ (PPAR-gamma); these receptors modulate the
expression genes involved in lipid and glucose metabolism, insulin signal transduction and
adipocyte tissue differentiation. (thus, they have an effect on plasma lipid profiles).
b. may cause a small decrease in hemoglobin and hematocrit; used cautiously in anemia.
c. May cause fluid retention, which can exacerbate or lead to heart failure, thus C.I. in
patients with Class III/IV heart failure, and existing fluid retention.
d. Associated with an increased fracture rate in the upper and lower limbs; women appear
to have a higher risk than men, use caution in patients with osteopenia or osteoporosis.
e. Pioglitazone is under an ongoing safety review for the potential increased risk of bladder
cancer, its dosage and duration of use dependent; but the Data available are contradictory
(several studies shows no risk, and several other trails shows proved risk).
f. Troglitazone (Rezulin®) was removed from the market in 1999 due to many several cases
of liver toxicity, (Pioglitazone and Rosiglitazone also reported some cases); although both
agents have been withdrawn from some countries in Europe.
g. When given for ∼6 months, Pioglitazone and Rosiglitazone reduce A1C values by ∼1.5%
and FPG levels by ∼60 to 70 mg/dL at maximal doses, Maximal glycemic-lowering effects may
not be seen until 3 to 4 months of therapy.
➢ Both drugs increase HDL, but Pioglitazone also reduce LDL and Triglyceride.
➢ Rosiglitazone also increase LDL cholesterol.
5. Saroglitazar is a dual peroxisome proliferator-activated receptor (PPAR) agonist indicated for
the treatment of hypertriglyceridemia in Type II diabetics; it contains two main classes of PPAR
agonists, which include PPARα (alpha) and PPARγ (gamma); It has both lipid and glucose-
lowering effects in a single molecule.
➢ It lowers the high blood triglycerides (increase HDL, lowers LDL and TG) as well as lowering
blood sugar and improves insulin resistance; Approved in India; still has no FDA approval yet.
6. DPP-4 inhibitors act by inhibiting the breakdown of GLP-1 secreted during meals, which in turn
increases pancreatic insulin secretion, limits glucagon secretion, slows gastric emptying, and
promotes satiety; The average reduction in A1C is ∼0.7% to 1% at maximum dose.
a. Sitagliptin, Saxagliptin, Alogliptin and Linagliptin are the only DPP-4 approved by the FDA.
b. Vildagliptin is approved in Europe only (not by the FDA).
c. Anagliptin, Teneligliptin, Trelagliptin and Omarigliptin are approved in Japan.
➢ Omarigliptin is a unique DPP-4 inhibitor; it’s given once weekly.
d. Evogliptin and Gemigliptin are approved in South Korea.
e. Gosogliptin is approved in Russia.
f. Used cautiously in an individual with a past medical history of pancreatitis and must be
discontinued if an individual develops pancreatitis, also may cause Hypersensitivity reactions
(include angioedema, severe skin rash, or difficulty breathing). (5)
g. DPP-IV inhibitors provide a glucose-dependent insulin secretion and thus are not
appropriate for individuals with Type1 DM.
h. Can cause severe joint pain, Upper respiratory and urinary tract infections.
i. DPP-4 inhibitors do not increase the risk of hypoglycemia when used as monotherapy or
in combination with medications that have a low incidence of hypoglycemia.
j. Safety studies of Saxagliptin and Alogliptin (but not Sitagliptin) have shown an increased
risk of heart failure hospitalization (studies still pending on Linagliptin).
k. Sitagliptin is the highest DPP-4 with risk of pancreatitis and hypersensitivity reactions.
l. Vildagliptin may cause hepatitis; thus, routine liver function tests should be performed.
m. Linagliptin is the only DPP-4 inhibitor (approved by the FDA) that doesn’t require dosage
adjustment in both hepatic or renal diseases.
7. Alpha-Glucosidase inhibitors (Acarbose, Miglitol); Slows the absorption of glucose from the
intestine to the bloodstream by slowing the breakdown of large carbohydrates into smaller
absorbable sugars, they are contraindicated in inflammatory bowel disease, colonic ulceration, or
obstructive bowel disorders.
a. Acarbose is also contraindicated in patients with hepatic impairment.
b. Average reductions in A1C of 0.3% to 1%; Also shown to decrease body weight.
c. Might not be effective in patients using low-carbohydrate diets.
8. Sodium glucose transporter 2 (SGLT2) inhibitors: SGLT2 is a transporter in the kidneys that is
responsible for approximately 90% of renal glucose reabsorption, the SGLT2 inhibitors are proposed
to inhibit this transporter, thus increasing the urinary excretion of glucose and lowering blood
glucose levels, these agents are unique in that they provide an insulin-independent mechanism of
action with near absence of hypoglycemia; Agents currently in clinical trials include: (Sergliflozin,
and Remogliflozin).
a. They have some effect on delaying GI glucose absorption.
b. Causes a 0.3%–1.0% reduction in A1C.
c. Effects both fasting and postprandial glucose concentrations; Associated with Mild weight loss.
d. The FDA issued a warning in 2015 that SGLT2 inhibitors may lead to ketoacidosis.
e. Canagliflozin is linked with possible increased bone fracture risk, decreased bone mineral
density, and causes increase of foot or leg amputations.
f. Empagliflozin can reduce cardiovascular morbidity in patients with type 2 DM with
established cardiovascular disease (FDA approved label).
g. Dapagliflozin has been approved by FDA for reducing hospitalization for heart failure (HF)
in adults with type 2 diabetes and other cardiovascular (CV) risk factors; Dapagliflozin also
demonstrate benefits in HF patients even if they do not have diabetes.
Combination Products of Oral Anti-Diabetic Drugs
Biguanides + Sulfonylureas
Metformin + Glibenclamide Tab Glucovance® (500 mg + 2.5 mg), (500 mg + 5 mg)
Metformin + Glipizide Tab Metaglip® (500 mg + 2.5 mg), (500 mg + 5 mg)
Metformin + Glimepiride Tab Amaryl-M® (500 mg + 2 mg)
Biguanides + Thiozolidinediones
Metformin + Rosiglitazone Tab Avandamet® (500 mg + 2 mg), (500 mg + 4 mg)
Metformin + Pioglitazone Tab Actoplus Met® (500 mg + 15 mg), (850 mg + 15 mg)
Biguanides + Meglitinides
Metformin + Repaglinide Tab PrandiMet® (500 mg + 1 mg), (500 mg + 2 mg)
Biguanides + DPP-4 inhibitors
Metformin + Sitagliptin Tab Janumet® (500 mg + 50 mg),
(1000 mg + 50 mg or 100 mg)
Metformin + Vildagliptin Tab Galvus Met® 850 mg + 50 mg
Metformin + Saxagliptin Tab Kombiglyze® (500 mg + 5 mg), (1000 mg + 2.5 mg),
(1000 mg + 5 mg)
Metformin + Alogliptin Tab Kazano® (500 mg + 12.5 mg),
(1000 mg + 12.5 mg)
Metformin + Linagliptin Tab Jentadueto® (500 mg + 2.5 mg), (850 mg + 2.5 mg),
(1000 mg + 2.5 mg)
Sulfonylureas + Thiozolidinediones
Glimepiride + Rosiglitazone Tab Avandary® (1 mg + 4 mg), (2 mg + 4 mg)
(2 mg + 8 mg), (4 mg + 8 mg)
Glimepiride + Pioglitazone Tab Duetact® (2 mg + 30 mg) , (4 mg + 30 mg)
Biguanides + (SGLT2) inhibitors
Metformin + Canagliflozin Tab , Invokamet®, (500 mg + 50 mg),
Tab XR Invokamet XR ® (1000 mg + 50 mg),
(1000 mg + 150 mg)
Metformin + Dapagliflozin Tab XR Xigduo XR ® (500 mg + 5 mg), (1000 mg + 5 mg),
(1000 mg + 10 mg)
Metformin + Empagliflozin Tab , Synjardy ,
® (500 mg + 5mg), (1000mg + 12.5mg)
Tab XR Synjardy XR® (1000 mg + 25 mg)
Metformin + Ertugliflozin Tab Segluromet® (500 mg + 2.5mg), (500 mg + 7.5mg)
(1000 mg + 7.5 mg)
DPP-4 inhibitors + (SGLT2) inhibitors
Linagliptin + Empagliflozin Tab Glyxambi® (5 mg + 10 mg) , (5 mg + 25 mg)
Saxagliptin + Dapagliflozin Tab Qturn® 5 mg + 10 mg
Sitagliptin + Ertugliflozin Tab Steglujan® (100 mg + 5 mg), (100 mg + 15 mg)
DPP-4 inhibitors + Thiozolidinediones
Alogliptin + Pioglitazone Tab Oseni® (12.5 mg + 15 mg), (25 mg + 15 mg)
Triple Combination Products
Metformin + Glimepiride + Pioglitazone Tab SR Debistal-GM® 500 mg + 2 mg + 15 mg
Glimepiride + Voglibose + Metformin Tab SR Glimkaire-VM2® 2 mg + 0.2 mg + 500 mg
Saxagliptin + Dapagliflozin + Metformin Tab XR Qternmet XR® (2.5 mg + 5 mg + 1000 mg),
(5 mg + 10 mg + 1000 mg)
Linagliptin + Empagliflozin + Metformin Pending FDA approval
Second: Insulin’s: (they are given for type I, and in some cases of type II diabetes).
1. Therapy with insulin is essential for the long-term survival of all patients with type 1 diabetes
mellitus; it is also needed for type 2 diabetes when other methods have failed to achieve
good control, and temporarily in the presence of current illness or pre-operatively.
➢ Pregnant women with type 2 diabetes may be treated with insulin.
2. The most frequent complication of insulin therapy is hypoglycemia; it is usually associated
with an excessive dosage of insulin or the omission of a meal by the patient.
3. The various formulations of insulin are classified, according to their duration of action after
subcutaneous injection, as short, intermediate, or long-acting.
➢ Some analogues, such as insulin Lispro and Aspart, are also short-acting, with a faster onset
and shorter duration of action than soluble insulin (Short acting) and are sometimes known
as rapid-acting insulins.
Type of insulin: Appearance Route(S)
Rapid-acting insulin Clear S.C, I.V
Insulin Lispro, Insulin Aspart, and insulin Glulisine (‫)صافي‬
Short-acting insulin Clear S.C, I.V,
(soluble, regular, neutral) and I.M
Intermediate-acting insulin S.C
Isophane insulin also called NPH (neutral protamine hagedorn) Cloudy only
Lente (‫)خابط‬
long-acting insulin S.C
Ultra-Lente (insulin zinc Susp. protamine zinc Susp.) Cloudy only
Insulin Glargine Clear
Insulin Detemir Clear
4. The primary sites used for injecting insulin are the lateral thigh, abdomen and upper arm.
Many practitioners recommend using the abdominal area because absorption from this site is
least affected by exercise and is the most predictable.
➢ Insulin is generally given by subcutaneous injection; the injection site should be rotated
to prevent local side effects (the lipid dystrophy); Short-acting insulin’s can also be
given by I.V route for urgent treatment.
5. Stability and Storage (see the product's leaflet also)
a. Insulin is a fragile molecule that can be damaged by temperature extremes, all commercially
available insulins are stable for at least 28 days (∼1 month) at room temperature (20◦–
30◦C); All un-opened vials or pen devices should be stored in the refrigerator (2◦–8◦C).
b. Insulin should not be used if it has been frozen or exposed to temperatures >37◦C.
c. Insulin preparations should be protected from light.
6. In practice, most patients store vials currently in use at room temperature because
injection of cold insulin is uncomfortable, this is wrong because the insulin will become un-
useful due to deterioration; they Should be stored in the refrigerator (2◦–8◦C).
a. To overcome the painful cold insulin injection, the patient should be advised to warm the
insulin with the palm of the hand just before injecting the insulin.
7. Administration of insulin S.C with a syringe (called insulin syringe) is still the most common
method of insulin administration, dose of insulin is expressed as units.
8. Insulin pen devices are also available for injecting insulin; Pen devices are often preferred as
they make insulin administration much easier, especially for patients who need to take their
insulin doses away from home.
Initial dosage of insulin:
First: T1DM:
Without concomitant infection or physiologic stress condition. Insulin should be dosed based on
weight and requires a calculation of the total daily dose (TDD). The total daily dose for an adult
with T1DM is estimated as 0.6 units/kg/day, which can then be applied to determine an initial
starting dose of insulin.
1. 50/50 rule: 50% of the TDD is given as a basal (e.g., NPH, glargine, detemir) dose and the
remaining 50% is given as the bolus (regular, lispro, aspart, glulisine) dose, divided between the
meals. For example, if a person who weighs 54 Kg is to start insulin, the estimated TDD would be
approximately 32 units. Half of the TDD (16 units) would be initiated as the basal insulin and the
remaining 16 units would be divided into an approximate bolus dose as follows :
a. Glargine or Detemir as a basal with short- or rapid-acting insulin as bolus: 16 units once
daily of basal insulin; 5 units t.i.d. of bolus insulin with meals.
b. NPH as a basal requires twice daily dosing in persons with T1DM. Also, when using NPH, the
total bolus dose should be decreased by 20% and given twice daily to prevent hypoglycemia.
Thus, the regimen for this example would be 8 units of NPH and 6 units of bolus, given b.i.d.
2. Premixed insulin should be initiated as two-third of the TDD in the morning and the remaining
one-third of the TDD in the evening, prior to meals. This means for the same example used earlier
with a TDD of 32 units, the insulin regimen would be 21 units in the morning prior to breakfast
and 11 units in the evening prior to the evening meal. It should be noted that this type of dosing
is not preferred for the individual with T1DM because it cannot be easily adjusted for changes in
diet, exercise, or health (sick days), nor does it allow the titration of one insulin type to target the
specific phase of insulin release that is primarily contributing to the impaired glycemic control.
Second: Type 2 DM:
1. Basal insulin alone may be initiated as 10 units once daily in the average-sized individual or 0.1
to 0.2 units/kg/day in the overweight or obese individual. If administered in the evenings, the
dose of insulin should be titrated as necessary to achieve fasting blood glucose levels in the target
range. Bolus insulin can be added as needed based on pre- and post-meal blood glucose
monitoring.
2. Premixed insulin should be initiated based on TDD of 0.2 units/kg/day, with two-thirds of the
TDD given in the morning prior to breakfast and one-third of the TDD given in the evening prior
to the last meal.
Insulin adjustment algorithms
Insulin adjustment algorithms allow for the correction of an elevated blood glucose level
ordosing for carbohydrate intake; Though useful for optimizing glycemic control, adjustment
algorithms are not for everyone.
A. Adjustment based on blood glucose level: Several variations exist in the dosing of correction
insulin for elevated blood glucose; The rule of 1500 is typically used for dosing short-acting (e.g.,
Regular) insulin, while the rule of 1800 is used for dosing rapid-acting insulin. However, there
are a myriad of algorithms used between 1500 and 2200. The higher the “rule” used, the lower
the risk of inducing hypoglycemia.
1. The rule of 1800 is used to determine the correction factor (i.e., how many mg/dL the blood
glucose will decrease with the injection of 1 unit of insulin); The calculation is: 1800/TDD =
correction factor (CF); For eg, for the individual with a TDD of 32, one unit of insulin should
change the blood glucose level by approximately 56 mg/dL (1800/32 = 56).
2. The correction factor can then be used as a point-of-care calculation to determine how much
insulin to inject. The calculation is: [Current blood glucose—target blood glucose]/CF. For the
individual previously mentioned, if the blood glucose level is 230 mg/dL, to achieve a target
of 120 mg/dL with the above calculated CF of 56 mg/dL, the individual would need to inject
2 units of rapid-acting insulin to bring the blood glucose back into the target range. The target
blood glucose is typically set by practice site protocol; The CF should be rechecked at least
once per year or when there is a significant change in weight, as this is a weight-based
calculation.
B. Adjustment based on carbohydrate intake uses the “rule of 500”; The “rule of 500” is as follows:
500/TDD = (x) grams of carbohydrate; This equation estimates how many grams of
carbohydrates will be covered by 1 unit of insulin. Use of this rule requires the ability of the
individual with diabetes or the caretaker to count carbohydrates.
Insulin adjustments for repeated, time-sequenced events of hypoglycemia or hyperglycemia:

1. When individuals experience repeated hypoglycemia or hyperglycemia at particular periods,
several factors should be taken into consideration (e.g., appropriateness of insulin dose(s), eating
habits, changes in exercise routine).
2. Adjustments to insulin dosing should be made based on clinical evaluation of the blood glucose
levels and on the knowledge of insulin onset, peak, and duration of action.
3. For example, if an individual who is taking 16 units of NPH insulin and 6 units of regular insulin
twice daily (6 a.m. and 6 p.m.) has in-target pre-lunch blood glucose levels, but is having
hypoglycemia pre-supper, a downward adjustment to the morning NPH dose would be most
appropriate based on its longer duration of action.
4. Adjusting the morning dose of Regular insulin would be inappropriate because the main effect of
Regular insulin in this instance would be on the pre-lunch blood glucose value.
5. Changes in insulin doses may also be necessary for the following causes of hyperglycemia:
a. Dawn phenomenon produces fasting hyperglycemia due to the release of counterregulatory
hormones, which typically occurs during the early morning hours (2:00 a.m. to 4:00 a.m.),
Evening basal insulin doses should be increased or moved to bedtime dosing to correct for
hyperglycemia attributed to dawn phenomenon.
b. Somogyi effect is considered rebound hyperglycemia; This can occur at any time (day or
night) and is when the blood glucose goes too low and counterregulatory hormones are
released to increase the blood glucose. When the somogyi effect produces fasting
hyperglycemia, the evening basal doses of insulin should be decreased to prevent
hypoglycemia.
Rapid-acting insulin
Scientific name D. form Trade name concentration Onset Peak Duration
Insulin Lispro Inj. Solu. Humalog®, 100 units/ml 5-15 min. 30 – 90 min. 3 – 5 hr.
Kwikpen®
Insulin Aspart Inj. Solu. NovoLog® 100 units/ml 5-15 min. 30 – 90 min. 3 – 5 hr.
Inj. Solu. Fiasp® 100 units/ml 2.5-5 min. 30 – 90 min. 3 – 5 hr.
Insulin Glulisine Inj. Solu. Apidra® 100 units/ml 5-15 min. 30 – 90 min. 3 – 5 hr.
Short-acting insulin
Regular Insulin Inj. Solu. Humulin R®, 100 units/ml, 30-60 min. 2 – 4 hr. 5 – 8 hr.
Novolin R® 500 units/ml
Velosulin Inj. Solu. Velosulin® 100 units/ml 30-60 min. 2 – 3 hr. 2 – 3 hr.
Notes
1. Insulin Aspart, Lispro, Glulisine are also available as prefilled 3 ml Pen ready to use.
2. Regular insulin has a relatively slow onset of action when given subcutaneously; requiring
injection 30 minutes prior to meals.
3. Lispro, Aspart, and Glulisine insulins are analogs that are more rapidly absorbed, peak faster,
and have shorter durations of action than regular insulin, this permits more convenient dosing
within 10 minutes of meals (rather than 30 minutes prior), produces better efficacy in lowering
postprandial blood glucose than regular insulin, and minimizes delayed post meal hypoglycemia
4. Rapid-acting insulin covers insulin needs for meals eaten at the same time as the injection,
this type of insulin is often used with longer-acting insulin.
5. Short-acting insulin covers insulin needs for meals eaten within 30-60 minutes.
6. The profile of Fiasp® is similar to NovoLog® (insulin aspart) 100 U/mL; but the formulation has
been adjusted to increase the speed of initial insulin absorption.
➢ Fiasp® can be taken at the start of a meal, or within 20 minutes of starting.
Intermediate-acting insulin
Scientific name D. form Trade name concentration Onset Peak Duration
Insulin NPH (N) or Inj. Solu. Humulin N®, 100 units/ml 1 - 4 hr. 6 - 8 hr. 12 - 16 hr.
Insulin Isophane Novolin N®
Insulin Lente * Inj. Solu. Humulin L® , 100 units/ml 1.5 hr. 4 - 8 hr. 24 hr.
Novolin L®
Long-acting insulin
Ultra-Lente * Inj. Solu. Novolin UL® 100 units/ml 4 - 6 hr. 14 - 24 hr. 28 - 36 hr.
Insulin Glargine Inj. Solu. Lantus®, 100 units/ml 1 hr. Peakless 20 - 26 hr.
Basaglar®
Insulin Detemir Inj. Solu. Levemir® 100 units/ml 1 hr. Peakless 20 - 26 hr.
Insulin Degludec Inj. Solu. Tresiba® 100 units/ml 1 hr. Peakless 42 hr.
Notes:
1. Lente and Ultra-Lente insulin was discontinued in the USA in 2005; one of the reasons for
discontinuation was declining in their use due to physicians favoring NPH insulin and other basal
insulin drugs.
2. Insulin Glargine, Detemir are also available as prefilled 3 ml Pen ready to use.
3. Glargine and Detemir should never be mixed in the same syringe with another insulin.
4. Glargine, Degludec and Detemir are long-acting, Peakless, human insulin analogs that result in less
nocturnal hypoglycemia than NPH insulin when given at bedtime.
5. Intermediate-acting insulin covers insulin needs for about half the day or overnight, while
Long-acting insulin covers insulin needs for about one full day.
6. Insulin glargine and insulin Degludec are given once daily, insulin Detemir is given once or twice daily
according to individual requirements.
7. These types of insulin are often combined, when needed, with rapid- or short-acting insulin.
Biphasic insulin are mixtures providing for both immediate and prolonged action.
➢ These combinations are usually used in a twice daily regimen.
➢ The most common combination found in our market is the 70% NPH insulin + 30% regular.
70% NPH insulin + Inj. Solu. Humulin 70/30 , Novolin 70/30 (70 unit + 30 unit)/ml
® ®
30% regular insulin Mixtard 70/30®

50% NPH insulin + Inj. Solu. Humulin 50/50® (50 unit + 50 unit)/ml
50% regular insulin
75% Lispro protamine + Inj. Solu. Humalog Mix 75/25® (75 unit + 25 unit)/ml
25% insulin Lispro
50% Lispro protamine + Inj. Solu. Humalog Mix 50/50® (50 unit + 50 unit)/ml
50% insulin Lispro
70% Aspart protamine + Inj. Solu. NovoLog Mix 70/30® (70 unit + 30 unit)/ml
30% insulin Aspart
50% Aspart protamine + Inj. Solu. NovoLog Mix 50/50® (50 unit + 50 unit)/ml
50% insulin Aspart
70% insulin Degludec + Inj. Solu. Ryzodeg® (70 unit + 30 unit)/ml
30% insulin Aspart
Note:
Inhalable insulin (Exubera®) was available at September 2006 as inhale powder as a new
method of delivering insulin, but withdrawn on October 2007 in the USA, due to the additional
costs is so much more than the S.C dosage form, which makes it unlikely to be cost-effective.
➢ Inhaled insulin may cause bronchospasm and is contraindicated in patients with asthma,
chronic obstructive pulmonary disease, or lung cancer.
➢ Requires spirometry testing at baseline, at 6 months of therapy, and annually thereafter.
Insulin Inhale Inhale powder Exubera ® 1 mg , 3 mg
Inhale Powder Afrezza ® 4 units , 8 units , 12 units
(single use cartridges) (per cartridge)
* 1 mg of Exubera is equivalent to 3 units of insulin, onset 10 – 20 min, duration 6 hr.
®
Third: Other anti-diabetic agents:

A) Pramlintide (synthetic amylin analog) for type 1 and 2 DM
Indicated as an adjunct to mealtime insulin therapy in patients with type 1 & 2 diabetes, it delays
gastric emptying, decreases postprandial glucagon secretion.
a. Administered by S.C injection and should be injected immediately before meals.
b. It causes a 0.5%–1% reduction in HbA1C.
c. Effective at controlling postprandial glucose excursions
d. When Pramlintide is initiated, the dose of rapid or short-acting insulin should be decreased by
50% prior to meals to avoid a risk of severe hypoglycemia.
e. Pramlintide is not to be mixed in the same syringe with any insulin preparation.
f. It has a Black box warning for severe hypoglycemia, especially in patients with T1D.
g. Contraindicated in Substantial gastroparesis and in HbA1C greater than 9%.
B) Bromocriptine (for type 2 DM)

1. Agonist for dopamine receptor D2 is thought to reset circadian rhythm, which can reduce caloric
intake and storage; other effects may be through α1 antagonism, α2-agonistic properties, and
modulation of serotonin and prolactin.
2. Indicated as adjunctive therapy only for the management of Type 2 DM.
3. Used with caution in persons with cardiovascular disease (myocardial infarction, arrhythmias),
dementia, psychosis, or peptic ulcer disease.
a. Cause a 0.1%–0.6% reduction in A1C; with Possible cardiovascular benefit.
b. Take 0.8 mg within 2 hrs. After waking in the morning; dose will be increased weekly until
the maximum tolerated dose is achieved (Maximal daily dosage 4.8 mg).
c. May cause gastrointestinal discomfort, nausea, or vomiting; Take with food to lessen
gastrointestinal discomfort.
C) Incretin Mimetics (or GLP-1 analogs) for type 2 DM

1. These include: Exenatide, Liraglutide, Lixisenatide, Dulaglutide, Semaglutide, Albiglutide.
2. Incretin hormones are responsible for 60 to 70 percent of postprandial insulin secretion, thus
these agents improve glucose-dependent insulin secretion, also slow gastric emptying time,
decrease food intake, decrease postprandial glucagon secretion, promote β-cell proliferation.
a. Exenatide, Liraglutide, Lixisenatide, Dulaglutide and Albiglutide all must be
administered subcutaneously (S.C.).
b. Exenatide should be injected twice daily within 60 minutes prior to morning and evening
meals, (also reformulated as Injection Susp. used as once weekly dosing).
c. Lixisenatide is administered once daily 1 hr. before the first meal.
d. Liraglutide is used in once-daily dosing without regard to meals.
➢ Liraglutide is also indicated for weight loss (see chapter 18, section 4).
➢ Liraglutide shown to reduce cardiovascular outcomes in high-risk patients, question
whether it’s a class effect or a drug specific, other cardiovascular trials are pending.
e. Dulaglutide and Albiglutide is administered once weekly.
f. Semaglutide is the first oral glucagon-like peptide (GLP-1) receptor analog protein
treatment approved for use by the FDA for type 2 DM; that does not need to be injected.
➢ Although, there is an injectable dosage form of Semaglutide, that is administered once
weekly.
➢ The oral form of Semaglutide is taken once a day.
g. Exenatide and Liraglutide have been associated with pancreatitis.
3. They cause a 0.5%–1.5% reduction in A1C, also Effects on postprandial hyperglycemia is better
than on fasting glucose concentrations; also causes a modest weight loss.
D) Bile acid Sequestrants: Colesevelam is the only studied and approved drug in this class.
1. Bile acid Sequestrants used primarily for cholesterol management; Its mechanism to reduce
serum glucose concentrations is not clearly understood; but it is thought to be an antagonist to
the farnesoid X receptor, which subsequently reduces hepatic gluconeogenesis; Used only in
conjunction with insulin or oral DM medications and cause an additional 0.3%–0.5% reduction
in A1C.
➢ C.I. in patients with a history of bowel obstruction or serum TG conc. greater than 500 mg/dL.
Amylin Analog
Pramlintide Inj. Solu. Symlin® 0.6 mg/ml
Pen injector Symlin Pen ® 15 mcg , 30 mcg , 60 mcg per dose
Incretin Mimetics (GLP-1 analogs)
Exenatide Inj. Solu. Byetta® 250 mcg/ml
Inj. Susp. Bydureon® 2 mg/vial
Liraglutide Prefilled pen Victoza ® 6 mg/ml , (18 mg/3 ml pen)
Prefilled pen Saxenda ® 6 mg/ml , (18 mg/3 ml pen)
Dulaglutide Prefilled pen Trulicity® 0.75 mg/0.5 ml , 1.5 mg/0.5 ml
Lixisenatide Prefilled pen Lyxumia , Adlyxin
® ® 50 mcg/ml , 100 mcg/ml
Albiglutide Pen injector Tanzeum ® 30 mg , 50 mg (per pen)
Semaglutide Pen injector Ozempic ® 1.34 mg/ml
Tab Rybelsus® 3 mg , 7 mg , 14 mg
Other Drugs For DM
Bromocriptine Tab Parlodel®, Cycloset® 2.5 mg
Colesevelam Tab , Cap WelChol , Cholestagel 625 mg
® ®
Note:
A new approach is suggested for patients with type 2 DM including Insulin + GLP-1 analog; in
which has the advantage of once daily dosing.
➢ The dose is adjusted individually for each patient, and the patient’s blood glucose should be
regularly tested to find the lowest effective dose.
Insulin Degludec + Liraglutide Pen inj. Xultophy® (100 IU + 3.6 mg) per ml
Insulin Glargine + Lixisenatide Pen inj. Soliqua® (100 IU + 33 mcg) per ml

Note:
There are a variety of antidiabetic medication; each one has its own advantages and
disadvantages, making the choice between them very hard regarding initiating DM treatment.
Metformin is the drug of choice, but sometimes alone it’s not enough to control DM; thus, the
table below will help to choose what add-on therapy should be considered with Metformin.
➢ Eventually; the best drug for DM management is insulin.
Agent or Class Glycemic Benefits Limitations and Precautions
Effect
Sulfonylurea Fasting and Efficacy, Weight gain, Hypoglycemia risk,
prandial Low Cost speeds Beta-cell dysfunction
Meglitinides Prandial Prandial focus, Hypoglycemia risk, Weight gain,
Used in kidney impairment Mealtime dosing
Pioglitazone Fasting and Improved insulin sensitivity Weight gain and edema,
prandial and pancreatic function, Risk of heart failure,
Low risk of hypoglycemia Risk of osteoporosis,
Possible bladder cancer risk?
α-Glucosidase Prandial No systemic absorption, Mealtime dosing,
inhibitor Prandial focus, Weight loss Modest A1C effect
DPP-4 inhibitor Prandial Well tolerated, Possible pancreatitis risk?
Weight neutral Modest A1C effect,
Possible increased heart failure
risk (Saxagliptin, Alogliptin),
Possible hepatitis risk? (Vilda.)
GLP-1 agonist Fasting and Greater effect on prandial Nausea and vomiting,
prandial glucose, Weight loss, Injection-site effects,
(depending on Improves pancreatic function? Questionable pancreatitis or
withier given Cardiovascular benefit? thyroid cancer risk?
daily, or weekly) (Liraglutide) High Cost
Colesevelam Prandial Lipid Benefits, Large pill size,
No systemic absorption burden GI side effects,
Small decrease in A1C
Avoid with high TG
Bromocriptine Fasting and Low risk of hypoglycemia, Small decrease in A1C,
prandial Possible Cardiovascular CNS adverse effects
benefit?
SGLT-2 Fasting and Low risk of hypoglycemia, Urinary tract, genital infections,
inhibitors prandial Efficacy, Weight loss, Diuresis,
Possible heart failure benefit Euglycemic DKA?
(Dapagliflozin, Empagliflozin)
Amylin agonist Prandial Modest weight loss, High risk of hypoglycemia,
Efficacy on post Prandial Must be taken with insulin,
glucose Frequent injections Injection-site
effects and GI adverse effects
Insulin Basal: Fasting Significant A1C reduction, Hypoglycemia, Weight gain,
Bolus: Prandial Flexibility in dosing strategies Injection-site effects
and titration
Clinical Tip
Vitamin D is used in the improvement of Gestational DM
(uncommon use), as women with lower serum levels of Vit.
D during the 1st trimester of pregnancy is at a great RISK for
developing Gestational DM.
That’s because the active metabolite of Vit. D acts as a
transcription factor in Glucose metabolism.

Fourth: Hypoglycemia
1. It’s represented by plasma glucose levels below 70 mg/dL. However, symptoms are the driving
determinant rather than an absolute glycemic value since the threshold for the onset of
symptoms varies among individuals.
2. Symptoms of mild hypoglycemia include sweating, shaking, vision changes, immediate hunger,
confusion, and lack of coordination. Severe hypoglycemia occurs when an individual is unable
to self-treat due to mental confusion, lethargy, or unconsciousness. Some individuals may have
neuroglycopenia and present with symptoms of crying, argumentativeness, inappropriate
giddiness, or euphoria.
3. Causes can include advanced age, poor nutrition, renal disease, excess of glucose-lowering
agents (insulin or insulin secretagogues), or strenuous activity.
4. Treatment of Hypoglycemia
a. Mild hypoglycemia: Individuals should check their blood glucose level prior to treating, if
possible, If the blood glucose level is low, the person should eat or drink 10 to 15 gm of a fast-
acting glucose source (4 oz. of fruit juice or regular soda, 3 pieces of peppermint candy) to
raise the plasma glucose level 30 to 45 mg/dL. If plasma glucose levels are below 50mg/dL,
treatment with 20 to 30 g of carbohydrate may be necessary; The blood glucose level should
be rechecked 15 to 20 min. after treatment; if blood glucose levels are low, then hypoglycemia
treatment can be repeated.
b. Severe hypoglycemia: Individuals able to swallow may be treated with glucose gel, syrup,
or jelly placed inside the individual’s check. If this is not possible, glucagon, which stimulates
hepatic glucose production, may be given by SQ or IM injection (Nausea and vomiting are
primary adverse effects of a glucagon injection), so the treated person may not immediately
feel like consuming further carbohydrates. However, the glycemic response to glucagon is
transient (approximately 1.5 hrs.), so a small snack should be eaten when the individual is
able to do so.
c. Chronic hypoglycemia: is usually treated with Diazoxide, administered by mouth (used for
chronic hypoglycemia from excess endogenous insulin secretion, either from an islet cell
tumor or islet cell hyperplasia It has no place in the management of acute hypoglycemia).
Diazoxide Tab Eudemine® 50 mg
Oral Susp. Proglycem® 50 mg/ml
Glucagon Inj. Powder GlucaGen® 1 mg/vial
Notes:
➢ Diazoxide (a Glucose elevating agent) is used to treat Hyper-insulinemic hypoglycemia.
a. Injectable form that was used for hypertensive emergency is no longer available.
➢ Glucagon (a Glucose elevating agent) is indicated for severe hypoglycemic reactions in patients
with diabetes treated with insulin, also indicated off-label for overdose of beta blockers or
calcium channel blockers.
5. Other types of hypoglycemia

a. Pseudo-hypoglycemia occurs when the individual perceives hypoglycemic symptoms, but
the blood glucose level may be normal, or slightly above normal. Some literature states that
there is no need to treat pseudo-hypoglycemia; however, providing 5 to 10 g of a rapid-acting
glucose source can diminish the symptoms without causing significant elevations in blood
glucose.
b. Hypoglycemia unawareness occurs when hormonal counter regulation and autonomic
symptoms disappear. However, individuals do typically have select symptoms, such as those
associated with neuroglycopenia, but they may be recognized too late to allow for timely
treatment.
Fifth: Hyperglycemic Emergencies
1. The two most common emergencies are diabetic ketoacidosis (DKA) and hyperosmolar
hyperglycemic state (HHS) or called Hyperosmolar Non-Ketotic Coma (HONKC), they differ
in the presence of ketoacidosis and the degree of hyperglycemia (see the table below)
a. DKA, which is caused by profound insulin deficiency, typically occurs in persons with T1DM,
but can also occur in those with T2DM, it is characterized by hyperglycemia, ketosis,
dehydration, and electrolyte imbalance.
b. HHS predominantly affects elderly individuals and is an extreme manifestation of impaired
glucose regulation. HHS is associated with a higher mortality than DKA, likely due to severe
metabolic changes, delay in diagnosis, or other medical complications that affect elderly.
2. Treatment of DKA and HHS is focused on correction of dehydration, hyperglycemia, and
electrolyte imbalance, treatment may include any of the following as necessary: IV fluids, insulin,
potassium, and/or sodium bicarbonate.
Approach for the treatment of DKA:

➢ To restore circulating volume if systolic blood pressure is below 90 mmHg (adjusted for age, sex,
and medication as appropriate), give 500 mL sodium chloride 0.9% by I.V. infusion over10-15
minutes; repeat if blood pressure remains below 90 mmHg.
➢ When blood pressure is over 90 mmHg, sodium chloride 0.9% should be given by intravenous
infusion at a rate that replaces deficit and provides maintenance.
➢ Include potassium chloride in the fluids unless anuria is suspected; adjust according to plasma
potassium concentration (measure at 60 minutes, 2 hours, and 2 hourly thereafter; measure
hourly if outside the normal range).
➢ Start an intravenous insulin infusion: soluble insulin should be diluted (and mixed
thoroughly) with sodium chloride 0.9% intravenous infusion to a concentration of 1 unit/mL;
infuse at a fixed rate of 0.1 units/kg/hour.
➢ Established subcutaneous therapy with long-acting insulin analogues (insulin Detemir or
insulin Glargine) should be continued during treatment of diabetic ketoacidosis.
➢ Monitor blood-ketone and blood-glucose concentrations hourly and adjust the insulin infusion
rate accordingly. Blood-ketone concentration should fall by at least 0.5 mmol/L/hour and blood-
glucose concentration should fall by at least 3 mmol/ L/hour.
➢ Once blood-glucose concentration falls below 14 mmol/L, Glucose 10% should be given by
intravenous infusion (into a large vein through a large-gauge needle) at a rate of 125 mL/hour,
in addition to the sodium chloride 0.9% infusion.
➢ Continue insulin infusion until blood-ketone concentration is below 0.3 mmol/L, blood pH is
above 7.3 and the patient is able to eat and drink; ideally give subcutaneous fast-acting insulin
and a meal, and stop the insulin infusion 1 hour later.
➢ Bicarbonate administration is not needed and may be harmful, especially in children.

6.2- Thyroid and anti-Thyroid drugs
First: Thyroid hormones (for Hypothyroidism):

1. Hypothyroidism is the inability of the thyroid gland to supply sufficient thyroid hormone, there
are varying degrees of hypothyroidism from mild, clinically insignificant forms to the life
threatening extreme, myxedema coma.
➢ Causes may be due to an Autoimmune-induced thyroid injury, Iodine deficiency, Pituitary
insufficiency (failure to produce adequate TSH secretion) or drug induced.
➢ The symptoms of adult hypothyroidism develop slowly and include: weight gain, mental
slowness, dry skin, hair loss, increased sensitivity to cold, and heavy menstrual periods.
➢ In babies, low levels of thyroxine cause permanent mental and physical retardation and, for
this reason, babies are tested for hypothyroidism shortly after birth.
2. Lifelong oral treatment with synthetic thyroid hormones (Levothyroxine T4), or (Liothyronine
T3) is the only option for patients with Hypothyroidism; Blood tests are performed regularly to
monitor treatment and permit dosage adjustments.
➢ Hypothyroidism due to panhypopituitarism requires replacement with glucocorticoids as
well as with Thyroid hormone; using Levothyroxine alone in such case can cause acute
adrenal insufficiency.
3. Thyroid hormone: Thyroxine (Levothyroxine) is used in hypothyroidism, (which is readily
treated by lifelong replacement therapy).
a. Absorption of Levothyroxine is optimal on an empty stomach, at least 60 minutes before
meals; it’s best taken on an empty stomach, usually before breakfast; or 30 minutes before
eating breakfast.
➢ Taking Levothyroxine at bedtime results in higher serum T4 and lower TSH levels.
b. Optimal starting dose range from 25 mcg – 50 mcg per day, or 1.6 mcg/kg per day.
➢ In those with existing cardiovascular disease, consider 12.5–25 mcg/day.
c. Can be given every other day (even every 2 or 3 days according to response).
d. Levothyroxine is the drug of choice for pregnant women.
e. Guidelines recommend against changing from brand to generic and vice versa; It is
recommended to stay with one product throughout therapy.
f. Ciprofloxacin has been reported to interact with Levothyroxine when given together,
resulting in elevated TSH and reduced Free T4 and Free T3 levels.
4. Other treatment options include: Thyroglobulin, Liothyronine and Liotrix, but these agents
are not preferred as levothyroxine.
➢ They are not recommended by leading professional organizations or clinical guidelines.
5. Excessive doses of thyroid hormone may lead to heart failure, angina pectoris, and myocardial
infarction (MI), allergic or idiosyncratic reactions.
➢ Levothyroxine is Linked to increased risk of fractures (usually at higher dosages or over-
supplementation).
6. Some patients use Levothyroxine for weight reduction, this is very wrong and dangerous;
Levothyroxine is ineffective for weight reduction in euthyroid patients (normal patients), and
may produce serious or even life-threatening manifestations of toxicity, particularly when given
with sympathomimetic amines such as those used for their anorectic effects.
Levothyroxine Tab Eltroxin , Levoxyl , Synthroid 25 mcg , 50 , 100 , 150 mcg
® ® ®
Cap Tirosint® 75 mcg , 150 mcg

Inj. Powder 200 mcg , 500 mcg
Thyroglobulin Tab Proloid ® 200 mg
Liothyronine Tab Cytomel , Triostat
® ® 5 mcg , 25 mcg , 50 mcg
Inj. Solu. 10 mcg/ml
Liotrix (T3:T4) Tab Thyrolar ® (6.25 mcg + 25 mcg),
(12.5 mcg + 50 mcg),
(25 mcg + 100 mcg)
Levothyroxine + Tab Cynoplus® 120 mcg + 30 mcg
Liothyronine
Levothyroxine + Tab Armour Thyroid® 38 mcg + 9 mcg
Liothyronine
Thyrotropin Alfa Inj. Powder Thyrogen® 1.1 mg/vial
Notes:
1. Thyroglobulin is a purified hog gland extract that is standardized biologically to give a T4:T3 ratio
of 2.5:1; It has no clinical advantages and is not widely used.
2. Liothyronine (synthetic T3) has uniform potency but has a higher incidence of cardiac adverse
effects, higher cost, and difficulty in monitoring with conventional laboratory tests.
3. Liotrix (synthetic T4:T3 in a 4:1 ratio) is chemically stable, pure, and has a predictable potency but
is expensive.
Second: Anti-Thyroid drugs (for Hyperthyroidism)

1. In this condition (also called thyrotoxicosis), the thyroid is overactive and produces too much
thyroxine, women are more commonly affected than men.
➢ Symptoms include anxiety, palpitations, weight loss, increased appetite, heat intolerance,
diarrhea, and menstrual disturbances.
2. Can be classified according to the cause into:
a. Toxic diffuse goiter or (Graves disease): the most common hyperthyroid disorder; an
Autoimmune disorder.
b. Pituitary adenomas: Produce excessive TSH secretion that does not respond to normal T3
negative feedback
c. Toxic adenoma: Nodule in thyroid, autonomous of pituitary, and TSH.
d. Toxic multinodular goiter or (Plummer disease): Several autonomous follicles that, if large
enough, cause excessive thyroid hormone secretion
e. Painful subacute thyroiditis: Self-limiting inflammation of the thyroid gland caused by viral
invasion of the parenchyma, resulting in the release of stored hormone.
f. Drug induced (excessive exogenous thyroid hormone dosages, amiodarone therapy).
3. Anti-thyroid drugs are used for hyperthyroidism; either to prepare the patients for
thyroidectomy or for long-term management.
4. Carbimazole, the commonly used drug, Inhibits iodination and synthesis of thyroid hormones
a. Rashes and pruritus are common side effects of Carbimazole but they can be treated
with antihistamines without discontinuing therapy.
b. Carbimazole induce agranulocytosis:
➢ Rarely, agranulocytosis can develop, and is the most serious adverse reaction
associated with this class of drugs.
➢ Patients or their careers should be told how to recognize such toxicity and should be
advised to seek immediate medical attention if mouth ulcers or sore throat, fever,
bruising, malaise, or nonspecific illness develop.
➢ Full blood counts should be performed, and treatment should be stopped immediately
if there is any clinical or laboratory evidence of neutropenia.
5. Other drugs options include: Methimazole, Propylthiouracil, and Potassium Iodide.
➢ Methimazole is the active metabolite of Carbimazole.
➢ Propylthiouracil (in addition to inhibiting iodination and synthesis of thyroid hormones); it
can block T4/T3 conversion in the periphery as well.
➢ Propylthiouracil is drug of choice during the first trimester of pregnancy, during the second
and third trimesters, Methimazole (hence Carbimazole) is the drug of choice.
➢ On 2009, the FDA published an alert notifying healthcare professionals of the risk of serious
liver injury, including liver failure and death, with the use of Propylthiouracil, as a
result, Propylthiouracil is no longer recommended in non-pregnant adults and in children as
the front line anti-thyroid medication.
6. Iodine’s and iodides (Lugol solution, saturated solution of potassium iodide) acts by
inhibiting the release of stored thyroid hormone, they have minimal effect on hormone synthesis.
➢ Helps to decrease vascularity and size of gland before surgery.
7. Other treatment options include: Radioactive iodine (RAI) and Subtotal thyroidectomy.
a. Advantages of RAI: High cure rate, Avoids surgical risks (such as adverse reaction to
anesthetics, hypoparathyroidism, nerve palsy, bleeding, and hoarseness).
b. Disadvantages of RAI: Risk of delayed hypothyroidism, risk of genetic damage, must be
given in multiple doses, this may delay therapeutic efficacy for a long period (several months
or even a year).
8. Propranolol and Nadolol (β-blockers) are useful for rapid relief of Thyrotoxic symptoms; as
(tachycardia, anxiety, tremor, and heat intolerance) and they can be used in conjunction with
other anti-thyroid drugs.
a. Propranolol usually dosed 20 to 40 mg four times daily.
b. In addition to providing symptomatic relief, propranolol at high doses (more than 160
mg/day) inhibit the peripheral conversion of T4 to T3.
c. Blockers are primary adjunctive therapy to RAI.
d. Centrally acting Sympatholytics (Clonidine) and calcium channel antagonists (Diltiazem)
may be useful for symptom control when C.I. to the β-blockade exist.
e. Antiadrenergic therapy with the short-acting agent (Esmolol) is preferred because it can be
used in patients with pulmonary disease or at risk for cardiac failure and because its effects
can be rapidly reversed.
Carbimazole Tab Neomercazole®, Vidalta® 5 mg
Methimazole Tab Northyx®, Tapazole® 5 mg , 10 mg
Propylthiouracil Tab PTU®, Propycil® 50 mg
Potassium Iodide Tab SSKI®, Iosat® 65 mg , 130 mg
Oral Solu. Pima Syrup® 65 mg/ml , 325 mg/5 ml
Oral Solu. ThyroSheild® 1 gm/ml
Notes:
1. Carbimazole is a pro-drug as after absorption it is converted to the active form, Methimazole.
2. Both Methimazole and Propylthiouracil (PTU) are class (D) in pregnancy (there is positive
evidence of human fetal risk).
How to prepare Lugol solution in Procedure:

your pharmacy • Dissolve 10 gm KI in about 20-30 ml of D.W.
Ingredients needed: • Then Add 5 gm Iodine and heat gently with constant
1. Potassium iodide (KI) 10 gm mixing until iodine is dissolved.
2. Iodine 5 gm • Dilute to 100 ml with distilled water.
3. Distilled water D.W. 100 ml • Store in amber glass-stoppered bottle in the dark.

6.3- Sex hormones
First: Female sex hormones:
1. There are two types of female sex hormones: Estrogen and Progesterone, in women, these
hormones are secreted by the ovaries from puberty until the menopause, each month, the levels
of estrogen and progesterone fluctuate, producing the menstrual cycle.
2. During pregnancy, estrogen and progesterone are produced by the placenta, the Production of
estrogen and progesterone is regulated by the two gonadotrophin hormones (FSH and LH)
produced by the pituitary gland.
➢ Estrogen is responsible for the development of female sexual characteristics, including
breast development and widening of the pelvis; they also increase fat store, stimulate
endometrial growth, increase uterine growth, increase vaginal lubrication, Thicken the
vaginal wall, Maintenance of vessel and skin, reduce bone resorption, increase bone
formation
➢ Progesterone prepares the lining of the uterus for implantation of a fertilized egg; it is also
important for the maintenance of pregnancy; it decreases contractility of the uterine smooth
muscle; it inhibits lactation during pregnancy and the fall in progesterone levels following
delivery is one of the triggers for milk production.
3. Sex drive is dependent on androgen levels only in the presence of estrogen, but without estrogen,
free testosterone level actually decreases sexual desire (instead of increasing sex drive), as
demonstrated for those women who have hypoactive sexual desire disorder, and the sexual
desire in these women can be restored by administration of estrogen.
A- Estrogens:
1. The two major uses of estrogens are for Hormone replacement therapy (HRT) and as
components of combination oral contraceptives (see chapter 7).
2. Hormone replacement therapy (HRT) with small doses of an estrogen (together with a
progestogen in women with a uterus) is appropriate for alleviating menopausal symptoms such
as vaginal atrophy or vasomotor instability; (In women with an intact uterus, the addition of
a progestogen reduces the additional risk of endometrial cancer).
a. Vasomotor symptoms include hot flashes, night sweats (The hot flash is a sensation of
heat that typically begins in the face and chest and quickly spreads).
b. Menopausal atrophic vaginitis may respond to a short course of a topical vaginal
estrogen (see chapter 7), which is used for a few weeks and repeated if necessary.
c. The effective dose of estrogen used for HRT is less than that in oral contraceptives.
d. An estrogen may be given orally or transdermally (avoids 1st-pass effect).
3. Other uses: Estrogen therapy mimicking the natural cyclic pattern and usually in combination
with a progestogen, is instituted to stimulate development of secondary sex characteristics
in young women (11 to 13 years of age) with primary hypogonadism; Continued treatment is
required after growth is completed; Similarly, estrogen and progestogen replacement therapy is
used for women who have premature menopause or premature ovarian failure. Replacement
therapy is usually continued until about age 50, the average age of normal menopause
4. Side effects of Estrogens include: Postmenopausal uterine bleeding, thromboembolic
events (DVT, PE), myocardial infarction, and breast and endometrial cancer is increased with
use of estrogen therapy alone (without progestin)
➢ If estrogen is contraindicated or is undesirable, other options may be considered as
Medroxyprogesterone (see progestin’s below) may provide some relief of vasomotor
symptoms for certain patients.
➢ the α2 adrenergic agonist clonidine diminishes vasomotor symptoms in some women, but
itself has also undesirable side effects.
5. The National American Menopause Society recommends that HRT to be prescribed at the
lowest effective dose for the shortest possible time to relieve menopausal symptoms.
Conjugated Estrogen Tab Premarin , Equin
® ® 0.3 mg , 0.625 mg , 0.9 mg ,
1.5 mg , 2.5 mg
Vag. Cream Estrin ® 0.625 mg
Estradiol Tab Estrofem , Delestrogen
® ® 0.45 mg , 0.9 mg , 2 mg
Tab SR Climaval , Elleste-Solo
® ® 1 mg , 2 mg
Patch Elleste-Solo MX®, 40 mcg , 80 mcg (per 24 hr.),
Estradot , Evorel
® ® 25 mcg , 50 mcg
Gel Climara®, Oestrogel® 0.06%
Vag. Tab Vivelle®, Minivelle® 10 mcg , 25 mcg
Vag. Cream Vagifem® 0.01%
Estriol Vag. Gel Blissel® 50 mcg/1 gm
Estradiol + Estriol Tab Hormonin® 0.6 mg + 0.27 mg
+ Estrone + 1.4 mg
Estropipate Tab Ortho-Est®, Ogen ® 1.5 mg , 3 mg , 6 mg
Tibolone * Tab Livial® 2.5 mg
* Tibolone has estrogenic, progestogenic and weak androgenic activity.
B- Selective Estrogen Receptor Modulators (SERMs):

These include: Raloxifene, Bazedoxifene, Ospemifene and Clomiphene:
1. Clomiphene is used for treatment of female infertility due to anovulation; by increasing
gonadotropin levels, primarily FSH, it enhances follicular recruitment.
a. In the new pharmacological classifications, it’s classified as an anti-Estrogen.
b. The usual oral dose is 50 mg daily for 5 days starting within about 5 days of onset of
menstruation (preferably on 2nd day). If ovulation does not occur, a course of 100 mg daily
for 5 days is given, the same dosing maybe used for lactation Suppression.
c. In some cases, Clomiphene is used in conjunction with human gonadotropins to induce
ovulation (usually given to reduce the no. of gonadotropin inj.).
d. Patients should be warned that there is a risk of multiple pregnancies (rarely more than
twins), also may cause ovarian cysts, hot flashes, and blurred vision.
e. Other side effects include: ovarian hyper-stimulation, in addition, clomiphene induced
cycles have a relatively high incidence of luteal phase dysfunction due to inadequate
progesterone production.
f. Prolonged use (≥12 cycles) may increase the risk of ovarian cancer.
g. The drug should NEVER be administered to pregnant women, category (X).
h. Clomiphene has been found very effective in the treatment of secondary male
hypogonadism in many cases; this has shown to be a much more attractive option than
testosterone replacement therapy (TRT).
i. Clomiphene may be given for men with Oligospermia (it increases sperm production in
men); dosed as 25-100 mg per day.
j. Clomiphene is commonly used by male users (usually athletes and bodybuilders) to bind
the estrogen receptors in their bodies, thereby blocking the effects of estrogen; and thus,
enhancing anabolic effects and musicalizing, it also restores the body's natural production
of testosterone.
2. Raloxifene is used in the treatment of Osteoporosis, it reduces the rate of bone loss and may
increase bone mass at certain sites; it does not reduce menopausal vasomotor symptoms.
➢ Raloxifene does not appear to increase the risk of developing endometrial cancer.
➢ Adverse effects include: hot flashes, deep vein thrombosis, and leg cramps.
3. Ospemifene is indicated for treatment of dyspareunia (pain during sexual intercourse)
encountered by some women, more often in those who are post-menopausal.
4. Bazedoxifene is combined with conjugated estrogens for the treatment of menopausal
osteoporosis and the treatment of moderate to severe hot flushes.
Clomiphene Tab Clomid®, Serophene®, Ovamit® 50 mg
Raloxifene Tab Evista® 60 mg
Ospemifene Tab Osphena® 60 mg
Bazedoxifene + Tab Duavee® 20 mg +
Conjugated Estrogen 0.45 mg
Note: Experimental SERM-Estrogen Combinations
➢ There is considerable interest in menopausal hormone therapy using combinations of a pure
estrogen agonist (as estradiol) with a SERM that has predominantly antagonist activity in the
breast and endometrium but does not distribute to the CNS.
➢ The strategy is to obtain the beneficial actions of the agonist (e.g., prevention of hot flashes and
bone loss) while the SERM blocks unwanted agonist action at peripheral sites (e.g., proliferative
effects in breast and endometrium) but does not enter the brain to cause hot flashes.
C- Estrogen receptor Antagonists:

These are related to the SERMs but mainly used for the treatment of breast cancer, they
include: Tamoxifen, Toremifene and Fulvestrant.
1. Tamoxifen is highly effective in the treatment of breast cancer, and it’s now indicated as the
hormonal treatment of choice for both early and advanced breast cancer in women of all ages .
a. Tamoxifen is used (off-label) to stimulate ovulation in women with anovulatory
infertility with doses of 5 – 40 mg every 12 hrs. For 4 days only.
b. Tamoxifen is used (off-label) to prevent estrogen related Gynecomastia, resulting from
elevated estrogenic levels; (thus used by some athletes and bodybuilders).
c. Adverse effects of Tamoxifen include hot flashes and nausea, Pulmonary Embolism,
menstrual irregularities and vaginal bleeding.
2. Toremifene has therapeutic actions similar to Tamoxifen, usually used in breast cancer; it is
also approved by the FDA in 2013 for the treatment of prostate cancer.
3. Fulvestrant may be efficacious in women who become resistant to Tamoxifen; it is
administered as a once-monthly injection.
Tamoxifen Tab Nolvadex® , Soltamox® 10 mg , 20 mg
Toremifene Tab Fareston®, Acapodene® 60 mg
Fulvestrant Inj. Solu. Faslodex® 50 mg/ml
D- Anti-Estrogens: (Estrogen-Synthesis Inhibitors)

1. Aromatase is an enzyme responsible for the extra-adrenal synthesis of Estrogen; it converts
Androgen into Estrogen in a process called Aromatization; which take place in the liver, fat,
muscle, skin and breast tissue, drugs inhibiting that enzyme is called Aromatase inhibitors, they
thus selectively block production of estrogens, they include:
a. Type 1: Formestane and Exemestane. (irreversibly inactivate aromatase)
b. Type 2: Anastrozole, Letrozole, and Vorozole. (reversible inactivation)
2. These agents (Anti-Estrogens) may be used as first-line treatment of breast cancer or as
second-line drugs after Tamoxifen. They are highly efficacious and actually superior to
Tamoxifen in adjuvant use for postmenopausal women.
➢ They have the added advantage of not increasing the risk of uterine cancer or venous
thromboembolism, because they dramatically reduce circulating as well as local levels of
estrogens, and they produce hot flashes.
➢ They lack the beneficial effect of Tamoxifen to maintain bone density, and thus are
usually administered with bisphosphonates.
➢ ONLY Exemestane, Letrozole, and Anastrozole are currently approved by the FDA.
3. Formestane possesses a weak anabolic activity, thus it’s abused by some athletes and
bodybuilders, Also Exemestane has androgenic properties; which cause acne and weight gain.
4. Letrozole is used (off-label) for ovulation induction, it acts by suppressing estrogen levels in
young women, and this causes the brain and pituitary gland to increase the output of FSH (follicle
stimulating hormone), thus in women that have polycystic ovary syndrome (PCOS) or
anovulation; the increase in FSH hormone can result in development of a mature follicle in the
ovary and ovulation of an egg.
➢ The most common dose is 2.5 mg daily for 5 days starting within about 5 days of onset of
menstruation (preferably on 2nd day), sometimes it is given in higher doses of 5 mg–7.5 mg.
Formestane Tab Lentaron® 250 mg
Exemestane Tab Aromasin® 25 mg
Anastrozole Tab Arimidex® 1 mg
Letrozole Tab Femara® 2.5 mg
Vorozole Tab Rivizor® 2.5 mg
E- Progestogens or Progestins:
1. The two most frequent uses of Progestins are for contraception, either alone or with an
estrogen, and in combination with estrogen for hormone therapy of postmenopausal women,
also may be used in menstrual disorders such as dysmenorrhea and menorrhagia associated
with dysfunctional uterine bleeding.
2. Progestogens may also be used in the management of endometriosis.
• Medroxyprogesterone is also given in Paraphilia in males (a psychiatric disorder in which
a person undergoes a sexual arousal toward things and objects or events that is normally non-
sexual to a normal person; ex: sexually attractive to animals or Anime).
• Medroxyprogesterone was also given as a treatment for homosexuality in men back then
when the medical Agencies considered homosexuality as a psychiatric disorder.
3. Some Progestogens as (Dydrogesterone, Hydroxyprogesteron, Allyl-Estrenol) have been
used for the prevention of spontaneous abortion in women with a history of recurrent
miscarriage (habitual abortion), They are locally called “pregnancy Fixer” in Arabic “‫”مثبت حمل‬,
this term is actually not related to their role in pregnancy, their use as fixers are not supported
by any scientific references, but experience and evidence based medicine proved them useful in
some cases.
a. Note that these Progestins are not useful in normal pregnancies as Fixers.
b. They should be prescribed only by professionals due their doses must be precise.
c. Their role in pregnancy is limited in the threatened abortion only (when there is vaginal
bleeding in pregnancy).
d. Also, can be used in IVF luteal phase as a support for the endometrium when there is a
deficiency in progesterone levels.
e. For more info about (infertility) and the progesterone role; refer to chapter 7.
4. Progestins also are used diagnostically for secondary amenorrhea; an oral progestin is given
to an amenorrheic woman for 5-7 days, if endogenous estrogens are present, withdrawal
bleeding will occur.
5. Side effects of Progestins include: are headache, depression, weight gain, and changes in
libido, also they increase the risk of thromboembolic events (DVT, PE).
6. Injectable Medroxyprogesterone has been associated with an increased risk of osteoporosis,
which has led to recommendations for limiting the duration of use to 2 years unless other forms
of contraception are unsatisfactory.
Progesterone (micronized) Cap Progesterone® 100 mg , 200 mg
Progesterone Amp Progesterone® 50 mg/2 ml
Vag. Insert Cyclogest®, Endometrin® 100 mg , 400 mg
Vag. Gel Crinone® 4% , 8%
Megestrol Tab Megace® 20 mg , 40 mg
Etonogestrel Implant Implanon® 68 mg
Levonorgestrel Tab Plan B® 0.75 mg , 1.5 mg
Norethisterone acetate Tab Camila® 0.35 mg
(or) Norethindrone Tab Primolut-N®, 5 mg
Normolut-N®
Lynestrenol Tab Orgametril® 5 mg
Tab Exluton® 0.5 mg
Medroxyprogesterone Tab Provera® 5 mg , 10 mg
Inj. Depo-Provera® 150 mg
Prefilled Inj. Depo-Provera Pen® 104 mg/0.65 ml
Dienogest Tab Visanne® 2 mg
Desogestrel Tab Cerazette® 1 mg
Nomegestrol Tab Lutenyl® 5 mg
Hydroxyprogesteron Amp Primolut-Depot®, Makena® 250 mg , 500 mg
Dydrogesterone Tab Duphaston® 10 mg
Allyl-Estrenol Tab Gestin® , Gestal® 5 mg
Progestogens and Estrogens Combinations for Contraception:

Note: EE = Ethinyl Estradiol (Estrogen)
Levonorgestrel + EE Tab Microgynon®, Nova®, Nora® 0.1 mg + 20 mcg
Drospirenone + EE Tab Yasmine® , Zahraa® 3 mg + 0.03 mg
Tab Yaz® , Gianvi®, Warda® 3 mg + 0.02 mg
Desogestrel + EE Tab Marvelon® 0.15 mg + 0.03 mg
Gestodene + EE Tab Gynera®,Femodene®, Katya® 0.075 mg + 0.03 mg
Tab Sunya® 0.075 mg + 0.02 mg
Norgestrel + EE Tab Cryselle® (0.3 mg + 30 mcg),
(0.5 mg + 50 mcg)
Etonogestrel + EE V. Ring NuvaRing® 0.12 mg + 0.015 mg
Norgestimate + EE Tab Mononessa® 0.25 mg + 35 mcg
Norethindrone + EE Tab Femhrt® , Jinteli® (0.4 mg + 35 mcg)
Etynodiol + EE Tab Zovia® 0.05 mg + 1 mg
Tab Kelnor® 0.035 mg + 1 mg
Norethindrone + Mestranol Tab Necon® 1 mg + 50 mcg
Dienogest + Estradiol Tab Natazia®, Qlairis®, Qlairista® 4 phase tab
Norelgestromin + EE Patch Evra® (150 mcg + 35 mcg) per day
Norethindrone + Estradiol Amp Mesocept® 50 mg + 5 mg
Progesterone + Estradiol Amp DE-Pro Lezum® 12.5 mg + 2.5 mg

Progestogens and Estrogens Combinations for HRT:
1. In menopause, there is a decline in the levels of estrogen and progesterone occurs naturally
following the age of 45-50 years, when the menstrual cycle ceases, the sudden reduction in levels
of estrogen often causes distressing symptoms, and many doctors suggest that hormone
supplements be used around the time of the menopause (hormone replacement therapy or HRT).
➢ Such hormone replacement therapy may also be prescribed for women who have undergone
early or premature menopause, for example, as a result of surgical removal of the ovaries or
radiotherapy for ovarian cancer.
➢ Estrogen is used together with a progestogen unless the woman has had a hysterectomy, in
which case estrogen alone is used. If dryness of the vagina is a particular problem, a cream
containing an estrogen drug may be prescribed for short-term use.
2. HRT is primarily used to alleviate symptoms of the menopause, such as hot flushes and vaginal
dryness, it may also be used to prevent or treat osteoporosis in some women; However, the
benefits of HRT must be weighed against the various increased health risks associated with its
use, such as breast cancer, stroke, and thromboembolism.
➢ Breasts: There is a slightly increased risk of breast cancer with long-term use of HRT; The
increase in risk is related to the length of time for which HRT is used, if HRT is stopped the
risk reduces to its pre-treatment level within about five years.
➢ Heart and circulation: HRT increase the risk of thromboembolism.
➢ Bones: For women who go through premature menopause, HRT reduces the thinning of bone
that occurs in osteoporosis and thus protects against fractures.
➢ Brain: HRT increases the risk of stroke.
➢ Vagina: Thinning of vaginal tissues leading to painful intercourse can be prevented by HRT.

Norgestrel + Estradiol Tab Progyluton® 11 tab (2 mg Estradiol only)
10 tab (2 mg Estradiol +
0.5 mg Norgestrel)
Norgestimate + Estradiol Tab Cilest® , Prefest® 15 tab (1 mg Estradiol only)
0.09 mg Norgestimate)
Norethindrone + Estradiol Tab Climagest® 16 tab (1 mg Estradiol only)
1 mg Norethindrone)
Patch Activella® (0.25 mg + 0.05 mg) per 24 hr.
Drospirenone + Estradiol Tab Angeliq® (0.25 mg + 0.5 mg),
(2 mg + 1 mg)
Norethindrone + Estradiol Tab Estalis® 0.1 mg + 0.5 mg
Norethindrone + Estradiol Tab Climesse® 0.7 mg + 2 mg
Norethindrone + EE Tab ------------ 1 mg + 5 mcg
Medroxyprogesterone + Tab Premphase® , Prempro® (2.5 mg + 0.625 mg),
Conjugated Estrogens (5 mg + 0.625 mg)
Medroxyprogesterone + Tab Premique® (1.5 mg + 0.3 mg),
Conjugated Estrogens (5 mg + 0.625 mg)
Levonorgestrel + Estradiol Patch Climara Pro® 1.39 mg + 4.4 mg
Progesterone + Estradiol Cap Bijuva® 100 mg + 1 mg

F- Anti-Progestins and Prostaglandins:
Anti-Progestins include: Mifepristone, Onapristone, Asoprisnil and Ulipristal.
Prostaglandins include: Misoprostol, Dinoprostone, Carboprost, Sulprostone and
Gemeprost. (For more info see Chapter 7, section 2).
1. Mifepristone is used clinically to induce abortions and for pregnancy termination, usually
combined with Misoprostol (or other Prostaglandin) for this purpose.
➢ Mifepristone also acts as Cortisol receptor blocker, and prevents cortisol receptor binding,
thus reduces the excess cortisol effects (as hyperglycemia) associated with Cushing
syndrome.
➢ Other Uses include: induce labor, and to treat uterine leiomyoma, endometriosis,
meningioma, and breast cancer.
2. Onapristone is an oral anti-progestin hormone blocker that has been shown in clinical trials to
exhibit anti-tumor activity in patients with breast cancer.
3. Asoprisnil shows mixed progesterone agonist/antagonist activity and endometrial
selectivity in animal and humans. In non-human primates and humans, Asoprisnil induced
amenorrhea and suppressed endometrial proliferation in the presence of normal estradiol (E2)
concentrations.
➢ Animal studies also shows its potential to control the production of prostaglandins in the
endometrium that are thought to play a role in endometriosis-related pain.
4. Ulipristal is a partial agonist at the progesterone receptor, used for emergency contraception.
➢ It remains effective up to 120 hours (5 days) after intercourse.
➢ Ulipristal is also used for pre-operative treatment of moderate to severe symptoms of
uterine fibroids in adult women of reproductive age in a daily dose of a 5 mg tablet.
5. Misoprostol was first introduced to prevent and treat stomach ulcers, but later on it has been
used to start labor, induce abortions and to treat postpartum bleeding due to insufficient
contraction of the uterus.
➢ It is approved for use in the prevention of NSAID-induced gastric ulcers.
Anti-Progestins
Mifepristone Tab Mifeprex® , Korlym® 200 mg , 300 mg
Ulipristal Tab Ella® , EllaOne® 30 mg
Tab Esmya® 5 mg
Prostaglandins
Vag. Tab Vagiprost® 200 mcg
Dinoprostone Vag. insert Cervidil® 10 mg , 20 mg
Carboprost Inj. Solu. Hemabate® 250 mcg\ml
Sulprostone Inj. Solu. Nalador® 500 mcg\vial
Gemeprost Vag. Tab Cervagem® 1 mg
Notes:
1. Both Mifepristone and Misoprostol should be only given by Authorized prescription, since
they can be abused for inducing illegal abortions.
2. Sulprostone is used I.M. for the Induction of termination of pregnancy (maternal or fetal
indication); induction of labor in the case of fetal death in utero. Treatment of postpartum atonic
hemorrhage.
3. Gemeprost is used as a treatment for obstetric bleeding (used in preparing the cervix
before uterine surgery), also it is used with mifepristone to terminate pregnancy up to 24
weeks gestation.
Second: Male sex hormones
1. Male sex hormones, or Androgens, are responsible for the development of male sexual
characteristics, the main androgen is Testosterone, which in men is produced by the testes from
puberty onwards; Women also produce testosterone in small amounts in the adrenal glands, but
its exact function in the female body is not known (it may have a role in female libido).
➢ Testosterone has two major effects: an androgenic effect and an anabolic effect, its
androgenic effect is to stimulate the appearance of the secondary sexual characteristics at
puberty, such as the growth of body hair, deepening of the voice, and an increase in genital
size; and its anabolic effects are to increase muscle bulk and accelerate growth rate.
➢ There are a number of synthetically produced derivatives of testosterone that produce
varying degrees of the androgenic and anabolic effects, Derivatives with mainly anabolic
effect are called Anabolic Steroids.
A- Androgens
1. The Androgens (as testosterone or its esters) are a group of steroids that have anabolic and/or
masculinizing effects in both males and females.
a. The primary indication for androgen is as replacement therapy in male hypo-gonadal
disorders (given to men to promote the development of male sexual characteristics when
hormone production is deficient); caused by either pituitary or testicular disorders.
b. They may also help to stimulate development of secondary male sexual characteristics and
to increase sex drive (libido) in adult men with inadequate testosterone levels.
c. Androgens are useless as a treatment of impotence and impaired spermatogenesis
unless there is associated hypogonadism.
2. Adverse effects of Androgens:
a. In females: they can cause masculinization, acne, growth of facial hair, deepening of the voice,
male pattern baldness, and excessive muscle development, menstrual irregularities.
b. In males: Excess androgens can cause priapism, impotence, decreased spermatogenesis, and
gynecomastia.
3. Danazol is a mild androgen, is used in the treatment of endometriosis (ectopic growth of the
endometrium) and fibrocystic breast disease.
a. Danazol also possess anti-estrogenic activity, it inhibits release of FSH and LH but has no
effect on the aromatase.
b. Danazol has been used—mostly off-label—for other indications, mainly management of
menorrhagia, fibrocystic breast disease, immune thrombocytopenic purpura,
premenstrual syndrome, breast pain (mastodynia).
c. Have many side effects, which include: Weight gain, acne, decreased breast size, deepening
voice, increased libido, and increased hair growth.
4. Mesterolone is Dihydrotestosterone (DHT) derivative, in the late 70s and early 80s, it was used
with some success in controlled studies of men suffering from various forms of depression, but
it’s no longer used for this purpose.
➢ It’s mainly prescribed for infertility in men caused by hypogonadism or to replace
testosterone in men with hypogonadism.
➢ Also used to treat various types of sexual dysfunction, which often result from a low
endogenous testosterone level. It can usually reverse problems of sexual disinterest and
impotency, and is sometimes used to increase the sperm count.
➢ Abused by some bodybuilders for its anabolic effect and anti-estrogenic effect.
5. Oxandrolone improves both short-term and long-term outcomes in people recovering from
severe burns and is well-established as a safe treatment for this indication.
Testosterone Inj. (I.M.) Sustanon , Nebido
® ® 100 mg/ml , 250 mg/ml
Inj. (I.M.) Virormone ® 50 mg/ml
S.C Inj. Depo-Testerone ® 75 mg
Tab Striant ® 30 mg
Cap Andriol Testocaps® 40 mg
Skin Gel Testim , Testogel
® ® 50 mg/ 5 gm tube
Methyl-Testosterone Tab , Cap Android , Testred
® ® 10 mg
Oxandrolone Tab Oxandrin® 2.5 mg , 10 mg
Mesterolone Tab Proviron ® 25 mg
Danazol Cap Danol , Danazol
® ® 100 mg , 200 mg
* All above androgens have a mild to moderate anabolic effect.
** Some uses Testosterone Gel for Erectile Dysfunction by applying it topically on the penis,
this is wrong and not applicable, and no benefit is achieved.
B- Anabolic steroids (Androgens with high anabolic effect)

1. Anabolic steroids are synthetically produced variants that mimic the anabolic effects of the
natural hormone Testosterone, they increase muscle bulk and body growth.
➢ Doctors occasionally prescribe anabolic steroids and a high-protein diet to promote recovery
after serious illness or major surgery; the steroids may also help to increase the production
of blood cells in some forms of anemia and to reduce itching in chronic obstructive jaundice.
➢ Anabolic steroids have been widely abused by athletes because these drugs speed up the
recovery of muscles after a session of intense exercise, this enables the athlete to go through
a more demanding daily exercise program, which results in a significant improvement in
muscle power and mass (size), they also decrease body fat, and enhance athletic
performance and body appearance.
➢ Their side effects range from acne and baldness to psychological changes (anger, depression,
etc.), fluid retention, reduced fertility in men and women, hardening of the arteries, a long-
term risk of liver disease, and certain forms of cancer.
2. Anabolic steroids can be used to treat senile osteoporosis and chronic wasting associated
with human immunodeficiency virus (HIV) or cancer; they may also be used as adjunct therapy
in severe burns and to speed recovery from surgery or chronic debilitating diseases.
a. Anabolic steroids are used to increase lean body mass, muscle strength, and endurance
in athletes and body builders.
b. Anabolic steroids have been given for osteoporosis in women; but they are no longer
advocated for this purpose.
c. Androgens act directly on the A.R in fat cells to affect fat burning; the stronger the androgen
binds to the A.R, the higher the lipolytic (fat burning) effect on adipose tissue; Since some
steroids even increase the numbers of A.R in muscle and fat, this fat loss effect would be
amplified with the concurrent use of other compounds, such as Testosterone.
d. Extra or Excess steroids in the human body will be transformed by aromatize enzyme into
Estrogen (natural process); thus, taking anabolic steroids without actually exercising will
result in feminization or Gynecomastia!!
3. Nandrolone is an anabolic steroid with high androgenic effect, it is usually given in the form of
oily intramuscular injections as an anabolic after debilitating illness.
➢ It has the advantage of providing joint pain relief.
4. Tetrahydrogestrinone (THG), a potent androgen that appears to have been designed and
synthesized in order to avoid detection by antidoping laboratories on the basis of its novel
structure and rapid catabolism.
5. Methandrostenolone (Dianabol®);
the most anabolic steroid abused worldwide, it’s the most
potent mass builder in terms anabolic activity; it can cause a notable increase in insulin levels, it
also suppresses the natural production of testosterone leading to testicular atrophy; thus an
exogenous testosterone supplement needs to be taken to combat these effects when taking it.
➢ It is a relatively strong estrogenic anabolic steroid; it is converted to methyl-estradiol rather
than estradiol; (which is far more powerful than estradiol); this can make side effects like
gynecomastia and water retention and elevated Blood Pressure very possible.
➢ To combat the estrogenic side effects, anti-estrogens are commonly recommended when
supplementing with this steroid such as (Tamoxifen, Letrozole).
➢ It can have a pronounced negative effect on cholesterol; This includes HDL cholesterol
suppression and increases in LDL cholesterol; thus, increasing the risk of CHD.
6. Trenbolone is very potent and can be 3-5 times stronger than testosterone; it doesn’t cause
water retention in the body as other anabolic steroids does (it reduce water content under the
skin), it can cause a major increase in aggression; it’s also affects the natural testosterone levels
and must be co administered with an exogenous testosterone supplement.
➢ Considered as a fat loss agent.
➢ Trenbolone chemical structure makes it resistant to the aromatize enzyme (conversion to
estrogen) thus absolutely no percentage of Trenbolone will convert to estrogen.
➢ It can easily cause adverse androgenic side effects in people who are prone to hair loss,
prostate enlargement, oily skin and acne.
➢ Trenbolone is also a strong progestin; thus, an anti-progestin is co administered (as
Letrozole); it also increases prolactin; thus (Bromocriptine or Cabergoline) are often
recommended to lower prolactin levels.
7. Stanozolol is a Dihydrotestosterone (DHT) derived anabolic androgenic steroid, (a structurally
altered form of DHT); it carries an anabolic rating of 320 and an androgenic rating of 20.
➢ Many studies have shown it can have a positive impact on strengthening tendons.
➢ This steroid is great for promoting weight loss (fat burner).
➢ It has no estrogenic activity; (does not aromatize at all), thus this steroid cannot cause
gynecomastia or excess water retention.
➢ Stanozolol is well known for reducing HDL cholesterol and increasing LDL cholesterol.
8. Clenbuterol; is not an anabolic steroid, in fact it is a powerful bronchodilator (B2 agonist) that is
used to treat breathing disorders like asthma; it has never been approved by the U.S. FDA, it’s
commonly used as a thermogenic and a fat burning agent.
➢ It does not actively burn fat by attacking fat cells, but rather stimulates the metabolism by
increasing the body’s temperature; this occurs due to the beta-2 agonist activity stimulating
the mitochondria of the cells to produce and release more heat; this heats up the body’s
temperature (slightly), enhances the metabolism and causes a burn body fat at a greater rate.
Nandrolone Inj. Deca-Durabolin® 25 mg , 50 mg
Fluoxymesterone (Amp.)
Tab Androxy® 2 mg , 5 mg , 10 mg
Oxymetholone Tab Anadrol® 50 mg
Metenolon Tab Primobolan® , Nibal® 50 mg
Dehydroepiandrosterone Tab DHEA® 25 mg , 50 mg
Methandrostenolone Tab Dianabol® 10 mg , 20 mg
Trenbolone Tab Tren® , Parabolan® 10 mg , 25 mg , 75 mg
Amp 100 mg/ml , 200 mg/ml
Stanozolol Tab Winstrol® 10 mg , 20 mg , 50 mg
Amp 50 mg/ml , 100 mg/ml
Clenbuterol Tab ThermoClen® 20 mcg
B- Anti-Androgens
1. Antiandrogens counter male hormonal action by interfering with the synthesis of androgens or
by blocking their receptors.
a. Ketoconazole inhibits several of the CYP450 enzymes involved in steroid synthesis.
b. Finasteride and Dutasteride are used for the treatment of benign prostatic hypertrophy;
inhibit 5α-reductase resulting in the decrease in formation of Dihydrotestosterone in
the prostate leading to a reduction in prostate size.
c. Flutamide, Bicalutamide and Nilutamide act as competitive inhibitors of androgens.
1. Cyproterone acetate is an anti-androgen; it was used in the 1990s for the control of excessive
libido in severe hyper-sexuality or sexual deviation in men.
a. Cyproterone acetate may be used with Ethinyl-estradiol (EE) in women for the control
of acne and hirsutism; it is given after food.
b. Has weak progestogen activity (acts like progesterone); Thus, it can be used to treat hot
flashes, and is also a component of some combined oral contraceptive pills.
c. Fatigue and lassitude may be produced by the drug which may impair performance
of skilled tasks (e.g. driving).
2. Spironolactone (K sparing diuretic) is an inhibitor of aldosterone that also is a weak inhibitor of
the androgen receptor and a weak inhibitor of testosterone synthesis.
a. Spironolactone can be used in women to treat hirsutism; it is moderately effective, but
may cause irregular menses.
Ketoconazole Tab Nizoral®, Ketonaz® 200 mg
Finasteride ** Tab Proscar®, Prostacare® 1 mg , 5 mg
Dutasteride Cap Avodart ® 0.5 mg
Flutamide Cap Drogenil , Cytomid
® ® 125 mg
Bicalutamide Tab Casodex® 50 mg
Nilutamide Tab Nilandron ® 150 mg
Cyproterone Tab Androcur ® 50 mg
** Finasteride also is approved for use in the treatment of male pattern baldness.
Other Anti-Androgens: (mainly used for prostate cancer)

Abiraterone Tab Zytiga® 250 mg
Degarelix Inj. Powder Firmagon® 80 mg , 120 mg (per Vail)
Enzalutamide Cap Xtandi® 40 mg
Some Combination products:

Anti-Androgen + Estrogen
Cyproterone + Ethinyl Estradiol Tab Diane® , Clairette® 2 mg + 0.035 mg
Androgen + Estrogen
Methyl-Testosterone + Tab Covaryx®, Estratest® (1.25 mg + 0.625 mg) ,
Esterified Estrogens (2.5 mg + 1.25 mg)
* Diane® was withdrawn from the markets in 2012 in Canada and France due the high risk
(4 times more risk) of venous thromboembolism (blood clots in veins) than other alternatives.
➢ Diane® should not be used in Contraception.

Third: Gonadotropins and related drugs
A) Gonadotropins types include:
a. Menotropins (human menopausal gonadotropins or hMG) are obtained from the urine of
postmenopausal women and contain FSH and luteinizing hormone (LH).
b. Chorionic gonadotropin (hCG) is a placental hormone structurally related to LH which is
an LH receptor agonist, it is also excreted in the urine.
c. Urofollitropin is FSH obtained from postmenopausal women and is devoid of LH.
d. Follitropin alpha and Follitropin beta are human FSH products manufactured using
recombinant DNA technology.
e. Lutropin Alfa is a synthetic LH, used usually concomitantly with FSH as separate injections.
f. Recombinant hMG contains both Follitropin Alpha and Lutropin Alfa
g. Gonadorelin is a synthetic LH releasing hormone (GnRH).
1. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) together, follicle-stimulating

hormone alone, or chorionic gonadotropin, are used in the treatment of infertility in women
with proven hypopituitarism or who haven’t responded to clomiphene.
➢ FSH stimulates ripening of the egg follicle.
➢ LH triggers ovulation and ensures that progesterone is produced to prepare the uterus for
the implantation of the egg.
2. All of these hormones are injected via the I.M. or subcutaneous route:
a. In Females: Injection of hMG or FSH over a period of 5 to 12 days causes ovarian follicular
growth and maturation, then with an injection of hCG ovulation occurs.
➢ Method of ovulation induction: (2nd line approach, see chapter 7, section 4)
1. Usually an Injection of hMG or FSH (75 IU every day) is initiated over usually a period
of 5 to 12 days to cause ovarian follicular growth and maturation; you may increase the
dose as needed every 7 days by 37.5 IU.
2. Addition of Clomiphene 50 mg tab decrease the number of hMG or FSH injections
needed to complete the cycle of ovarian follicular maturation.
3. Maximum daily dose of hMG or FSH is 300 IU daily.
4. Maximum duration of this cycle is 35 days.
5. Then an injection of hCG (5000 IU) or (250 mcg of recombinant hCG) is given to
cause ovulation. (Injected after 1 day after the last hMG or FSH inj.)
6. Then Fertilization must occur within 36 hours after hCG administration, either by
intercourse (normal Sex) or intra-uterine insemination (IUI).
b. In men (who are deficient in gonadotropins) treatment with hCG causes external sexual
maturation, and with the subsequent injection of hMG or Follitropin, spermatogenesis
occurs.
3. In female, adverse effects include ovarian enlargement and possible hypovolemia, multiple
births are common; Men may develop Gynecomastia with overdose.
➢ LH or hCG can cause tiredness, headaches, and mood changes.
➢ FSH can cause the ovaries to enlarge, producing abdominal discomfort.

Menotropin (hMG) Inj. Merional® , Pergonal® (75 IU + 75 IU),
(FSH + LH) (150 IU + 150 IU)
Chorionic gonadotropin Inj. Pregnyl® , Choragon® 5000 IU, 1500 IU,
(hCG) 10,000 IU
FSH (Urofollitropin) Inj. Diclair FSH®, Fastimon® 75 IU , 150 IU
Follitropin Alfa Prefilled Inj. Gonal-F® 75 IU (5.5 mcg)
Prefilled Inj. Gonal-F® 300 IU (22 mcg)
Lutropin Alfa Inj. Powder Luveris® 75 IU , 82.5 IU
Recombinant hMG Inj. Pergoveris® 150 units (11 mcg) +
(Follitropin Alfa + 75 units (3 mcg)
Lutropin Alfa)
Follitropin Beta Inj. Puregon® 50 IU
Choriogonadotropin Alfa Prefilled Inj. Ovitrelle® 250 mcg/0.5 ml (6500 I.U)
Corifollitropin Alfa Prefilled Inj. Elonva® 100 mcg/0.5 ml ,
150 mcg/0.5 ml
Gonadorelin Inj. Powder Lutrepulse® 0.8 mg/vial
B) Gonadotropin-releasing hormone (GnRH) Analogs (agonists):

1. Also called Gonadorelin analogs, they include: Nafarelin, Histrelin, Buserelin, Goserelin,
Leuprolide, and Triptorelin
2. Administration of Gonadorelin analogues produces an initial phase of stimulation of follicle
stimulating hormone (FSH) and luteinizing hormone (LH); (thus they are useful in treatment of
infertility; but the continued administration is followed by down-regulation of gonadotropin-
releasing hormone receptors, thereby reducing the release of gonadotropins (FSH and LH);
which in turn leads to inhibition of androgen (testosterone) and estrogen production; thus they
are useful in prostate cancer (where testosterone is high), and in breast cancer (where estrogen
is high) or endometriosis.
3. Gonadorelin analogues are used in the treatment of Endometriosis, Other uses include the
treatment of precocious puberty, infertility, anemia due to uterine fibroids (together with
iron), breast cancer, and before intra-uterine surgery, Use of Leuprorelin and Triptorelin for
3 to 4 months before surgery reduces the uterine volume, fibroid size and associated bleeding (1).
Nafarelin Nasal Spray Synarel® 2 mg/ml
Histrelin Implant Vantas® 50 mg
Buserelin Nasal Spray Suprefact® 150 mcg/dose
Inj. (S.C) Metrelef® 5.5 mg/5.5 ml
Goserelin Implant Zoladex®, 3.6 mg (for 1 month),
(S.C) Zoladex LA® 10.8 mg (for 3 months)
Leuprolide Inj. Lupron® 5 mg/ml
Triptorelin Inj. (S.C.) Decapeptyl® 0.1 mg/ 1ml
Inj. Powder Trelstar®, Trelstar depot® 3.75 mg , 11.25 mg , 22.5 mg
Notes:
1. Nafarelin may be used in the treatment of endometriosis or uterine fibroids, to treat central
precocious puberty, and to control ovarian stimulation in IVF.
2. Goserelin Acetate is used to treat hormone-sensitive cancers of the breast (in pre- and peri-
menopausal women) and prostate cancer, and some benign gynecological disorders
(endometriosis, uterine fibroids and endometrial thinning).
3. Leuprolide has been tested as a treatment for reducing sexual urges, High doses are sometimes
used to chemically castrate sexual offenders.
➢ Also used for Endometriosis.
4. Triptorelin (0.1 mg) is prescribed to women who are unable to conceive, it helps to assist
pregnancy in certain women who suffer from fertility problems by stimulating the release of
pituitary gonadotropins, but higher Conc. (3.75 mg, 11.25 mg) is given for Prostate Cancer.

C) Gonadotropin-releasing hormone (GnRH) Antagonists:
1. A GnRH receptor antagonist that inhibits endogenous GnRH signaling by binding competitively
to GnRH receptors in the pituitary gland. Administration of these drugs results in dose-
dependent suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH),
leading to decreased blood concentrations of the ovarian sex hormones, estradiol and
progesterone.
2. These include: Cetrorelix and Ganirelix, they inhibit the release of gonadotrophins (LH, FSH).
➢ They are used in the treatment of infertility by assisted reproductive techniques (IVF).
➢ Also, may be used to treat hormone-sensitive cancers of the prostate and breast.
Cetrorelix Inj. Cetrotide® 0.25 mg , 3 mg kit
Ganirelix Prefilled Inj. Antagon®, Orgalutran® 250 mcg/0.5 ml
Abarelix Inj. Plenaxis 100 mg
Elagolix Tab Orilissa® 150 mg , 200 mg
Relugolix Tab Relumina® 40 mg
Notes:
1. Cetrorelix is used to treat female infertility as either:
a. Single dose regimen: 3 mg SC when serum estradiol levels show appropriate stimulation
response (range days 5-9) usually day 7; if hCG not administered within 4 days, continue
dose at 0.25 mg/day until hCG administered
b. Multiple dose regimen: 0.25 mg SC morning or evening of stimulation day 5 or morning
of stimulation day 6; continue until hCG administered
2. Ganirelix is used treat female infertility as 250 mcg SC qDay during mid-to-late follicular phase
after initiating follicle-stimulating hormone on day 2 and 3 of the cycle, continue therapy until
day of hCG administration.
3. Elagolix is specifically indicated for the management of moderate to severe pain associated with
Endometriosis; Elagolix significantly decreases symptoms of dysmenorrhea (menstrual pelvic
pain), non-menstrual pelvic pain, and dyspareunia (pain during sexual intercourse) in women
with Endometriosis.
➢ The duration of use of Elagolix in the treatment of endometriosis should be limited due
to a progressive risk of bone loss, and the lowest effective dosage should be used.
➢ Elagolix can be used for up to 24 months at the 150 mg once per day dosage and for up to
6 months at the 200 mg twice per day dosage.
4. Relugolix is approved in Japan (only) for the treatment of uterine fibroids (uterine leiomyoma)
in women; It is used at a dosage of 40 mg once daily.
➢ It is under development for the treatment of Endometriosis, Prostate Cancer in the USA.

6.4 -Posterior pituitary hormones
1. The pituitary gland, which lies at the base of the brain, produces a number of hormones that
regulate physical growth, metabolism, sexual development, and reproductive function.
2. Many of these hormones act indirectly by stimulating other glands, such as the thyroid, adrenal
glands, ovaries, and testes, to release their own hormones; (as discussed in the sections above).
A. Thyroid-stimulating hormone: stimulates production and release of thyroid hormones.
B. Prolactin: stimulates glands in the breast to produce milk in women.
C. Corticotrophin (ACTH): controls production and release of adrenal corticosteroid
hormones.
D. Gonadotrophins: (FSH) and (LH) act on the sex glands to stimulate egg production and
release in females, and sperm production in males; They also control the output of the sex
hormones estrogen, progesterone, and testosterone.
E. Growth hormone: promotes normal growth and development.
F. Melanocyte-stimulating hormone: controls skin pigmentation.
G. Antidiuretic hormone: (ADH or vasopressin) regulates the output of water in the urine.
3. In this section, we’ll talk about the remaining hormones which are secreted from the posterior
part; These include: Vasopressin, (Desmopressin) and Oxytocin (see chapter 7).
➢ Vasopressin acts on the kidneys, controlling the amount of water retained in the body and
returned to the blood, a lack of ADH is usually caused by damage to the pituitary; this in turn
causes diabetes insipidus.
4. In Diabetes Insipidus (DI), the kidneys cannot retain water and large quantities pass into the
urine; The chief symptoms are constant thirst and production of large volumes of urine.
o Classified into two types: Central DI (in which no vasopressin is secreted), and
Nephrogenic DI (due the lack of antidiuretic hormone effect in the kidneys).
5. Central Diabetes insipidus is treated with ADH or a related synthetic drug, Desmopressin, they
replace naturally produced ADH.
o Adjunctive therapies include: Chlorpropamide, Indomethacin, Carbamazepine.
o Thiazide diuretics may be prescribed for Nephrogenic DI (see Diuretics, chapter 3);
The usual effect of such drugs is to increase urine production, but in diabetes insipidus
they have the opposite effect, reducing water loss from the body.
Notes:
1. Vasopressin (antidiuretic hormone, ADH) is used in the treatment of pituitary (cranial)
diabetes insipidus as is its analogue Desmopressin, also used for nocturnal enuresis.
a. Desmopressin is more potent and has a longer duration of action than Vasopressin;
unlike vasopressin it has no vasoconstrictor effect (It is given by mouth or by intranasal
route for maintenance therapy).
b. Patients being treated for primary nocturnal enuresis should be warned to limit fluid
intake to minimum from 1 hour before dose until 8 hours afterwards; and to stop taking
Desmopressin during an episode of vomiting or diarrhea (until fluid balance normal).
c. Side effects include: Headache, facial flushing, nausea, hyponatremia, seizures.
d. The nasal formulation of Desmopressin is no longer indicated for Nocturnal
Enuresis by the FDA, due to reports of seizures in children using the nasal spray.
2. Other rare uses:
a. Desmopressin is also used to boost factor VIII concentration in mild to moderate
hemophilia and in von Willebrand’s disease, also given for the treatment of Uremic
bleeding in acute or chronic renal failure.
b. Terlipressin, a derivative of vasopressin, is used to control Esophageal Variceal
bleeding in portal hypertension in patient with liver cirrhosis.
Vasopressin Inj. Solu. Pitressin ® 20 units/ml
Desmopressin Nasal Spray Minirin , Stimate
® ® 0.1 mg/ml (5 ml),
1.5 mg/ml (2.5 ml)
Tab Minirin® 0.1 mg , 0.2 mg
Inj. Solu. Stimate® 4 mcg/ml
Terlipressin Inj. Powder Teripress , Glypressin
® ® 1 mg
Notes:
1. Desmopressin 5 ml Nasal spray delivers 10 mcg per spray, while the 2.5 ml Nasal spray delivers
150 mcg per spray. (the 2.5 ml container is 15 times more potent than the 5 ml container).
→ (good luck trying to convene your patients about this fact)
2. Terlipressin is used as a vasoactive drug in the management of hypotension. It has been found
to be effective when norepinephrine does not help; other Indications for use include
norepinephrine-resistant septic shock and hepato-renal syndrome.
3. Vasopressin related drugs: Also called vasopressin V2-receptor antagonist, they can be used in
the treatment of hyponatremia resulting from inappropriate secretion of antidiuretic hormone
Conivaptan * Inj. Solu. Vaprisol® 5 mg/ml
Tolvaptan ** Tab Samsca® 15 mg , 30 mg
* Conivaptan must be pre-mixed with D5W before administration. (As 20 mg/100 ml).
** Tolvaptan acts as vasopressin antagonist.
6.5– Other pituitary hormones (anterior):

A) Growth Hormone (GH) and its analogs
1. Also called Somatotropin, the synthetic form (Somatropin) is the only form used in medicine,
since the GH derived from animal sources is ineffective in humans.
2. GH influences a wide variety of biochemical processes; for example, through stimulation of
protein synthetic processes, cell proliferation and bone growth are promoted.
a. Used in the treatment of GH deficiency or growth failure in children.
b. Indicated for growth failure due to Prader-Willi syndrome, management of AIDS wasting
syndrome, short bowel syndrome, and GH replacement in adults with GH deficiency.
c. Abused by some athletes seeking to enhance their performance, GH is not approved for
this purpose, and some who have taken it have developed diabetes (DM).
d. It should not be used in pediatric patients with closed epiphyses, it should also be avoided in
patients with increased intracranial pressure, diabetic retinopathy, and obese patients with
Prader-Willi syndrome.
3. Mecasermin is a recombinant form of human insulin-like growth factor 1 (IGF-I) which is used
in the long-term treatment of growth failure and short stature in children with severe primary
IGF-I deficiency, for instance due to growth hormone deficiency or Laron syndrome (growth
hormone insensitivity).
Somatropin Inj. Powder Genotropin , Saizen
® ® 1.33 mg , 5 mg , 8.8 mg , 12 mg
Inj. Solu. Norditropin , Nutropin 5 mg/1.5 ml , 10 mg/2 ml ,
® ®
20 mg/2 ml
Recombinant human Prefilled Inj. Caretropin® 22 IU (7.5 mg)
growth hormone
Mecasermin Inj. Solu. Increlex® 10 mg/ml

B) GH inhibiting hormone and its analogs
1. Also called Somatostatin, it suppresses the GH and thyroid-stimulating hormone release, insulin,
glucagon, and gastrin, mainly used for the treatment of Acromegaly; It has 3 approved
analogs including: Octreotide, Lanreotide and Pasireotide.
➢ Octreotide is 40-45 times more potent than endogenous somatostatin.
➢ Octreotide reduce both GH and IGF-1; while Lanreotide reduce GH and normalize IGF-1.
2. Octreotide, Lanreotide is used in the treatment of acromegaly caused by hormone-secreting
tumors and in secretory diarrhea associated with tumors producing vasoactive intestinal
peptide, Both Octreotide, Lanreotide have a risk of causing gallbladder problems.
3. About Octreotide:
a. Used in Esophageal Variceal Bleeding to stop the bleeding.
b. Used in the treatment of Sulfonylurea Overdose.
c. Used in the treatment of VIPOMAS (a neuroendocrine tumors).
d. Used also in Several types of diarrhea including: (AIDS-related, Ileostomy-related,
Chemotherapy-related) and in Dumping syndrome.
e. Depot formulation (LAR) can be administered once every 4 weeks.
4. Pasireotide is indicated for treatment of adults with Cushing disease in whom pituitary
surgery is not an option or has not been curative.
5. Adverse effects of Somatostatin analogs include: diarrhea, abdominal pain, flatulence, nausea,
and steatorrhea; Gallbladder emptying is delayed, and asymptomatic cholesterol gallstones can
occur with long-term treatment; also, they can cause Arrhythmias and Hypothyroidism.
6. Pegvisomant, is a GH receptor antagonist; it binds to liver GH receptors and inhibits IGF-1.
➢ Indicated for the treatment of acromegaly.

Somatostatin analogs (GH inhibitors)
Octreotide Inj. Solu. Sandostatin® 0.1 mg/ml , 0.5 mg/ml , 1 mg/ml
Depot Inj. Sandostatin LAR ® 10 mg , 20 mg , 30 mg
Lanreotide Prefilled Inj. Somatuline ® 60 mg , 90 mg , 120 mg
Pasireotide S.C. Inj. Signifor® 0.2 mg/ml , 0.6 mg/ml ,
0.9 mg/ml
GH receptor antagonist
Pegvisomant Inj. Powder Somavert® 10 mg , 15 mg , 20 mg
C) Prolactin, Bromocriptine and Cabergoline

1. Prolactin, also called lactogenic hormone, is produced in both men and women; In women
prolactin controls the secretion of breast milk following childbirth; The disorders associated with
prolactin are all concerned with overproduction (Hyperprolactinemia).
➢ Prolactin normal range (0 – 20 ng/ml).
➢ High levels in women can cause Galactorrhea (lactation that is not associated with
pregnancy and birth), Amenorrhea (lack of menstruation), and infertility.
➢ If excessive prolactin is produced in men, the result may be Galactorrhea, Erectile
Dysfunction, Gynecomastia and infertility.
➢ In addition, it decreases sexual drive and reproductive function in both men and women.
2. Some drugs, such as Methyldopa, Estrogen, and the phenothiazine antipsychotics, can raise the
prolactin level in the blood; the increased prolactin levels are usually treated with
Bromocriptine or Cabergoline, (D2-receptor agonists); which inhibit prolactin production.
Notes:
1. Bromocriptine is a stimulant of dopamine receptors in the brain; it also inhibits release of
prolactin by the pituitary, Cabergoline has actions and uses similar to those of Bromocriptine,
but its duration of action is longer.
a. Bromocriptine inhibits the secretion of prolactin from the anterior pituitary and is used in
the treatment of prolactinoma (prolactin-secreting pituitary adenomas) and
endocrinological disorders associated with hyperprolactinemia, including amenorrhea,
galactorrhea, and infertility in both men and women.
b. Bromocriptine is also FDA approved for the treatment of Diabetics type 2 (DM); (it’s
thought to act throw resetting the circadian clock as in a winter rhythm; thus, increasing
the dopaminergic neuron activity in morning, which leads to increased glucose tolerance).
c. Growth hormone secretion may be suppressed by Bromocriptine in some patients with
acromegaly.
d. Because of its dopaminergic activity Bromocriptine is also used in the management of
Parkinson’s disease.
e. With Bromocriptine In patients with peripheral vascular disease, a worsening of the
vasospasm occurs, and in patients with peptic ulcer, there is a worsening of the ulcer.
also, it has the potential to cause pulmonary and retroperitoneal fibrosis.
2. About Cabergoline:
➢ More Potent than Bromocriptine, due to Higher affinity for D2 receptors
➢ Used in infertility due to hyperprolactinemia, dose usually is 0.5 – 1 mg twice a week.
➢ Used as a lactation suppressant (dose: half tablet every 12 hr. for 2 days only), this is not
(FDA) approved; also used after Abortion to stop milk production, (dose: 2 tabs once only).
➢ Cabergoline has been found to raise a man's chances of sustaining multiple orgasms during
sex (Enhance erection and libido in men), don’t try this at home, it’s not (FDA) approved.
➢ Co-administration with Clarithromycin is C.I.; it causes severe Vasospasm.
3. Adverse Effects (3):
a. Nausea is the most common adverse effect at the beginning of treatment with
Bromocriptine, but vomiting, dizziness, and orthostatic hypotension may also occur, Syncope
has followed initial doses.
b. Adverse effects are generally dose-related and may therefore be more frequent with the
higher doses; Nausea may be reduced by gradual increase of the dose, taking
Bromocriptine with food; Domperidone may also be given at least 1 hour before
Bromocriptine, for the first few days of therapy.
4. Quinagolide a non-ergot with high D2 affinity; approved only in Europe for hyperprolactinemia.
5. Excessive daytime sleepiness and sudden onset of sleep can occur with dopamine-receptor
agonists, patients starting treatment with these drugs should be warned of the risk and of the
need to exercise caution when driving or operating machinery; Those who have experienced
excessive sedation or sudden onset of sleep should refrain from driving or operating machines
until these effects have stopped occurring.
6. The BNF stated that Cabergoline should be dispense in original container (contains
desiccant) (1). (A desiccant is a hygroscopic substance that induces or sustains a state of dryness
(desiccation) in its vicinity); This mediation is usually expensive which forces the patient
sometime to buy it as one tab or two, this makes the pharmacist to open the original container
and sells the tab in another bag, which may lead to desiccation and maybe tab deformity.
Cabergoline Tab Dostinex® , Cabaser® 0.5 mg
Quinagolide Tab Norprolac 25 mcg , 50 mcg , 75 mcg
6.6 - Drugs for Adrenal Gland Disorders
Hyper-function of the adrenal glands involves excess production of the adrenal hormones cortisol
(resulting in Cushing syndrome) or aldosterone (resulting in hyperaldosteronism); Adrenal gland
hypo-function is associated with primary (Addison disease) or secondary adrenal insufficiency.
1. Hypersecretory cortisol diseases (Cushing syndrome)

Cushing syndrome results from effects of supraphysiologic glucocorticoid levels originating from
either exogenous administration (as corticosteroid abuse) or endogenous overproduction
by the adrenal gland (adrenocorticotropic hormone [ACTH] dependent) or by abnormal
adrenocortical tissues (ACTH independent).
➢ The most common findings in Cushing syndrome are central obesity and facial rounding (90%
of patients). Peripheral obesity and fat accumulation occur in 50% of patients. Fat
accumulation in the dorsocervical area (buffalo hump) is nonspecific, but increased
supraclavicular fat pads are more specific for Cushing syndrome. Patients are often described
as having moon faces and a buffalo hump.
Treatments available include: Metyrapone, Ketoconazole, Etomidate, Mitotane,
Cyproheptadine, Pasireotide and Mifepristone.
1. Metyrapone inhibits 11 β-hydroxylase, thereby inhibiting cortisol synthesis; Initially, patients
can demonstrate increased plasma ACTH concentrations because of a sudden drop in cortisol,
this can increase androgenic and mineralocorticoid hormones, resulting in hypertension, acne,
and hirsutism. Nausea, vomiting, vertigo, headache, dizziness, abdominal discomfort, and allergic
rash have been reported after oral administration.
2. Ketoconazole inhibits cytochrome P-450 enzymes, including 11 β-hydroxylase and 17 α-
hydroxylase; It is effective in lowering serum cortisol levels after several weeks of therapy; It also
has antiandrogenic activity, which may be beneficial in women but can cause gynecomastia
and hypogonadism in men.
➢ Because of the risk of severe hepatotoxicity, monitoring should include liver function tests
at baseline followed by weekly monitoring of serum ALT throughout therapy.
➢ Ketoconazole may be used concomitantly with Metyrapone to achieve synergistic reduction
in cortisol levels; in addition, ketoconazole’s antiandrogenic actions may offset the
androgenic potential of Metyrapone.
3. Etomidate is an imidazole derivative similar to ketoconazole that inhibits 11 β-hydroxylase.
4. Mitotane is a cytotoxic drug that inhibits the 11-hydroxylation of 11-deoxycortisol and 11-
desoxycorticosterone in the adrenal cortex, reducing synthesis of cortisol and corticosterone.
Similar to ketoconazole, Mitotane takes weeks to months to exert beneficial effects.
➢ Mitotane can cause significant neurologic and GI side effects, Lethargy, somnolence, and other
CNS effects are also common.
5. Cyproheptadine, a nonselective serotonin receptor antagonist and anticholinergic drug, can
decrease ACTH secretion in some patients with Cushing disease. However, side effects such as
sedation and weight gain significantly limit its use.
6. Pasireotide is a somatostatin analogue that binds and activates somatostatin receptors, thereby
inhibiting ACTH secretion, leading to decreased cortisol secretion. It is approved for treatment of
adults with Cushing disease for whom pituitary surgery is not an option or has not been curative.
➢ Has a LAR dosage form that is given once every 4 weeks.
7. Mifepristone is a progesterone and glucocorticoid-receptor antagonist that inhibits
dexamethasone suppression and increases endogenous cortisol and ACTH levels in normal
subjects. Evidence suggests that mifepristone is highly effective in reversing the manifestations
of hypercortisolism (hyperglycemia, hypertension, and weight gain); It is FDA approved for
treatment of endogenous Cushing’s syndrome in patients who have type 2 diabetes or glucose
intolerance and who are not eligible for, or have had poor response to, surgery.
Steroidogenesis Inhibitors
Metyrapone Cap Metopirone® 250 mg
Ketoconazole Tab Nizoral ® 200 mg
Etomidate Inj. Solu. Amidate ® 2 mg/ml
Adrenolytic Agents
Mitotane Tab Lysodren® 500 mg
Neuromodulators of ACTH Release *
Cyproheptadine Tab ---------- 4 mg
Pasireotide S.C inj. Signifor® 0.3 mg/ml , 0.6 , 0.9 mg/ml
Vial (I.M.) Signifor LAR ® 20 mg , 40 mg , 60 mg
Glucocorticoid-Receptor Blocking Agents
Mifepristone Tab Korlym® 300 mg
Tab Mifeprex® 200 mg
• Other Neuromodulators of ACTH Release include: Bromocriptine, Cabergoline, Valproic acid,
Octreotide, Lanreotide, Rosiglitazone, and Tretinoin.
2. Hyperaldosteronism
Hyperaldosteronism involves excess aldosterone secretion and is categorized as either primary
(stimulus arising from within the adrenal gland) or secondary (stimulus from extra adrenal).
➢ Patients may complain of muscle weakness, fatigue, paresthesias, headache, polydipsia, and
nocturnal polyuria; Signs may include hypertension and tetany/paralysis.
➢ Treated with aldosterone receptor antagonists (Spironolactone, Eplerenone, Amiloride):
o Spironolactone is a nonselective aldosterone receptor antagonist that competes with
aldosterone for binding at aldosterone receptors, thus preventing the negative effects of
aldosterone receptor activation.
o Eplerenone is a selective aldosterone receptor antagonist with high affinity for aldosterone
receptors and low affinity for androgen and progesterone receptors; it elicits fewer sex-
steroid–dependent effects than spironolactone.
o Amiloride is a potassium-sparing diuretic, is less effective than spironolactone.
(for more info, see chapter 3 diuretics).
3. Hyposecretory adrenal disorders

1. Primary adrenal insufficiency (Addison disease) usually involves destruction of all regions of the
adrenal cortex. There are deficiencies of cortisol, aldosterone, and the various androgens, and
levels of CRH and ACTH increase in a compensatory manner.
2. Secondary adrenal insufficiency most commonly results from exogenous corticosteroid use,
leading to suppression of the hypothalamic-pituitary-adrenal axis and decreased ACTH release,
resulting in impaired androgen and cortisol production.
3. Patients commonly complain of weakness, weight loss, GI symptoms, salt craving, headaches,
memory impairment, depression, and postural dizziness; Signs of adrenal insufficiency include
increased skin pigmentation, postural hypotension, fever, decreased body hair, vitiligo,
amenorrhea, and cold intolerance.
4. Hydrocortisone and prednisone are the glucocorticoids of choice, administered twice daily at
the lowest effective dose while mimicking the normal diurnal adrenal rhythm of cortisol
production; while in primary adrenal insufficiency, Fludrocortisone 0.05 to 0.2 mg orally once
daily can be used to replace mineralocorticoid loss. (for corticosteroids see chapter 11).
6.7- Bone disorders (Osteoporosis, Osteomalacia)
1. Osteoporosis is a bone disorder characterized by low bone density, impaired bone architecture,
and compromised bone strength predisposing to fracture; occurs most commonly in
postmenopausal women and in those taking long-term oral corticosteroids.
➢ Bone loss occurs when resorption exceeds formation, usually from high bone turnover when
the number or depth of bone resorption sites greatly exceeds the ability of osteoblasts to form
new bone; (osteoblast is responsible for bone formation, and osteoclast for resorption).
2. World Health Organization (WHO) Definitions Based on T-scores (T-score indicates that for
every standard deviation [SD] below the mean young adult bone mineral density [BMD], fracture
risk increases 2-fold)
o Normal = BMD within 1 SD of the young adult mean.
o Low bone mass (osteopenia) = BMD 1–2.5 SD below the young adult mean (often seen as
T-score between -1 and -2.5).
o Osteoporosis = BMD at least 2.5 SD below the young adult mean (often seen as T-score of
less than -2.5).
3. In osteomalacia (called rickets when it affects children), a lack of vitamin D leads to loss of
calcium, resulting in softening of the bones. There is pain and tenderness and a risk of fracture
and bone deformity; while in children, growth is retarded.
First: Bisphosphonates
1. They include (oral: Alendronate, Ibandronate and Risedronate or I.V: Zoledronic acid); they
inhibit bone resorption by binding very tightly to bone matrix, preventing its removal.
2. Uses of Bisphosphonates:
a. Bisphosphonates have an important role in the prophylaxis and treatment of osteoporosis
(postmenopausal osteoporosis) and corticosteroid-induced osteoporosis.
b. Because bone resorption increases plasma Calcium concentrations, the bisphosphonates are
used as adjuncts to the treatment of severe hypercalcemia, especially when associated
with malignancy.
c. They are also used in other disorders associated with excessive bone resorption and turnover,
such as Paget’s disease of bone, as well as in the management of bone Metastases.
3. Some bisphosphonate preparation may be given once daily (10 mg alendronate tablet), once
weekly (70 mg alendronate tablet, Risedronate 35 mg tablet), as well as once monthly
(Ibandronic acid 150 mg tablet).
4. Administration:
a. Because bioavailability is very poor for bisphosphonates and to minimize GI side effects, each
oral dose should be taken with at least 6 ounces of plain tap water (not coffee, juice,
mineral water, or milk) at least 30 (60 for Ibandronate) minutes before consuming any
food, supplements (including calcium and vitamin D), or medications.
b. The patient should also remain upright (either sitting or standing) for at least 30 minutes
after alendronate and Risedronate and 1 hour after Ibandronate administration.
c. A patient who misses a weekly dose can take it the next day. If more than 1 day has lapsed,
that dose is skipped until the next scheduled ingestion. If a patient misses a monthly dose, it
can be taken up to 7 days before the next administration.
5. Esophageal reactions: Severe esophageal reactions reported with all oral bisphosphonates;
patients should be advised to stop tablets and seek medical attention for symptoms of
esophageal irritation such as dysphagia, pain on swallowing, retrosternal pain, or heartburn.
6. Oral Bisphosphonate can cause osteonecrosis of the jaw (BRONJ), you should inform any
patient who has dental appointments or has dental problems.

Alendronate Tab Fosamax ® 10 mg , 35 mg , 70 mg
Oral Solu. Borgalendro ® 70 mg/75 ml
Risedronate Tab DR Actonel ® 35 mg
Ibandronate Tab Boniva ® 150 mg
Prefilled Inj. 1 mg/ml (3 ml)
Etidronate Tab Didronel ® 200 mg , 400 mg
Tiludronate Tab Skelid ® 200 mg
Pamidronate I.V. Solu. Aredia® 30 mg , 60 mg , 90 mg
Zoledronic acid I.V. Solu. Reclast , Zometa , Aclasta
® ® ® 4 mg/5 ml , 5 mg/100 ml
Risedronate + Ca + Vit D3 Tab Actonel Combi® 35 mg + 1000 mg + 880 IU
Alendronate + Ca + Vit D3 Tab Fosamax Plus D® 70 mg + 140 mg + 5600 IU
Alendronic acid Tab Fosavance® 70 mg
+ Cholecalciferol + 5600 I.U
Note1: (8)
Several Bisphosphonates are available; are they all the same? Below some clinical facts:
1. Alendronate: 10 mg/day or 70 mg/week; decreases vertebral fractures by 47% and hip
fractures by 51%.
2. Risedronate: 35 mg/week or 150 mg once monthly; decreases non-vertebral fracture risk
by 33%–39% and vertebral fracture by 41%–49%.
3. Ibandronate: 150 mg once monthly, Increases BMD at spine and hip; but studies show only
a decreased risk of vertebral fractures.
4. Zoledronic acid: 5 mg intravenously reduces non-vertebral fracture risk by 25%, hip
fracture by 40%, and vertebral fracture risk by 70%.
Note2:
• Bisphosphonates have a
different relative resorptive
potencies; (their ability to get
attached to the osteoclast
cells in the bone matrix), as
follows in the table:
Note3:
• In a recent study; Endoscopic
Comparison of Esophageal
and Gastroduodenal Effects of
Risedronate and Alendronate
in Postmenopausal Women;
showed that at doses used for the treatment of osteoporosis, Risedronate was associated with a
significantly lower incidence of gastric ulcers than Alendronate; These findings confirm that
bisphosphonates differ in their potential to damage the gastroesophageal mucosa. (7)
Note4:
• In another study; comparing Alendronate and Risedronate, head to head; Alendronate 70 mg
Once Weekly yielded significantly greater BMD gains and larger decreases in bone turnover
marker levels than Risedronate 35 mg Once Weekly over 24 months, with no difference in upper
GI tolerability. (9)
Second: Calcium Metabolism Modifiers:
These include: Calcitonin, Denosumab, Romosozumab, Teriparatide, and Abaloparatide.
1. Calcitonin reduces bone resorption, but it is less effective than the bisphosphonates, a unique
property of calcitonin is the relief of pain associated with osteoporotic fracture.
➢ It acts by inhibiting osteoclast activity in the bone.
➢ Nasal Calcitonin reduces the incidence of new vertebral fractures by 36%.
➢ Dosage: 200 international units/day in one nostril, alternating nostrils daily.
2. Denosumab is a monoclonal antibody that targets receptor activator of nuclear factor kappa -B
ligand (RANKL); (a cytokine essential for formation, function, survival of Osteoclasts), thus blocks
osteoclast activation; it is approved for treatment of postmenopausal osteoporosis in women at
high risk of fracture, it’s also used for bone destruction caused by Rheumatoid Arthritis.
a. It is administered 60 mg via S.C. injection every 6 months.
b. Increased hip (6%) and spine (9%) BMD.
c. Reduced spinal fracture risk by 68%, hip fracture risk by 40%.
d. Considered alternative first-line therapy by AACE and ACP guidelines.
e. Denosumab has been associated with an increased risk of infections, secondary malignancies,
hypocalcemia, and dermatological reactions.
f. It should be reserved for women intolerant or unresponsive to other therapies.
3. Romosozumab is a bone-forming monoclonal antibody that works by inhibiting the activity of
sclerostin, resulting in increased bone formation and to a lesser extent decreased bone
resorption; its FDA approved to treat osteoporosis in postmenopausal women at high risk for
fracture; it’s administered as once-monthly injections for a 12-month course to therapy.
➢ Treatment with Romosozumab should be followed by an antiresorptive agent to maintain and
enhance its therapeutic effect.
➢ It may increase the risk of heart attacks, strokes, and deaths from cardiovascular disease.
4. Teriparatide is a recombinant segment of human parathyroid hormone that is administered
subcutaneously for the treatment of osteoporosis.
a. Parathyroid hormone given continuously leads to dissolution of bone’ However, when it is
given by intermittent dose S.C. once daily, bone formation is the predominant effect by
preferentially stimulating osteoblastic activity over osteoclastic activity.
b. It is the first approved treatment for osteoporosis that stimulates bone formation; other
drugs approved for this indication inhibit bone resorption.
c. Decreases vertebral fractures by 65% and non-vertebral fractures by 53%; but not shown to
decrease hip fractures.
d. Effective in the treatment of glucocorticoid-induced osteoporosis.
e. Contraindications: Hypercalcemia, bone metastases, disorders that predispose women to
bone tumors such as Paget’s disease
5. Abaloparatide (related to Teriparatide); a modified Recombinant human parathyroid hormone;
it is indicated for the treatment of post-menopausal women with osteoporosis at high risk for
fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or
patients who have failed or intolerant to other available osteoporosis therapy.
➢ Decreases vertebral fractures by 86% and non-vertebral fractures 43%; but not shown to
decrease hip fractures.
➢ It Has the advantage over Teriparatide that it has no contraindications.
Calcitonin salmon Inj. Solu. Miacalcin® , Fortical® 200 I.U/ml
Nasal Spray 3.7 ml (200 I.U)
Teriparatide Prefilled Inj. Forteo® 250 mcg/ml (2.4 ml)
Abaloparatide Prefilled Inj. Tymlos® 80 mcg/40 mcl
Romosozumab Prefilled Inj. Evenity® 105 mg/1.17 ml
Denosumab Prefilled Inj. Prolia® 60 mg/ml (1 ml)
Prefilled Inj. Xgeva® 70 mg/ml (1.7 ml)
Strontium Ranelate Sachet Protelos® 2 gm (granules for oral use)
Menaquinone-7 (granules)
Cap MenaQ7® 45 mcg , 180 mcg
Extra Notes:
1. Strontium increases bone formation in bone tissue culture as well as osteoblast precursor replication and
collagen synthesis in bone cell culture.
➢ Strontium stimulates the calcium-sensing receptors and leads to the differentiation of pre-osteoblast
to osteoblast which increases the bone formation; it also stimulates osteoblasts to secrete
osteoprotegerin in inhibiting osteoclasts formed from pre-osteoclasts in relation to the RANKL
system, which leads to the decrease of bone resorption.
➢ It showed significant reduction in vertebral fractures with 41% and hip fractures with 36% compared
with patients treated with placebo.
➢ Strontium increased the risk of venous thromboembolism, pulmonary embolism and serious
cardiovascular disorders, including myocardial infarction.
2. Menaquinone-7 (also called Vitamin K2) as a supplementation it helps to decrease bone loss.
Third: Vitamin D Analogs:

1. Usually is given as a prophylactic treatment for vitamin D deficiency or as a supplement with
calcium for bone disorders, or for babies with rickets.
➢ Alfacalcidol, Ergocalciferol, Calciferol, Cholecalciferol and 1,25-dihydroxycholecalciferol are
all the same drug (Vitamin D3).
➢ Calcitriol, Calcifediol, Doxercalciferol, Paricalcitol are also Vit. D analogues but they are
indicated for secondary hyperparathyroidism associated with Vit D insufficiency in
patients with stage 3 or 4 chronic kidney disease (CKD).
➢ There are also Topical Vit. D analogues used mainly for psoriasis (see chapter 14, sec 12)
Alfacalcidol Cap One-Alpha® 0.25 mcg , 0.5 mcg , 1 mcg
Oral Drops 2 mcg/ml
Inj. Solu. (I.V.) 2 mcg/ml
Ergocalciferol Oral Solu. (only) Sterogyl 15 “A” ® 600,000 IU/1.5 ml
Oral Solu. (and) Sterogyl 15 “H” ® 600,000 IU/1.5 ml
I.M. Inj. Solu.
Oral Drop Sterogyl D® 2 Million IU/100 ml (20 ml)
Cholecalciferol Oral Drops Dibase® 10,000 IU/ml
Oral Solu. 25,000 IU , 50,000 IU /2.5 ml
Inj. Solu. 100,000 IU , 300,000 /ml
Vit D analogues for 2ndry hyperparathyroidism
Calcitriol Cap Rocaltrol® , Calcijex® 0.25 mcg , 0.5 mcg
Oral Solu. 1 mcg/ml
Inj. Solu. 1 mcg/ml
Calcifediol Cap Rayaldee® 30 mcg
Doxercalciferol Cap Hectorol® 0.5 mcg , 2.5 mcg
Inj. Solu. 2 mcg/ml
Paricalcitol Cap Zemplar® 1 mcg , 2 mcg , 4 mcg
Inj. Solu. 2 mcg/ml
Note: How to calculate the required Vit D3 dose for patients
➢ Use the following equation; (75 – lab test ng/ml) × (Age in yrs.) × (wt. in kg) = dose per month IU
➢ Divide by 30 = dose per day, divide by 4 = dose per week, given for at least 2 months.
6.8– Calcimimetics
1. A Calcimimetic is a drug that mimics the action of calcium on tissues, by allosteric activation
of the calcium-sensing receptor that is expressed in various human organ tissues. Calcimimetics
are used to treat secondary hyperparathyroidism (SHPT).
➢ In the treatment of SHPT patients on dialysis, they do not appear to affect the risk of early
death in those patients.
➢ they do decrease the need for a parathyroidectomy but caused more issues with low blood
calcium levels and vomiting.
2. Currently there are two Calcimimetics available: Cinacalcet and Etelcalcetide (formerly
Velcalcetide), they mimic calcium at the parathyroid hormone receptor. This binding will
increase the sensitivity of calcium-sensing receptors (CaSR) on the parathyroid gland. As a result
of the receptor "thinking" there is sufficient calcium, parathyroid hormone (PTH) secretion will
be reduced; Lower calcium levels will be seen as well; they can be used concomitantly with
vitamin D therapy.
➢ Common side effects include: nausea and vomiting, hypocalcemia, and adynamic bone
disease if intact parathyroid hormone (iPTH) levels drop below 100pg/ml.
Cinacalcet Tab Sensipar® 30 mg , 60 mg , 90 mg
Etelcalcetide Vial (Solu.) Parsabiv® 5 mg/ml , 10 mg/2 ml
** Etelcalcetide = Velcalcetide, they are the same drug.
6.9 - Other Endocrine drugs: (5-6)

Cysteamine Cap , Cap DR Cystagon® , Procysbi® 150 mg , 75 mg (DR Cap)
Trientine Cap Syprine® 250 mg
Sevelamer Tab Renvela® , Renagel® 400 mg , 800 mg
Fenoldopam I.V infusion Corlopam® ------------
Miglustat Cap Zavesca® 100 mg
Imiglucerase Vial Cerezyme® 200 units , 400 units
Riluzole Tab Rilutek® 50 mg
Notes:
1. Cysteamine is used in the treatment of disorders of Cysteine excretion; and for Nephropathic
cystinosis.
2. Trientine is a chelating agent, and is used to bind up and remove copper in the body to treat
Wilson's disease, and to treat Mg+ toxicity.
3. Sevelamer is a PO4 scavenger, used for the treatment of hyperphosphatemia.
4. Fenoldopam is a D1-dopamine receptor agonist: rapid-acting vasodilator; decreases peripheral
resistance and increases renal blood flow; has minimal adrenergic effects
a. It is also diuretic, natriuretic and used to treat a hypertensive crisis, beneficial in
hypertensive patients with concomitant renal insufficiency.
b. Used with Caution in patients with glaucoma or raised intraocular pressure as
Fenoldopam raises intraocular pressure.
c. Concomitant use of Fenoldopam with a beta-blocker should be avoided if possible, as
unexpected hypotension can result from beta-blocker inhibition of sympathetic-mediated
reflex tachycardia in response to Fenoldopam.
5. Miglustat is Used to treat type 1 Gaucher’s disease and Neimann-Pick disease.
6. Riluzole is an NMDA receptor antagonist, it’s the only drug approved for the spasmolytic
treatment of ALS (Amyotrophic Lateral Sclerosis).
6.10- Rare Drugs used in Rare Metabolic Disorders
Disease Name Explanation Drug Name (Sci.) Brand Name
Porphyria A disease due to a mutation in one Heme arginate, NormoSang®,
of the genes that make Heme Hematin Panhematin®
Fabry‘s disease known as lysosomal storage Agalsidase Alfa Fabrazyme®
diseases; the genetic mutation that
causes Fabry disease interferes
with the function of an enzyme
which processes biomolecules
known as sphingolipids, leading to
these substances building up in the
walls of blood vessels and other
organs.
Carnitine deficiency primary (inborn errors of Levocarnitine Carnitor®
metabolism) or 2ndry (in
hemodialysis patients)
Gaucher‘s disease a rare genetic disorder Imiglucerase, Cerezyme®,
characterized by the deposition of Velaglucerase Alfa, Vpriv®,
glucocerebroside in cells of the Miglustat Zavesca®
macrophage-monocyte system.
The disorder results from the
deficiency of the enzyme
glucocerebrosidase.
Homocystinuria an inherited disorder of the Betaine Anhidra®
metabolism of the amino acid Or
methionine due to a deficiency of (Trimethylglycine)
cystathionine beta synthase.
eading to accumulation of
homocysteine and its metabolites
(homocystine, homocysteine-
cysteine complex, and others) in
blood and urine.
Mucopolysaccharidosis caused by the absence or Elosulfase Alfa, Vimizim®,
malfunctioning of lysosomal Idursulfase, Elaprase®,
enzymes needed to break down Laronidase Aldurazyme®
glycosaminoglycans (GAGs). These
long chains of sugar carbohydrates
occur within the cells that help
build bone, cartilage, tendons,
corneas, skin and connective tissue.
GAGs are also found in the fluids
that lubricate joints.
Nephropathic a lysosomal storage disease Mercaptamine Cystagon®
cystinosis characterized by the abnormal (Cysteamine)
accumulation of the amino acid
cystine.
Niemann-Pick Type C rare progressive genetic disorder Miglustat Zavesca®
disease characterized by an inability of the
body to transport cholesterol and
other fatty substances (lipids)
inside of cells. This leads to the
abnormal accumulation of these
substances within various tissues
of the body, including brain tissue.

Pompe disease Glycogen storage disease type II, Alglucosidase Alfa Myozyme®
also called Pompe disease, is an
autosomal recessive metabolic
disorder; which damages muscle
and nerve cells throughout the
body. It is caused by an
accumulation of glycogen in the
lysosome due to deficiency of the
lysosomal acid alpha-glucosidase
enzyme.
Tyrosinaemia type I a genetic disorder characterized by Nitisinone Orfadin®
elevated blood levels of the amino
acid tyrosine, a building block of
most proteins. This condition is
caused by a shortage of the enzyme
fumarylacetoacetate hydrolase,
one of the enzymes required for the
multi-step process that breaks
down tyrosine
Urea cycle disorders Hyperammonaemia due to Carglumic acid Carbaglu®
N-acetylglutamate synthase
deficiency
Long-term treatment of urea cycle Sodium Buphenyl®
disorders phenylbutyrate
Wilson‘s disease genetic disorder in which copper Penicillamine Cuprimine®
builds up in the body; Symptoms
are typically related to the brain
and liver.
Acute hepatic group of four inherited diseases of Givosiran Givlaari®
porphyrias (AHPs) heme biosynthesis that present
with episodic, acute neurovisceral
symptoms.
References
1- BNF 82.
2- Mary Anne, koda-kimble (ed.), Applied Therapeutics: The clinical use of drugs, 11th Ed.
4- Current Challenges in Management of Hypothyroidism. Supplement to U.S. Pharmacist
7- Gastroenterology Magazine 2000; 119:631–638
8- ACCP Updates in Therapeutics® 2018: Pharmacotherapy
10- Richards KA, Liou JI, Cryns VL, et al. J Urol. 2018.
OBSTETRICS AND
GYNECOLOGY
Chapter Seven: Obstetrics and Gynecology
7.1- Drugs used in Obstetrics 7.5 – Polycystic ovary syndrome

A. Tocolytics (PCOS)
B. Induction and augmentation of
labor
7.6 - Vaginal Gels to aid natural
C. Prevention and treatment of
Postpartum hemorrhage fertility
D. Anti-D Immunoglobulin injection
E. Obstetric Gels that Facilitate 7.7– Infertility in Women
Delivery A. Ovulation induction
F. Thromboembolic Events in B. Controlled Ovarian Stimulation
Pregnancy C. Assisted Reproductive Technology
D. IVF Protocols
7.2- Galactagogues (Breastmilk 7.8 – Sexual Dysfunction in

boosting drugs) Women
A. Low Sexual Desire in Women
7.3- Preparations for vaginal and B. Female Sexual Arousal Disorder
vulvar conditions
A. Topical and Systemic Hormonal 7.9 – Vaginal Douches (Female
replacement therapy (HRT) for Hygiene products)
vaginal atrophy
B. Vaginal infections
➢ Fungal infections (Thrush)
➢ Bacterial infections
➢ Trichomoniasis infections
➢ Chlamydia infections
➢ Combination Products for
Vaginal Infections
➢ Other Vaginal products
7.4- Contraception methods

1. Combination oral contraceptives
2. Progestin-only pills
3. Transdermal patches
4. Injectable progestins
5. Spermicidal contraceptives
6. Vaginal ring
7. Progestin intrauterine device
8. Progestin implants
9. Barrier Female Contraceptives
10. Post-coital contraception:
(Emergency Contraception)
Sam’s Guide: Chapter 7 – Obs & Gyne
Chapter Seven: Obstetrics and Gynecology
7.1- Drugs used in Obstetrics
1. Normal labor has three stages; In the first stage, the uterus begins to contract, initially irregularly
and then gradually more regularly and powerfully, while the cervix dilates until it is fully
stretched. During the second stage, powerful contractions of the uterus push the baby down the
mother’s birth canal and out of her body; The third stage involves the delivery of the placenta.
➢ Term labor: Weeks 37–40.
➢ Preterm labor: Uterine contractions with cervical changes before week 37.
2. Drugs may be required during one or more stages of labor for any of the following reasons: to
induce or augment labor; to delay premature labor and to relieve pain, or to terminate pregnancy.
A) Tocolytics:
1. When contractions of the uterus start before the 34th week of pregnancy, doctors usually advise
bed rest and may also administer a drug that relaxes the muscles of the uterus (Tocolytics), and
thus halts labor; the drug is given in hospital by injection, but it may be continued orally at home.
2. Also called Myometrium relaxants, they inhibit uterine contractions, especially if cervix
dilated less than 4 cm and membranes intact; the purposes of Tocolytic therapy are threefold:
a. Postpone delivery long enough to allow for the maximum effect of antenatal steroid
administration.
b. Allow for transportation of the mother to a facility equipped to deal with high-risk deliveries.
c. Prolongation of pregnancy when there are underlying, self-limited conditions that can cause
labor, such as pyelonephritis or abdominal surgery that are unlikely to cause recurrent
preterm labor.
3. Prophylaxis for patients with a history of preterm labor 16–36 weeks: Hydroxyprogesteron
acetate (Primolut-Depot®) 250 mcg I.M. every week from 16 to 36 weeks’ gestation.
4. Tocolytics inhibit uterine contractions and are used in premature labor to delay early
delivery; Examples of Tocolytics include: β2-agonists (like salbutamol, Terbutaline) and
calcium-channel blockers (Nifedipine), magnesium sulfate and NSAIDs as (Sulindac and
indomethacin), All have been used for their Tocolytic actions.
➢ β2-agonists: salbutamol and terbutaline are licensed for inhibiting uncomplicated
premature labor by I.V. route between 22 and 37 weeks of gestation to permit a delay in
delivery of up to 48 hours; Oral therapy is no longer recommended.
o They have FDA warning for I.V. use beyond 48 hours because of severe adverse effects in
the mother such as elevated heart rate, transient hyperglycemia, hypokalemia, cardiac
arrhythmias, pulmonary edema, and myocardial ischemia.
➢ Nifedipine (unlicensed indication) can be given initially in a dose of 20 mg followed by 10–
20 mg 3–4 times daily adjusted according to uterine activity.
➢ Magnesium sulfate inhibits uterine activity by antagonism of calcium, it’s the drug of choice
in patients with diabetes.
➢ NSAIDs have the risks of Premature closure of ductus arteriosus, necrotizing enterocolitis,
intracranial hemorrhage, and their use is strictly limited to 72 hours only.
5. Atosiban (oxytocin receptor antagonist) is licensed in Europe (not approved in USA) for the
inhibition of uncomplicated premature labor between 24 and 33 weeks of gestation, it’s may be
preferable to a beta agonist because it has fewer side effects.
Atosiban Inj. Tractocile® 7.5 mg/ml
B) Induction and augmentation of labor:
1. Induction of labor may be advised when a doctor considers it risky for the health of the mother
or baby for the pregnancy to continue, if natural labor does not occur within two weeks of the
due date or when a woman has pre-eclampsia; Other common reasons for inducing labor include
premature rupture of the membrane surrounding the baby (breaking of the waters), slow growth
of the baby due to poor nourishment by the placenta, or death of the fetus in the uterus.
➢ When labor needs to be induced, oxytocin may be administered I.V.
➢ Alternatively, a prostaglandin pessary (Supp.) may be given to soften and dilate the cervix.
➢ If these methods are ineffective or cannot be used because of potential adverse effects; a
caesarean delivery may have to be performed.
2. Oxytocin (the natural hormone); is responsible for signaling contractions of the womb during
labor; The hormone stimulates the uterine muscles to contract, so labor begins; it also increases
the production of prostaglandins, which move labor along and increases contractions even more.
➢ Once the baby is born, Oxytocin promotes lactation by moving the milk into the breast.
➢ Studies of Oxytocin also have found that it is an important chemical messenger that controls
some human behaviors and social interaction.
➢ It is oxytocin that triggers the bond between a mother and an infant, and it may also play a
role in recognition, sexual arousal, trust and love.
➢ It is sometimes referred to as the "love hormone" because levels of oxytocin increase during
hugging and sex orgasm; Females usually have higher levels than males.
Notes:
1. Oxytocin is administered by slow I.V. infusion (or by Pump) to induce or augment labor (2).
➢ Oxytocin may also be used to strengthen the force of contractions in labor that has started
spontaneously but has not continued normally.
➢ A combination of Oxytocin and another uterine stimulant (Ergometrine) is given to most
women as the baby is being born or immediately following birth to prevent excessive bleeding
after the delivery of the placenta; This combination encourages the uterus to contract after
delivery, which restricts the flow of blood.
➢ Adverse effects: Uterine rupture, uteroplacental hypoperfusion, fetal distress from hypoxia.
2. Carbetocin and Demoxytocin are Oxytocin analogs with longer half-life (not FDA approved yet).
3. Castor Oil is also given to induce or augment labor by oral route.
4. Misoprostol was first introduced to prevent and treat stomach ulcers, but later on it has been
used to start labor, induce abortions and to treat postpartum bleeding due to insufficient
contraction of the uterus.
➢ It is approved for use in the prevention of NSAID-induced gastric ulcers.
➢ Adverse effects: Headache, nausea, vomiting, diarrhea, abdominal pain, and uterine hyper
stimulation
5. Misoprostol and Dinoprostone is given orally or vaginally for the induction of labor (and the
termination of pregnancies).
a. The most commonly encountered side effects are uterine hyper stimulation and meconium-
stained amniotic fluid.
b. Use of misoprostol is contraindicated in women with a previous uterine scar because of its
association with uterine rupture, a catastrophic medical event.
6. Sulprostone is used I.M. for the Induction of termination of pregnancy (maternal or fetal
indication); induction of labor in the case of fetal death in utero; Treatment of postpartum atonic
hemorrhage.
7. Gemeprost is used as a treatment for obstetric bleeding (used in preparing the cervix before
uterine surgery), also it is used with mifepristone to terminate pregnancy up to 24 weeks
gestation.
Castor Oil Oral Solu. Castor Oil® , Emulsoil® 30 ml
Oxytocin Inj. Pitocin®, Syntocinon® 10 units\ml
®
Carbetocin Inj. )Pabal® 100 mcg\ml

Demoxytocin Buccal Tab Sandopart 100 mcg
Prostaglandins
Vag. Insert Vagiprost® 200 mcg
Dinoprostone Vag. Insert Cervidil® , Propess® 10 mg
Vag. Supp. Prepidil® 20 mg
Vag. Gel Prostin E2® 400 mcg\ml , 800 mcg\ml
Inj. Solu. I.V. Prostin E2® 1 mg\ml , 10 mg\ml
Carboprost Inj. Solu. Hemabate® 250 mcg\ml
Sulprostone Inj. Solu. Nalador® 500 mcg\vial
Gemeprost Vag. Tab Cervagem® 1 mg
** All these medications above may be abused to induce illegal abortions, NEVER give them without an
Authorized prescription.
C) Prevention and treatment of Postpartum hemorrhage:

1. If the uterus fails to contract adequately after delivery (uterine atony), or if retained placental
remnants prevent retraction of the placental bed, postpartum hemorrhage may occur; these two
causes account for about 80% of cases of postpartum hemorrhage.
2. Postpartum hemorrhage may be fatal to the mother unless promptly dealt with, and
management generally involves:
a. Removal of the placenta if it has not been expelled.
b. The use of Oxytocic’s to contract the uterus.
c. Blood Transfusion, if blood loss is severe.
3. Parenteral oxytocin, or an ergot alkaloid (Ergometrine or Methylergometrine), is the oxytocic
generally used to control bleeding due to uterine atony.
4. Methylergonovine, Carboprost, misoprostol and Dinoprostone (see above) have all been
used to stop postpartum hemorrhage; but less evidence of efficacy is available for misoprostol
and Dinoprostone.
5. Anti-Fibrinolytics as (Tranexamic acid and Aminocaproic acid) can be effective in reducing
blood loss only in injections with high doses, this is a controversy option due to safety concerns
with high doses; (see chapter 3, section 17 for more info on anti-Fibrinolytics).
Ergometrine Tab , Inj. Ergotrate® , Ergonovine® 0.2 mg (tab)
0.2 mg/ml (Inj. 1 ml)
Ergometrine + Inj. Syntometrine® (500 mcg + 5 units)/ml
Oxytocin
Methylergometrine Tab , Inj. Methergine® 0.125 mg , 0.2 mg (tab)
0.2 mg/ml (Inj.)
** NEVER give them without an Authorized prescription.

Tranexamic acid Amp Exacyl® , Cyklokapron® 100 mg , 50 mg
Tab Cyklokapron® , Lysteda® 500 mg , 650 mg
Aminocaproic acid Tab Amicar® , Cyclo-C® 500 mg
Aprotinin Inj. Solu. Trasylol® 10 million IU/ml
D) Anti-D Immunoglobulin injection:
1. Given as I.M. injection that is used to prevent the immunological condition known as Rhesus
disease (or hemolytic disease of newborn); The medicine is a solution of IgG Anti-D (anti-RhD)
antibodies that suppresses the mother's immune system from attacking Rh-positive blood cells
which have entered the maternal blood stream from fetal circulation.
2. It is for the pregnant women carrying factor Rhesus negative (Rh-) with a positive husband (Rh+),
and the blood group was positive (Rh+), usually given in the 2nd pregnancy due to the 1st one is
often passes safely; Time of Administration: given between the 24 and 38 weeks of pregnancy
to the mother, or immediately after birth within 72 hours of birth.
Anti-D Immunoglobulin Inj. Rhoclone® , RhoGAM® 150 mcg , 300 mcg
Inj. WinRho SDF® 120 mcg , 300 mcg
E) Obstetric Gels for labor facilitation

1. These are sterile obstetric gels that is to be applied by doctor below the cervix via a soft vaginal
Catheter, then the gel immediately begins to form a lubricating film on the surface of the birth
canal, they help both the mother and the baby by reducing friction in the second stage of labor
and significantly shortening time taken to deliver the baby.
2. Usually these product’s effects are physical and it contains no active pharmaceutical or
hormonal ingredients, the perineum should also be massaged during labor.
Trade name D. form Scientific names concentration
Natalis 1®, Obs. Gel Hydroxyethyl cellulose, glycerol, xanthan gum, 15 ml ,
DiaNatal® sodium chloride, propylene glycol, water 11 ml
F) Thromboembolic Events in Pregnancy

1. Pregnancy increases the risk of venous thromboembolism (VTE) 4 to 5 fold over that in the
non-pregnant state; The two manifestations of VTE are deep venous thrombosis (DVT) and
pulmonary embolus (PE); this risk is also doubled to 8-10 folds with co-current use of
Progestins (Dydrogesterone, Hydroxyprogesteron, Allyl-Estrenol); which are used in pregnancy
for Prophylaxis of preterm labor and habitual abortion.
➢ Obesity, low movement or Immobilization, prolonged bed rest and smoking; all increase
risks of VTE; Cesarean delivery has twice the risk of VTE as vaginal delivery.
➢ Pregnancy after the age of 35 years augments the risk of VTE, as does multigravidas of
more than four pregnancies.
2. Although most reports suggest that VTE can occur at any trimester in pregnancy, studies suggest
that VTE is more common during the first half of pregnancy.
➢ Thus; prophylaxis treatment in high risk group is preferred to start in the 4th or 5th month
of pregnancy.
3. Sequelae of DVT and PE include complications such as pulmonary hypertension, post-thrombotic
syndrome, and venous insufficiency.
4. One study found that 80% of pregnant women with DVT experience pain and swelling of the
lower extremity (usually pain in the leg or gulf, unilateral on one side), DVT will evolve to PE
if not treated; Patients with massive PE may end with Syncope, Hypotension and sudden death.
➢ VTE (DVT, PE) is the second most common cause of death during pregnancy.
5. Heparin UFH (unfractionated) and Low Molecular Weight Heparins (LMWHs) are the
preferred drugs for managing VTE in pregnancy, But LMWHs is preferred over heparin.
➢ Prophylaxis: Enoxaparin 4000 IU S.C. daily.
➢ Treatment: Enoxaparin 100 IU/kg S.C. every 12 hours.
6. Prophylaxis with LMWHs or UFH should be discontinued 12–24 hours before cesarean section
or vaginal delivery; while Therapeutic doses should be discontinued 24–36 hours before
cesarean section or vaginal delivery; then Continue anticoagulation for 6 weeks postpartum.
7. Heparin dose in prophylaxis: 5000–7500 units S.C every 12 hours for first trimester, 7500–
10,000 units S.C. every 12 hours for second trimester, and 10,000 units S.C. every 12 hours for
third trimester; while Heparin dose in treatment is 10,000 units S.C. every 12 hours.
Injectable Anticoagulants
Unfractionated Inj. Solu. Heparin® 1000 IU/ml , 2500 IU/ml ,
Heparin 5000 IU/ml
LMW Heparins
Enoxaparin Prefilled Syringe Lovenox®, Clexan® 2000 IU , 4000 IU , 6000 IU
Multidose Vial 100 mg/ml (3 ml vial)
Dalteparin Prefilled Syringe Fragmin® 2500 IU , 5000 IU , 7500 IU
Inj. Solu. 10,000 IU/ml , 25,000 IU/ml
Tinzaparin Multidose Vial Innohep® 20,000 IU/2ml , 40,000 IU/2ml
Prefilled Syringe 3500 IU , 7000 IU , 10,000 IU
7.2- Galactagogues (Breastmilk boosting drugs)

1. Galactagogues are substances that aid the initiation and maintenance of milk supply at a level
which meets the needs of the baby; The production of milk is controlled by the hormone
prolactin, Nipple stimulation controls the release of prolactin whilst oxytocin controls the release
of the milk, experienced as the letdown.
2. Poor milk supply can result from:
a. Less than perfect positioning and attachment of the baby at the breast resulting in
incomplete breast drainage.
b. Infrequent, restricted, limited feeds.
3. Reduction in milk supply is frequently noted after premature delivery with milk supply
maintained only by expression over a period of weeks, also, Smoking is associated with decreased
milk production and smokers are more likely to wean earlier because of low milk supply or to
notice inhibition of letdown.
4. Most medications that act as galactagogues work by increasing prolactin levels; Examples of
Galactagogues:
a. Domperidone is a prescription drug used for decades for gastrointestinal disorders. The
most recent systematic review of five randomized control trials of women expressing for
premature babies demonstrated a moderate increase in daily breastmilk volume of
88.3mL/day with the use of domperidone compared with placebo; These studies suggest that
domperidone has few side effects. However, there have been recommendations that
domperidone not be used in women with a history of cardiac arrhythmias.
➢ The normal dose is 10 mg three times a day.
b. Metoclopramide is another prescription drug used to treat gastrointestinal disorders.
Metoclopramide has been used for nearly three decades to increase breastmilk production.
However, it crosses the blood-brain barrier, unlike domperidone. This means that
metoclopramide has the potential to cause central nervous system side effects such as
restlessness, drowsiness, fatigue and depression.;
➢ Clinical studies have shown that it increases prolactin levels and consequentially milk
supply at a dose of 10 mg three times daily.
c. Fenugreek is an herbal spice, which is a member of the pea family; Its mechanism of action
has been theorized as stimulation of sweat production (the breast is a specialized sweat
gland). The recommended dose is 2-3 capsules three times a day; Milk production is to
increase within 24-72 hours.
➢ Fenugreek can also interact with insulin and warfarin
➢ It also stimulates the uterus and should not be used in pregnancy.
➢ Hypoglycemic effects have also been reported with chronic use.
5. Other natural remedies said to increase milk supply include anise, basil, blessed thistle, caraway,
chasteberry and fennel but evidence is anecdotal rather than scientific.
6. One 2011 study compared Domperidone and Metoclopramide as galactagogues; This study
showed that there were no statistically significant differences between these two drugs in terms
of increased milk production or side effects; This study found that both domperidone and
metoclopramide were very effective at increasing breastmilk production and had minimal (and
all non-life-threatening) side effects.
Metoclopramide Tab Placil®, Meclodin® 5 mg , 10 mg
Domperidone Tab Motilium® , Motinorm® 10 mg
Herbal Combination
Fenugreek seed powder Tab Stimulact® (DaVinci) 500 mg
+ Vit. D + Vit. E + Niacin + 100 IU + 7 IU + 7 mg
+ Folic acid + Calcium + 200 mcg + 250 mg
Fenugreek + Marshmallow Cap Lactation Support® 1,115 mg herbal blend
+ Fennel + Red Raspberry
+ Blessed Thistle
Fenugreek seed powder Cap Nursing Blend® 1,360 mg herbal blend
+ Fennel seed + Anise + Multivitamins
+ Chamomile flower
+ Multivitamin Combo
7.3- Preparations for vaginal and vulvar conditions

A) Topical and Systemic (HRT) for vaginal atrophy:
1. Atrophic vaginitis is inflammation of the vagina as a result of tissue thinning due to not enough
estrogen; Symptoms may include pain with sex, vaginal itchiness or dryness, and an urge to
urinate or burning with urination.
2. Estrogen plays a vital role in keeping vaginal tissues lubricated and healthy, when levels of
estrogen are low, vaginal tissue becomes atrophic, thin, dry and shrunken; also, the vagina may
become more prone to inflammation in an atrophic state.
3. Low Estrogen levels are related to menopause, breastfeeding or due to some medications as
oral contraceptives pills.
4. A cream containing an Estrogen may be applied on a short-term basis to improve the vaginal
epithelium in menopausal atrophic vaginitis, also oral estrogen may be given but the topical
estrogen comes with less side effects profile.
5. It is important that topical estrogens should be used in the smallest effective amount to
minimize systemic effects.
➢ Topical estrogens are also used in postmenopausal women before vaginal surgery for
prolapse when there is epithelial atrophy.
➢ The risk of endometrial hyperplasia and carcinoma is increased when systemic estrogens are
administered alone for prolonged periods.
Topical Estrogens
Estradiol Vag. Cream Vagifem® 0.01%
Vag. Tab Vivelle®, Minivelle® 10 mcg , 25 mcg
Gel Climara® 0.06%
Estriol Vag. Gel Blissel® 50 mcg/1 gm
Vag. Cream Gynest® , Ovestin® 0.01% , 0.1%
Vag. insert Ortho-Gynest® 500 mcg
Conjugated Estrogen Vag. Cream Estrin® 0.625 mg
Systemic Estrogens
Conjugated Estrogen Tab Premarin®, Equin®, Estrin® 0.625 mg , 0.9 mg , 2.5 mg
Estradiol Tab Estrofem®, Delestrogen® 0.45 mg , 0.9 mg , 2 mg
Vag. Ring Estring® 7.5 mcg/24 hr.
Estropipate Tab Ortho-Est®, Ogen ® 1.5 mg , 3 mg , 6 mg
B) Vaginal infections:
First: Fungal infections (Thrush):
1. The discharge associated with thrush is curd-like or cottage cheese-like with little or no odor,
it can occur in any age group, the onset of symptoms is sudden.
2. Vaginal candidiasis is treated primarily with antifungal pessaries or cream inserted high into
the vagina (including during menstruation – can be taken during the period)
3. Single-dose preparations offer an advantage when compliance is a problem.
4. Imidazole drugs (Clotrimazole, Econazole, and Miconazole) are effective against candida in
short courses of 1 to 14 days according to the preparation used; treatment can be repeated if
initial course fails to control symptoms or if symptoms recur.
5. All internal preparations should be administered at night (this give the drug time to be
absorbed, and eliminate the possibility of accidental loss).
6. Oral treatment of vaginal infection (Fluconazole or Itraconazole) is also effective.

Clotrimazole Vag. Cream Canestene®, Gyne-Mycelex® 1% , 2%
Vag. Tab Canestene® 100 mg , 200 mg
Butoconazole Vag. Cream Femstat® 2%
Miconazole * Vag. Cream Gyno-Daktarin®, Mycoheal® 2% , 4%
Monistat®
Vag. Supp. Gyno-Mikazole® 200 mg , 400 mg
Nystatin * Vag. Tab Monicure® 100,000 Units
Terconazole Vag. Cream Terazole® 0.4% , 0.8%
Vag. Supp. 80 mg
Tioconazole Vag. Oint. Vagistat®, Topazole V® 6.5%
Fenticonazole Vag. Cream Gynoxin® 2%
Vag. Cap 200 mg , 600 mg
Econazole Vag. Supp. Ecorex® 150 mg
Vag. Cream Gyno-Pevaryl® 1%
* Miconazole and Nystatin comes in many combination products of vaginal creams and supp.
* For other types of antifungal → see chapter 5, Section 2.

7. Therapeutic regimens: 1- and 3-day regimens may take up to 7 days for full effect, (see table
below); Recurrent vulvovaginal candidiasis (four or more episodes a year): Needs
prescription drug treatment = Initial topical treatment for 7–14 days + fluconazole 100 , 150 , or
200 mg dose every third day for three doses.
Second: Bacterial infections:

1. Bacterial vaginosis is associated with a white discharge that has a strong fishy odor.
2. Odor is worse after sexual intercourse and may worsen during menses; Itching and soreness
are not usually present.
3. Metronidazole or Clindamycin either orally or vaginally are effective treatment (for 7 days).
➢ Metronidazole 500 mg orally twice daily for 7 days or clindamycin 2% cream, 1 full applicator
intravaginally at bedtime for 7 days, or metronidazole 0.75% gel, 1 full applicator
intravaginally once daily for 5 days.
➢ Alternatives: Clindamycin ovules 100 mg intravaginally at bedtime for 3 days, clindamycin
300 mg orally twice daily for 7 days, tinidazole 2 gm orally once daily for 2 days, tinidazole 1
gm orally once daily for 5 days, Secnidazole 2 gm packet of granules once.
➢ Pregnant women: Oral or vaginal therapy regimens of metronidazole (as above); try not to
use Clindamycin cream during pregnancy, because it increases the risk of preterm delivery.
➢ Treatment of sexual partners is not necessary.
Metronidazole Tab Flagyl® , Flazole® 250 mg , 500 mg
Infusion 500 mg/100 ml
Solu.
Vag. Gel Zidoval® , Vandazole® 0.75% (37.5 mg)
Va Supp.
Vag. 500 mg , 1 gm
Tinidazole Tab Fasigyn®, Tindamax® 500 mg
Tinidazole + Norfloxacin Cap Tinidol plus® 600 mg + 400 mg
Clindamycin Cap Cleocin® , Clindamycin® 75 mg , 150 mg
Vag. Cream Clindamax® 2% (Cream),
Vag. Supp. 100 mg (Supp.)
Secnidazole Tab Flagentyl®, Sindose® 500 mg
Ornidazole Tab Avrazor® , Borneral® 500 mg
Vag. Supp. Ornidaz® 500 mg

Third: Trichomoniasis infections (4)
1. Trichomoniasis, a protozoan infection is primarily transmitted through sexual intercourse; it is

uncommon compared to bacterial vaginosis and thrush, up to 50% of patients are asymptomatic.
2. If symptoms are experienced a profuse, frothy, greenish-yellow and malodorous discharge
accompanied by vulvar itching is typical; other symptoms can include vaginal spotting, dysuria
and urgency.
3. Metronidazole, Tinidazole (and their relatives) or clindamycin either orally or vaginally are
effective treatment. (See above).
➢ Metronidazole 2 gm orally in a single dose or tinidazole 2 gm orally in a single dose.
➢ Alternative: Metronidazole 500 mg orally twice daily for 7 days.
➢ All sexual partners should be treated.
Forth: Chlamydia infections (4)

1. Chlamydia is known as the "Silent Epidemic" because in women, it may not cause any symptoms
in 70–80% of cases and can linger for months or years before being discovered.
2. Symptoms that may occur include unusual vaginal bleeding or discharge, pain in the
abdomen, painful sexual intercourse (dyspareunia), fever, painful urination or the urge to
urinate more frequently than usual (urinary urgency).
3. Can transfer from the pregnant women to the baby causing Blindness.
4. Also occur in men.
5. Current treatment guidelines recommend Azithromycin, Doxycycline, Erythromycin, or
Ofloxacin; agents recommended for pregnant women include Erythromycin or Amoxicillin.
➢ Azithromycin 1 g in a single dose or doxycycline 100 mg twice daily for 7 days.
➢ Alternatives: Erythromycin 500 mg orally four times daily for 7 days, ofloxacin 300 mg orally
twice daily for 7 days, levofloxacin 500 mg/day orally for 7 days,
➢ Abstain from sexual intercourse for at least 7 days and until sexual partners are treated.
Combination Products for Vaginal Infections

Monicure Plus® Vag. Supp. Miconazole + Nystatin 100 mg + 100,000 I.U
Monicure NH® Vag. Supp. Miconazole + Nystatin + 100 mg + 100,000 I.U
Neomycin + Hydrocortisone 50 mg + 5 mg
Mixovul® Vag. Ovule Metronidazole + Miconazole 750 mg + 200 mg
+ Lidocaine + 100 mg
PolyGynax® Vag. Cap Neomycin + Nystatin 35,000 I.U + 100,000 I.U
+ Polymyxin B Sulphate + 35,000 I.U
+ Dimethylpolysiloxane * + 2.2 gm
Ginal Cent® Vag. Cap Metronidazole + Miconazole 400 mg + 100 mg
+ Neomycin + Centella Asiatica + 45 mg + 15 mg
+ Polymyxin B Sulphate + 5 mg
Gynocaps® Vag. Cap Miconazole + Metronidazole 100 mg + 500 mg
Gyno-D® Vag. Supp. Miconazole + Metronidazole 150 mg + 500 mg
Gyno-D Zole® Pessaries Miconazole + Metronidazole 150 mg + 500 mg
Ovumix® Vag. Ovules Miconazole + Metronidazole 200 mg + 750 mg
Gynomix® Vag. Supp. Tioconazole + Tinidazole 6% + 4%
Dektacort V® Vag. Cream Miconazole + Hydrocortisone (20 mg + 10 mg) per 1 gm
Furazole plus® Vag. Supp. Furazolidone + Nifuroxime 7.5% + 12 mg
* Dimethylpolysiloxane = Dimethicone, they are the same drug.
Other Vaginal Infections products
Resulen® Vag. Supp. Policresulen -----------------
V-Gel® Vag. Cream Herbal preparation -----------------
Fluomizin® Vag. Tab Dequalinium Chloride 10 mg
Premeno® duo Vag. Ovule Hyaluronic acid Na+ 5 mg
Xaluron® Vag. Supp. Hyaluronic acid Na+ 5 mg
Relactagel® Vag. Gel lactic acid + Glycogen 4.5% + 0.1%
* Policresulen is a topical hemostatic and antiseptic, it’s also can be used for common anal disorders,
such as hemorrhoids.
** Dequalinium Chloride is an antiseptic and disinfectant, it is a topical bacteriostatic, used in wound
dressings and mouth infections and may also have antifungal action, it also may cause skin ulceration with
high concentrations
** Hyaluronic acid is given for vaginal Dryness.
7.4- Contraception methods

1. Drugs are available that decrease fertility by a number of different mechanisms, such as
preventing ovulation, impairing gametogenesis or gamete maturation, and interfering
with gestation; (For hormonal replacement therapy HRT see chapter 6, section 3)
2. All hormonal contraceptive methods (oral pills, Injections, patches) have side effects on the
women, which maybe disturbing; So why don’t men just use condoms?
➢ But to be scientifically fair; oral contraception has benefits (aside from pregnancy prevention)
that include treatment of acne, hirsutism, premenstrual syndrome (PMS), and menstrual
cycle regulation.
Major classes of contraceptives (9 methods):

A. Combination oral contraceptives (COCs):
1. Products containing a combination of an estrogen and a progestin are the most common type of
oral contraceptives, combination of Estrogen (prevent the development of the dominant
follicle) and Progestin (prevent ovulation), have these types:
a. Monophasic pills contain a constant dose of estrogen and progestin given over 21 days.
b. Triphasic oral contraceptive products attempt to mimic the natural female cycle and most
contain a constant dose of estrogen with increasing doses of progestin given over three
successive 7-day periods.
c. Extended-cycle contraception (84 active pills followed by 7 days of placebo).
d. Continuous oral contraceptive product (active pills taken 365 days of the year).
2. Adverse effects (and their relevance) of COCs include: Bleeding irregularities (32%), Nausea
(19%), Weight gain (14%), Mood swings (Rage, Sadness, Depression) (14%), Breast tenderness
(11%), Headache (11%) and Acne (8%).
➢ If the Nausea is very troublesome; Suggest the patient take the pill at night before bed.
➢ Acne is related to the androgenic properties of Progestin.
3. When using COCs watch out for these serious adverse effects (ACHES):
➢ A = Abdominal pain; could signal liver problems or gallbladder.
➢ C = Chest pain, shortness of breath; could signal myocardial infarction or blood clot in lung.
➢ H = Headaches (severe); could signal stroke, blood clot.
➢ E = Eye problems (blurred vision, flashing lights); could signal optic neuritis, stroke, clots.
➢ S = Severe leg pain with or without swelling; could signal DVT.
Levonorgestrel + EE Tab Microgynon®, Nova®, Nora® 0.15 mg + 0.03 mg
Drospirenone + EE ** Tab Yasmine® , Zahraa® 3 mg + 0.03 mg
Tab Yaz® , Gianvi®, Warda® 3 mg + 0.02 mg
Desogestrel + EE Tab Marvelon® 0.15 mg + 0.03 mg
Gestodene + EE Tab Gynera®, Femodene® 0.075 mg + 0.03 mg
Tab Sunya® 0.075 mg + 0.02 mg
Norgestrel + EE Tab Cryselle®, Eugynon® (0.3 mg + 30 mcg),
(0.5 mg + 50 mcg)
Norgestimate + EE Tab Mononessa®, Cilest® 0.25 mg + 35 mcg
Norethindrone + EE Tab Femhrt® , Jinteli® 0.4 mg + 35 mcg
Etynodiol + EE Tab Zovia® 0.05 mg + 1 mg
Norethindrone + Mestranol Tab Necon® 1 mg + 50 mcg
Dienogest + Estradiol Tab Qlairis® , Qlairista® 4 phase tab
Dienogest + Estradiol Tab Natazia® 4 phase tab
* EE = Ethinyl Estradiol * Bold marked are the items that’s found in our market.
** Drospirenone is an Analog of spironolactone, similar to spironolactone 25 mg but with no diuretic effect.
Note: Products containing Drospirenone

a. Drospirenone is an Analog of spironolactone, similar to spironolactone 25 mg.
b. When using Drospirenone; Exercise caution with drugs that increase potassium such as high
doses of NSAIDs, heparin, ACEIs, and potassium-sparing diuretics; it has No diuretic effect,
has anti-mineralocorticoid effects; thus, it decreases bloating effect of Ethinyl estradiol.
c. It has Antiandrogenic effects: Best for acne, hirsutism, or male pattern balding in women.
d. It has a Possible increased risk of DVT and PE.
B. Progestin-only pills (POPs):

1. Products containing a progestin only, these preparations are less effective than the combination
pill, the progestin-only pill may be used for patients who are breastfeeding (unlike estrogen,
Progestins do not have an effect on milk production), who are intolerant to estrogen,
smokers, or have other contraindications to estrogen-containing products.
➢ There are no hormone-free days with the POPs, may start on any day or on first day of period.
2. Indications of Progestin-only Pills: those who cannot use or tolerate combined hormonal
contraceptives (see list below) or those seeking long-term contraception:
a. History or current MI, stroke, DVT, CVD.
b. Atrial fibrillation or with Blood pressure ≥ 160/100 mm Hg.
c. Active, symptomatic liver disease or History of cholestasis.
d. Migraine headache with neurologic impairment or aura.
e. Retinopathy or neuropathy because of diabetes.
f. Surgery within the past 4 weeks.
3. Adverse effects caused by Progestins: Headaches Increased appetite, Increased weight gain,
Depression, fatigue, Changes in libido, Androgenic effects (Hair loss, hirsutism, Acne, oily skin).
Medroxyprogesterone Tab Provera® 5 mg , 10 mg
Inj. Depo-Provera® 150 mg
Lynestrenol Tab Exluton® 0.5 mg
Levonorgestrel Tab Norgeston® 30 mcg
Desogestrel Tab Cerazette® 1 mg
Norethindrone Tab Camila®, Lyza® , Errin® 0.35 mg
Advantages of progestin only pills Disadvantages of progestin only pills
1. Oral progestogen-only preparations may 1. They must be taken more regularly than COCs,
offer a suitable alternative when the they are taken as One tablet daily, on a continuous
estrogens are contra-indicated (including basis, starting on day 1 of cycle and taken at the
those patients with venous thrombosis or same time each day (if delayed by longer than 3
a past history of venous thrombosis) (2). hours’ contraceptive protection may be lost) (3)
2. Confusion with pill taking is minimized 2. They may have a higher failure rate than
because there is no placebo week and all combined preparations (1) (from 0.3% to 8%) (5).
28 pills in each pack are the same .
(5)
The use of oral contraceptives during breast-feeding:

1. The American College of Gynecology (ACOG) recommends waiting at least 6weeks before
starting any estrogen-containing contraceptive regardless of breast-feeding status (By this
time, the increased risk of thrombosis that occurs during pregnancy should be reduced to
baseline), However, COCs have been reported to decrease milk quantity and quality. Therefore,
many providers suggest avoiding COCs in women who are exclusively breastfeeding.
2. For non–breast-feeding women, a progestin-only contraceptive may be used immediately
postpartum and 6 weeks postpartum if solely breast-feeding and in some cases 3 weeks
postpartum if partially breast-feeding.
The Selection of appropriate contraceptive pills:
This depends on the side effects developed by the women taking COC pills:
➢ (Nausea, Dizziness, bloating, breast enlargement, tension, and migraines headaches) are all due
the higher Estrogenic content, so switch to a COC progestin dominant as: Microgynon®,
Eugynon®.
➢ (Acne, weight gain, vaginal dryness,
depression/lethargy, scanty menses)
are all due higher progestin content,
switch to a COC estrogen dominant as:
Marvelon®, Gynera®.
➢ This table will help you to decide which

contraceptive pills is suitable for the
patient.
C. Transdermal patches:
An alternative to combination oral contraceptive pills is a transdermal contraceptive patch
containing (Ethinyl estradiol and the progestin Norelgestromin)
a. One contraceptive patch is applied each week for 3 weeks to the abdomen, upper torso,
or buttock; week 4 is patch free, and withdrawal bleeding occurs.
b. It has been shown to be less effective in women weighing greater than 90 kg.
Norelgestromin + EE Patch Evra® (0.15 mg + 0.02 mg) per day
Xulane® (0.15 mg + 0.035 mg) per day

D. Injectable Progestins:
1. Medroxyprogesterone is an injectable contraceptive (commonly used) that is administered
every 3 months (11–13 weeks), Weight gain is a common adverse effect.
a. Preferred start: First 5 days of menses; or at Any time in cycle if not pregnant.
b. Wait a few hours before massaging area where shot was given.
c. Return to normal fertility may be delayed for several months after discontinuing use.
d. May contribute to bone loss and predispose patients to osteoporosis and/or fractures,
Therefore, the drug should not be continued for more than 2 years unless the patient is
unable to tolerate other contraceptive options.
➢ All patients using injectable Progestins should be taking sufficient calcium (1000–1200
mg/day) and exercising regularly.
Medroxyprogesterone Inj. Solu. (I.M) Depo-Provera® 150 mg
Inj. Susp (S.C.) Sayana-Press® 104 mg/0.65 ml
Norethisterone Inj. Noristerat® 200 mg/ml
E. Spermicidal contraceptives (Nonoxinol):

1. Vaginal spermicides (a chemical that kills sperm such as Nonoxinol 9) may be used as foam,
creams, gels or pessaries - dissolvable tablets, inserted into the vagina after sex.
2. The vaginal pessaries/dissolvable tablets required about 15 minutes to produce its effect
(onset of action) and has a duration of action of about 1 hour.
➢ They preferably used adjunctively with other forms of contraceptives to provide additional
protection against unwanted pregnancy; because they are generally considered relatively
ineffective when used as the sole method of contraception.
Nonoxinol 9 Vag. Supp. Nonoxinol® 100 mg
Vag. Gel Gygel® 2%
Nonoxinol 9 + Vag. Supp. Today-Plus® 100 mg + 4.6 mg
Benzethonium CL
Menfegol Vag. Foam tab Menfegol® 60 mg
Monalazone Vag. tab Monalazone® 9.5 mg
F. Vaginal ring:
1. An additional contraceptive option is a vaginal ring containing Ethinyl Estradiol and
Etonogestrel, the ring is inserted into the vagina and is left in place for 3 weeks; week 4 is ring
free, and withdrawal bleeding occurs.
a. The contraceptive vaginal ring has efficacy, contraindications, and adverse effects similar to
those of oral contraceptives.
b. Should not be removed during intercourse; Even if the partner feels it.
c. Disadvantage with the vaginal ring is that it may slip or be expelled accidentally; also, it may
Decreased libido (maybe a psychological effect); and cause Vaginal discomfort and secretions.
Etonogestrel + EE * Vag. Ring NuvaRing® 0.12 mg + 0.015 mg
* Etonogestrel is the active form of Desogestrel.

G. Intrauterine Device (IUD):
1. Levonorgestrel releasing intra-uterine system (L-IUD) offers a highly effective method of
long-term contraception; This intrauterine device provides contraception for up to 5 years.
➢ It is a suitable method of contraception for women who already have at least one child
and do not have a history of pelvic inflammatory disease or ectopic pregnancy.
➢ Increased risk of infection for 20 days after insertion.
2. Another type of intra-uterine system includes Copper IUD (which acts mainly as Spermicide);
Copper ions inhibit sperm motility and acrosomal enzyme activation so that sperm seldom
reaches fallopian tube and are unable to fertilize the ovum.
➢ long term contraception; for about 10 years.
➢ Increased risk of infection for 20 days after insertion.
➢ C.I. to Copper IUD include: Women with current or recent (within 3 months) sexually
transmitted infection (STI), Uterus less than 6 cm or greater than 9 cm, Allergy to
copper; Wilson’s disease, and recent Endometrial infection (past 3 months).
Copper IUD IUD Paragard® 380 mm2
Levonorgestrel IUD Mirena® 20 mcg/24 hr.
Kyleena® 17.5 mcg/24 hr.
H. Progestin implants:
1. A sub-dermal implant containing Etonogestrel offers long-term contraception; one 4-cm
capsule is placed sub-dermally in the upper arm and provides contraception for approximately
3 years, the implant is nearly as reliable as sterilization, and the effect is totally reversible when
surgically removed and return to fertility within 1–3 months
a. Once the progestin-containing capsule is implanted, this method of contraception does
not rely on patient compliance.
b. Principal side effects of the implants are irregular menstrual bleeding and headaches.
c. The Etonogestrel implant has not been studied in women who weigh more than 130%
of ideal body weight and may be less effective in overweight women.
Etonogestrel Implant (subdermal) Implanon® , Nexplanon® 68 mg
I. Barrier Female Contraceptives

1. As males have condoms as a barrier contraceptive; Females also does have such methods, these
include (Female condoms, Cervical Caps, Diaphragms and Contraceptive Sponge); in all
which act similarly as physical barriers to sperms.
2. Female condoms are made from soft, thin synthetic latex or latex; They're worn inside the
vagina to prevent semen getting to the womb; If used correctly, they are 95% effective.
➢ It may cause UTIs if left in the vagina for a prolonged period.
3. Cervical cap is a little cup made from soft silicone and shaped like a sailor's hat; its inserted deep
inside the vagina to cover the cervix, stopping sperm from joining an egg, in order for a cervical
cap to work best, it must be used with spermicide (a cream or gel that kills sperm).
➢ Inserted at least 15 min. before sexual intercourse, and can be left for 48 hours.
4. Diaphragm is a shallow, bendable cup that is inserted inside the vagina; It covers the cervix
during sex to prevent pregnancy (a shallow cup shaped like a little saucer that's made of soft
silicone; it bends into half and inserted inside the vagina to cover the cervix).
➢ Inserted before the sexual intercourse and remains in the vagina for 6-8 hours.
5. The contraceptive sponge prevents sperm from entering the uterus; It is soft and disk-shaped,
and made of polyurethane foam, it contains spermicide, which blocks or kills sperm, before
having sex, its inserted deep inside the vagina so that it covers the cervix; the vaginal muscles
hold it in place, it has a strap on one side for easier removal.
➢ Can be left inside for 24 hours.
J. Post-coital contraception: (Emergency Contraception)

1. Emergency contraception uses high doses of Progestin (0.75 mg or 1.5 mg Levonorgestrel) or
high doses of Estrogen (100 mcg Ethinyl Estradiol) plus Progestin (0.5 mg Levonorgestrel)
administered within 72 hours of unprotected sex (the morning-after pill).
➢ For these regimens, a second dose of emergency contraception should be taken 12 hours
after the first dose, and for maximum effectiveness, emergency contraception should be
taken as soon as possible after unprotected sex and preferably within 72 hours.
➢ Progestin-only Emergency Contraceptive pills are not effective for those with a BMI of 30
kg/m2 or greater (not effective in women who weigh more than 80 kg).
2. Recently there is new drug approved for emergency contraception (Ulipristal), used orally as
soon as possible (within 120 hr. or 5 days) after unprotected sex.
➢ Ulipristal is a selective progesterone receptor modulator (SPRM), which is also used
for pre-operative treatment of moderate to severe symptoms of Uterine Fibroids in adult
women of reproductive age in a daily dose of a 5 mg tablet.
➢ Not approved for use during breastfeeding.
➢ Not recommended for women with a BMI greater than 35 kg/m2.
➢ Recommended to wait 5 days before initiating or resuming hormonal contraception after
taking Ulipristal; Starting hormonal contraception before waiting 5 days might alter the
effect of Ulipristal as well as the effect of hormonal contraception
Levonorgestrel Tab Plan B®, I-pill® 1.5 mg
Ulipristal Tab Ella® , EllaOne® 30 mg
Tab Esmya®, Fibristal® 5 mg
7.5– Polycystic ovary syndrome (PCOS)

1. Polycystic ovary syndrome (PCOS) is a set of symptoms due to elevated androgens (male
hormones) in females; Signs and symptoms of PCOS include irregular or no menstrual periods,
heavy periods, excess body and facial hair, acne, pelvic pain, difficulty getting pregnant, and
patches of thick, darker, velvety skin.
➢ Can be a cause of infertility in up to 20% of infertile couples
➢ Mainly considered to be caused by androgen excess or hyperandrogenism.
➢ Underlying cause appears to be insulin resistance (in patients with and without obesity),
with subsequent compensatory insulin hypersecretion or increased insulin action, this
increased action stimulates androgen secretion by the ovaries or adrenal cells, leading to
increased luteinizing hormone (LH) secretion but normal or low follicle-stimulating hormone
(FSH) concentrations, with a subsequent decrease in follicular maturation and anovulation.
o That’s why Metformin and Pioglitazone are useful in PCOS (they’re insulin sensitizers).
2. Risk factors include: obesity, a lack of physical exercise, a family history of someone with the
condition; and Diagnosis is based on two of the following three findings: no ovulation, high
androgen levels, and ovarian cysts (Cysts may be detectable by ultrasound).
➢ DDx = Elevated free or total serum testosterone, and LH/FSH ratio greater than 2.
3. PCOS has no cure; Treatment may involve lifestyle changes such as weight loss and exercise,
oral contraceptive pills may help with improving the regularity of periods, excess hair growth,
and acne, Metformin and anti-androgens may also help, other typical acne treatments and hair
removal techniques may be used, Efforts to improve fertility include weight loss, clomiphene, or
metformin; In vitro fertilization (IVF) is used by some in whom other measures are not effective.
4. Pharmacotherapy for PCOS: Fertility improvement: using Clomiphene, Gonadotropin, and
Letrozole (see Infertility section below).
Symptomatic improvement:
➢ Hormonal contraceptives (Estrogen/Progestin combination): Endocrine Society first-
line therapy for menstrual abnormalities, hirsutism, or acne.
o They increase sex hormone binding globulin production, which increases binding of free
testosterone; This reduces the symptoms of hirsutism caused by high testosterone and
regulates return to normal menstrual periods.
➢ Metformin: Effective for metabolic and glycemic abnormalities, if present, but only modestly
effective for hirsutism (Alternative to hormonal contraception for irregular menses when
hormonal contraceptives are contraindicated); Few data to support use for increased fertility
(may improve pregnancy rate but not shown to improve rates of live births).
o Used to treat insulin resistance seen in PCOS; also supports ovarian function and return
to normal ovulation.
➢ Spironolactone: Often added to hormonal contraceptives, it can help with hirsutism, it is
used for its antiandrogenic effects.
➢ Pioglitazone: Questionable whether benefits outweigh risks in PCOS; Not recommended in
Endocrine Society guidelines. (9)
o Although several studies show benefit of Pioglitazone in PCOS.
5. Inositol: A 2017 review concluded that while both myo-inositol and D-chiro-inositol may
regulate menstrual cycles and improve ovulation, but there is a lack of evidence regarding effects
on the probability of pregnancy; a 2012 and 2017 review have found myo-inositol
supplementation appears to be effective in improving several of the hormonal disturbances of
PCOS; also, Myo-inositol reduces the number of gonadotropins injections and the length of
controlled ovarian hyperstimulation in women undergoing in vitro fertilization.
Metformin Tab Glucophage , Siofor , Riomet 500 mg , 850 mg , 1000 mg
® ® ®
Tab XR 500 mg , 750 mg , 1000 mg

Herbal Combinations for PCOS
Inositol + Choline Tab Choline & Inositol® 500 mg + 500 mg
Inositol + Choline + Folic Acid Tab Forte Choline & 500 mg + 500 mg + 200 mcg
+ Vit. K2 + Co-Q10 + ALA Inositol ®
Inositol + Folic Acid Sachet OvuSitol® 2000 mg + 200 mcg

Myo-Inositol + Folate Sachet Myofol® 2000 mg + 200 mcg
+ White kidney Bean Extract + 100 mg
Myo-Inositol + D-chiro-inositol Caplet PolySitol® (AMS) 2000 mg + 50 mg
+ Multivitamin Combo

7.6- Vaginal Gels to aid natural fertility
1. These Vaginal gels creates an environment in which sperm has the best chances of reaching a
woman’s eggs; with a neutral pH of 7.2 they protect sperm from too acidic environment, thereby
ensuring their survival; also, their osmotic properties provide optimum room for maneuver, and
thus Sperm motility is boosted.
2. Some formulations contain Magnesium (Mg2+) and Calcium (Ca2+) Ions for Fertility Support.
3. They inserted into the vagina 5-10 minutes before sexual intercourse, they also act as a lubricant.
Prefert® Vag. Gel Sodium Chloride + Sodium Phosphate 6 ml Gel
+ Potassium Phosphate + Arabinogalactan
+ Hydroxyethyl cellulose + Polyhexanide
Conceive Plus Vag. Gel Deionized Water + Hypromellose + Sodium Chloride 4 gm Gel
®
+ Glycerol + Sodium Phosphate + Methylparaben

+ Potassium Chloride + Magnesium Chloride
+ Calcium Chloride
7.7 – Infertility in Women

1. Infertility is defined as the inability to conceive after one year of unprotected intercourse, many
factors affect infertility rates, but advancing maternal age appears to be a prominent influence,
an important focus when evaluating causes of infertility is ovulatory function, which is associated
with up to 40% of female factor infertility
➢ Ovarian function is regulated through complex feedback mechanisms within the
hypothalamic-pituitary-ovarian axis, this involves release of gonadotropin-releasing
hormone (GnRH) from the hypothalamus, follicle-stimulating hormone (FSH) and luteinizing
hormone (LH) from the pituitary, and Estrogen and progesterone from the ovaries,
Anovulation results from the disruption of communication at any of these levels and is
associated with a variety of causes.
2. Conditions such as Thyroid dysfunction, Hyperprolactinemia, and Polycystic Ovary
Syndrome (PCOS) can induce anovulation, and each is treated separately.
➢ Fertility improves with BMI of 20–25 kg/m2 or within 15% of ideal body weight; fertility
decreased in those less than 95% of ideal body weight or in those greater than 125%.
➢ Impaired cervical mucus production or quality is an additional structural factor that can
impact sperm motility and the fertilization process.
3. Treatment Approaches:
A. The treatment approach is empiric but typically incorporates medications to stimulate
ovulation; This may or may not be combined with intrauterine insemination or other
infertility procedures, there are two general treatment strategies that focus on ovulation:
“ovulation induction” (OI) and “controlled ovarian stimulation” (COS), the approach
depends on a patient’s underlying ovulatory function.
➢ Ovulation induction: is pursued in patients who are not ovulating to promote an ovulatory
cycle, this method may be accompanied by timed natural intercourse or the use of
insemination procedures to achieve pregnancy.
➢ Controlled ovarian stimulation: incorporates many of the same medications, but is
appropriate for women who are already having ovulatory cycles but are still experiencing
infertility, also it’s appropriate for infertility procedures where the development of multiple
ovarian follicles is desirable.
B. The physician may add (Cabergoline or Bromocriptine) for the treatment of Infertility caused
by hyperprolactinemia to the main prescription, Doses:
1. Cabergoline = 0.5 mg – 1 mg twice a week. (For more info see chapter 6, section 5-C).
2. Bromocriptine = start with 1.25 mg – 2.5 mg every day, then increase gradually by 2.5
mg\week till achieving clinical response.
C. Also, the physician may add Mucolytics such as (N-Acetyl-Cysteine, Guaifenesin,
Bromhexine) in high doses to decrease Cervical Mucus thickness and thus enhancing sperm
motility and thus enhancing Fertility.
D. A new study found that daily low dose Aspirin (81 mg) increase the chances of conception
by 17% for women who previously miscarried; this is though due to reducing the systemic
inflammation which improves the environment in which an embryo grows.
First: Ovulation induction:

This process is designed to mimic the hormonal patterns of the normal menstrual cycle, the choice
of medications for Ovulation induction is dictated by hypothalamic-pituitary- ovarian function.
➢ Ovulation Induction in Patient with adequate hypothalamic function:
1. An oral regimen of Clomiphene (which exhibits estrogenic agonist and antagonist activity) is
often utilized first line. Clomiphene inhibits estrogenic binding in the hypothalamus to stimulate
release of GnRH and pituitary gonadotropins and induce ovarian follicular development.
Ovulation is successful in 80% of patients using Clomiphene.
➢ Clomiphene Dose: 50 mg daily for 5 days starting within about 5 days of onset of
menstruation (preferably on 2nd day); if ovulation does not occur, a course of 100 mg daily
for 5 days may be given. (for more info see chapter 6, section 3-B)
2. Oral aromatase inhibitors (Letrozole) are not approved by the US (FDA) for Ovulation Induction,
but used off-label to increase release of GnRH and pituitary gonadotropins through an estrogenic
antagonist effect.
➢ Dose: 2.5 mg daily for 5 days starting within about 5 days of onset of menstruation
(preferably on 2nd day), sometimes it is given in higher doses of 5 mg or 7.5 mg per day. (i.e.;
same dosing as Clomiphene).
Clomiphene Tab Clomid®, Serophene®, Ovamit® 50 mg
For Hyperprolactinemia
Cabergoline Tab Dostinex® , Cabaser® 0.5 mg
➢ Ovulation Induction in Patient with Hypothalamic or pituitary dysfunction

(or if oral regimens are not successful)
Injectable Gonadotropins are administered in the following manner:
1. Usually an Injection of hMG or FSH (75 IU every day) is initiated over usually a period of 5
to 12 days to cause ovarian follicular growth and maturation; you may increase the dose as
needed every 7 days by 37.5 IU.
2. Addition of Clomiphene 50 mg tab (or Letrozole) decrease the number of hMG or FSH
injections needed to complete the cycle of ovarian follicular maturation.
3. Maximum daily dose of hMG or FSH is 300 IU daily.
4. Maximum duration of this cycle is 35 days.
5. Then an injection of hCG (5000 IU) or (250 mcg of recombinant hCG) is given to cause
ovulation. (Injected after 1 day after the last hMG or FSH inj.)
6. Then Fertilization must occur within 36 hours after hCG administration, either by
intercourse (normal Sex) or intra-uterine insemination.

Menotropin (hMG) Inj. Merional , Pergonal
® ® (75 IU + 75 IU),
(FSH + LH) (150 IU + 150 IU)
Chorionic gonadotropin Inj. Pregnyl , Choragon
® ® 5000 IU , 1500 IU ,
(hCG) 10,000 IU
FSH (Urofollitropin) Inj. Diclair FSH , Fastimon 75 IU , 150 IU
® ®
Follitropin Alfa Prefilled Inj. Gonal-F® 75 IU (5.5 mcg)

Prefilled Inj. Gonal-F ® 300 IU (22 mcg)
Lutropin Alfa Inj. Powder Luveris ® 75 IU , 82.5 IU
Recombinant hMG Inj. Pergoveris ® 150 units (11 mcg) +
(Follitropin Alfa + 75 units (3 mcg)
Lutropin Alfa)
Follitropin Beta Inj. Puregon® 50 IU
Choriogonadotropin Alfa Prefilled Inj. Ovitrelle® 250 mcg/0.5 ml (6500 I.U)
Corifollitropin Alfa Prefilled Inj. Elonva® 100 mcg/0.5 ml ,
150 mcg/0.5 ml
Gonadorelin Inj. Powder Lutrepulse® 0.8 mg/vial
Second: Controlled Ovarian Stimulation (COS)

1. The oral and injectable medications used for Ovulation Induction are also incorporated into
regimens for COS; they are administered in doses and schedules intended to develop multiple
ovarian follicles, rather than one dominant follicle.
2. This results in a greater number of oocytes available for fertilization, this is mostly achieved by
injections of gonadotropins directly (as method above), and this treatment can be combined
with intra uterine insemination (IUI).
Third: Assisted Reproductive Technology (ART)

1. Procedures using ART provide a valuable treatment option for many couples who are not
candidates for OI/COS alone or with intra-uterine insemination (IUI).
➢ The primary ART is IVF (in vitro fertilization), which involves retrieval of oocytes after COS,
fertilization in vitro, and transfer of the embryo directly to the uterus through the cervix,
bypassing the fallopian tubes.
➢ Intra-cytoplasmic sperm injection (ICSI), or the injection of sperm directly into the oocyte
during the fertilization process, accompanies IVF if severe sperm dysfunction is evident.
2. Alternate procedures for ART include gamete intra-Fallopian transfer and zygote intra-
Fallopian transfer, which alter the timing of fertilization and location of transplantation.
➢ In gamete transfer, the retrieved oocytes are transferred with the sperm to the fallopian
tube to allow for natural fertilization.
➢ In zygote transfer, the oocytes are fertilized in vitro, but are transferred at an earlier stage
of development to the fallopian tubes, rather than the uterus.

3. The basic steps in an IVF protocol include: COS, oocyte retrieval, fertilization, embryo culture
and embryo transfer. Medications are primarily used during three main stages of IVF: COS, oocyte
retrieval, and luteal phase support.
Fourth: IVF Protocol Albumin administration around the time of oocyte

retrieval reduce the risk of severe ovarian hyper
stimulation syndrome (OHSS).
7.8– Sexual Dysfunction in Women

A. Human Female Sexual response cycle consist of 4 stages or phases; which all lead to normal
sexual process; any dysfunction in any stage will lead to a Sexual Dysfunction:
1. Excitement (Desire, Libido) phase: in which the heart rate increase, breathing rate
increase, blood pressure increase and the body temperature increase; leading to flushing (sex
flush); in this phase the women’s Clitoris swells, and the muscles of the vagina undergo
relaxation and produce lubricating liquid, and the nipples become hardened and erect.
2. Plateau (Arousal) phase: the period between sexual excitement and orgasm, in which the
Clitoris becomes extremely sensitive, and the vagina produces further lubricating liquid.
3. Orgasmic phase: accompanied by quick cycles of muscle contractions in the lower pelvic
muscles, which surround both the anus and the sexual organs; orgasms are accompanied with
euphoric sensation; although orgasm intensity varies widely from women to another, the
overall sensation is similar to that of male orgasm.
4. Resolution phase: if orgasm is achieved; resolution may last 10-15 minutes with sensation
of calmness and relaxation, and if the orgasm is not achieved; irritability and discomfort can
result, in which it can last for several hours.
B. Factors Effecting Libido in women:
1. Hormones and Neurotransmitters:
• Dopamine increase libido, while Prolactin decrease libido (Prolactin play an important
role to control sexual desire in females); thus, libido is low in lactating women.
• Estrogen, Progesterone and Norepinephrine all increase libido.
• Testosterone (male hormone); in females: testosterone levels rise gradually and reach to
highest levels in ovulation days, and during this period the female desire for sex increases.
• Oxytocin is responsible for the orgasm and sexual pleasure.
• Serotonin decrease libido.
2. Psychological Factors: Lack of privacy, lack of intimacy (no love feelings), stress, fatigue,
distraction, depression; all decrease libido.
3. Medications: hormonal contraceptive decrease free testosterone levels; which ↓ libido.
First: Low Sexual Desire in Women

1. Also Called Hypoactive sexual desire disorder (HSDD), and also referred as inhibited sexual
desire (ISD) is considered a sexual dysfunction and is characterized as a lack or absence of sexual
fantasies and desire for sexual activity, as judged by a clinician.
2. If a male had a sexual problem, he’ll take Sildenafil or Tadalafil and the problem is solved, but
what if the female had such problem?
➢ Unfortunately; there are many products marketed for sexual arousal for females and they
have no scientific background or any evidence of efficacy, (as gums, drops and sprays).
➢ Many other combinations are found in the market, they may include multi-vitamins, Zinc,
proteins, B-complex, vitamin E …. etc. (all may be beneficial as a secondary supplement).
3. Sometimes the low sexual desire in women are due hormonal imbalance; thus, correcting
these imbalances may result in sexual activity improvement:
➢ Very Low testosterone levels: treated with testosterone supplementation, for short term
therapy only (as it may cause weight gain, acne and excess body hair).
➢ Low Estrogen levels: systemic Estrogens or Topical Estrogens.
➢ High Prolactin levels: treated with Cabergoline or Bromocriptine.
4. The only drug approved by the FDA for Hypoactive sexual desire disorder (HSDD) in women
is Flibanserin, the medication increases the number of satisfying sexual events per month by
about one half over placebo from a starting point of about two to three.
➢ Flibanserin was originally developed as an antidepressant, before being repurposed for the
treatment of HSDD, it’s a 5-HT1A agonist (increase Dopamine and Norepinephrine; which is
both responsible for sexual excitement), and a 5-HT2A antagonist (decrease Serotonin;
which is responsible for sexual inhibition).
➢ Dose 100 mg one daily at bedtime, dosed at bedtime because administration during waking
hours increases risks of hypotension, syncope and CNS depression.
➢ Not indicated to enhance sexual performance (not useful for normal females).
➢ The most commonly reported adverse events included dizziness, nausea, feeling tired,
sleepiness, and trouble sleeping.
5. Yohimbine, a selective α2 receptor blocker, may be useful for general sexual problems in
women, it acts by increasing blood flow and nerve impulses to the vagina; but unfortunately, its
without strong evidence of benefit.
6. Dehydroepiandrosterone (DHEA) is a precursor to Estrogen and Testosterone, it has been
used off-label to increase libido in postmenopausal women.
7. Several other products are used off-label to enhance libido in females, which include:
(Amphetamine, Methylphenidate and Bupropion), in which they all act by enhancing
Dopamine release or by increasing its release.
8. Ginkgo Biloba, Ginseng and Fish Roe (Caviar) are herbal products that is thought to increase
general sexual heath (including enhancing sexual desire), in both males and females; but this
claim is not supported or confirmed by strong studies or trails.
Flibanserin Tab Addyi® 100 mg
Yohimbine Cap Aphrodien® 2.5 mg , 6 mg , 10 mg
Dehydroepiandrosterone Tab DHEA® 25 mg , 50 mg
Lyophilized Fish Roe + Cap Aphrofem® 475 mg + 25 mg
Ginkgo Biloba
Second: Female Sexual Arousal Disorder (FSAD):

1. It’s the inability to complete sexual activity with adequate lubrication, it’s similar to Erectile
Dysfunction in males; Symptoms include: lack of vaginal lubrication or dilation, decreased genital
swelling and decreased nipple or genital sensation.
2. Causes may psychological (no desire in the partner, no intimacy), or due hormonal imbalances
(low Estrogen, Low Testosterone), or due menopause (atrophic vaginitis) or due infection
(Vaginitis); Each cause is treated individually.
3. Bremelanotide is used to treat Female Sexual Arousal disorder
➢ It is also used for Low Sexual Desire which occurs before menopause and is not due to
medical problems, psychiatric problems, or problems within the relationship.
➢ Bremelanotide is a non-selective agonist of the melanocortin receptors, MC1 to MC5
(with the exception of MC2)
➢ It is given by an injection just under the skin of the thigh or abdomen; used at least 45 minutes
before anticipated intercourse, only one dose per 24 hours or no more than eight doses per
month is recommended.
➢ Not indicated to enhance sexual performance (not useful for normal females).
➢ It should be stopped after eight weeks if there is no improvement in sexual desire and
associated distress.
➢ It may also cause a temporary increase in blood pressure and decrease in heart rate after each
dose, and darkening of the gums, face, and breasts.
4. Tibolone is a synthetic steroid molecular with estrogenic, progestogenic and androgenic action.
In addition to improvements in vasomotor symptoms and vaginal atrophy when used as
hormonal replacement therapy (HRT) in postmenopausal women, Tibolone has been shown to
improve sexual desire compared with placebo.
➢ Tibolone is also being investigated as a possible treatment for Female Sexual Arousal
Disorder (FSAD) and for Hypoactive Sexual Desire Disorder (HSDD).

Bremelanotide Prefilled Inj. Vyleesi® 1.75 mg/0.3 ml
Tibolone Tab Livial®

7.9- Vaginal Douches (Female Hygiene products)
1. Douching is the act of washing or cleaning out the vagina with water and other ingredients, this
practice is not recommended by most doctors; (Douching is connected as a main cause for
Infertility and Ectopic pregnancy). (8)
➢ Douching may interfere with both the vagina's normal self-cleaning and with the natural
bacterial culture of the vagina.
2. Some women chose to use douches; typically, by using a pre-made mixture is bought in a plastic
bottle with a nozzle that can be squirted into the vagina. (8)
➢ Douching is used for personal hygiene or aesthetic reasons, for preventing or treating an
infection, to cleanse after menstruation or sex (Douching after sexual intercourse is not
an effective form of birth control).
Germ X® Vag. Douche Povidone-Iodine 10% (pH = 5.5)
Gyno Baking Soda® Vag. Douche Sodium Bicarbonate + 2% + 0.025% (pH = 8.9)
Sodium Carbonate
FemmeCare Baking Vag. Douche Sodium Bicarbonate + 2% + 0.025%
Soda® Sodium Carbonate (pH = 8.0 – 9.0)
FemmeCare Astri®, Vag. Douche Benzalkonium Chloride + 0.04% + 0.90%
Femigiene Astri® Aluminum Potassium Sulfate
FemmeCare Vinegar® Vag. Douche Acetic Acid + Sorbic Acid 1.25% (pH =2.8 – 3.5)
FemmeCare Vag. Douche Chamomile Extract 0.063%
Chamomile®
Gyno Foam® Vag. Douche Hexamidine + Chamomile Ex. + (pH = 4.2)
Na Benzoate + Allantoin + Others
Evita ® Vag. Douche Various Ingredients --------------------
Canesten Sensicare ® Vag. Douche Various Ingredients (pH = 5)
Femin-X® Intimate Vag. Douche Various Ingredients (pH = 3.8) , (pH = 4.2)
Lactacyd® Vag. Douche Various Ingredients --------------------
References
2- Lippincott’s pharmacology 7 Ed.
3- Rosemary R Berardi. Handbook of Nonprescription Drugs, 18th Edition
4- Community Pharmacy: Symptoms, Diagnosis and Treatment, By Paul Rutter, 4th Ed.
8- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1380405/

GENITO-URINARY SYSTEM
Chapter Eight: Genito-Urinary System
8.1- Drugs for Benign Prostatic

Hyperplasia (BPH)
a. α1-blokers
b. 5α-reductase inhibitors
c. Combination Products
d. Other drugs may be used for BPH
8.2- Urinary Incontinence (UI)

a. Bladder over-activity
b. Urethral under-activity
8.3- Overflow Incontinence
8.4- Nocturnal Enuresis
8.5- Drugs for Erectile Dysfunction

a. Phosphodiesterase type-5 inhibitors
b. Testosterone-Replacement Regimen
c. Alprostadil injection
d. Other agents for ED
e. Herbal combination Products for ED
8.6- Drugs for Men Ejaculation

Problems
a. Drugs for Premature Ejaculation
b. Delayed Ejaculation
c. Retrograde Ejaculation
8.7- Infertility in Men
8.8- Sexually Transmitted

Diseases (STDs)
8.9- Kidney Stones
8.10- Alkalization of Urine
8.11- Other Urologic drugs

Sam’s Guide: Chapter 8 – Genito-Urinary
Chapter Eight: Genito-Urinary System
8.1- Drugs for Benign Prostatic Hyperplasia (BPH):
1. BPH is also called prostate enlargement, is a noncancerous (benign) increase in size of the
prostate gland; Symptoms may include frequent urination, trouble starting to urinate, weak
stream, inability to urinate, or loss of bladder control.
2. BPH is the most common cause of lower urinary tract symptoms (LUTS), which are divided
into storage, voiding, and symptoms which occur after urination.
➢ Storage symptoms (Irritative) include the need to urinate frequently, waking at night to
urinate, urgency (compelling need to void that cannot be deferred), involuntary urination,
including involuntary urination at night, or urge incontinence (urine leak following a strong
sudden need to urinate).
➢ Voiding symptoms (Obstructive) include urinary hesitancy (a delay between trying to
urinate and the flow actually beginning), intermittency (not continuous), involuntary
interruption of voiding, weak urinary stream, straining to void, a sensation of incomplete
emptying, and uncontrollable leaking after the end of urination.
➢ These symptoms may be accompanied by bladder pain or pain while urinating, called Dysuria.
3. The α1-selective alpha blockers (like: Alfuzosin, Doxazosin, Tamsulosin and terazosin) relax
smooth muscle in BPH producing an increase in urinary flow-rate and an improvement in
obstructive (voiding) symptoms.
➢ α1-blokers can cause orthostatic hypotension which may be severe and produce syncope
after the initial dose; this reaction can be avoided by starting treatment with a low dose,
(preferably at night), Patient should be warned to lie down if symptoms such as dizziness,
fatigue or sweating develop, and to remain lying down until they abate completely.
➢ Tamsulosin and Silodosin are selective for prostatic α1A receptors; therefore, they are
less likely to cause orthostatic hypotension.
➢ Intraoperative floppy iris syndrome is a concern with α-blockers, especially Tamsulosin;
Men with LUTS being offered α-blockers should avoid cataract surgery.
4. The 5α-reductase inhibitors (Finasteride and Dutasteride): decreases the conversion of
testosterone to the more active form: Dihydrotestosterone (DHT), thus reduce prostate volume,
thus relieving storage (irritative); but this takes a number of months (at least 6 months).
➢ Finasteride competitively inhibits type II 5-α-reductase and lowers prostatic DHT by 80%.
➢ Dutasteride is a nonselective inhibitor of both type I and II 5-α-reductase, has the advantage
that is Prostatic DHT production is quickly suppressed with this agent.
➢ Both can reduce Prostate size by about 25% during 6 months.
➢ Both can cause a marked decrease in libido.
➢ Long-term therapy with an α-reductase inhibitor can increase the risk of high-grade tumors
of the prostate in healthy men without a history of prostate cancer.
5. Alpha1-blokers can produce rapid symptomatic relief only (not affect the prostate volume)
while 5α-reductase inhibitors reduce prostate volume but this effect is delayed; therefore, both
drugs may be used together in combination for a better outcome.
6. Phosphodiesterase type 5 inhibitors (Tadalafil 5 mg once daily) is approved for use in BPH,
mechanism is thought to be caused by phosphodiesterase-induced smooth muscle relaxation in
the bladder, urethra, and prostate.
➢ Recommended to be Used as monotherapy; the FDA does not recommend use in
combination with α-blockers because the combination has not been adequately studied for
BPH, and there is a risk of lowering the blood pressure.
➢ In common practice, most physicians combine Tadalafil 5 mg with Finasteride 5 mg once
daily for less than 26 weeks; as the benefit of Tadalafil is reduced gradually after the 4th week.

7. Tamsulosin may be used also for expulsion of lower ureteral stones; by reducing ureteral
spasm, increasing pressure proximal to the stone, and relaxing the ureter in the region of and
distal to the stone; (Used for both males and females).
➢ Maybe useful for small stones only (less than 5 mm), as a Double-blind, placebo-controlled
trial found Tamsulosin did not significantly increase stone passage rate compared with
placebo for stones <9 mm. (9)
➢ Tamsulosin is also used as an add-on treatment for acute urinary retention, patients may
void more successfully after catheter removal if they are taking Tamsulosin; also, they are less
likely to need re-catheterization.
8. Regarding Finasteride:
➢ It could produce feminization of a male fetus if used in pregnant women; therefore, it’s
recommended that women who are or may become pregnant should not handle crushed or
broken Finasteride tablets.
➢ It has been detected in semen; therefore, use of a condom is recommended if the patient’s
sexual partner is, or may become, pregnant.
➢ Used in treatment alopecia (hair loss) in men, Finasteride is given orally in a low dose (1mg
daily); while the dose used for BPH is 5 mg daily. (6)
➢ Some men may experience sexual dysfunction, depression, anxiety, or breast enlargement.
➢ It has been found to be effective in the treatment of Hirsutism (excessive facial and/or
body hair growth) in women, in a study of 89 women with hyperandrogenism due to
persistent adrenarche syndrome, low dose (1 mg) Finasteride produced a 93% reduction in
facial hirsutism and a 73% reduction bodily hirsutism after 2 years of treatment. (10)
α1-blockers
Doxazosin Tab Cardura® , Cardosyr® 1 mg , 2 mg , 4 mg
Prazosin Tab Minipress® , Prazo® 1 mg , 2 mg , 5 mg
Terazosin Tab Hytrin® 1 mg , 2 mg , 5 mg , 10 mg
Alfuzosin Tab Xatral® 2.5 mg , 5 mg , 10 mg
Tamsulosin Cap Flomax® , Omnic® 0.4 mg
Tab Omnic OCAS® 0.4 mg
Silodosin Cap Rapaflo®, Urorec® , Flopadex® 4 mg , 8 mg
Indoramin Tab Doralese® 20 mg
5α-reductase inhibitors
Finasteride Tab Proscar®, Prostacare® 1 mg , 5 mg
Dutasteride Cap Avodart®, Doxaten® 0.5 mg
Phosphodiesterase type 5 inhibitors
Tadalafil Tab Cialis® 5 mg , 20 mg
Dutasteride + Tamsulosin Cap Jalyn®, ComboDart®, Urimax-D® 0.5 mg + 0.4 mg
Tamdus D®, OmiDurt®, Bioprost®
Dutasteride + Alfuzosin Tab ER Alfamax-D® 0.5 mg + 10 mg
Silodosin + Tamsulosin Tab Vesomni® 6 mg + 0.4 mg
Other drugs may be used for BPH
Flutamide Cap Drogenil® , Cytomid® 125 mg
Bicalutamide Tab Casodex® 50 mg , 150 mg
Leuprolide Inj. Lupron® 5 mg/ml
Megestrol acetate Tab Megace® 20 mg , 40 mg
8.2- Urinary incontinence (UI)
1. Normal bladder emptying occurs with a decrease in urethral resistance and contraction of the
bladder muscle; Aging causes a decrease in bladder elasticity and capacity, thus resulting in more
frequent voiding, decline in bladder outlet and increase in urethral resistance.
➢ Also, urethral resistance occurs in women with loss of estrogen, and decrease in flow rate
occurs in men with prostatic enlargement.
2. Urinary incontinence (UI) occurs as a result of over-functioning or under-functioning of the
urethra, bladder, or both; Urethral under-activity is known as stress UI, while Bladder over-
activity is known as Urge UI (bladder muscle is overactive and contracts inappropriately).
The choice of pharmacologic therapy depends on the type of UI

1. Bladder over-activity or Urge Urinary incontinence (U-UI) is associated with increased
urinary frequency and urgency, with or without urge incontinence, the detrusor muscle is
overactive and contracts inappropriately during the filling phase.
a. The pharmacotherapy of first choice for Urge UI is anticholinergic/antispasmodic drugs,
which antagonize muscarinic cholinergic receptors.
b. The anti-muscarinic (Oxybutynin) has direct smooth muscle relaxant properties and has
been most widely used for Urge UI, (used twice or 3 times daily).
➢ Side effects include: dry mouth, constipation, vision impairment, confusion, tachycardia,
orthostatic hypotension, sedation and weight gain.
c. Tricyclic antidepressants have also been used in urge incontinence because of their anti-
muscarinic activity; These include only: (Imipramine, doxepin, Nortriptyline, or
Desipramine) given at bed time.
➢ Their use today is limited; due their potential to cause cardiac side-effects.
d. Purified bovine collagen implant (Contigen®) is indicated for urinary incontinence caused
by intrinsic sphincter deficiency (poor or non-functioning bladder outlet mechanism), the
implant should be inserted only by surgeons or physicians trained in the technique for
injection of the implant.
e. Flavoxate is used to treat urinary bladder spasms, indicated for symptomatic relief of
interstitial cystitis, dysuria, urgency, nocturia, suprapubic pain, frequency and incontinence
f. Mirabegron activates the β3 adrenergic receptor in the detrusor muscle in the bladder,
which leads to muscle relaxation and an increase in bladder capacity.
Drugs for Bladder over-activity (anticholinergic/antispasmodic)
Oxybutynin Tab Ditropan® 5 mg
Syrup Ditronin® 5 mg/5 ml
Patch Oxytrol® , Kentera® 3.9 mg/day
Topical Gel Gelnique® 3% , 10%
Solifenacin Tab Vesicare® 5 mg , 10 mg
Tolterodine Tab Detrol®, Detrusitol® 1 mg , 2 mg
Cap Detrol LA®, Detrusitol R® 2 mg , 4 mg
Fesoterodine Tab ER Toviaz® 4 mg , 8 mg
Darifenacin Tab ER Enablex® , Emselex® 7.5 mg , 15 mg
Propiverine Tab Detrunorm® 15 mg
Propantheline Tab Pro-Banthine® 15 mg
Trospium Chloride Tab Sanctura®, Madaus®, Regurin® 20 mg
Cap Sanctura XR® 60 mg
Flavoxate Tab Urispas® , Genurin® 100 mg , 200 mg
Mirabegron Tab ER Myrbetriq® , Betmiga® 25 mg , 50 mg
Drugs for Bladder over-activity (Tricyclic antidepressants)
Imipramine Tab , Cap Tofranil® 10 mg , 25 mg & 75 mg (Cap)
Desipramine Tab Norpramin® 10 mg , 25 mg , 50 mg
Doxepin Tab , Cap Sinequan® 10 mg , 25 mg , 50 mg
Nortriptyline Cap Pamelor® , Aventyl® 10 mg , 25 mg , 50 mg
* Only these TCAs above are FDA approved for the treatment of U-UI.
2. Urethral under-activity or Stress Urinary incontinence (S-UI) occurs during activities such
as exercise, lifting, coughing, and sneezing, the urethral sphincter no longer resists the flow of
urine from the bladder during periods of physical activity.
a. The goal of treatment of S-UI is to improve urethral closure by stimulating the α-
adrenergic receptors in the smooth muscle of the bladder neck and proximal urethra,
enhancing supportive structures underlying the urethral epithelium, or enhancing serotonin
and norepinephrine effects in the micturition reflex pathways.
b. Generally managed by non-drug methods (specific types of exercise).
c. Duloxetine (SSRI) is licensed for the treatment of moderate to severe stress incontinence in
women; Even though not FDA approved, duloxetine is first-line therapy; most adverse
events diminish with time, Also Imipramine can be used for S-UI.
d. α -Adrenergic agonists is used for S-UI as Pseudoephedrine (15–60 mg three times daily)
with food, water, or milk and Phenylephrine (10 mg four times daily)
➢ Contraindications include hypertension, tachy-arrhythmias, coronary artery disease,
myocardial infarction, hyperthyroidism, renal failure, narrow-angle glaucoma.
Drugs for Bladder Under-activity

Duloxetine Cap Cymbalta® 30 mg , 60 mg
Pseudoephedrine Tab Sudafed® 30 mg , 60 mg , 120 mg
Phenylephrine Tab Contact D® 25 mg , 50 mg , 75 mg
8.3- Overflow incontinence

1. It is a form of urinary incontinence, characterized by the involuntary release of urine from an
overly full urinary bladder, often in the absence of any urge to urinate.
2. This condition occurs in people who have a blockage of the bladder outlet (benign prostatic
hyperplasia, prostate cancer, or narrowing of the urethra), or when the muscle that expels urine
from the bladder is too weak to empty the bladder normally. Overflow incontinence may also be
a side effect of certain medications.
3. It is usually treated with Bethanechol, (it stimulates parasympathetic receptors to increase
bladder muscle tone, which in turn causes contraction and stimulates micturition); Used as 25–
50 mg 3 or 4 times daily on an empty stomach, (Short-term use only).
➢ Avoid use if patient has asthma or heart disease.
➢ Never give I.V. or I.M. because of life-threatening cardiovascular reactions.
➢ Also, may be used for relieving urinary retention, by increasing detrusor muscle
contraction. However, it has only a limited role in the relief of urinary retention; its use has
been superseded by catheterization.
Bethanechol Tab Urecholine® , Myotonine® 5 mg , 10 mg , 25 mg , 50 mg
8.4- Nocturnal Enuresis
1. Nocturnal enuresis (NE), also called bedwetting, is involuntary urination while asleep after the
age at which bladder control usually begins; The etiology of NE is not fully understood, although
there are three common causes: excessive urine volume, poor sleep arousal, and bladder
contractions; also, may be related to low amounts of antidiuretic hormone (ADH).
➢ Some recent studies relate NE to stress.
➢ Urinary tract infections (UTIs) is also linked to NE.
2. Treatment is not appropriate in children under 5 years and it is usually not needed in those
aged less than 7 years and in cases where the child and parents are not anxious about the
bedwetting; however, children over 10 years usually require treatment.
➢ The most important reason for treating enuresis is to minimize the embarrassment and
anxiety of the child and the frustration experienced by the parents; The knowledge that
another family member had and outgrew the problem can be therapeutic.
3. An enuresis alarm should be first-line treatment for well-motivated, well-supported children
aged over 7 years because alarms have a lower relapse rate than drug treatment when
discontinued; (The alarm sounds when the first drop of urine contacts the probe).
4. Desmopressin: an analogue of vasopressin is used for nocturnal enuresis; it is given by oral or
by sublingual administration, Particular care is needed to avoid fluid overload.
➢ Should be administered 1 hour before bedtime, (it reduces urine production during sleep).
➢ Treatment should not be continued for longer than 3 months without interrupting
treatment for 1 week for full re-assessment.
➢ The nasal formulation of Desmopressin is no longer indicated for enuresis by the FDA,
due to reports of seizures in children using the nasal spray.
➢ Patients being treated for primary nocturnal enuresis should be warned to limit fluid intake
to minimum from 1 hour before dose until 8 hours afterwards; and to stop taking
Desmopressin during an episode of vomiting or diarrhea (until fluid balance normal).
➢ Side effects include: Headache, facial flushing, nausea, hyponatremia, seizures.
5. Tricyclic antidepressants such as (Imipramine) are used but relapse is common after
withdrawal; Treatment should not normally exceed 3 months unless a full physical
examination is made and the child is fully re-assessed.
➢ The relapse rate is high when the medication is discontinued.
➢ The usual dose, taken 1-2 hours before bedtime, is 25 mg for patients aged 6-8 years and
50-75 mg for older children and adolescents.
6. An anticholinergic (Oxybutynin) might be helpful in some patients, especially those with
overactive bladder, dysfunctional voiding, or neurogenic bladder; This drug reduces uninhibited
detrusor contractions, increase the threshold volume at which an uninhibited detrusor
contraction occurs, and enlarge the functional bladder capacity.
➢ Oxybutynin is given in a dose of 2.5-5 mg administered at bedtime.
➢ The combination of Desmopressin and Oxybutynin might be efficacious in children with
overactive bladder or dysfunctional voiding who respond to anticholinergic therapy with
improved daytime symptoms but who continue to wet at night.
Vasopressin Inj. Solu. Pitressin® 20 units/ml
Desmopressin Nasal Spray Minirin® , Stimate® 0.1 mg/ml (5 ml),
1.5 mg/ml (2.5 ml)
Tab Minirin® 0.1 mg , 0.2 mg
Inj. Solu. Stimate® 4 mcg/ml
** Desmopressin 5 ml Nasal spray delivers 10 mcg per spray, while the 2.5 ml Nasal spray delivers 150
mcg per spray. (i.e.: the 2.5 ml container is 15 times more potent than the 5 ml container) → (good
luck trying to convene your patients about this fact).
8.5- Drugs for Erectile Dysfunction (ED)
A. Human Male Sexual response cycle consist of 4 stages or phases; which all lead to normal
sexual process; any dysfunction in any stage will lead to a Sexual Dysfunction:
1. Excitement (Desire, Libido) phase: in which the heart rate increase, breathing rate
increase, blood pressure increase and the body temperature increase leading to flushing (sex
flush); the penis becomes partially erected (and fully erected if there is enough sexual
stimulations) and the testicles are drawn upward the body.
2. Plateau (Arousal) phase: the period between sexual excitement and orgasm, in which the
urethral sphincter contract (to prevent urine from mixing with semen, and to prevent
retrograde ejaculation), during this phase a viscous fluid is emitted from the urethra and the
testicles are drawn closer to the body.
3. Orgasmic phase: accompanied by quick cycles of muscle contractions in the lower pelvic
muscles, which surround both the anus and the sexual organs; orgasms are accompanied with
euphoric sensation.
4. Resolution phase: if orgasm is achieved; resolution may last 10-15 minutes with sensation
of calmness and relaxation, and if the orgasm is not achieved; irritability and discomfort can
result, in which it can last for several hours.
➢ Thus, masturbation can be harmful sometimes; due it doesn’t give the body the time to go
throw the natural physiological human male sexual response cycle; and it may not
produce sufficient orgasm to feed the sexual hunger and thus the restoration phase will
end with more irritability and discomfort.
B. Factors Effecting Libido in men:
1. Hormones and Neurotransmitters:
• Dopamine increase libido, while Prolactin decrease libido, (Dopamine directly inhibits
Prolactin release from the pituitary gland).
• Testosterone and Norepinephrine both increase libido.
• Oxytocin is responsible for the orgasm and sexual pleasure.
• Serotonin decrease libido.
2. Psychological Factors: Lack of privacy, lack of intimacy (no love feelings), stress, fatigue,
distraction, depression; all decrease libido.
3. Physical Factors: Hypothyroidism, obesity, anemia, heavy smoking; all decrease libido.
Notes:
1. Erectile dysfunction (ED) is the failure to achieve or maintain a penile erection suitable for
sexual intercourse, Patients often refer to it as Impotence.
➢ It’s different from low sexual desire (which is psychological related).
➢ May be due Hormonal abnormalities because of excess prolactin (hyperprolactinemia) or
decreased testosterone concentrations (hypogonadism).
➢ Being overweight and getting too little exercise raise the chances for ED, Studies show that
men who exercise regularly have a lower risk of ED.
➢ Stress, depression, low self-esteem, and anxiety can prevent the process that leads to an
erection; these factors can also make the problem worse if ED is due a physical problem.
2. Normally, when a man is sexually aroused, the arteries in the penis relax and widen, allowing
more blood than usual to flow into the organ, Impulses from the brain and genital nerves start
the process of filling the penis tissues, and as these tissues expand and harden, the veins that
carry blood out of the penis are compressed, reducing outflow and resulting in an erection.
➢ Thus, drugs that increase blood flow into the penis, can produce an erection.
➢ Phosphodiesterase type-5 inhibitors (PDE-5 I) not only increase the blood flow into the
penis but also prevent the muscle wall from relaxing, so the blood does not drain out of the
blood vessels and the penis remains erect.
3. Treatment options include:
a) Phosphodiesterase type-5 inhibitors (PDE-5 I).
b) Testosterone-Replacement Regimens.
c) Alprostadil Intracavernosal injection (inj. Directly to the penis).
d) Other agents, mainly vasodilators (some are not FDA approved)
First: Phosphodiesterase type-5 inhibitors (PDE-5 I)

1. These include: Sildenafil, Tadalafil, Vardenafil and Avanafil; licensed for the treatment of
Erectile dysfunction (ED), they Inhibits PDE-5 in the penile tissue, preventing the breakdown of
cyclic guanosine monophosphate, thus increasing smooth muscle relaxation in the corpora
cavernosa and increasing penile rigidity.
a. They have no effect on the penis in the absence of sexual stimulation, (Adequate sexual
stimulation is needed to trigger the events leading to erection).
b. Adverse effects are vasodilatation related which include: Headache, hypotension, flushing,
visual disturbances (blurred vision), difficulty discriminating blue from green.
c. PDE-5 Inhibitors may potentiate the hypotensive effects of nitrates, and are therefore
contraindicated in patients receiving such drugs.
d. Avoid use in CVD, hypotension, uncontrolled HT, MI, or stroke within 6 months.
e. Macrolides (Azithromycin Family) increases PDE-5 Inhibitors levels in blood stream.
2. They have different extra indications: Sildenafil, and Tadalafil are licensed for the treatment
of pulmonary arterial hypertension (in both males and females), Tadalafil is also indicated
for treatment of signs and symptoms of BPH.
3. The usual dose of Sildenafil is 50-100 mg about one hour before sexual intercourse, which its
effect last for 4-5 hours; the dose may be increased or decreased depending on response, the
maximum recommended dose is 100 mg, and it should not be taken more than once in 24 hr.
4. Tadalafil is a longer-acting drug, it can be used as required, but can also be used as a regular
lower daily dose to allow for spontaneous (rather than scheduled) sexual activity or in those who
have frequent sexual activity; (effects may last up to 36 hours).
5. Vardenafil is very similar to Sildenafil, its effect lasts for 4-5 hours; but it has the advantage of
that it’s being useful in the treatment of Premature Ejaculation.
6. Avanafil has the advantage that it has very fast onset of action compared with other PDE-5
inhibitors, (usually acts within 10 - 15 minutes), with a duration of effect for 6 hours.
7. The Onset of effect of Sildenafil may be delayed if taken with food; But Tadalafil and Vardenafil
are not affected by food; Dose to be taken (Avanafil: 15–30 minutes, Sildenafil: 1 hour, Tadalafil:
at least 30 minutes, and Vardenafil 25–60 minutes) before sexual activity.
Sildenafil Tab Viagra®, Kamagra®, Novagra® 25 mg , 50 mg , 100 mg
Oral Jelly Kamagra® 50 mg , 100 mg
Inj. Solu. Revatio® 10 mg/12.5 ml
Tadalafil Tab Cialis® 5 mg , 10 mg , 20 mg
Oro D tab 5 mg
Vardenafil Tab Levitra® , Fast-Fix® 5 mg , 10 mg , 20 mg
Oro D tab Staxyn® 10 mg
Avanafil Tab Stendra® , Spedra® 50 mg , 100 mg , 200 mg
Note:
• Sildenafil in Gynecology: tablet may be administered intra-vaginally to reduce the
menstrual cramps; it dilates the blood vessels and increase blood flow to the uterus, which help
to relieve pain.
Second: Testosterone-replacement regimens
1. These restore serum testosterone levels to the normal range (300–1,100 ng/dL; 10.4–38.2
nmol/L); These regimens are indicated for symptomatic patients with hypogonadism as
confirmed by both a decreased libido and low serum testosterone concentrations.
a. Testosterone-replacement regimens correct secondary ED by improving libido, usually
within days or weeks of starting therapy, they restore muscle strength and sexual drive
and improve mood.
b. Testosterone can be replaced orally, parenterally, or transdermally.
2. Testosterone replacement can cause sodium retention, which can cause weight gain or
exacerbate hypertension, congestive heart failure, edema, gynecomastia, serum lipoprotein
changes, and polycythemia; Exogenous testosterone can also exacerbate BPH and enhance
prostate cancer growth.
3. Testosterone Injectable regimens are preferred because they are effective, are inexpensive,
and do not have the bioavailability problems or adverse hepatotoxic effects of oral regimens,
Testosterone patches and gel are more expensive than other forms and should be reserved for
patients who refuse injections.
Testosterone Inj. (I.M.) Sustanon® 100 mg/ml , 250 mg/ml
S.C Inj. Depo-Testerone® 75 mg
Tab , Cap Striant®, Andriol Testocaps® 30 mg (tab), 40 mg (cap)
Patch Androderm® 4 mg/24 hr.
Gel Androgel® 1.62%
Implant Testopel 75 mg pellet
Topical Solu. Axiron 30 mg/actuation
Nasal Gel Natesto 5.5 mg/actuation
Methyl-Testosterone Tab , Cap Android® , Testred® 10 mg
Oxandrolone Tab Oxandrin® 2.5 mg , 10 mg
Third: Alprostadil injections

1. Alprostadil (prostaglandin E1), stimulates adenyl cyclase to increase production of cyclic
adenosine monophosphate, a neurotransmitter that ultimately enhances blood flow to and blood
filling of the corpora, it has 2 dosage forms:
a) Intracavernosal Alprostadil injection (inj. Directly to penis), is effective in 70% to 90% of
patients, acts rapidly, with an onset of 5 to 15 minutes, the duration of action is dose related
and within the usual dosage range lasts <1 hour.
➢ The usual dose is 10 to 20 mcg up to a maximum of 60 mcg.
➢ Should be injected 5 to 10 minutes before intercourse using a 0.5 in, 27- or 30-gauge
needles or an auto-injector.
➢ The maximum number of injections is one daily and three weekly.
b) Intra-urethral Alprostadil pellet: 125 mcg to 1,000 mcg - should be administered 5 to 10
minutes before intercourse, and effects lasts 30-60 min.
➢ Before administration, the patient should empty his bladder and void completely; No
more than two doses daily are recommended.
➢ Associated with pain in 24% to 32% of patients.
➢ Female partners may experience vaginal burning, itching, or pain, which is probably
related to transfer of Alprostadil from the man’s urethra to the woman’s vagina during
intercourse.
2. Adverse effects include: Penile pain, cavernosal scarring, priapism (erect penis do not return to
normal flat), hypotension; Do not use with PDE-5 inhibitors.
3. Alprostadil I.V. injection is also used in maintaining a patent ductus arteriosus in newborns;
this is primarily useful when there is threat of premature closure of the ductus arteriosus in an
infant with ductal-dependent congenital heart disease.
4. Topical Alprostadil cream is only approved in Canada and used there as 1st line treatment for
erectile dysfunction (its applied into the urethra, not by rubbing the external part of the penis).
Alprostadil Inj. Intracavernosal Caverject® 10 mcg , 20 mcg , 40 mcg
Inj. Solu. Edex® 500 mcg/ml
Intraurethral Muse® 125 mcg, 250 mcg, 500 mcg
Pellet/Supp. 1000 mcg
Cream Vitaros® 3 mg/g
Fourth: Other agents for ED

1. These include: Trazodone (α1 receptor antagonist + antidepressant related to SSRIs),
Yohimbine (α2 receptor blocker), Papaverine (vasodilator), Phentolamine (α blocker),
Apomorphine (narcotic analgesic), and other herbal combinations.
2. Trazodone has also antianxiety (anxiolytic/hypnotic) effects.
3. Papaverine is also used to improve blood flow in patients with circulation problems. It works
by relaxing the blood vessels so that blood can flow more easily to the heart and through the
body; Papaverine is also an antiarrhythmic medication (for visceral spams and vasospasms).
➢ Some uses it for Erectile Dysfunctions as an intracavernous inj. (direct inj. To the penis!), It
should not be injected into the penis; This practice has resulted in painful or prolonged
erection that may require surgery to correct.
➢ A topical gel is also available for Erectile Dysfunction treatment, which is safer and more
efficient than the injectable dosage form.
4. Phentolamine is a short-acting α1-blocker (non-selective); usually used for the control of
hypertensive emergencies, most notably due to Pheochromocytoma.
5. Yohimbine, a selective α2 receptor blocker, it increases norepinephrine; thus raises blood
pressure and heart rate; its medically used for general sexual problems in both men and women,
arouse sexual excitement, for erectile dysfunction (ED), sexual problems caused by selective-
serotonin reuptake inhibitors (SSRIs); It acts by increasing blood flow and nerve impulses to the
penis or vagina.
➢ Yohimbine also has fat burning effect, it acts by promoting lipolysis.
6. Apomorphine when taken sublingually; It exerts its effect on hypothalamic centers involved in
the triggering of the erection cascade (it’s a dopaminergic agonist with affinity for dopamine
receptor sites - mostly D2 - within the brain known to be involved in sexual function), it dissolves
rapidly and results in an erection in responders in approximately 20 min.

Trazodone Tab Desyrel®, Oleptro® 50 mg , 100 mg , 150 mg
Yohimbine Tab Yocon®, Aphrodyne® 5.4 mg
Papaverine Cap ER Para Time® 150 mg
Inj. Solu. Pavabid® 30 mg/ml
Gel TriMix® 2%
Phentolamine Inj. Powder Regitine® 5 mg
Inj. Solu. Oraverse® 0.4 mg/1.7 ml
Apomorphine Sub lingual Ixense®, Uprima® 3 mg
Tab

Herbal Combinations for ED
Gentaplex® men Cap Lyophilized Fish Roe + Ginkgo Biloba 570 mg + 30 mg
Aphrofem® women Cap Lyophilized Fish Roe + Ginkgo Biloba 475 mg + 25 mg
Penamax® Cap Acetyl-L-carnitine + Propionyl-L-Carnitine 1600 mg blend
+ L-Arginine + Ginkgo Biloba + Butea Superba
Ultra T Male® Tab Fenugreek Extract + Grape-Apple Extracts 400 mg + 300 mg
+ (Curcuma + Ginseng + Garlic Extracts) + 200 mg
+ Propionyl-L-Carnitine + Rhodiola Rosea + 50 mg + 50 mg
+ Tongkat Ali + Vit. C + Vit. E + Vit. B6 + Ca + 100 mg
+ Magnesium + Zinc + Selenium
Testrogain® Cap Acetyl-L-Carnitine + L-Methionine 500 mg + 400 mg
+ Beta-Sitosterol + DHEA + 200 mg + 50 mg
+ Tribulus Terrestris + Saw Palmetto + 150 mg + 120 mg
+ Soy Bean + Vit. B6 + Magnesium + Zinc + 50mg + 2mg + 71mg
Notes:
1. Fish Roe is commercially known as Caviar, which is well known for its aphrodisiac effects.
2. Ginkgo Biloba dilates blood vessels (by increasing NO levels) to promote blood flow to the
sexual organs, but might increase the risk of bleeding.
3. Acetyl-L-carnitine and Propionyl-L-Carnitine act by boosting energy metabolism.
4. L-Arginine which enhances blood circulation, by increasing the amount of nitric oxide in the
body, they stimulate blood vessels to become larger (thus also used by bodybuilders). This
improves blood flow, which could help a man get an erection
5. Butea Superba is an herb that helps to restore erectile function.
6. Tribulus Terrestris is claimed to increase testosterone levels; However, there is no strong
evidence that it does that.
7. Many other combinations are found in the market, they may include multi-vitamins, Zinc,
proteins, B-complexes, vitamin E …. Etc. (all may be beneficial as secondary supplement).
8.6- Drugs for Men Ejaculation Problems

First: Premature Ejaculation (PE):
1. Premature ejaculation occurs when a man ejaculates sooner during sexual intercourse than
they or their partner would like, it occurs when a man experiences orgasm and expels semen
soon after sexual activity (usually 1 min. after entering the vagina) and with minimal penile
stimulation; Treatment options include: Antidepressants, Dapoxetine, Vardenafil, Tramadol,
Cabergoline and Topical anesthetic
2. Antidepressants (A side effect of certain antidepressants is delayed orgasm), usually SSRI as
Sertraline, Paroxetine, Fluoxetine, and others like Clomipramine.
➢ These medications are taken on demand pre-intercourse.
➢ Patients who can’t tolerate antidepressants side effects can take Clomipramine 25 mg tab.
➢ There is evidence that a combination of Sildenafil with SSRI is better than SSRI alone.
3. Dapoxetine is the first SSRI developed specially for the treatment of premature ejaculation
(PE) in men 18–64 years old, it was rejected by the FDA in 2011, (and still non-FDA approved).
➢ It’s fast acting property makes it suitable for the treatment of PE but not as an antidepressant.
➢ Must be taken BEFORE 2 HOURS from intercourse to work effectively.
➢ Dapoxetine may increase the central nervous system depressant (CNS depressant) activities
of Ethanol, thus its contraindicated to drink alcohol and take Dapoxetine.
➢ In a study comparing Dapoxetine and Sertraline on demand pre-intercourse; the sertraline
group was better compared with the Dapoxetine group as regards ejaculation latency,
ejaculation control, and patient satisfaction. (7)
➢ Combining Dapoxetine with PDE-5 I (as Tadalafil) for the treatment of ED accompanied by
PE has better results in increasing latency than using either products alone.
4. In a study comparing Vardenafil and Sertraline for the treatment of PE, Vardenafil improved
premature ejaculation more than Sertraline. (11, 12)
5. Tramadol (oral analgesic generally used to treat mild pain), it increased ejaculatory latency to
4-20 times in more than 90% of men used it.
6. Cabergoline has been found to raise a man's chances of sustaining multiple orgasms during sex,
(enhance Erection and libido), But don’t try this at home, it’s not (FDA) approved.
7. Topical anesthetic (desensitizing) creams and sprays (containing Lidocaine or Prilocaine
and Vitamin E), these dull the sensation on the penis to help delay ejaculation and applied a short
time before intercourse (usually 15 to 20 minutes).
➢ Their use is sometimes disliked due to the reduction of sensation in the penis as well as for
the partner (due to the medication rubbing onto the partner).
➢ If applied too much it may cause swelling and soreness.
Dapoxetine Tab Priligy®, Longus®, D-Late® 30 mg , 60 mg
Sertraline Tab Zoloft® , Lustra® 50 mg , 100 mg
Vardenafil Tab Levitra® , Fast-Fix® 5 mg , 10 mg , 20 mg
Oro D tab Staxyn® 10 mg
Dapoxetine + Tadalafil Tab Tada Plus®, Bebos Plus® 60 mg + 20 mg
Sildenafil + Tramadol Tab Vegdol Plus® 100 mg + 100 mg
Sildenafil + Lidocaine Cream The Pilot 20 gm cream
Lidocaine Gel , Spray Xylocaine® 2% , 5%
Lidocaine + Prilocaine Cream EMLA® (2.5% + 2.5%)\30 gm
Second: Delayed Ejaculation:

1. Also called Retarded Ejaculation; it is a man's inability for or persistent difficulty in achieving
orgasm, despite typical sexual desire and sexual stimulation.
2. Generally, a man can reach orgasm within a few minutes of active thrusting during sexual
intercourse, whereas a man with delayed ejaculation either does not have orgasms at all or
cannot have an orgasm until after prolonged intercourse which might last for 30–45 min or more.
➢ Some women may actually like a prolonged intercourse; but the majority finds it very tiring
and exhausting and painful.
3. In some cases, delayed ejaculation presents the condition in which the man can climax and
ejaculate only during masturbation, but not during sexual intercourse.
4. Causes for delayed ejaculation is multifactorial, including physical, Psychological and lifestyle
factors, or even due some medications or diseases.
5. All the available drugs for delayed ejaculation are not FDA approved for that cause; all are used
as off-label; these drugs include:
a. Amantadine (antiparkinsonian + antiviral); has benefit in treating delayed ejaculation by
potentiating dopaminergic actions, used 100-400 mg on demand before intercourse.
b. Bupropion (antidepressant, used for smoking cessation); when given as 150 mg once daily
for 2 months, it improves overall ejaculation time.
c. Cyproheptadine (antihistamine, the famous appetite stimulant); has been associated with
improvements in delayed ejaculation, used 8-12 mg on demand (2-3 tabs), 1-2 hours before
intercourse.
d. Oxytocin 24 IU intranasal used minutes just before intercourse is useful for treatment of
delayed ejaculation.
Third: Retrograde Ejaculation:
1. Retrograde ejaculation occurs when semen which would, in most cases, be ejaculated via the
urethra is redirected to the urinary bladder.
2. Normally, the sphincter of the bladder contracts before ejaculation, sealing the bladder which
besides inhibiting the release of urine also prevents a reflux of seminal fluids into the male
bladder during ejaculation; the semen is forced to exit via the urethra, the path of least resistance.
3. When the bladder sphincter does not function properly, retrograde ejaculation may occur; the
retrograde-ejaculated semen, which goes into the bladder, is excreted with the next urination.
➢ Retrograde ejaculation is sometimes referred to as a (dry orgasm), it can cause male
infertility.
4. Drug treatment for Retrograde Ejaculation include: Pseudoephedrine, Midodrine or
Imipramine; they all act by tightening the bladder neck muscles and preventing the semen from
going backwards into the bladder; They are used 1-2 hours before intercourse.
8.7- Infertility in Men

1. Male factor infertility is often an outcome of impaired sperm production or function, which
can originate from a variety of causes, Problems with male fertility can be caused by a number of
health issues and medical treatments, some of these include:
➢ Varicocele: A Varicocele is a swelling of the veins that drain the testicle; It's the most
common reversible cause of male infertility; This may prevent normal cooling of the
testicle by blocking proper blood drainage, leading to reduced sperm count and fewer moving
sperm, treating the Varicocele can improve sperm numbers and function, and may potentially
improve outcomes when using assisted reproductive techniques such as in vitro fertilization.
➢ Infection: Some infections can interfere with sperm production or sperm health, or can cause
scarring that blocks the passage of sperm, these include some sexually transmitted infections,
including chlamydia and gonorrhea; inflammation of the prostate (prostatitis); and inflamed
testicles due to mumps (mumps orchitis); Although some infections can result in permanent
testicular damage, most often sperm can still be retrieved.
➢ Ejaculation issues: Retrograde ejaculation occurs when semen enters the bladder during
orgasm instead of emerging out the tip of the penis; various health conditions can cause
retrograde ejaculation, including diabetes, spinal injuries, medications, and surgery of the
bladder, prostate or urethra, some men with spinal cord injuries or certain diseases can't
ejaculate semen, even though they still produce sperm, in these cases sperm can still be
retrieved for use in assisted reproductive techniques.
➢ Antibodies that attack sperm: Anti-sperm antibodies are immune system cells that
mistakenly identify sperm as harmful invaders and attempt to eliminate them.
o Sometimes a man's body makes antibodies that attack his own sperm; Antibodies are
most often made because of injury, surgery or infection.
➢ Undescended testicles: In some males, during fetal development one or both testicles fail to
descend from the abdomen into the sac that normally contains the testicles (scrotum).
Decreased fertility is more likely in men who have had this condition.
➢ Hormone imbalances: Infertility can result from disorders of the testicles themselves or an
abnormality affecting other hormonal systems including the hypothalamus, pituitary, thyroid
and adrenal glands. Low testosterone (male hypogonadism) and other hormonal problems
have a number of possible underlying causes.
➢ Sperm duct defects: The tubes that carry sperm (sperm ducts) can be damaged by illness or
injury, some men experience blockage in the part of the testicle that stores sperm
(epididymis) or a blockage of one or both of the tubes that carry sperm out of the testicles;
men with cystic fibrosis and some other inherited conditions may be born without sperm
ducts altogether.
➢ Problems with sexual intercourse: These can include trouble keeping or maintaining an
erection sufficient for sex (erectile dysfunction), premature ejaculation, painful intercourse,
anatomical abnormalities such as having a urethral opening beneath the penis (hypospadias),
or psychological or relationship problems that interfere with sex.
➢ Celiac disease: A digestive disorder caused by sensitivity to gluten, celiac disease can cause
male infertility; Fertility may improve after adopting a gluten-free diet.
➢ Certain medications: Testosterone replacement therapy, long-term anabolic steroid use,
cancer medications (chemotherapy), certain antifungal medications (Ketoconazole), some
ulcer drugs (cimetidine) and certain other medications can impair sperm production.
➢ Weight: may play a role in male fertility due to elevated Estrogen and lower Testosterone
levels observed in obese men.
➢ Overheating the testicles: Frequent use of saunas or hot tubs may temporarily lower your
sperm count. Sitting for long periods, wearing tight clothing, the type of underwear you wear
is likely to make a significant difference in male fertility.
➢ Reactive Oxygen Species (ROS): they are small molecules found in many bodily fluids, they
are found in white blood cells and in the sperm cells in semen, ROS can help prepare the sperm
for fertilization, but too much ROS can hurt other cells, Sperm are easily harmed by ROS.
Recent studies have shown more ROS molecules in the semen of infertile men.
2. Treatment for men infertility depends on the underlying cause, which is usually multifactorial:
a. Hypogonadism (low Testosterone levels): the doctor may add Androgens or synthetic
Testosterones such as Mesterolone (over dosing may cause testosterone to get even lower).
b. Hyperprolactinemia: treatment with Cabergoline or Bromocriptine.
c. Retrograde ejaculation: treatment with Pseudoephedrine, Midodrine or Imipramine.
d. High Estrogen levels: treatment with Tamoxifen, Anastrozole or Letrozole.
e. Low FSH or LH levels: treatment with Gonadotropins; usually 1500 or 5000 IU hCG.
f. High (ROS) levels: treatment with antioxidants (Vitamin E, Co-Q10, Selenium)
g. Clomiphene may be given for men with Oligospermia (it increases sperm production in men
by increasing FSH and LH levels); dosed as 25-100 mg per day.
h. Pentoxifylline (peripheral vasodilator) may improve sperm count, motility and shape in
patients using it for 3 to 6 months.
i. Immunologic Infertility: the doctor may add an anti-inflammatory drug (prednisolone)
to lower anti-sperm antibodies and prevent immune system related infertility (prevent
immune system damage); although success rates are not high, and in vitro fertilization (IVF)
with Intracytoplasmic Sperm Injection (ICSI) is now preferred for fertility problems caused
by the immune system.
3. Sometimes the male infertility is due to low count of sperms, or abnormal morphology of
sperms, or Low motility of sperms and abnormal Viscosity:
➢ Agents that increase sperm Count: herbals (Fenugreek, Ginseng, Black seed, Maca Root,
Witharia Somnifera, Mucuna Pruriens, Horny goat weed) and antioxidants (Selenium,
Coenzyme Q10, Vitamin E, Asthaxanthin, L-Carnitine, L-Glutathione, Omega-3, Zinc).
➢ Agents that enhance sperm Morphology: Lycopene, Vitamins C & E, Coenzyme Q10, Folic
acid, D-Ribose, L-Lysine.
➢ Agents that enhance sperm Motility: Pentoxifylline, N-Acetyl-Cysteine, L-Arginine, L-
Carnitine, Myo-Inositol, L-Methionine, Quercetin, L-Citrulline (precursor of L-Arginine).
➢ Agents that enhance sperm Viscosity: N-Acetyl-Cysteine, Mucolytics (Bromhexine,
Ambroxol).
Many Male Fertility blends contain a combination of these products, their results upon enhancing
Sperm quality and quantity is seen after a duration of use for 3 months. (this is because the
spermatogenesis cycle lasts for about 74 days).
8.8- Sexually Transmitted Diseases (STDs)
1. The term sexually transmitted disease (STD) is used to refer to an infection passed from one
person to another through sexual contact, patient can contract an STD by having unprotected
Vaginal, Anal, or Oral sex with someone who has the STD.
➢ Vaginal and Anal sex aren’t the only way STDs are transmitted; It’s also possible to contract
or transmit an STD through Oral sex, STDs can be passed from one person’s genitals to
another person’s mouth or throat and vice versa.
2. That doesn’t mean sex is the only way STDs are transmitted; Depending on the specific STD,
infections may also be transmitted through sharing needles, sharing toothbrushes and Towels,
unclean shaving devices or scissors, Tattoos and tooth medical devices.
3. It’s possible to contract an STD without developing symptoms; but some STDs cause obvious
symptoms, in men common symptoms include:
➢ Pain or discomfort during sex or urination.
➢ Sores, bumps, or rashes on or around the penis, testicles, anus, buttocks, thighs, or mouth.
➢ Unusual discharge or bleeding from the penis.
➢ Painful or swollen testicles.
4. Many different types of infections can be transmitted sexually; The most common STDs are
described below (Herpes Simplex Virus (HSV) Infection, Syphilis, Chlamydia infection,
Gonococcal Infection (Gonorrhea), Human Papillomavirus (HPV), Pubic Lice, Trichomoniasis and
HIV); for HIV see chapter 5, Antivirals for more info.
First: Herpes Simplex Virus (HSV) Infection

1. Herpes is the shortened name for the herpes simplex virus (HSV), there are two main strains of
the virus, HSV-1 and HSV-2, both can be transmitted sexually.
2. HSV-1 primarily causes oral herpes, which is responsible for cold sores; However, HSV-1 can also
be passed from one person’s mouth to another person’s genitals during oral sex, when this
happens, HSV-1 can cause genital herpes; HSV-2 primarily causes genital herpes.
3. The most common symptom of herpes is blistery sores, in the case of genital herpes, these sores
develop on or around the genitals; in oral herpes, they develop on or around the mouth.
➢ Other Symptoms include itching, genital burning, vesicle formation, and ulcer formation.
➢ From 50% to 80% of patients will have a recurrent infection.
4. Treatment options:
➢ For Initial HSV infection: Acyclovir 400 mg orally three times daily for 7–10 days.
➢ For Recurrent HSV infection: Acyclovir 800 mg orally twice daily for 5 days.
➢ For Herpes encephalitis (HSV spread through neural routes): I.V. Acyclovir for 21 days.
Second: Syphilis
1. Syphilis is caused by bacteria (Treponema pallidum), it often goes unnoticed in its early stages.
2. The first symptom to appear is a small round sore, known as a chancre; it can develop on the
genitals, anus, or mouth, it’s painless but very infectious.
➢ if left untreated, late-stage syphilis can lead to: loss of vision, loss of hearing, loss of memory,
mental illness, infections of the brain or spinal cord, heart disease and death.
3. Recommended treatment:
➢ Primary syphilis, Secondary syphilis: Benzathine penicillin G 2.4 million units I.M. in a single
dose, or Doxycycline 100 mg orally twice daily for 2-4 weeks.
➢ Tertiary syphilis: Benzathine penicillin G 2.4 million units I.M. every week for 3 weeks.
➢ Neurosyphilis: Ceftriaxone 2 gm/day by I.M./I.V. for 10–14 days.

Third: Chlamydia infection
1. Caused by (Chlamydia trachomatis), many people with chlamydia have no noticeable symptoms,
when symptoms do develop, they often include: pain or discomfort during sex or urination, green
or yellow discharge from the penis and pain in the lower abdomen
2. If left untreated, chlamydia can lead to: infections of the urethra, prostate gland, or testicles,
pelvic inflammatory disease and infertility.
3. Treatment strategy:
➢ Azithromycin 1 gm in a single dose or Doxycycline 100 mg twice daily for 7 days.
➢ Alternative Rx: Ofloxacin 300 mg twice for 7 days or Levofloxacin 500 mg once for 7 days.
➢ Abstain from sexual intercourse for at least 7 days.
Fourth: Gonococcal Infection (Gonorrhea)

1. Caused by infection with the bacterium (Neisseria gonorrhea); also known as “the clap.”
2. Many people with gonorrhea develop no symptoms; but when present, symptoms may include:
➢ a white, yellow, beige, or green-colored discharge from the penis or vagina.
➢ pain or discomfort during sex or urination.
➢ more frequent urination than usual.
➢ itching around the genitals and sore throat
3. Treatment strategy:
➢ Ceftriaxone I.M. injection or Cefixime Capsule + treatment that covers chlamydia
(Azithromycin 1 g single dose).
➢ Alternative: Gemifloxacin 320 mg + Azithromycin 2 gm orally once.
➢ Abstain from sexual intercourse for at least 7 days.
Fifth: Human Papillomavirus (HPV)

1. Human papillomavirus (HPV) is a virus that can be passed from one person to another through
intimate skin-to-skin or sexual contact; there are many different strains of the virus, some are
more dangerous than others; The most common symptom of HPV is warts on the genitals,
mouth, or throat; Some strains of HPV infection can lead to cancer.
2. 90% of HPV infections (9 out of 10) go away on their own within two years, according to the
CDC; But when the virus doesn’t go away on its own, it can cause serious health problems; these
include genital warts and warts in the throat (known as recurrent respiratory papillomatosis).
3. While most cases of HPV don’t become cancerous, some strains of the virus are more likely to
cause cancer than others. According to the National Cancer Institute, most cases of HPV-related
cancer in the USA are caused by HPV 16 and HPV 18; These two strains of HPV account for 70
percent of all cervical cancer cases.
4. There’s no treatment for HPV, HPV infections often clear up on their own, there’s also a vaccine
available to protect against some of the most dangerous strains, including HPV 16 and HPV 18.
➢ Genital Warts are treated with Imiquimod 5% cream (Aldara®), 3 time per week for up to 16
weeks, or by Podophyllotoxin 0.5% solution or gel (Wartec®), twice daily for 3 days, then 4
days of no therapy and repeating this cycle for up 4 times if necessary.
Sixth: Pubic lice

1. Crabs is another name for pubic lice, they’re tiny insects that can take up residence on the pubic
hair; Like head lice and body lice, they feed on human blood.
2. Common symptoms of pubic lice include: itching around the genitals or anus, small pink or red
bumps around the genitals or anus, low-grade fever; The patient might also be able to see the lice
or their tiny white eggs around the roots of pubic hair.
3. If left untreated, pubic lice can spread to other people through skin-to-skin contact or shared
clothing, bedding, or towels; also Scratched bites can also become infected. It’s best to treat pubic
lice infestations immediately.
4. Treatment as with head or Body lice; Permethrin, Ivermectin.
Seventh: Trichomoniasis
1. Also known as “trich.” It’s caused by a protozoan organism (Trichomonas vaginalis); that can be
passed from one person to another through genital contact; it’s more common in females.
2. According to the CDC, less than one-third of people with trich develop symptoms, but When
symptoms do develop, they may include: discharge from the vagina or penis, burning or itching
around the vagina or penis, pain or discomfort during urination or sex, frequent urination.
3. Treatment options: Metronidazole 2 gm orally or Tinidazole 2 gm orally in a single dose
8.9- Kidney Stones

1. Kidney stone disease, also known as urolithiasis, is when a solid piece of material (kidney stone)
occurs in the urinary tract; Kidney stones typically form in the kidney and leave the body in
the urine stream, a small stone may pass without causing symptoms; If a stone grows to more
than 5 millimeters (0.2 in) it can cause blockage of the ureter resulting in severe pain in the lower
back or abdomen; A stone may also result in blood in the urine, vomiting, or painful urination.
2. There are four different types of kidney stones. It’s important to gain a basic understanding
of each one so you can establish a plan to counteract them—which includes a healthy diet, extra
hydration, and certain medications
A) Calcium stones
Calcium stones make up the majority of all kidney stones at 80%; There are two types of
calcium stones, calcium oxalate (most common) and calcium phosphate—both of which can
be seen on a plain x-ray; both formed in an acidic urine.
a. Oxalates are a natural element in food. But, when there’s an overabundance of oxalates in
the system, they can stick to calcium in the urine to form a calcium oxalate stone. It’s
important if the patient is a calcium stone former, to consume fewer foods on the
high oxalate list, which unfortunately also includes healthy food options such as leafy greens
(kale, spinach), beets, and nuts.
b. Phosphate stones are much less common and typically develop in patients with metabolic
or hormonal disorders such as hyperparathyroidism and renal tubular acidosis.
B) Uric Acid Stones
Uric acid stones make up approximately 10% of all kidney stones. They’re usually formed in
people with a high animal protein diet and people who suffer from gout. If the patient has gout,
then he is 60 percent more likely to develop a kidney stone! Like calcium stones, these stones
are formed in acidic urine (pH less than 7) but are not as visible on a plain x-ray.
➢ Uric acid stones are the only stones that can be dissolved using a diet which in part consists
of increased levels of citric acid and apple cider vinegar.
C) Cysteine Stones
Cysteine stones are the least common stones comprising only four percent of cases. The result of
an inherited (genetic) disorder, Cysteine stones occur when there’s an excess of the amino
acid Cysteine in the body. These stones are recurring and typically larger in size.
D) Struvite Stones
Struvite, or infectious stones, comprise 6 percent of all kidney stones, which in contrast to
most stones, form in an alkaline urine. Struvite stones are more common in women, infants, and
the elderly, and are often associated with recurrent bacterial urinary tract infections.
➢ It is common for Struvite stones to start as calcium stones and then colonize with
bacteria that develop the Struvite component of the stone.
➢ Usually patient is given Acetohydroxamic Acid.
3. There are some uncommon stone types; these include: Calcium Carbonate, Calcium Citrate
and Ammonium Urate (this occurs due laxative abuse).
➢ Also, some drugs and their metabolite may cause renal stones when over-used and
abused, these include: Aminophylline, Ciprofloxacin, Phenazopyridine, Sulfamethoxazole,
Phenytoin, Amoxicillin, and Guaifenesin.
4. Diet is important to prevent the recurrence of renal stones; the patient should be advised to
stick to the following diet:
➢ Calcium = 1.0 gm/day.
➢ Protein = 1.0 gm/kg/day or less low purine content.
➢ Sodium = 100 mEq/day
5. Treatment strategy and options:
a. Prevention is by drinking fluids as many as possible such that more than two liters of urine
are produced per day.
b. In those with Calcium stones: thiazide diuretics (Hydrochlorothiazide) and citrate are
effective; Allopurinol is effective for those with high uric acid levels in the blood or urine.
c. It is recommended that soft drinks containing phosphoric acid (as Pepsi, Cola) be avoided.
d. Large stones may be helped to pass with Tamsulosin (Speed the passage of stones in the
ureter) appear to be effective for stones over 4 mm but less than 10 mm in size.
e. Urine alkalization: increasing the pH of the urine, Acetazolamide is a medication that
alkalinizes the urine.
f. Acetohydroxamic Acid (which is an antibiotic indicated for chronic UTS caused by urea-
splitting bacteria); given 250 mg 3-4 times daily.
g. Certain dietary supplements can cause alkalization of the urine: These include Sodium
Bicarbonate, Potassium Citrate, Magnesium Citrate, and Bicitra (a combination of citric
acid monohydrate and sodium citrate dihydrate).
➢ The mainstay for medical management of uric acid stones is alkalization.
➢ Aside from alkalization of the urine, these supplements have the added advantage of
increasing the urinary citrate level, which helps to reduce the aggregation of calcium
oxalate stones.
➢ They can reduce the efficacy of some antibiotics as (Nitrofurantoin) when co-
administered together; since some antibiotics require acidic media to be active.
Notes:
1. If the stone size is less than 5 mm = most of them will pass spontaneously; with simple
remedies and pain control; but if > 5mm = less than 20% chance of passage and may need a
referral to urologic intervention.
2. Increasing the urine pH to around 6.5 provides optimal conditions for dissolution of uric
acid stones. Increasing the urine pH to a value higher than 7.0 increases the risk of calcium
phosphate stone formation.
3. Urine should be kept acidic all the time; PPIs and H2 blocker should be prohibited or used in
less quantities in those patients who are suffering from peptic ulcer; Vitamin D should be
stopped or used in very low quantity.
4. One of the medical therapies for prevention of stones is the thiazide and thiazide-like
diuretics, such as Chlorthalidone or Indapamide; These drugs inhibit the formation of calcium-
containing stones by reducing urinary calcium excretion; Sodium restriction is necessary for
clinical effect of thiazides, as sodium excess promotes calcium excretion.
5. For people with hyperuricosuria and calcium stones, Allopurinol is one of the few treatments
that have been shown to reduce kidney stone recurrences.
6. Several agents, including alpha adrenergic blockers (such as Tamsulosin) and calcium channel
blockers (such as Nifedipine), have been found to be effective to speed the spontaneous
passage of stones in the ureter.
8.10- Alkalization of Urine
1. The alkalinizing action may relieve the discomfort of cystitis caused by lower urinary tract
infections; Also used for the (Prevention) of uric acid stones.
2. Also, Alkalization of urine can be undertaken with potassium citrate, and Sodium bicarbonate is
used as a urinary alkalinizing agent in some metabolic and renal disorders.
3. Some formulations contain a urinary antiseptic and/or antispasmodic.
• Hexamine is hydrolyzed to Formaldehyde which exerts potent antimicrobial effect against
Gram-positive and Gram-negative bacteria and fungi.
• Khellin is an antispasmodic that relieves urinary smooth muscle spasm and hypermotility
associated with infection.
4. Piperazine citrate, adjusts the pH of urine to the appropriate value that helps dissolve uric acid
and prevents formation and deposition of urate calculi.
Citrogran® Granules NaHCO3 + Tartaric acid + Citric acid ------------------
+ Sucrose
Uralyt-U® Powder Potassium Sodium Hydrogen Citrate 3 gm per dose
Urosolvine® Eff. Powder Piperazine + Colchicine + Atropine 195mg + 0.3mg + 2mg
Uricol Plus® Eff. Powder Piperazine + Colchicine + Khellin 195mg + 0.3mg + 1.83mg
Sankol® Oral drop Herbal preparation 30 ml
Cystone® Tab, Syrup Herbal preparation -------------------
Ural® Powder Sodium bicarbonate 1.76 gm
(sachets) + Citric acid + Sodium citrate + 0.72 gm + 0.63 gm
+ Tartaric acid + 0.89 gm
Urical® Sachets Sodium bicarbonate 1.58 gm
+ Citric acid + Sodium citrate =
+ 0.646 gm + 0.566 gm
+ Tartaric acid + 0.79 gm
Uri Care® Sachets Sodium bicarbonate + Khellin 2.81 gm + 0.62 gm
+ Citric acid + Sodium citrate + 0.5 gm + 1.2 mg
Uricol®, Pharocol® Sachets Hexamine + Piperazine + Khellin 500mg +190mg +1.83mg
Harntee 400 N® Granules Herbal Tea combination ------------------
Kellagon® Cap Herbal preparation ------------------
Proximol® Effervescent Halfa bar extract + Hexamine* 18.6 mg + 6 gm
granules + Piperazine + 1 gm
Foncitril 4000® Sachets Citric acid + Potassium Citrate 1.189 gm + 1.730 gm
+ Sodium Citrate + 1.845 gm
Kalinor® Effervescent Potassium Citrate + 2.17 gm +
Tab Potassium Carbonate + 2.0 gm +
Citric acid 2.057 gm
Uro 3® Sachets Potassium Bicarbonate 2 gm
+ Potassium Citrate + Mg Citrate + 1 gm + 1 gm
+ Phyllanthus + Horse tail + 220 mg + 200 mg
+ Celery + Golden Rod + 100 mg + 100 mg
+ Chrysanthellum + Vit. B6 + 55 mg + 50 mg
Mega Renal-Pro® Sachets Potassium Citrate + Mg Citrate 1 gm + 1 gm
+ Phyllanthus + Horse tail + 220 mg + 200 mg
+ Celery + Golden Rod + 100 mg + 100 mg
+ Chrysanthellum + Vit. B6 + 55 mg + 50 mg
Lithostat® Tab Acetohydroxamic Acid 250 mg
* Hexamine is contraindicated with Sulpha drugs (as Trimethoprim).
8.11- Other Urologic drugs
A. Phenazopyridine exerts an analgesic effect on the mucosa of the urinary tract and is used to
provide symptomatic relief of pain and irritability in conditions such as cystitis and prostatitis,
and urethritis. It is given after food; it causes discoloration of urine.
• If given with an antibacterial for the treatment of urinary-tract infections,
treatment should usually not exceed 2 days.
• (Urinary analgesics also may mask signs and symptoms of UTIs not responding to
antimicrobial therapy).
B. Rowatinex® and Rawachol® are terpene mixtures
• Rowatinex is used for urolithiasis (kidney stones) for the expulsion of calculi.
• Rawachol is used for prevention of liver stones.
• They are given before food, 4 times per day (or 2 Caps. twice daily).
C. Cranberry is used for prophylaxis of urinary tract infections (only); it’s not useful once the
infection has happened, it acts by inhibiting adhesion of uropathogenic E. coli to the urinary tract.
• Administration of standard cranberry preparations is recommended by European
Urological Association (EUA) for prophylaxis.
• It can contribute to nephrolithiasis progression and enhance anticoagulation action of
indirect anticoagulant drugs.
• Available as Capsule, chewable tablet and oral solution.
D. Propolis (extracted from bees); is thought to have antibacterial, antiviral, antifungal, and anti-
inflammatory properties; But scientific research on Propolis is limited; usually found in
combination with other products.
Urisept®, Azo-Mond® Tab Phenazopyridine 100 mg , 200 mg
Spasmo-Cibalgin®
Rowatinex® Cap Terpene mixture -------------------
Rawachol® Cap Terpene mixture -------------------
Alinan Uractiv® Syrup Cranberry + Propolis 10 mg + 12 mg
+ Rosehip + Vit. C + 15 mg + 20 mg (per 5 ml)
References
3- Rosemary R Berardi., Handbook of Nonprescription Drugs 18th Ed.
4- Community Pharmacy: Symptoms, Diagnosis and Treatment, By Paul Rutter 4th Ed.
7- https://journals.lww.com/humanandrology/Abstract/2016/12000/
9- JAMA Intern Med. 2018 Aug 1;178(8):1051-1057
10- Blume-Peytavi U, Whiting DA, Trüeb RM (26 June 2008). Hair Growth and Disorders. Springer Science
& Business Media. p. 369. ISBN 978-3-540-46911-7.
11- https://www.questia.com/magazine/1G1-149202880

PAIN, PAINKILLERS AND
MUSCULOSKELETAL SYSTEM
Chapter Nine: Pain, Painkillers and Musculoskeletal
system
9.1- Analgesics (Non-Narcotics) 9.8-Anti-Migraine drugs
a. Paracetamol, Nefopam, Flupirtine a. Treatment of acute migraine
b. Aspirin b. Prophylaxis of Migraine
c. NSAIDs c. Combination products for Migraine
➢ Some Combination Products d. Medical devices that is FDA
➢ NSAIDs as eye drops approved for Migraine
d. Selective cyclo-oxygenase (COX-2)
inhibitors 9.9- Cannabinoid Analgesics
➢ Some Combination Products
9.2-Analgesics (Narcotics - Opioids)

a. Natural Opiates
b. Semi-Synthetic Opioids
c. Full Synthetic Opioids
9.3-Analgesics Combinations
➢ Special analgesic combinations
9.4-Muscle Relaxants
➢ Muscle Relaxants Combinations
9.5-Neuropathic pain
➢ Drugs used for Neuropathic pain
➢ Vitamin B12 types
➢ Special combinations indicated for
Neuropathic Pain
9.6-Rubefacients, Topical NSAIDs,

and Capsaicin
➢ Topical NSAIDs
➢ Combination products
➢ Topical Rubefacients
➢ Other Topical products for Pain
Relief
9.7-Opioid Antagonists
Sam’s Guide: Chapter 9 – Pain & Painkillers
Chapter Nine: Pain, Painkillers and Musculoskeletal system
1. Pain is an unpleasant sensory and emotional experience that is associated with actual or
potential tissue damage or described in terms of such damage.
2. Damage to body tissues as a result of disease or injury is detected by nerve endings that transmit
signals to the brain; Interpretation of these sensations can be affected by a person’s psychological
state, so that pain is worsened by anxiety and fear, thus reassuring explanation of the cause of
discomfort can make pain easier to bear and may even relieve it altogether.
3. Pain is usually classified into:
a) Acute pain lasts 30 days longer than the usual healing process for that type of injury, and
occurs after muscle strains and tissue injury, such as trauma or surgery.
b) Chronic pain is persistent or episodic pain of a duration or intensity that adversely affects
the function or well-being of the patient and can persist after the resolution of an injury. Some
define it as lasting more than 6 months.
c) Neuropathic pain is a result of an injury or malfunction of the nervous system; it is described
as aching, throbbing, burning, shooting, stinging, and tenderness of the skin.
d) Migraine pain is characterized by a severe headache generally associated with nausea and
light and sound sensitivity.
4. Analgesics are divided into the Opioids (Narcotics) (with similar properties to drugs derived
from opium, such as morphine) and Non-Opioids (Non-Narcotics).
➢ Non-opioids include all the other analgesics, including paracetamol, Nefopam, and non-
steroidal anti-inflammatory drugs (NSAIDs); The non-opioids are less powerful as painkillers
than opioids.
9.1- Analgesics (Non-Narcotics):

These include aspirin, Acetaminophen (Paracetamol), Nefopam, non-steroidal anti-inflammatory
drugs (NSAIDs), selective cyclo-oxygenase 2 (COX-2) inhibitors.
These act as pain killers (analgesics), anti-pyretic, anti-inflammatory (except Paracetamol).
A) Paracetamol, Nefopam and Flupirtine

1. Paracetamol has analgesic and antipyretic effects but has no anti-inflammatory effect,
Paracetamol is a suitable analgesic for children.
2. Over-dosage is particularly dangerous as it may cause hepatic damage.
3. Patient should be advised not to take more than 1 gm (usually 2 tablets of 500 mg) at any one
time, and not more than 8 tablets (4 gm) in 24 hours.
4. A new statement from FDA states that Paracetamol combination drugs must contain at maximum
325 mg of Paracetamol only. (To avoid hepatic damage).
5. Nefopam is a new non-narcotic analgesic that may have a place in the relief of persistent pain
unresponsive to other non-opioid analgesics.
6. Flupirtine is a non-opioid analgesic with neuroprotective and muscle relaxant effect, it works
as a selective activator of neuronal K ± channels - by indirect antagonism to NMDA-receptors,
activating the descending pain modulation mechanisms and GABAergic processes.
Paracetamol Tab Panadol®, Emidol®, Adol® 500 mg
Caplet Panadol Joint® , Directol Extra® 625 mg
Cap Doliprane®, Kernadol® 500 mg , 1000 mg
Syrup Tempra®, Antipyrol® 125 mg/5ml , 250 mg/5 ml
Amp. Hayamol® 300 mg , 600 mg
Supp. Ultramol®, Panatol®, 125 mg , 250 mg
Doliprane® 150 mg , 300 mg
Oral Drops Tempra® , Adol® 120 mg/5 ml
Nefopam Tab Accupan® 30 mg
Amp 20 mg/2 ml
Flupirtine Cap Katadolon® 100 mg
B) Aspirin
1. Also considered as NSAID, two 325-mg tablets administered four times daily produce analgesia,
whereas 12 to 20 tablets per day produce both analgesic and anti-inflammatory activity.
2. Aspirin is used in low doses (75 mg to 160 mg) as platelet aggregation inhibitor, and for the
prophylaxis of myocardial infarction (MI).
3. Aspirin is used off-label as a Mouth Gargle (300 mg in water) for Sore Throat and Tonsillitis.
4. Aspirin is given for pregnant to prevent Pre-eclampsia in those with anti-phospholipid syndrome.
Aspirin Tab (Various) 75 mg , 81 mg , 100 mg ,
325 mg , 500 mg
Effervescent Tab Aspin-C® 100 mg
Powder (oral) Aspegic® 500 mg , 1000 mg
Vial (powder) Aspegic® 500 mg , 1000 mg
* Aspegic® Formulated as DL-Lysine Acetylsalicylate.
C) Non-steroidal anti-inflammatory drugs (NSAIDs):

1. NSAIDs have analgesic, anti-inflammatory, and antipyretic properties. NSAIDs are used for
the relief of mild to moderate pain, minor febrile conditions, and for acute and chronic
inflammatory disorders such as osteoarthritis, and rheumatoid arthritis.
➢ Differences in anti-inflammatory activity between NSAIDs are small, but there is
considerable variation in individual response and tolerance to these drugs, about 60% of
patients will respond to any NSAID; of the others, those who do not respond to one may well
respond to another.
➢ Pain relief starts soon after taking the first dose and a full analgesic effect should normally
be obtained within a week, whereas an anti-inflammatory effect may not be achieved (or
may not be clinically assessable) for up to 3 weeks.
2. NSAIDs are prostaglandin inhibitors and prevent peripheral nociception by vasoactive
substances such as prostaglandins and bradykinins. Most NSAIDs inhibit both COX-1, which
produces prostaglandins that are believed to be cytoprotective of the stomach lining, and
COX-2, which produces prostaglandins responsible for pain and inflammation.
3. Some NSAIDs are applied topically for the relief of muscular and rheumatic pain, and some are
used in ophthalmic preparations for ocular inflammatory disorders (1).
4. The adverse effects of NSAIDs are generally gastrointestinal disturbances, such as
gastrointestinal discomfort; These are usually mild and reversible; although in some patient’s
NSAID may cause peptic ulceration and severe gastrointestinal bleeding.
5. NSAIDs are contra-indicated in patients with Active peptic ulceration.
6. To reduce the risk of gastrointestinal effects:
➢ NSAIDs may be taken with or after food or milk.
➢ Taking H2-antagonists, or proton pump inhibitors such as omeprazole.
➢ Using enteric-coated formulations.
➢ Using some specific NSAIDs like Celecoxib (called selective COX-2 inhibitors) where the risk
of serious upper gastro-intestinal side effects is lower.
7. NSAIDs should be used with caution in patients with asthma (cause respiratory depression),
and hypertension (they cause sodium and water retention).
8. The Use of more than one NSAID together should be avoided because of the increased risk
of adverse effects.
9. Owing to an association with Reye’s syndrome, Aspirin and NSAIDs should not be given to
children under 16 years, unless specifically indicated; (Reye’s syndrome may occur when
aspirin and other salicylates are given during viral infections)
10. NSAIDs are classified as FDA pregnancy category C risk during the first and second trimesters
and category D during the third trimester.
Diclofenac Na+ Tab Voltaren®, Refen®, Diclogesic® 25 mg , 50 mg , 100 mg
Cap Olfen® 75 mg , 100 mg
Cap SR Zorvolex® 18 mg , 35 mg
Powder (oral) Voltafast®, Olfen Despersable® 50 mg , 75 mg
Amp Almiral®, Olfen® 75 mg
Supp. Voltamed® 12.5 mg , 25 mg , 50 , 100 mg
Skin Gel Voltarin®, Voltamed® 10 mg/gm (50 gm tube)
Skin Patch Voltaheat® , Olfen® 140 mg/day
Spray Votrarin Emugel® 1% (75 ml)
Diclofenac K+ Tab Cataflam®, Zipsor® 50 mg , 100 mg
Ibuprofen Tab Advil® , Brufen® , Apifen® 200 mg , 400 mg , 600 mg
Oral Susp. Profinal® , Mufen® 100 mg/5 ml
I.V. Solu. Caldolor® , Neoprofen® 100 mg/ml
Mefenamic acid Cap/Tab Ponstan® , Mefex® 250 mg , 500 mg
Oral Susp. Mefen® 50 mg/5 ml
Tolfenamic acid Cap , Tab Flocur® 20 mg
Ketoprofen Tab/Cap Profenid® 50 mg , 75 mg , 100 mg
Cap ER Bi-Profenid® 200 mg
Amp Profenid®, Isofenal® 100 mg/2 ml
Oral Syrup Toprec® 1 mg/ml (150 ml Bottle)
Skin Gel Profenid Gel® , Fastum® 2.5% (60 gm tube)
Dexketoprofen Tab , Eff. Tab Keral® , Dexday® 25 mg , 50 mg
Indomethacin Cap Indocin® 25 mg , 50 mg
Supp. Indocid® 50 mg , 100 mg
Spray Elmetacin® 1%
Aceclofenac Tab Preservex®, Loflam® 100 mg
Acemetacin Cap Emflex®, Rantudil® 60 mg , 90 mg
Naproxen Tab Aleve®, Naprox® 250 mg , 500 mg
Flurbiprofen Tab Ansaid® , Froben®, Maximus® 50 mg , 100 mg
Dexibuprofen Tab Seractil® 300 mg , 400 mg
Fenoprofen Cap Nalfon® , Fenopron® 200 mg , 400 mg
Loxoprofen Tab Loxonin® , Roxonin® , Oxeno® 60 mg , 120 mg
Oxaprozin Tab Daypro® 600 mg
Tiaprofenic acid Tab Surgam® 100 mg , 300 mg
Etofenamate Amp Flexo® 1 gm/2 ml
Skin Gel Dolo-Denk Gel® 10%
Nabumetone Tab Relafen® 500 mg , 750 mg
Etodolac Tab Dolarit® 400 mg
Tab MR Etopan XL®, Lodine SR® 600 mg
Ketorolac Tab Tradol® 10 mg
Inj. Solu. Ketro , Tradol
® ® 15 mg/ml , 30 mg/ml
Nimesulide Tab , Supp. Coxtal , Nimalox , Ache-off 100 mg (both)
® ® ®
Amp Relaxonim® 75 mg/2 ml

Piroxicam Cap Felden® 10 mg , 20 mg
Tab (subling.) Felden Flash ® 20 mg
Amp Flexase , Felden
® ® 20 mg/2 ml , 20 mg/ml
Skin Gel Felden Gel , Picam
Supp. 20 mg
Meloxicam Tab Mobic , Neoxicam
® ® 7.5 mg , 15 mg
Cap SR Vivlodex ® 5 mg , 10 mg
Amp , Supp. Mobic ® 15 mg/1.5 ml , 15 mg (Supp)
Tenoxicam Tab Admiral , Tilcotil
® ® 20 mg
Vial (powder) Mobiflex® , Trocmetam® 20 mg
Lornoxicam Tab Quando® , Xefo® 8 mg , 16 mg
Vial (powder) Xefo® 8 mg
Metamizol Tab , Inj. Novalgin®, Nolotil® 500 mg , 575 mg
Some Extra Notes:
1. NSAIDs within a group tend to have similar characteristics and tolerability; There is little
difference in clinical efficacy among the NSAIDs when used at equivalent doses, differences among
compounds usually relate to dosing regimens (related to the compound's elimination half-life), route
of administration, and tolerability profile.
2. Naproxen is the only NSAID that does not appear to increase the risk of CV events; therefore, its
use is preferred in patients with CV risk factors per the ACG guidelines; However, in Feb. 2014, FDA
panel voted against label changes that would indicate a lower CV risk.
➢ Naproxen onset of action for analgesia is 1 hour, duration of effect is about 7 hours.
➢ Onset of action for anti-inflammatory effect is 2 weeks.
3. Diclofenac has potent anti-inflammatory effect with medium analgesic effect, but its associated with
the highest risk of heart attack and stroke among non-selective NSAIDs.
4. Aceclofenac is the glycolic ester of Diclofenac, it’s very similar to Diclofenac in potency and activity;
but has the advantage of having lower side effects profile, (4-folds lesser than Diclofenac).
5. The CHMP has recommended restrictions on the use of Piroxicam because of the increased risk
of gastro-intestinal side effects and serious skin reactions; The CHMP has advised that:
➢ Piroxicam should not be used as first-line treatment.
➢ Piroxicam dose should not exceed 20 mg daily.
➢ Treatment should be reviewed 2 weeks after initiating, and periodically thereafter.
6. Meloxicam has dose dependent COX 2 selectivity (7.5 mg is more COX 2 selective than 15 mg), and
short term 7.5 mg daily is less likely than Naproxen or Diclofenac to be associated serious GI
complications; but it may cause elevates in liver function tests in about 15% of patients.
7. Nimesulide has been withdrawn from market in many countries, due to concerns about the risk
of hepatotoxicity; the use of Nimesulide in children under the age of 12 is C.I.
➢ Nimesulide exerts COX-2 selectivity similar to celecoxib.
8. Ibuprofen onset of analgesia is 30 minutes and Duration is about 4-6 hours.
➢ At low dose it has low risk of causing GI side effects, but this advantage is lost at high doses.
➢ The safest option for breastfeeding women (has a short half-life, and excreted in very small
amount in breast milk).
➢ It’s used for the treatment of acne, because of its anti-inflammatory properties, and has been
sold in Japan as a topical form for adult acne.
➢ Ibuprofen may be useful in the treatment of severe orthostatic hypotension.
➢ Dexibuprofen is the active enantiomer of Ibuprofen; It has similar properties to Ibuprofen.
9. Oxaprozin also has a mild Uricosuric properties and is used in the treatment of gout.
➢ It has a rapid onset of action, and a very long duration of action (half-life 50-60 hours).
10. Acemetacin is a pro-drug, which is converted into Indomethacin.
11. Tiaprofenic acid can cause severe cystitis, thus it should not be given to patients with urinary-tract
disorders and should be stopped if urinary symptoms develop.
12. Sulindac, an analog of Indomethacin, is unique among the NSAIDs in not inhibiting prostaglandin
synthesis in the kidneys, thus it may be one of the safest drugs for treating osteoarthritis in elderly.
➢ Have similar anti-inflammatory potency with Indomethacin; but less toxic.
13. Indomethacin is very potent anti-inflammatory and analgesic, but has high cardiovascular risk
and significant GI toxicity; it should not be used by children <14 years.
➢ Ankylosing Spondylitis responds better to Indomethacin; It is probably related to its stronger
inhibition of prostaglandin synthesis.
14. Ketoprofen has the advantage that (unlike other NSAIDs) it inhibits the synthesis of leukotrienes
and leukocyte migration into inflamed joints, in addition to inhibiting the biosynthesis of
prostaglandins; it also stabilizes the lysosomal membrane during inflammation, resulting in
decreased tissue destruction.
15. Metamizol is a potent analgesic and antipyretic, but week anti-inflammatory drug.
➢ Metamizol was banned in the USA and some European countries due to several reported
cases of agranulocytosis; but it has been extensively used in India and other countries.
16. Etodolac has the Lowest risk of gastrointestinal damage in the NSAIDs group; Although Etodolac
is no more potent than other NSAIDs.
17. Flurbiprofen has very high analgesic effect compared to other NSAIDs, 536-fold more potent than
Aspirin and 26 times more potent than Ibuprofen.
18. Ketorolac is the most COX-1 selective NSAID, it’s the most potent and most effective NSAID
analgesic, with efficacy comparable to opioids; The analgesic effect of 30 mg of ketorolac is similar
to 10 mg of morphine; (thus recommended for 5-day use only).
➢ But it has the highest incidence of side effects; This drug is about five times more gastro toxic
than other NSAIDs; and the risk of adverse effects is higher when ketorolac is used in higher doses,
in elderly patients, and for more than 5 days.
➢ Ketorolac is banned in France and Germany since 1993, due to high risks of Gastrointestinal
bleeding and renal failure.
Some Combination Products of NSAIDs

These combination below are designed to decrease the direct gastrointestinal side effects of NSAIDs by
combining them with PPIs, H2 Blocker and Misoprostol.
Ketoprofen + Omeprazole Cap Axorid® (100mg + 20mg), (200mg + 20mg)
Naproxen + Esomeprazole Tab Vimovo® 500 mg + 20 mg
Meloxicam + Esomeprazole Tab Rumonal Pro® 15 mg + 20 mg
Ibuprofen + Famotidine Tab Duexis® 800 mg + 26.6 mg
Diclofenac Na+ + Misoprostol Tab Arthrotec® , Misofen® 50 mg + 200 mcg
Naproxen + Misoprostol Tab Napratec® 500 mg + 200 mcg
NSAIDs as eye drops

They are used to suppress the optical mast cell responses to allergens including (but not limited
to) aerosolized dust particles and other allergens, also used as ophthalmic analgesics or in allergic
conjunctivitis to reduce the eye inflammation.
➢ For more info, see chapter 12.

D) Selective cyclo-oxygenase 2 (COX-2) inhibitors:
1. These are also NSAIDs, but they are selective for inhibition of COX-2 (responsible for
inflammation and pain), this selectivity against COX-2 provides a therapeutic advantage over
nonselective COX inhibitors, allowing the proper management of chronic inflammatory
conditions. (6), They have been shown to be associated with less GI bleeding and dyspepsia.
➢ Contraindicated in patients who are allergic to sulfur. (Except Etoricoxib).
2. They are associated with an increased risk of serious (and potentially fatal) adverse
cardiovascular thrombotic events, including myocardial infarction and stroke.
➢ They Increase the risk of major cardiovascular problems by about 37%.
➢ Thus (Celecoxib, Etoricoxib, and Parecoxib) are contra-indicated in ischemic heart
disease, cerebrovascular disease, peripheral arterial disease, and mild to severe heart
failure; They should be used with caution in patients with a history of cardiac failure, left
ventricular dysfunction, hypertension, in patients with edema for any other reason, and in
patients with other risk factors for cardiovascular events.
➢ Although; a shocking trail (discussed below) shows that CV risk is not a COX-2 inhibitor
class effect, and CV risk was the same in Celecoxib compared with Naproxen and Ibuprofen.
➢ And due that trail; an FDA advisory panel in 2018 concluded that Celecoxib poses no
greater risk for causing heart attacks and strokes than the commonly-used NSAIDs
Ibuprofen or Naproxen and recommended that the FDA consider changing its advice to
physicians regarding celecoxib's safety. (7)
3. Celecoxib and Etoricoxib are licensed for the relief of pain in osteoarthritis, rheumatoid
arthritis, and ankylosing spondylitis; but Etoricoxib is also licensed for the relief of pain from
acute gout; as follows:
➢ Etoricoxib tablet 60 mg – 90 mg once daily for Osteoarthritis, Rheumatoid arthritis,
Ankylosing spondylitis and Acute pain conditions.
➢ Etoricoxib tablet 120 mg once daily for Acute Gout, limited for use for 7 days only.
➢ Etoricoxib tablet 90 mg once daily for postoperative dental pain surgery, for 3 days only.
➢ Etoricoxib is approved in more than 80 countries worldwide, but it’s not approved by the
US FDA, and not allowed to be sold in the USA; as the (FDA) requires additional safety and
efficacy data for Etoricoxib before it will issue approval. (Due to the other 3 withdrawals in
this family).
Celecoxib Cap Celebrex , Coxib
® ® 100 mg , 200 mg
Rofecoxib Tab Vioxx , Ceoxx
® ® 12.5 mg , 25 mg , 50mg
Valdecoxib Tab Bextra ® 10 mg , 20 mg
Parecoxib Vial (powder) Dynastat ® 40 mg
Lumiracoxib Cap Prexige ® 100 mg
Etoricoxib Tab Arcoxia® , Atoxia® , Etoxia® 60 mg , 90 mg , 120 mg
Mavacoxib Tab Trocoxil ® 75 mg
Notes:
1. Rofecoxib and Valdecoxib were withdrawn from the market on 2004, 2005 respectively;
because of concerns about increased risk of heart attack and stroke associated with long-term,
high-dosage use.
2. Parecoxib is an injectable prodrug of Valdecoxib; it is approved through much of Europe for
short term perioperative pain control, has no effect on platelet function and therefore does not
promote bleeding during or after surgery.
➢ The drug is not approved for use after cardiac surgery in Europe.
3. Lumiracoxib has been withdrawn from the market in several countries, mostly due to
hepatotoxicity concerns; It has never been approved for use in the USA.
4. Mavacoxib was rejected several times as a human Drug; then it was approved as veterinary drug
Note1: PRECISION trail (8)
1. Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or

Naproxen, a randomized controlled trial to prospectively examine the CV safety of long term
NSAID use in arthritis patients with, or at high risk for CV disease.
2. The trail included (24,081) patients for (10 years); which used Celecoxib 100 mg BID, Ibuprofen
600 mg TID and Naproxen 375 mg BID.
3. The summery of the trail was (with mean drug exposure ±20 months):
➢ Celecoxib demonstrated similar incidence of CV events compared to Naproxen and
Ibuprofen, and the rate of hospitalization for hypertension was also significantly lower with
Celecoxib compared to Ibuprofen.
➢ Celecoxib treatment also resulted in lower rates of gastrointestinal events than did either
comparator: Ibuprofen and Naproxen
➢ Celecoxib was also demonstrated significantly lower rate of renal events than with
Ibuprofen, and similar to Naproxen
➢ CV risk is not COX-2 inhibitors class effect, and not all COX-2 inhibitors are the same.
4. This trial was funded and supported by Pfizer (the brand & originator of Celecoxib).
Note2: Some Combination Products of COX-2 Inhibitors

Celecoxib + Orphenadrine Tab Caditar Flex® 200 mg + 25 mg
Celecoxib + Pregabalin Cap Lyca-C® 200 mg + 75 mg
Etoricoxib + Paracetamol Tab Nucoxia-P® 60 mg + 500 mg
Etoricoxib + Pregabalin Tab , Cap Cilonerve®, Neurobem® 90 mg + 75 mg
Etoricoxib + Thiocolchicoside Tab Nucoxia-MR® (60mg + 4mg), (60mg + 8mg)
* Orphenadrine and Thiocolchicoside are muscle relaxants (see below).
* Pregabalin is an anticonvulsant that used for neuropathic pain.
Note3: what to choose?! (9)

Too many NSAIDs are available; both traditional and new COX-2 selective, which one is better than
others? Are they all the same? To answer these questions, see the notes below:
1. The analgesic benefit and anti-inflammatory properties of NSAIDs are COX-2 dependent
(this means the more COX-2 selective the more anti-inflammatory effect).
2. Oral NSAIDs have no significant differences in general analgesic potency.
3. The gastrointestinal (GI) side effects from NSAIDs are directly related to inhibition of COX-1, thus
Selective COX-2 inhibitors showed the least likelihood of GI side effects including perforation,
bleeding, or obstruction.
➢ Diclofenac showed a 2-fold increase in GI side effects, while Ibuprofen and Naproxen
showed a 4-fold increase than Celecoxib.
4. Nearly all NSAID regimens displayed a 2-fold increase in the risk of hospitalization due to heart
failure, possibly related to sodium retention.
➢ Naproxen did not show the increased risk of major coronary or vascular events.
➢ In a large, country-wide observational study in Denmark, researchers found a correlation
between NSAID use and death rate, with COX-2 selective inhibitors having an increased
hazard ratio for death; Ibuprofen used in quantities greater than 1,200 mg were associated
with an increased hazard ratio for the composite end-point of myocardial infarction (MI) and
death, as was Diclofenac dosages greater than 100 mg.
➢ In 2015, the US FDA strengthened its warning that NSAIDs (both selective and non-selective)
can cause adverse cardiovascular outcomes, include M.I., stroke, and heart failure.
5. Prolonged NSAID use can limit prostaglandins synthesis below the required level, resulting in
acute kidney injury; elevated risks were noted for selective and partially selective NSAIDs
(Diclofenac, Meloxicam, Celecoxib).
Note4: it’s all about COX-2 selectivity
1. The more COX-2 selective the more potent anti-inflammatory (also more CV side effect??)
2. The less COX-2 selective the more potent analgesic (also more GI side effects??)
3. The table below shows NSAIDs Classification by COX selectivity, done by (in vitro assessment of
COX-1/COX-2 activity):
Note5: I feel lost, need an easier approach

1. If you feel you don’t have any time to look and read about all the NSAIDs notes above, and in the
textbooks, or by Googling; below a simple table to help you choose a NSAID:

9.2- Analgesics (Narcotics - Opioids):
1. These drugs are related to opium, an extract of poppy seeds; They act directly on several sites in
the central nervous system to block the transmission of pain signals, because they act directly on
the parts of the brain where pain is perceived, opioids are the strongest analgesics and are
therefore used to treat the pain arising from surgery, serious injury, and cancer.
➢ The use of these powerful opioids is strictly controlled because the euphoria produced can
lead to abuse and addiction; but when these opioids are given under medical supervision to
treat severe pain, the risk of addiction is negligible.
2. Opioid analgesics are usually used to relieve moderate to severe pain, (the Repeated
administration may cause dependence and tolerance).
3. Opioids such as (Codeine or Dextropropoxyphene) are used in the treatment of less severe
pain, and are often combined with non-opioid analgesics such as aspirin, or Paracetamol.
4. More potent opioids such as Morphine are used in severe acute and chronic pain.
5. Tramadol produces fewer of the typical opioid side-effects (notably, less respiratory
depression, less constipation and less addiction potential (2), (However, Tramadol is abused by
many addicts, locally and worldwide); Tramadol is a serotonin releaser, reuptake inhibitor
of norepinephrine (SNRI) and a weak μ-opioid receptor agonist.
➢ Tramadol painkilling action starts in less than 1 hour, but wears off after about 4 hours.
➢ In the USA, the doctor can only prescribe Tramadol in maximum of five refills for the same
patient, and a new prescription is required every 6 months.
➢ Tramadol is used off-label for the treatment of premature ejaculation (PE).
6. The most common side-effects include nausea and vomiting (particularly in initial stages),
and constipation (2); also, opioid (Narcotic) analgesics may prevent clear thought and cloud
consciousness; thus, the Narcotic addict is very dangerous.
➢ Other possible adverse effects depressed breathing; when they are taken in overdose, these
drugs may induce a deep coma and lead to fatal breathing difficulties.
7. Opioids should be used with caution in patients with impaired respiratory function (avoid
in chronic obstructive pulmonary disease) and asthma (avoid during an acute attack), also
avoided in obstructive or inflammatory bowel disorders.
8. Long-term use of opioid analgesics can cause hypogonadism and adrenal insufficiency in
both men and women. This is thought to be dose related and can lead to amenorrhea, reduced
libido, infertility, depression, and erectile dysfunction.
9. Also, Long-term use of opioid analgesics has also been associated with a state of abnormal pain
sensitivity (hyperalgesia), which is more diffuse and less defined than normal pain.
10. Can be classified into:
a. Natural opiates: alkaloids contained in the resin of the opium poppy, as Morphine, Codeine.
b. Semi-synthetic opioids: created from either the natural opiates or morphine esters, such as
hydromorphone, hydrocodone, oxycodone, Oxymorphone, buprenorphine.
c. Fully synthetic opioids: such as Fentanyl, Pethidine, Levorphanol, Methadone,
Tramadol and Dextropropoxyphene.
11. A combination of opioid and non-opioid analgesics is used to treat postoperative pain, the use of
intra-operative opioids affects the prescribing of postoperative analgesics, a postoperative
opioid analgesic should be given with care since it may potentiate any residual respiratory
depression.
12. Opioid analgesics are relatively ineffective in dental pain, also they often cause nausea and
vomiting which limits its value in dental pain.
13. Other opioids include (Loperamide, Difenoxin, Diphenoxylate), are used mainly in the
treatment of diarrhea (see chapter 2, section 6, for more details).
Natural Opiates
Morphine Tab ER Arymo ER® 15 mg , 30 mg
Inj. Susp. (ER) Depodur®, Kadian® 10 mg/ml
Inj. Solu. Avinza® 0.5 mg/ml , 1 mg/ml
Inj. Solu. Infumorph® 200 mg/20 ml , 500 mg/20 ml
Codeine * Tab Codam® 15 mg , 30 mg , 60 mg
Inj. Solu. 15 mg/ml , 30 mg/ml
* Codeine is also used in the treatment of dry cough as an antitussive, and also used as
antidiarrheal (off-label).
Semi-Synthetic Opioids
Hydromorphone Tab Dilaudid , Exalgo
® ® 2 mg , 4 mg , 8 mg , 12 mg , 16 mg
Inj. Solu. 2 mg/ml , 4 mg/ml , 10 mg/ml
Hydrocodone Cap Zohydro® 10 mg , 15 mg , 20 mg , 40 mg
Oxycodone * Tab Roxicodone , Oxecta
® ® 10 mg , 15 mg , 20 mg , 30 mg
Oxymorphone Tab Opana , Opana ER
® ® 5 mg , 10 mg , 15 mg , 20 mg
Buprenorphine ** Tab (subling.) Buprenex , Temgesic
® ® 2 mg , 8 mg
Inj. Solu. Subutex ® 0.3 mg/ml
Skin Patch Butrans ® 5 mcg , 10 mcg , 20 mcg (per hr.)
* Oxycodone is pregnancy (B) risk factor, but becomes (D) with high doses or long-term use.
** Buprenorphine’s high-dose sublingual tablet preparations indicated for detoxification and
long-term replacement therapy in opioid dependency (opioid addiction treatment), and the
drug is now used predominantly for this purpose.
Fully Synthetic Opioids

Fentanyl or Inj. Solu. Sublimaze® 0.05 mg/ml
(Fentanil) Intra-nasal Lazanda® 100 mcg/0.1 ml ,
(Contains only 8 sprays/bottle) 400 mcg/0.1 ml
Skin Patch Duragesic® 12.5 mcg , 25 mcg , 50 mcg
Remi-Fentanyl Vial (Solu.) Ultiva® 1 mg , 2 mg , 5 mg
Sufentanil Tab , SubLing Dsuvia 30 mcg
Inj. Solu. Sufenta 0.05 mg/ml
Pethidine (or) Tab , Demerol® 50 mg , 100 mg (tab)
Meperidine (in USA) Inj. Solu. 25 mg/ml , 50 mg/ml (inj.)
Levorphanol Tab Levo-Dromoran® 2 mg
Methadone Tab Dolophine® 5 mg , 10 mg
Inj. Solu. 10 mg/ml
Dextropropoxyphene Tab Darvon® , Darvocet® 65 mg , 100 mg
Nalbuphine Inj. Solu. Nubain® 10 mg/ml , 20 mg/ml
Butorphanol Inj. Solu. Stadol® 1 mg/ml , 2 mg/ml
Nasal Spray 10 mg/ml
Pentazocine Inj. Solu. Talwin® 30 mg/ml
Tramadol Tab , Cap Tramal® , Ultram® , Topalgic® 50 mg , 100 mg , 200 mg
Inj. (Amp) Zydol®, Trabar® 50 mg/ml , 100 mg/2 ml
Tapentadol Tab Palexia® 50 mg , 100 mg , 200 mg
Extra Notes:
1. Dextropropoxyphene has been taken off the market in Europe, USA in 2010, due to concerns of fatal
overdoses and heart arrhythmias, it’s still used in our market.
2. Nalbuphine is indicated for the relief of moderate to severe pain. It can also be used as a supplement to
balanced anesthesia, for preoperative and postoperative analgesia, and for obstetrical analgesia during
labor, and as a treatment for morphine induced pruritus.
3. Butorphanol is used in management of migraine using the intranasal spray formulation. It may also be
used parenterally for management of moderate-to-severe pain, as a supplement for balanced general
anesthesia, and management of pain during labor.
a. Butorphanol is more effective in reducing pain in women than in men.
b. Recently was discontinued by the manufacturer; It’s now only available in generic.
4. Tapentadol produces analgesia by two mechanisms. It is an opioid-receptor agonist and it also inhibits
noradrenaline reuptake.
9.3- A) Analgesics Combinations

1. Analgesics are frequently used in combination, such as the Paracetamol and codeine preparations found
in many non-prescription pain relievers.
2. The use of Paracetamol, Aspirin, Ibuprofen, Naproxen and other NSAIDS concurrently with weak to
mid-range Narcotics has synergistic effects by combatting pain at multiple sites of action.
Antidol®, Pain Stop® Cap Dextropropoxyphene + 32.5 mg +
Paracetamol 325 mg
Relief® Tab Diclofenac Na + Paracetamol + 50 mg + 500 mg
Chlorpheniramine + 100 mg
No-Pain®, Ibex®, Cap Paracetamol + Ibuprofen 325 mg + 200 mg
Novafen® + Caffeine + 30 mg
Dologan Denk Tab Paracetamol + Ibuprofen 250 mg + 250 mg
+ Caffeine + 50 mg
Cilopan® Tab Paracetamol + Nefopam 325 mg + 30 mg
Megafen® Tab Paracetamol + Ibuprofen 325 mg + 200 mg
Susp. Paracetamol + Ibuprofen 162.5 mg + 100 mg
Pain Leave®, Tab Paracetamol + Diclofenac Na 500 mg + 50 mg
Relief Extra® + Chlorpheniramine + 4 mg
+ Mg-Trisilicate + 100 mg
Stopain®, Tab Paracetamol + Caffeine 300 mg + 50 mg
Panalgrine® + Propyphenazone + 150 mg
Saridon® Tab Paracetamol + Caffeine 250 mg + 50 mg
+ Propyphenazone + 150 mg
Excedrin® Tab Paracetamol + Aspirin + Caffeine 250 mg + 250 mg + 65 mg
Citramon® Tab Paracetamol + Aspirin + Caffeine 200 mg + 220 mg + 27 mg
Diclomol® Tab Paracetamol + Diclofenac Na 500 mg + 50 mg
Actinac Plus®, Tab Paracetamol + Aceclofenac 500 mg + 100 mg
Pyxinac Plus®
Nimo Plus® Tab Paracetamol + Nimesulide 500 mg + 100 mg
Azur®, Zerlor®, Panlor® Tab Paracetamol + Caffeine+ Codeine 350 mg + 50 mg + 30 mg
Panamax® Tab Paracetamol + Caffeine+ Codeine 500 mg + 30 mg + 10 mg
Synalgos® Tab Aspirin + Caffeine + Codeine 356 mg + 30 mg + 16 mg
Co-Codamol® Tab Paracetamol + Codeine 500 mg + 8 mg
Talacen® Tab Paracetamol + Pentazocine 650 mg + 25 mg

Ultracet®, Zafin® Cap, Tab Paracetamol + Tramadol HCL 325 mg + 37.5 mg
Sudamed Plus®, Tab Paracetamol + Diclofenac Na 350 mg + 50 mg
Sudafed® + Tramadol HCL + 25 mg
Mega-Relief Forte® Cap Paracetamol + Diclofenac Na 350 mg + 50 mg
+ Tramadol HCL + Codeine + 25 mg + 8 mg
Advil PM® Tab, Cap Ibuprofen + Diphenhydramine 200 mg + 25 mg
Combunox® Tab Ibuprofen + Oxycodone 400 mg + 5 mg
Ibudone®, Tab Ibuprofen + Hydrocodone (200 mg + 2.5 mg),
Vicoprofen® (200 mg + 5 mg)
Percodan®,Oxycodan® Tab Aspirin + Oxycodone 325 mg + 5 mg
Midol Max®, Tab, Cap Paracetamol + Pamabrom * 500 mg + 25 mg
Pamprin® + Pyrilamine ** + 15 mg
Pamprin PMS® Tab, Cap Paracetamol + Pamabrom 500 mg + 25 mg
+ Pyridoxine + 50 mg
* Pamabrom is a diuretic. ** Pyrilamine is an antihistamine.
9.3- B) Special analgesic combinations: (may be useful for Neuropathic pain)

Difen B12® Tab Diclofenac K + Betamethasone 50 mg + 0.3 mg
+ Cyanocobalamin (Vit. B12) + 5 mg
(Amp + Vial) Diclofenac K + Betamethasone 75 mg + 2.63 mg
To be Mixed + Hydroxocobalamin (Vit. B12) + 10 mg
Dioxaflex B12®, Tab Diclofenac Na + Betamethasone 50 mg + 0.3 mg
Panclo B12®, + Cyanocobalamin (Vit. B12) + 5 mg
Rodinac B12® 1 Amp (only) Diclofenac Na + Betamethasone 75 mg + 2 mg
+ Hydroxocobalamin (Vit. B12) + 10 mg
Difen Flex®, Tab Diclofenac Na + Pridinol* (50 mg + 4 mg)
Oxadisten® Amp Diclofenac Na + Pridinol* (75 mg + 2.2 mg)
Mio Virobron®, Tab Meloxicam + Pridinol* 15 mg + 4 mg
Bronax Flex®
Tremecox® Cap Meloxicam + Gabapentin* 15 mg + 300 mg
Dorsal® Tab Meloxicam + Carisoprodol* 15 mg + 100 mg
Flexicamin® Tab Piroxicam + Carisoprodol* 10 mg + 350 mg
Flexicamin B12®, Tab Piroxicam + Carisoprodol* 10 mg + 350 mg
Flogiatrin B12® + Dexamethasone + 1 mg
+ Vit. B6 + Vit. B12 (Hydroxo B12) + 150 mg + 2.5 mg
(2 Amp) Piroxicam (20 mg) Piroxicam only Amp
To be mixed + Dexamethasone + Vit. B6 (2 mg + 250 mg + 10 mg)
+ Vit. B12 (Hydroxocobalamin)
Pirocomplex® Amp Piroxicam + Prednisolone 20 mg + 7.5 mg
+ Hydroxocobalamin + 10 mg
Delta-Tomanil B12 Tab Diclofenac Na + Prednisolone 50 mg + 1.25 mg
+ Cyanocobalamin + 2.5 mg
Amp Diclofenac Na + Prednisolone 75 mg + 7.5mg
+info:
+ Hydroxocobalamin + 10 mg
http://www.doctoraliar.com/me
Buta-Rut B12® Tab Piroxicam + Vit. B12
dicamento/delta+tomanil+b12- 20 mg + 0.5 mg
Self-Assessment Medications Guide 3.1 ed. 84614 Page | 287
Dolotol 12® (Amp + Vial) Aspirin Lysine + Glycine + 1.8 mg + 200 mg +
Lidocaine Hydrochloride + 30 mg +
Vit. B1 + Vit. B12 + Vit. B6 100 mg + 1 mg + 100 mg
Diclo-Neurobion (2 Amp)
® (Diclofenac Na + Vit. B12), (75 mg + 5 mg)
To be mixed (Vit. B1 + Vit. B6 + Lidocaine) (100 mg + 100 mg + 20 mg)
Caditar Flex ® Tab Celecoxib + Orphenadrine * 200 mg + 25 mg
Lyca-C ® Cap Celecoxib + Pregabalin 200 mg + 75 mg
Lavica-M plus® Cap Celecoxib + Pregabalin + Vit. B12 200 mg + 75 mg + 750 mcg
Nucoxia-P ® Tab Etoricoxib + Paracetamol 60 mg + 500 mg
Cilonerve®, Tab , Etoricoxib + Pregabalin * 90 mg + 75 mg
Neurobem®, Cap
Neurocoxib®
Prega Plus®, Tab Etoricoxib + Pregabalin + Vit. B12 90 mg + 75 mg + 750 mcg
Atox P®
Nucoxia-MR® Tab Etoricoxib + Thiocolchicoside * (60mg + 4mg),(60mg + 8mg)
Gabamin ® Tab Gabapentin + Mecobalamin (B12) 300 mg + 500 mcg
Nidesef® Cap Gabapentin + Tramadol 300 mg + 25 mg
* Carisoprodol and Pridinol are Muscle relaxants, (Centrally acting).
* Orphenadrine and Thiocolchicoside are muscle relaxants (see below).
* Gabapentin and Pregabalin are anticonvulsants that used for neuropathic pain.
9.4- Muscle Relaxants

1. Muscle spasm is the involuntary, painful contraction of a muscle or a group of muscles that can
stiffen an arm or leg or make it almost impossible to straighten the back.
➢ There are various causes: it can follow an injury, or come on without warning; it may also be
brought on by a disorder like osteoarthritis, as the pain in the affected joint triggering
abnormal tension in a nearby muscle.
➢ Lower limbs (legs) muscle spasms are commonly mistaken with DVTs (deep vein
thrombosis); in such cases (pain in the gulf or lower extremities); DVT should be ruled out
first before starting any muscular relaxant.

2. Muscle Relaxants are group of drugs which affects skeletal muscle function and decreases the
muscle tone; they may be used to alleviate symptoms such as muscle spasms, pain, reduce
spasticity in a variety of neurological conditions and in hyperreflexia.
3. These drugs do not act directly on the muscles; rather they act centrally (in the brain) and
are more of a total body relaxant, they generally work by either enhancing the level of
inhibition, or reducing the level of excitation, Inhibition is enhanced by mimicking or
enhancing the actions of endogenous inhibitory substances, such as GABA.
➢ Because of the enhancement of inhibition in the CNS, most spasmolytic agents have the side
effects of sedation, drowsiness and may cause dependence with long-term use; several of
these agents also have abuse potential.
➢ Muscle relaxants are very powerful drugs which may produce negative effects, including
heart failure and paralysis.
4. They include: Baclofen, Tizanidine, Dantrolene, Methocarbamol, Carisoprodol,
Chlorzoxazone, Cyclobenzaprine, Metaxalone, Tolperisone and Orphenadrine.
5. (Diazepam, Gabapentin, and Pregabalin) all have muscular relaxant activity.
Baclofen Tab Lioresal , Lioraz
® ® 10 mg , 25 mg
Intrathecal Gablofen ® 500 mcg/ml , 1000 mcg/ml
Inj. 2000 mcg/ml
Tizanidine Tab Sirdalud® , Zanaflex® 2 mg , 4 mg
Chlorzoxazone Tab Lorzon® 375 mg , 500 mg , 750 mg
Cyclobenzaprine Tab Flexeril® , Amrix® 5 mg , 7.5 mg , 10 mg
Cap Fexmid ® 15 mg , 30 mg
Dantrolene Cap Dantrium ® 25 mg , 50 mg , 100 mg
Inj. Powder Revonto ® 20 mg
Metaxalone Tab Skelaxin ® 800 mg
Thiocolchicoside Tab , Cap Coltramyl , Muscoril , Muscoflex 4 mg
® ®
Methocarbamol Tab Robaxin® 500 mg , 750 mg

Inj. Solu. 100 mg/ml
Orphenadrine Tab Norflex® 100 mg
Amp Norflex® 30 mg/ml
Tolperisone Tab Mydocalm® 150 mg
Pridinol Tab Blokium® 4 mg
Eperisone Tab Myonal® 50 mg
Carisoprodol Tab Soma® 250 mg , 350 mg
Extra Notes:
1. When Baclofen is administered by intrathecal Injection, it may cause CNS depression accompanied
with cardiovascular collapse and respiratory failure.
2. Tizanidine can be very strong even at the 2 mg dose and may cause hypotension, so caution is
advised when it is used in patients who have a history of orthostatic hypotension.
3. Orphenadrine is an anticholinergic drug; it is closely related to diphenhydramine
(antihistamine), thus used against pain and muscle spasm of various etiologies.
➢ May have a slight Euphoria effect (mood enhancement): thus some countries started to
withdraw it from its public markets, it’s useful in Neuropathic pain.
4. Eperisone acts by relaxing both skeletal muscles and vascular smooth muscles.
5. Carisoprodol is a potent centrally acting skeletal muscle relaxant; causes heavy sedating, relaxant,
and anxiolytic effects; thus, it can produce psychological and physical dependence; it has been taken
off in some markets due to problems with dependence, abuse and side effects.
➢ Abused by many addicts in our market. (Don’t give by Hand)
Note1: Muscle Relaxants Combinations:
Norgesic , Kanagesic Tab
® ® Paracetamol + Orphenadrine 450 mg + 35 mg
Myogesic®, Muscerol®
Norgesic Forte® Tab Orphenadrine + Aspirin + Caffeine (25 mg + 385 mg + 30 mg),
(50 mg + 770 mg + 60 mg)
Myolgin®, Relaxon® Cap Paracetamol + Chlorzoxazone 300 mg + 250 mg
Paraxone ®
Myofen® Cap Ibuprofen + Chlorzoxazone 200 mg + 250 mg
Flexofan® Cap Ketoprofen + Chlorzoxazone 50 mg + 250 mg
Leodex Plus ® Tab Dexketoprofen + Thiocolchicoside 25 mg + 4 mg
Dolozox® Tab Paracetamol + Diclofenac K 325 + 50 mg
+ Chlorzoxazone + 250 mg
Relaxofine® Tab Ibuprofen + Nimesulide 200 mg + 100 mg
+ Chlorzoxazone + 250 mg
Dimra ® Tab Diclofenac K + Methocarbamol 50 mg + 500 mg
Distem ® Tab Paracetamol + Methocarbamol 300 mg + 380 mg
Somadril® Tab Paracetamol + Caffeine 160 mg + 32 mg
+ Carisoprodol + 200 mg
Soma Forte ® Tab Carisoprodol + Aspirin + Codeine 200 mg + 325 mg + 16 mg
Note2: Orphenadrine or Chlorzoxazone

Which one of these common muscle relaxants is better than the other?
➢ Orphenadrine has an additional analgesic effect; (plus its muscle relaxant effect); although side
effects are like diphenhydramine’s antihistaminic and anticholinergic effects, including dry
mouth, blurred vision, and urinary retention; (thus not preferred in elderly pt. and Glaucoma).
o Onset of Action is 1 hour; duration is about 6 hours.
➢ Chlorzoxazone muscle relaxant effect is related to its sedative properties; it acts primarily at
the level of the spinal cord and subcortical areas of the brain; (thus preferred in pt. with anxiety).
o Onset of Action is 0.5 – 1 hour; duration is about 3 – 4 hours.
Note3: Tolperisone & European Medicines Agency (EMA) (10)

1. The EMA has recommended restricting the use of Tolperisone; After review and a subsequent
re-examination in 2012, the Agency concluded the safety and adverse reaction risks of this
drug outweigh the benefits, and that there is weak support for its efficacy, in all but one
indication (muscle stiffness or spasticity after stroke), and specifically, due to the prevalence of
hypersensitivity symptoms such as flushing, rash, severe skin itchiness (with raised lumps),
wheezing, difficulty breathing, and swallowing, fast heartbeat and fast decrease in blood pressure
(basically anaphylaxis).
2. Their recommendations included ceasing advertising in Europe and ceasing injections,
updating patient information leaflets, changing to another medicine for existing users, and for
prescribers to only use it stroke patients when administered by mouth, not injection.
Note4: Botox for muscle spasms

1. Botulinum Toxin (BTX) is produced from Clostridium botulinum and is injected locally to
inhibit presynaptic release of Acetylcholine (Ach) in the neuromuscular junction, resulting in
paralysis of the muscle; the onset of effect varies depending on the indication but is typically 14
days for spasticity and cervical dystonia, the effect typically lasts approximately 3 months.
2. The effect diminishes when motor neurons develop new nerve terminals that start releasing Ach;
resistance to the paralytic effect could develop with repeated injections due to development of
antibodies against the toxin.
3. Adverse effects include rash and muscle weakness at the injection site and flu-like symptoms.
9.5- Neuropathic pain
1. Neuropathic pain occurs as a result of damage to neural tissue; it may be continuous and/or
episodic (paroxysmal); Neuropathic pain may be divided into peripheral neuropathic pain,
central neuropathic pain, or mixed (peripheral and central).
2. Central neuropathic pain is found in spinal cord injury, multiple sclerosis and some strokes; Aside
from diabetes (diabetic neuropathy) and other metabolic conditions, the common causes of
painful peripheral neuropathies are herpes zoster infection, HIV-related neuropathies,
nutritional deficiencies, and toxins.
➢ Neuropathic pain is common in cancer as a direct result of cancer on peripheral nerves (e.g.,
compression by a tumor), or as a side effect of chemotherapy (chemotherapy-induced
peripheral neuropathy)
3. Fibromyalgia is a neuropathic disorder characterized by widespread musculoskeletal pain
accompanied by fatigue, sleep, memory and mood issues. Researchers believe that fibromyalgia
amplifies painful sensations by affecting the way brain processes pain signals.
➢ Only 3 drugs are FDA approved for the treatment of Fibromyalgia: (Pregabalin, Duloxetine
and Milnacipran. (for more info on Fibromyalgia see chapter 10, section 7)
4. Neuropathic pain can be very difficult to treat, with only some 40-60% of patients achieving
partial relief; it is generally managed with a tricyclic antidepressant as (Amitriptyline) or with
certain antiepileptic drugs (Gabapentin, Pregabalin and Carbamazepine), or with SSRIs as
(Paroxetine, Fluoxetine, Citalopram), and SNRIs antidepressants as (Duloxetine,
Venlafaxine). (2) (see chapter 4 for more info)
➢ Duloxetine is recommended as a first line agent for the treatment of chemotherapy-
induced neuropathy by the American Society of Clinical Oncology.
5. Neuropathic pain may respond to Opioid analgesics (Narcotics); especially Tramadol and
Oxycodone (centrally-acting narcotic analgesics); they are combined with other treatments
when patients do not respond to first-line treatments.
6. Some Doctors also use vitamin B-Complex as 2ndry supplement for relieving neuropathic pain
(especially Vit. B12); although it’s useful only in neurological diseases caused by its deficiency.
7. Alpha Lipoic acid (ALA) supplements can help with neuropathy (nerve damage) caused by
diabetes or cancer treatment; it seems to reduce symptoms like pain, tingling, and prickling in
the feet and legs, when given at a dosage of 600 mg once daily over a period of three weeks, it
leads to a significant and clinically relevant reduction in neuropathic pain. (11)
8. In neuropathies, both neurons and Schwann cells may be affected; the involvement of Schwann
cells causes demyelination of the axons, which leads to the failure of nerve transmission, Axon
functionality is recovered through the remyelination process, where the synthesis of
phospholipids and sphingolipids plays a crucial role; Nucleotides such as CMP (Cytidine
monophosphate) and UMP (Uridine monophosphate) are basic substrates in the synthesis of
these compounds and exogenous supplementation of CMP and UMP ensures the proper supply
of substrates required to enable regenerative processes to accelerate.
9. Topical drugs for Diabetic Neuropathy (DN):
➢ Topical Capsaicin: is the topical treatment used most often in painful DN, it produces the
activation and subsequent P substance depletion of C fiber nerve endings; Multiple controlled
studies collected in a meta-analysis have shown that the topical application of Capsaicin is
effective in the treatment of pain related to DN.
➢ Topical Nitrates: the application of an Isosorbide Dinitrate spray or Isosorbide
Trinitrate patches have been shown to decrease the pain and burning associated with DN.

Antiepileptic drugs
Gabapentin Cap Neurontin , Gabamed
® ® 100 mg , 300 mg , 400 mg
Pregabalin Cap Lyrica ® 75 mg , 150 mg
Carbamazepine Tab , Tab ER Tegretol , Taver , Tegral
® ® ® 200 mg , 400 mg
Tricyclic antidepressants (TCAs)
Amitriptyline Tab Deprezole®, Elavil® , Levate® 10 mg , 25 mg , 50 mg
Imipramine Tab , Cap Tofranil® 10 mg , 25 mg & 75 mg
Clomipramine Tab , Cap Anafranil ® (Cap)
25 mg , 50 mg
Maprotiline Tab Ludiomil ® 25 mg , 50 mg , 75 mg
Selective Serotonin Reuptake Inhibitors (SSRIs)
Fluoxetine Cap Prozac® 20 mg , 40 mg
Cap DR Sarafem® 90 mg
Paroxetine Tab Seroxat , Paxil , Pexeva
® ® ® 10 mg , 20 mg , 40 mg
Cap Seroxat CR ® 30 mg
Citalopram Tab Celexa , Cipramil
® ® 10 mg , 20 mg , 40 mg
Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)
Duloxetine Cap , Cap CR Cymbalta® 30 mg , 60 mg
Venlafaxine Tab Effexor ® 25 mg , 50 mg
Cap Effexor XR ® 75 mg , 150 mg
Narcotics (Opioids)
Tramadol Tab , Cap Tramal® , Ultram® , Topalgic® 50 mg , 100 mg , 200 mg
Inj. (Amp) Zydol®, Trabar® 50 mg/ml , 100 mg/2 ml
Oxycodone Tab Roxicodone , Oxecta
® ® 10 mg , 15 mg , 20 mg , 30
Nucleotides + Combinations mg
Cytidine + Uridine Cap Nucleo CMP® 5 mg + 1.33 mg
Amp 10 mg + 6 mg
Uridine + Folic acid + Vit. B12 Cap Keltican ® 75 mg + 0.4 mg + 3 mcg
Uridine + Vit. B12 + L-Methylfolate Tab Neural Plactive ® 200mg + 2.5mcg + 400mcg
+ Pyrroloquinoline + Magnesium + 20 mg + 56 mg
Uridine + Folic acid Tab Biolevox Neuro® 50 mg + 400 mcg
+ Vit. B1 + Vit. B3 + Vit. B6 +Vit. B12 +4mg + 20mg + 6mg + 10mcg
Cytidine + Uridine + Folic acid Tab Axonal® 50 mg + 30 mg + 400 mcg
+ Alpha Lipoic acid + Vit. B1 + B3 + 200 mg + 58 mg + 20 mg
+ Vit B6 + B12 + N-Acetyl Cysteine + 58mg + 100mcg + 300mg
Other Drugs for Neuropathy
Alpha Lipoic acid Cap Lipoic Forte® 600 mg
Tab ALA® 100 mg , 200 mg
Capsaicin Cream Zostrix® , Sorex® 0.025% , 0.075%
Isosorbide Dinitrate Spray Isoket® 1.25 mg/spray
Isosorbide Trinitrate Patch Deponit® 5 mg , 10 mg
Note1: Vit. B12 comes in 3 types:

Cyanocobalamin Tab Cobalamine® 100 mcg , 250 , 500 , 1000 mcg
Amp Cobalamine® 1000 mcg/ml
Amp (Oral) B12 Gerda® 1000 mcg/4 ml
Cyanocobalamin Oral Vial Maddovit B12®
25 mcg/7 ml
Nasal Spray Nascobal , CaloMist
® ® 25 mcg/spray
Methylcobalamin Amp Methycobal ® 500 mcg
Tab Methycobal , Mecobalamine 250 mcg , 500 mcg
® ®
Hydroxocobalamin Amp Cobalin-H® 1000 mcg/ml

Vial Cyanokit® 5 gm/vial
Notes:
1. Cyanocobalamin turns inside the body to (Methylcobalamin) then to (Hydroxocobalamin) which is
the active form of B12
a. Methylcobalamin ampule and tablets should be protected from light and moisture, (Light decreases
the active ingredient content and may turn reddish with exposure to moisture.)
b. Cyanocobalamin is the least expensive and least painful type at the injection site, and is used once a
week I.M. ONLY, but it is the least efficient.
2. Methylcobalamin, also called (Mecobalamin); is more efficient than Cyanocobalamin because it does
not need to switch to another form inside the body.
a. It has a better absorption profile.
b. More painful at the injection site and can be given I.M, I.V.
c. The best choice for smokers, due to their inability to convert Cyanocobalamin to Methylcobalamin
because of the presence of the heavy metals & toxins in the liver.
d. Its methyl group stimulates Serotonin production in CNS; (thus has a mood supporting effect).
e. High doses can be effective in the treatment of Multiple Sclerosis.
3. Hydroxocobalamin is the most bioactive form, and is the most type commonly used.
a. It’s better to be given I.V., due to its very painful at injection site unless mixed with local anesthetic,
stay inside the body for a longer period, which reduces the no. of injections.
b. The (5 gm vial) is used in the treatment of Cyanide poisoning as I.V infusion.
Note2: Special combinations for Neuropathic Pain:

Trade name D. form Scientific name(s) Concentration
Neurobion® (merck) Tab Vit. B1 + Vit. B6 + Vit. B12 100 mg + 200 mg + 200 mcg
Amp Vit. B1 + Vit. B6 + Vit. B12 (100mg+100mg+1mg)/3 ml
Neurorubin® (Acino) Tab Vit. B1 + Vit. B6 + Vit. B12 200 mg + 50 mg + 1000 mcg
Amp Vit. B1 + Vit. B6 + Vit. B12 (100mg+100mg+1mg)/3 ml
Ancopir® Tab Vit. B1 + Vit. B6 + Vit. B12 200 mg + 100 mg + 0.3 mg
Amp Vit. B1 + Vit. B6 + Vit. B12 200 mg + 50 mg + 1 mg
+ Lidocaine + 10 mg (per 2 ml)
Benexol B12®, Apikobal® Tab Vit. B1 + Vit. B6 + Vit. B12 250 mg + 250 mg + 1 mg
Livabion® Amp Vit. B1 + Vit. B6 + Vit. B12 5 mg + 4 mg + 2500 mcg
+ Folic Acid + Nicotinamide + 1 mg + 20 mg
Inzitan® Amp Dexamethasone + Vit. B12 4 mg + 250 mcg
+ Vit. B1 + Lidocaine + 50 mg + 60 mg (per 2 ml)
Gavindol® Tab Gabapentin + Vit. B1 + Vit. B12 300 mg + 100 mg + 20 mcg
Dicloneurovit forte® Tab Diclofenac + Vit. B1 + B6 + B12 50 mg + 50 mg + 50 mg + 1 mg
Beneday®, Tab Vit. B1 + Vit. B6 + Vit. B12 250 mg + 250 mg + 1 mg
Apikobal Plus® + Alpha Lipoic acid + 300 mg
Notes:
1. Neurobion®, Neurorubin® are also indicated for muscle soreness and back pain with unknown etiology,
and as an adjuvant in the treatment of neurotic pain (acute or chronic neuritis & polyneuritis); They both
should not be used as a replacement therapy for Vitamin B deficiency, or deficiency due to pregnancy
or malnutrition; because their concentrations are at the super-therapeutic doses range.
2. Inzitan® Indications include: myalgia, neuralgia, neuritis.
9.6- Rubefacients, Topical NSAIDs, and Capsaicin:
1. They may provide some relief of pain in musculoskeletal conditions; they act by causing
dilation of the capillaries and an increase in blood circulation.
2. Rubefacients include: Oil of Wintergreen, Methyl Salicylate, Eucalyptus Oil, Menthol and
Capsaicin.
3. Topical NSAIDs include: Diclofenac Na+, Ibuprofen, Ketoprofen, Piroxicam, Etofenamate,
Indomethacin, Felbinac, Trolamine or (Triethanolamine) and Nimesulide.
4. Camphor is readily absorbed through the skin and produces a feeling of cooling similar to that
of menthol, and acts as slight local anesthetic and antimicrobial substance. There are anti-
itch gels and cooling gels with camphor as the active ingredient. Camphor is an active ingredient
(along with menthol) in vapor-steam products.
5. Capsaicin is the active component of chili peppers, produces a sensation of burning in any tissue
with which it comes into contact; it is used as an analgesic in topical ointments, and dermal
patches to relieve pain.
Topical NSAIDs
Diclofenac Na+ Skin Gel Voltarin®, Voltamed® 10 mg/gm (50 gm tube)
Patch Olfen®
Spray Voltarin® 1% (75 ml)
Ibuprofen Skin Gel Ibugel® , Fenbid® 10% (100 gm tube)
Ketoprofen Skin Gel Profenid Gel® , Fastum® 2.5% (60 gm tube)
Piroxicam Skin Gel Felden Gel® , Picam® 5 mg/gm (60 gm tube)
Nimesulide Skin Gel Sulide® 50 mg/1 gm (20 gm tube)
Indomethacin Spray Elmetacin® 1%
Etofenamate Skin Gel Dolo-Denk Gel® 10% (20 gm tube)
Idrocilamide Cream Srilane® 5%
Felbinac ** Gel Traxam® 3%
Trolamine ** Cream Aspercreme® 10%
Diclofenac + Pridinol* Cream Oxadisten® 1.45% + 0.34% (100 gm tube)
Diclofenac + Capsaicin Cream Diclofex DC® 1.5% + 0.025 %
Diclofenac + Menthol Gel Divon®,
Relief G® 1.16% + 5%
+ Methyl Salicylate + 10%
+ Linseed Oil + 3%
* Pridinol is a muscle relaxant.
** Felbinac = Biphenyl Acetic Acid = Biphenylylacetic Acid, they are all the same drug.
** Trolamine = Triethanolamine, they are the same drug.
Topical Rubefacients
Moov® Gel , Menthol + Oil of Wintergreen 10% + 3%
Spray + Camphor + Eucalyptus Oil + 11% + 2%
Rheumalgin® Cream Methyl Salicylate + Menthol 15 gm + 1 gm
+ Turpentine Oil + Camphor + 1 gm + 1 gm
+ Capsicum + Peppermint Oil + 0.5 gm + 2 gm (per 100gm)
Deep Heat® Cream Methyl Salicylate + Menthol 12.8% + 5.91%
+ Eucalyptus Oil + Turpentine + 1.97% + 1.47%
Arthi-Flex® Cream Menthol + Eucalyptus Oil 4% + 1%
Directol Super Heat® Gel Menthol + Eucalyptus Oil 2.5% + 0.5%
+ Capsicum + Gaultheria Oil + 0.125% + 8%
Directol Super Ice® Gel Menthol + Eucalyptus Oil 2% + 0.5%
Radian® Cream Menthol + Camphor 2.54% + 1.43%
+ Methyl Salicylate + Capsicum + 0.42% + 0.005%
Muscle Rub® Cream Menthol + Methyl Salicylate 1% + 15%
Thera-Gesic® Cream Menthol + Methyl Salicylate 1% + 15%
Thera-Gesic Plus® Cream Menthol + Methyl Salicylate 4% + 25%
Rubicalm® Cream Diethylamine Salicylate + 12 gm + 0.1 gm + 0.5 gm
Menthol + Chlorbutol
Joint-Flex® Gel Camphor 3.1%
+ Other Non-Medical Subs.
Note: Other Topical products for Pain Relief:

Reparil N® Gel Aescin + Diethylamine Salicylate 1 gm + 5 gm
Arceclox® Cream Celadrin + Menthol 7.5% + 1.25%
Gothaplast® Plaster Nonivamide 2.43 mg
Jointace Gel® Gel Glucosamine + Chondroitin Blend of 40 gm tube
+ Menthol + Eucalyptus Oil
+ Other Oils
Notes:
1. Diethylamine salicylate (derivative of salicylic acid); has anti-inflammatory and painkilling actions acts
as a counter-irritant.
2. Aescin is the main active component in horse chestnut, it has anti-inflammatory, vasoconstrictor and
Vasoprotective effects; It induces endothelial nitric oxide synthesis by making endothelial cells more
permeable to calcium ions, and also induces release of prostaglandin.
3. Arceclox® is also found as soft gel Capsules for the treatment of Osteoarthritis.
4. Nonivamide is a synthetic analogue of Capsaicin that is used in topical preparations for the relief of
muscular and rheumatic pain; Nonivamide has also been used as a food flavor and in (pepper sprays) for
law enforcement and self-defense.
9.7- Opioid Antagonists:

1. Naloxone and Naltrexone are commonly used opioid antagonist drugs which are competitive
antagonists that bind to the opioid receptors with higher affinity than agonists but do not activate
the receptors; this effectively blocks the receptor, preventing the body from responding to
opiates and endorphins, used in opioid dependence, alcohol withdrawal, and to reverse
coma and respiratory depression with opioid overdose.
➢ Naloxone cannot be absorbed orally.
➢ Naltrexone is active orally and has a longer duration of action than Naloxone.
Naltrexone Tab Revia® , Depade® 50 mg
Inj. (I.M.) Vivitrol® 380 mg
Naloxone Inj. (Vial) Narcan® 0.4 mg/ml , 1 mg/mL
Nalmefene Tab Selincro® 18 mg
Inj. Revex® 1 mg/ml (10 ml)
Naloxone + Tab Suboxone® (0.5 mg + 2 mg) ,
Buprenorphine (sublingual) (1 mg + 4 mg) , (2 mg + 8 mg)
9.8- Anti-Migraine drugs (6)
1. Migraine is a term applied to recurrent severe headaches affecting only one side of the head and
probably caused by changes in the blood vessels around the brain and scalp; it may be
accompanied by nausea and vomiting and preceded by warning signs, usually an impression
of flashing lights or numbness and tingling in the arms, also the speech may be impaired.
2. The underlying cause of migraine is uncertain, but an attack may be triggered by a blow to the
head, physical exertion, certain foods and drugs, or emotional factors such as excitement, tension,
or shock; a family history of migraine also increases the chance of an individual suffering from it.
3. The symptoms of a migraine attack begin when blood vessels surrounding the brain constrict,
producing the typical migraine warning signs (The constriction is thought to be due to certain
chemicals found in food or produced by the body); The neurotransmitter serotonin causes large
blood vessels in the brain to constrict.
➢ Pizotifen and Propranolol block the effect of chemicals on blood vessels, preventing attacks.
4. The next stage of a Migraine attack occurs when blood vessels in the scalp and around the eyes
dilate (widen); and as a result, chemicals called prostaglandins are released, producing pain.
➢ NSAIDs and Paracetamol relieve this pain by blocking prostaglandins.
➢ Codeine acts directly on the brain, altering pain perception
➢ Ergotamine and 5HT1 agonists (Triptans) relieve pain by narrowing dilated blood vessels.
5. Analgesic rebound headache: If patients use analgesics often (usually defined as more than 3
times weekly), they can develop analgesic rebound headache, Patients with this condition usually
present with a chronic daily headache, for which they take simple or narcotic analgesics.
➢ Treatment consists of the withdrawal of all analgesics (but not prophylactic medications).
A) Treatment of Acute Migraine

1. Treatment of a migraine attack should be guided by response to previous treatment and the
severity of the attacks, a simple analgesic such as Aspirin, Paracetamol (preferably in a soluble
or dispersible form) or a NSAIDs is often effective.
➢ The NSAID Tolfenamic acid is licensed specifically for the treatment of an acute attack of
migraine; Diclofenac K+, Flurbiprofen, and Ibuprofen are also licensed for use in migraine.
2. Peristalsis is often reduced during Migraine attacks; thus, the medication may not be
sufficiently well absorbed to be effective; and that’s why dispersible or effervescent preparations
are therefore preferred.
3. Concomitant anti-emetic treatment may be required (as Cyclizine in Migril®), due to Migraine
attack is usually associated with nausea).
4. If treatment with an analgesic is inadequate, an attack may be treated with a specific anti-
migraine compound such as a 5HT1-receptor agonist (Triptan); like Sumatriptan.
5. The value of Ergotamine for migraine is limited by its side-effects; it is best avoided.
➢ To avoid habituation, the frequency of administration of ergotamine should be limited to no
more than twice a month; It should never be prescribed prophylactically but in the
management of cluster headache a low dose.
6. Triptans and Ergotamine are contra-indicated in ischemic heart disease, previous
myocardial infarction, coronary vasospasm (including Prinzmetal’s angina), and uncontrolled
or severe hypertension.
a. Also C.I. in pregnancy, Epilepsy, renal and hepatic impairment.
b. Triptans and Ergotamine should not be administered within 24 hours of each other.
c. Triptans should not be given with (Cabergoline, Bromocriptine), co-administration will
lead to life threatening Vasospasm.
d. Propranolol increases serum concentrations of Rizatriptan; thus, a 5-mg dose should be
used with propranolol, and the dose should not exceed 15 mg/day.
7. The maximum recommended doses of Ergotamine preparations should not be exceeded
(they should not exceed the maximum dose per attack, the maximum dose per day as well as the
maximum dose per week).
a. Excessive use of acute treatments for migraine (opioid and non-opioid analgesics, 5HT1
receptor agonists, and ergotamine) is associated with medication-overuse headache
(analgesic-induced headache); therefore, increasing consumption of these medicines needs
careful management.
b. Ergotamine preparations can cause dry gangrene of hand and feet, also may cause
coronary vasospasm, (thus they are C.I. in patients with heart diseases).
8. Orally disintegrating tablets are available for Zolmitriptan and Rizatriptan if patients do not
have access to water; however, they do not work faster than oral tablets and are not absorbed
sublingually. (12)
➢ Triptans Dose may be repeated after 2 hours, don’t use more than 2 doses within 24 hours.
➢ Its not recommended to use Triptans more than 2-3 days each week.
9. Butorphanol is indicated for Sever Migraine Pain, using the intranasal spray formulation.
10. The FDA approved a new drug (Lasmiditan) for the acute (active but short-term) treatment of
migraine with or without aura (a sensory phenomenon or visual disturbance) in adults;
Lasmiditan is not indicated for the preventive treatment of migraine.
Butorphanol Inj. Solu. Stadol® 1 mg/ml , 2 mg/ml
Nasal Spray 10 mg/ml
5HT1-receptor agonist (Triptans)

Scientific name Dosage form Trade name concentration Max Day Dose
Sumatriptan Tab Imitrex , Imigran 25 mg , 50 mg , 100 mg
® ® Tab = 200 mg
Inj. (S.C.) Sumavel ® 4 mg/0.5 ml , 6 mg/0.5 ml Inj. = 12 mg
Inj. Auto Sumavel DosePro® 4 mg/0.5 ml , 6 mg/0.5 ml Nasal = 20 mg
Nasal Spray Imitrex® (5 mg , 20 mg)/actuation
Skin Patch Zecuity ® 6.5 mg / 4 hr.
Zolmitriptan Tab Zomig , Zomitan
® ® 2.5 mg , 5 mg Tab = 10 mg
Nasal Spray (2.5 mg , 5 mg)/spray Nasal = 10 mg
Almotriptan Tab Almogran® , Axert® 6.25 mg , 12.5 mg Tab = 25 mg
Eletriptan Tab Relpax ® 20 mg , 40 mg Tab = 80 mg
Frovatriptan Tab Frova , Migard
® ® 2.5 mg Tab = 7.5 mg
Naratriptan Tab Amerge , Naramig 1 mg , 2.5 mg
® ® Tab = 5 mg
Rizatriptan Tab Maxalt ® 5 mg , 10 mg Tab = 30 mg
Melt Wafers 10 mg
Lasmiditan Tab Reyvow ® 100 mg , 200 mg Tab = 200 mg
* Frovatriptan has the highest half-life (26 hours), compared with other Triptans (1-4 hours).
Ergotamines
Scientific name Dosage form Trade name concentration Max Dose
Ergotamine Tab Cafergot®, Megral® 1 mg 6 mg/day
Subling. Tab Bellergal S® 2 mg 10 mg/week
Dihydro- Inj. DHE® 1 mg/ml 3 mg/day
Ergotamine Nasal Spray Migranal® 0.5 mg/actuation 6 mg/week

B) Prophylaxis of Migraine
1. If the migraine attacks are frequent, preventive treatment for migraine should be considered,
drugs that are used for prophylaxis of migraine include:
a) Beta-blockers (Propranolol is the most commonly used).
b) Tricyclic antidepressants and antiepileptics (Topiramate, sodium valproate, Valproic
acid, and gabapentin) are also effective for preventing migraine.
c) Pizotifen (but it is of limited value and may cause weight gain).
d) Clonidine (not recommended; it can aggravate depression and cause insomnia).
2. Beta-Blockers (Propranolol, Nadolol, Timolol, Atenolol, and Metoprolol) are the most
widely used treatment for prevention of migraine. They are reported to reduce the frequency of
attacks by 50% in 60% to 80% of patients; β-Blockers with intrinsic sympathomimetic
activity are ineffective.
3. Amitriptyline appears to be the tricyclic antidepressant (TCA) of choice, but Doxepin,
Nortriptyline have also been used; Their beneficial effects in migraine prophylaxis are
independent of antidepressant activity and may be related to down regulation of central 5HT2
and adrenergic receptors.
4. Topiramate is approved by the FDA for migraine prophylaxis. The dose is initiated at 25
mg/day and increased slowly to minimize side effects; Gabapentin may also have a role in
migraine prophylaxis.
5. Flunarizine is a drug classified as a calcium antagonist which is used for various indications;
it’s effective in the prophylaxis of migraine, occlusive peripheral vascular disease, vertigo
of central and peripheral origin, and as an adjuvant in the therapy of epilepsy.
➢ It has been shown to significantly reduce headache frequency and severity in both adults
and children; It’s is contraindicated in patients with depression, in the acute phase of a
stroke, and in patients with extrapyramidal symptoms or Parkinson's disease; It is also
contraindicated in hypotension, heart failure and arrhythmia.
6. Botulinum toxin type A is licensed for the prophylaxis of headaches in adults with chronic
migraine; that has not responded to at least three prior pharmacological prophylaxis therapies
and whose condition is appropriately managed for medication overuse.
7. All the Migraine Prophylaxis agents are not effective in relieving migraine attack once it’s in
progress.
8. Prophylaxis of cluster headache is considered if the attacks are frequent, last over 3 weeks, or
if they cannot be treated effectively, Verapamil or lithium (both unlicensed use) are used for
prophylaxis.
9. Prednisolone can be used for short-term prophylaxis of episodic cluster headache
(unlicensed use) either as monotherapy, or in combination with verapamil during verapamil
titration, the dose of prednisolone for monotherapy or adjunctive therapy is 60-100 mg once
daily for 2–5 days followed by a dose reduction of 10 mg every 2–3 days until it is discontinued.
10. A new generation of monoclonal antibodies is available for prophylaxis of migraine; they are
called calcitonin gene-related peptides (CGRP) antagonists.
➢ During a migraine attack the cerebral nerves and blood vessels release substances including
Calcitonin Gene-Related Peptide (CGRP); which is a neuropeptide that has been implicated in
different pain processes, including migraine; it also functions as a vasodilator.
➢ CGRP antagonists acts by inactivating the CGRP molecule (by binding to it), or by blocking
its receptor, thus preventing migraine from developing.
➢ These include: Fremanezumab, Galcanezumab, Erenumab and Eptinezumab; all given by
S.C. inj. Once monthly; except Eptinezumab which is given by I.V. inj. Once every 3 months.
➢ Rimegepant; A new oral CGRP monoclonal antibody is currently Pending FDA approval.
Drugs for Migraine Prophylaxis
Pizotifen Tab Sandomigraine® 0.5 mg
Cap Innopran® 80 mg , 120 mg
Inj. Inderal® 1 mg/1 ml
Topiramate Tab Topamax® 25 mg , 50 mg , 100 mg
Flunarizine Tab Sibelium® 5 mg
Doxepin Tab , Cap Sinequan® 10 mg , 25 mg , 50 mg
Clonidine Tab Dixarit® , Catapres® 25 mcg
Botulinum Toxin A* Inj. Powder Botox® 50 units – 100 – 200 U/vial
CGRP monoclonal antibodies
Fremanezumab S.C. inj. Ajovy® 225 mg/1.5 ml
Galcanezumab Prefilled inj. Emgality® 100 mg/ml , 120 mg/ml
Erenumab Prefilled inj. Aimovig® 70 mg/ml , 140 mg/ml
Eptinezumab Inj. Solu.
Pending FDA approval
Rimegepant Tab
* Also called Onabotulinumtoxina.
C) Combination products for Migraine

Ergotamine + Caffeine Tab Migraine® 1 mg + 100 mg
Supp. Migergot® 2 mg + 100 mg
Ergotamine + Cyclizine Tab Migril® 2 mg + 50 mg
+ Caffeine + 100 mg
Ergotamine + Tab Asia Migraine® 1 mg +
Belladonna + Caffeine 0.1 mg + 50 mg
Meprobamate + 150 mg +
Phenobarbital 10 mg
Ergotamine + Tab No-Migraine® 1 mg +
Caffeine + 100 mg +
Paracetamol + 250 mg +
Domperidone 10 mg
Ergotamine + Tab Migra-nial® 1 mg +
Caffeine + 50 mg +
Meprobamate* + 150 mg +
Analagin (Dipyrone) 200 mg
+ Pentobarbital + 10 mg
Ergotamine + Tab Migranil® 1 mg +
Caffeine + 100 mg +
Belladonna Extract + 10 mg +
Paracetamol 250 mg
Sumatriptan + Naproxen Tab Treximet® 85 mg +
500 mg
* Meprobamate is an anxiolytic drug.

D) Medical devices that is FDA approved for Migraine
A relatively new concept in treating migraine is using neuromodulation devices instead of
traditional headache medications; These devices are sometimes referred to as stimulators,
although they often turn down brain activity rather than stimulate it.
Neuromodulation devices can be electrical, temperature-altering, or magnetic, and while they
can be portable, some require surgical placement; there are several non-invasive
neuromodulation devices that have been approved by the FDA for headache and are no longer
considered experimental. Each of them is labeled by the FDA as “minimal risk,” meaning no
significant side effects are expected.
1. Transcutaneous Supraorbital NeuroStimulator: The first neuromodulation device receiving
U.S. approval was a Transcutaneous Supraorbital NeuroStimulator (tSNS); Also called the Cefaly
device, it is approved in Europe and Canada, too. This device, now in a smaller, revised stimulator
called Cefaly 2, is temporarily placed on the forehead and turned on daily for 20 minutes to
prevent migraine. The study leading to FDA approval showed a significant number of migraine
patients who wore the device daily for the designated amount of time had at least a 50% decrease
in headache days; The Cefaly device electrically activates forehead nerves and creates a buzzing
sensation. The signal goes into the brain turning headache pathways down slowly over time. This
results in fewer headache days. The Cefaly is currently being studied for whether it might stop
migraine acutely on an as-needed basis as well.
2. SpringTMS: The second approved device is a single-pulse transcranial magnetic stimulator,
called SpringTMS or sTMS, this is a magnet placed on the back of the head and turned on for a
split-second pulse, which usually has no side effects. Two pulses of the magnet stopped migraine
with aura in around 40% of patients, so the FDA approved it for treating the pain of migraine
with aura; sTMS is in its third design, called the “mini,” and has also been found to stop the pain
of migraine without aura and prevent migraine. sTMS is currently before the FDA to decide if the
approved use of the device can be broadened to include migraine prevention. The preventive
approach involves pulsing the magnet four times twice a day, plus extra pulses on an as-needed
basis. It is already being used for this in the United Kingdom.
3. GammaCore: The third FDA approved device is a non-invasive vagal nerve stimulator (nVNS),
called GammaCore, and is also approved in Canada and Europe. This device is placed on the neck
over a gel and turned on to electrically stimulate the vagus nerve for 90 seconds to two minutes,
generally in two cycles, causing mild buzzing and twitching neck sensations. The FDA approved
nVNS for stopping the pain of an acute cluster headache attack in patients with episodic cluster
headache, and it has also shown promise in preventing cluster headache when given in 2 cycles
3 times per day, and in treating migraine. Further studies are underway exploring its future use.
4. Nerivio Migra: The FDA has cleared a noninvasive device to relieve acute migraine pain, Nerivio
Migra is a "first-in-category product," according to Theranica, the company that makes it; It is
worn on the upper arm and uses smartphone-controlled electronic pulses to relieve migraine
pain; The device is for the acute treatment of migraine with or without aura in adults who
don’t have chronic migraine, The FDA approved the device on the basis of results of a
randomized, double-blind, placebo-controlled study involving 252 patients who had 2-8
migraines per month.
5. Cerena: it is intended to be used when a patient feels a headache coming on or when the pain
begins. It’s the first medical device granted marketing by the FDA to relieve pain caused by
migraine headaches that are preceded by an aura.
➢ How does it work? Using both hands to hold the device against the back of the head, the
patient presses a button to release a very short (less than one second) magnetic pulse to
stimulate the brain’s occipital cortex (the back part of the brain that processes visual
information); Transcranial Magnetic Stimulator (TMS) technology, used in the Cerena device,
has been studied for quite some time but has only recently been authorized for use.
6. There are several neuromodulation devices currently being studied, but they are without FDA
approval; these include:
a. Caloric vestibular stimulator, called the Scion device. The Scion device is worn for 20
minutes once or twice a day as a pair of headphones with small cones in the ears. The device
heats and cools the vestibular nerves of the ear and has been shown to prevent migraine by
three months of use. A second US study on this device is underway.
b. There are also neuromodulation devices that require surgical placement and are not yet FDA
approved for headache management. In Europe there is the sphenopalatine ganglion (SPG)
stimulator (Pulsante), a small device that is placed above the teeth and screwed in as a
preventive treatment of cluster headache; This device does not have wires or batteries and
cannot be seen when in place. It is activated by a rechargeable, programmable remote
controller that the patient turns on and off. It is currently in a 2017 U.S. approval study.
c. Occipital nerve stimulators (ONS) have been studied for prevention of migraine, but with
mixed results. These are inserted in the back of the head and require a wire and battery placed
in the chest or hip. ONS approval for headache in Europe was withdrawn in 2014 because of
side effects.
9.9- Cannabinoid Analgesics

1. These are reserved for symptomatic relief of neuropathic pain in Multiple Sclerosis and as
adjunctive analgesic treatment in patients with advanced cancer who experience moderate
to severe pain during the highest tolerated dose of strong opioid therapy for persistent
background pain, should not be prescribed to any other types of pain.
Sativex® Buccal Spray Tetrahydrocannabinol + (27 mg + 25 mg) per ml
Cannabidiol
References
3- Rosemary R Berardi, Handbook of Nonprescription Drugs 17th Ed
4- Community Pharmacy: Symptoms, Diagnosis and Treatment, By Paul Rutter 2018 Ed.
5- Mary Anne koda-kimble (ed.), Applied Therapeutics: The clinical use of drugs, 11th
7- Stein, Rob (25 April 2018). "FDA Panel Affirms Safety of Painkiller Celebrex". NPR. Retrieved 19 May 2018.
8- https://www.nejm.org/doi/10.1056/NEJMoa1611593
9- https://www.clinicalcorrelations.org/2018/02/01
10- https://www.ema.europa.eu/en/medicines/human/referrals/tolperisone
12- ACCP Updates in Therapeutics® 2021: Pharmacotherapy

RHEUMATOLOGY &
NEUROLOGY
Chapter Ten: Rheumatology & Neurology
Part one: Rheumatology: Part two: Neurology:

10.1- Glucosamine and Chondroitin 10.7- Fibromyalgia
10.2- Intra-articular injections for 10.8- Drugs for Multiple Sclerosis

OA and RA
a. Intra-articular corticosteroid 10.9- Drugs that Enhance
b. Intra-articular Hyaluronic acids Neuromuscular Transmission
a. Anticholinesterases
10.3- Disease Modifying Anti- b. Acetylcholine-release enhancers
Rheumatic Drugs (DMARDs)
➢ Other DMARDs (less frequently 10.10- Central monoamine depleting
agent
used)
10.11- Other Neurological Drugs
10.4- Biological DMARDs
10.5- Drugs for Gout ➢ For drugs used in Epilepsy; see chapter
a. Acute attacks of Gout 4, section 4.
b. Prophylactic therapy of Gout ➢ For drugs used in Parkinsonism see
c. Other drugs that increase uric acid chapter 4, section 5.
excretion ➢ For anti-Alzheimer drugs see chapter
4, section 7.
10.6- Other Rheum. Drugs ➢ For painkillers see chapter 9.
➢ For special analgesic combination that
act on neuropathic pain see the
previous chapter, (chapter 9, section 3
for analgesic combinations, and
section 5 for neuropathic pain).
Sam’s Guide: Chapter 10 – Rheum & Neuro
Chapter Ten: Rheumatology & Neurology
Part one: Rheumatology:
1. This part describes the following conditions: Osteoarthritis (OA), Rheumatoid arthritis (RA),
Gout and Hyperuricemia, (For Osteoporosis see chapter 6, section 7)
2. Note that these conditions cause chronic pain, so most of the analgesics mentioned in the previous
chapter (Chapter 9) can be used in these conditions to relief acute pain.
Simple Introduction:
1) Osteoarthritis (OA) is a common chronic condition of articular cartilage degeneration.
Secondary changes can occur in the bone, leading to pain, decreased functioning, disability.
2) Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that involves
inflammation in the membrane lining of the joints and often affects internal organs, most patients
exhibit a chronic fluctuating course of disease that can result in progressive joint destruction,
deformity, and disability.
3) Gout is a disease that is characterized by recurrent painful acute attacks of urate crystal induced
arthritis, it may include tophi-deposits of monosodium urate in and around the joints and
cartilage and in the kidneys, as well as uric acid nephrolithiasis.
10.1- Glucosamine and Chondroitin

1. Glucosamine sulfate and Chondroitin sulfate is considered as dietary supplements. Both
compounds are found naturally in the body and are essential to the formation of cartilage, the
combination is believed to have a synergistic effect by:
a. Stimulating cartilage production (by Glucosamine).
b. Inhibiting its destruction (by Chondroitin).
2. They are used for mild to moderate Osteoarthritis, therapy should continue for several months;
but their effectiveness is conflicted; some studies show a modest benefit, while other studies
show no difference compared to placebo, although they still to date a supplement (not a drug).
3. Dosing should be at least Glucosamine 1,500 mg/day and Chondroitin 1,200 mg/day in
divided doses, these are the least effective doses.
➢ Glucosamine adverse effects are mild and include GI gas, bloating, and cramps.
➢ The most common adverse effect of Chondroitin is nausea, prolonged bleeding time.
4. Glucosamine and Chondroitin come in many combinations products; sometimes combined
with Collagen, MSM (Methylsulfonylmethane), Vitamin D3, Calcium, Gingko Biloba, and many
others; (All these are considered as a supplements by the FDA).
Trade name Dosage form Scientific name(s) Conc. (per 2 servings)
Jointace® Original Tab Glucosamine + Chondroitin 1000 mg + 400 mg
+ Vit. D3 + Other Vitamins + 20 mcg (per 2 Tabs)
Jointace® Omega-3 Cap Glucosamine + Omega-3 400 mg + 400 mg
+ Cod Liver Oil + Other Vitamins + 400 mg (per 2 Caps)
Jointace® Collagen Tab Glucosamine + Chondroitin 1000 mg + 100 mg
+ Collagen + Other Vitamins + 300 mg (per 2 Tabs)
Jointace® Rose Hip Tab Glucosamine + Chondroitin 1000 mg + 200 mg
+ Rose Hip + Other Vitamins + 300 mg
Arthi-Flex® Tab Glucosamine + Hyaluronic Acid 1500 mg + 80 mg
+ MSM (Methylsulfonylmethane) + 1500 mg + 965 mg
+ Collagen + Other Vitamins
FlexaMin Plus® Tab Glucosamine + Chondroitin 1500 mg + 1200 mg
+ MSM + Collagen + Hyaluronic (blend of 1300 mg)
+ Other Vitamins
Joint-Flex® Tab Glucosamine + Chondroitin 1500 mg + 1200 mg
+ MSM + Hyaluronic Acid + 500 mg + 30 mg
Chondro-Aid® Cap Glucosamine + Chondroitin 1500 mg + 1200 mg
Fort + Vit E + Selenium
Chondro-Aid® Sachet Collagen + Hyaluronic acid 10000 mg + 25 mg
Restructurant + Vit D + Vit C
Vita-Joint® Tab Glucosamine + MSM 1500 mg + 400 mg
+ Other Vitamins
NutroCare Joint-V® Tab Glucosamine + Chondroitin 1500 mg + 400 mg
+ Other Vitamins
Osteo Bi-Flex® Caplet Glucosamine + Chondroitin 1500 mg +
+ MSM + Collagen + Hyaluronic (blend of 1288 mg)
+ Other Vitamins
Revmatol® Tab Glucosamine + Chondroitin 750 mg + 100 mg
+ MSM + Collagen type II + Vit. D + 250 mg + 150 mg
+ ginger root + Other Vit. + 10 mcg + 50 mg
Bioflex® Cap Glucosamine + Chondroitin 375 mg + 300 mg
+ MSM + Boswellia Extract + 125 mg + 50 mg
Effervescent Glucosamine + Chondroitin 750 mg + 600 mg
Tab + MSM + Boswellia Extract + 300 mg + 20 mg
Topical Gel Glucosamine + Chondroitin 0.02% + 0.02%
+ MSM + Collagen + others + 0.02% + 0.2%
Dorofen®, Glucofen® Cap , Tab Glucosamine + Gingko Biloba 500 mg + 50 mg
Dolo Mecanyl® Sachets Glucosamine + Meloxicam 1500 mg + 15 mg
10.2- Intra-articular injections for OA and RA

First: Intra-articular corticosteroid injections:
Methylprednisolone or Triamcinolone may be useful when only a few joints are affected in
case of osteoarthritis and rheumatoid arthritis; they are also injected locally in some other
conditions, they can provide excellent pain relief particularly when a joint effusion is present.
➢ Average doses for injection of large joints in adults are: Methylprednisolone 20 - 40 mg, or
Triamcinolone 10 - 20 mg.
➢ They should be limited to 3 or 4 injection per year.
Methylprednisolone Prefilled Inj. Depo-Medrol ® 40 mg/ml , 80 mg/ml
Inj. Solu. (vial)
Triamcinolone Inj. Solu. (vial) Kenalog® 20 mg/ml , 40 mg/ml
(Acetonide) 200 mg/5 ml
Triamcinolone Vial (single dose) Zilretta ® 32 mg/vial
(Acetonide) ER
Triamcinolone Inj. Solu. (vial) Aristospan® 20 mg/ml , 25 mg/5 ml ,
(Hexacetonide) 100 mg/5 ml
Betamethasone Inj. Solu. (vial) Betneso® 4 mg/ml
Dexamethasone Inj. Solu. (vial) Depo-Dexa® 4 mg/ml
Hydrocortisone Inj. Solu. (vial) Hydrocortistab ® 25 mg/ml
* Triamcinolone has 2 salts; Acetonide and Hexacetonide, the last has the advantage of long
acting (it remains in the joint for 21 days); while other steroids last about 8-14 days.
Second: Intra-articular Hyaluronic acid injection:
1. These are intended to improve elasticity and viscosity of synovial fluid; they are indicated for
the treatment of knee 0steoarithritis (OA) when treatment failures to other therapies.
2. There are several types of hyaluronic acid injections, (also called viscosupplementation), they
are made from either rooster or chicken combs, or are derived from bacteria, and are injected
directly into the joint. It may take more than one injection for the pain to go away.
3. Typically, the patient will receive a series of three to five shots one week apart over three to five
weeks; on average, it takes about five weeks to experience the full benefits of HA injection.
➢ Also, there is formulation that is designed to be given every 3 or 6 months.
4. In contrast, relief from corticosteroid injections occurs within days, though this relief
diminishes significantly after about a month or two.
5. The theory behind these injections is that because people with OA have a lower than normal
amount of Hyaluronic acid (HA) in their joints, adding HA to the joint will improve symptoms by
helping to cushion the joint; The injection seems to work by temporarily restoring the thickness
of the joint fluid, allowing better joint lubrication and perhaps directly affecting pain receptors.
➢ Some Research shows that HA may also interfere with prostaglandins and cytokines
(naturally occurring compounds that promote inflammation in the body); other research
has shown that HA may actually help encourage the joint to make new cartilage since
hyaluronic acid is a major building block of cartilage.
6. The evidence regarding HA is mixed, with many studies show no benefit over placebo,
physicians may try this therapy in case it may work in a particular patient, for example as a
temporizing measure before considering surgery.
7. Some studies have shown that HA injections can reduce pain for up to six months, but
others have shown more limited results, with 30 to 40 percent of those receiving the injections
showing no improvement; A recent study, presented last year at the EULAR conference, found
that there were certain characteristics that make a person less likely to show improvement with
HA injections, including obesity, severe arthritis, being older than 65, and/or having HA or
corticosteroid shots in the past.
8. The American Academy of Orthopedic Surgeons (AAOS) no longer recommends HA injections
for knee OA because it says that there isn’t enough evidence the therapy provides “clinically
important improvement.”
Sodium Hyaluronate Intra-articular Inj. Hyalgan®, Euflexxa® 10 mg/ml , 20 mg/ml
Hylan polymers Intra-articular Inj. Synvisc®, Synvisc-One® 8 mg/ml (2 ml, 6 ml Inj.)
Hyaluronan Intra-articular Inj. Orthovisc® 30 mg/2 ml
Hyaluronic Acid Intra-articular Inj. Hyalone® 60 mg/4 ml
Intra-articular Inj. Durolane® 60 mg/3 ml
Intra-articular Inj. Monovisc® 88 mg/4 ml
Hyaluronic acid Intra-articular Inj. Cingal® (88 mg + 18 mg)/4 ml
+ Triamcinolone
(Hexacetonide)
** Most benefits are seen after the last dose (in the last week).

10.3- Disease-Modifying Anti-Rheumatic Drugs (DMARDs)
1. Also called Non-Biological DMARDs, these drugs affect the immune response and can
suppress the disease process in Rheumatoid Arthritis (RA) which is the main indication of
them; Examples: Penicillamine, Hydroxychloroquine, Chloroquine, Methotrexate,
Leflunomide and Sulfasalazine.
2. They usually need 3 months to produce a notable therapeutic effect, thus combination
therapy with NSAIDs and Corticosteroids is established until then.
Methotrexate Tab Rheumatrex® , MTX® 2.5 mg , 5 mg , 10 mg
Inj. Solu. Trexall® 25 mg/ml
Chloroquine Tab Aralen® 250 mg , 500 mg
Penicillamine Tab Cuprimine® , Distamine® 250 mg
Cap Depen® , Artamin® 125 mg , 250 mg
Sulfasalazine Tab Salazopyrin® , Azulfidine® 500 mg
Leflunomide Tab Arava® , Vamid® 10 mg , 20 mg , 100 mg
Notes:
1. Methotrexate is an antimetabolite and anti-folate drug; it is used in treatment of Cancer,
autoimmune diseases as Rheumatoid Arthritis (RA), Ectopic Pregnancy, and for the
induction of medical abortions, it acts by inhibiting the metabolism of folic acid.
a. Used as a treatment for autoimmune diseases, including Rheumatoid Arthritis, Juvenile
dermatomyositis, Psoriasis, Psoriatic Arthritis, Lupus, Sarcoidosis, Crohn's disease,
Eczema, and many forms of vasculitis.
b. It’s Considered as the 1st line DMARD for the treatment of RA.
c. Usually given once weekly for RA, also can be combined with other DMARDs or Biologicals.
d. Methotrexate is used (generally in combination with misoprostol) to terminate pregnancies
during the early stages (as an abortifacient), it is also used to treat ectopic pregnancies.
e. MTX is contraindicated in pregnant and nursing women, chronic liver disease,
immunodeficiency, pleural or peritoneal effusions, leukopenia, and thrombocytopenia.
f. Usually Co-administered with Folic acid, to reduce the side effects (given all the other days
of the week except the day of MTX administration)
2. Hydroxychloroquine and Chloroquine are also Anti-Malarials, they can cause ocular (eye)
toxicity, and therefore the patient should be asked about visual symptoms and monitor visual
acuity annually using the standard reading chart, C.I. in patients with G6PD.
3. Penicillamine is also a chelating agent used in Arsenic and Lead poisoning and some other
Heavy metals, also used in the treatment of Wilson’s disease.
4. Sulfasalazine is also used in the treatment of Ulcerative Colitis and Crohn’s Disease.
5. Leflunomide loading dose of 100 mg/day for the first 3 days may result in a therapeutic
response within the first month; the usual maintenance dose of 20 mg/day may be lowered to 10
mg/day in cases of GI intolerance, complaints of hair loss, or other dose related toxicity.
a. May cause liver toxicity and is contraindicated in patients with liver disease.
b. may cause bone marrow toxicity; a complete blood cell count with platelets is recommended
monthly for 6 months, then every 6 to 8 weeks thereafter.
c. It is teratogenic and should be avoided during pregnancy; in fact; women should wait to
become pregnant for at least 2 years after discontinuation of treatment (to increase its
elimination, take Cholestyramine 8 gm TID for 11 days).
Note: Other DMARDs (less frequently used)
Cyclosporine Cap Sandimmune , Gengraf
® ® 25 mg , 50 mg , 100 mg
Inj. Solu. Neoral ® 50 mg/ml
Cyclophosphamide Tab Cytoxan® 25 mg , 50 mg
Inj. Powder 500 mg , 1 gm
Aurothiomalate Na Inj. Solu. Myocrisin ® 20 mg/ml
Auranofin Cap Ridaura® 3 mg
Anakinra Prefilled Inj. Kineret ® 100 mg/0.67 ml
** All these are used as Immunosuppressant’s.
Combination therapy with two or more Non-Biologic DMARDs may be effective when single
DMARDs treatment is unsuccessful, recommended combinations include:
(1) MTX plus Hydroxychloroquine (2) MTX plus Leflunomide (3) MTX plus Sulfasalazine.
10.4- Biological DMARDs

1. Also called Cytokine modulators, they act as Immunosuppressant’s.
2. They can reduce or prevent joint damage, preserve joint integrity and function in patient
with moderate to severe Rheumatoid Arthritis (RA); Biologic DMARDs are effective for patients
who fail treatment with other DMARDs.
3. They include: the anti-TNF agents (Etanercept, Infliximab, Adalimumab, Certolizumab, and
Golimumab), Abatacept, Tocilizumab, and Rituximab.
4. These drugs carry an increased risk for infection, Tuberculin skin testing is recommended
prior to treatment so that latent tuberculosis can be detected; These agents should be avoided
in patients with preexisting infection and in those at high risk for developing Infection, and
treatment should be discontinued temporarily if an infection develops.
Etanercept Inj. Solu. Enbrel® 50 mg/ml
Inj. Power 25 mg/vial
Golimumab Prefilled Inj. Simponi® 50 mg/0.5 ml , 100 mg/0.5 ml
Belimumab Inj. Powder Benlysta® 120 mg , 400 mg (per vial)
Anakinra Prefilled Inj. Kineret® 100 mg
Abatacept Prefilled Inj. Orencia® 125 mg/Inj.
I.V. infusion 250 mg/vial
Tocilizumab Inj. Solu. Actemra® 20 mg/ml
Prefilled Inj. RoActemra® 162 mg/0.9 ml
Rituximab Inj. Solu. Rituxan® 10 mg/ml
Ustekinumab Inj. Solu. Stelara ® 45 mg/0.5 ml
Sarilumab Prefilled Inj. Kevzara ® 150 mg/1.14 ml , 250 mg/1.14 ml
Notes:
1. Etanercept is also used in the treatment of Psoriasis.
2. Infliximab, Adalimumab, Certolizumab and Golimumab are also used in the treatment of
Psoriasis (Psoriatic Arthritis and Plaque Arthritis), severe cases of Crohn’s Disease and
Ulcerative Colitis, Ankylosing Spondylitis.
3. Rituximab is also used in the management of NH Lymphoma, CL Leukemia.
10.5- Drugs for Gout
1. Gout is a disorder that arises when the blood contains increased levels of uric acid, which is a
by-product of normal body metabolism, when its concentration in the blood is excessive, uric
acid crystals may form in various parts of the body, especially in the joints of the foot (most often
the big toe), the knee, and the hand, causing intense pain and inflammation known as gout.
2. Crystals may form as white masses, known as tophi, in soft tissue, and in the kidneys as stones.
Attacks of gout can recur, and may lead to damaged joints and deformity known as gouty arthritis.
Kidney stones can cause kidney damage; An excess of uric acid can be caused either by
increased production or by decreased elimination by the kidneys, which remove it from the
body; the disorder tends to run in families and is far more common in men than women, the risk
of attack is increased by high alcohol intake, the consumption of certain foods (red meat,
sardines, anchovies, yeast extract, and offal such as liver, brains, and sweetbreads), and obesity.
3. An attack may be triggered by drugs such as thiazide diuretics, or excessive alcohol drinking;
Changes in diet and a reduction in the consumption of alcohol is an important part of treatment.
First: Acute attacks of Gout:

1. These are usually treated with high doses of NSAIDs, FDA approved NSAIDs for Gout include:
(Indomethacin, Naproxen and Sulindac); although other NSAIDs are also useful and effective.
a. Etoricoxib 120 mg is indicated for the relief of acute attack of Gout, used for 7 days only.
b. Colchicine is an alternative in patients in whom NSAIDs are contraindicated.
c. Aspirin is not indicated in gout (using small doses may trigger Gout attacks).
d. Urate-lowering drugs (Allopurinol and Febuxostat) should not be given until the acute
attack is controlled, as these drugs may prolong the attack by causing a change in uric acid
equilibrium, Urate-lowering agents can begin within 1 to 2 weeks after the resolution.
e. Corticosteroid intra-articular injections are also useful, Systemic corticosteroid therapy
is another option, when either NSAIDs or colchicine cannot be given or haven’t been effective.
2. Colchicine impairs leukocyte migration to inflamed areas and disrupts urate deposition and the
subsequent inflammatory response; (it has no effect on serum urate levels).
a. It relieves the pain and the inflammation within 12-24 hours of use.
b. It causes a dose related side effects (GI side effects) including diarrhea.
c. Should be avoided in patients with peptic ulcer disease and other GI disorders.
d. Chronic colchicine therapy may result in neuro-myopathy (numbness, paresthesias,
and/or weakness), it is best to limit colchicine therapy to 6-month duration; also, chronic
use may cause alopecia, and neutropenia.
e. In a shocking study; in patients with a recent myocardial infarction, colchicine at a dose of 0.5
mg daily led to a lower risk of ischemic cardiovascular events than placebo. (5)
3. Canakinumab (recombinant monoclonal antibody) can be used for the symptomatic treatment
of frequent Gouty arthritis attacks (at least 3 in the previous 12 months); it is licensed for use in
patients whose condition has not responded adequately to treatment with NSAIDs or colchicine,
or who are intolerant of them.
➢ It may cause increased risk of infections and Neutropenia.
Second: Prophylactic therapy of Gout:

There are 3 families that is used for prophylaxis:
1. Urate-reducing drugs include the xanthine oxidase inhibitors: (Allopurinol, Febuxostat) which
reduce uric acid production, and Selective uric acid reabsorption inhibitor (SURI): Lesinurad.
2. Uricosuric agents (Probenecid, Benzbromarone and Sulfinpyrazone); which increases renal
uric acid excretion; Both families are also used as a prophylaxis against uric acid stone.
3. Recombinant Urate oxidase enzymes (Pegloticase, Rasburicase); or called Uricase enzymes,
which act by oxidizing Uric acid to Allantoin (which is inactive, nontoxic, and easily excreted).
➢ Urate Oxidase is not found in the human body; although it’s found in nearly all organisms
(except in the humans; the perfect design?).
Notes:
1. Allopurinol is given in a once daily dose of 100 mg, and then increased gradually to 300 mg/day.
➢ The 300 mg once daily is the most commonly prescribed dose, but this may be an inadequate
dose; a dose of up to 800 mg/day (in two to three divided doses) may be needed to achieve
the desired 6 mg/dL serum uric acid level.
➢ Side effects occurring in 3% to 5% of patients include rash (Allopurinol sensitivity),
diarrhea, drug fever, leukopenia or thrombocytopenia.
➢ It has a drug-drug interaction profile with ACEIs and ARBs.
➢ It’s currently been studied for the treatment of Schizophrenia (refractory aggression).
4. Febuxostat:
➢ It has a Higher incidence of cardiovascular thromboembolic events than with Allopurinol;
FDA issued a new Black boxed warning for Febuxostat: stating that patients who take the drug
could be at an increased risk of death, especially death from heart-related issues.
➢ Indicated for patients who have Allopurinol sensitivity.
➢ No dosage adjustment needed in renal or hepatic failure.
➢ No drug interaction with ACEIs or ARBs.
5. Pegloticase is a form of uricase (urate oxidase), which catalyzes the oxidation of uric acid to
Allantoin, which is water soluble and easily excreted.
➢ It needs to be given by IV infusion every 2 to 4 weeks.
➢ Duration of effect is 12 days, (half-life 14 days).
➢ Patients need to be closely monitored for anaphylaxis and infusion reactions; thus, Pre-
treatment with antihistamines and corticosteroids is a must.
➢ May cause a life-threatening Hemolysis in patients with G6PD deficiency.
6. Rasburicase is licensed for the prophylaxis and treatment of acute hyperuricemia.
➢ Its FDA approved for the treatment of hyperuricemia caused by Tumor Lysis Syndrome (TLS).
➢ Also has a risk of anaphylaxis and infusion reactions, and G6PD hemolysis risk.
7. Lesinurad is a selective uric acid reabsorption inhibitor (SURI), it’s indicated to be used with a
Xanthine oxidase inhibitor (i.e.: it should not be used as a monotherapy).
A) Has a Black-Box warning of the possible risk of causing acute renal failure.
Colchicine Tab Colcrys ® 0.5 mg , 0.6 mg , 1 mg
Allopurinol Tab Zyloric , Hyporic , Zyloprim 100 mg , 300 mg
® ® ®

Febuxostat Tab , Cap Uloric , Adenuric , Feburic
® ® ® 40 mg , 80 mg
Pegloticase Inj. Solu. Krystexxa ® 8 mg/ml
Canakinumab Inj. Powder ILaris ® 180 mg/vial
Rasburicase Inj. Powder Fasturtec®, Elitek® 1.5 mg , 7.5 mg (per vial)
Lesinurad Tab Zurampic ® 200 mg
Uricosuric Drugs
Probenecid Tab Benemid® 500 mg
Benzbromarone Tab Desuric® 80 mg
Sulfinpyrazone Tab , Cap Anturane® 100 mg , 200 mg
Colchicine + Probenecid Tab Colcrys Plus® 0.5 mg + 500 mg
Colchicine + Allopurinol Cap Colpuril® 0.5 mg + 100 mg
Colchicine + Opium powder Tab Colchimax® 1 mg + 12.5 mg
+ Tiemonium methylsulfate + 50 mg
Lesinurad + Allopurinol Tab Duzallo® 200 mg + 300 mg
Allopurinol + Benzbromarone Tab Harpagin® , Allo-Comp® Lanolone® 100 mg + 20 mg
Note: Other drugs that increase uric acid excretion:
These include Guaifenesin (an expectorant), Losartan, Fenofibrate, Oxaprozin, and Vit. C.
a. Losartan, an angiotensin II receptor blocker (ARB), might be a useful anti-hypertensive agent in
the patient who has both hyperuricemia and hypertension because this agent can lower serum
uric acid levels by inhibiting the uptake of uric acid, this effect is minimal or not seen in other
ARBs.
b. Fenofibrate is used to treat elevated cholesterol and triglyceride levels; It has been shown to
decrease serum uric levels by increasing renal uric acid clearance and would be a useful
agent in the patient with both hyperlipidemia and hyperuricemia.
c. Oxaprozin (a NSAID) also has Uricosuric properties and is used in the treatment of gout.
d. Vitamin C may lower the serum uric acid level, a study noted a 0.5 mg/dL decrease in serum uric
acid when 500 mg Vit. C was given daily.
10.6- Other Rheum Drugs:

These below some of the drugs that are un-categorized, their short notes are below:
CH-Alpha ® Oral Vials Collagen Hydrolysate 10 gm/vial
CH-Alpha Plus® Oral Vials Collagen Hydrolysate + Vit. C 10 gm/vial
+ Rose hips Extract + Selenium
Benlysta® I.V. Solu. Belimumab 120 mg/vial , 400 mg/vial
Swiss Microlactin ® Cap Microlactin 500 mg
Xeljanz® Tab Tofacitinib 5 mg
Arceclox ® Cap , Celadrin (cap) 525 mg (Cap)
Cream Celadrin + Menthol (Cream) 7.5% + 1.25% (Cream)
Limbrel® Cap Flavocoxid + citrated zinc 250 mg , 500 mg
Semazin® Cap Serratiopeptidase ----------------
Diora®, Zondar® Cap Diacerein 50 mg
Verboril® Cap SR Diacerein 50 mg , 100 mg
Reparil® Tab Aescin 20 mg , 40 mg
Piascledine 300® Cap Avocado oil + Soybean oil 100 mg + 200 mg
Notes:
1. CH-Alpha® Contains Bioactive Collagen Peptides that keeps joints flexible through the natural
regeneration of joint cartilage.
2. Belimumab is a human monoclonal antibody that inhibits B-cell activating factor, indicated in
Systemic lupus erythematosus, Rheumatoid arthritis, Sjögren’s Syndrome.
3. MicroLactin® is a patented milk protein concentrate (Hyperimmune milk) that helps relieve joint
pain that results from osteoarthritis; Results is seen in as little as 2 weeks, (it’s a form of milk that is
acquired by giving lactating cows immunostimulants, which produces a larger amount of antibodies
in their secreted milk.
4. Tofacitinib (Xeljanz®) is currently approved for the treatment of Rheumatoid arthritis (RA) in
the United States and Russia, and is being studied for treatment of psoriasis, inflammatory bowel
disease, and other immunological diseases, as well as for the prevention of organ transplant rejection.
5. Arceclox® decreases inflammation and lubricates cell membranes throughout the body, restoring
fluids that cushion bones and joints to promote flexibility and mobility.
6. Limbrel® is a Medical food product indicated for the clinical dietary management of the metabolic
processes of osteoarthritis (weakly inhibit COX-1 and COX-2).
7. Semazin® has anti-inflammatory and anti-swelling effects.
8. Diacerein is used in the treatment of osteoarthritis, it works by inhibiting interleukin-1.
9. Aescin has Anti-exudative, Anti-inflammatory and Anti-edema effects.
10. Piascledine® is indicated for the symptomatic slow-acting treatment of hip and knee osteoarthritis,
taken 1 cap daily with food; for about 3 to 6 months.
Part two: Neurology:
1. This part describes the following: Fibromyalgia, Multiple sclerosis, Drugs that enhance
Neuromuscular transmission and Central monoamine depleting agent
- For drugs used in Epilepsy; see chapter 4, section 4.
- For drugs used in Parkinsonism see chapter 4, section 5.
- For anti-Alzheimer drugs see chapter 4, section 7.
- For painkillers see chapter 9.
- For special analgesic combination that act on neuropathic pain see the previous chapter, (chapter 9, section
3 for analgesic combinations, and section 5 for neuropathic pain).
10.7- Fibromyalgia
1. Fibromyalgia is classed as a disorder of pain processing due to abnormalities in how pain
signals are processed in the central nervous system, it is characterized by chronic widespread
pain, and Differences in psychological and autonomic nervous system profiles among affected
individuals may indicate the existence of fibromyalgia subtypes.
2. The defining symptoms of fibromyalgia are chronic widespread pain, fatigue, sleep disturbance,
and heightened pain in response to tactile pressure (allodynia), other symptoms may include
tingling of the skin (paresthesias), prolonged muscle spasms, weakness in the limbs, nerve pain,
muscle twitching, palpitations, and functional bowel disturbances
3. A 2007 review divides individuals with fibromyalgia into 4 groups:
1. Extreme sensitivity to pain but no associated psychiatric conditions (may respond to
medications that block the 5-HT3 receptor)
2. Fibromyalgia and comorbid, pain-related depression (may respond to antidepressants)
3. Depression with concomitant fibromyalgia syndrome (may respond to antidepressants)
4. Fibromyalgia due to somatization (may respond to psychotherapy)
Drugs usually used for Fibromyalgia include: (Duloxetine, Pregabalin and Milnacipran) (4)
Duloxetine Cap , Cap CR Cymbalta® 30 mg , 60 mg
Pregabalin Cap Lyrica® 75 mg , 150 mg
Milnacipran Tab Savella® 12.5 mg , 25 mg , 50 mg
Note: For antidepressant drugs see chapter 4, for Neuropathic pain see chapter 9
10.8- Drugs for Multiple Sclerosis:

1. Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), etiology
of multiple sclerosis (MS) is unknown, and currently there is no cure, characterized by central
nervous system demyelination and axonal damage, and appears to be autoimmune in nature.
2. Treatment of MS falls into three broad categories: symptomatic therapy, treatment of acute
attacks, and disease-modifying therapies (DMTs) to alter the natural course of the disease:
A) Symptomatic therapy (see the table 64-4 below)
B) Acute exacerbations or relapses of MS can be disabling. When this is the case, acute
exacerbations and relapses are treated with high-dose glucocorticoids, such as
methylprednisolone 500 to 1,000 mg/day by I.V. route, onset of response within 3- 5 days.
C) Treatment of relapsing-remitting MS with the disease-modifying therapies (DMTs)
Interferon-Β (see chapter 14 for Interferons), Glatiramer, Natalizumab, Mitoxantrone,
Fingolimod, Fampridine, Dalfampridine, Teriflunomide and Dimethyl Fumarate; can
reduce annual relapse rate, lessen severity of relapses ,slow progression of changes on
magnetic resonance imaging scans, slow progression of disability, slow cognitive decline.
D) Newer agents in the treatment of MS are the Monoclonal antibodies ex: (Alemtuzumab,
Daclizumab, Ocrelizumab), these have a promising result but usually very expensive and
has the disadvantageous of significantly increasing the risk for opportunistic infections.
Glatiramer Inj. Solu. Copaxone ® 20 mg/ml , 40 mg/ml
Natalizumab Inj. Solu. Tysabri ® 300 mg/15 ml
Mitoxantrone Inj. Solu. Novantrone ® 2 mg/ml
Fingolimod Cap Gilenya® 0.5 mg
Fampridine Tab , Cap Fampyra , Neurelan
® ® 10 mg
Dalfampridine Tab ER Ampyra ® 10 mg
Teriflunomide Tab Aubagio ® 7 mg , 14 mg
Dimethyl Fumarate Cap Tecfidera ® 120 mg , 240 mg
Alemtuzumab Vial Lemtrada , Campath
® ® 12 mg/1.2 ml , 30 mg/ml
Daclizumab Prefilled Inj. Zinbryta ® 150 mg/ml
Ocrelizumab Vial Ocrevus ® 300 mg/ml
Siponimod Tab Mayzent ® 0.25 mg , 2 mg
Extra Notes: (3)
1. Natalizumab is also indicated for Crohn’s disease and ulcerative colitis.
2. Mitoxantrone is also used for prostate cancer and acute non-lymphocytic Leukemia.
3. Fingolimod may cause first-dose bradycardia, it’s associated with increased risk of infections.
➢ C.I. in patients with myocardial infarction, Angina, Stroke, heart failure.
4. Dalfampridine is indicated to improve walking in patients with MS by ↑ walking speed.
5. Fampridine is licensed for the improvement of walking in patients with multiple sclerosis who
have a walking disability, it is also used for the treatment of spinal cord injury.
6. Dimethyl Fumarate is also used for Friedreich’s ataxia.
7. Alemtuzumab is also indicated for chronic lymphocytic leukemia (CLL), and used off-label
in kidney transplantation.
a. It is a monoclonal antibody that binds to CD52, a protein present on the surface of mature
lymphocytes, but not on the stem cells from which these lymphocytes are derived, then these
CD52-bearing lymphocytes are targeted for destruction.
8. Ocrelizumab was approved by the FDA in March 2017 as a treatment for multiple sclerosis, and
the first FDA approved drug for the primary progressive form of MS.
a. At launch, the drug was priced at $ 65,000 (annual cost, for two infusions per year).
b. It is an immunosuppressive drug; it binds to CD20, which is selectively made by B cells, and
when Ocrelizumab binds to CD20 it kills B cells by causing antibody-dependent cell-
mediated cytotoxicity and to a lesser extent, complement-dependent cytotoxicity.
Symptomatic therapy: →
Table
1. Tremor
Cerebellar symptoms such as tremor can be
troubling and difficult to control. Medications
that can be helpful include propranolol,
Primidone, and isoniazid.
2. Major Depression
Major depression is common in patients with MS,
and the risk of suicide may be increased
markedly compared with healthy Subjects,
Patients should be monitored closely for the
development of major depressive
symptomatology and treated accordingly.
➢ Interferon products and Natalizumab
should be used cautiously in patients with
significant depression.

3. Sexual Dysfunction
Sexual dysfunction in both men and women are common in MS and counseling should be offered
to both partners. Sildenafil, Tadalafil and Vardenafil are very effective for men with MS who
have erectile dysfunction. Other options for men include Alprostadil injection or intra-urethra
suppositories (MUSE). (See chapter 8, section 5, for more info)
➢ Sildenafil is currently being studied in females with MS and sexual dysfunction; in patients
needing antidepressant therapy for whom sexual dysfunction is a concern, bupropion is
preferable to SSRIs as it has a much lower incidence of sexual side effects.
4. Cognition
Cognitive dysfunction is common in MS, affecting up to 50% or more of patients. It generally
manifests itself as word finding difficulties and problems with concentration and short-term
memory; Cognitive dysfunction can be treated with stimulants or cholinesterase inhibitors.
5. Emotional incontinence; or Pseudobulbar affect (PBA), is a type of emotional disturbance
characterized by uncontrollable episodes of crying and/or laughing, or other emotional displays;
PBA occurs secondary to a neurologic disorder (as MS) or brain injury. Patients may find
themselves crying uncontrollably at something that is only moderately sad, being unable to stop
themselves for several minutes, Episodes may also be mood-incongruent: a patient may laugh
uncontrollably when angry or frustrated, for example. Sometimes, the episodes may switch
between emotional states, resulting in the patient crying uncontrollably before dissolving into
fits of laughter. (The last Joker movie 2019).
➢ Antidepressants such as Sertraline, Fluoxetine, Citalopram, And Amitriptyline have been
prescribed with some efficacy in the treatment of PBA.
➢ Dextromethorphan/Quinidine combination is the first FDA-approved drug for the
treatment of PBA; Dextromethorphan is used as a cough suppressant, Quinidine affects the
way the heart beats, and is generally used in people with certain heart rhythm disorders. It is
also used to treat malaria.
Dextromethorphan + Tab Nuedexta® 20 mg
Quinidine + 10 mg
10.9- Drugs that Enhance Neuromuscular Transmission

A) Anticholinesterases
1. Anticholinesterases are used as first-line treatment in ocular myasthenia gravis and as an adjunct
to immunosuppressant therapy for generalized myasthenia gravis.
2. Anticholinesterase drugs enhance neuromuscular transmission in voluntary and involuntary
muscle in myasthenia gravis; They prolong the action of acetylcholine by inhibiting the action of
the enzyme acetylcholinesterase. Excessive dosage of these drugs can impair neuromuscular
transmission and precipitate cholinergic crises by causing a depolarizing block. This may be
difficult to distinguish from a worsening myasthenic state.
3. Neostigmine produces a therapeutic effect for up to 4 hours. Its pronounced muscarinic action
is a disadvantage, and simultaneous administration of an Antimuscarinic drug such as Atropine
or Propantheline may be required to prevent colic, excessive salivation or diarrhea.
➢ It’s indicated for the treatment and diagnosis of Myasthenia Gravis.
➢ Also indicated for post-op distention or urinary retention.
4. Pyridostigmine is less powerful and slower in action than neostigmine but it has a longer
duration of action, it is preferable to neostigmine because of its smoother action and the need for
less frequent dosage.
Neostigmine Tab Prostigmin ® 15 mg
Inj. Solu. 0.5 mg/ml , 1 mg/ml
Pyridostigmine Tab Mestinon , Regonol
® ® 60 mg , 180 mg (CR tab)
Inj. Solu. 5 mg/ml
B) Acetylcholine-release Enhancers
1. Amifampridine is licensed for the symptomatic treatment of Lambert-Eaton myasthenic
syndrome (LEMS); a rare disorder of neuromuscular transmission
2. Fampridine is licensed for the improvement of walking in patients with multiple sclerosis who
have a walking disability, it is also used for the treatment of spinal cord injury.
Amifampridine Tab Firdapse® 10 mg
Fampridine Tab , Cap Fampyra® , Neurelan® 10 mg
10.10- Central monoamine depleting agent

1. These agents are used to treat hyperkinetic movement disorders and involuntary movements
or chorea associated with Huntington’s disease and tardive dyskinesia.
2. They include: Tetrabenazine, Deutetrabenazine and Valbenazine.
Tetrabenazine Tab Xenazine®, Revocon® 12.5 mg , 25 mg
Deutetrabenazine Tab Austedo® 6 mg , 9 mg , 12 mg
Valbenazine Cap Ingrezza® 40 mg , 80 mg
10.11- Other Neurological Drugs

Ataluren Oral Susp. Translarna® 125 mg, 250 mg, 1,000 mg
Riluzole Tab Rilutek® 50 mg
Edaravone I.V. Solu. Radicava® 30 mg/100 ml
Amp Aravon® 1.5 mg/ml (20 ml amp)
Elamipretide
Masitinib
Nusinersen Vial Spinraza® 12 mg/5 ml
Notes:
1. Ataluren is indicated for Duchene Muscular Dystrophy.
2. Riluzole is an NMDA receptor antagonist, it’s the only drug approved for the spasmolytic
treatment of ALS (Amyotrophic Lateral Sclerosis).
➢ Riluzole is also a neuroprotective agent with anticonvulsant properties.
➢ Research and studies are ongoing for Riluzole in the treatment of severe mood, anxiety, and
impulsive disorder
3. Edaravone, Masitinib are indicated for Amyotrophic Lateral Sclerosis (ALS).
a. Edaravone is administered 60 mg IV infusion over 60 min qDay for 14 days; followed by a
14-day drug-free period.
b. Edaravone was approved for ALS by the FDA in 2017 based on a small randomized controlled
clinical trial with people who had early-stage ALS in Japan, who were administered the drug
for 6 months; it had failed two earlier trials in people with all stages of ALS.
c. Edaravone is used to help people recover from stroke in Japan.
4. Elamipretide is indicated for primary mitochondrial myopathy; which is characterized by
muscle weakness in patients with genetic mitochondrial diseases.
5. Nusinersen is indicated for the treatment of Spinal Muscular Atrophy (SMA).
a. Administered by intrathecal route, initially 4 loading doses (first three doses at intervals of
14 days; then the 4th dose at interval of 30 days).
b. Then a Maintenance dose once every 4 months.
References
1- Sean C. Sweetman. Martindale: 38th Edition.
3- Comprehensive Pharmacy Review for NAPLEX, 8th Edition.
4- Pharmacotherapy: A Pathophysiologic Approach, 11th Ed.

CORTICOSTEROIDS
Chapter Eleven: Corticosteroids
First: Introduction:
1. Physiological effects of
Glucocorticoids
2. Physiological effects of
Mineralocorticoids
3. Corticosteroids side effects
4. Therapeutic uses of the
corticosteroids
Second: Types of corticosteroids

A. Inhaled corticosteroids
B. Corticosteroids for Nasal Cavity
C. Oral and Injectable Corticosteroids
D. Intra-articular corticosteroid
injections
E. Topical Corticosteroids
• Low Potency
• Medium Potency
• High Potency
• Very High Potency
F. Ophthalmic Corticosteroids
G. Intra-vitreal Corticosteroids
H. Otic Corticosteroids
I. Rectal corticosteroids
Third: Corticosteroids related

drugs
a. Corticotropin
b. Corticorelin
c. Tetracosactide
Sam’s Guide: Chapter 11 – Corticosteroids
Chapter Eleven: Corticosteroids
1. Physiological effects of Glucocorticoids:
a. Promote normal intermediary metabolism: Glucocorticoids stimulates gluconeogenesis
and stimulate protein catabolism and increase lipolysis (increase free fatty acids).
b. Decrease insulin sensitivity in the muscles and adipose tissue.
c. Increase resistance to stress: By raising plasma glucose levels, glucocorticoids provide the
body with the energy it requires to combat stress caused, for example, by trauma, fright,
infection, bleeding, or debilitating disease.
d. They cause a modest rise in blood pressure, (they have positive inotropic effect throw
stimulation of Na/K ATPase and Beta-adrenergic receptors); also, they cause Na and water
retention (increase blood volume); they also potentiate the vasoconstrictor effect of
Norepinephrine and Angiotensin II.
e. Alter blood cell levels in plasma: Glucocorticoids cause a decrease in eosinophil’s,
basophils, monocytes, and lymphocytes by redistributing them from the circulation to
lymphoid tissue. In contrast to this effect, glucocorticoids increase the blood levels of
hemoglobin, erythrocytes, platelets, and polymorph-nuclear leukocytes. [Note: The
decrease in circulating lymphocytes and macrophages compromises the body’s ability to fight
infections. However, this property is important in the treatment of leukemia].
f. Have anti-inflammatory action; they suppress phospholipase A2 activity (thus decrease
arachidonic acid synthesis, which in turn will cause a decrease in prostaglandins and
leukotrienes synthesis); also, they suppress cyclooxygenase (COX) activity.
• They suppress proinflammatory cytokines and other inflammatory mediators such as
tumor necrosis factor (TNF) and interleukins.
• They suppress leukocytes and microphages migration.
• They decrease capillary permeability, which in turn decrease inflammatory edema.
g. Have anti-allergic action; they decrease tissue response to allergic mediators and
decrease histamine release throw stabilization of mast cells and basophils.
h. Have immunosuppressant effect; they inhibit the function of macrophages, TNF,
interleukins and prevents T-cells proliferation.
i. Affect other components of the endocrine system: Feedback inhibition of corticotrophin
production by elevated glucocorticoids causes inhibition of further synthesis of both
glucocorticoid and thyroid-stimulating hormones.
j. Can have effects on other systems: Adequate cortisol levels are essential for normal
glomerular filtration (they increase GFR), also increase reabsorption of water, Na and CL.
• High doses of glucocorticoids stimulate gastric acid and pepsin production and may
exacerbate ulcers.
• Effects on the central nervous system that influence mental status have been identified;
they decrease seizure threshold and increase intracranial pressure.
• Chronic glucocorticoid therapy can cause severe bone loss and myopathy; they
decrease the absorption of Calcium and Phosphate from the intestine.
k. They can cause osteoporosis throw several pathways; including decreasing osteoblast
numbers and reducing its functionality, and by increasing osteoclast survival and activity.
2. Physiological effects of Mineralocorticoids:

a. Control the body’s water volume and concentration of electrolytes, especially sodium
and potassium. Aldosterone acts on kidney tubules and collecting ducts, causing reabsorption
of sodium, bicarbonate, and water.
b. Aldosterone decreases reabsorption of potassium, which, with H+ is then lost in the urine.
Enhancement of sodium reabsorption by aldosterone also occurs in gastrointestinal mucosa
and in sweat and salivary glands.
c. Elevated aldosterone levels may cause alkalosis and hypokalemia, whereas retention of
sodium and water leads to an increase in blood volume and blood pressure.
3. The corticosteroids are used in physiological doses for replacement therapy in adrenal
insufficiency. (3) While the Pharmacological doses are used when anti-inflammatory or
immunosuppressant effects are required (for so many different diseases).
4. The effects of different corticosteroids vary qualitatively as well as quantitatively, and it
may not be possible to substitute one for another in equal therapeutic amounts. Thus, whereas
cortisone and hydrocortisone have very appreciable mineralocorticoid (or sodium-
retaining) properties relative to their glucocorticoid (or anti-inflammatory) properties,
prednisolone have considerably less, and others, such as betamethasone and dexamethasone,
have none or virtually none.
5. As a rough guide, the approximate equivalent doses of the main corticosteroids in terms of their
glucocorticoid (or anti-inflammatory) properties alone, are:
Betamethasone 0.75 Mg = Cortisone Acetate 25 Mg = Dexamethasone 0.75 Mg =
Hydrocortisone 20 Mg = Methylprednisolone 4 Mg = Prednisolone 5 Mg = Prednisone 5 Mg
= Triamcinolone 4 Mg (3).
a. The use of pharmacological doses of corticosteroids suppresses the endogenous secretion of
steroids by the anterior pituitary.
b. The adrenal suppression is less when the corticosteroid is given as a single dose in the
morning, and even less if this morning dose is given on alternate days or less frequently
c. Sudden withdrawal in dosage may precipitate acute adrenocortical insufficiency.
d. Gradual withdrawal of systemic corticosteroids is required for:
➢ Patient who received more than 40 mg prednisolone (or equivalent) daily for more than
1 week.
➢ Patient who received more than 3 weeks’ treatment.
6. Corticosteroids have numerous side effects including nearly all body systems:
a. Osteoporosis is the most common adverse effect: due to the ability of glucocorticoids to
suppress intestinal Ca2+ absorption, inhibit bone formation, and decrease sex hormone
synthesis; (Alternate-day dosing does not prevent osteoporosis; also, Patients are advised to
take calcium and vitamin D supplements).
b. The classic Cushing-like syndrome (redistribution of body fat, puffy face, increased body
hair growth, acne, insomnia, and increased appetite).
c. Hyperglycemia may develop and lead to diabetes mellitus. Diabetic patients should
monitor their blood glucose and adjust their medications accordingly.
d. Decreased growth in children, increased risk of infection, Emotional disturbances.
e. Peptic ulcers, Hypertension and Peripheral edema.
f. Corticosteroids (especially dexamethasone) are frequently abused in Iraq. (Prolonged use
glucocorticoids have a dramatic effect on body fat distribution, resulting in the characteristic
appearance of moon face).
7. Therapeutic uses of the corticosteroids:
a. Replacement therapy for primary adrenocortical insufficiency (Addison disease): usually
Hydrocortisone and Fludrocortisone are indicated in this condition.
b. Replacement therapy for secondary or tertiary adrenocortical insufficiency.
c. Diagnosis of Cushing syndrome: by dexamethasone suppression test.
d. Relief of inflammatory symptoms: they redness, swelling, heat, and tenderness that are
commonly present at the inflammatory site, also stabilize mast cell and basophil membranes
(thus, inhibiting histamine release) and diminishing the activation of the kinin system.
e. Treatment of allergies: treatment of the symptoms of bronchial asthma; allergic rhinitis;
and drug, serum, and transfusion allergic reactions.
f. Acceleration of lung maturation: Respiratory distress syndrome is a problem in premature
infants. Fetal cortisol is a regulator of lung maturation.; Consequently, a dose of
betamethasone or dexamethasone is administered intramuscularly to the mother 48 hours
prior to birth, followed by a second dose 24 hours before delivery.
A) Inhaled Corticosteroids (ICS):

1. An inhaled corticosteroid is used regularly for prophylaxis of asthma; they are ineffective for
acute asthmatic attack.
2. May cause oral candidiasis (oral fungal infection) and this side effect can be reduced by
rinsing the mouth with water after inhalation of a dose; or by using spacer device.
Beclomethasone Inhaler Qvar , Beclosone , Becotid
® ® ® 50 mcg , 100 , 250 mcg
Budesonide Inhaler Pulmicort ® 200 mcg
Nub. Solu. 200 mcg
Inhale Cap Miflonide ® 200 mcg
Fluticasone Aerosol Flixotide , Flovent
® ® 110 mcg , 100 mcg (Diskus)
Ciclesonide Inhaler Alvesco ® 80 mcg
Flunisolide Aerosol Aerospan® 80 mcg
Mometasone Inhaler Asmanex , Twist-haler
® ® 110 mcg , 220 mcg
Triamcinolone Inhaler Azmacort ® 55 mcg , 100 mcg
* Comes in combination with long acting beta2 agonist for Rx of Asthma (see chapter 1).
B) Corticosteroids for Nasal Cavity:

1. Nasal preparations containing corticosteroids have a useful role in the prophylaxis and
treatment of allergic rhinitis.
2. Regular use is essential for full benefit and it takes several days before full effect is reached.
Betamethasone Nasal drop Methadin® 0.1 % (10 ml)
Beclomethasone Nasal spray Beconazse® 42 mcg/spray
Budesonide Nasal spray Rhinocort Aqua®, Cortinase® 32 mcg , 64 mcg (per Actuation)
Mometasone Nasal spray Nasonex® 50 mcg/spray
Triamcinolone Nasal spray Nasacort® 55 mcg/spray
Ciclesonide Nasal spray Omnaris® 50 mcg (per Actuation)
Flunisolide Nasal spray Aerospan nasal® 25 mcg (per Actuation)
Fluticasone Nasal spray Flonase® , Flixonase® 50 mcg/spray
Fluticasone + Nasal spray Dymista® (50 mcg + 137 mcg)/spray
Azelastine *
* Azelastine is anti-histamine.
C) Oral and Injectable Corticosteroids:

1. These are used in many diseases, as a replacement therapy in adrenal insufficiency, as anti-
inflammatory, in autoimmune diseases such as (Ulcerative Colitis, Crohn’s disease), as
Immunosuppresants (in high doses) … etc.


Hydrocortisone Tab Cortef ® 5 mg , 10 mg , 20 mg
Vial Hyamol® , H.C.® 100 mg , 250 mg
Fludrocortisone Tab Florinef® 0.1 mg
Betamethasone Tab Celestone® 0.5 mg
Amp Celeston®, Betacort® 4 mg/ml , 6 mg/ml
Prednisolone Tab Deltacortil® , Predine® 5 mg , 20 mg
Syr. Xilone® 5 mg/5 ml , 15 mg/5 ml
Prednisone Tab Cortancyl® , Rayos® 20 mg , 50 mg
Oral Solu. Deltasone® 5 mg/5 ml
Dexamethasone Tab Decadron® , Dexon® 0.5 mg , 1 mg
Tab DR Baycadron® 4 mg , 6 mg
Syr. Dexon®, Orazone® 0.5 mg/5 ml
Amp Decadron®, Dexamed® 4 mg/ml , 8 mg/2 ml
Methylprednisolone Tab Medrol® 4 mg , 8 mg , 16 mg
Inj. (vial) Depo-Medrol® 40 mg/ml , 80 mg/ml
Inj. (powder) Solu-Medrol® 250 mg , 500 mg , 1 gm
Triamcinolone Inj. (vial) Kenacort A®, Trivaris® 20 mg/ml , 40 mg/ml
Oral Gel Kenalog® 1 mg/gm (10 gm tube)
Notes:
1. Dexamethasone has the strongest anti-inflammatory effect, while Hydrocortisone has the
lowest anti-inflammatory effect.
2. Triamcinolone has the longest half-life (300 min); Prednisone has the lowest (60 min).
3. Fludrocortisone is intended for use as a mineralocorticoid only, (used only for
Adrenocortical Insufficiency, Addison Disease) and used (off-label) in the treatment of severe
orthostatic hypotension.
4. Prednisolone is a pro drug, its converted by the liver into Prednisone
a. Prednisone is preferred in pregnancy because it minimizes steroid effects on the fetus.
b. Many doesn’t know that there is a difference between Prednisolone and Prednisone.
(Don’t be one of them)
5. Triamcinolone Oral Gel is used for the temporary relief of symptoms from mouth sores, oral
inflammatory lesions and ulcerative lesions; it works by reducing the swelling, itching, and pain
that can occur with mouth sores.

D) Intra-articular corticosteroid injections:
Methylprednisolone or Triamcinolone may be useful when only a few joints are affected in
case of osteoarthritis and rheumatoid arthritis; they are also injected locally in some other
conditions; they can provide excellent pain relief particularly when a joint effusion is present.
➢ They should be limited to 3 or 4 injection per year.
➢ (see chapter 10, section 2, for details)
E) Topical Corticosteroids:
1. Topical corticosteroids are effective in many inflammatory and proliferative skin diseases, used
to help relieve redness, itching, swelling, or other discomfort caused by skin conditions including:
atopic dermatitis, psoriasis, seborrheic dermatitis, contact dermatitis, and nummular
eczema. (2-4)
2. They come in different potencies (Low, Medium, High, and Very High); Their Potencies are
commonly classified according to the vasoconstrictor assay, based on the degree to which an
agent causes cutaneous vasoconstriction on normal human subjects.
• Changing the salt form will also change the potency.
3. Absorption of topical corticosteroids is highest on mucous membranes, followed by the scrotum,
eyelid, face, chest, back, arms and legs, dorsa of hands and feet, and palms and soles.
4. Chromic Topical therapy with Corticosteroids can cause skin atrophy, ecchymosis, purple
striae, dermatoses, and cataracts.
• With chronic use, topical corticosteroids (especially the potent agents) show decreased
efficacy, a phenomenon known as “tachyphylaxis”.
• They mask the symptoms of infections such as Tinea (fungal) and scabies.
• For more info see the dermatology chapter.
F) Ophthalmic Corticosteroids:
1. Used to prevent permanent damage to the eye, which may occur with certain eye problems (as
Iritis, Keratitis and Conjunctivitis), they also provide relief from redness, irritation, itching
and allergic reactions affecting the eye.
2. They should be used with caution for patients with the Glaucoma & Cataract, and they are
preferably not to be used more than about 7 – 10 days.
Betamethasone Eye Drop Methadin ® 0.1 % (10 ml)
Dexamethasone Eye Drop Maxidex ® 0.1%
Eye Oint. 0.05%
Hydrocortisone Eye Drop Hyrocort , Opticort
® ® 1%
Eye Oint. 1%
Fluorometholone Eye Drop FML® , Flucon® , FML Forte® 0.1% , 0.25% (Forte)
Prednisolone Eye Drop Pred Mild® , Pred Forte® 0.12% , 1% (Forte)
Loteprednol Eye Drop Alrex® , Lotemax® 0.2% , 0.5%
Eye Gel Lotemax® 0.5%
Rimexolone Eye Drop Vexol® 1%
Difluprednate Eye Drop Durezol® 0.05%
** For combination products with antibiotics see chapter 12, page 155.

G) Intra-vitreal * Corticosteroids Injections:
1. Intra-vitreal injections are commonly used to treat retinal diseases such as diabetic retinopathy,
macular degeneration, macular edema, and retinal vein occlusion.
2. The medication is injected directly into the eye, may be administered as frequently as once a
month, depending on the condition being treated.
Dexamethasone Intra-vitreal Implant Ozurdex® 0.7 mg (0.4 mg/0.1 ml)
Fluocinolone Intra-vitreal Insert Retisert® 0.59 mg
Triamcinolone Intra-vitreal Inj. Triesence® 4 mg/0.1 ml
* For more details on this tech. see chapter 12, page 160.
H) Otic Corticosteroids:
1. Used in the ear to relieve the redness, itching, and swelling caused by certain ear problems, used
usually to treat inflammation, and eczema or dermatitis in the ears.
2. Generally ophthalmic (eye) preparations containing corticosteroids can be used in the ears.
They rarely found alone, usually comes in combinations with antibiotics. (See chapter 13)
Betamethasone Ear drop Methadin® 0.1 % (10 ml)
Dexamethasone Ear drop Dexonium® 10 mg/10 ml
Fluocinolone Ear drop Dermotic® 0.01%
I) Rectal corticosteroids:
1. Also called Gastrointestinal Corticosteroids, are used to treat mild or moderate ulcerative
colitis and Crohn’s Disease. They also may be used along with systemic (oral or injection)
corticosteroids or other medicines to treat severe disease or mild to moderate disease that has
spread too far to be treated effectively by medicine inserted into the rectum alone.
2. Rectal corticosteroids also are used to help relieve swelling, itching, and discomfort of some other
rectal problems, including hemorrhoids and inflammation of the rectum.
3. Some of these medicines may be taken as pills. If the disease affects only the lower part of the
colon, corticosteroids can be given by enema. For disease that only affects the rectum,
suppositories and topical creams can be used.
Budesonide Rectal Enema Entocort® 2 mg (0.02 mg/ml)
Cap , Tab 3 mg (Cap) , 9 mg (Tab)
Hydrocortisone Rectal Enema Proctol® , Anusol HC® 100 mg/60 ml
Rectal Supp. 25 mg , 30 mg
Hydrocortisone + Cream, Lotion Procort® , Pramosone® (1% + 1%),
Pramoxine * , Rectal Foam (2.5% + 1%)
Hydrocortisone + Rectal Gel AnaMantle® 2.5% +
Lidocaine * 2%
Fluocinolone + Oint , cream , Proctoheal® 0.1 mg +
Lidocaine * Supp. 20 mg
* Pramoxine and Lidocaine Are Local Anesthetics.
** For Ulcerative Colitis and Crohn’s disease: See chapter 2
** For Hemorrhoids: See chapter 2
Third: Corticosteroids related drugs:
Corticotropin Inj. Solu. Acthar Gel® 80 units/ml
Corticorelin Inj. (I.V.) Acthrel® 100 mcg/2 ml
Deflazacort Tab Emflaza® 6 mg , 18 mg , 30 mg
Oral Susp. 22.75 mg/ml
Tetracosactide Amp Synacthen® 250 mcg/ml
Amp Synacthen Depot® 1 mg/ml
Notes:
1. Corticotropin is used to treat relapsing multiple sclerosis (MS), infantile spasms, and
nephrotic syndrome (a collection of symptoms that indicate kidney damage),
dermatomyositis (a chronic inflammatory disease of skin and muscle) and polymyositis (an
autoimmune inflammatory disease of muscle).
a. Acthar Gel® should never be given intravenously, also should not be used in patients with a
skin condition called scleroderma, bone density loss (osteoporosis), infection throughout the
body, eye infection (ocular herpes simplex), recent surgery, history of or a current stomach
ulcer, heart problems, high blood pressure.
b. May cause side effects similar to side effects that happen due to treatment with steroids
2. Corticorelin is used as a diagnostic test in adrenocorticotropic hormone (ACTH)-dependent

Cushing's syndrome to differentiate between pituitary and ectopic production of ACTH.
3. Deflazacort is a glucocorticoid which has an anti-inflammatory and immunosuppressant

effects; but it’s indicated only for Duchene muscular dystrophy (DMD).
4. Synacthen® (250 mcg Amp) is intended for administration for diagnostic purposes only
(Synacthen Test) as a single intramuscular or intravenous dose; it is not to be used for
therapeutic administration. (2)
➢ While the Synacthen® Depot (1 mg Amp) is used to treat Ulcerative Colitis, Crohn’s
disease, Steel disease, Rheumatoid Arthritis, Osteoarthritis and some inflammatory skin
conditions like (Pemphigus, Sever Eczema, Psoriasis).
References
3- Comprehensive Pharmacy Review for NAPLEX, 8th Edition
5- Lippincott’s pharmacology 7 Ed.

OPHTHALMOLOGY
Chapter Twelve: Ophthalmology (The Eye)
12.1- Administration of drugs to
the Eye (Teach the patient) Fourth: Other Types of
Ophthalmic Drops
First: Anti-Glaucoma Eye Drops A. Drops that Extend the Iris
A. Beta-blockers eye drops (Mydriatics/Cycloplegics)
B. Prostaglandin analogues drops ➢ Combination products
C. α2 – agonists B. Anesthetic Eye Drops
D. Carbonic Anhydrase Inhibitors ➢ Combination products
E. Miotics or Cholinergic agents C. Anti-Cataract Eye Drops
F. Kho kinase inhibitor ➢ Combination products
G. Combination Products for Glaucoma D. Other types of Eye Drops
Second: Conjunctivitis
A. Eye Drops for Allergic/Irritant
Conjunctivitis Fifth: Intra-vitreal Eye Injections
1. Anti-histamine Eye Drops
2. Mast cell stabilizer Eye Drops Sixth: Other drugs for retinal
3. Corticosteroids Eye Drops disorders:
4. NSAIDs Eye Drops
5. Decongestant or (Decongestant +
Anti-histamine) Eye Drops
B. Drops for other types of
Conjunctivitis
1. Ophthalmic Quinolones
2. Ophthalmic Aminoglycosides
3. Ophthalmic Macrolides
4. Other Ophthalmic Antibacterials
5. Combination products of
Antibacterial Eye Drops
6. Antibacterial Ophthalmic
preparations combined with a
corticosteroid
7. Special Eye Drop Combinations
8. Ophthalmic Antivirals
9. Ophthalmic Antifungals
Third: Lubricating Eye Drops

(Tear’s Deficiency)
➢ Drops with preservatives
➢ Drops free of preservatives
➢ In Form of Gel
➢ Eye lubricants + Decongestant
Sam’s Guide: Chapter 12 – The Eye
Chapter Twelve: Ophthalmology (The Eye)
12.1- Administration of drugs to the eye (Teach the patient)
1. Administration guideline for eye drops and ointments are shown in the tables below:
2. one drop is all that is needed. Instillation of more than one drop should be discouraged because
it may increase systemic side-effects.
3. When two different eye-drop preparations are used at the same time of day, dilution and
overflow may occur when one immediately follows the other; The patient should therefore leave
an interval of at least 5 minutes between the two.
4. If using a suspension, shake well before instilling, if using the suspension with another dosage
form, place the suspension drop last, because it has prolonged retention time in the tear film
(1) (most steroid eye drops present as a suspension).
5. If both drop and ointment therapy are indicated, instill the drops at least 10 minutes before
the ointment so that the ointment does not become a barrier to the drops' penetrating the tear
film or cornea.
6. Discard or replace eye drop bottles 30 days after the sterility safety seal is opened (unless
stated otherwise by manufacturer). The manufacturer's expiration date does not apply once the
seal is broken.
7. Some eye drops (like Latanoprost (Xalatan®) need to be stored at refrigerator.
8. Patients should be warned not to drive or perform other skilled tasks until vision is clear after
using eye drops or eye ointments.
9. It is common to use drops during the day and then use eye ointment in the evening or at
night upon retiring when the blurring of vision will be less inconvenient.
10. Contact lenses and drug treatment: In general, patients should be counseled not to place any
ophthalmic solution, suspension, gel, or ointment into the eye when contact lenses are in
place; the lenses should be removed before drop instillation and not worn during the period of
treatment.
First: Anti-Glaucoma Eye Drops
1. Drugs that reduce intra-ocular pressure by different mechanisms are available for managing
glaucoma; All are used topically (as Eye drops) except Acetazolamide and Methazolamide;
which are available as an oral tablet (and less commonly as an injection).
2. Glaucoma (high eye pressure); Occurs as a result of the imbalance between the secretion of fluid
called (aqueous humour) – which its Concentration is about 4 cc inside the eye – and between
the speed of its discharge, leading to its accumulation inside the eye suppressing the optic nerve,
and if it continues to put pressure on the nerve → this will cause damage to the eye and lost vision.
➢ In the most common type, called chronic (or open-angle) glaucoma, reduced drainage of fluid
from the eye causes pressure inside the eye to build up slowly; Progressive reduction in the
peripheral field of vision may take months or years to be noticed.
➢ Acute (or closed-angle) glaucoma occurs when drainage of fluid is suddenly blocked by the
iris. Fluid pressure usually builds up quite suddenly, blurring vision in the affected eye. The
eye becomes red and painful, and a headache and sometimes vomiting also occur; The main
attack is often preceded by milder warning attacks, such as seeing haloes around lights in the
previous weeks or months.
3. Usually; the damage is gradual without any symptoms or pain, especially in the elderly and with
increasing pressure patient may feel severe pain in the head, eye and blurred vision with redness
and tears.
4. Drops work to reduce intraocular pressure to below 20 (normal range), and if it fails the doctor
is resorted to the option of laser treatment.
5. These drops reduce intraocular pressure in two ways:
a. Slowing the production of fluid inside the eye (Aqueous Fluid)
b. By improving the flow of fluid out of the eye through the drainage angle (drainage).
6. The treatment options for Glaucoma:
A) Beta-blockers eye drops: act by reducing the formation of the aqueous humour.
B) Prostaglandin analogues: Improve Fluid discharge, thus reduce intraocular pressure.
C) α2 - agonists: Reduce the secretion of fluid and also facilitate the process of discharge.
D) Carbonic Anhydrase Inhibitors (CAI): reduce the formation of the aqueous humour.
E) Miotics or Cholinergic agents: Improve liquid discharge cycle outside of the eye.
F) Kho kinase inhibitor: increase trabecular outflow.
7. To get both benefits of reducing the formation of the aqueous humour and increasing its
discharge → a combination of Beta-blocker plus Prostaglandin analogues or CAI is used.
A) Beta-blockers eye drops: (Reduce Formation of Fluid)

1. Beta blockers drops can be absorbed into the body and can affect the lungs, heart, and circulation.
As a result, a Cardioselective beta blocker, such as Betaxolol, is prescribed with caution to people
with asthma or certain circulatory disorders and, in some cases, such drugs are withheld
altogether.
2. The amount of the drug absorbed into the body can be reduced by pressing on the lacrimal (tear)
duct in the corner of the eye while applying the number of eye drops
3. Beta blocker drops are usually given twice daily.
Betaxolol Eye drop Betoptic®, Eltaxol® 0.5% , 0.25%
Timolol Eye drop Lithimole®, Ophtamolol®, Timoptof® 0.5% , 0.25%
Carteolol Eye drop Ocupress® , Carteol® 1% , 2%
Levobunolol Eye drop Betagan® 0.5% , 0.25%
Metipranolol Eye drop OptiPranolol® 0.3%
B) Prostaglandin analogues drops: (Improve Fluid discharge)
1. Prostaglandin analogues are usually applied once daily, preferably in the evening, and should
not be increased to twice daily, as this may decrease effectiveness.
2. Patients receiving Prostaglandin analogues drops should be instructed to refrigerate unopened
medication, once opened Latanoprost can stored at room temperature for 6 weeks.
3. Prostaglandin analogues may cause, darkening, thickening and lengthening of eye lashes
(reversible upon stopping treatment).
➢ Some women actually uses it for this effect to have a more thickened eye lash.
➢ Commercially; a topical gel of Latanoprost is available for eye lash thickening.
4. Before initiating treatment, patients should be warned of a possible change in eye color as an
increase in the brown pigment in the iris can occur, which may be permanent; particular care is
required in those with mixed colored irises and those receiving treatment to one eye only

Latanoprost Eye drop Xalatan® , Latano® 0.005%
Bimatoprost Eye drop Lumigan® , Latisse® 0.01% , 0.03%
Travaprost Eye drop Travatan® 0.004%
Tafluprost Eye drop Taflotan® , Saflutan® 0.0015 %
Unoprostone Eye drop Rescula® 15%
Latanoprostene Eye drop Vyzulta® 0.024%
C) α2 – agonists: (Reduce secretion and facilitate discharge)

1. α2 – agonists are usually given 3 times a day.
2. Brimonidine is also formulated as a gel for the treatment of Facial Flushing Rosacea.
3. Apraclonidine usually used for maximum 1 month (short-term adjunctive treatment)
Brimonidine Eye drop Alphagan®, Brimogan®, Brimo® 0.1% , 0.15% , 0.2%
Apraclonidine Eye drop Lopidine®, Iopidine® 0.5% , 1%
D) Carbonic Anhydrase Inhibitors (CAI): (reduce formation of fluid)

1. CAIs are usually given 3 times a day.
2. Acetazolamide is also used as a diuretic in CHF edema or drug induced edema.
3. Acetazolamide, brinzolamide, and Dorzolamide are contra-indicated if history of
sulphonamide hypersensitivity.
➢ Acetazolamide may cause troublesome adverse effects, including tingling of the hands and
feet, the formation of kidney stones, and, rarely, kidney damage; thus, people with existing
kidney problems are not usually given this drug.
Dorzolamide Eye drop Trusopt® , Dorzoptic® , Xola® 2%
Brinzolamide Eye drop Azopt® 1%
Methazolamide Tab Neptazane® 25 mg , 50 mg
Acetazolamide Tab Cidamix® 125 mg , 250 mg
Cap ER Diamox Sequels® 500 mg
Inj. (powder) Diamox Sequels® 500 mg/vial

E) Miotics or Cholinergic agents: (Improve liquid discharge)
1. Miotics are usually given 3 times a day.
2. People receiving miotic eye drops are likely to notice darkening of vision and difficulty in seeing
in the dark. Increased shortsightedness may be noticeable.
Pilocarpine Eye drop Isopto Carpine® , Dropil® 10 mg (1%) , 20 mg (2%)
Carbachol Eye drop Miostat® 1.5 % , 3 %
Intraocular Solu. 100 mcg/ml
Echothiophate Eye drop Phospholine® 0.125%
F) Kho Kinase inhibitor

Netarsudil is a Rho kinase inhibitor with norepinephrine transport inhibitory activity that
reduces production of aqueous humour; it specifically targets the conventional trabecular
pathway of aqueous humour outflow to act as an inhibitor to the rho kinase and norepinephrine
transporters found there as opposed to affecting prostaglandin F2-alpha analog like mechanisms
in the unconventional uveoscleral pathway that many other glaucoma medications demonstrate.
➢ Netarsudil is indicated for the reduction of elevated intraocular pressure (IOP) in patients
with open-angle glaucoma or ocular hypertension
Netarsudil Eye drop Rhopressa® 0.02% (0.2 mg/ml)
Note: Combination Products for Glaucoma:

Those combine both the benefits of reducing the formation of the Aqueous Humor and increasing its
discharge.
Beta-blocker + CAI
Dorzolamide + Timolol Eye drop Cosopt® , Dorzoptic Plus® 2% + 0.5%
Xolamol®
Brinzolamide + Timolol Eye drop Azarga® (10 mg + 5 mg)/ml
Beta-blocker + α2–agonist
Brimonidine + Timolol Eye drop Combigan® 0.2% + 0.5% , (2 mg+5 mg)/ml
Beta-blocker + Prostaglandin analog
Latanoprost + Timolol Eye drop Xalacom® , Latancom® (50 mcg + 5 mg)/ml
Bimatoprost + Timolol Eye drop Ganfort® (0.3 mg + 5 mg)/ml
Travaprost + Timolol Eye drop Duotrav® (40 mcg + 5 mg)/ml
Beta-blocker + Miotic
Pilocarpine + Timolol Eye drop Fotil® , Fotil Forte® (20 mg + 5 mg)/ml
α2–agonist + CAI
Brimonidine + Eye drop Simbrinza® 0.2% +
Brinzolamide 1%
Prostaglandin analog + Kho kinase inhibitor
Latanoprost + Netarsudil Eye drop Rocklatan® 0.02% + 0.005%
** if the patient used a combination eye drop product of (Beta-blocker + α2–agonists or
Prostaglandin analog) and still not reduced the eye pressure to normal levels → the Physician
can add oral CAI to the regimen.
Second: Conjunctivitis
1. It’s simply mean inflammation of the conjunctiva and is characterized by varying degrees of
ocular redness, irritation, itching and discharge.
2. It can be due 3 main causes: (bacterial, viral and allergic forms), the table below will help to
distinguish between those 3 main types:
Notes:
1. Muco-purulent discharge is more suggestive of bacterial conjunctivitis especially if the eyes are
glued together in the absence of itching.
2. Photophobia is usually associated with serious eye pathology, ex: keratitis and uveitis.
3. Redness of the eyes with itching and pain with Vomiting suggests glaucoma
A) Eye Drops for Allergic/Irritant Conjunctivitis:

1. Irritation to the eye usually occurs when exposed to an irritant or allergen (such as pollen, dust),
or due a chemical substance that causes eye sensitization, Symptoms of eye irritation include:
Redness and itching with tears and possible swelling with a tingling feeling in the eye.
2. Allergic Conjunctivitis occurs in people who suffer other types of allergies, such as seasonal
allergies or asthma or allergic skin, so it may appear during certain times of the year such as the
spring and usually have severe redness and burning with tears.
3. So, for these two conditions there is a variety of treatment options:
1. Anti-histamine eye drops. 2. Mast cell stabilizer eye drops.
3. Corticosteroid eye drops. 4. NSAIDs eye drops.
5. Decongestant or (Decongestant + Anti-histamine) eye drops.
1. Anti-histamine Eye Drops:

Ophthalmic anti-histamines can be used for allergic conjunctivitis that is often associated with
allergic rhinitis, usually used 2 – 3 times daily.
Olopatadine * Eye Drop Pataday® , Patanot® , Olopat® 0.1% & 0.2%
Azelastine Eye Drop Optivar®, Allergodil® 0.05%
Ketotifen * Eye Drop Zaditor , Alaway , Cleroptic 0.025%
® ® ®
Cetirizine Eye Drop Zerviate® 0.24%

Alcaftadine Eye Drop Lastacaft ® 0.25%
Emedastine Eye Drop Emadine® 0.05%
Bepotastine Eye Drop Bepreve ® 1.5%
Epinastine * Eye Drop Elestat ® 0.05%
Levocabastine Eye Drop Livostin® 0.05%
* Olopatadine, Ketotifen and Epinastine also have a Mast cell stabilizing effect.

2. Mast cell stabilizer eye drops:
1. Mast cell stabilizers inhibits type-I immediate hypersensitivity reaction; also, may inhibit mast
cell release of inflammatory mediators.
2. All Mast cell stabilizers are used 4 times per day, Except Nedocromil which is used twice daily,
Treatment course is usually ranges from 4 weeks to 6 weeks.
Na+ Cromoglycate Eye drop Crolom® , Opticrom® , 4% (10 ml) ,
(or) Cromolyn Na+ Allergotin® 2% (10 ml)
Lodoxamide Eye drop Alomide® 0.1%
Nedocromil Eye drop Alocril® 2%
Pemirolast Eye drop Alamast® 0.1% (1 mg/ml)
3. Corticosteroids eye drops:

1. Used to prevent permanent damage to the eye, which may occur with certain eye problems (as
Iritis, Keratitis and Conjunctivitis), they also provide relief from redness, irritation, itching and
allergic reactions affecting the eye.
2. They should be used with caution for patients with the Glaucoma & Cataract, and they are
preferably not to be used more than about 7 – 10 days.
3. Topical corticosteroids are applied frequently for the first 24–48 hours; once inflammation is
controlled, the frequency of application is reduced.
Betamethasone Eye drop Methadin® 0.1 % (10 ml)
Dexamethasone Eye Drop Maxidex® 0.1%
Eye Oint. 0.05%
Hydrocortisone Eye Drop Hyrocort®, Opticort® 1%
Eye Oint. 1%
Fluorometholone Eye Drop FML® , Flucon® , FML Forte® 0.1% , 0.25% (Forte)
Fluorometholone + Eye Drop Fluca® (0.1% + 2 %)
Na+ Cromoglycate
Prednisolone Eye Drop Pred Mild® , Pred Forte® 0.12% , 1% (Forte)
Loteprednol Eye Drop Alrex® , Lotemax® 0.2% , 0.5%
Eye Gel Lotemax® 0.5%
Rimexolone Eye Drop Vexol® 1%
Difluprednate Eye Drop Durezol® 0.05%
4. NSAIDs eye drops:

1. They are used to suppress the optical mast cell responses to allergens including (but not
limited to) aerosolized dust particles and other allergens, also used as ophthalmic analgesics
or in allergic conjunctivitis to reduce the eye inflammation, they should be avoided in patient
with aspirin allergy.
Diclofenac Na+ Eye drop Diclogesic® , Voltaphtha® 0.1 %
Indomethacin Eye drop Indocollyre® 0.1 %
Flurbiprofen Eye drop Ocufen®, Fluroptic® 0.03 %
Bromfenac Eye drop Bromday® , Prolensa® 0.07 % , 0.09 %
Nepafenac Eye drop Nevanac® , ILevro® 0.1 % , 0.3 %
Ketorolac Eye drop Acular® , Acular LS® 0.5 % , 0.4 % (LS)

5. Decongestant or (Decongestant + Anti-histamine) eye drops:
1. These should be used for only a short time, to avoid a condition called (conjunctivitis
medicamentosa) that cause frequent redness and congestion of the eye, Used cautiously in
patients with Glaucoma, (Relative contraindication in Glaucoma).
2. They work by producing a temporary constriction of the conjunctival blood vessels, thereby
reducing eye redness.
3. Decongestants eye drops are beneficial when there is a swelling in the eye due to the
inflammation and vasodilation.
Decongestants
Naphazoline * Eye drop Naphcon® , Antistine® 0.025% , 0.1%
Phenylephrine Eye drop Apifrin®, Mydfrin® 2.5%
Oxymetazoline Eye drop OcuClear® , Nasordin® 0.05%
Tetrahydrozoline Eye drop Tetryzoline® , Tyzine® 0.05% , 0.01%
Decongestant + Anti-histamine
Naphazoline + Eye drop Naphcon A® , Visine A® 0.025% +
Pheniramine 0.3%
Naphazoline + Eye drop Antistine-Privine® , Apihist® , 0.025% +
Antazoline Ophtazoline® 0.5%
Naphazoline + Eye drop Nozeylin® , Prisoline® (0.5 mg + 0.5 mg)/ml
Chlorpheniramine
Decongestant + Ocular Wash
Naphazoline + Sulfophenate Eye drop Oftalmil® (0.16 gm + 0.2 gm)/10 ml
Naphazoline + Glycerin Eye drop Clear Eyes® 0.03% + 0.5%
Tetrahydrozoline + Zinc Sulfate ** Eye drop Visine AC® 0.5%
0.05% + 0.25%
* (Naphazoline and Naphthazoline) is the same drug.
** Zinc sulfate act as astringent to relief burning and itching.
B) Drops for other types of Conjunctivitis:

These include:
1. Antibacterial eye preparations for Bacterial Conjunctivitis
2. Combination drops containing (Antibacterial + Corticosteroid) for mixed type of
Conjunctivitis.
3. Antiviral eye preparation for Viral Conjunctivitis
4. Antifungal eye preparation for fungal keratitis
Bacterial eye infections are generally treated topically with eye drops and eye ointments (3),
Frequency of application depends on the severity of the infection.
a. Drops are applied as frequent as 1 drop every 2 hours, continue for 48 hours after
healing.
b. Eye ointment, apply either at night (if eye drops used during the day) or 3–4 times daily
(if eye ointment used alone).
Common anti-infective’s available as an eye preparation include:
1. Quinolones: ciprofloxacin, levofloxacin, moxifloxacin, and ofloxacin.
2. Aminoglycosides: gentamicin, neomycin, and tobramycin
3. Macrolides: Azithromycin, Erythromycin.
4. Others: Chloramphenicol, Tetracycline, Polymyxin B, Fusidic acid.
5. Anti-Virals (Mainly Acyclovir), and Anti-Fungals.

A) Ophthalmic Quinolones:
Ciprofloxacin Eye drop/Oint. Ciprodar® , Ciloxan® 0.3% (both)
Ofloxacin Eye drop Ocuflox® 0.3%
Norfloxacin Eye drop Chibroxin® , Apiflox® 0.3%
Lomefloxacin Eye drop Okacin® 0.3%
Levofloxacin Eye drop Iquix® , Quixin® , Vefloxin® 0.5% , 1.5%
Moxifloxacin Eye drop Vigamox® , Moxeza® 0.5%
Eye Oint. Moxicip® 0.5%
Besifloxacin Eye drop Basivance® 0.6% (5 ml)
Gatifloxacin Eye drop Zymar® , Tequin® , Zymaxid® 0.3% , 0.5%
B) Ophthalmic Aminoglycosides:
Gentamicin Eye drop/Oint. Gentak , Gendin
® ® 0.3%
Tobramycin Eye drop/Oint. Tobrex ® 0.3%
Natamycin * Eye drop Natacyn , Pimaricin
® ® 5%
Neomycin Comes in Combinations Only
* Natamycin also has an anti-fungal activity. (2)
C) Ophthalmic Macrolides:
Azithromycin Eye drop Azasite® , Azyter® 1% , 1.5% (2.5 ml)
Eye Oint. Optithrocin® 1%
Erythromycin Eye Oint. ILotycin® , Erythrocin® 0.5%
D) Other Ophthalmic Antibacterial preparations:

Chloramphenicol Eye Oint. Samaphenicol® 1%
Eye drop 0.5%
Tetracycline Eye Oint. Samacycline® 1%
Fusidic acid Eye Oint. Fucithalmic ® 1% (5 mg/Tube)
Polymyxin B Comes in Combinations Only
Bacitracin Eye Oint. Beocin® 500 Unit/gm (3.5 gm)
Sulfisoxazole Eye drop Gantrisin® 4%
Sulfacetamide Eye drop Cetamide® , Ocusulf® 10% , 20% , 30%
Eye Oint. 10%
Note1: Combination products of antibacterial eye drops

Polymyxin B + Bacitracin Eye Oint. Polycin® (10,000 Unit + 500 Unit)/gm
Neomycin + Polymyxin B Eye Oint. Neo-Polycin® (400 Unit + 3.5 gm
+ Bacitracin + 10,000 Unit)/gm
Neomycin + Polymyxin B Eye Oint. , Neo-Sporin® 3.5 gm (Oint.) ,
+ Gramicidin Eye Drop 10 ml (drop)
Polymyxin B + Eye Drop Polytrim® (10,000 Unit + 1 mg)/ml
Trimethoprim
Note2: antibacterial ophthalmic preparations combined with corticosteroid (2)
Scientific name(s) Dosage form Trade name concentration
Betamethasone + Eye drop Methadin-N®, 0.1% +
Neomycin Ophamesone-N ® 0.5%
Dexamethasone + Eye drop Neo-dexon® 0.1% +
Neomycin 0.5%
Tobramycin + Eye drop, Tobradex® (0.3% + 0.05%),
Dexamethasone Eye Oint. (0.3% + 0.1%)
Tobramycin + Eye drop Zylet® 0.3% +
Loteprednol 0.5%
Chloramphenicol + Eye drop Dexachlor® (4 mg + 1 mg)/ml
Dexamethasone
Dexamethasone + Eye drop, Maxitrol® , Dexasporin®, (0.1%+3.5gm+10,000 Unit)/ml
Neomycin + Eye Oint. PND®, Dexatrol®
Polymyxin B (0.1%+3.5gm+10,000 Unit)/gm
Framycetin + Eye drop, Sofradex ® 5 mg +
Gramicidin + Ear Drop 0.05 mg +
Dexamethasone 0.5 mg
Framycetin + Eye drop Frakidex® 630,000 IU +
Dexamethasone 100 mg (per 100 ml)
Gentamycin + Eye drop, Pred G® (0.3% + 1%) drop,
Prednisolone Eye Oint. (0.3% + 0.6%) Oint.
Sulfacetamide + Eye drop, Cetapred ,
® 10% +
Prednisolone Eye Oint. Blephamide ® 0.2%
Note3: Special Eye drop Combinations
Trade Name D. form Scientific name(s) concentration
Tafazol ® Eye drop Sulfacetamide + Phenolsulphonate (30 mg + 5 mg
+ Naphazoline + Lidocaine + 0.05 mg + 7.5 mg) Per ml
Vasosulf® Eye drop Sulfacetamide + Phenylephrine 15%
Clogenta® Eye drop Gentamycin + Diclofenac Na+ (3 mg + 1 mg)/ml
Loxtra® Eye drop Ofloxacin + Prednisolone (3 mg + 2 mg + 0.4 mg)/ml
+ Tetrahydrozoline
Ocumethyl® Eye drop Naphazoline + Diphenhydramine (10 mg + 10 mg
+ Zinc Sulfate + 10 mg) (per 10 ml)
E) Ophthalmic Antivirals: (For Viral Conjunctivitis)

Commonly used antivirals are (Acyclovir or Ganciclovir) for herpes simplex infections.
Frequency of administration may reach 5-6 times a day, duration range 14-20 days
Acyclovir Eye Oint. Zovirax , Veramed
® ® 1%
Idoxuridine * Eye drop Idoxol , Dendrid
® ® 0.1%
Eye Oint. Dendrid ® 0.5%
Ganciclovir * Eye Gel Zirgan , Vitrasert
® ® 0.15% (5 gm)
Ocular Implant * 4.5 mg
Vidarabine Eye drop Vira-A® 3%
Trifluridine Eye drop Viroptic ® 1%
* Idoxuridine is used only topically due to cardio toxicity. (2), it’s not available in USA.
** Ganciclovir Ocular Implant is inserted as intra-vitreal every 5 to 8 months. (2)
F) Ophthalmic Antifungals:
1. Used in the treatment of fungal keratitis (although I.V. Antifungals as Amphotericin B is the 1st
line therapy for such cases), Available Ophthalmic antifungals include: Fluconazole, Natamycin
and Boric acid.
2. Boric acid has mild antibiotic properties against fungal or bacterial infection, it is also used
as an eye wash to cleanse or irrigate the eyes. It provides soothing relief from eye irritation, and
helps remove pollutants from the eye such as smog, chlorine, or other chemicals.
Fluconazole Eye drop Fluzamed® 3 mg/ml (5 ml)
Itraconazole Eye drop Entozole® 1% (5 ml)
Natamycin * Eye drop Natacyn® , Pimaricin® 5%
Micafungin Eye drop MCFG® 0.1%
Boric acid Eye drop Collyrium Fresh® -------------
* Natamycin also has an antibacterial activity.
Third: Lubricating Eye Drops (Tear’s Deficiency)

1. Artificial tear preparations act by stabilizing the tear film (by increasing the viscosity of tear
thus decrease evaporation), Examples are: Hypromellose (hydroxypropyl methylcellulose),
Carmellose, polyvinyl alcohol and Carbomers.
2. Some of these products may be available as pack that contain single dose eye drops (28 or 30
single dose eye drops); that contain small volume usually 0.4 mL and each drop is intended for
single use only.
3. Some of these products may be available as preservative free eye drops; if a patient is likely to
be using artificial tears for a long time, a preservative-free preparation should be considered
because the prolonged exposure of the eye to the preservative (mostly it is Benzalkonium
Chloride) can produce damage to the cornea.
4. Artificial tears are used for the treatment of dry eye in the following cases:
a. Dry eye caused by conditions such as the temporary use of the computer for long periods
of time or because of the sun, wind, eye fatigue or for whatever reason.
b. Dry eye caused due to aging, as well as post-menopausal women.
c. Dry eye resulting from the use of certain medications such as antihistamines and birth
control pills, as well as chemical treatments for cancer patients.
d. Dry eye caused by some diseases that affect the eye’s ability of secreting tears (Sjögren’s
syndrome, rheumatoid arthritis, and collagen vascular diseases).
e. Dry eye caused by a defect in the eyelid, which makes the eyelid does not close completely,
as happens in cases of nerve VII damage.
f. Dry eye resulting from the use of or contact lenses after LASIK operations.
5. The function of these drops is adding some elements of the natural tears that already exist in the
eye, that give some comfort.
6. Decongestant eye drops must be avoided in such cases, it may remove redness shortly, but
in the long term of use it will cause dryness of the eye.
Eye Lubricants are divided into three types:

A) Drops with preservatives:
1. Often come in multi-dose bottles and contain preservatives that inhibit the growth of bacteria
and used 3-4 times per day, Examples include: (Genteal, Optive, Refresh Tears, Isotears, Hylo-
Comod, Hameron)
2. Most eye drops contain preservatives that inhibit bacterial growth and keep them safer, but
some people are sensitive or even allergic to these preservatives, so keep in mind that eye
drops containing preservatives actually can cause irritation, redness and more dryness, rather
than easing these symptoms.
3. Classification of Preservatives:
a. Detergent Preservatives: cause bacterial cell death by way of interrupting the lipid
component of cell membranes. The contents of the microbial cell are extruded from the cell
due to membrane instability, ex: Benzalkonium Chloride (BAK) and cetrimonium,
Chlorobutanol, Edetate Disodium, Polyquaternium-1, Polyhexamethylene.
b. Oxidizing Preservatives: alter the lipid membrane of microbes in a different fashion to
detergent preservatives, by penetrating the membrane and altering the DNA, protein and
lipid components of bacterial cells, ex: sodium perborate, stabilized oxychloro complex.
c. Ionic-buffered Preservatives: a combination of boric acid, zinc, sorbitol and propylene
glycol, they induce less cytotoxicity to the ocular surface compared with conventional
preservatives, Ex: SofZia.
Trade Name D. form Scientific name(s) concentration
Genteal® Eye Drop Hypromellose 0.3%
Artelac® Eye Drop Hypromellose 1.6 mg/0.5 ml
Slezin® Eye Drop Hypromellose + Dextran (3 mg + 1 mg)/ml (15 ml)
Septoclear Tears®, Eye Drop Hypromellose + Dextran 70 0.3% + 0.1%
Tears Natural® (Benzalkonium CL as presrev.)
Tears Natural II® Eye Drop Hypromellose + Dextran 70 0.3% + 0.1%
(Polyquaternium as presrev.)
Optive® Eye Drop Carmellose + Glycerol 10 ml
Refresh Tears® Eye Drop Carboxymethylcellulose Na+ 0.5%
Refresh Optive® Eye Drop Carboxymethylcellulose Na+ 0.5% + 1% + 0.5%
+ Glycerin + Polysorbate 80
Liquifilm Tears® Eye Drop Polyvinyl alcohol 1.4%
Natural Tears® Eye Drop Polyvinyl alcohol + Povidone 0.5% + 0.6% (15 ml)
Isotears® Eye Drop Methylcellulose 0.3 %
Hylo-Comod®, Eye Drop Sodium Hyaluronate 1 mg/1 ml (10 ml)
Hameron®, HeyFresh®
* Hypromellose = Hydroxypropyl methylcellulose, they are the same.
* Carmellose = Carboxymethylcellulose, they are the same.
B) Drops free of Preservatives:

1. These drops are best used when there is a moderate or severe Dryness and usually each dose
comes in a separate package for single use only, such as: TheraTears, Refresh Plus, Catinorm
and Systane.
Trade Name Dosage form Scientific name(s) concentration
TheraTears® Eye drop Carmellose sodium 2.5 mg/ml (0.25%)
Refresh Plus® Eye drop Carboxymethylcellulose Na+ 0.5%
Artelac Advanced Eye drop
® Hyaluronic acid 0.2%
Refresh Optive ® Eye drop Carboxymethylcellulose Na + 0.5% + 1% + 0.5%
Advanced + Glycerin + Polysorbate 80
Catinorm® Eye drop Glycerol + Tyloxapol + 10 ml
Poloxmar 188
Systane ® Eye drop Polyethylene Glycol 400 + 0.4% + 0.3%
Propylene Glycol (15 ml, 30 ml)
C) In Form of Gel:
1. It is the best option for chronic use, used only before going to sleep (because it causes Blurred
vision), their effect is characterized by long term and give comfort for a longer period; they
include: Viscotears Gel, Refresh Celluvisc, Refresh Liquigel, Genteal Gel, and Liposic Gel.
Genteal Gel® Eye Gel Hypromellose 0.2%
Viscotears Gel® , Eye Gel Carbomer 2.0 mg/g
Liquivisc® , Liposic®
Refresh Celluvisc® Eye Gel Carboxymethylcellulose Na+ 1% (Preservative Free)
Refresh Liquigel® Eye Gel Carboxymethylcellulose Na+ 1%
Systane Gel® Eye Gel Polyethylene Glycol 400 + 0.4% + 0.3%
Propylene Glycol (Preservative Free)
Note: Some Eye lubricants also contain a decongestant as:
Clear Eyes® Triple Eye drop Polyvinyl alcohol + Povidone 0.5% + 0.6%
Action + Tetrahydrozoline + 0.05%
Clear Eyes® Maximum Eye drop Glycerin + Naphazoline 0.25% + 0.012%
Eye Relief + Zinc sulfate + 0.25%
Clear Eyes® Complete Eye drop Hypromellose + Naphazoline 0.2% + 0.025%
Symptom Relief + Polysorbate 80 + Zinc Sulfate + 0.5% + 0.25%
Fourth: Other Types of Ophthalmic Drops:

A) Drops that Extend the Iris (Mydriatics/Cycloplegics):
1. These are used during eye examination to let the doctor to see the details of the interior of the
eye (cause Mydriasis), also used for children when prescribing glasses for them. Ex: Atropine.
2. These are Anti-Cholinergics, they block the action of acetylcholine resulting in relaxation of the
cholinergic innervated sphincter muscle of the iris, also cholinergic stimulation of the
accommodative ciliary muscle of the lens is also blocked, leading to the dilation of the pupil
(Mydriasis) and paralysis of accommodation (Cycloplegia).
3. The use of these drops causes blurred vision for a period ranging between 3 - 8 hours,
especially for near vision, so it is advisable to avoid driving a car meanwhile.
Atropine Eye drop Isopto Atropine® 0.5% , 1%
Eye Oint 1%
Tropicamide Eye drop Mydriacyl®, Midax®, Mydrapid® 0.5% , 1% (15 ml)
Cyclopentolate Eye drop Cyclogyl® 0.5% , 1% (15 ml)
Homatropine Eye drop Isopto Homatropine® 2% , 5%
Scopolamine Eye drop Isopto Hyoscine® 0.25%
Note: Some Mydriatics comes in combination product, which has been shown to induce
Mydriasis greater than of each drug alone.
Scientific name (s) D. form Trade name concentration
Cyclopentolate + Phenylephrine * Eye drop Cyclomydril ® 0.2% + 1%
Scopolamine + Phenylephrine Eye drop Murocoll-2® 0.3% + 10%
Tropicamide + Hydroxyamphetamine Eye drop Paremyd ® 0.25% + 1%
* Phenylephrine acts directly on alpha-adrenergic receptors in eye producing contraction of dilator
muscle of pupil & constriction of arterioles in conjunctiva.
B) Anesthetic Eye Drops:
1. Ophthalmic Anesthetics are used in the initial assessment of minor eye trauma, the removal of
superficial foreign bodies; measurement of intraocular pressure using applanation tonometry
and in ocular surgery, a recent application in the correction of strabismus is being explored.
2. These agents should not be used for long-term management of ocular pain: they are toxic
to the corneal epithelium; they also abolish the corneal reflex so increasing the risk of corneal
damage.
Lidocaine Eye drop Akten® 35 mg/ml
Eye Gel 3.5%
Proparacaine Eye drop Alcaine® , Ophthaine® 0.25% , 0.5%
Tetracaine Eye drop Pontocaine® , TetraVisc® 0.5%
Benoxinate * Eye drop Novesine , Burokain
® ® 0.4%
Oxybuprocaine * Eye drop Colircusi® 0.4%
* Comes in a single dose unit containing 0.5 ml, each carton contains 20 single unit. (2)
* Benoxinate = Oxybuprocaine, they are the same drug.
Combinations products of Ophthalmic Anesthetics:

Oxybuprocaine + Tetracaine Eye drop Colircusi Double ® (4 mg + 1 mg)/1 ml
Oxybuprocaine + Chlorhexidine Eye drop Désomédine ® (4 mg + 0.6 mg)/1 ml
Benoxinate + Fluorescein * Eye drop Fluress® , Fluorox® (0.4% + 0.25%)
Proparacaine + Fluorescein Eye drop Fluorocaine® (0.5% + 0.25%)
* Fluorescein when gets in contact with aqueous humor it increases intensity of green
fluorescence (helps to see the details of the interior eye).
C) Anti-Cataract Eye Drops:

1. A cataract is a clouding of the lens in the eye that blurs vision, changes the way you see colors
(they seem faded) and generally reduces visual acuity; Cataracts usually are age-related, and
may occur due Diabetes and other metabolic disorders, and due accumulated free-radical
damage to the protein molecules that form the lens of the eye; once cataracts form, they tend to
grow, clouding larger and larger areas of the lens.
2. Cataracts are the most common cause of blindness, and are conventionally treated with
surgery; Visual loss occurs because opacification of the lens obstructs light from passing and
being focused on to the retina at the back of the eye; Also, the use of the oral antioxidants can
be useful in cases of accumulated free-radical damage.
Azapentacene Eye drop Cataxol® , Lutrax® 0.15 mg/ml (15 ml)
Pirenoxine Eye drop Catalin®, Clarvisan® 0.8 mg /15 ml
N – Acetyl Carnosine Eye drop Can-C® 1%
Combination drops for Cataracts
N – Acetyl Carnosine + Eye drop Oxymoist® 10 mg +
Carboxymethylcellulose 3 mg
+ Boric Acid + Glycerin + 3 mg + 10 mg
K+ Iodide + Na+ Iodide Eye drop Vitreolent® 0.3% + 0.3% (10 ml)
K+ Iodide + Ca+ Chloride Eye drop Catagon® , Catarest® (3.3% + 1% + 0.83%)/(5 ml)
+ Na+ Chloride
D) Other Drops Types:
Taurine * Eye drop Bestoxol® 0.4 gm /8 ml
Cysteamine ** Eye drop Cystaran® 0.44%
Cyclosporine ** Eye drop Restasis® 0.05%
Notes:
1. Taurine is an organic amino acid which has anti-inflammatory and analgesic properties,
Taurine Eye Drops is used to treat cataracts caused by taurine metabolic disorders also can be
used for the treatment of herpes conjunctivitis, viral conjunctivitis, adjuvant therapy, and acute
conjunctivitis, also can be used for Glaucoma (open-angle).
2. Cysteamine is indicated for Corneal Cysteine Crystal accumulation.
3. Cyclosporine (immunosuppressant) drop is designed to increase tear production in patients
with dry eyes, (it appears to work by decreasing swelling in the eyes; thus, increasing tear flow).
➢ It’s licensed for severe keratitis in patients with dry eye disease.
Fifth: Intra-vitreal Eye Injections:

1. Intra-vitreal is a route of administration of a drug directly into the eye; it has become a popular
method of treatment of many retinal diseases, commonly including AMD, Diabetic Retinopathy,
and Retinal Vein Occlusions.
2. This technique is very helpful and has the advantage of the direct effect and the fast onset,
BENEFITS of Intra-vitreal Injections depend on the ocular pathology being treated, but mainly
include improvement of vision or prevention of worsening of the vision (in the case of AMD or
DR). In the case of an infection, the benefit is direct delivery of the antibiotic/antifungal into the
eye close to the nidus of the infection.
3. But it’s also associated with many Risks, including: Pain, Bleeding, retinal tear/detachment,
Cataract (from inadvertently hitting the lens), Loss of vision, Increased IOP, with damage to optic
nerve.
4. This procedure is performed in your doctor's office and requires only a local anesthetic. Before
the medication is injected, the eye is numbed with anesthetic eye drops to help minimize
discomfort; the eye is then cleaned with an antiseptic solution; the medication is then injected
directly into the eye.
5. Intra-vitreal injections may be administered as frequently as once a month, depending on the
condition being treated, in order to maintain eye health and optimize the vision.
6. Common available Intra-vitreal Medications:
a. Bevacizumab (Avastin®) 1.25 mg/0.05 ml (0.675 mg/0.03 ml if considering using for
treatment of Zone I+ ROP in an infant)
b. Ranibizumab (Lucentis®) 0.5 mg/0.05 ml
c. Ganciclovir Intra-vitreal 2.5 mg/0.05 ml (twice weekly for CMV Retinitis)
d. Foscarnet Intra-vitreal 2.4 mg/0.1ml
e. Vancomycin 1 mg/0.1ml
f. Ceftazidime 2.25 mg/0.1ml
g. Amikacin 0.4 mg/0.1ml
h. Amphotericin B 0.1 ml of 5-10 mcg/ml
i. Dexamethasone 0.4 mg/0.1 ml
j. Triamcinolone 0.1cc of 4mg/ml (Triesence® is alcohol-free preparation that is FDA
approved for intraocular use)

Sixth: Other drugs for retinal disorders:
Available pharmacological option(s) for different retinal disorders are listed below:
Retinal disorder Available pharmacological option(s)
Age-related macular Aflibercept, Pegaptanib, Ranibizumab and Brolucizumab
degeneration (vascular endothelial growth factor inhibitors)
Fluocinolone acetonide, Aflibercept,
Macular edema
Dexamethasone, and Ranibizumab,
Optic neuropathy Idebenone (nootropic and antioxidant)
Vitreomacular traction Ocriplasmin (recombinant proteolytic enzymes)

Aflibercept Intra-vitreal inj. Eylea® 2 mg/0.05 ml (40 mg/ml)
Pegaptanib Intra-vitreal inj. Macugen® 0.3 mg/90 mcl
Ranibizumab Intra-vitreal inj. Lucentis® , Accentrix® 0.3 mg , 0.5 mg
Brolucizumab Intra-vitreal inj. Beovu® 6 mg/0.05 ml
Ocriplasmin Intra-vitreal inj. Jetrea® 0.5 mg/0.2 ml
Verteporfin Vial Visudyne® 15 mg
References
1- Rosemary R. Berardi. Handbook of Nonprescription Drugs: 18th Edition
5- Sean C. Sweetman. Martindale: The Complete Drug Reference, 38th Edition. Ph. Press
7- Comprehensive Ophthalmology, 4th Edition, by A.K. Khurana.

EAR, NOSE, AND THROAT
Chapter Thirteen: Ear, Nose, and Throat
13.1- Drugs acting on the Ear
(Otics)
1. Guidelines for administering Ear
drop (teach the patient)
2. Treatment of Otitis Externa
3. Treatment of Otitis Media
4. Removal of Ear Wax (Cerumen)
5. Complications of the Otitis Media
➢ Vertigo
➢ Ménière’s disease:
➢ Tinnitus
13.2 - Drugs acting on the Nose

➢ How to use Nasal Products: (teach
the patient)
1. Drugs used in Nasal Allergy
A. Nasal Corticosteroids
B. Nasal Mast-cell stabilizers
and Anticholinergics
C. Nasal Antihistamine
2. Sinusitis
A. Topical Nasal Decongestants
B. Oral Decongestants
13.3 - Drugs acting on the

Oropharynx (Mouth & Throat)
First: Mouth Ulcers
➢ Topical corticosteroids (For Mouth
Ulcers)
Second: Oral Thrush

➢ Topical antifungals
➢ Other Products for Oral Thrush
Third: Third: Dry Mouth (Xerostomia)
Fourth: Mouth Products

A. Mouthwashes and Gargles
B. Mouth sprays
C. Lozenges
D. Tooth Pastes
Sam’s Guide: Chapter 13 – ENT
Chapter Thirteen: Ear, Nose, and Throat
13.1-Drugs acting on the ear (Otics)
13.1.1 Guidelines for administering Ear drop (teach the patient)
1-Wash your hands with soap and warm water; then dry them thoroughly.
2-Carefully wash and dry the outside of the ear, taking care not to get
water in the ear canal.
3-Warm eardrops to body temperature by holding the container in
the palm of your hand for a few minutes. Do not warm the container
in hot water. Hot eardrops can cause ear pain, nausea, and dizziness.
4-If the label indicates, shake the container.
5-Tilt your head (or have the patient tilt his or her head) to the side,
as shown in drawing A. Or lie down with the affected ear up, as shown
in drawing B. Use gentle restraint, if necessary, for an infant or a
young child.
6-Open the container carefully. Position the dropper tip near, but not
inside, the ear canal opening. Do not allow the dropper to touch the
ear, because it could become contaminated or injure the ear. Eardrop
bottles must be kept clean.
7-Pull your ear (or the patient's ear) backward and upward to open
the ear canal (see drawing A). If the patient is a child younger than 3
years old, pull the ear backward and downward (see drawing B).
8-Place the proper dose or number of drops into the ear canal.
Replace the cap on the container.
9-Gently press the small, flat skin flap (tragus) over the ear canal
opening to force out air bubbles and push the drops down the ear
canal.
10-Stay (or keep the patient) in the same position for the length of
time indicated in the product instructions. If the patient is a child who
cannot stay still, the primary care provider may tell you to place a clean piece of cotton gently
into the child's ear to prevent the medication from draining out. Use a piece large enough to
remove easily, and do not leave it in the ear longer than an hour.
11-Repeat the procedure for the other ear, if needed.
12-Gently wipe excess medication off the outside of the ear, using caution to avoid getting
moisture in the ear canal.
13.1.2 - Treatment of Otitis Externa
1. Otitis Externa is a general term used to describe inflammation of the skin of the external
auditory canal that may be due to infection with bacteria, viruses, or fungi or secondary to skin
disorders such as eczema.
2. Otitis Externa may be acute or chronic; the treatment of both acute and chronic otitis Externa
includes thorough cleansing and the use of appropriate antibacterial ear drops, with or
without a corticosteroid, even though some have doubted the value of topical Antibacterials
(Topical corticosteroids are used to treat inflammation and eczema in otitis Externa; if infection
is present, the corticosteroid is used in combination with a suitable anti-infective).
3. Ear drops containing aminoglycosides (Gentamicin, Neomycin, Framycetin, or Polymyxin)
should not be used when the ear drum is perforated (the risk of ototoxicity).
4. Generally ophthalmic preparations containing antibiotics and/or corticosteroids can be used in
the ears.
• See chapter 12, for ophthalmic antibiotics.
• See chapter 12, for ophthalmic Corticosteroids and NSAIDs.
• See chapter 12, for combinations of antibiotics + Corticosteroids.
5. These drops are designed for Otic use:
Acetic Acid * Otic Drop VoSol® 2%
Ciprofloxacin Otic Drop Cetraxal® 0.2% (0.25 ml single use)
Ofloxacin Otic Drop Floxin® 0.3%
Finafloxacin Otic Drop Xtoro 0.3%
* Acetic Acid has an antibacterial/antifungal activity.
6. Otic Combination Products:

Phenazone + Chlorbutol * Otic Drop Otocalm® 5% + 1%
Phenazone + Lidocaine * Otic Drop Otipax® 0.64 gm + 0.16 gm
Ciprofloxacin + Otic Drop Ciprodex® 0.3% + 0.1%
Dexamethasone
Ciprofloxacin + Otic Drop Cipro HC® 0.2% + 1%
Hydrocortisone
Ciprofloxacin + Otic Drop Otovel® 0.3% + 0.025%
Fluocinonide
Acetic Acid + HC Otic Drop VoSol Plus® 2% + 1%
Clotrimazole * + Otic Drop Candid® 1% +
Lignocaine 2% (per 10 ml)
Hydrocortisone + Otic Drop Otosporin , Cortisporin
® ® (1% + 0.35% + 10,000 Unit)
Neomycin + Polymyxin B Per 1 ml
Hydrocortisone + Otic Drop Coly-Mycin S® (3.3 mg + 10 mg + 3 mg
Neomycin + Colistin + 0.5 mg) Per 1 ml
+ Thonzonium
Polymyxin B + Neomycin Otic Drop Flavaco® 0.1% + 0.25%
+ Hydrocortisone + + 0.02% +
Aminacrine + Benzocaine 0.1% + 2%
* Phenazone (Tropex ) is an analgesic, a NSAID drug and an antipyretic.
®
* Chlorbutol (or Chlorobutanol) has mild antibacterial and antifungal properties.

* Clotrimazole is a topical antifungal, Lignocaine is a topical anesthetic.
13.1.3 - Treatment of Otitis Media

1. Otitis media is a general term used to describe inflammation of the middle ear that usually
results from dysfunction of the Eustachian tube after a viral infection of the nasopharynx. It is one
of the most frequent childhood illnesses seen in general practice.
2. Acute otitis media is the commonest cause of severe ear pain in small children.
3. Its common practice to prescribe a systemic antibacterial with an analgesic for otitis media,
although the need for routine antibacterial treatment is questionable.
4. The American Academy of Pediatrics has produced guidelines for the diagnosis and management
of uncomplicated acute otitis media (AOM) in children from 2 months to 12 years of age; they
suggest that these children should be given symptomatic treatment and observed for 48 to
72 hours; if the illness worsens during the observation period or there is no improvement
then systemic Antibacterials should be considered.
5. Pain management is important, and appropriate analgesics should be offered, if antibacterial
treatment is given → high dose amoxicillin (80 to 90 mg/kg daily) is recommended for most
children, Alternative choices include cephalosporins or macrolide antibiotics, if there is no
improvement after three days, switching antibiotics should be considered.
13.1.4 - Removal of Ear Wax (Cerumen)
A) Non-pharmacologic Therapy:
1. The only recommended non-pharmacologic method of removing cerumen is to use a wet,
wrung-out washcloth draped over a finger.
2. The common use of cotton-tipped swabs to remove earwax is ineffective and potentially
dangerous, increasing the risk of Otitis Externa and leading to perforation of the eardrum.
B) Pharmacologic Therapy (Cerumenolytics):
These agents used to soften ear wax examples are:
1. Sodium bicarbonate (freshly prepared): This product should be instilled two to three times
a day for up to 3 days.
2. Docusate (dioctyl sodium sulpho-succinate) (Dewax®): The manufacturers of Dewax®
recommend that adults and children use enough ear drops to (Fill) the affected ear on not
more than two consecutive nights (don’t use more than 2 days).
3. Carbamide peroxide: when it makes contact with the tissue, oxygen is released, producing
a foaming action. This foaming action softens impacted cerumen, (used as 5 – 10 drops every
12 or 8 hours), don’t use more than 4 days.
4. Olive oil (sweet oil) is used to soften earwax and alleviate itching.
5. Hydrogen peroxide may be diluted 1:1 with warm water and instilled in the ear to aid in
cerumen softening and removal.
Dioctyl Sodium Sulpho- Otic Drop Dewax ® 5 mg/ml
Succinate
Carbamide Peroxide Otic Drop Debrox®, Oticlean®, Murine® 6.5% , 10%
Triethanolamine Otic Drop Cerumenex® 10%
Arachis Oil + Chlorobutanol Otic drop Cerumol ® Herbal Combination
+ Dichlorobenzene
13.1.5 – Complications of the Otitis Media

A) Vertigo:
Vertigo is a spinning sensation in the head often accompanied by nausea and vomiting, it is
usually caused by a disease affecting the organ of balance in the inner ear; It is a loss of
equilibrium in which one might describe a room as spinning, the vestibular compartment of the
inner ear is responsible for maintaining balance and Equilibrium, and the autonomic system may
become involved if the vertigo is severe, producing dizziness, pallor, sweating, and nausea.
B) Ménière’s disease:
a disorder in which excess fluid builds up in the inner ear, causing vertigo, noises in the ear,
and gradual deafness; In severe cases of Ménière disease; the doctors sometimes tend to do
some kind of destructive surgery by injecting an aminoglycoside to the inner ear, to benefit
from its side effect (vestibular ototoxicity) in controlling the Tinnitus.
➢ It is usually treated with Cinnarizine, Betahistine, Prochlorperazine, or an anti-anxiety
drug. A diuretic may also be given to reduce the excess fluid in the ear.
C) Tinnitus:
It’s may be described by patients as a ringing, buzzing, hissing, whistling, or humming noise
Lasting from seconds to minutes. Tinnitus has been linked to a variety of causes, including
Ménière disease, head injuries, otitis media, syphilis, temporomandibular-joint (TMJ)
dysfunction, and certain medications (NSAIDs, loop diuretics, and chemotherapeutic agents).
Note: Betahistine and Cinnarizine are used in the treatment of Vertigo and Tinnitus.
(See Chapter 4, section 6, for more details)
Betahistine Tab Betaserc® 8 mg , 16 mg
Cinnarizine Tab Stugeron® 25 mg
Cap 75 mg
13.2 - Drugs acting on the Nose

1. Allergic rhinitis, also known as hay fever, is a type of inflammation in the nose which occurs
when the immune system overreacts to allergens in the air; signs and symptoms include a runny
or stuffy nose, sneezing, red, itchy, and watery eyes, and swelling around the eyes.
2. Treatment options include:
1. Intra nasal corticosteroids (1st line therapy), see below.
2. Oral antihistamine (1st line therapy), see chapter 1.
3. Oral Leukotriene receptor antagonist, see chapter 1.
4. Intra nasal antihistamine, see below.
5. Decongestants, see below; and for more combination products see chapter 1
6. Intra nasal mast cell stabilizer, see below.
7. Intra nasal muscarinic/anticholinergic, see below.
➢ Nasal sprays are preferable for adults and children aged over 6 years because spray has
a faster onset of action and cover a large surface area.
➢ Nasal drops are preferable for children aged below 6 years because their nostrils are not
sufficiently wide to allow effective use of sprays.
How to use Nasal Products: (teach the patient)

13.2.1 - Drugs used in Nasal Allergy:
A) Intra Nasal Corticosteroids
1. Nasal preparations containing corticosteroids have a useful role in the prophylaxis and
treatment of allergic rhinitis (3), Regular use is essential for full benefit and it takes several
days before full effect is reached; Considered as 1st line therapy; they reduce sneezing, itching,
rhinorrhea and congestion; They are more effective than intra nasal/oral antihistamines in
the treatment of persistent or sever rhinitis.
2. Triamcinolone, Mometasone, Fluticasone Furoate can be used form age of 2 years and above.
3. Beclomethasone, Budesonide, Ciclesonide can be used from age of 6 years and above.
Scientific name Dosage form
Trade name concentration
Betamethasone Nasal dropMethadin® 0.1 % (10 ml)
Beclomethasone Nasal spray
Beconazse® 42 mcg/spray
Budesonide Nasal spray
Rhinocort Aqua®, Cortinase® 32 mcg , 64 mcg (per Actuation)
Mometasone Nasal spray
Nasonex® , Momate® 50 mcg/spray
Triamcinolone Nasal spray
Nasacort® 55 mcg/spray
Ciclesonide Nasal spray
Omnaris® 50 mcg (per Actuation)
Flunisolide Nasal spray
Aerospan nasal® 25 mcg (per Actuation)
Fluticasone Nasal spray
Flonase® , Flixonase® 50 mcg/spray
Combination products
Fluticasone + Azelastine * Nasal spray Dymista® (50 mcg + 137 mcg)/spray
Mometasone + Azelastine Nasal spray Momate AZ® (50 mcg + 140 mcg)/spray
* Azelastine is an anti-histamine.
B) Mast-cell stabilizers and Anticholinergics

1. Such as Nedocromil, and sodium Cromoglicate, they are an alternative to corticosteroids in
the prophylactic treatment of allergic rhinitis; (but may be less effective).
2. All Mast cell stabilizers are used 4 times per day, Except Nedocromil which is used twice daily,
Treatment course is usually ranges from 4 weeks to 6 weeks.
3. It’s useful for patients with specific known allergy who plan on getting in contact with that
allergen. (intended prophylaxis use).
4. Ipratropium bromide (anticholinergic) is available as intranasal spray for Rhinorrhea
associated with allergic and non-allergic rhinitis.
These are ophthalmic products, but can be used nasally.
Na Cromoglycate Eye drop
+ Crolom®, Opticrom®, 4% (10 ml),
(or) Cromolyn Na+ Allergotin® 2% (10 ml)
Lodoxamide Eye drop Alomide® 0.1%
Nedocromil Eye drop Alocril® 2%
Pemirolast Eye drop Alamast® 0.1% (1 mg/ml)
Ipratropium Nasal spray Atrovent Nasal® 0.03% , 0.06%
C) Intra nasal Antihistamine

1. Topical antihistamines are considered less effective than topical corticosteroids but probably
more effective than Cromoglicate.
2. Approved for use from age of 5 years and above.
3. Azelastine is useful for controlling breakthrough symptoms in allergic rhinitis.
Azelastine Nasal Spray Astelin , Allergodil , Astepro , Rhinolast 0.1%
® ® ® ®
Olopatadine Nasal Spray Patanase® 6%

13.2.2 - Sinusitis
1. Symptoms → Headache, face pain around sinus area, yellowish discharge, sinus congestion,
Cough & Loss of smell, Additional symptoms may include Fever, Bad breath, Fatigue.
2. Acute sinusitis may be diagnosed when a person has two or more symptoms and/or by the
Presence of thick, green, or yellow nasal discharge .
3. Viral Nasopharyngitis (common cold) commonly spreads to involve the Para-nasal sinuses but
this usually subsides within 2-3 days without treatment; However, secondary bacterial infection
of sinuses may occur and results in persistence of purulent nasal discharge, high fever or
persistent cough; Management includes :
1. Antibiotic therapy: An oral broad-spectrum antibiotic for 10-14 days is indicated for control
and eradication of bacterial infection. Choices are
a. Broad spectrum Penicillins as ampicillin or amoxicillin (50-100 mg/kg/day); The newer
drugs as sultamicillin (ampicillin + sulbactam) or Co-Amoxiclave (amoxicillin + clavulanic
acid) are more effective than either drug alone.
b. Second generation Cephalosporins as cefuroxime (40 mg/kg/day) are effective.
c. Macrolides as clarithromycin or azithromycin can be also used.
2. Nasal decongestants: Oral nasal decongestants can be used in the first 4-5 days of therapy
to reduce sinus congestion.
3. Analgesic and antipyretics: Paracetamol or other antipyretics may be needed in the first
few days to control fever and pain.
A) Topical Nasal Decongestants

1. Intra-nasal Sympathomimetics such as phenylephrine, Naphazoline, Oxymetazoline, and
Xylometazoline may be useful for short-term treatment to relieve severe nasal congestion,
(Symptoms of nasal congestion associated with rhinitis and the common cold can be relieved by
the short-term use (usually not longer than 7 days) of decongestant nasal drops and sprays).
2. Not to use these products for longer than 7 days because of rebound congestion (with
congestion returning after stopping the drug often worse than before).
3. Some of these products may present in 2 concentrations (one for children and for adults).
4. Nasal drop containing normal saline is preferred for infants (may relieve nasal congestion by
helping to liquefy mucous secretions).
5. Xylometazoline is also available as a topical cream 1%, indicated for the topical treatment of
persistent facial erythema associated with rosacea in adults.
➢ Xylometazoline can be abused by addicts to obtain the psychoactive effects of inhaled
Xylometazoline; which include excitation and feeling of strength.
Xylometazoline Nasal Drop / Otrivin Adult®, Triaminic®, 0.1%
Nasal Spray Xylo-mepha®
Nasal Drop Otrivin Child® 0.05%
Oxymetazoline Nasal Drop Afrin® , Dristan® , Nasordine® 0.05%
Phenylephrine Nasal Spray/Drop NeoSynephrine® 0.25% , 0.5%
Naphazoline Nasal Spray/Drop Privine® 0.05%
Tetrahydrozoline Nasal Drop Visine® , Burnil® 0.05% , 0.1%
Propylhexedrine Nasal inhaler Benzedrex® 250 mg
Notes:
1. All topical Sympathomimetics are not recommended to use in children below 6 years, Except
for Xylometazoline 0.05% which can be used in children above 2 years old, younger children
(below 2 years) are to use NaCl nasal drops for treatment of decongestion .
2. Adverse effects of topical decongestants are: burning, stinging, sneezing, and dryness.
B) Oral Decongestants
1. Systemic decongestants are sympathomimetic agents that act on adrenergic receptors in the nasal
mucosa to produce vasoconstriction, shrink swollen mucosa, and improve ventilation.
2. Usually comes in combinations of sympathomimetic like pseudoephedrine and phenylephrine
(they reduce nasal congestion) and antihistamine (like Triprolidine) (they reduce rhinorrhea and
sneezing).
3. Systemic decongestants should be used with caution in hypertension, hyperthyroidism, and
ischemic heart diseases.
Trade name D.form
Scientific name(s) Concentration
Actifed® Tab Triprolidine + Pseudoephedrine 2.5 mg + 60 mg
Actifed®, Samafed® SyrupTriprolidine + Pseudoephedrine (1.25 mg + 30 mg)/5ml
Semprex D® Cap Acrivastine + Pseudoephedrine 8 mg + 60 mg
Snip® Tab Paracetamol + Pseudoephedrine 325 mg + 15 mg
Salzone® Cap Paracetamol + Phenylephrine 500 mg + 6.1 mg
Clarinase® Tab Loratadine + Pseudoephedrine 5 mg + 120 mg
Xinase®, Clearest® Tab Cetirizine + Pseudoephedrine 5 mg + 120 mg
Coldin® Tab Paracetamol + Promethazine 450 mg + 5 mg
Phenylephrine 5 mg
** For more info, see chapter 1, section 3.
13.3 - Drugs acting on the Oropharynx (Mouth & Throat)

First: Mouth Ulcers:
1. Aphthous ulcers, more commonly known as mouth ulcers, is a collective term used to describe
various different clinical presentations of superficial painful oral lesions that occur in
recurrent episodes, it’s not due infection but several other causes have linked to it including:
stress, trauma, food sensitivities, nutritional deficiencies (Iron, Zinc and Vitamin B12), but none
have so far been proven.
➢ Sometimes Aphthous ulcers occurs in smoking patient when the quite smoking; the use
of Nicotine replacement therapy for people who have developed oral ulceration after
stopping smoking is recommended in such cases; although, starting smoking again does not
usually lessen the condition.
2. Treatment options include
a. Topical products containing anesthetics or analgesics
b. Topical corticosteroids
c. Amlexanox; an anti-inflammatory and anti-allergic immunomodulator used to treat
recurrent Aphthous ulcers, and (in Japan) used for several inflammatory conditions; This
drug has been discontinued in the U.S.
d. Benzydamine; a topical anti-inflammatory and anesthetic, indicated for acute pharyngitis
and Aphthous ulcers.
e. herbal remedies as alternative treatments, including aloe vera, myrtus communis, Rosa
damascena, potassium alum, zinc sulfate.
Topical corticosteroids (For Mouth Ulcers)

1. Triamcinolone in orabase (oral gel) (Kenalog in orabase®) is used for mouth ulcer, it is applied
2-4 times daily after food (after food, as food is likely to rub the paste off).
2. Hydrocortisone Lozenges (pellets): used 4 times daily.
3. Betamethasone Mouth wash: comes as a tablet (0.5 mg) that dissolves in water (in 15 ml) then
wash with it the mouth for 5 minutes, used 4 times a day. (Do not swallow it).
Triamcinolone Oral gel/Paste Kenalog , Danticort
Lidocaine + Aminoacridine Gel Medijel ® (2 mg + 0.15 mg)/gm
Rhubarb + Salicylic Acid oromucosal Solu. Pyralvex ® (50 mg + 10 mg)/ml
Hydrocortisone Pellets Corlan ® 2.5 mg
Betamethasone Tab Betnesol ® 0.5 mg
Amlexanox Oral Paste Aphthasol® 5%
Second: Oral Thrush

1. Oropharyngeal candidiasis (oral thrush) is an opportunistic mucosal infection and is unusual
in healthy adults; The very young (neonates) and the very old are most likely to suffer from it.
2. The classical presentation of oral thrush is of creamy-white soft elevated patches that can be
wiped off revealing underlying erythematous mucosa, Pain, soreness, altered taste and a
burning tongue can be present. Lesions can occur anywhere in the oral cavity but usually affect
the tongue, palate, lips and cheeks.
Topical antifungals
1. Topical antifungals for thrush include Nystatin (as an oral drop (as a Susp.) and Miconazole (as
an oral gel).
• Nystatin dose: Adult and child 100,000 units (1ml of the drop) 4 times daily after food
(hold in mouth), usually for 7 days (continued for 48 hr. after lesions have resolved);
Nystatin is used safely for any child age (it’s non-absorbable by the guts).
• Miconazole is applied twice daily for 5 days. (Used in patient older than 4 months Only),
treatment should be continued for at least 7 days after lesions have healed or symptoms have
cleared, to be administered after meals, retain near oral lesions.
Nystatin Oral Drop Mycostatin® 100,000 units
Miconazole Oral paste Daktarin®, Miconaz® 20 mg
Clotrimazole Lozenges Mycelex Troche® 10 mg
Other products for Oral Thrush
Metronidazole Oral Gel Metrogel® , Elyzol® 25% (250 mg/gm)
Gentian Violet * Topical Solu. Gentian® 1%
* Gentian Violet is a dye that kills bacteria and fungi; It can be an effective treatment for thrush, it’s
applied topically ONLY using a cotton swab to apply a very small amount, it should not be given to
new-borns, because it can cause open sores (ulcers) in the mouth.
Third: Dry Mouth (Xerostomia)

1. Dry mouth may be caused by drugs with antimuscarinic (anticholinergic) side effects, by
diuretics, by irradiation of the head and neck region or by damage to or disease of the salivary
glands, as in Sjögren’s syndrome (an autoimmune disease; in which the immune system attacks
the glands that make tears and saliva); Patients with a persistently dry mouth may develop a
burning or scalded sensation and have poor oral hygiene; they may develop increased dental
caries, periodontal disease, and oral infections (particularly candidiasis).
2. Dry mouth may be relieved in many patients by simple measures such as frequent sips of cool
drinks or sucking pieces of ice or sugar-free fruit pastilles; Sugar-free chewing gum stimulates
salivation in patients with residual salivary function.
3. Artificial saliva can provide useful relief of dry mouth, also Salivary stimulants (Cevimeline and
Pilocarpine, are indicated for xerostomia in patients with Sjögren’s syndrome.
➢ They are effective only in patients who have some residual salivary gland function, and
therefore should be withdrawn if there is no response
Cevimeline Cap Evoxac® 30 mg
Pilocarpine Tab Salagen® 5 mg
Fourth: Mouth Products

A) Mouthwashes and Gargles:
1. Mouthwashes are employed for the improvement of oral hygiene; For example,
Chlorhexidine, Hexetidine are both an effective antiseptic which has the advantage of inhibiting
plaque formation on the teeth.
a. They are also useful in minor mouth infections including thrush.
b. Used as an aid in the prevention and treatment of gingivitis.
c. Used in the management of sore throat and recurrent Aphthous Ulcers.
2. Notes regarding Chlorhexidine containing Mouthwashes:
a. Dose: rinse mouth with 10 mL for about 1 minute twice daily.
b. It may cause reversible brown staining of teeth.
c. Chlorhexidine gluconate may be incompatible with some ingredients in toothpaste;
so, leave an interval of at least 30 minutes between using mouthwash and toothpaste.
Chlorhexidine Mouthwash Corsodyl®, Zak®, BioFresh K® 0.12%
Hexetidine Mouthwash Oraldene® 0.1%
Cetrimide + Lidocaine Mouthwash Citrolin® (25 mg + 3 mg)/100 ml
Cetrimide + Lidocaine Mouthwash Citrolin F ® (25 mg + 3 mg + 20 mg
+ Chlorhexidine + 50 mg )/100 ml
+ Sodium Fluoride
Chlorhexidine Mouthwash Parodontax® 0.06% + 0.055%
+ Sodium Fluoride
Sodium Fluoride + Mouthwash Sensodine Fresh® 0.055% +
Cetylpyridinium Cl + 0.05% +
Zinc Cl 0.1%
Permethol + Vit. B5 Mouthwash BioFresh P® 0.1% + 0.5%
Chlorhexidine + Mouthwash Listermix Plus® 0.1% +
Menthol + Thymol + 0.042% + 0.064% +
Eucalyptol + Clove Oil 0.092% + 0.06%
Menthol + Thymol Mouthwash Listerine® 0.042% + 0.064%
+ Methyl salicylate + 0.06%
+ Eucalyptol + 0.092%
* Cetrimide, Cetylpyridinium are antiseptics.

B) Mouth sprays:
These usually contain antiseptics and anesthetics or an anti-inflammatory, maybe used to relief
pain after teeth removal or pain due gingivitis.
Cetrimide + Lidocaine Spray Lido spray ® 5% , 10%
Cetrimide + Lidocaine Spray Lido Plus ® (1 gm + 8 gm + 0.2 gm)
+ Chlorhexidine Per 100 ml
Dequalinium Chloride + Lidocaine Spray Bucco-spray , ® ------------------
Buccosan ®
Dequalinium Chloride + Dibucaine Spray Decatylen Neo® ------------------

Dequalinium Chloride + Enoxolone Spray Anginovag ® 100 mg + 60 mg
+ Lidocaine + Hydrocortisone + 100 mg + 60 mg
+ Tyrothricin + 400 mg
Notes:
1. Dequalinium Chloride is an antiseptic and disinfectant. It is a topical bacteriostatic, used in
wound dressings and mouth infections and may also have antifungal action. It may cause skin
ulceration with high concentrations.
2. Lidocaine and Dibucaine are topical anesthetics.
3. Enoxolone is also called glycyrrhetinic acid (Mild antibacterial + anti-inflammatory).
4. Tyrothricin is local antibiotic effective against gram-positive bacteria.
C) Lozenges:
1. They are medicated tablet intended to be dissolved slowly in the mouth to temporarily stop
coughs and lubricate and soothe irritated tissues of the throat (usually due to a sore throat). (1-3)
2. Lozenges may contain benzocaine, Lidocaine (an anesthetic), or eucalyptus oil, Non-menthol
throat lozenges generally use zinc gluconate, glycine or pectin as an oral demulcent. Several
brands of lozenges contain dextromethorphan (antitussive) and Ambroxol (mucolytic).
3. Some contain menthol, peppermint oil and/or spearmint as their active ingredient(s), Honey
lozenges are also available, some contains Flurbiprofen, and some contain Vit. C.
4. The recommended dosage is one lozenge every 2–3 hours for adults.
Here are some selected lozenges available in our Market (Not All of them)
Orofar ® lozenges Benzoxonium + Lidocaine 1 mg + 1 mg
ZeCuf ® lozenges Herbal Blend ----------------
Strepsils ® lozenges Dichlorobenzyl alcohol + 1.2 mg + 0.6 mg
Amylmetacresol
Pectol® lozenges Eucalyptus oil + Vit. C ------------
Trocal ® lozenges Dextromethorphan 7.5 mg
Boxol ® lozenges Ambroxol 20 mg
Strefen® lozenges Flurbiprofen 8.75 mg
D) Tooth Pastes:
1. There is a variety of tooth paste products in the market, so check them by yourself …. They
include: Sensodine, Crest, Colgate, Parodontax … etc.
2. Availability of adequate Fluoride confers significant resistance to dental caries; It is now
considered that the topical action of fluoride (tooth paste, mouthwash) on enamel and plaque is
more important than the systemic effect (tablet, oral drop).
Note1:
Generally, tooth pastes contains the following; each ingredient with its benefit:
Note2:
Fluoride is also available as oral tablets, and indicated for the Prophylaxis of dental caries.
Trade Name Dosage form Scientific name concentration
Zymafluor® Tab Sodium Fluoride 0.25 mg , 0.5 mg , 1 mg
Zymafluor D® Tab Sodium Fluoride + Vit. D3 (0.25 mg + 500 IU),
(0.25 mg + 1000 IU)
Note3: Magic Mouth Wash

Its one of the old Rx, prescribed by the old dentists or prepared locally in the pharmacy, or in the
hospital wards for the patients with mouth infections, or immunocompromised patients; there
are several forms of this Rx; choose what’s suits your need:
➢ 80 ml viscous lidocaine 2% + 80 ml diphenhydramine 12.5 mg/ml elixir + 80 ml Nystatin
100,000 IU Susp. + 80 ml Prednisolone 15 mg/5 ml + 80 ml Distilled water.
➢ 80 ml viscous lidocaine 2% + 80 ml Maloox Susp. + 80 ml diphenhydramine 12.5 mg/ml elixir.
➢ 100 ml dexamethasone 0.5 mg/5 ml + 60 ml Nystatin 100,000 IU Susp. + 100 ml
diphenhydramine 12.5 mg/ml elixir + 3 capsule of 500 mg Tetracycline.
All used every 6 hours as needed, it can be swallowed if there is an esophageal involvement.
References
1- Rosemary R Berardi. Handbook of Nonprescription Drugs, 18th Edition
2- Sean C. Sweetman. Martindale: The Complete Drug Reference, 38th Edition. Ph. Press.
3- Lexi-comp, Drug information handbook, 2022 Ed.
DERMATOLOGY
Chapter Fourteen: Dermatology
Part one: Introduction
14.1- Dermatologic Drug Delivery 14.14- Acne and Rosacea
Systems A. Acne
14.2- Common Skin Diseases, by Body B. Rosacea
Location ➢ Topical Products
➢ Oral Products
14.3- Anti-infective skin preparations
A. Antibacterial preparations 14.15- Preparations for Warts and
➢ Combination products of some Calluses
topical anti-Bacterials 14.16- Sunscreen preparations
➢ Combination products of Anti-
Bacterials + Corticosteroids 14.17- Hair Loss
B. Antifungal preparations A. Androgenetic Alopecia
➢ Combination Products: (Anti- B. Alopecia Areata
Fungal + Corticosteroid) 14.18- Products for treating
➢ Combination Products: (Anti- Hirsutism
Fungal + Anti-Bacterial +
Corticosteroid) 14.19 – Vitiligo
C. Antiviral preparations 14.20 – Skin Aging and wrinkles
14.4- Parasiticidal preparations 14.21 – Antiperspirants
A. Scabies (body lice)
B. Head lice 14.22 – Skin Bleachers/Skin
C. Pubic lice whitening (Depigmenting Agents)
14.5- Topical Corticosteroids 14.23 – Dark spots under the Eyes
14.6 - Preparations for minor cuts and 14.24 – Topical Products for Scars
abrasions 14.25 – Wound Care Products
14.7- Skin Cleansers, and antiseptics 14.25 – Burns and Burn care products
14.8- Emollients and Barrier prep.
14.9- Topical Antihistamines and
antipruritics
14.10- Topical Anesthetics
14.11 - Shampoos for Dandruff
14.12 - Preparations for Psoriasis
A. Topical Therapies
B. Combination Topical Products
C. Oral/Systemic Therapies
D. Biological Agents
14.13 - Preparations for Eczema
Sam’s Guide: Chapter 14 – Dermatology
Chapter Fourteen: Dermatology
Introduction:
1. The skin waterproofs, cushions, and protects the rest of the body and is, in fact, its largest organ;
it provides a barrier against innumerable infections and infestations, it helps the body to retain
its vital fluids, helps in the synthesis of vitamin D; and it plays a major role in temperature control,
and it houses the sensory nerves of touch.
2. The skin consists of two main layers: a thin, tough top layer, the Epidermis, and below it a thicker
layer, the Dermis. The epidermis also has two layers: the skin surface, or stratum corneum
(horny layer) consisting of dead cells, and below, a layer of active cells.
3. The cells in the active layer divide and eventually die, maintaining the horny layer, living cells
produce Keratin, which toughens the epidermis and is the basic substance of hair and nails.
4. Some living cells in the epidermis produce Melanin, a pigment released in increased amounts
following exposure to sunlight.
5. The dermis contains different types of nerve ending for sensing pain, pressure, and temperature;
sweat glands to cool the body; sebaceous glands to lubricate and waterproof the skin; and white
blood cells that help to keep the skin clear of infection.
6. Human skin shows high skin color variety from the darkest brown to the lightest pinkish-white,
(Human skin shows higher variation in color than any other single mammalian species and is the
result of natural selection), skin pigmentation in humans evolved to primarily regulate the
amount of ultraviolet radiation (UVR) penetrating the skin, controlling its biochemical effects.
7. The actual skin color of different humans is affected by many substances, although the single
most important substance determining human skin color is the pigment Melanin; it is produced
within the skin in cells called melanocytes and it is the main determinant of the skin color of
darker-skinned humans; The skin color of people with light skin is determined mainly by the
bluish-white connective tissue under the dermis and by the hemoglobin circulating in the veins
of the dermis (The red color underlying the skin becomes more visible, especially in the face,
when, as consequence of physical exercise or the stimulation of the nervous system (anger, fear),
arterioles dilate).
8. There is a correlation between the geographic distribution of UV radiation (UVR) and the
distribution of indigenous skin pigmentation around the world; Areas that highlight higher
amounts of UVR reflect darker-skinned populations, generally located nearer towards the
equator, Areas that are far from the tropics and closer to the poles have lower concentration of
UVR, which is reflected in lighter-skinned populations.
9. In the same population it has been observed that adult human females are considerably lighter
in skin pigmentation than males; Females need more calcium during pregnancy and lactation,
and vitamin D which is synthesized from sunlight helps in absorbing calcium; and for this reason,
it is thought that females may have evolved to have lighter skin in order to help their bodies
absorb more calcium.
14.1 – Dermatological Drug Delivery Systems:

A range of dermatologic formulations is
available: solutions, suspensions or shake lotions,
powders, lotions, emulsions, gels, creams,
ointments, and aerosols.
Each dermatologic delivery vehicle has specific
characteristics and uses based on the type, and
location of the lesion.
1. Powders are used mainly in intertriginous
areas (e.g., groin, under the breasts, or in skin
folds) to decrease friction, which can cause
mechanical irritation.
They also are useful in the treatment of Tinea
pedis (athlete’s foot), Tinea cruris (jock itch),
and diaper dermatitis (diaper rash).
2. Lotions are suspensions or solutions of powder
in a water vehicle (semi-liquid preparations); They are especially advantageous in the treatment
of conditions characterized by significant inflammation and tenderness. In these situations,
creams or ointments may cause pain on application; Also, lotions are useful for hairy areas of
the body and scalp.
3. Gels are jelly-like in consistency and are often water-based, they are used increasingly for a wide
variety of topical skin treatments because they are easy to apply, usually non-greasy, and more
rapidly absorbed than ointments, they are most useful when applied to hairy areas or other
areas such as the face or scalp, where it is considered cosmetically unacceptable to have the
residue remain on the skin.
4. Creams are the most commonly used vehicle in dermatology, these have an emollient effect,
they are usually composed of an oil-in-water emulsion and are used in the treatment of dry skin
disorders; the most common mistake made by patients when applying creams is that they use
too much or do not rub them in fully; Generally, if the cream can be seen on the skin after
application, the patient has made one or both of these application mistakes.
5. Ointments are usually greasy and are suitable for treating wet (weeping) eczema and very dry
chronic lesions (they are most useful on chronic lesions), relieving dryness, brittleness, and
protecting fissures owing to their occlusive properties; They should not be used on acutely
inflamed lesions. Ointments should not be applied to intertriginous or hairy areas because they
tend to trap heat and promote maceration. Ointments are greasy and may be cosmetically
unacceptable.
6. Collodions are painted on the skin and allowed to dry to leave a flexible film over the site of
application (dry out to form a protective film).
14.2 - Common Skin Diseases, by Body Location
14.3 - Anti-infective skin preparations

o The skin is the body’s first line of defence against infection. Yet the skin can also become infected
itself, especially if the outer layer (epidermis) is damaged by a burn, cut, scrape, insect bite, or an
inflammatory skin condition – for example, eczema or dermatitis.
o Several different types of organism may infect the skin: bacteria, viruses, fungi, and yeasts.
A) Antibacterial preparations
1. Topical Antibacterials and antiseptics may be useful for superficial skin infections, but
Antibacterials should only be used short term because of the risks of inducing bacterial resistance
and contact allergy.
➢ Any topical antibiotic product can irritate the skin or cause an allergic reaction.
➢ Irritation is sometimes provoked by another ingredient of the preparation rather than the
active drug, such as a preservative contained in the product.
2. An antibiotic or antibacterial skin cream may also be used to prevent infection when the doctor
considers this to be a particular risk (for example, in the case of severe burns).
3. Other skin disorders in which topical antibiotics may be prescribed include Impetigo, Cellulitis
Infected Eczema, Bedsores, and Nappy Rash.
4. To minimize the development of resistant organisms it is advisable to limit the choice of
Antibacterials applied topically to those not used systemically.
5. Silver sulfadiazine is used in the treatment of infected burns.
6. Metronidazole is used topically for the treatment of Rosacea and to reduce the odor associated
with anaerobic infections.
7. Acute Impetigo (caused by Staphylococcus aureus) on small areas of the skin may be treated by
short-term topical application of Fusidic acid.
➢ Mupirocin should be used only to treat methicillin-resistant Staphylococcus aureus.
➢ If the impetigo is extensive or longstanding, an oral antibacterial such as flucloxacillin (or
clarithromycin in penicillin allergy) should be used.
8. Cellulitis is a rapidly spreading deeply seated inflammation of the skin and subcutaneous tissue,
requires systemic antibacterial treatment

Gentamycin Cream Gendin , Garamycin
® ® 0.3%
Oint. 0.1%
Tetracycline Oint. Samacycline ® 3%
Erythromycin Gel/Oint. Erythrodar , Erythrocin
® ® 2%
Gel Spotex® 4%
Clindamycin Gel/Lotion Cleocin T , Clindacyn T
® ® 1%
Bacitracin Oint./Powder Beocin , Baciquent
® ® 500 Unit/gm
Fusidic acid Cream/Oint. Fucidin®, Fucine®, Fucibact® 2%
Silver Sulfadiazine Cream Silvadene®, Floumizine® 1%
Nadifloxacin Cream Nadixa , Magnis
® ® 1%
Metronidazole Gel Rozex ® 0.75%
Ozenoxacin Cream Xepi ® 1%
Mafenide Cream, Sulfamylon ® --------------
Topical Solu.
Mupirocin Cream/Oint. Bactroban®, Avoban® 2%
Retapamulin Oint. Altabax® 1% (5 gm , 10 gm Tubes)
Nitrofurazone Cream Furacin® 2 mg/gm
Fusafungine Oro/Nasal Locabiotal® , Bioparox® 1% (500 mcg)
Spray
Notes:
1. Erythromycin and Clindamycin are usually used topically in the treatment of Acne.
2. Bacitracin: (bacteriostatic), used only for the prevention of superficial skin infections caused by
the susceptible bacteria. (Not substantially absorbed from intact or denuded skin, wounds, or
mucous membranes).
3. Fusidic acid: (bacteriostatic), the only indication for their use is in infections caused by
penicillin-resistant staphylococci; It’s also used in the treatment of burns.
a. Occasionally used as a treatment for acne.
b. Comes in combination with hydrocortisone or betamethasone.
4. Nadifloxacin is a topical fluoroquinolone antibiotic for the treatment of acne vulgaris; It is
also used to treat bacterial skin infections, it also showed potent antibacterial activity against
methicillin-resistant Staphylococcus aureus (MRSA).
5. Ozenoxacin is a topical fluoroquinolone antibiotic licensed for the treatment of Impetigo.
6. Silver Sulfadiazine and Mafenide are usually used for infective burns.
7. Mupirocin: used for furuncle, impetigo, open wounds, do not apply to eyes; do not apply topical
to mucous membranes
8. Retapamulin: for treatment of bacterial skin infections such as impetigo.
9. Nitrofurazone is indicated as an adjunctive therapy for second- and third-degree burns.
10. Fusafungine: for the treatment of nasal and throat infection; It also possesses anti-inflammatory
properties.
Note1: Combination products of some topical anti-Bacterials:

Scientific name(s) D. Form Trade name concentration
Polymyxin B + Bacitracin Cream/Oint Polysporin® (10,000 unit + 500 unit) per gm
Neomycin + Polymyxin B + Cream, TAO® (3.5 mg + 5,000 unit + 400 unit)
Bacitracin Oint. Per 1 gm
Neomycin + Polymyxin B + Oint. TriBiozene® (3.5 mg + 10,000 unit + 500 unit
Bacitracin + Pramoxine + 10 mg ) per 1 gm
Note2: Combination products of Anti-Bacterial + Corticosteroids:
Fusidic acid + Betamethasone Cream Fucibet , Fucibact B 2% + 0.1% (15 gm tube)
® ®
Fusidic acid + Hydrocortisone Cream Fucidin H® 2% + 1% (15 gm tube)

Gentamicin + Betamethasone Oint. Betnosam – G® 0.1% + 0.1%
Neomycin + Betamethasone Oint. Betnosam – N® 0.5% + 0.1%
Neomycin + Fluocinolone Cr/Oint Synalar N® 0.5% + 0.025%
Neomycin + Polymyxin B .Cream Cortisporin® 3.5 mg + 10,000 Unit + 5 mg
+ Hydrocortisone
Bacitracin + Neomycin + Oint. Cortimyxin® 400 Unit + 3.5 mg +
Polymyxin B + Hydrocortisone 5,000 Unit + 1 mg
Clioquinol + Hydrocortisone Cr/Oint. Corque , Viocort
® ® 3% + 1%
Clioquinol + Betamethasone Cream Beta-Vioform® 3% + 0.1%
Iodoquinol + Hydrocortisone Cream Dermazene®,Vytone® (10 mg + 10 mg)/gm
* Iodoquinol and Clioquinol has both antifungal and antibacterial properties. (5)
** Iodoquinol is also an anti-parasitic drug; it’s given orally as an amebicide (anti-protozoal). (5)
B) Antifungal preparations
1. Most localized fungal infections are treated with topical preparations.
2. To prevent relapse, local antifungal treatment should be continued for 1–2 weeks after the
disappearance of all signs of infection.
3. Combination products of an antifungals and corticosteroids are available to treat fungal
infection associated with inflammation.
4. Duration of therapy is dependent on the site of the infection and may extend to a number of
months (2 to 8 weeks for infections of the hair and skin, up to 6 months for infections of the
fingernails, and 12 months or more for infections of the toenails).
5. Pityriasis versicolor, or called tinea versicolor (Patches of skin that may be darker or lighter
than your normal skin color, or may be red, brown or pink, they tend to develop gradually and
may join up to form larger patches over time); can be treated with ketoconazole shampoo (apply
once daily for maximum 5 days, leave preparation on for 3–5 minutes before rinsing).
Butenafine Cream Lotrimin®, Mentax® 1%
Ciclopirox Cream, Lotion, Loprox®, Penlac® 0.77%
Gel
Shampoo 1%
Nail Lacquer 8%
Clotrimazole Cream, Lotion Gynomizole® , Mycelex® 1%
Econazole Cream Ecostatin®, Spectazole® 1%
Efinaconazole Cream, Nail Lacq. Topazole® 10%
Ketoconazole Cream, Gel, Foam Nizoral® , Ketonaz® 2%
Shampoo 1% , 2%
Luliconazole Cream Luzu® , Lulican® 1%
Miconazole Cream Desenex®, Fungoid®, Daktarin® 2%
Naftifine Cream, Gel Naftin® 1% , 2%
Nystatin Cream, Oint Pediaderm®, Mycostatin® 100,000 Units/gm
Oxiconazole Cream, Lotion Oxistat® 1%
Sertaconazole Cream Ertaczo®, Dermofix®,Onabet® 2%
Eberconazole Cream Ebernet® 1%
Sulconazole Cream, Lotion Exelderm ® 1%
Terbinafine Cream, Lotion Lamisil , Lamifin , Terbisil
® ® ® 1%
Tolnaftate Cream, Powder Tinactin , Aftate
® ® 1%
Note1: Combination Products: (Anti-Fungal + Corticosteroid)

Miconazole + Hydrocortisone Cream/Oint. Daktacort®, Monicort® (20 mg +10 mg) /1 gm
Miconazole + Betamethasone Cream Micosone® 2% + 0.1%
Miconazole + Mometasone Cream Elica-M®, Avocom-M® 2% + 0.1%
Miconazole + Fluprednidene Cream Domycotin® 2% + 0.1%
Isoconazole + Diflucortolone Cream Travazole®, Oly Plus® 10 mg + 1 mg
Azonit-D®
Clotrimazole + Hydrocortisone Cream Canesten HC® 1% + 1%
Clotrimazole + Betamethasone Cream Fougera®, Lotrisone® 1% + 0.05%
Opizole-B®
Nystatin + Triamcinolone Cream/Oint. Mycolog II® 100,000 Unit + 0.1%
Ketoconazole + Hydrocortisone Gel Ketocon Plus® 2% + 1%
Note2: Combination Products: (Anti-Fungal + Anti-Bacterial + Corticosteroid)

Gentamycin + Clotrimazole Cream Tetraderm® (0.1 gm + 1 gm + 0.05 gm)
+ Betamethasone Per 100 gm
Gentamycin + Miconazole Cream Momenta® (0.1% + 2% + 0.1%)
+ Mometasone Per 1 gm
Gentamicin + Tolnaftate + Cream Quadriderm®, 1 mg + 10 mg +
Clioquinol + Betamethasone Mixderm®, Quard® 10 mg + 0.5 mg
Gramicidin + Neomycin + Cream, Nystagram®, (0.025% + 0.25% +
+ Nystatin + Triamcinolone Oint. Nystacort® (SDI) 100,000 IU + 0.1%)/gm
Neomycin + Nystatin Cream Dioderm®, 1% + 0.5%
+ Hydrocortisone Nystacort N® + 1%
Neomycin + Nystatin Cream, Dermovate NN® 1% + 0.5%
+ Clobetasol Oint. + 0.05%
Oxytetracycline + Nystatin Cream Trimovate® 3.0% + 0.5%
+ Clobetasone + 0.05%
Chlorhexidine + Nystatin Cream, Nystaform HC (1.15% + 100,000 IU
+ Hydrocortisone Oint. + 1%)/gm
Chlorhexidine + Nystatin Cream, Nystacort® (UM) (1.15% + 100,000 IU
+ Dexamethasone Oint. + 0.1%)/gm
* Clioquinol = iodochlorohydroxyquin, they are the same drug; which has both antifungal and
antibacterial properties.

C) Antiviral preparations
1. These include: Acyclovir, Penciclovir and Docosanol.
2. About Acyclovir:
a. Acyclovir cream can be used for the treatment of initial and recurrent labial herpes simplex
infections (cold sores); also used for initial Genital Herpes.
b. Acyclovir is best applied at the earliest possible stage, usually when prodromal changes of
sensation are felt in the lip and before vesicles appear.
c. Systemic acyclovir treatment may be necessary in herpes zoster (shingles).
3. Penciclovir and Docosanol are mainly used for recurrent labial herpes.
➢ Penciclovir needs to be applied more frequently than acyclovir cream.
4. Systemic anti-viral treatment is necessary for buccal or vaginal infections and for herpes zoster.
Acyclovir Cream/Oint. Zovirax® , Veramed® 5%
Penciclovir Cream Denavir® 1%
Docosanol Cream Abreva® 10%
Combination product
Acyclovir + Hydrocortisone Cream Xerese®, Lipsovir® 5% + 1%
14. 4 - Parasiticidal preparations

1. Mites and lice are the most common parasites that live on the skin; One common mite causes the
skin disease scabies. The mite burrows into the skin and lays eggs, causing intense itching.
Scratching the affected area results in bleeding and scab formation, as well as increasing the risk
of infection.
2. There are three types of lice, each of which infests a different part of the human body: the head
louse, the body (or clothes) louse, and the crab louse, which often infests the pubic areas but is
also sometimes found on other hairy areas such as the eyebrows.
3. All of these lice cause itching and lay eggs (nits) that look like white grains attached to hairs.
4. Both mites and lice are passed on by direct contact with an infected person (during sexual
intercourse in the case of pubic lice) or, particularly in the case of body lice, by contact with
infected bedding or clothing.
A) Scabies (body lice)

1. A contagious skin infection caused by the mite (Sarcoptes scabiei), the mite is usually not
directly visible; it burrows under the host's skin, causing intense allergic itching.
2. Treatment options include: Permethrin, Ivermectin, Lindane, Benzyl Benzoate, Crotamiton,
Malathion, Isopropyl Myristate, Spinosad and Sulfur preparations (usually 10%).
3. All members of the affected household should be treated simultaneously; Treatment should
be applied to the whole body including the scalp, neck, face, and ears, particular attention should
be paid to the webs of the fingers and toes and lotion brushed under the ends of nails.
4. The itch and eczema of scabies persists for some weeks after the infestation has been eliminated
and treatment for pruritus and eczema may be required.
➢ Application of Crotamiton (a topical Scabicidal and general antipruritic) is used to control
itching after treatment of scabies.
➢ A topical corticosteroid may help to reduce itch and inflammation after scabies has been
treated successfully; however, persistent symptoms suggest that scabies eradication was
not successful; Oral administration of a sedating antihistamine at night may also be useful.
➢ Some Dermatologist actually add a corticosteroid during the treatment.
Notes:
1. Permethrin 5% cream is the drug of choice due to ease of administration and high cure rate.
2. Ivermectin oral tablet has been used in combination with Permethrin, for the treatment of
hyperkeratotic (crusted) scabies that does not respond to topical treatment alone; although
dermatologists use it for any type of scabies, for a better accelerated result.
3. The use of Benzyl benzoate emulsion is decline nowadays because the cure rate is about 50%,
and up to 25% of patient’s experience side-effects such burning, irritation and itching on
application, in addition its application is less convenient than Permethrin cream.
4. Sulfur Oint. is prepared in the pharmacies by mixing 10 mg of sulfur with Vaseline.
Scientific name D. form Application

Permethrin 5% - 2.5% The treatment is applied to the entire body, from neck
Cream and down-words (including web spaces of fingers and toes,
Lotion the genitalia, and under the nails), but not the neck, face
and scalp in adults; However, in children age under 2
years and the elderly (aged 70 and over) the advice now
is to include the scalp, neck, face (avoiding the eyes and
mouth) and ear in the application unless the product
packaging contraindicates this, they should be treated
again with cream. Repeat application after 7 days. (3)
Ivermectin 6 mg, 12 mg Taken as two doses, 200µg/kg/dose, one week apart
Tablet
Benzyl 5% - 10% Application: Apply over the whole body except the head
benzoate Emulsion and neck and left to dry on skin, repeat (without bathing
or washing of the first application) on the following day.
The second application is washed off 24 hours later. (3)
A third application may be required in some cases. (3)
Scabicidals
Permethrin Cream/Lotion Nix®, Scalix®, Scabicore® 2.5% , 5%
Benzyl benzoate Emulsion Scabanca® 5% , 10%
Ivermectin Lotion Sklice® 0.5%
Tab Scav®, Gmectin® 6 mg , 12 mg
Lindane Lotion, Lindane® 1%
Shampoo
Malathion Lotion Ovide® 0.5%
Crotamiton * Cream/Lotion Eurax®, Crotaphil® 10%
Isopropyl Lotion, Resultz® 120 mL
Myristate ** Shampoo
Spinosad ** Topical Susp. Natroba® 0.9%
Notes:
1. Malathion is intended for use on persons 6 years of age and older; it can be irritating to the skin.
Malathion lotion is flammable; do not smoke or use electrical heat sources.
2. Crotamiton is also an anti-pyretic, it’s related to antihistamine in chemical structure.
3. Isopropyl Myristate dissolves the waxy shell of mite and lice, causing water loss from their
body, once they lose this protective layer, they dehydrate, become immobile and die.
4. Spinosad causes neuronal excitation in insects (interferes with GABA neurotransmission),
followed by hyper-excitation, paralysis, and then death (what a lame way to die?)
B) Head lice
1. Head lice are wingless insects spending their entire life on the human scalp and feeding
exclusively on human blood, although any part of the scalp may be colonized, lice favor the nape
of the neck and the area behind the ears, where the eggs are usually laid.
2. Head lice infestation (pediculosis) should be treated using lotion or liquid formulations
(Shampoos are diluted too much in use to be effective).
3. A contact time of 8–12 hours or overnight treatment is recommended for lotions and liquids.
4. In general, a course of treatment for head lice should be 2 applications of product 7 days apart
to kill lice emerging from any eggs that survive the first application; all affected household
members should be treated simultaneously.
5. A new formula contains Dimeticone; which kills the lice by a physical process rather than by
any chemical effect. It is thought to work by blocking the tubes used by the lice to breathe and by
blocking the way the lice pass out water, which kills them.
➢ It causes complete eradication of lice and nits after a single use; and all the lice and nits
will be dead in 10 minutes; although treatment should be repeated after 7 days to make
sure of complete eradication; Resistance is unlikely to develop because it uses a physical
mode of action to eradicate head lice and nits.
Dimeticone Lotion, Spray Dimeticone® 10% , 20%
Solu. Nadia® , DeLice® 92%
Phenothrin Shampoo Parasidose® , Full Marks® 0.5%
Isopropyl Myristate Lotion, Shampoo Resultz® 120 mL
Lindane Lotion, Shampoo Lindane® 1%
Malathion Lotion Ovide® , Prioderm® 0.5%
Shampoo Derbac-M® 1%
Permethrin Shampoo Nix® , Pyrifoam®, Sali® 1%
Permethrin + Malathion Spray Para Plus® 1% + 0.5%
Pyrethrins + Shampoo Lycid® (0.165 gm + 1.65 gm)
Piperonyl Butoxide Per 100 ml
Piperonyl Butoxide + Shampoo Lice Killer® (4% + 0.33%)
Pyrethrum Extract
Dimeticone + Vitamin E Spray Butolice® 80% m/v
+ Diisopropyl
Na Laureth Sulfate + Shampoo Stop Lice® -----------------
Kocamad P-Bettine +
Permethrin
C) Pubic lice
1. Crabs is another name for pubic lice, they’re tiny insects that can take up residence on the pubic
hair; Like head lice and body lice, they feed on human blood.
2. Common symptoms of pubic lice include: itching around the genitals or anus, small pink or red
bumps around the genitals or anus, low-grade fever; The patient might also be able to see the lice
or their tiny white eggs around the roots of pubic hair .
3. If left untreated, pubic lice can spread to other people through skin-to-skin contact or shared
clothing, bedding, or towels; also Scratched bites can also become infected. It’s best to treat pubic
lice infestations immediately.
4. Treatment as with head or Body lice; Permethrin and Ivermectin, (see above).
14.5 - Topical Corticosteroids
1. Topical corticosteroids are used for the treatment of inflammatory conditions of the skin
(other than those arising from an infection), like Eczema, Dermatitis, And Insect Stings.
➢ Also, may be prescribed for the treatment of psoriasis.
➢ They do not affect the underlying cause of skin irritation, and the condition is therefore likely
to recur unless the substance (allergen or irritant) that has provoked the irritation is
removed, or the underlying condition is treated.
➢ Topical corticosteroids are of not recommended in the treatment of urticaria and they
may worsen ulcerated or secondarily infected lesions.
2. Irritation of the skin, caused by exposure to allergens or irritant factors, provokes white blood
cells to release substances that dilate the blood vessels, making the skin hot, red, and swollen.
➢ Applied to the skin surface, corticosteroids are absorbed into the underlying tissue; There,
they inhibit the action of the substances that cause inflammation, allowing the blood
vessels to return to normal and reducing the swelling.
3. Application of Corticosteroids:
a. They should be applied no more than twice daily; Increasing the application from twice
daily to four times daily does not produce superior responses, and may lead to increased
frequency of topical and systemic adverse effects.
b. One fingertip unit (approximately 500 mg) is sufficient to cover an area that is twice that of
the flat adult palm.
4. Preparations should be rubbed in thoroughly and, when possible, applied while the skin is
moist (after bathing). Hydration of the skin increases percutaneous absorption and the
resultant therapeutic effect of topical steroids (1).
5. Children, especially infants, are particularly susceptible to side-effects; thus, a mild
corticosteroid such as hydrocortisone 1% ointment or cream is useful for treating nappy rash
and for atopic eczema in childhood; a moderately potent or potent corticosteroid may be
appropriate for severe atopic eczema on the limbs, for 1–2 weeks only, switching to a less potent
preparation as the condition improves.
6. Thinning of the skin, telangiectasia (a visible permanent dilatation of small cutaneous blood
vessels), localized fine hair growth, hypopigmentation, and striae (pink, red or purple lines or
bands) can result from repeated application of topical corticosteroids.
a. With chronic use, topical corticosteroids (especially the potent agents) show decreased
efficacy, a phenomenon known as “tachyphylaxis”.
b. They mask the symptoms of infections such as Tinea (fungal) and scabies.
7. Prolonged use of a topical corticosteroid on the face should be avoided, some advocate using
only hydrocortisone 0.5% or 1% cream on the face.
8. They come in different potencies (Low, Medium, High, and Very High); their Potencies are
commonly classified according to the vasoconstrictor assay, based on the degree to which an
agent causes cutaneous vasoconstriction on normal human subjects.
• Changing the salt form will also change the potency.
Low Potency Topical Corticosteroids
Alclometasone Cream, Oint. Aclovate® 0.05%
Desonide Cream, Oint. Desonate® , Verdeso® 0.05%
Gel
Hydrocortisone Cream, Oint. Dermacort® 1% , 2.5 %

Dexamethasone Cream, Gel Dexacare® 0.075% , 0.4%
Medium Potency Topical Corticosteroids
Betamethasone Cream, Oint. Betnovate®, Betnosam® 0.05% ,
(Valerate) Lotion 1%
Fluocinolone Cream, Oint. Synalar®, Capex®, Sinoderm® 0.025% , 0.01% , 0.1%
Fluticasone Cream, Oint. Cutivate® 0.05%
Budesonide Cream Biosonide® 0.025%
Hydrocortisone Cream, Locoid®, Aquax-H® 1%
(Butyrate) Lotion
Hydrocortisone Cream, Oint. Westcort® , Hydroval® 0.2%
(Valerate)
Triamcinolone Cream, Oint. Aristocort®, Kenalog®, Triacet® 0.025% , 0.05% , 0.1%
Oral Gel Kenalog® 1 mg/gm (10 gm tube)
Topical Spray Flutex® 0.147 gm/gm
High Potency Topical Corticosteroids
Betamethasone Cream, Oint. Diprosone® , Alphatrex® 0.05%
(Dipropionate) Lotion
Desoximetasone Cream, Oint. Topicort® 0.05% , 0.25%
Gel
Topical Spray Topicort Fast® 0.25%
Fluocinonide Cream, Oint. Lidemol® , Lidex® 0.05% , 1%
Gel
Halcinonide Cream, Oint. Halog® 0.1%
Mometasone Cream, Oint. Elocom® , Elica® 0.1%
Very High Potency Topical Corticosteroids
Clobetasol Cream, Oint. Temovate®, Dermovate® 0.05%
Topical Spray Promax , Clobex , Dermodin 0.05%
® ® ®
Topical Solu. 0.5 mg/ml

Shampoo 0.05%
Halobetasol Cream, Oint. Utravate ® 0.05%
Diflorasone Oint. Psorcon , Apexicon
® ® 0.05%
Other Topical Corticosteroids (less frequently prescribed)

Amcinonide Cream, Oint. Cyclocort ® 0.1%
Clocortolone Cream Cloderm ® 0.1%
Flurandrenolide Cream, Lotion Cordran ® 0.025% , 0.05%
Prednicarbate * Cream, Oint. Peitel® , Dermatop® 0.25% , 0.1%
Crisaborole Oint. Eucrisa ® 2%
* Prednicarbate has a favorable benefit-risk ratio, with an inflammatory action similar to that
of a medium potency corticosteroid, but with a low potential to cause skin atrophy.
** Topical Corticosteroids Comes in many Combinations with topical antibiotics, antifungals,
Emollients, etc. (See above).

14.6 - Preparations for minor cuts and abrasions
o They are applied as necessary but should not be used on large wounds or for prolonged periods
because of the possibility of hypersensitivity, these are generally used for cuts, grazes, insect
bites, minor wounds, spots, minor burns ONLY, napkin rash, abrasions and scalds.
Cetrimide Cream Savlon First Aid® 0.5%
Spray Wound Wash® 0.5%
Chlorhexidine Cream/Solu. Betasept® , Chlorostat® 0.1% , 4% (solution)
Cetrimide + Chlorhexidine Cream Savlon® , Celavex® 0.5% + 0.1%
Liquid Savlon Liquid ® 3% + 0.3%
Cetrimide + Dimeticone Cream Boots Nappy Rash ® 0.5% + 10%
Cetrimide + Benzalkonium Cream Drapolene® 0.2% + 0.01%
Cetrimide + Urea + Cream Cymex ® 0.5% + 1% +
Dimeticone + Chlorocresol 9% + 0.1%
Cetrimide + Lidocaine + Cram Dermidex ® 0.5% + 1.2% +
Chlorobutanol + Alcloxa 1% + 0.25%
Cetrimide + Lidocaine + Cream Lypsyl ,® 0.5% + 2% + 1%
Zinc Sulphate Savlon® Bites & Stings
Proflavine Cream/Lotion Proflavine® 0.1%
Magnesium Sulfate Paste ------------ 45 gm
• Cetrimide, Chlorhexidine, Proflavine are disinfectants having bactericidal activity.
• Dimethicone is water repellent and will protect the skin against water soluble irritants.
• Urea has keratolytic properties.
• Magnesium sulfate pastes are used to treat carbuncles and boils.
14.7 - Skin Cleansers, and antiseptics

1. Wound cleansing is required to remove any dirt or foreign bodies and to remove exudate and
slough (pus and necrotic tissue); This helps to prevent infection and aids healing, commonly used
cleansing solutions are: sodium chloride 0.9%, hypochlorite, hydrogen peroxide, Povidone-
iodine, and Chlorhexidine.
2. Alcohol Solution (95%) Indications: skin preparation before injection, Cautions: flammable;
avoid broken skin.
3. Wound dressings and packing preparations help to protect the wound and provide the correct
environment for wound healing. Some also help by absorbing exudates; (sofra-tulle®).
Scientific name D.form Trade name concentration
Sodium Chloride 0.9% Solu. (Various Trade names) 0.9%
Hypochlorite Solu. (Various Trade names) 0.5%
Hydrogen Peroxide Solu./Cream Crystacide® 3% , 6%
Povidone-Iodine Solu./patch Betadine ® 5% , 10%
K+ Permanganate Tab for Solu. Permitabs® 400 mg (0.1%)
Chlorhexidine Solu. (Various Trade names) 1% , 2.5% , 4%
Notes:
1. Antiseptics such as chlorhexidine or Povidone-iodine are used on intact skin before surgical
procedures; their antiseptic effect is enhanced by an alcoholic solvent.
2. Antiseptic solutions containing Cetrimide can be used if a detergent effect is also required.
3. Hydrogen peroxide, an oxidizing agent, can be used in solutions of up to 6% for skin
disinfection, such as cleansing and deodorizing wounds and ulcers; hydrogen peroxide is also
available as a cream for superficial bacterial skin infections.
4. Potassium permanganate solution 1 in 10,000, a mild antiseptic with astringent properties, can
be used for exudative eczematous areas; treatment should be stopped when the skin becomes
dry, it can stain skin and nails especially with prolonged use.
14.8 - Emollients and Barrier preparations
1. Emollients (like Soft Paraffin) soothe, smooth and hydrate the skin and are indicated for all
dry or scaling disorders (like napkin rash, eczema).
2. Barrier preparations (Zinc oxide, castor oil) often contain water-repellent substances and are
used to protect the skin against hydration and irritations (as in nappy rash), also used on the
skin around stomas, bedsores, and pressure areas in the elderly where the skin is intact.
3. Notes concerning Napkin Rash:
a. The first line of treatment is to ensure that nappies are changed frequently. The rash may
clear when left exposed to the air and a barrier preparation can be helpful.
b. If the rash is associated with a fungal infection, an antifungal cream such as Clotrimazole
cream is useful.
c. A mild corticosteroid such as hydrocortisone 1% is useful in moderate to severe
inflammation. The barrier preparation is applied after the corticosteroid preparation.
d. Preparations containing hydrocortisone should be applied for no more than a week.
e. Using Higher Potency Corticosteroids are not recommended for such age.
Zinc Oxide Oint. -------------- 15%
Zinc Oxide + Castor Oil Cream -------------- 7.5% + 50%
Zinc Oxide + Castor Oil Cream Proskin ® Blend of 30 gm
+ Simethicone + Vit. E
Dexpanthenol Cream/Oint. , Bepanthine® 0.05 gm/1 gm
Body Lotion
Dexpanthenol Cream Bepanthine Plus® (50 mg + 5 mg)/30 gm
+ Chlorhexidine
14.9- Topical Antihistamines and antipruritics

1. They can be used as an emollient, and may be of value where the pruritus is associated with dry
skin, Preparations containing Crotamiton are sometimes used but are of uncertain value,
Preparations containing calamine are often ineffective.
2. Calamine preparations are of little value for the treatment of insect stings or bites.
Crotamiton Cream/Lotion Eurax® 10%
Crotamiton + Hydrocortisone Cream Crotaphil-H® 100 mg
Calamine Lotion Calamine® + 2.5 mg
10%
Calamine + Glycerin + Camphor Cream Dermocal® 8% + 10% + 0.1%
Calamine + Zinc Oxide Lotion Calamyl® (8 gm + 8 gm)/100 ml
Calamine + Zinc Oxide Lotion Calamyl-D® (8 gm + 8 gm + 1 gm)
+ Diphenhydramine Per 100 ml
Diphenhydramine Gel Banophen® 1% , 2%
Diphenhydramine + Zinc Acetate Cream, Spray Banophen® Plus 2% + 0.1%
Diphenhydramine + Menthol Spray Dermamycin® 2% + 1%
Diphenhydramine + Allantoin Cream Allerga® 2% + 0.5%
Pramoxine Cream/Lotion Tronolane® , Prax®1%
Spray/Gel Eczemin®
Pramoxine + Zinc Acetate Lotion Caladryl® 1% + 0.1%
Pramoxine + Calamine Cream/Lotion Avenoo® (1% + 8%) lotion ,
(1% + 3%) Cream
Pramoxine + Menthol Cream Gold Bond® 1% + 1%
14.10 – Topical Anesthetics
o Topical local anesthetics are only marginally effective and occasionally cause sensitization.
o Can be used for insect stings and insect bites, but a short course of a topical corticosteroid
is more appropriate; Short-term treatment with an oral sedating antihistamine may help in
insect stings where sedation is desirable.
Lidocaine Cream , Gel Xylocaine ® 4% , 5%
Benzocaine Gel Benzocaine ® 10% , 20%
Dibucaine Oint. Nupercainal ® 10%
Lidocaine + Gel , Patch AnaMantle® 2% + 2.5%
Hydrocortisone
Lidocaine + Cream , Pliaglis® , Synera® 7% + 7%
Tetracaine Patch
Lidocaine + Cream , Emla® , Oraqix® 2.5% + 2.5%
Prilocaine Dental Gel
14.11 - Shampoos for Dandruff

1. Dandruff is an irritating, but harmless, condition that involves an acceleration in the normal
shedding of skin cells from the scalp; Extensive dandruff is considered to be a mild form of a type
of dermatitis known as seborrheic dermatitis, which is caused by an overgrowth of a yeast
organism that lives in the scalp.
2. In severe cases, a rash and reddish-yellow scaly pimple appear along the hairline and on face.
3. Shampoos containing Selenium Sulphide may have beneficial effects.
4. Ketoconazole shampoo should be considered for more persistent or severe dandruff or for
seborrheic dermatitis of the scalp.
5. A cream/ointment/Solution containing coal tar and salicylic acid is reserved for resistant
Dandruff; it is also very helpful in psoriasis that affects the scalp.
➢ Coal tar and salicylic acid preparations reduce the overproduction of new skin cells and
break down scales which are then washed off while shampooing.
Scientific name Dosage form Application
Ketoconazole Shampoo Treatment of seborrheic dermatitis and dandruff
apply twice weekly for 2–4 weeks (prophylaxis apply
once every 1–2 weeks).
Treatment of pityriasis versicolor apply once daily for
max. 5 days (prophylaxis apply once daily for up to 3
days before sun exposure.
Selenium Shampoo Seborrheic dermatitis and dandruff, apply twice
Sulphide weekly for 2 weeks then once weekly for 2 weeks and
then as necessary.

Ketoconazole Shampoo Nizoral® , Ketonaz® 1% , 2%
Selenium Sulphide Shampoo Selsun® 2.5% (120 ml)
Shampoo Selsun Blue® 1%
Pyrithione zinc Shampoo Head and Shoulders® 1%

Combination Products for Dandruff
Irox Sebarox® Shampoo Climbazole + Ciclopirox * 120 ml
+ Salicylic acid + Vit. B5
GAM Pyrithione® Shampoo Pyrithione zinc + Salicylic acid 2% (275 ml)
GAM Pirox® Shampoo Octopirox + D-Panthenol 1% (275 ml)
Ketazole Pluse® Shampoo Ketoconazole + Salicylic acid 130 ml
Scalpex® , Ketros® Shampoo Ketoconazole + Pyrithione zinc 2% + 1% (60 ml)
Fungicide® Lotion Ketoconazole + Pyrithione zinc 2% + 1% (90 ml)
Silkin® Shampoo Ketoconazole + Pyrithione zinc 100 ml
+ Aloe Vera
* Ciclopirox = Cyclopyrox, they are the same drug.
14.12 - Preparations for Psoriasis

1. The skin is constantly being renewed; as fast as dead cells in the outer layer (epidermis) are shed,
they are replaced by cells from the base of the epidermis; Psoriasis occurs when production of
new cells increases while shedding of old cells remains normal; As a result, the live skin cells
accumulate and produce patches of inflamed, thickened skin covered by silvery scales.
2. Thus, Psoriasis is a chronic inflammatory skin disorder characterized by enhanced epidermal
proliferation leading to erythema, scaling, and thickening of the skin.
3. There are several types of psoriasis including guttate,
flexural, pustular, and erythrodermic, but chronic plaque
psoriasis (psoriasis vulgaris) is the most common form.
In chronic plaque psoriasis the area’s most commonly
affected are the extensor sides of the knees, elbows, and
hands, and the scalp and sacrum.
4. In Psoriasis, there is no cure, treatments are designed to
induce a remission or suppress disease to a tolerable level.
5. Drug therapies for psoriasis are summarized in table 4.
6. A recent study published on JAMA dermatology, showed that
people with Psoriasis have an increased risk of developing
cancer and dying of it. (6)
7. Topical drugs are the treatment of first choice for chronic
plaque psoriasis.; Psoriasis refractory to topical therapy may
respond to systemic drugs.
8. A cream/ointment containing coal tar and salicylic acid
(Keratolytic) is very helpful in psoriasis that affects the scalp
or the skin, they remove the layers of dead skin cells.
9. Calcipotriene and Tacalcitol are analogues of vitamin D, that affect cell division and
differentiation; (by inhibiting keratinocyte proliferation and enhancing their differentiation).
10. Topical Tacrolimus and Pimecrolimus have a role in the treatment of psoriasis (they act by
blocking synthesis of several inflammatory cytokines); they are indicated also for atopic eczema.
11. Acitretin is a metabolite of etretinate, a retinoid (vitamin A derivative).
➢ Acitretin reduce production of keratin, the hard protein that forms in the outer layer of skin.
➢ Acitretin is teratogenic; In women with a potential for child-bearing, the possibility of
pregnancy must be excluded before treatment and effective contraception must be used
during treatment and for at least 3 years afterwards.
➢ Monitor serum-triglyceride, cholesterol, and liver function before and during treatment.
➢ Taken with or just after meal, Patient should protect the skin from sunlight; even on a bright
but cloudy day.
A) Topical Therapies:
Calcipotriene * Cream/Oint. Dovonex® , Daivonex® , Sorilux® 0.005% (50 mcg)
Tacalcitol Oint./Lotion Curatoderm® , Bonalfa® 0.0004% (4 mcg)
Calcitriol Oint. Vectical® 0.0003% (3 mcg)
Tazarotene Gel , Cream Zorac®, Fabior® , Avage® 0.05% , 1%
Methoxsalen Lotion Uvadex® 1%
Crisaborole Oint. Eucrisa 2%
Anthralin * Oint. , Paste Dithrocream® , Micanol® 0.1% , 0.5% , 1%
Fluorouracil ** Cream Fluoroplex® , Efudex® 0.5% , 1% , 5%
Tacrolimus ** Oint. Protopic®, Tacrus® , Talimus® 0.03% , 0.1%
Pimecrolimus ** Cream Elidel® , Pacroma® 1%
* Calcipotriene = Calcipotriol, they are the same drug. * Anthralin = Dithranol, they are the same drug.
** Tacrolimus, Pimecrolimus and Fluorouracil are immunosuppressants.
B) Combination Topical Products:
Calcipotriene + Betamethasone Oint, Gel, Foam Dovobet® , Daivobet® 50 mcg + 0.5 mg
Salicylic Acid + Betamethasone Oint./Lotion Diprosalic® 30 mg + 0.5 mg
Salicylic Acid + Mometasone Oint. Elica-sal® 5% + 0.1%
Salicylic Acid + Dexamethasone Oint. Salidex® 30 mg + 1.2 mg
Dithranol + Coal Tar + Salicylic acid Oint. Psorin® 0.11% + 1% + 1.6%
Salicylic Acid + Zinc Oxide Paste Lassar’s Paste® 2% + 24%
Fluocinolone + Tar Extract Oint. Cinolone Tar® 0.25 mg + 50 mg
Halobetasol + Tazarotene Lotion Duobrii® 0.01% + 0.045%
C) Oral/Systemic Therapies:
Acitretin Cap Soriatane® , Neotigason® 10 mg , 25 mg
Methoxsalen Cap , Tab Uvadex® , Neo-Medanine® 10 mg
Inj. Solu. 20 mcg/ml (10 ml Vial)
Cyclosporine Cap Sandimmune® , Gengraf® 50 mg , 100 mg
Apremilast Tab Otezla® , Aprezo® 10 mg , 20 mg , 30 mg
Fluorouracil Inj. Solu. Adrucil® 50 mg/ml
C) Biological Agents:
1. Biological agents are manufactured proteins that interrupt the immune process involved in
psoriasis, unlike generalized immunosuppressive drug therapies such as methotrexate,
biological agents target specific aspects of the immune system contributing to psoriasis, These
medications are generally well-tolerated and limited long-term outcome data have demonstrated
them to be safe for long-term use in moderate to severe plaque psoriasis, However, due to their
immunosuppressive actions, they have been associated with a small increase in the risk for
infection, Guidelines regard biologics as third-line treatment for plaque psoriasis following
inadequate response to topical treatment, phototherapy, and non-biologic systemic treatments.
• Individuals with psoriasis may develop neutralizing antibodies against monoclonal
antibodies, specifically, neutralization occurs when the antidrug antibody binds to the
binding site instead of TNF-α; Thus, it no longer decreases inflammation, and psoriasis may
even worsen.
Biological Agents for Psoriasis
Alefacept Inj. powder Amevive® 7.5 mg , 15 mg (per vial)
Efalizumab Prefilled Inj. Raptiva 30 mg
Ustekinumab Inj. Solu. Stelara® 45 mg/0.5 ml
Secukinumab Prefilled Inj. Cosentyx® 150 mg
Brodalumab Prefilled Inj. Siliq® 210 mg/1.5 ml
Dupilumab Prefilled Inj. Dupixent® 300 mg/2 ml
Guselkumab Prefilled Inj. Tremfya® 100 mg/ml
Ixekizumab Prefilled Inj. Taltz® 80 mg/ml
Notes:
1. Infliximab, Adalimumab, Golimumab and Etanercept are also used in the treatment of severe
cases of Crohn’s Disease and Ulcerative Colitis, Ankylosing Spondylitis, Rheumatoid arthritis.
2. Alefacept and Efalizumab are the only two drugs that target T cells.
o They are monoclonal antibodies that specifically targets the CD11a subunit of LFA-1, it also
blocks the adhesion molecules on the endothelial cells that lines the blood vessels, which
attract T cells.
o Efalizumab was voluntarily withdrawn from the European market in February 2009 and from
the US market in June 2009 by the manufacturer due to the medication's association with cases
of progressive multifocal leukoencephalopathy.
3. Brodalumab binds to the interleukin-17 receptor and so prevents interleukin 17 (IL-17) from
activating the receptor. In 2017 it received US FDA approval to treat moderate to severe plaque
psoriasis in people who have not improved with other treatments.
4. For other Biological Agents see chapter 10, Immunologics.
14.13 - Preparations for Eczema

1. Eczema is a skin condition causing a dry, itchy rash that may be inflamed and blistered.
2. Eczema can be triggered by allergy but often occurs for no known reason. In the long term, it can
thicken the skin as a result of persistent scratching; The most common type is Atopic Eczema, in
which there is often a family history of eczema, asthma, or allergic rhinitis.
3. Atopic Eczema commonly appears on the hands, due to detergents, and the feet, due to warm,
moist conditions in enclosed footwear.
4. Contact dermatitis, (another common form of eczema), is caused by chemicals, detergents, or
soaps; it may appear only after repeated exposure to the substance, but strong acids or alkalis can
cause a reaction within minutes; It can also result from irritation of the kin by traces of detergent
on clothes and bedding.
5. Allergic contact dermatitis can appear days or even years after initial contact has been made
with triggers such as nickel, rubber, elastic, or drugs (antibiotics, antihistamines, antiseptics, or
local anesthetics); Sunlight can also trigger contact dermatitis following use of aftershave or
perfume.
6. Nummular Eczema causes circular dry, scaly, itchy patches to develop anywhere on the body,
and bacteria are often found in these areas, all types of Eczema can become infected.
➢ Thus, some dermatologists combine routinely a topical antibiotic (Fusidic acid) with topical
corticosteroids in the treatment of infected Eczema or Nummular Eczema.
7. Treatment options for Eczema:
o Emollients soften and moisten the skin; Coal tar may be used for chronic atopic eczema.
o Oral antihistamines may be prescribed for a particularly itchy rash (topical antihistamines
make the skin more sensitive and should not be used).
o Topical corticosteroids may be needed to help control a flare up.
o severe cases that are resistant to other treatments may need to be treated with the
immunosuppressant drugs as (ciclosporin).
o Oral corticosteroids may be used to treat contact dermatitis.
o Nummular eczema usually requires corticosteroid treatment; If it is resistant, antibiotics may
be prescribed because infection is likely.
o Topical phosphodiesterase inhibitors; (Crisaborole); FDA approved for atopic dermatitis.
14.14 - Acne and Rosacea

1. Acne, known medically as Acne Vulgaris, is a common condition caused by excess production of
the skin’s natural oil (sebum), leading to blockage of hair follicles, it mainly affect adolescents but
it may occur at any age, due to certain drugs, exposure to industrial chemicals, oily cosmetics, or
hot, humid conditions.
2. Acne primarily affects the face, neck, back, and chest, the primary symptoms are blackheads,
papules (inflamed spots), and pustules (raised pus-filled spots with a white center).
o Mild acne may produce only blackheads and an occasional papule or pustule.
o Moderate cases are characterized by larger numbers of pustules and papules.
o In severe cases of acne, painful, inflamed cysts also develop; These can cause permanent
pitting and scarring.
A) Acne
Drug treatment nan be classified according to the severity (into mild, moderate and sever):
1. Mild acne is treated topically, in particular with benzoyl peroxide, Retinoids, and Antibacterials.
2. Moderate acne is best treated with oral rather than topical Antibacterials, of which
Tetracyclines (Tetracycline, Doxycycline) appear to be the drugs of first choice; Alternatives to
the Tetracyclines include erythromycin, and co-trimoxazole.
3. Severe acne is usually treated with oral Isotretinoin.
Specific notes for the topical preparations for acne:

a. Topical preparations, such as benzoyl peroxide, salicylic acid, and tretinoin, have a keratolytic
effect; Benzoyl peroxide also has an antibacterial effect.
b. It is usual to start with a lower strength and to increase the concentration of benzoyl peroxide
gradually (to minimize skin irritation).
c. Benzoyl peroxide can bleach clothing and bedding; If it is applied at night, white sheets and
pillowcases are best used and patients can be advised to wear an old T-shirt or shirt to minimize
damage to good clothes.
d. Topical Antibacterials are probably best reserved for patients who wish to avoid oral
Antibacterials or who cannot tolerate them; Topical preparations of Erythromycin and
Clindamycin are effective for inflammatory acne.
e. Topical Tretinoin (isomer of Isotretinoin), and Adapalene (a retinoid-like drug), are useful for
treating mild to moderate acne; Patients should be warned that some redness and skin peeling
can occur initially but settles with time; thus, Topical retinoids should be applied at night, a half
hour after cleansing the area effected with acne.
f. Topical Retinoids are contraindicated in pregnancy; women of child-bearing age must use
effective contraception.
g. Dapsone 5%, 7.5% gel is approved by the (FDA) for the treatment of acne vulgaris in adults and
children older than 12 years, Although Dapsone has antibacterial and anti-inflammatory
activity, the mechanism of action in the treatment of acne is unknown.
B) Rosacea
1. Rosacea is a skin condition that is sometimes confused with acne; It is a common chronic
inflammatory disorder of the facial pilosebaceous units, coupled with an increased reactivity of
capillaries leading to flushing and telangiectasia.
2. Rosacea has characteristic features of reddening (flushing), papules (a raised solid lesion,
usually less than 0.5 cm in diameter) and pustules (an accumulation of pus in the skin, in rosacea
there are no comedones (as in acne); age of onset of rosacea is 30 to 50 years.
o Severe rosacea can result in the thickening of facial skin, especially around the nose. The nose
can become bulbous and enlarged (rhinophyma); This is a very rare complication, and tends
to affect males much more than females.
o Ocular rosacea: There is a burning, gritty sensation in the eyes, making them bloodshot; The
inside of the eyelid may become inflamed (blepharitis) and appear scaly, causing
conjunctivitis; Some people may not tolerate contact lenses and sties may develop, In very
rare cases, vision can become blurred.
3. Oral Antibacterials (Doxycycline, Tetracycline) have been widely used, but clarithromycin,
erythromycin, and metronidazole are suitable alternatives.
4. Topical therapies, particularly Metronidazole and Azelaic acid, provide effective alternatives
to oral drugs; Other topical therapies that may be useful include Retinoids.
5. Topical Brimonidine is licensed for the treatment of facial erythema in rosacea
6. Ivermectin cream 1%; is FDA approved for the treatment of inflammatory lesions of Rosacea.
7. Oxymetazoline is an alpha1A adrenoceptor agonist; which acts as a vasoconstrictor, it is
specifically indicated for the topical treatment of persistent facial erythema associated with
Rosacea in adults.
First: Topical Products for Acne:

Benzoyl peroxide Gel, Lotion, Brevoxyl , Benoxide
® ® 2.5% , 5% , 10%
Cream
Azelaic acid Cream, Gel Skinoren®, Azelex®, Finacea® 20% , 15%
Topical Retinoids
Tretinoin Cream, Gel Retin A®, Retinoid® 0.025% , 0.05% , 0.1%
Lotion , Soap Acretin®
Tazarotene Gel , Cream Zorac®, Fabior® , Avage® 0.05% , 1%
Lotion Arazlo® 0.045%
Iso-Tretinoin Gel Isotrex® 0.05%
Adapalene Cream, Gel Differin® , Surecure® 0.1%
Trifarotene Cream Aklief® 0.005%
Topical Antimicrobials
Clindamycin Lotion/Gel Dalacin T® 1%
Erythromycin Gel/Oint. Erythrodar® , Erythrocin® 2%
Gel Spotex® 4%
Other Products for Rosacea/Acne
Metronidazole Gel Rozex® 0.75%
Dapsone Gel Aczone® 5 %, 7.5% (30, 60 gm tube)
Ivermectin Cream Soolantra® 1%
Brimonidine Gel Mirvaso® 0.33%
Oxymetazoline Cream Rhofade® 1%

Combination Topical Products for Acne
Benzoyl peroxide + Clindamycin Gel Duac® 5% + 1%
Benzoyl peroxide + Erythromycin Gel Benzamycin® 5% + 3%
Benzoyl peroxide + Adapalene Gel Epiduo® 2.5% + 0.1%
Isotretinoin + Erythromycin Gel Isotrexin® 0.05% + 2%
Erythromycin + Zinc Acetate ** Lotion Zineryt® (40 mg + 12 mg) per ml
Tretinoin + Erythromycin Solu. ,
Aknemycin® Plus (solu.), (0.025% + 4%)
Gel Retinomycin®, Eramax®
Tretinoin + Clindamycin Gel Veltin® , Ziana® 0.025% + 1.2%
Tretinoin + Salicylic acid Cream Lino Riten A ® 0.1% + 1%
+ Allantoin + D-Panthenol + 0.5% + 1%
** Zinc will increase the wound healing and increase the absorption of Erythromycin.
Second: Oral Products for Acne:

A) Oral Retinoid for acne:
1. Isotretinoin reduces sebum secretion, soothes inflammation, and helps to unblock hair follicles;
It is used for the systemic treatment of severe acne.
o Treatment with Isotretinoin often causes dry and scaly skin, particularly on the lips, also
the skin may become itchy and some hair loss may occur.
o its Teratogenic and must not be given to women of child-bearing age unless they practice
effective contraception or at least one month before treatment, during treatment, and for at
least one month after stopping.
o Isotretinoin sometimes increases blood lipid levels.
o It is given for at least 15-20 weeks; repeat courses are not normally required.
o Dosed as 0.5-1 mg/kg/day orally divided by two (twice daily).
o Dosed as 2 mg/kg/day if disease is very severe or is primarily manifested on the trunk.
Isotretinoin Cap Roaccutane®, Retane®, Decutan® 5 mg , 10 mg , 20 mg
Cap Isocor® 10 mg , 20 mg
Alitretinoin Cap Toctino® 10 mg , 30 mg
Acitretin Cap Soriatane® , Neotigason® 10 mg , 25 mg
B) Oral Hormonal treatment for Acne:

1. Products usually contains an anti-androgen; it is no more effective than an oral broad
spectrum antibacterial but is useful in women who also wish to receive oral contraception.
2. Improvement of acne with hormone therapy probably occurs because of decreased sebum
secretion which is under androgen control; Some women with moderately severe hirsutism may
also benefit because hair growth is also androgen-dependent.
3. Contra-indications include pregnancy and a predisposition to thrombosis.
Cyproterone Tab Androcur ® 50 mg
Cyproterone + Tab Diane * , Clairette
® ® 2 mg + 0.035 mg
Ethinyl Estradiol
Drospirenone + EE Tab Yasmine® , Zahraa® 3 mg + 0.03 mg
* Diane was withdrawn from the markets in 2012 in Canada, France due the high risk (4 times
®
more risk) of venous thromboembolism (blood clots in veins) than other alternatives.
14.15 - Preparations for Warts and Calluses
1. Warts (verrucas) are caused by a human papillomavirus (HPV), which most frequently affects
the hands, feet (plantar warts), and the anogenital region; treatment usually relies on local
tissue destruction.
2. Preparations of salicylic acid (keratolytic) are suitable for the removal of warts on hands and
feet; it is also suitable for the removal of corns and calluses.
3. Other treatment options include: Formaldehyde, Glutaraldehyde or Silver nitrate.
4. Paints and liquids contain salicylic acid, often in a collodion-based vehicle. Collodions
contain a nitrocellulose derivative, dissolved in a volatile solvent such as ether, acetone or
alcohol. On application, the solvent evaporates, leaving on the skin an adherent, flexible, water-
repellent film containing the medicament. This has the advantage of maintaining the salicylic
acid at the site of application.
5. Note: do not let adjacent area of normal skin come in contact with drug (apply some
Vaseline around the area). If they do, wash off the solution immediately with soap and water.
➢ Or simply use the Gel Dosage form (instead of Solu.), it delivers the salicylic acid and lactic
acid through a continuous release, allowing deeper penetration, and longer action whilst
simultaneously protecting the surrounding normal skin
6. The treatment is helped by prior soaking of the affected hand or foot in warm water for 5–
10 min to soften and hydrate the skin, increasing the action of the salicylic acid.
7. Lactic acid is included in some preparations with the aim of enhancing availability of the salicylic
acid which may enhance the effects of salicylic acid; However, it appears that combination
therapy has no additional benefit over salicylic acid alone.
8. Salicylic acid plasters: Corn and callus plasters contain high conc. (usually 40%), they should
be changed every 1–2 days for about a week, after which the callosity should lift away easily.
Salicylic acid + Lactic acid Solu. Duofilm® 16.7% + 16.7%
Gel Cornex® 16.7% + 16.7%
Salicylic acid + Lactic acid Solu. Cuplex® 11% + 4%
Salicylic acid + Lactic acid Gel Salatac® 12% + 4%
Salicylic acid + Lactic acid Solu. Collomak® 2 gm + 0.5 gm
+ Polidocanol * + 0.2 gm
Formaldehyde Gel Veracur® 0.75%
Glutaraldehyde Solu. Glutarol® 10%
Urea + Salicylic acid Cream GAM US® 20% + 2%
Silver Nitrate Pen, Stick Avoca® ** 75% , 95%
* Polidocanol is a local anesthetic and antipruritic.
** Avoca® is used for removing warts including verruca and excess tissue, it works by destroying tissue
on the surface layers of warts and verruca.
9. The treatment of Anogenital Warts should be accompanied by screening for other sexually
transmitted infections.
a. Soft non-keratinized external anogenital warts are usually treated with topical application of
Podophyllin (Podophyllotoxin); while Keratinized lesions may be better treated with Cryo-
therapy or other forms of physical ablation.
b. Genital Warts are treated with Imiquimod 5% cream (Aldara®), 3 time per week for up to 16
weeks, or by Podophyllotoxin 0.5% solution or gel (Wartec®), twice daily for 3 days, then 4
days of no therapy and repeating this cycle for up 4 times if necessary .
10. Imiquimod acts by enhancing the immune system to produce interferons to fight the virus
causing the wart; it is licensed for the treatment of external anogenital warts; it may be used for
both keratinized and non-keratinized lesions. It is also licensed for the treatment of superficial
basal cell carcinoma and actinic keratosis.
Podophyllotoxin Solu. Condyline ® 0.5%
Genital Solu. Condylox® 0.5% (3.5 ml)
Cream Warticon , Wartec
® ® 0.15%
Podophyllum resin + Paint Podowart ® (20% + 10% + 2%)/10 ml
Benzoin + Aloe Vera
Podophyllum resin + Paint Podowart S® (20% + 10% + 2% + 5%)
Benzoin + Aloe Vera Per 10 ml
+ Salicylic acid
Imiquimod Cream Aldara® , Zyclara® 5% , 3.75%
14.16 - Sunscreen preparations

1. People vary in their sensitivity to sunlight. Fair-skinned people generally have the least tolerance
and tend to burn easily when exposed to the sun, while those with darker skin, especially brown
or black skin, can withstand exposure to the sun for longer periods.
2. The light from the UVA spectrum is responsible for skin tanning and UVB light causes
sunburn; Sunburn is an inflammatory response to excessive exposure to ultraviolet which result
in vasodilatation and increase capillary permeability.
3. The rays of the sun are the most direct and damaging between 10 am and 3 pm, therefore the
customer should avoid sun exposure during this time of day as much as possible.
4. Sunscreen preparations contain substances that protect the skin against UVA and UVB
radiation, which usually contains 3 types of materials:
o Physical sunscreens: acts as a physical barrier to reflect and scatter about 99% of the light,
these include: Titanium dioxide, Red Petrolatum and Zinc oxide.
o Chemical sunscreens: these protect the skin by absorbing the light particles; when the light
is absorbed, a chemical reaction occurs which leads to destroying these light particles, this
chemical reaction generates free radicals (which may cause a secondary free radical damage
if used for a long period); these include: PABA (para amino benzoic acid), Cinoxate,
Octocrylene, Ethyl Salicylate, Homo salicylate, Oxybenzone, Dioxybenzone,
Avobenzone and Sulisobenzone.
o Antioxidants: these are usually included to prevent or reduced the damage from the free
radicals that is generated during the chemical sunscreen process; these include: Vitamin E,
green tea extract etc.
So, a prefect sunscreen usually contains these 3 types of ingredients to ensure the maximum
protection; commercially available sunscreens usually contain these materials.
5. The sun protection factor (SPF) gives a rough estimate of the efficiency of the product to block
UVB: For example, if a person normally show a signs of burning in 30 minutes without protection,
then a product with a SPF of 6 would extend the period of time until burning begins to 3 hours
(it extends the time taken to burn by 6 times), and so on with SPF of 15, 30, …. (However, in
practice, users do not apply sufficient sunscreen product and the protection is lower than that
found in experimental studies). (3)
6. SPF higher amount doesn’t affect that much and can be misleading; as follows:
SPF 15 = protects 93% of UVB, SPF 30 = protects 97% of UVB
SPF 50 = protects 98% of UVB, SPF 100 = protects 99% of UVB
7. Application:
➢ Sunscreen must be applied to all exposed areas of the body including the nose ad lips
(avoid contact with eye); Sunscreen should be reapplied every 2-3 hours; and for most
sunscreen product, they should be applied 15-30 min. before sun exposure.
14.17 - Hair Loss
First: Androgenetic Alopecia
1. It’s mainly a hair loss due to the presence of high serum amounts of Dihydrotestosterone
(the potent form of testosterone); it’s a condition that is very related to Genetics.
2. Finasteride (1 mg tablet) is licensed for the treatment of Androgenetic alopecia in men.
Continuous use for 3–6 months is required before benefit is seen, and effects are reversed 6–
12 months after treatment is discontinued.
➢ It’s a 5α-reductase inhibitor (inhibits the enzyme responsible for metabolizing Testosterone
into Dihydrotestosterone; which is related to androgenic alopecia).
➢ Finasteride could produce feminization of a male fetus if used in pregnant women;
therefore, it recommended that women who are or may become pregnant should not handle
crushed or broken Finasteride tablets.
➢ Finasteride has been detected in semen, therefore use of a condom is recommended if the
patient’s sexual partner is, or may become pregnant.
3. Alfatradiol is a 5α-reductase inhibitor (like Finasteride) used topically for the treatment of
androgenic alopecia (hair loss) in men and women.
4. Minoxidil:
a. Topical application of Minoxidil may stimulate limited hair growth in a small proportion of
adults, but only for as long as it is used.
b. Minoxidil acts by lengthening the duration of the anagen phase of the hair follicle; it also
increases the blood supply to the hair follicle (it acts as a potassium channel opener; thus,
widening blood vessels; which allows more oxygen, nutrients supply to the follicles).
c. Minoxidil is available as 2% and 5% products: however, women should use 2% products
(since females respond better to minoxidil than males); women should not use the 5%
products, since it can cause hirsutism at other sites, such as the face, chest, ear rim, and back.
➢ Dose: Apply 1 mL twice daily to dry hair and scalp.
5. The combination of both oral Finasteride and topical Minoxidil has a better result than if used
each alone in the treatment of hair loss.
6. For females; the use of oral antiandrogens (Cyproterone) or Spironolactone (diuretic with
mild antiandrogen activity) may be useful in cases of hair loss due androgenic alopecia.
7. There are several herbal combinations for hair loss, such as the Cysteine B6 Shampoo and
tablets, these prove efficacy by live examples.
8. Some anti-hair loss Shampoos contain Caffeine; which can help to promote hair growth in the
initial phase of hair growth; it does that through inhibiting DHT (Dihydrotestosterone).
9. Procyanidin B2 is an innovative new molecule (which is extracted from Green Apples), which in
some studies have shown 200% more effective than 1% Minoxidil, it Increases both the total
number of hair and the thickness of hair, and can be used in men and women.
➢ It’s considered as a topical 5α-reductase inhibitor (topical antiandrogen).
Finasteride Tab Propecia® , Pro-hair® 1 mg
Alfatradiol Scalp Solu. Pantostin® 100 ml
Minoxidil Spray, Shampoo Regaine®, Rogaine®, Minoxidil® 2% , 5%
Topical Solu. Avogain® , Minostyl® 2% , 5%
Topical Solu. Minoxidil MAX® 6.5%
Minoxidil + Finasteride Topical Solu. Coverit Plus® 5% + 0.1%
Procyanidin B2 Scalp Solu. Mostal® 50 ml
Cysteine + B6 Shampoo Cystine B6 Shampoo® 200 ml
Cysteine + B6 Tab Cystine B6 bailleul® 76% + 2%
+ Zinc + Arginine + 2% + 1%
Second: Alopecia Areata
1. It’s a hair loss due to an autoimmune disease, in which the immune (the T-lymphocytes)
attacks its own hair follicles, causing round patches of hair loss.
2. Alopecia Areata is genetically related to other autoimmune diseases as atopic dermatitis, Vitiligo
and asthma; which can effect both males, females and children.
3. It most often affects the scalp; however it can also affect any hair-bearing areas, including
beard, eyebrows and eyelashes.
4. Treatment options include: intralesional corticosteroids injections, topical corticosteroids,
topical/systemic immunosuppressants, Minoxidil and Anthralin.
5. Intralesional corticosteroids are the 1st line of therapy for localized conditions of alopecia
areata, and are superior to topical corticosteroids.
➢ Triamcinolone is the most common corticosteriod used; less than 0.1 ml is injected per site,
and injections are spread out to cover all the affected areas (usually 1 cm between each
injection site); injections are given every 4-6 weeks.
6. Minoxidil is mainly used for androgenic alopecia, but its of a little value in Alopecia Areata,
(response rate vary from 8%-44%); initial regrowth may be seen withen 12 weeks of treatment
(5% solution applied twice daily).
7. Anthralin alters the skin’s immune system (its mainly used for Psoriasis); used for Areata as
short contant therapy, applied to the skin and left for 20-50 minutes before washing it out.
8. Some cases of Alopecia Areata (AA) responed to PRP therapy (platelet rich plasma).
9. Some studies shows a benefit of oral Zinc Gluconate (30-50 mg/day) in the treatment of AA.
10. In the cases of hair loss in eye lashes, Latanoprost and Bimatoprost are used (they are
prostaglandin analogs, which are usually used to treat Glucoma); they are shown to increase the
number, length and thickness of eyelashes.

Anthralin * Oint. , Paste Dithrocream® , Micanol® 0.1% , 0.5% , 1%
* Anthralin = Dithranol, they are the same drug.
14.18 – Products for treating Hirsutism

1. Hirsutism (excessive hair growth) may result from hormonal disorders, or as a side-effect of
drugs such as Minoxidil, corticosteroids, anabolic steroids, androgens, Danazol, and
Progestogens.
2. Eflornithine (an antiprotozoal drug), inhibits the enzyme ornithine decarboxylase in hair
follicles, (thus Blocks putrescine that is necessary for the growth of hair follicles); Topical
Eflornithine can be used as an adjunct to laser therapy for facial hirsutism in women; it
should be discontinued in the absence of improvement after treatment for 4 months.
➢ The best solution for excessive hair is laser therapy; but unfortunately, laser therapy doesn’t
work for gray-white hair, (Eflornithine works both on all hair types including gray ones).
3. Other option for treating hirsutism include: Metformin, Spironolactone and Cyproterone.
➢ Metformin is used for Hirsutism in women with polycystic ovary syndrome (PCOS); Systemic
treatment is required for 6–12 months before benefit is seen.
➢ Spironolactone (diuretic + mild antiandrogenic activity) and Cyproterone (antiandrogen)
are useful when Hirsutism is due high androgen levels.
Eflornithine Cream Vaniqa® 11.5%
Cream Florexa® 13.9%

14.19 – Vitiligo
1. Vitiligo is a long-term skin condition characterized by patches of the skin losing their pigment
(due to losing melanin, the pigment that determines the color of skin, hair and eyes), The
patches of skin affected become white and usually have sharp margins; The hair from the skin
may also become white, often the patches begin on areas of skin that are exposed to the sun
and It is more noticeable in people with dark skin (Its occurs mainly when the cells that produce
melanin (melanocytes) die or no longer produce melanin).
2. The exact cause of vitiligo is unknown; but it is believed to be due to genetic susceptibility that is
triggered by an environmental factor such that an autoimmune disorder, which results in the
destruction of skin pigment cells.
3. There is no known cure for vitiligo (the treatment goal is to stop or slow the progression of
pigment loss); For those with light skin, sunscreen and makeup are all that is typically
recommended, other treatment options may include corticosteroid creams or phototherapy to
darken the light patches; Alternatively, efforts to lighten the unaffected skin, such as with
hydroquinone can be sometimes usefull.
4. Treatment options for Vitiligo include:
a. Immune mediators, which include Topical Corticosteroids (can help to return the color to
skin, Repigmenting), and calcineurin inhibitors (such as tacrolimus or pimecrolimus).
b. Topical Vitamin D analogs (Calcipotriene, which can be combined with other therapies).
c. Photochemotherapy (Psoralen + Ultraviolet A) or called PUVA.
d. Laser therapy (Excimer laser, which can be used for small areas of vitiligo).
e. Depigmentation the darker skin (using Hydroquinone or Monobenzone).
14.20- Skin Aging and wrinkles

1. As skin ages, it becomes thinner and more easily damaged; Intensifying this effect is the
decreasing ability of skin to heal itself as a person ages, and among other things, skin aging is
noted by a decrease in volume and elasticity.
2. There are many internal and external causes to skin aging (called Intrinsic aging and extrinsic
aging); also, aging skin receives less blood flow and lower glandular activity, chronic topical
corticosteroid using causes degradation of collagen, which accelerate skin aging.
➢ Intrinsic aging is influenced by internal physiological factors alone, and extrinsic aging by
many external factors (also called chronologic aging); extrinsic aging is most often referred
to as photoaging; also free radicals cause a direct damaging effect on the dermal fibers.
3. A validated comprehensive grading scale has categorized the clinical findings of skin aging as
laxity (sagging), rhytids (wrinkles), and the various facets of photoaging, including erythema
(redness), and telangiectasia, dyspigmentation (brown discoloration), solar elastosis
(yellowing), keratoses (abnormal growths) and poor texture.
4. Intrinsic aging is sometimes referred to as chronological aging and is an inherent degenerative
process due to declining physiologic functions and capacities; aging process may include
qualitative and quantitative changes and includes diminished or defective synthesis of collagen
and elastin in the dermis.
5. Extrinsic aging of skin is a distinctive declination process caused by external factors, which
include ultra-violet radiation, cigarette smoking, air pollution.
➢ Radiation from sunlight has the most widespread documentation of its negative effects on the
skin, because of this, extrinsic aging is often referred to as photoaging.
➢ Photoaging may be defined as skin changes caused by chronic exposure to UV light.
Photodamage, implies changes beyond those associated with aging alone, defined as
cutaneous damage caused by chronic exposure to solar radiation and is associated with
emergence of neoplastic lesions.
6. Wrinkles are a by-product of the aging process, As people age, skin cells divide more slowly, and
the middle layer of the skin (dermis) begins to thin; the dermis is composed of a network of
elastin and collagen fibers, which offer support and elasticity, as this network loosens and
unravels with time, depressions are created on the skin surface; Aging skin is also less able
to retain moisture, less efficient in secreting oil, and slower to heal, and all these factors
contribute to the development of wrinkles.
➢ Lines on the forehead, between the eyebrows (frown lines), and jutting from the corner of the
eyes (crow's feet) are believed to develop because of small muscle contractions; Smiling,
frowning, squinting and other habitual facial expressions cause these wrinkles to become
more prominent, over time, these expressions coupled with gravity contribute to the
formation of wrinkles.
➢ Exposure to UV light breaks down collagen fibers and leads to the production of
abnormal elastin; when ultraviolet light damages skin tissue, an enzyme called
metalloproteinase is produced; this enzyme creates and reforms collagen, and during the
process some healthy collagen fibers are damaged, resulting in solar elastosis (the
disorganized formation of fibers); Wrinkles develop when the rebuilding process occurs over
and over, less efficiently each time.
7. Wrinkles fall into two functional categories: fine surface lines (caused by ultraviolet light) and
deep furrows (caused by muscle contractions from facial expressions due aging); Wrinkle
treatments are in general much more effective for fine lines; Deeper creases may require
techniques that are more aggressive.
8. Treatments available for skin wrinkles include topical medical treatments (such as vitamin A
acid or its derivatives as Tretinoin, alpha hydroxy acids, antioxidants, and moisturizers) and
more invasive procedures (such as glycolic acids peels, deep peels, dermabrasion, laser
resurfacing, surgical procedures, injection of fillers, and Botox).
➢ Dermabrasion or mechanical peeling (sanding layers away), and chemical peels (dissolving
skin away) are two of the traditional methods used in skin resurfacing; common chemical
peels include: Alpha Hydroxy Acid (AHA), Beta Hydroxy Acid (BHA), Trichloroacetic
Acid (TCA), Lipo Hydroxy Acid (LHA), Salicylic Acid and Phenol.
➢ Tretinoin decreases cohesiveness of follicular epithelial cells, it also stimulates mitotic
activity and increased turnover of follicular epithelial cells; other Tretinoin derivatives
include Retinol, Retinyl Palmitate and Retinaldehyde (Retinal); which are found in most
antiwrinkles creams.
➢ Topical glycosaminoglycans supplements (Topical Hyaluronic acid) can help to provide
temporary restoration of enzyme balance to slow or prevent matrix breakdown and
consequent onset of wrinkle formation, Glycosaminoglycans (GAGs) are produced by the
body to maintain structural integrity in tissues and to maintain fluid balance (Hyaluronic
acid promotes collagen synthesis, repair, and hydration) it also serve as a natural
moisturizer and lubricant between epidermal cells to inhibit the production of matrix
metalloproteinases (MMPs).
➢ Argireline (Acetyl Hexapeptide-3) relaxes facial muscles to prevent wrinkles and fine lines
formation; Topical Vitamin C aids in the healing process, it also stimulates the synthesis of
collagen; and also act as antioxidant; Topical antioxidants, as Vitamin E (Tocopherol),
topical Co-enzyme Q10, helps to reduce the damage caused by free radicals.
➢ Dermal fillers are injectable products frequently used to correct wrinkles, and other
depressions in the skin, they are injected into the face to help fill in facial wrinkles and
restoring a smoother appearance, The most common Filler products are Hyaluronic Acid,
Calcium Hydroxylapatite, Collagen, Polycaprolactone, Polymethylmethacrylate and
Polyacetic Acid.

➢ Botulinum toxin (Botox) is a neurotoxin protein produced by the bacterium Clostridium
botulinum; Besides its cosmetic application, Botox is used in the treatment of other conditions
including migraine headache and cervical dystonia (spasmodic torticollis) (a neuromuscular
disorder involving the head and neck).
o Botulinum toxin treats wrinkles by immobilizing the muscles which cause wrinkles
(when injected in small doses into muscles; it blocks the chemical signals that cause
muscle to contract – inhibits Acetylcholine), and when the muscles relax; the skin
flattens and appears smoother with less wrinkles.
o It is not appropriate for the treatment of all wrinkles; it is indicated for the treatment
of glabellar lines or frown lines (between the eyebrows), lines across the forehead and for
crow’s feet (corners of the eyes) in adults.
➢ Laser resurfacing is FDA-cleared skin resurfacing procedure in which lasers are used to
improve the condition of the skin; Two types of lasers are used to reduce the appearance of
fine lines and wrinkles on the face; an ablative laser that removes thin layers of skin and a
nonablative laser that stimulates collagen production; Nonablative lasers are less effective
than ablative ones but they are less invasive and recovery time is short, after the procedure
people experience temporary redness, itching and swelling.

Ardene C20® Cream Vitamin C + Glycolic Acid 20% + 6%
+ Vitamin E + Grape seed oil
+ Retinyl Palmitate + others
Duolys CE ® (ACM) Serum Vitamin C concentrate 15 ml
H3 Retinol ® (Gerovital) Cream Retinol + antioxidants 40 gm
Derma Anti-Wrinkles Cream Retinyl Palmitate + Hyaluronic acid 30 gm cream
®
Biopeptide CL + Ronacare AP *
Derma Instant Youth® Cream Argireline + Hyaluronic acid 30 gm cream
* Ronacare AP = Bis-Ethylhexyl Hydroxydimethoxy benzlmalonate, which is an antioxidant.
14.21- Antiperspirants
1. Hyperhidrosis (excessive sweating) can be generalized or focal, affecting the palms of the
hands, soles of the feet, or axillae, People with hyperhidrosis may sweat even when the
temperature is cool or when they are at rest, those with hyperhidrosis appear to have
overactive sweat glands.
2. Excessive sweating may be controlled with strong anti-perspirants, they act by forming gel
spheres in sweat glands that absorb sweat leading to negative feedback to decrease sweating.
➢ Antiperspirants can cause skin irritation, and large doses of aluminum chlorohydrate can
damage clothing.
➢ Deodorants do not prevent sweating, but are helpful in reducing body odor.
3. Anticholinergic drugs, such as Glycopyrrolate, help to prevent the stimulation of sweat glands;
Although effective for some patients, these drugs have not been studied as well as other
treatments, their Side effects include dry mouth, dizziness, and problems with urination.
4. Beta-blockers or benzodiazepines may help reduce stress-related sweating.
5. Botulinum toxin type A (Botox) is FDA approved for the treatment of severe underarm
sweating, a condition called primary axillary hyperhidrosis; their effect lasts for several months.
➢ Small doses of purified botulinum toxin injected into the underarm temporarily block the
nerves that stimulate sweating.; Side effects include injection-site pain and flu-like symptoms.
➢ Botox can be used for the sweating of the palms; but it can cause mild, but temporary
weakness and intense pain.
6. Drug therapy should be tried initially but is often ineffective in severe cases.
➢ Aluminum salts, such as aluminum chloride or aluminum chlorohydrate in alcoholic
solvents applied topically, may be successful in milder forms of focal hyperhidrosis.
➢ Initially a patient may need to use Aluminum salts three to seven times a week; and after
sweating becomes normal, the person may need to use it only once every one to three weeks.
➢ In more severe cases specialists use Glycopyrronium Bromide as a (0.05%) solution in the
iontophoretic treament of hyperhidrosis of plantar and palmar area.
Aluminum Chloride Solu. , Spray Anhydrol®, Driclor® 20%
Hexahydrate
Aluminum Chlorohydrate Cream Aquax-Deo® 75 gm Cream
Aluminum zirconium Soap Secret® 19%
tetrachlorohydrix
Glycopyrronium Bromide Powder Robinul® 3 gm
Glycopyrronium tosylate * Cloth , pouch Qbrexza® 2.4%
* The drug solution is on a pre-moistened cloth for application to the skin; approved for use only
in underarms q24 hours (not suitable for other areas).
14.22 – Skin Bleachers/Skin whitening (Depigmenting Agents)

1. Hyperpigmentation is the darkening of an area of skin caused by the increased melanin in that
spot, it can be caused by sun damage, inflammation, and skin injuries including Acne.
2. There are two main types of hyperpegmintation, Melasma and post-inflammatory
hyperpigmentation (PIH).
➢ Melasma is more common in females than males, can be tiggered during sun exposure
(worsen during summer), its common in pregnant women and those who are taking
contraceptive or hormonal replacment therapy (HRT).
➢ post-inflammatory hyperpigmentation (PIH) is a temporary pigmentation that follows
skin injury (sun burn, dermatitis, skin infections, Acne).
3. Topical depigmenting agents inhibit melanogenesis (the pigmentation pathway by which cells
produce melanin), they are applied on the skin, on the affected area to treat hyperpigmentation
or to whiten the skin. (5), these include: Hydroquinone, Monobenzone, Tretinoin, Azelaic Acid,
Cysteamine and Glutathione.
➢ Hydroquinone inhibits tyrosinase (an enzyme involved in the production of melanin).
➢ Monobenzone works by increasing elimination of melanin from skin cells.
➢ Tretinoin increases keratinocytes turnover.
➢ Azelaic Acid decrease the activity of melanocytes.
➢ Cysteamine works by inhibiting melanin synthesis pathway.
➢ Glutathione cause skin lightening by converting melanin to a lighter color and deactivating
the enzyme tyrosinase, which helps produce the pigment.
4. Other products that cause skin lightening when used topically include: Kojic Acid, Arbutin,
Licorice extracts, Mequinol, Niacinamide (vit B3), N-Acetyl Glucosamine, Aloe vera and Soy.
5. Oral Tranexamic acid has shown to provide rapid and sustained lightening in melasma; by
decreasing melanogenesis in epidermal melanocytes.
➢ Although, some dermatologists use topical Tranexamic acid for whitening combinations.
6. Other intervesions for skin whitening include:
➢ Chemical peeling, using (Alpha Hydroxy Acid (AHA), Beta Hydroxy Acid (BHA),
Trichloroacetic Acid (TCA), Lipo Hydroxy Acid (LHA), Salicylic Acid and Phenol.
➢ Mechanical peeling, using either microdermabrasion or dermabrasion.
➢ Laser therapy by either pulsed CO2 or Q-switched alexandrite.
Hydroquinone Cream Melquin , Eldopaque
® ® 2% , 4%
Cream Avoquin ® 1.9%
Soap Eldoquin ® 4%
Monobenzone Cream Benoquin ® 20%
Azelaic acid Cream, Gel Skinoren®, Azelex®, Finacea® 20%, 15% (gel)
Azeclear®
Cysteamine Cream Cyspera® 5%
Mequinol + Retinol Topical Solu. Solage® (2% + 0.01%),
(10% + 1%)
Hydroquinone + Tretinoin Cream Derma Lightening® 2% + 0.025%
Hydroquinone + Fluocinolone Cream Tri-Luma®, Triderma® 4% + 0.01%
+ Tretinoin + 0.05%
Hydroquinone + Mometasone Cream Melacare® , Getlite® 2% + 0.1%
+ Tretinoin Makcare® + 0.025%
Hydroquinone + Hydrocortisone Cream Pigmanorm® 4% + 1%
+ Tretinoin + 0.1%
Hydroquinone + Vit. C + Vit. E Cream Ardene Skin lightener® 30 gm combo
+Kojic acid + Milfoil Extract
Hydroquinone + Vitamin C Cream Avalon Whitening® 1.9%
+ Vitamin E + (sunscreen)
Glutathione Soap G Soap® , Glutathione® ------------
Vial RM Glutathione ® 100 mg/vial
Cap Glutawhite® 500 mg
Spray Ivory Caps ® 30 ml
Other products for skin whitening/depigmenting

Aquax Whitening® Cream β-white 50 gm cream
Alpha Plus® Cream Arbutin + Glabridin 1% + 0.5%
Eva® Serum Vitamin C + Salicylic Acid 20% + 2%
+ Hyaluronic acid + Niacinamide + 5% + 3.5%
+ Retinol + MSM + 2% + 10%
Rexsol Pigment® Serum Hydroquinone + Lactic acid 60 ml Solu.
+ Citric acid
Rilastil D-Clar® Serum Butyl Resorcinol + Vitamin C 30 ml Solu.
+ Alpha Hydroxy Acid
Notes:
1. β-White is a complex combination of a Transforming growth factor-β1 (TGF-β1) agonist peptide
encapsulated in a liposome vehicle, recently TGF-β1 was described for its role in melanogenesis,
it has demonstrated an inhibitory activity on melanin synthesis.
2. Glabridin, a component of licorice, it is a tyrosinase inhibitor.
3. Arbutin (a glycoside; a glycosylated hydroquinone), is a naturally derived substance found in
plants such as bearberry, cranberries, blueberries, wheat, and pears. Our bodies break down
arbutin into glucose and hydroquinone; Since hydroquinone is released slowly by arbutin, it is
less irritating to skin than directly applied synthetic hydroquinone.
4. Kojic acid works by blocking tyrosine from forming, which then prevents melanin production.
5. Resorcinol exerts a keratolytic activity; mainly used for acne.
14.23 – Dark spots under the Eyes
1. The area under the eyes is very thin, the venous circulation underneath the skin contributes to
the dark color of the area, which is mainly due lack of enough sleeping or due to tiredness.
➢ Also, Oversleeping, extreme fatigue, or just staying up a few hours past your normal bedtime
can cause dark circles to form under your eyes.
2. The dark circles are also due to the accumulation of hemoglobin and its metabolism’s by-products
(bilirubin and iron) in the tissues underneath the eyes, both in the corium and in the epidermis.
3. Causes of dark circles:
➢ Hereditary factors: The thinnest the skin, the more intense the blue tone; also, the bone
structure may also form cavities in the face, causing the dark circles to look even more intense
due to the shadows created.
➢ Allergies, asthma and eczema: Histamine release is also causing dark coloration of the skin,
rubbing of the skin due to itching intensifies the appearance of dark circles; also, it’s more
common for people with seasonal allergy, food allergy etc.
➢ Medication: All drugs causing vasodilation are also intensifying the problem of dark circles.
➢ Iron deficiency anemia: The iron deficiency can also intensify the appearance of dark circles
due to lower quantity of oxygenated blood (which has intense red color).
➢ Tiredness: It increases skin’s paleness and allows the circulation of the blood to be more
apparent underneath the skin.
➢ Hepatic disturbance: Dark circles under the eye can also be a symptom of a systemic disease.
➢ Pregnancy and Menstruation: These conditions can be associated with dark circles due to
lower quantity of iron in the blood
➢ Ageing: With age and the loss of collagen the skin becomes thinner and more transparent; in
such a case dark circles are becoming more intense and they are often associated with bags
or sacs under the eyes.
➢ Nutrition: In rare cases lack of vitamins can cause dark circles. A healthier nutrition is helping
reduce the appearance of the dark circles.
➢ Sun exposure: intensifies the appearance of dark circles as the sun is causing the increase of
melanin synthesis.
4. The treatment for your dark circles depends upon their severity and the underlying cause;
Multiple interventions can be used to address the pigmentation around the eyes, but each
treatment may not work for all types of dark circles; A number of cosmetic products may help
lighten skin discoloration while improving collagen synthesis; (the two factors that can
minimize the appearance of dark circles.)
➢ Retinoids are among the most widely used topical agents that aim to enhance the structural
quality and appearance of the skin.
➢ Other skin-enhancing compounds that can be used to address under-eye hyperpigmentation
include Hydroquinone, Azelaic Acid, Kojic Acid, Arbutin, Vitamin C, Vitamin K, Haloxyl.
o These compounds can only help diminish the visibility of dark circles when applied in the
right dosage; Overuse of such skin products can lead to irritation and other side effects.
5. Other interventions for dark areas include:
➢ Chemical peeling may help lighten the dark circles caused by surface-level
hyperpigmentation; Given that the skin covering the lower lids is extremely thin, only a mild
exfoliant such as glycolic acid is used to prevent potential skin damage.
➢ Laser therapy: Both invasive and noninvasive lasers have been used to improve under-eye
darkening, the type of laser depends on the underlying issue with the skin:
o Q-switched laser targets pigmentation, radiofrequency helps with collagen production
and skin tightening, and intense pulsed light (IPL) can improve mild pigmentation
secondary to sun damage.
o Ablative laser resurfacing is a more powerful invasive laser that can improve skin
pigmentation, stimulate collagen production, and soften fine lines, this laser has the ability
to target multiple factors contributing to under-eye circles.
➢ Hyaluronic acid gel soft tissue fillers: If the dark circles are the result of irregularly shaped
lower eyelids, hyaluronic acid (HA) fillers may be used to flesh out the under-eye hollows.
➢ Blepharoplasty: a surgery involves cutting into the lower eyelid area to scoop out the excess
fat deposits, muscle, and skin that may be casting a shadow under your eyes.
o Even though this surgery is one of the more invasive measures, it is also one of the most
effective ways to correct the contour irregularities that contribute to baggy eyelids and
dark circles.
Derma Under Eye ® Gel Haloxyl + Hyaluronic acid 2% + 5% (30 gm gel)
Cetaphil Hydrating Cream Hyaluronic Acid + Licorice Extract 14 gm cream
Eye® + Vitamin Complex
Rilastil Micro Eye Cream Retinol + Haloxyl + Hyaluronic Acid 15 gm cream
Contour ® + Vitamin Complex
* Haloxyl = a combination of (N-hydroxy succinimide, chrysin, palmitoyl tripeptide1, palmitoyl
tripeptide7); which when applied topically solubilize the accumulated iron for easier elimination
and stimulates the enzyme that is responsible for clearance of bilirubin.
14.24 - Topical Products for Scars

1. Topical applications include the use of products such as silicone gels or sheeting, creams or
salves, vitamins E and A (retinoic acid), herbal remedies, and others, these are the most widely
used approaches by patients because they are easy to use and are of low cost.
2. Depressed scars can be filled with temporary or permanent filler materials.
3. Silicone gel or silicone sheeting may be applied over healing wounds to promote scar
improvement, The improvement in scarring is purportedly due to the water retention in tissues
beneath the occlusive silicone dressings, Other petroleum-based ointments also provide this
occlusive effect, promoting hydration and improving scar appearance.
4. Topical applications including vitamin A have been shown to improve the aesthetic properties
of scars, Vitamin A as applied to the skin is 0.05% retinoic acid and is an effective resurfacing
agent; Scars exposed to retinoic acid are typically less irritated, less elevated, and softer.
The topical route of administration is preferred because the systemic toxicity of vitamin A is more
easily avoided than with oral intake of the vitamin.
5. Vitamin E penetrates deeply into the dermis and has an antioxidant effect, If applied to a wound
in the early stages of healing, the recovery of tensile strength may be adversely affected; Lastly,
creams or salves containing herbal remedies have been shown to be largely ineffective in
changing the attributes of scars, or at best, are of unproven efficacy.
6. Intralesional injections allow for greater penetration of the scar by the therapeutic agent and
for delivery of greater concentrations locally than with topical or systemic administrations.
7. The 2 most common intralesional injections are corticosteroids and antimitotic agents.
Intralesional corticosteroid injection has been extensively studied and proven to reduce the size
of hypertrophic scars and keloids. (1)
a. Steroids exert several effects on healing scars, including reducing fibroblast populations,
reducing the formation of new vasculature, and decreasing fibrosis.
b. Antimitotic agents such as 5-fluorouracil or bleomycin are used intralesionally to inhibit
proliferation of scar tissue; These agents are contraindicated in pregnancy.

Contractubex® Gel Heparin Na + Allantoin 5000 IU + 1 gm
+ Extractum cepae (onion) + 3 gm
Patch Cepalin + Allantoin ---------------------
Mebo Scar® Lotion Sesame + Cactus + Beeswax extracts ---------------------
+ Linoleic acid + Tyramine
Acnethro® Gel , Soap Allantoin + Aloe Vera + Vit E ---------------------
NewGel+® Gel , Patch Silicon dioxide 30 gm gel
Scarmed® Gel Silicon dioxide 15 gm gel
Dermatix®, Gel Polysiloxane + Silicon dioxide 10 gm gel
Vaniza®
Opexa® Gel Dimeticone + 10 gm gel
Ascorbyl Testraisopalmitate
Dermatix Ultra® Gel Cyclopentasiloxane + Vit. C ester ---------------------
Mederma® Cream/Gel PEG-4, Allium Cepa, Bulb Extract, ---------------------
Xanthan Gum, Allantoin
14.25 – Wound Care Products:

1. These products help in wound cleansing and moisturizing; some also help in the healing process.
2. There are simple techniques which are applied for wound care and cleaning, they include:
a. Negative pressure wound therapy (NPWT), this therapy is also called wound vacuum, or
wound vac. therapy. A vacuum device uses suction to remove fluid and waste from the wound
and pull the edges closer together. NPWT may also increase blood flow and new tissue growth
in the wound. (1)
b. Hyperbaric oxygen therapy (HBO) is used to get more oxygen into the body. The oxygen is
given under pressure inside of a tube-like chamber called a hyperbaric or pressure chamber.
3. Topically applied Simvastatin may have significant therapeutic potential for enhanced wound
healing in patients with impaired microcirculation such as that in diabetes; (by enhancing
angiogenesis and lymphangiogenesis).
4. Phenytoin Spray enhance the formation of granulation tissue; promoting deposition of collagen
and other connective tissue components, thus enhance wound healing.
5. Appling Insulin Topically or by injecting it around the wound and burn can increase and
accelerate the wound healing.
Dermabond® prefilled appl. 2-octyl cyanoacrylate * -----------------
Regranex® Gel Becaplermin 0.01%
Prontosan® Gel , Solution Betaine + Polyhexanide 0.1% + 0.1%
Iodosorb® Gel Cadexomer iodine 0.9%
Santyl® Oint. Collagenase 250 units/gm
Hametan® Cream Hamamelis Virginiana extract 536 mg/30 gm tube
Madecassol® Oint. Centella Asiatica + Neomycin (10 mg + 3.5 mg)/1 gm
Eletone® , Cream Petrolatum + Mineral oils 100 gm tube
Tropazone®
Mebo® Oint. β-Sitosterol 0.25%
Magic Cream® Cream β-Sitosterol 0.25%
Solcoseryl® Oint. Protein-free hemodialysate 5%
Solcoseryl® Jelly Gel Protein-free hemodialysate 10%
Healsol® Spray Phenytoin -----------------
Notes:
1. Dermabond® is indicated to hold closed easily approximated skin edges of wounds.
a. Countraindicated in Wounds with active infection, gangrene.
2. Becaplermin is a Recombinant human PDGF-BB; stimulates chemotactic recruitment of wound-
healing cells; promotes angiogenesis and induces fibroblast proliferation and differentiation to
promote wound healing; also granulation tissue enhancer.
a. this drug should be used with caution in patients with known malignancy.
b. increase risk of mortality secondary to malignancy in patients treated with 3 or more
tubes of becaplermin gel.
3. Betaine Acts as surfactant/detergent to aid with debridement, Polyhexanide is a Preservative,
The combination of these 2 products provides a lower surface tension than water and improves
biofilm removal in wounds, they are indicated for wound irrigation for acute/chronic wounds
4. Cadexomer Cleans wet ulcers & wounds; reduces microbial load including MRSA, absorbs
exudate, helps in debridement, creates moist wound environment, & retards eschar formation
a. Releases iodine that has antimicrobial function
5. Collagenase is a Collagen-degrading enzyme; digests collagen in necrotic tissue but not in
healthy tissues.
6. Petrolatum + Mineral oils combination is indicated for superficial wounds, minor abrasions,
dermal ulcers, donor sites, 1st and 2nd degree burns, including sunburns and radiation
dermatitis.
7. Mebo® is indicated for acute/chronic wounds, 1st and 2nd type burns.
8. Solcoseryl® Oint. Is used for dry wounds and simple burns only, while the Solcoseryl® Jel is
used for weeping wounds and burns.
14.25– Burns and Burn care products

1. A burn is a type of injury to skin, or other tissues, caused by heat, cold, electricity, chemicals,
friction, or radiation; Burns that affect only the superficial skin layers are known as superficial
first-degree burns, They appear red without blisters and pain typically lasts around three days.
2. When the injury extends into some of the underlying skin layer, it is a partial-thickness or
second-degree burn, Blisters are frequently present and they are often very painful, Healing can
require up to eight weeks and scarring may occur.
3. A full-thickness or third-degree burn, the injury extends to all layers of the skin, Often there is
no pain and the burnt area is stiff, Healing typically does not occur on its own.
4. A fourth-degree burn additionally involves injury to deeper tissues, such as muscle, tendons, or
bone, The burn is often black and frequently leads to loss of the burned part.
6. Treatment of burns depends on the type and extent of the injuries; Most minor burns can be
treated by using over-the-counter products , They usually heal within a few weeks.
7. Some Clinical Notes about burns:
a) Calculation of Total Burned Body Surface Area (TBSA) by using the RULE OF NINE:
• Head & Neck = 9% , Each upper extremity (Arms) = 9%
• Each lower extremity (Legs) = 18% , Anterior trunk= 18%
• Posterior trunk = 18% , Genitalia (perineum) = 1%
b) Vascular changes resulting from burn injuries: Circulatory disruption occurs at the burn site
immediately after a burn injury; Blood flow decreases or cease due to occluded blood vessels
and Damaged macrophages within the tissues release chemicals that cause constriction of
vessel; Blood vessel thrombosis may occur causing necrosis.
c) Fluid shift resulting from burn injuries: Occurs after initial vasoconstriction, then dilation;
Blood vessels dilate and leak fluid into the interstitial space Known as third spacing or
capillary leak syndrome Causes decreased blood volume and blood pressure; Occurs within
the first 12 hours after the burn and can continue to up to 36 hours.
d) Fluid imbalances resulting from burn injuries: Occur as a result of fluid shift and cell damage;
these include Hypovolemia, Metabolic acidosis, Hyperkalemia, Hyponatremia,
Hemoconcentration (elevated blood osmolarity, hematocrit/hemoglobin) due to dehydration
e) Curling’s ulcer: Acute ulcerative gastro duodenal disease Occur within 24 hours after burn
Due to reduced GI blood flow and mucosal damage; Treat clients with H2 blockers,
mucoprotectants, and early enteral nutrition
f) For serious burns, after appropriate first aid care and wound assessment, the treatment may
involve I.V. Fluids, pain medications and antibiotics, wound dressings, and surgery; The
goals of treatment are to control pain, remove dead tissue, prevent infection, reduce scarring,
regain function and address emotional needs.
➢ I.V. fluids is calculated based on the TBSA using Parkland formula (burn >20% TBSA):
4 x Wt(kg) x %TBSA = mL/24 hours ; Deliver 1/2 volume over 1st 8hrs then Deliver
2nd half over next 16 hours.
Medications used in Burns:

a. Antimicrobial ointments (such as silver sulfadiazine, mafenide, silver nitrate, and povidone-
iodine) are used to reduce risk of infection.
b. Bacitracin may be used for first-degree burns; One study found that parrafin gauzes are valuable for
superficial burns while silver-based dressings are preferable for deep burns.
➢ Silver Sulfadiazine is used only for 2nd and 3rd degree burns, and used with caution in patients
with sulpha allergy.
➢ Nitrofurazone is indicated as an adjunctive therapy for second- and third-degree burns.
c. Antibiotics (Gentamicin) are used to treat infection; Antibiotics will also probably be used if the risk of
developing infection is high (for example, when the body surface area of the burn is large).
d. Pain medications (such as paracetamol with codeine, morphine, or meperidine) are used for severe
burns; Anabolic steroids, such as oxandrolone, may be used for severe burns to help decrease wound
healing time.
Bacitracin Oint./Powder Beocin® , Baciquent® 500 Unit/gm
Silver Nitrate Topical Solu. ------------ 10% , 25% , 50%
Povidone-Iodine Solu. Betadine® 5% , 10%
Fusidic acid Cream/Oint. Fucidin®, Fucine®, Fucibact® 2%
Silver Sulfadiazine Cream Silvadene®, Floumizine® 1%
Nitrofurazone Cream Furacin® 2 mg/gm
Silver Sulfadiazine Cream Argiderm® 15 gm
+ Panthenol *
Silver Sulfadiazine Spray Sofargen® 10 gm/125 ml can
+ Kaolin
Mafenide Cream , Sulfamylon® --------------
Topical Solu.
* Panthenol is used as a moisturizer and to improve wound healing.
References
3- BNF 82.
4- Handbook of Dermatology: A Practical Manual, 2018 Ed, Margaret W. Mann
5- http://www.ncbi.nlm.nih.gov/pubmed/23138019
6- https://jamanetwork.com/journals/jamadermatology/fullarticle/2753127
BLOOD PRODUCTS AND
HEMATOLOGY
Chapter Fifteen: Blood products and Hematology
15.1- Anemia
First: Iron Deficiency Anemia
A. Oral Iron
B. Parenteral Iron
Second: Megaloblastic Anemia

A. Vitamin B12 types
B. Folic acid
C. Combination Products for Mixed
types of Anemia
Third: Hemolytic Anemia

A. (G6PD) Deficiency
B. Sickle cell anemia
C. Thalassemia
15.2- Recombinant Human

Erythropoietins
15.3- Iron Chelating Agents
15.4- Drugs used in platelet

disorders
A. Idiopathic thrombocytopenic
purpura (ITP)
B. Drugs for Thrombocytopenia
(Platelet-stimulating agents)
C. Essential Thrombocythemia
15.5- Drugs for Neutropenia (Colony

stimulating factors)
15.6- Hematopoietic stem cell

Mobilizers
15.7- Sclerosing agents
15.8- Others Hematological products

Sam’s Guide: Chapter 15 – Hematology
Chapter Fifteen: Blood products and Hematology
15.1 – Anemia
1. Anemia is a group of diseases characterized by a
decrease in either hemoglobin (Hb) or the volume of red
blood cells (RBCs), which results in decreased oxygen-
carrying capacity of the blood.
2. Anemia is defined by the World Health Organization as:
1. Hb <13g/dL (<130 g/L; <8.07 mmol/L) in men.
2. Hb <12g/dL (<120 g/L; <7.45 mmol/L) in women.
3. Newborn: 17 - 19 g/dL.
4. Children: 14 - 17 g/dL.
First: Iron Deficiency Anemia:
Iron-deficiency anemia (IDA) is characterized by decreased levels of ferritin (most sensitive
marker) and serum iron, as well as decreased transferrin saturation. Hb and hematocrit decrease
later. RBC morphology includes hypochromia and microcytosis.
A) Oral Iron
1. The oral dose of elemental iron for iron-deficiency anemia should be 100 to 200 mg daily.
2. The iron content of various iron salts is tabulated in the table.
3. Oral iron preferably taken on an empty stomach because food, especially dairy products,
decreases the absorption by 40% to 50%; (However, many patients must take iron with food
because they experience gastrointestinal upset when iron is administered on an empty stomach.)
(4), the patient should be told that oral iron therapy produces dark stools.
4. Oral iron preparations sometimes produce gastrointestinal irritation and abdominal pain with
nausea and vomiting; Adverse effects can be reduced by giving it with or after food or by
beginning therapy with a small dose and increasing gradually.
5. Oral Liquid preparations containing iron salts should be well diluted with water and
swallowed through a straw to prevent discoloration of the teeth.
6. Iron should be stored in a safe place, inaccessible to her young children; Accidental ingestion
of even small amounts (3-4 tabs) of iron can cause serious consequences in small children.
7. Preparations containing iron and folic acid are used during pregnancy in women who are at
high risk of developing iron and folic acid deficiency.
Ferrous Sulphate Tab Ferrosam® 200 mg
Oral Drops 25 mg/ml
Ferrous Gluconate Tab Ferrosam® 300 mg
Oral Syr. Ferrosam® 400 mg/15 ml
Oral Vials Viofer® 300 mg (37.5 mg Fe +2)
Ferrous Fumarate Tab , Tab ER Feostat® 63 mg , 150 mg
Polysaccharide Iron Cap Niferex® , Ferrex® 150 mg
Iron Protein-succinylate Oral Vials Ferplex® 800 mg (equal 40 Fe+3)
Dextriferron Chew Tab Referum® 100 mg
Ferric Hydroxide Oral Vials, Ferimax®, Ferlos® 100 mg/5 ml
Polymaltose Complex Syrup Veltifer®
Syrup Ferimax® 50 mg/5 ml
Carbonyl Iron Tab Feosol® , Icron® , Icar® 45 mg , 66 mg

Chew Tab Icar Ped® 15 mg
Susp. Icar Ped® 15 mg /1.25 mg
Iron Gluconate + Oral Amp Tot’heme® 50 mg +
Manganese Gluconate + 1.33 mg +
Copper Gluconate 0.70 mg
Iron Pyrophosphate Tab SiderAL Forte® 30 mg
+ Vit. C + 70 mg
* Ferric Hydroxide Polymaltose Complex = Dextriferron, they are the same drug.
* Vit. C enhance the absorption of Iron.
Note: A new study suggests that iron supplementation may be a simple solution to the
persistent dry cough associated with the use of ACE inhibitors (ACEIs).
B) Parenteral Iron
1. Parenteral iron is generally reserved for use when oral therapy is unsuccessful.
2. Required Dose calculation:
Volume of product required (ml) = [weight (kg) × (14 – actual Hb) × (2.145)] ÷ C
Where C = concentration of elemental iron (mg/ml) in the product being used:
For Iron Dextran C= 50 mg/ml, For Iron Sucrose C= 20 mg/ml
3. With the exception of patients with severe renal failure receiving hemodialysis, parenteral iron
does not produce a faster hemoglobin response than oral iron provided, that the oral iron
preparation is taken reliably and is absorbed adequately.
4. Anaphylactic reactions occur in less than 1% of patients treated with parenteral iron therapy
and are more commonly associated with iron dextran.
5. Test dose:
a. It is suggested that all patients considered for iron dextran injection receive a test dose.
Patient should be observed for more than 1 hour for untoward (chest pain, hypotension),
if no reaction occurs, the remainder of the dose can be given.
➢ If an anaphylactic–like reaction occurs, it generally responds to (I.V.) epinephrine,
diphenhydramine, and corticosteroids.
b. A Test dose of 0.2 mL (10 mg) has been suggested for children weighing less than 10 kg, 0.3
mL (15 mg) for those weighing 10 to 20 kg, and 0.5 mL (25 mg) for adults.
6. It’s important to monitor Iron storage levels when using chronic or prolonged parenteral iron
therapy; to avoid serious toxicity associated with iron over load.
➢ Excess iron is deposit in the heart, liver, pancreas and other organs; which can lead to organ
failure and even death.
7. Iron dextran is given most commonly by IM route; In these cases, undiluted drug should be
administered using a Z-track technique to avoid staining the skin; (The skin should be pulled
laterally before injection; then the drug is injected and the skin is released to avoid leakage of
dextran into the subcutaneous tissue).
8. Iron sucrose (I.V. only) can be administered undiluted as a slow IV injection (rate not to
exceed 20 mg/minute) or as an IV infusion (dilutes in a maximum of 100 mL of 0.9% NaCl and
infuses at a rate of 100 mg for 15 minutes); A test dose is not indicated because of the lower
incidence of serious anaphylactic reactions.
9. New Iron Complexes (Ferumoxytol, Ferric Carboxymaltose and Iron Isomaltoside) can be
administered at much higher doses than the older complexes; with very low incidence to iron
overload or toxicity, and they do not require a test dose.
Iron Dextran Amp Dexferrum®, CosmoFer® 50 mg /ml
Iron Sucrose Amp Venofer® 20 mg/ml
Ferric Gluconate Amp Ferrlecit® , Ferralet® 12.5 mg/ml (10 ml)
Ferric Carboxymaltose Inj. Solu. Injectafer ® 750 mg/15 ml (50 Fe+)
Inj. Solu. Ferinject® 50 mg/ml (20 ml vial)
Ferumoxytol * I.V. Solu. Feraheme , Rienso
® ® 30 mg/ml
Ferric Pyrophosphate Solu. Triferic ® 27.2 mg/5 ml
Iron Isomaltoside ** Inj. Solu. Monofer® 100 mg/ml (10 ml vial)
* Ferumoxytol is indicated in Iron Deficiency Anemia in Chronic Kidney Disease.
** A complex of ferric iron and Isomaltoside containing 10% (100 mg/mL) of iron.
Second: Megaloblastic Anemia (Either B12 deficiency or Folate Deficiency, or both)

1. Vitamin B12 deficiency, a macrocytic anemia, can be due to inadequate intake, malabsorption
syndromes, and inadequate utilization; Anemia caused by lack of intrinsic factor, resulting in
decreased vitamin B12 absorption, is called pernicious anemia.
2. Neurologic symptoms can be present and can become irreversible if the vitamin B12 deficiency is
not treated promptly
3. Risk of Vitamin B12 deficiency increases with age, and with the use of gastric acid–suppressing
agents (PPIs, H2 Blockers); which may inhibit the release of Cobalamin from food, Oral or
parenteral therapy can be used for replacement.
A) Vitamin B12 comes in 3 types

Cyanocobalamin* Tab Cobalamine ® 100 mcg , 250 , 500 , 1000 mcg
Amp Cobalamine ® 1000 mcg/ml
Amp (oral) B12 Gerda ® 1000 mcg/4 ml
Oral Vial Maddovit B12 ® 25 mcg/7 ml
Nasal Spray Nascobal , CaloMist
® ® 25 mcg/spray
Methylcobalamin Amp Methycobal ® 500 mcg
** Tab Methycobal®, Mecobalamine® 250 mcg , 500 mcg
Hydroxocobalamin Amp Cobalin-H® 1000 mcg/ml
Vial Cyanokit ® 5 gm/vial
* (Cyanocobalamin) turns inside the body to (Methylcobalamin) then to (Hydroxocobalamin)
which is the active form of B12
** Methylcobalamin ampules and tablets should be protected from light and moisture, (Light
decreases the active ingredient content and may turn reddish with exposure to moisture)
Notes:
1. Cyanocobalamin is the least expensive and least painful type at the injection site, and is used
once a week I.M. ONLY, but it is the least efficient.
2. Methylcobalamin, also called (Mecobalamin); is more efficient than Cyanocobalamin
because it does not need to switch to another form inside the body.
a. It has a better absorption profile.
b. More painful at the injection site and can be given I.M, I.V.
c. The best choice for smokers, due to their inability to convert Cyanocobalamin to
Methylcobalamin because of the presence of the heavy metals & toxins in the liver.
d. Its methyl group stimulates Serotonin production in CNS; (thus has a mood supporting effect).
e. High doses can be effective in the treatment of Multiple Sclerosis.
3. Hydroxocobalamin is the most bioactive form, and is the most type commonly used.
a. It’s better to be given I.V. due to its very painful at injection site unless mixed with local
anesthetic, stay inside the body for a longer period, which reduces the no. of injections.
b. The (5 gm vial) is used in the treatment of Cyanide poisoning as I.V infusion.
B) Folic acid
1. Human beings cannot synthesize Folate endogenously; thus, it has to be supplied throw diet
or by supplementation; the human body needs Folate to make and repair DNA, it also acts as a
cofactor in several biological reactions.
2. Folic acid is an oxidized form; it must be converted to the active form (Tetrahydrofolate) in the
body (by the liver) to be beneficial inside the human body.
Notes:
1. Prevention of neural tube defects (NTD)
a. Folic acid supplements taken before and during pregnancy can reduce the occurrence of
neural tube defects.
b. For women of child-bearing potential at high risk of having a pregnancy affected by NTD (if
they have had a previous pregnancy affected by a neural tube defect), the dose of folic acid is
4 mg or 5 mg daily starting before pregnancy (in the USA the recommendation is 4 weeks
before) and continued through the first trimester (until week 12 of pregnancy).
c. For women at a low risk of having a child with a NTD the dose is 400 micrograms daily
and continued through the first trimester (until week 12 of pregnancy).
d. Higher doses than 400 mcg of Folic acid is related in some studies to Autism.
2. Other indications for folic acid include:
A- Folate-deficient Megaloblastic anemia.
B- Prevention of methotrexate-induced side-effects.
C- Prophylaxis of folate deficiency in dialysis.
E- Fertility aid in both men and women.
3. Folic acid may reduce the risk of stroke in elderly (due it decreases Homocysteine conc.), as
the patients with heart disease with high homocysteine levels are more than four times as likely
to suffer the most common type of stroke compared with those with low homocysteine levels.
Folic Acid Tab Folvite® , Folix® 400 mcg, 1 mg , 4 mg , 5 mg
Oral Solu. Mega Folic® 400 mcg/5 ml
Oral Drops 400 mcg/1 ml
Inj. Solu. 5 mg/ml
L-5 Methyl- Tab FolaPro®, 800 mcg ,
Tetrahydrofolate Folimax® 400 mcg
Folic Acid + Iron Cap Fefol® , F.F® 5 mg + 150 mg
* Folic acid Inj. Solu. is used in the treatment of methanol toxicity and Methotrexate toxicity
** L-5-Methyl-Tetrahydrofolate (L-5-MTHF) = Metafolin = Methylfolate, all are the same.
Combination Products for Mixed types of Anemia

Quatre B12® Tab Methyl-Tetrahydrofolate + Vit. B12 400 mcg + 1000 mcg
SiderAL Folic® Oral Solu. Iron Pyrophosphate + Vit. C + Folic acid 30 mg + 70 mg + 400 mcg
(Sticks) + Vit. D + Vit. B6 + Vit. B12 + 10 mcg + 1 mg + 1.75 mcg
Soft Iron ® Cap Iron Bisglycinate + Vit. C + Folic acid 28 mg + 40 mg + 400 mcg
+ Vit. B6 + Vit. B12 + 1.4 mg + 2.5 mcg
Hema-Plex® Tab Iron amino acid complex + Vit. C 85 mg + 300 mg
+ Tetrahydrofolate + Vit. B12 + 400 mcg + 500 mcg
+ (other minerals and vitamins)
Third: Hemolytic Anemia:
1. These include:
A. Glucose 6-phosphate dehydrogenase (G6PD) deficiency B. Sickle cell anemia
C. Thalassemia
2. Those patients don’t need Iron therapy, they are at risk of developing iron overload and
require chelation therapy with (Deferoxamine, Desferiprone or Deferasirox).
3. They are generally given Folic acid supplementation.
A) (G6PD) Deficiency:
1. G6PD is essential for the production of (NADPH) in erythrocytes, and (NADPH) is essential for
keeping Glutathione (Glutathione helps erythrocytes to deal with oxidative stress).
2. So, in G6PD deficiency, if the erythrocytes are
exposed to an oxidizing agent, the cell
membrane becomes damaged; the
hemoglobin becomes oxidized and forms
what are known as Heinz bodies, some of the
red cells undergo hemolysis and others have
their Heinz bodies removed by the Spleen to
form ‘bite cells’.
3. Individuals with G6PD deficiency are
susceptible to developing acute hemolytic
anemia when they take a number of
common drugs (1); so it’s best to avoid them
in such patients.
B) Sickle cell Anemia

1. Patients with sickle cell disease (SCD) have a different form of hemoglobin; Patients with the
most common variant of sickle cell disease have hemoglobin S (Hb S).
➢ Normal hemoglobin is usually designated as Hb A.
2. The membrane of red cells containing hemoglobin S is damaged, which leads to intracellular
dehydration, Also Sickle cells are less flexible than normal cells (flexibility allows normal cells to
pass through the micro-circulation), the inflexibility leads to impaired blood flow through the
micro-circulation, resulting in local tissue hypoxia.
3. Vaso-occlusive crisis (VOC) is the most common clinical manifestation of SCD; it occurs when
the microcirculation is obstructed by sickled RBCs, causing ischemic injury to the organ supplied
and resultant pain - approximately half of individuals with SCD experience VOC; Pain crises begin
suddenly and may last several hours to several days, the pain can affect any body part but often
involves the abdomen, bones, joints and soft tissue, VOC result in a decrease in quality of life and
an increase in the risk of death.
4. Treatment goal is to decrease hemoglobin S (Hb-S) proportions and increase hemoglobin F;
which don’t turn into sickle cells; Treatment option include: Hydroxycarbamide, Hydroxyurea,
and Recombinant Human Erythropoietins (see next Section).
5. Hydroxycarbamide and Hydroxyurea are the same drug, but they differ in the way of
manufacturing; Hydroxyurea is semi-synthetic drug, while Hydroxycarbamide is a fully-
synthetic drug.
6. Hydroxyurea (Hydroxycarbamide) are antineoplastic drugs, used in the treatment of
Polycythemia Vera and in the treatment of Essential Thrombocythemia.
➢ In Sickle cell anemia they are used to reduce the rate of painful attacks; they act by increasing
hemoglobin F levels; (their effects take a minimum 3 months to appear).
6. Voxelotor is an oral, once-daily therapy for the treatment of sickle cell disease (SCD); it’s a sickle
hemoglobin (Hb S) polymerization inhibitor, Voxelotor works by increasing the affinity of
hemoglobin for oxygen, this stabilizes red blood cells in an oxygenated state, preventing
hemoglobin polymerization and the resultant sickling and destruction of the red blood cells.
7. Inclacumab is a fully human monoclonal antibody designed to bind to and selectively inhibit P-
selectin, an adhesion molecule found on endothelial cells and platelets that contributes to the
cell-cell interactions that are involved in the pathogenesis of Vaso-occlusive crisis (VOCs).
8. Crizanlizumab (an anti-P-selectin antibody); it is approved by the FDA to reduce the frequency
of Vaso-occlusive crises (VOCs), or pain crises, in adult and pediatric patients aged 16 years and
older with sickle cell disease.
Hydroxycarbamide Cap Hydrea ® 500 mg
Hydroxyurea Cap Hydrine , Droxia
® ® 300 mg , 500 mg
Voxelotor Tab Oxbryta ® 500 mg
Crizanlizumab Inj. Solu. Adakveo ® 10 mg/ml (10 ml)
Inclacumab Pending FDA approval
C) Thalassemia
1. In β thalassemia, there is a reduced or absent production of the globin β chain, this leads to a
relative excess of α chain which when unpaired become unstable and precipitates in the red cell
precursors; there is ineffective erythropoiesis and those mature cells that reach the circulation
have a shortened life span
2. In α thalassemia, the pathology is slightly different, the deficiency of α chains leads to an excess
of γ or β chains, this time erythropoiesis is less affected, but the hemoglobin produced
(hemoglobin Bart's or Hemoglobin H) is unstable when the cells are in the circulation and
precipitates as the cells grow older, this leads to a shortened life span with the spleen trapping
many of the cells.
3. Many patients with severe forms are dependent on blood transfusions from an early age; This
inevitably leads to iron overload, Deferoxamine, Deferiprone and Deferasirox are needed for
such patients; also, it is likely that a combination of drugs (Hydroxycarbamide and
Erythropoietin) will provide some clinical improvement. (See above).
4. A new drug is developed for the treatment of β thalassemia: Luspatercept, the first-in-class
erythroid (red blood cell) maturation agent used to treat patients who have blood disorders
associated with ineffective erythropoiesis (it’s a recombinant fusion protein that binds several
TGF-beta superfamily ligands, thereby diminishing Smad2/3 signaling).
➢ the FDA approved Luspatercept for treatment of anemia in adult patients with beta
thalassemia who require regular red blood cell transfusions.
Luspatercept Vial (Solu.) Reblozyl® 25 mg , 75 mg
15.2 – Recombinant Human Erythropoietins

1. They stimulate erythropoiesis via division and differentiation of progenitor cells in bone marrow,
they are used in Sickle Cell anemia, Thalassemia and in Anemia due chronic renal disease.
2. The most common side effects include: hypertension and thrombotic complications.
3. In controlled trials with CKD patients on Erythropoietin therapy, patients experienced greater
risks for death, serious adverse cardiovascular reactions, and stroke when administered
Erythropoietins to target hemoglobin level of greater than 11 g/dl.
4. Supplementation with Iron may be required to ensure an adequate response.
Epoetin Alfa Inj. Solu. Eprex , Espogen 4000 , 10,000 , 20,000 Unit/ml
® ®
Epoetin Beta Inj. Solu. NeoRecormon® 4000 , 10,000 , 20,000 Unit/ml

Epoetin Theta Inj. Solu. Eporatio® 4000 , 10,000 , 20,000 Unit/ml
Epoetin Zeta Inj. Solu. Retacrit® 4000 , 10,000 , 20,000 Unit/ml
Darbepoetin Alfa Prefilled Inj. Aranesp ® 100 , 150 , 200 , 500 mcg
Methoxy polyethylene Prefilled Inj. Mircera® 120 mcg/0.3 ml , 200 mcg/0.3 ml ,
glycol Epoetin Beta 360 mcg/0.3 ml , 800 mcg/0.6 ml
Peginesatide Vial (Multi-use) Omontys® 10 mg , 20 mg (Vials multi-use) ,
, Prefilled Inj. (1, 2, 3, 4, 5, 6 mg/0.5 ml) Prefilled
Notes:
1. Epoetin Alfa is given (50-100 units/kg) 3 times a week.
• Subcutaneous (SC) administration of Epoetin Alfa is preferred because the SC dose that
maintains target indices is 15% to 30% lower than the IV dose.
• Same dosing for Beta, Theta and Zeta types of Epoetin.
2. MPG Epoetin Beta is given every 2 weeks, or in a loading dose every month.
3. Darbepoetin is given (0.45 mcg/kg) once a week.
4. Peginesatide is given (0.04-0.08 mg/kg) once monthly.
• For patients previously receiving Epoetin Alfa, the first dose of Peginesatide should be
administered 1 week after the last Epoetin Alfa dose was administered.
• For patients previously receiving Darbepoetin Alfa, the first dose of Peginesatide should be
administered at the next scheduled dose in place of Darbepoetin Alfa.
• The Brand Company has withdrawn Peginesatide due reports of serious hypersensitivity
reactions and deaths.
Note: Two randomized controlled trials published in 2013 found that the effectiveness of
Peginesatide was not inferior to Epoetin for patients receiving dialysis (the EMERALD study),
or to Darbepoetin for patients with chronic kidney disease who were not receiving dialysis (the
PEARL study) However, the safety endpoint of cardiovascular events and death was worse
for Peginesatide than for Darbepoetin in the PEARL study.
15.3 – Iron Chelating Agents

1. These chelates iron by forming a stable complex that prevents the iron from entering into further
chemical reactions; also chelates iron readily from ferritin and hemosiderin but not readily from
transferrin; does not combine with the iron from cytochromes and hemoglobin; the chelate
is readily soluble and is renally excreted (if parenteral chelating is used), or excreted with stool
(if oral chelating is used).
2. Available Chelating agents include: Deferoxamine (Parenteral I.M. I.V. or S.C.), Deferiprone and
Deferasirox (both oral), these agents defer in their chelating affinity:
➢ Deferoxamine 100 parts of weight can bind 8.5 parts of Ferric Iron.
➢ Deferiprone 3 molecules can bind 1 atom of Iron.
➢ Deferasirox 2 molecules can bind 1 atom of Iron.
3. Deferiprone is given 3 times a day; while Deferasirox is given once daily.
Deferoxamine Inj. powder Desferal ® 500 mg , 2 gm (vial)
Deferiprone Tab, Oral Solu. Ferriprox ® 500 mg (tab) , 100 mg/ml
Deferasirox Tab Exjade® 125 mg , 250 mg , 500 mg
Tab Jadenu ® 90 mg , 180 mg , 360 mg
* Deferoxamine = Desferrioxamine, they are the same drug.
* Deferiprone = Desferiprone, they are the same drug.
15.4 – Drugs used in platelet disorders
A) Idiopathic thrombocytopenic purpura (ITP)
1. Acute idiopathic thrombocytopenic purpura is usually self-limiting in children.
2. In adults, idiopathic thrombocytopenic purpura can be treated with a corticosteroid, e.g.
prednisolone 1 mg/kg daily, gradually reducing the dose over several weeks.
➢ Splenectomy is considered if a satisfactory platelet count is not achieved or if there is a
relapse on reducing the dose of corticosteroid or withdrawing it.
➢ Immunoglobulins are also used in idiopathic thrombocytopenic purpura or where a
temporary rapid rise in platelets is needed, usually by a dose of 0.4 gm/kg/day.
➢ D(Rh0) immunoglobulin is effective in raising the platelet count in about 80% of
unsplenectomized rhesus-positive individuals; its effects may last longer than normal
immunoglobulin for intravenous use, but further doses are usually required.
o Dose usually 125 – 250 IU/Kg, infused over 3-5 min.
➢ Other therapy that has been tried in refractory idiopathic thrombocytopenic purpura
includes azathioprine, cyclophosphamide, vincristine, cyclosporine, and Danazol.
➢ For patients with chronic severe thrombocytopenia refractory to other therapy, Tranexamic
acid may be given to reduce the severity of hemorrhage.
3. Eltrombopag and Romiplostim (see below) are thrombopoietin receptor agonists licensed for
the treatment of chronic idiopathic thrombocytopenic purpura in splenectomized patient’s
refractory to other treatments, such as corticosteroids or immunoglobulins, or as a second-line
treatment in non-splenectomized patients when surgery is contra-indicated
B) Drugs for Thrombocytopenia (Platelet-stimulating agents)

1. A normal human platelet counts ranges from 150,000 to 450,000 platelets per microliter of blood,
these limits are determined by the 2.5th lower and upper percentile, so values outside this range
do not necessarily indicate disease. One common definition of thrombocytopenia is a platelet
count below 50,000 per microliter.
2. Treatment is guided by etiology and disease severity. The main concept is to eliminate the
underlying problem.
3. Corticosteroids (usually prednisolone or Dexamethasone) may be used to increase platelet
production. Lithium carbonate or Folate may also be used to stimulate the bone marrow
production of platelets.
4. Platelet transfusions may be used to stop episodic abnormal bleeding caused by a low platelet
count. However, if platelet destruction results from an immune disorder, platelet infusions may
have only a minimal effect and reserved for life-threatening bleeding.
5. Specific treatment plans depend on the underlying etiology of the thrombocytopenia, and
platelet stimulating agents should be prescribed by professional medical staff only under
supervision; since these medications have a wide side effects profile (liver failure, anaphylaxis).
Eltrombopag Tab Promacta® , Revolade® 12.5 , 25 , 50 , 75 , 100 mg
Lusutrombopag Tab Mulpleta® 3 mg
Romiplostim Vial (S.C.) Nplate® 250 mcg , 500 mcg
Oprelvekin S.C. Inj. Neumega®, Interleukin 11® 5 mg/vial
Notes:
1. Eltrombopag may cause severe liver damage, so routine check for liver functions is required.
2. Romiplostim is indicated as a long-term treatment for chronic ITP in adults who have not
responded to other treatments, such as corticosteroids, intravenous immunoglobulin, Rho (D)
immune globulin or splenectomy.

3. Oprelvekin is contraindicated in Patients with severe or decompensated heart failure; because
it may cause excessive fluid retention with edema and cardiac decompensation, it also has
caused very serious allergic reaction (edema of the face and tongue, shortness of breath;
wheezing; chest pain; hypotension (including shock); dysarthria; loss of consciousness, rash,
urticaria, flushing, and fever.)
 A number of potentially serious side-effects may develop when using Platelet stimulation agents
including: myalgia, joint and extremity discomfort, insomnia, thrombocytosis, which may lead
to potentially fatal clots, and bone marrow fibrosis, the latter which may result in an unsafe
decrease in the red blood count.
C) Essential Thrombocythemia
Anagrelide inhibits platelet formation. It is licensed for essential Thrombocythemia in patients
at risk of thrombo-hemorrhagic events who have not responded adequately to other drugs or
who cannot tolerate other drugs. Anagrelide should be initiated under specialist supervision.
Anagrelide Cap Xagrid® 500 mcg
15.5- Drugs for Neutropenia (Colony stimulating factors)

1. These drugs are used to increase the number of white blood cells when the white blood cell
count is low; they act by stimulating the bone marrow to increase production of neutrophils.
2. Causes of neutropenia include chemotherapy and bone marrow transplantation; a reduced
level of white blood cells causes an increased susceptibility to infections.
➢ Thus; treatment can be used to stimulate bone marrow to produce more neutrophils to fight
infection in patients undergoing chemotherapy.
3. Available drugs include: (Filgrastim, Tbo-filgrastim, Pegfilgrastim, Lenograstim) which are
considered a recombinant human granulocyte colony-stimulating factor (G-CSF) and
Sargramostim, which differ from the rest as its considered as a human recombinant granulocyte
macrophage colony-stimulating factor (GM-CSF).
➢ Filgrastim and Tbo-filgrastim both have half-life of 3-4 hours inside the body.
➢ Pegfilgrastim has a long half-life 15-80 hours.
4. Sargramostim is primarily used for myeloid reconstitution after autologous or allogeneic bone
marrow transplantation.
➢ It is also used to treat neutropenia induced by chemotherapy during the treatment of acute
myeloid leukemia.
➢ Used in treating Crohn's disease and other GI inflammatory disorders.
➢ This medication is being investigated in trials to treat Autoimmune Pulmonary Alveolar
Proteinosis (PAP).
Pegfilgrastim S.C. Inj. Neulasta®, Neulastim®, 6 mg/0.6 ml (Prefilled Inj.)
Imupeg®
Sargramostim Inj. Solu. Leukine® 500 mcg/ml
Inj. Powder 250 mcg/vial
Filgrastim Inj. Solu. Neupogen , Zarzio
® ® 300 mcg/ml , 480 mcg/1.6 ml
Prefilled Inj. 300 mcg/0.5 ml , 480 mcg/0.8 ml
Tbo-filgrastim Granix
Lenograstim Inj. Powder Granocyte® 105 mcg , 263 mcg
15.6 - Hematopoietic stem cell Mobilizers
Hematopoietic stem cell mobilizer binds to the CXCR4 chemokine receptor and inhibits the
binding of its ligand, stromal cell-derived factor-1-alpha (SDF-1-alpha), this leads to mobilization
of hematopoietic stem cells to the peripheral blood.
Ancestim Inj. Powder Stemgen® 1875 mcg/vial
Plerixafor Inj. Solu. Mozobil® 24 mg/vial (20 mg/ml)
15.7 - Sclerosing agents

Sclerosing agents are used in sclera-therapy of varicose veins, where the irritant solution is
injected into the blood vessels. (Sclerosing agents are used to treat varicose veins).
Ethanolamine Inj. Solu. Ethamolin ® 50 mg/ml
Morrhuate Na Inj. Solu. Scleromate ® 50 mg/ml
Polidocanol I.V. Inj. Asclera , Varithena
® ® 0.2% , 1% (2 ml amp)
I.V. Inj. Aethoxysklerol® 2% (2 ml amp)
Na Tetradecyl Sulfate Inj. Solu.
+ Trombovar , Sotradecol
® ® 1% , 3%
15.8 - Others Hematological products

Icatibant S.C. Inj. Firazyr® 30 mg (prefilled Inj.)
Etamsylate Tab , Amp Dicynone® 250 mg
Notes:
1. Icatibant is a selective and specific antagonist of bradykinin B2 receptors. It has been approved
for the treatment of acute attacks of hereditary angioedema (HAE).
2. Etamsylate is a hemostatic drug, it acts by increasing capillary endothelial resistance and
promoting platelet adhesion; indicated for Prophylaxis and control of hemorrhages from
small blood vessels, neonatal intra-ventricular hemorrhage capillary bleeding of different
etiology, including: menorrhagia, hematuria, epistaxis, prevention of periventricular
hemorrhages in prematurely born children.
References
1- BNF 82.
2- Sean C. Sweetman. Martindale: The Complete Drug Reference, 38th Edition. Ph.P

IMMUNOLOGICS AND
ONCOLOGY
Chapter Sixteen: Immunologics & Oncology
Part One: Immunology Part Two: Oncology
First: Immunosuppressive Agents First: Introduction
1. Corticosteroids Second: Anti-Cancer Groups
2. Selective Inhibitors of Cytokine Production 1. Cytotoxic antineoplastics
and Function ➢ Alkylating Cytotoxic Agents
3. Drugs That Disrupt cell metabolism ➢ Platinum compound
a. Alkylating agents ➢ Anthracycline (antibiotics)
b. Antimetabolites ➢ Microtubule Inhibitors
c. Antibodies (Polyclonal and ➢ Topoisomerase inhibitors
Monoclonal) ➢ Antimetabolite Cytotoxic Agents
➢ Anti-Thymocyte globulins ➢ Retinoid derivatives
(Polyclonal) ➢ Other Cytotoxic agents
➢ Drugs for cytotoxic drug-induced
➢ Muromonab-CD3 (Monoclonal)
side effects
➢ IL-2-receptor antagonists
2. Antineoplastic monoclonal antibodies
(Monoclonal) 3. Hormonal Antineoplastics
➢ Other Monoclonal Antibodies 4. Immunotherapy antineoplastics
4. Other immunosuppressive agents 5. Proteasome inhibitors antineoplastics
6. Kinase inhibitor antineoplastics
7. Histone deacetylase inhibitors
Second: Immune Globulins
Third: Interferons
Fourth: Immunomodulators
Fifth: Immunostimulants
Sam’s Guide: Chapter 16 – Immunologics/Oncology
Chapter Sixteen: Immunologics and Oncology
Part one: Immunology
First: Immunosuppressive Agents
1. Immunosuppressive drugs (or antirejection medications) are drugs that inhibit or prevent
activity of the immune system; They are used in immune-suppressive therapy to:
a. Prevent the rejection of transplanted organs and tissues (as in those with bone marrow, heart,
kidney and liver transplant).
b. Treat autoimmune diseases or diseases that are most likely of autoimmune origin (rheumatoid
arthritis, multiple sclerosis, myasthenia gravis, systemic lupus erythematosus, sarcoidosis,
focal segmental glomerulo-sclerosis, Crohn's disease ulcerative colitis, Behcet's Disease).
c. Treat some other non-autoimmune inflammatory diseases (long term allergic asthma).
2. The principal approach to immunosuppressive therapy is to alter lymphocyte function
using drugs or antibodies against immune proteins, Because of their severe toxicities when
used as monotherapy, a combination of immunosuppressive agents, usually at lower doses,
is generally employed.
3. Immunosuppressive drug regimens usually consist of anywhere from two to four agents with
different mechanisms of action that disrupt various levels of T-cell activation.
4. A common side-effect of many immunosuppressive drugs is immunodeficiency, because the
majority of them act non-selectively, resulting in increased susceptibility to infections; There
are also other side-effects, such as hypertension, dyslipidemia, hyperglycemia, peptic ulcers,
lipodystrophy, liver and kidney injury.
5. Immunosuppressive drugs can be categorized according to their mechanisms of action:
a) Corticosteroids
b) Interfere with cytokine production or action.
c) Disrupt cell metabolism, preventing lymphocyte proliferation.
d) Mono and polyclonal antibodies that block T-cell surface molecules.
e) Other immunosuppressive agents
1) Corticosteroids (see chapter 12 for more information)

1. In pharmacologic (supra-physiologic) doses, glucocorticoids are used to suppress various
allergic, inflammatory, and autoimmune disorders. They are also administered as post
transplantory Immunosuppressants in high doses to prevent the acute transplant rejection and
graft-versus-host disease.
2. The steroids are able to rapidly reduce lymphocyte populations by lysis or redistribution.
3. The most common agents are prednisone or methylprednisolone, whereas prednisone or
prednisolone are used for autoimmune conditions; (Note: In transplantation, they are used in
combination with other agents).
2) Selective Inhibitors of Cytokine Production and Function

1. Cytokines are soluble, antigen-nonspecific, signaling proteins that bind to cell surface receptors
on a variety of cells, the term cytokine includes the molecules known as interleukins (ILs),
interferons (IFNs), tumor necrosis factors (TNFs), transforming growth factors, and
colony-stimulating factors, these cytokines collectively activate natural killer cells,
macrophages, and cytotoxic T lymphocytes.
2. They include: (Cyclosporine, Tacrolimus, Sirolimus, Everolimus and Pimecrolimus)
Cyclosporine Cap Sandimmune® , Gengraf® 25 mg , 50 mg , 100 mg
Inj. Solu. 50 mg/ml
Tacrolimus Cap Prograf® , Hecoria® 0.5 mg , 1 mg , 5 mg
Inj. Solu. Prograf® 5 mg/ml
Oint. Protopic® , Talimus® 0.03% , 0.1%
Sirolimus Tab Rapamune® 0.5 mg , 1 mg , 2 mg
Everolimus Tab Afinitor® 0.25 mg , 0.5 mg , 0.75 mg
Pimecrolimus Cream Elidel® , Pacroma® 1%
Notes:
1. Cyclosporine is an alternative to methotrexate for the treatment of severe, active rheumatoid
arthritis, it can also be used for patients with recalcitrant psoriasis that does not respond to other
therapies, and it is also used for xerophthalmia.
2. The antiproliferative action of Sirolimus has found use in cardiology; Sirolimus-coated
stents inserted into the cardiac vasculature inhibit restenosis of the blood vessels by reducing
proliferation of the endothelial cells.
3. Sirolimus and Everolimus both cause hyperlipidemia.
3) Drugs That Disrupt cell metabolism

They inhibit cell division; in immunotherapy they are used in smaller doses than in the
treatment of Cancers; They affect the proliferation of both T cells and B cells. Due to their highest
effectiveness, purine analogs are most frequently administered.
1. Alkylating agents
1. The only alkylating agent that maybe used as immunosuppressant is the nitrogen mustard
(cyclophosphamide); others are used to treat cancers (mentioned in the next part, page 390).
2. Cyclophosphamide is probably the most potent immunosuppressive compound.
In small doses, it is very efficient in the therapy of systemic lupus erythematosus,
autoimmune hemolytic Anemias, Wegener's granulomatosis, and other immune diseases. High
doses cause pancytopenia and hemorrhagic cystitis.
3. Cyclophosphamide decreases the immune system's response to various diseases and
conditions; Therefore, it has been used in autoimmune diseases where disease-modifying anti-
Rheumatic drugs (DMARDs) have been ineffective, as in: systemic lupus erythematosus, severe
rheumatoid arthritis, Wegener's granulomatosis and multiple sclerosis.
a. It is also used to treat some types of cancer.
b. Cyclophosphamide is itself carcinogenic, potentially causing transitional cell
carcinoma of the bladder as a long-term complication, and other serious potential side
effect is acute myeloid leukemia, referred to as secondary AML.
c. The risk may be dependent on dose and a number of other factors, including the condition
being treated, other agents or treatment modalities used (including radiotherapy),
treatment intensity and length of treatment.
Cyclophosphamide Tab Cytoxan® 25 mg , 50 mg
Inj. Powder a. m
g
2. Antimetabolites ,
Antimetabolites interfere with the synthesis of nucleic acids. These include: 1
a. Folic acid analogues, such as Methotrexate g
b. Purine analogues, such as Azathioprine and Mercaptopurine m
c. Pyrimidine analogues, such as Fluorouracil ,
d. Others, such as Mycophenolate. 2
g
m
Methotrexate Tab Rheumatrex , MTX
® ® 2.5 mg , 5 mg , 10 mg
Inj. Solu. Trexall® 25 mg/ml
Mercaptopurine Tab 6MP® , Puri-nethol® 50 mg
Fluorouracil Inj. Solu. Adrucil® 50 mg/ml
Mycophenolate Cap , Tab CellCept® , Myfortic® 250 mg , 500 mg
Notes:
1. Methotrexate is a folic acid analogue. It binds dihydrofolate reductase and prevents synthesis of
tetrahydrofolate, it is used in the treatment of autoimmune diseases (for example Rheumatoid
Arthritis, Crohn’s disease, Behcet's Disease) and in transplantations.
2. Azathioprine is extensively used to control transplant rejection reactions, it is non-
enzymatically cleaved to Mercaptopurine, which acts as a purine analogue and an inhibitor of
DNA synthesis, Mercaptopurine itself can also be administered directly; it is also efficient in the
treatment of autoimmune diseases.
➢ Concomitant use with (ACEIs) or co-trimoxazole in patients with renal diseases can lead to
an exaggerated leukopenic response.
3. Mycophenolate has replaced azathioprine because of its safety and efficacy; the most common
adverse effects include diarrhea, nausea, vomiting, abdominal pain, leukopenia, and anemia.
Higher doses of Mycophenolate (3 gm/day) were associated with a higher risk of CMV infection.
4) Antibodies (Polyclonal and Monoclonal)

1. Antibodies are sometimes used as a quick and potent immunosuppressive therapy to prevent the
acute rejection reactions as well as a targeted treatment of lymphoproliferative or autoimmune
disorders (Psoriasis, Eczema, Asthma, Multiple Sclerosis, Osteoporosis, etc.).
2. They are prepared either by immunization of rabbits, mice
and horses with human lymphoid cells (producing a
mixture of polyclonal antibodies directed against a number
of lymphocyte antigens), or by Hybridoma technology
(producing antigen-specific, monoclonal antibodies).
Hybridomas are produced by fusing mouse antibody-
producing cells with immortal malignant plasma cells; they
are generally prepared in the below method:
a. In the laboratory, scientists analyze a specific
antigen on the surface of the target cells to
determine a protein to match the antigen.
b. Then using protein from mice (murine) or humans
(humanized) to create a special antibody that will
attach to the target antigen (on the target cells).
c. Monoclonal antibodies are produced by immunizing
an animal (usually a mouse), multiple times with a
specific antigen.
d. B cells from the spleen of the immunized animal are then removed, and they are fused
with cancerous B cells called myeloma cells; to yield Hybridoma cells.
e. The Hybridoma cells (which are capable of growing continuously in culture while
producing antibodies) are then screened for the desired monoclonal antibody.
f. This process is very expensive and time consuming; thus, Monoclonal antibodies are
generally expensive.
3. The names of monoclonal antibodies conventionally contain “muromab” if they are from a
murine (mouse) source, and “ximab” if they are chimerized (65% human-mouse), and “zumab”
if they are humanized (95% human), and “umab” if they are fully 100% human; The suffix “mab”
(monoclonal antibody) identifies the category of drug.
4. Monoclonal antibodies are directed towards exactly defined antigens; Therefore, they cause
fewer side-effects than Polyclonal antibodies, especially the IL-2 receptor-(CD25-) and CD3-
directed antibodies.
A) Anti-Thymocyte globulins (Polyclonal)

1. Thymocytes are cells that develop in the thymus and serve as T-cell precursors. The antibodies
developed against them are prepared by immunization of large rabbits or horses with human
lymphoid cells and, thus are polyclonal.
2. Rabbit formulations (1.5 mg/kg) of polyclonal anti-Thymocyte globulin are more commonly
used over the horse preparation (10-30 mg/kg) due to greater potency.
3. Their adverse effects include chills and fever, leukopenia and thrombocytopenia, infections due
to CMV or other viruses and skin rashes.
Anti-Thymocyte globulin Equine Inj. Solu. Atgam® , ATG equine® 50 mg/ml
Anti-Thymocyte globulin Rabbit Inj. Solu. Thymoglobulin® , ATG Rabbit® 25 mg/vial
B) Muromonab-CD3 (Monoclonal)
1. Muromonab-CD3 is a mouse monoclonal antibody that is synthesized by Hybridoma technology
and directed against the glycoprotein CD3 antigen of human T cells.
2. The antibody is administered IV. Initial binding of muromonab-CD3 to the antigen transiently
activates the T cell and results in cytokine release (cytokine storm). It is, therefore, customary
to pre-medicate the patient with methylprednisolone, diphenhydramine, and acetaminophen to
alleviate the cytokine-release syndrome.
3. The symptoms can range from a mild, flu-like illness to a life-threatening, shock-like reaction.
High fever is common. Central nervous system effects, such as seizures, encephalopathy,
cerebral edema, aseptic meningitis, and headache, may occur. Infections can increase, including
some due to CMV.
4. Muromonab-CD3 is contraindicated in patients with a history of seizures, in those with
uncompensated heart failure, in pregnant women, and in those who are breast-feeding; Because
of these muromonab-CD3 is rarely used today.
Muromonab-CD3 Inj. Solu. Orthoclone® , OKT3® 1 mg/ml
C) IL-2-receptor antagonists (Monoclonal)

1. Interleukin-2 is an important immune system regulator necessary for the clone expansion and
survival of activated lymphocytes T; the IL-2a is expressed only by the already-activated T
lymphocytes.
2. Basiliximab and Daclizumab, act by binding the IL-2a receptor's α chain, preventing the IL-2
induced clonal expansion of activated lymphocytes and shortening their survival. They are used
in the prophylaxis of the acute organ rejection after bilateral kidney transplantation, both being
similarly effective and with only few side-effects.
3. Both antibodies are given IV, Basiliximab is about 10-fold more potent than Daclizumab as a
blocker of IL-2 stimulated T-cell replication, but the serum half-life of Daclizumab is about 20
days, and the blockade of the receptor is 120 days. Five doses of
4. Daclizumab are usually administered, and the serum half-life of Basiliximab is about 7 days,
usually two doses of this drug are administered.
Basiliximab Inj. Powder Simulect® 10 mg , 20 mg
Daclizumab Inj. Solu. Zenapax® 5 mg/ml
D) Other Monoclonal Antibodies (Monoclonal)

These drugs vary in their uses, ranges from the treatment of cancers to immunosuppressive
therapies and auto-immune diseases treatments (Psoriasis, Arthritis, Asthma .. etc.).
➢ Note: there are a lot of other Monoclonal antibodies that is mainly used for the treatment of
cancers, they are mentioned in the next oncology part, page 395.
Natalizumab Inj. Solu. Tysabri® 300 mg/15 ml
Abatacept Prefilled Inj. Orencia® 125 mg/Inj.
I.V. infusion 250 mg/vial
Tocilizumab Inj. Solu. Actemra® 20 mg/ml
Prefilled Inj. 162 mg/0.9 ml
Rituximab Inj. Solu. Rituxan® 10 mg/ml
Canakinumab Inj. Powder ILaris® 180 mg/vial
Raxibacumab Inj. Solu. Raximab® 50 mg/ml
Ustekinumab Inj. Solu. Stelara® 45 mg/0.5 ml
Alemtuzumab Inj. Solu. CamPath® 10 mg/ml , 30 mg/ml
Notes:
1. Infliximab, Adalimumab, Certolizumab and Natalizumab are FDA Approved for the treatment
of Crohn’s disease and Ulcerative colitis, and are also used in the treatment of Psoriasis (Psoriatic
Arthritis and Plaque Arthritis), Rheumatoid Arthritis, and Ankylosing Spondylitis.
2. Golimumab is indicated for all the above except Crohn’s disease and Ulcerative colitis.
3. Tocilizumab is indicated for Rheumatoid Arthritis and systemic sclerosis.
4. Etanercept is used in the treatment of Psoriasis and Rheumatoid Arthritis.
5. Rituximab is also used in the management of NH Lymphoma, CL Leukemia.
6. Raxibacumab is indicated for treatment of inhalation anthrax in combination with antibiotics.
7. Ustekinumab is used in the treatment of Psoriasis (Psoriatic Arthritis and Plaque Arthritis).
8. Alemtuzumab is approved for the treatment of refractory B-cell chronic lymphocytic leukemia.
5) Other immunosuppressive agents:

Auranofin Cap Ridaura® 3 mg
Gold Na+ Thiomalate Inj. Solu. Aurothiomalate® 25 mg/ml , 50 mg/ml
Belatacept Inj. Powder Nulojix® 250 mg/vial
Leflunomide Tab Arava®, Vamid® 10 mg , 20 mg , 100 mg
* Hydroxychloroquine is also an antimalarial, its uses as a DMARD in Rheumatoid Arthritis.
** Leflunomide is mainly used in Rheumatoid Arthritis.
Second: Immune Globulins:
1. Immunoglobulin (also called gamma globulin or immune globulin) is a substance made from
human blood plasma. The plasma, processed from donated human blood, contains antibodies
that protect the body against diseases. When you are given an immunoglobulin, your body uses
antibodies from other people's blood plasma to help prevent illness; and even though
immunoglobulins are obtained from blood, they are purified so that they can't pass on diseases
to the person who receives them.
2. Specific types of immunoglobulin are made to protect against specific diseases, such as hepatitis,
chickenpox, or measles. Immunoglobulin injections may:
a. Give short-term protection against or reduce the severity of certain diseases.
b. Protect your fetus if you are pregnant and at risk for Rh sensitization.
c. Decrease the immune system's ability to attack body tissues in some cases of autoimmune
disease.
d. Help people who have an inherited problem making their own antibodies or those who are
having treatment for certain types of cancer (such as leukemia).
e. Treatments for some cancers can cause the body to stop producing its own antibodies, making
immunoglobulin treatment necessary.
1. Disease prevention
1. You may be given an immunoglobulin if you are exposed to certain infectious diseases, such as
hepatitis A, rubella, or measles. The immunoglobulin may prevent or reduce the severity of the
illness if given shortly after exposure. The time period during which an injection provides this
benefit ranges from days to months, depending on the disease.
2. Immunoglobulins do not provide long-term protection in the same way as a traditional vaccine.
The protection they provide is short-term, usually lasting a few months. It is still possible to get
the disease after the immunoglobulin has worn off.
2. Rh sensitization
1. When a Rh-negative woman becomes pregnant with a Rh-positive fetus (which can occur when
the father's blood is Rh-positive), the pregnant woman's immune system makes antibodies that
can destroy the fetus's blood in a future pregnancy. This antibody response is called Rh
sensitization and occurs only if the fetus's blood mixes with the pregnant woman's, which can
happen during birth.
2. To prevent Rh sensitization during pregnancy, you must have a Rh immunoglobulin injection if
you are Rh-negative. This is done during your pregnancy and after delivery to protect the fetus
of a future pregnancy. (See chapter 7, section 1, for more information).
3. Idiopathic thrombocytopenic purpura (ITP)

1. Immunoglobulin is sometimes used to treat idiopathic thrombocytopenic purpura (ITP), an
immune disorder in which the body attacks the cells responsible for blood clotting (platelets),
resulting in bleeding; The cause of ITP is not known (idiopathic).
2. People who have this disorder may have bruises or black-and-blue marks (purpura) on the skin.
Internal bleeding is a more serious complication that can occur.
3. Some cases of ITP may go away on their own and do not require treatment. In other cases,
treatment may be needed to control bleeding. Some medicines can help the body make more
platelets. Steroids (such as prednisone) or other medicines may be needed to suppress the
immune system. An intravenous (IV) infusion of a substance made from human blood plasma
(immunoglobulin) may be given. Sometimes you will need to have platelet transfusions. In rare
cases, the spleen may need to be removed.

Immune Globulin I.V. Inj. Solu. Flebogamma , Gamunex
® ® 1 gm , 5 gm
Immune Globulin I.M. Inj. Solu. Gamastan ® 150-180 mg/ml
Immune Globulin S.C. Inj. Solu. Hizentra ® 20% , 10%
Hepatitis B Immune Globulin Inj. Solu. HepaGam B®, HyperHep®
Rabies Immune Globulin Inj. Solu. HyperRAB®, Imogam® 150 IU/ml
Tetanus Immune Globulin Inj. Powder HyperTET® 250 IU
Vaccinia Immune Globulin Inj. Solu. VIGIV® 50 mg/ml
Varicella Zoster Immune Inj. Powder VariZIG® 125 IU/vial
Globulin
Cytomegalovirus Immune Inj. Solu. CytoGam® 50 mg/ml
Globulin
Botulism Immune Globulin * Inj. Powder BabyBIG® 100 mg/vial
Anti-D Immune Globulin Inj. Solu. Rhoclone® , RhoGAM® 150 mcg , 300 mcg
(Rho(D) IG) Inj. Solu. WinRho SDF® 120 mcg , 300 mcg
Antithymocyte globulin Inj. Solu. Atgam®, ATG equine® 50 mg/ml

Equine
Antithymocyte globulin Inj. Solu. Thymoglobulin®, 25 mg/vial
Rabbit ATG Rabbit®
* Botulism Immune Globulin is only indicated for infants below 1-year-old.
Note: There are five major types of antibodies are:

1. IgA antibodies are found in areas of the body such the nose, breathing passages, digestive tract,
ears, eyes, and vagina. IgA antibodies protect body surfaces that are exposed to outside foreign
substances. This type of antibody is also found in saliva, tears, and blood. About 10% to 15% of
the antibodies present in the body are IgA antibodies. A small number of people do not make IgA
antibodies.
2. IgG antibodies are found in all body fluids. They are the smallest but most common antibody
(75% to 80%) of all the antibodies in the body. IgG antibodies are very important in fighting
bacterial and viral infections. IgG antibodies are the only type of antibody that can cross the
placenta in a pregnant woman to help protect her baby (fetus).
3. IgM antibodies are the largest antibody. They are found in blood and lymph fluid and are the
first type of antibody made in response to an infection. They also cause other immune system
cells to destroy foreign substances. IgM antibodies are about 5% to 10% of all the antibodies in
the body.
4. IgE antibodies are found in the lungs, skin, and mucous membranes. They cause the body to
react against foreign substances such as pollen, fungus spores, and animal dander. They are
involved in allergic reactions to milk, some medicines, and some poisons. IgE antibody levels are
often high in people with allergies.
5. IgD antibodies are found in small amounts in the tissues that line the belly or chest. How they
work is not clear.

Third: Interferons:
1. Interferons are a family of naturally-occurring proteins that are made and secreted by cells of the
immune system (for example, white blood cells, natural killer cells, fibroblasts, and epithelial
cells); Three classes of interferons have been identified:
1. Alpha 2. Beta 3. Gamma
2. Each class has many effects, though their effects overlap. Commercially available Interferons are
human Interferons manufactured using recombinant DNA technology. The mechanism of action
of interferon is complex; Interferons modulate the response of the immune system to
viruses, bacteria, cancer, and other foreign substances that invade the body. Interferons do not
directly kill viral or cancerous cells; they boost the immune system response and reduce the
growth of cancer cells by regulating the action of several genes that control the secretion of
numerous cellular proteins that affect growth.
3. Although Interferons are very similar, they affect the body differently, therefore, different
Interferons are used for different conditions.
a. Interferon Alphas are used for treating cancers and viral infections.
b. Interferon Betas are used for treating multiple sclerosis
c. Interferon Gamma is used for treating chronic granulomatous disease.
4. Since Interferons enhance the immune system in many ways, they are used for many diseases
that involve the immune system. For example:
1. Interferon alfa-2a is FDA-approved to treat hairy cell leukemia, AIDS-related Kaposi's
sarcoma, and chronic myelogenous leukemia.
2. Interferon alfa-2b is approved for the treatment of hairy cell leukemia, malignant
melanoma, condylomata acuminata, AIDS-related Kaposi's sarcoma, chronic hepatitis C,
and chronic hepatitis B.
3. Ribavirin combined with interferon alfa-2b, interferon alfacon-1, Pegylated
interferon alfa-2b, or Pegylated interferon alpha-2a, all are approved for the
treatment of chronic hepatitis C.
4. Interferon beta-1b (Betaseron®) and interferon beta-1a (Avonex®) are approved for the
treatment of multiple sclerosis.
5. Interferon alfa-n3 (Alferon-N®) is approved for the treatment of genital and perianal
warts caused by human papillomavirus (HPV).
6. Interferon gamma-1B (Actimmune®) is approved for the treatment of chronic
granulomatous disease, and severe, malignant osteoporosis.
5. Side effects include Flu-like symptoms following each injection (fever, chills, headache, muscle
aches and pains, malaise), occur with all of the Interferons. These symptoms vary from mild to
severe and occur in up to half of all patients; The symptoms tend to diminish with repeated
injections and may be managed with analgesics such as acetaminophen and antihistamines such
as diphenhydramine.
Interferon Alfa-2a Vial Roferon A 18 million IU
Interferon Alfa-2b Inj. Solu. Intron A® 6 , 10 million IU/ml
Inj. Powder 10 , 18 , 30 million IU/vial
Interferon Alfa-n3 Inj. Solu. Alferon N® 5 million IU/ml
Interferon Alfacon-1 Inj. Solu. Infergen® 9 mcg/0.3 ml , 15 mcg/0.5 ml
Interferon Beta-1a Prefilled Inj. Avonex® 30 mcg/0.5 ml
Prefilled Inj. Rebif® 22 mcg/0.5 ml , 44 mcg/0.5 ml
Interferon Beta-1b Inj. Powder Betaseron® , Extavia® 0.3 mg/vial
Interferon Gamma 1b Inj. Solu. Actimmune® 100 mcg/0.5 ml

Peg-Interferon Alfa-2a Vial Pegasys® 180 mcg/ml (single use)
Prefilled Inj. 180 mcg/0.5 ml (single use)
Peg-Interferon Alfa-2b Inj. Powder Sylatron® 444 mcg/vial , 888 mcg/vial
Prefilled Inj. PEG Intron® 80 mcg , 120 mcg , 180 mcg
Notes:
1. Peg-Interferon alfa-2b, comes in combination pack with (Ribavirin 200 mg cap.); for the
treatment of chronic hepatitis C.
2. The dose of Peg-INF alfa-2b is weight dependent, while the alfa-2a dose is fixed.
3. Conventional IFN therapy has been virtually replaced with PEG-IFN, because of the ease of
administration (once-weekly injections), fewer side effects, and improved efficacy.
4. Lamivudine (100 mg daily given orally) in combination with PEG-IFN resulted in greater HBV
DNA suppression.
Fourth: Immunomodulators:
Immunomodulators are medications used to help regulate or normalize the immune system.
They can be used as an add-on therapy to treat asthma or to treat hereditary angioedema.
C1 inhibitor Inj. Powder Berinert , Cinryze
® ® 500 Unit/vial
Ecallantide Inj. Solu. Kalbitor® 10 mg/ml (single use)
Icatibant Prefilled Inj. Firazyr® 30 mg (10 mg/ml)
Rilonacept Inj. Powder Arcalyst® 220 mg/vial
Notes:
1. C1 inhibitor is also indicated for routine prophylaxis against angioedema attacks in adolescent
and adult, and for Capillary Leakage Syndrome.
2. Rilonacept is indicated for Cryopyrin Associated Periodic Syndrome.
Fifth: Immunostimulants:
1. Immunostimulators are substances (drugs and nutrients) that stimulate the immune system by
inducing activation or increasing activity of any of its components.
2. There are two main categories of Immunostimulants:
a. Specific Immunostimulants provide antigenic specificity in immune response, such as
vaccines or any antigen.
b. Non-specific Immunostimulants act irrespective of antigenic specificity to augment
immune response of other antigen or stimulate components of the immune system
without antigenic specificity, such as adjuvants and non-specific Immunostimulators.
3. Many endogenous substances are non-specific Immunostimulators. For example, female sex
hormones are known to stimulate both adaptive and innate immune responses
4. Some autoimmune diseases such as lupus erythematosus strike women preferentially, and their
onset often coincides with puberty.
5. Some publications point towards the effect of deoxycholic acid (DCA) as an immunostimulant of
the unspecific immune system, activating its main actors, the macrophages. According to these
publications, a sufficient amount of DCA in the human body corresponds to a good immune
reaction of the unspecific immune system.

Types of Immunostimulants:
1. Colony stimulating factors: are glycoproteins that promote production of white blood cells
(mainly granulocytes such as neutrophils), in response to infection. Administration of exogenous
colony stimulating factors stimulates the stem cells in the bone marrow to produce more of the
particular white blood cells; The new white blood cells migrate into the blood and fight the
infection.
➢ Colony stimulating factors are used in patients who are undergoing cancer treatment that
causes low white blood cell counts (neutropenia) and puts the patient at risk of infection.
Colony stimulating factors tend to reduce the time where patients are neutropenic.
➢ These include: Filgrastim, Pegfilgrastim, Sargramostim and Lenograstim
(See chapter 15, section 5 for more info)
2. Interleukins:
A group of cytokines which are synthesized by lymphocytes, monocytes, macrophages, and
certain other cells; they function especially in regulation of the immune system.
Aldesleukin Vial Proleukin ® 22 million IU/vial (1.3 mg)
Oprelvekin S.C. Inj. Neumega , Interleukin 11
® ® 5 mg/vial
Notes:
o Aldesleukin has been shown to possess the biological activities of human native interleukin-2,
the immunoregulatory properties include:
a. Enhancement of lymphocyte mitogenesis and stimulation of long-term growth of human
interleukin-2 dependent cell lines and Enhancement of lymphocyte cytotoxicity.
b. Induction of killer cell - lymphokine-activated (LAK) and natural (NK) – activity and
Induction of interferon-gamma production.
o Oprelvekin is indicated for the prevention of severe thrombocytopenia.
3. Bacterial vaccines: Contain killed or attenuated bacteria that activate the immune system.
Antibodies are built against that particular bacteria, and prevents bacterial infection later.
4. Viral vaccines: Contain either inactivated viruses or attenuated viruses. (Alive but not capable
of causing disease), Inactivated or killed viral vaccines contain viruses, which have lost their
ability to replicate and in order for it to bring about a response it contains more antigen than live
vaccines; Attenuated or live vaccines contain the live form of the virus. These viruses are not
pathogenic but are able to induce an immune response.
5. Vaccine combinations merge antigens that prevent different diseases or that protect against
multiple strains of infectious agents causing the same disease, into a single product. This reduces
the number of injections required to prevent some diseases.
6. Therapeutic vaccines: are vaccines which are intended to treat or cure a disorder or disease by
stimulating the immune system; Therapeutic vaccines may be used to treat certain types of
cancer, by stimulating the body's immune system to help it respond against certain cancer cells.
They may also be used in the prevention of tuberculosis in persons not previously infected with
M. tuberculosis who are at high risk for exposure.

Part Two: Oncology
1. New cells are continuously needed by the body to replace those that wear out and die naturally
and to repair injured tissue. Normally, the rate at which cells are created is carefully regulated;
However, sometimes abnormal cells are formed that multiply uncontrollably, and they may form
lumps of abnormal tissue.
2. These tumors are usually confined to one place and cause few problems; these are benign
growths, such as warts; while in other types of tumors, the cells may invade or destroy the
structures around the tumors, and abnormal cells may spread to other parts of the body, forming
satellite or metastatic tumors; These are malignant growths, also called cancers.
3. Uncontrolled multiplication of cells leads to the formation of tumors that may be benign or
malignant; Benign tumors do not spread to other tissues; while malignant (cancerous)
tumors does spread to other tissues.
➢ Carcinomas: affect the skin and cells in the tissue lining internal organs.
➢ Sarcomas: affect muscles, bones, and fibrous tissues and lining cells of blood vessels.
➢ Leukemia: affects white blood cells.
➢ Lymphomas: affect the lymph glands.
4. Cancer is a general term that covers a wide range of disorders, ranging from the leukemias (blood
cancers) to solid tumors of the lung, breast, and other organs; In all cancers, a group of cells
escape from the normal controls on cell growth and multiplication; As a result, the malignant
(cancerous) cells begin to crowd out the normal cells and a tumor develops.
➢ Cancerous cells are frequently unable to perform their usual functions, and this may lead to
progressively impaired function of the organ or area concerned.
➢ Cancers may develop from cells of the blood, skin, muscle, or any other tissue.
➢ Malignant tumors spread into nearby structures, blocking blood vessels and compressing
nerves and other structures.
➢ Fragments of the tumor may become detached and carried in the bloodstream to other parts
of the body, where they form secondary growths (Metastases).
5. A single cause for cancer has not been identified, and an individual’s risk of developing cancer
may depend both upon genetic predisposition (some families seem prone to cancers of one or
more types) and upon exposure to external risk factors, known as carcinogens; These include
chronic tobacco smoking (which increases the risk of lung cancer), chronic heavy alcohol
consuming, and ultraviolet light (which makes skin cancer more likely in those who spend long
periods in the sun), Radiation (X-Rays) and Environmental Pollution.
➢ Long-term suppression of the immune system by disease (as in AIDS) or by drugs (those given
to prevent rejection of transplanted organs) increases the risk of developing infections and
also certain cancers.
6. In cancer treatment, conventional chemotherapy involves using cytotoxic (cell-killing drugs) to
eliminate abnormally dividing cells; These slow the growth rate of tumors and sometimes
lead to their complete disappearance.
➢ Because these drugs act against all rapidly dividing cells (including Hair; which explains
severe hair loss in patients receiving cytotoxics), they also reduce the number of normal cells,
including blood cells, being produced from bone marrow; This can produce serious adverse
effects, such as anemia and neutropenia in cancer patients.
➢ Newer anticancer drugs are more selective in the cells they target; For ex: Trastuzumab
targets a specific protein produced by certain types of breast cancer cells.
7. Treating cancer is a complicated process that depends on the type of cancer, its stage of
development, and the patient’s condition and psychology; Any of the following treatments may
be used alone or in combination with the others: surgery, radiation treatment, and drug therapy.
8. Hormone treatments are suitable for only a few types of cancer and cytotoxic drugs, although
valuable, can have severe side effects because of the damage that they do to normal tissues.
9. In recent years, as understanding of cancer biology has increased, new anticancer drugs have
been developed, these drugs include Cytokines, such as Interferon and Interleukin-2, that
stimulate the immune system to attack certain cancers, and Monoclonal Antibodies and
Growth Factor Inhibitors that attack the cancer cells much more selectively.
Second: Treatment Types:

1. Induction Chemotherapy: the first line treatment for cancer with chemotherapeutic agent.
2. Combined Modality Chemotherapy: the use of drugs with other cancer treatments as (surgery,
radiation, or hyperthermia therapy).
3. Consolidation Chemotherapy: the drug treatment that is given after remission in order to
prolong the overall disease-free time, and to improve overall survival, the drug is the same drug
used in the Induction Chemotherapy.
4. Intensification Chemotherapy: same as Consolidation; but a different drug is used than the one
being used in the Induction Chemotherapy.
5. Adjuvant chemotherapy: drug treatment used after surgery, especially for breast and bowel
tumors, to prevent regrowth of the cancer from cells left behind after surgery.
6. Neoadjuvant or (Primary Chemotherapy): drug treatment that is used before surgery to
reduce the size or shrink the tumor.
7. Hormone treatment is offered in cases of hormone-sensitive cancer, such as breast, uterine, and
prostatic cancers, where it can be used to relieve disease symptoms or provide palliative
treatment in advanced disease.
8. Salvage Chemotherapy or (Palliative Chemotherapy): the drug treatment that is given
without the intent of cure, but simply to increase life expectancy as long as possible; while having
the most possible life quality.
9. Cytokines, Monoclonal Antibodies, and Growth Factor Inhibitors are increasingly used
alongside or instead of conventional chemotherapy; Sometimes these can be curative but often
they produce or prolong disease remission.
Notes:
1. The Efficacy of chemotherapy greatly depends on the type and stage of Cancer.
2. Most anticancer drugs, especially cytotoxic drugs, have side effects, which are sometimes severe,
and so treatment decisions have to balance possible benefits against the side effects, and
often a combination of several drugs is used.
➢ Common side effects include: Severe vomiting, stomatitis, bone marrow suppression (which
predisposes to infections) and Alopecia (hair loss).
3. Special regimes of different drugs that are used together and in succession have been devised to
maximize their activity and minimize the side effects; also, Certain anticancer drugs are also used
for their effect in suppressing immune system activity.
4. Some cancer cells (as melanoma) are inherently resistant to most anti-cancer drugs; some tumor
types may acquire resistance to the cytotoxic effects of anti-cancer drugs by mutating (usually
after prolonged administration of sub-optimal drug doses).
5. Also, Tumor resistance to chemotherapy can develop by: (decreased drug uptake into the cells,
increased drug efflux outside the cells, activation of detoxifying systems, activation of DNA repair
mechanisms, and by evasion of drug-induced apoptosis).
➢ Some drugs as (Verapamil) in high doses, can interfere with the pumps that cause the efflux
of anti-cancer drugs outside the cells; thus, reducing drug resistance.

Third: How Anti-Cancer drugs work:
Anticancer drugs work in many different ways; the main groups of drugs and how they work:
1. Cytotoxic drugs: There are several classes of cytotoxic drugs, including the Alkylating Agents,
Anthracyclines (Cytotoxic Antibiotics), Antimetabolites, Taxanes Platinum compounds
and Vinca Alkaloids, and; Each class has a different mechanism of action, but all act by
interfering with basic processes of cell replication and division.
➢ They are particularly potent against rapidly dividing cells; These include cancer cells but also
certain normal cells, especially those in the hair follicles, gut lining, and bone marrow.
➢ This explains their side effects and why treatment needs careful scheduling.
2. Hormone therapies: Hormone treatments act by counteracting the effects of the hormone that
is encouraging growth of the cancer; for example, some breast cancers are stimulated by the
female sex hormone estrogen; the action of estrogen is opposed by the drug Tamoxifen, other
cancers are damaged by very high doses of a particular sex hormone; An example is
Medroxyprogesterone, a progesterone that is used to halt the spread of endometrial cancer.
3. Cytokines: The Cytokines, Interferon Alfa and Interleukin-2, stimulate the immune system to
attack certain cancers.
4. Monoclonal antibodies: Antibodies are a fundamental building block of the immune system,
they recognize and bind very specifically to foreign proteins on the surface of bacteria, viruses,
and parasites, marking them out for destruction by other parts of the immune system.
➢ Monoclonal antibodies are produced in tissue culture using cells genetically engineered to
make antibodies against a particular target protein; If the target is carefully selected, the
antibodies can be used to identify cancer cells for destruction; If the target is found only on
cancer cells, or on the cancer cells and the normal tissue from which it arose, the damage to
healthy tissues during treatment is limited.
➢ These antibodies are very specific for certain types of cancer, and they cause little of the
toxicity of conventional chemotherapy; They can, however, cause allergy-type reactions,
especially at the beginning of treatment.
5. Growth factor inhibitors: The growth of cells is controlled by a complex network of growth
factors that bind very specifically to receptor sites on the cell surface, this triggers a complex
series of chemical reactions that transmit the “grow” message to the nucleus, triggering cell
growth and replication. In many cancers, this system is faulty and there are either too many
receptors on the cell surface or other abnormalities that result in inappropriate “grow” messages.
The extra or abnormal cell surface receptors can be used as targets for monoclonal antibodies.
➢ Another new area of cancer treatment is the use of drugs that inhibit the growth of new blood
vessels to tumors (anti-angiogenesis agents), thereby depriving the tumors of the nutrients
and oxygen they need to grow.

Notes:
1. Cytotoxic drugs are generally associated with more side effects than other anticancer drugs, at
the start of treatment, adverse effects of the drugs may be more noticeable than benefits; the
most common side effect is nausea and vomiting, for which an anti-emetic drug will usually be
prescribed, effects on the blood are also common; many cytotoxic drugs cause hair loss because
of their effect on the hair follicle cells, but the hair usually starts to grow back after chemotherapy
has been completed; Individual drugs may produce other side effects.
➢ In some cases, they cause symptoms of anemia (weakness and fatigue) and an increased risk
of abnormal or excessive bleeding may develop as a result of treatment with anticancer drugs.
➢ Reduction in the number of white blood cells may result in an increased susceptibility to
infection. A simple infection such as a sore throat may be a sign of depressed white cell
production in a patient taking anticancer drugs.
➢ Also, some wounds may take longer to heal, and susceptible people can develop gout as a
result of increased uric acid production due to cells being broken down.
2. Cytotoxic drugs are, in most cases, administered in the highest doses that can be tolerated in
order to kill as many cancer cells as quickly as possible.
3. The unpleasant side effects of intensive chemotherapy, combined with a delay of several weeks
before any beneficial effects are seen and the seriousness of the underlying disease, often lead to
depression in those who are receiving anticancer drugs.
➢ Thus; Specialist counselling, support from family and friends may have huge beneficial effects
on the therapy, and in some cases, treatment with antidepressant drugs may be helpful.
4. Not all cancers respond to treatment with anticancer drugs; Some cancers can be cured by
drug treatment; In other cancers, drug treatment can only slow or temporarily halt the disease’s
progress, in certain cases, drug treatment has no beneficial effect but other treatments, such as
surgery, often produce significant benefits.
The main cancers that fall into each of the first two groups are described here:
a. Cancers that can often be cured by drugs: (Some cancers of the lymphatic system
(including Hodgkin’s disease), Acute leukemias (forms of blood cancer), Choriocarcinoma
(cancer of the placenta), Germ cell tumors (cancers affecting sperm and egg cells), Wilms’
tumor (a rare form of kidney cancer that affects children), and Cancer of the testis.
b. Cancers in which drugs may produce worthwhile benefits: Breast cancer, Ovarian cancer,
some leukemias, Multiple myeloma (a bone marrow cancer), Many types of lung cancer, Head
and neck cancers, Cancer of the stomach, Cancer of the prostate, some cancers of the
lymphatic system, Bladder cancer, Endometrial cancer (cancer affecting the lining of the
uterus), Cancer of the large intestine, Cancer of the esophagus, Cancer of the pancreas, and
Cancer of the cervix.
5. Successful drug treatment of cancer usually requires repeated courses of anticancer drugs
because the treatment needs to be halted periodically to allow the blood-producing cells in the
bone marrow to recover.
6. Imaging (CT, MRI, PET) is frequently done after 2 to 3 cycles of therapy to evaluate response;
Therapy continues if there is a clear response.
➢ If the tumor progresses despite therapy, the regimen is often changed or stopped.
➢ If the disease remains stable with treatment and the patient can tolerate therapy, then a
decision to continue is reasonable with the understanding that the disease will eventually
progress.

Fourth: Anti-Cancer Groups
A. Cytotoxic antineoplastics
1. Alkylating Cytotoxic Agents
a. Compounds that work by adding an alkyl group to the guanine base of the DNA molecule,
preventing the strands of the double helix from linking as they should; This causes breakage
of the DNA strands, affecting the ability of the cancer cell to multiply.
b. Alkylating agents are used to treat several cancers, but they are also toxic to normal cells,
particularly cells that divide frequently, such as those in the gastrointestinal tract, bone
marrow, hair follicles, testicles and ovaries, which can cause loss of fertility.
c. Alkylating agents are mutagenic and Carcinogenic, and can lead to secondary malignancies
such as acute Leukemia.
Bendamustine Vial Treanda® , Ribomustin® 100 mg
Busulfan Vial Myleran® , Busulfex® 60 mg/10 ml
Tab 2 mg
Carmustine Vial BiCNU® , Gliadel® 100 mg
Chlorambucil Tab Leukeran® 2 mg
Cyclophosphamide Vial Cytoxan® , Endoxan® 500 mg , 1 gm
Tab 25 mg , 50 mg
Procarbazine Tab Matulane® , Natulan® 50 mg
Dacarbazine Vial DTIC® , Celdaz® 100 mg , 200 mg
Estramustine Cap Estracyt® 140 mg
Ifosfamide Vial Ifex® 1 gm/20 ml , 3 gm/60 ml
Lomustine Cap Gleostine® 10 mg , 40 mg , 100 mg
Melphalan Vial Alkeran® 50 mg
Tab 2 mg
Temozolomide Cap Temodal® 100 mg , 140 mg
Vial 100 mg
Thiotepa Vial Thioplex® , Tespa® 15 mg
Treosulfan Vial Trecondi® 1 gm , 5 gm
Streptozocin Vial Zanosar® 1 gm
Altretamine Cap Hexalen® 50 mg
2. Platinum compound Cytotoxic agents

a. They are coordination complexes of platinum; These are a heavy-metal complex that exerts a
cytotoxic effect by binding DNA, forming cross-links which disrupt the ability of replication
and transcription, thus inducing cell apoptosis.
b. Platinum-based antineoplastic agents are sometimes described as (alkylating-like) due to
similar effects as alkylating antineoplastic agents, although they do not have an alkyl group.
c. Common side effects include neurotoxicity, which is manifested by peripheral neuropathies
including polyneuropathy.
d. Have a synergistic effect when combined with other Alkylating agents and Taxanes.
Carboplatin Vial Paraplatin® , Kemocarb® 150 mg , 450 mg , 600 mg
Cisplatin Vial Platamin® 50 mg , 100 mg , 200 mg
Oxaliplatin Vial Eloxatin ® 50 mg , 100 mg
Nedaplatin Vial Aqupla ® 10 mg
Dicycloplatin Pending FDA approval
3. Anthracycline (antibiotics) Cytotoxic Agents
a. They are extracted from Streptomyces bacterium; They are derived from antibiotics that
inhibit DNA and RNA synthesis by intercalating between base pairs of the DNA/RNA strand;
Cytotoxicity is primarily due to inhibition of topoisomerase II after the enzyme induces a
break in DNA, preventing religation of the break and leading to cell death.
b. They also produce free radicals, which plays a major role in their cytotoxic effect.
c. Two major dose limiting toxicities of Anthracyclines include myelosuppression and
cardiotoxicity; which is dose-dependent and cumulative.
➢ Dexrazoxane is used with Anthracyclines to reduce their cardio-toxic effect, it’s a
derivative of EDTA (chelates Iron and thus reducing metal iron complexed with
Anthracyclines; which leads to decrease in the formation of superoxide radicals).
➢ Liposomal Doxorubicin has lower cardio-toxic effects than the older formulation.
d. They may cause a red color urine; and the veins at the site of injection may become dark red.
Daunorubicin Vial Daunomycin® , Cerubidine® 20 mg/4 ml , 50 mg/10 ml
Doxorubicin Vial (Solu.) Adriamycin® , Rubex® 20 mg , 50 mg , 100 mg
Doxorubicin Vial Doxil® 20 mg , 50 mg
(Liposomal)
Epirubicin Vial Ellence® 10 mg , 20 mg , 100 mg
Idarubicin Vial Idamycin® 5 mg , 10 mg , 20 mg
Mitoxantrone Vial Novantrone® 20 mg , 25 mg , 30 mg
Pixantrone Vial Pixuvri® 29 mg
Bleomycin Vial Blenoxane® 15 units , 30 units
Mitomycin Vial Mutamycin® 10 mg , 20 mg , 40 mg
Dactinomycin * Vial Cosmegen® 500 mcg
* Dactinomycin = Actinomycin D, they are the same drug.
4. Microtubule Inhibitors
1. Mitotic spindle is an intracellular skeleton (cytoskeleton), that is essential for the movements of
structures occurring in the cytoplasm of all eukaryotic cells; the mitotic spindle consist of
chromatin and microtubules (which is composed of tubulin protein); the mitotic spindle is
essential for all cell division.
2. Several anti-cancer groups act to disturb the microtubules; usually affecting the equilibrium
between the polymerized and depolymerized forms of the microtubules; thus, causing
cytotoxicity, these groups include: Vinca Alkaloids and Taxanes.
A) Vinca Alkaloid Cytotoxic agents

a. They disrupt microtubule formation; they also have many effects on cellular activities,
including inhibition of mitotic spindle formation and mitotic arrest; All Vinca alkaloids bind
to tubulin, a protein comprised of α and β subunits, inhibiting its polymerization.
Polymerization of tubulin is responsible for the formation of the mitotic spindle during the
metaphase period of mitosis
b. Thus, Vinca alkaloids inhibit cell division in the M phase of the cell cycle.
c. Vinblastine and Vincristine are natural alkaloids, while Vindesine, Vinorelbine and
Vinflunine are semisynthetic derivatives.
d. The most common side effect is Neurotoxicity, including peripheral neuropathy, also SIADH
may occur (syndrome of inappropriate secretion of antidiuretic hormone).
➢ Liposomal Vincristine has a lower neurotoxicity side effect.

Vinblastine Vial Velban ® 10 mg/10 ml
Vincristine * Vial Oncovin , Vincasar
® ® 1 mg , 2 mg
Vincristine Liposomal Vial Marqibo ® 5 mg
Vindesine Vial Eldisine® 5 mg
Vinorelbine Vial Navelbine ® 10 mg , 50 mg
Vinflunine Vial Javlor® 50 mg , 250 mg
* Vincristine = Leurocristine, they are the same drug.
B) Taxanes Cytotoxic agents

a. As their name suggests, Taxanes were first derived from natural sources, but some have been
synthesized artificially; Taxanes present difficulties in formulation as medicines because they
are poorly soluble in water.
b. Also called Cytoskeletal disruptors or anti-microtubulars, they produce antitumor activity
by causing stabilization of cellular microtubules, thereby inhibiting cell division.
c. They have high binding affinity to microtubules with enhancement of tubulin polymerization.
d. Limitations to Taxanes use include the risk of life-threatening hypersensitivity reactions,
hematopoietic toxicity and cumulative neurotoxicity.
Cabazitaxel Vial Jevtana® 60 mg
Docetaxel Vial Taxotere® , Docax® 20 mg , 80 mg , 120 mg , 160 mg
Paclitaxel Vial Taxol® 30 mg , 100 mg , 300 mg
Other Microtubules inhibitors
Ixabepilone * Vial Ixempra® 15 mg , 45 mg
Eribulin Amp , Vial Halaven® 0.5 mg , 1 mg
* Ixabepilone is also an Epothilone B analog; which is a highly potent agent, capable of
damaging cancer cell in very low concentrations; it retains activity in cases were tumor cells are
insensitive to Taxanes or Anthracyclines.
5. Topoisomerase inhibitors
a. Topoisomerase enzymes aids in the DNA unwinding, thus inhibiting them prevents re-
ligation of the DNA strands; and by doing so, DNA strand break down, (Cancer cells rely on
this enzyme more than healthy cells, because they divide more rapidly).
b. Groups inhibiting these enzymes include: Podophyllotoxin derivatives and Camptothecins.
➢ Podophyllotoxin derivatives forms a complex with Topoisomerase II forming single
stranded DNA breaks, prevents repair by topoisomerase II binding; Accumulated breaks
in DNA prevent entry into the mitotic phase of cell division, and lead to cell death.
➢ Camptothecins inhibits Topoisomerase I resulting in the stabilization of the cleavable
complexes, causing reversible single stranded DNA breaks, preventing DNA re-ligation
and therefore causes DNA damage which results in apoptosis.
Podophyllotoxin derivatives
Etoposide Cap Toposar® , Etopophos® 50 mg
Vial 100 mg , 500 mg
Teniposide Vial Vumon® 50 mg
Camptothecins
Irinotecan Vial Camptosar® 40 mg , 100 mg
Topotecan Vial Hycamtin® 4 mg
6. Antimetabolite Cytotoxic Agents
a. Antimetabolites are drugs that interfere with one or more enzymes or their reactions that are
necessary for DNA synthesis; They affect DNA synthesis by acting as a substitute to the actual
metabolites that would be used in the normal metabolism (antifolates as methotrexate interfere
with the use of folic acid); competitive inhibition can occur, and the presence of antimetabolites
can have toxic effects on cells, such as halting cell growth and cell division,
b. They are structurally similar to normal compounds that exist within the cell; they interfere with
the availability of normal Purine or Pyrimidine Nucleotides; thus inhibiting synthesis of DNA and
RNA (Antimetabolites generally impair DNA replication machinery, either by incorporation of
chemically altered nucleotides or by depleting the supply of deoxynucleotides needed for DNA
replication and cell proliferation).
c. Many Antimetabolites are available; they differ in their mechanism of action, indications and their
side effects profile.
Folate Analogs
Methotrexate Tab Rheumatrex® , MTX® 2.5 mg , 5 mg , 10 mg
Vial Trexall ® 25 mg/ml
Pemetrexed Vial Alimta ® 100 mg , 500 mg
Pralatrexate Vial Folotyn ® 20 mg/ml , 40 mg/2 ml
Purine Analogs
Mercaptopurine Tab Purinethol® , 6-MP® 50 mg
Fludarabine Vial Fludara® 50 mg/2 ml
Cladribine Vial Leustatin ® 10 mg/10 ml
Tab Mavenclad ® 10 mg
Nelarabine Vial Arranon ® 50 mg
Tioguanine * Tab Tabloid , 6-TG
® ® 40 mg
Clofarabine Vial Clolar ® 20 mg/10 ml
Pentostatin ** Vial Nipent ® 10 mg
Pyrimidine Analogs
Fluorouracil * Vial Adrucil® , 5-FU® 50 mg/ml (1gm , 2.5 gm)
Capecitabine Tab Xeloda® 500 mg
Floxuridine Vial Fudr® 500 mg
Cytidine Analogs
Cytarabine Vial Cytosar® , Ara-C® 500 mg , 1 gm , 2 gm
Azacitidine Vial Vidaza , Xpreza
® ® 100 mg
Gemcitabine Vial Gemzar , Gemsiban
® ® 200 mg , 1 gm , 2 gm
Decitabine Vial Dacogen ® 50 mg
Tegafur + Gimeracil Cap Teysuno® ** (15 mg + 4.35 mg + 11.8 mg),
+ Oteracil (20 mg + 5.8 mg + 15.8 mg)
Trifluridine + Tab Lonsurf ® (15 mg + 6.14 mg),
Tipiracil (20 mg + 8.19 mg)
Notes:
1. Fluorouracil is also available as a topical cream.
2. Tioguanine = Thioguanine; and Pentostatin = Deoxycoformycin, they are the same drug.
3. Tegafur is a prodrug of Fluorouracil (5-FU), Gimeracil inhibits the degradation of Fluorouracil
which results in higher 5-FU levels and a prolonged half-life; Oteracil reduces the production of 5-
FU and Lowers 5-FU levels in the gut resulting in a lower gastrointestinal toxicity.
4. Trifluridine is a nucleoside analog; Tipiracil is a thymidine phosphorylase inhibitor, it prevents
rapid metabolism of Trifluridine, increasing the drug bioavailability.
7. Retinoid derivatives Cytotoxic agents
The retinoic acid receptors (RARs) regulate cell differentiation and proliferation whereas
retinoid X receptors (RXRs) regulate apoptosis.
➢ These agents bind to RXRs and induce cell apoptosis.
Bexarotene Cap Targretin® 75 mg
Gel 1%
Tretinoin Cap Vesanoid® 10 mg
Alitretinoin Gel Panretin® 0.1%
8. Other Cytotoxic agents

Arsenic trioxide Amp , Vial Trisenox® 10 mg
Asparaginase Vial Leunase® 5,000 IU , 10,000 IU
Crisantaspase Vial Erwinase® 5,000 IU , 10,000 IU
Hydroxyurea Cap Hydrea®, Hydrine® 500 mg
(Hydroxycarbamide) Droxia®
Mitotane Tab Lysodren® 500 mg
Panobinostat Cap Farydak® 20 mg
Pegaspargase Vial Oncaspar® 3,750 IU
Raltitrexed Vial Tomudex® 2 mg
Trabectedin Vial Yondelis® 0.25 mg , 1 mg
Olaparib Cap , Tab Lynparza® 50 mg , 100 mg , 150 mg
Venetoclax Tab Venclexta® 10 mg , 100 mg
Vismodegib Cap Erivedge® 150 mg
Note:
Drugs for cytotoxic drug-induced side effects are listed below:
Scientific name D. form Trade name concentration Indications
Dexrazoxane Vial Zinecard®, 250 mg, Prevention of chronic cumulative
Cardioxane® 500 mg cardiotoxicity caused by doxorubicin or
Epirubicin, Anthracycline extravasation
Palifermin Vial Kepivance® 6.25 mg Management of oral Mucositis in patients
with hematological malignancies
Mesna Vial Mesnex® 1 gm Cytotoxic induced urothelial toxicity
Amp 200 mg , 400 mg associated with cyclophosphamide
Amifostine Vial Ethyol® 500 mg To prevent Xerostomia, and to protect
against nephropathy and bone marrow
damage.
Palifermin Vial Kepivance® 6.25 mg For severe oral Mucositis
Folinic acid Tab Leucovorin® 800 mcg Prevention of methotrexate-induced
adverse effects, As an antidote to
Levofolinic acid Vial Leucovorin 50 mg, 100 mg methotrexate, Adjunct to fluorouracil in
Inj. ® 200 mg, 350 mg colorectal cancer
Glucarpidase Vial Voraxane® 1000 unit Converts methotrexate to glutamate and
di-amino methylpteroic acid, used for
prevention of methotrexate-induced
adverse effects
Rasburicase Vial Fasturtec®, 1.5 mg, 7.5 mg Prophylaxis and treatment of acute
Elitek® hyperuricemia, before and during
initiation of chemotherapy
B. Antineoplastic monoclonal antibodies
1. Monoclonal antibodies are a type of targeted cancer therapy; they are directed at specific
targets and they usually have fewer adverse effects (compared to other cancer medications).
➢ For more info on monoclonal antibodies see the previous part (immunology page 378)
2. Monoclonal antibodies can be used alone, or to carry drugs, toxins or radioactive substances
directly to the cancer cells.
3. Most recently, anticancer monoclonal antibodies that target 2 or even 3 antigens have been
developed; These monoclonal antibodies target a cancer-related antigen and a normal antigen on
T cells with the objective of enhancing T-cell killing of cancer cells.
4. Monoclonal antibodies differ greatly in their exact mechanism of action; and thus, differ in
their indications and their side effects profile; below some of the most common notes about them:
➢ Rituximab has the risk of severe infusion reactions (fatal) and Tumor Lysis Syndrome risk.
➢ Both Trastuzumab and Pertuzumab have the risk of causing Heart Failure (risk is increased
or worsen when combined with Anthracyclines).
➢ Bevacizumab has a high risk of causing internal bleeding.
Alemtuzumab * Vial Lemtrada®, Campath® 12 mg/1.2 ml , 30 mg/ml
Atezolizumab Vial Tecentriq® 1200 mg
Avelumab Vial Bavencio® 200 mg
Bevacizumab Vial Avastin® 100 mg , 400 mg
Blinatumomab Vial Blincyto® 35 mcg
Brentuximab Vial Adcetris® 50 mg
Catumaxomab Prefilled Inj. Removab® 10 mcg , 50 mcg
Cetuximab Vial Erbitux® 100 mg , 200 mg
Cemiplimab Vial Libtayo® 350 mg
Daratumumab Vial Darzalex® 100 mg , 400 mg
Denosumab ** Vial Xgeva® 120 mg
Durvalumab Vial Imfinzi® 120 mg , 500 mg
Dinutuximab Vial Unituxin® 17.5 mg
Elotuzumab Vial Empliciti® 300 mg , 400 mg
Gemtuzumab Vial Mylotarg® 4.5 mg
Ipilimumab Vial Yervoy® 50 mg , 200 mg
Mogamulizumab Vial Poteligeo® 20 mg
Necitumumab Vial Portrazza® 800 mg
Nivolumab Vial Opdivo® 40 mg , 100 mg
Obinutuzumab Vial Gazyva® 1000 mg
Olaratumab Vial Lartruvo® 190 mg , 500 mg
Ofatumumab Vial Arzerra® 1000 mg
Panitumumab Vial Vectibix® 100 mg
Pembrolizumab Vial Keytruda® 50 mg , 100 mg
Pertuzumab Vial Perjeta® 420 mg
Ramucirumab Vial Cyramza® 100 mg , 500 mg
Rituximab Vial Rituxan®, MabThera® 100 mg , 500 mg
Siltuximab Vial Sylvant® 100 mg , 400 mg
Tositumomab Vial Bexxar® 35 mg , 225 mg
Trastuzumab Vial Herceptin® , Herzuma® 150 mg , 440 mg
Ado-Trastuzumab Vial Kadcyla® 100 mg , 160 mg
* Alemtuzumab is also used for Multiple Sclerosis.
** Denosumab is also used for osteoporosis (Prolia).
Monoclonal antibodies Combinations
Ado-Trastuzumab Emtansine Vial Kadcyla® 100 mg , 160 mg
Inotuzumab Ozogamicin Vial Besponsa ® 0.9 mg
Gemtuzumab Ozogamicin Vial Mylotarg® 4.5 mg
* Emtansine is a microtubule inhibitor (Cytotoxic agent).
* Ozogamicin is a cytotoxic agent
C. Hormonal Antineoplastics
1. A Hormone-sensitive cancer or (hormone-dependent cancer) is a type of cancer that depends on
hormone for growth; as in Breast cancer (which depends on Estrogens like Estradiol), or
Prostate cancer (which depends on Androgens like Testosterone).
2. Hormonal anticancer drugs are used to reduce or prevent proliferation of cancers that are
responsive to specific levels of hormones.
3. Hormones are signaling molecules that bind to target cells receptors and stimulates or blocks the
cells function; Hormonally responsive cancer can be treated by reducing the level of hormone
that is needed for tumor cell growth and survival, by using inhibitors of hormone synthesis or
hormone receptor antagonist, some cancers may be inhibited by increased level of a specific
hormone therefore supplementing with a hormone agonist is used to treat these types of cancer.
4. Hormonal therapy is particularly useful in prostate cancer, which grows in response to
androgens; Other cancers with hormone receptors on their cells (breast, endometrium) can often
be palliated by hormone antagonist therapy or hormone ablation.
5. Hormonal agents may block the secretion of pituitary hormones (luteinizing hormone–releasing
hormone agonists), block the androgen (Bicalutamide, Enzalutamide) or estrogen receptor
(Tamoxifen), suppress the conversion of androgens to estrogens by aromatase (Letrozole), or
inhibit the synthesis of adrenal androgens (Abiraterone).
6. All hormonal blockers can cause symptoms related to hormone deficiency (such as hot flashes)
and the androgen antagonists also induce a metabolic syndrome that increases the risk of
diabetes and heart disease.

Anti-androgens Antineoplastics
Abiraterone Tab Zytiga® 250 mg , 500 mg
UM Tab Yonsa® 125 mg
Apalutamide Tab Erleada® 60 mg
Bicalutamide Tab Casodex® 50 mg , 150 mg
Enzalutamide Cap Xtandi® , Azel® 40 mg
Flutamide Tab Eulexin® , Cytomid® 250 mg
Cap 125 mg
Nilutamide Tab Nilandron® 150 mg
Degarelix * Vial Firmagon® 80 mg , 120 mg
Estrogens antineoplastics
Diethylstilbestrol Tab Distilbene® 1 mg , 5 mg , 25 mg
Somatostatin analogues antineoplastics
Lanreotide Prefilled Inj. Sumatuline Depot® 60 mg , 90 mg , 120 mg
Octreotide Inj. Solu. Sandostatin® 0.1 mg , 0.5 mg , 1 mg
Depot Inj. Sandostatin LAR® 10 mg , 20 mg , 30 mg
Pasireotide S.C Inj. Signifor® 0.2 mg/ml, 0.6 mg/ml,
0.9 mg/ml
Progestogens antineoplastics
Megestrol acetate Tab Megace® 40 mg , 160 mg
Gonadotropin releasing hormone (GnRH) analogs
Leuprolide ** Inj. Lupron® 5 mg/ml
Triptorelin Inj. (S.C.) Decapeptyl® 0.1 mg/ 1ml
Inj. Powder Trelstar®, Trelstar depot® 3.75 mg , 11.25 mg , 22.5 mg
Anti-Estrogens antineoplastics
Fulvestrant Prefilled Inj. Faslodex® 250 mg
Tamoxifen Tab Nolvadex® 10 mg , 20 mg
Toremifene Tab Fareston® 20 mg , 60 mg
Aromatase inhibitors antineoplastics
Anastrozole Tab Arimidex® 1 mg
Exemestane Cap Aromasin ® 25 mg
* Degarelix is also an Anti-gonadotrophin releasing hormones antineoplastics.
** Leuprolide = Leuprorelin, they are the same drug.
D. Immunotherapy antineoplastics
1. Immunotherapy is the artificial stimulation of the immune system to treat cancer, improving on
the immune system's natural ability to fight the cancer., by enabling it to recognize, target, and
eliminate cancer cells throughout the body.
2. Immunotherapy can be given alone, or in combination with other types of cancer treatments.
It’s already proven to be an effective treatment for patients with various types of cancers.
3. Solid tumors produce growth factors that form new blood vessels necessary to support ongoing
tumor growth; the drugs that inhibit this process is called (Angiogenesis inhibitors), they
include: Thalidomide, Lenalidomide and Pomalidomide
Talimogene Laherparepvec Vial Imlygic® , TVEC® 1 million PFU, 100 million PFU
(PFU = Plaque-Forming Unit)
Interferon Alfa 2b Vial Multiferon® , Intron A® 3 million IU , 5 M , 10 M IU
Interferon Alfa 2a Vial Roferon A® 18 million IU
Aldesleukin Vial Proleukin® 22 million IU
Bacillus Calmette-Guérin Vial Onco BCG® 40 mg/ml
(BCG)
Histamine dihydrochloride VialCeplene® 0.5 mg/0.5 ml
Mifamurtide VialMepact ® 4 mg
Lenalidomide Tab Revlimid , Lenalid
® ® 10 mg , 25 mg
Pomalidomide Cap Pomalyst® , Imnovid® 1 mg , 2 mg , 4 mg
Pomalid ®
Thalidomide Cap Thalomid® , Thalix® 50 mg , 100 mg

* Thalidomide is a sedative drug discovered at the end of the 50s, which caused a worldwide
tragedy; The drug has been prescribed to many pregnant women in order to relieve pregnancy
nausea, it was later found that thalidomide caused irreversible damages to the fetus and
thousands of children were born with severe congenital malformations, many of them did not
survive more than a few days after they were born.

E. Proteasome inhibitors antineoplastics
Proteasome is an enzyme that degrades unwanted cellular proteins; thus, inhibition of this
enzyme results in accumulation of polyubiquinated proteins, which may cause cell cycle arrest,
apoptosis and inhibition of tumor growth.
Bortezomib Vial Velcade® 1 mg , 2 mg , 3.5 mg
Carfilzomib Vial Kyprolis® 10 mg , 30 mg , 60 mg
Ixazomib Cap Ninlaro® 2.3 mg , 3 mg , 4 mg
F. Kinase inhibitor antineoplastics

1. A Tyrosine Kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a
cell; it functions as an "on" or "off" switch in many cellular functions.
2. Phosphorylation of proteins by kinases is an important mechanism in communicating signals
within a cell (signal transduction) and regulating cellular activity, such as cell division.
3. Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular
processes but also to have a critical role in the development, progression of many types of cancer.
4. Protein kinases can become mutated, stuck in the "on" position, and cause unregulated growth
of the cell, which is a necessary step for the development of cancer; Therefore, kinase inhibitors,
(such as Imatinib) are often effective cancer treatments.
5. Many Tyrosine Kinase inhibitors are available (they differ in their exact cellular mechanism; and
thus, differ in their indications and their side effect profile), and these agents have a wide variety
of applications in the treatment of cancer.
6. Some notes regarding Tyrosine Kinase inhibitor antineoplastics:
➢ Imatinib may cause fluid retention, and has a risk of causing sever congestive heart failure.
➢ Nilotinib may cause fluid retention and prolong QT interval.
➢ Dasatinib has the risk of causing Pulmonary Arterial Hypertension.
➢ Erlotinib may cause Pneumonitis and Pulmonary Fibrosis.

Tyrosine Kinase inhibitor antineoplastics
Acalabrutinib Cap Calquence® 100 mg
Afatinib Tab Gilotrif , Xovoltib
® ® 20 mg , 30 mg , 40 mg , 50 mg
Alectinib Cap Alecensa® 150 mg
Avapritinib Tab Ayvakit® 100 mg , 200 mg , 300 mg
Axitinib Tab Inlyta® 1 mg , 5 mg
Brigatinib Tab Alunbrig® 30 mg , 90 mg , 180 mg
Bosutinib Tab Bosulif® 100 mg , 500 mg
Cabozantinib Tab Cabometyx ® 20 mg , 40 mg , 60 mg
Ceritinib Cap Zykadia , Spexib , Noxalk
® ® ® 150 mg
Cobimetinib Tab Cotellic® 20 mg
Crizotinib Cap Xalkori ® 200 mg , 250 mg
Dacomitinib Tab Vizimpro ® 15 mg , 30 mg , 45 mg
Dasatinib Tab Sprycel® 20 mg , 50 , 70 , 100 mg
Entrectinib Cap Rozlytrek ® 100 mg , 200 mg
Erlotinib Tab Tarceva® 100 mg , 150 mg
Gefitinib Tab Iressa , Geftinat
® ® 250 mg
Gilteritinib Tab Xospata ® 40 mg

Ibrutinib Tab Imbruvica® 140 mg , 280 mg , 420 mg
Cap 70 mg , 140 mg
Idelalisib Tab Zydelig® 100 mg , 150 mg
Imatinib Tab Gleevec ® 100 mg , 400 mg
Lapatinib Tab Tykerb , Herduo
® ® 250 mg
Lenvatinib Cap Lenvima® 4 mg , 10 , 14 , 20 , 24 mg
Lorlatinib Tab Lorbrena ® 25 mg , 100 mg
Midostaurin Cap Rydapt ® 25 mg
Neratinib Tab Nerlynx® 40 mg
Nilotinib Cap Tasigna ® 150 mg , 200 mg
Osimertinib Tab Tagrisso , Osicent
® ® 80 mg
Pacritinib Pending FDA approval
Pazopanib Tab Votrient® 200 mg , 400 mg
Pexidartinib Cap Turalio ® 200 mg
Ponatinib Tab Iclusig® 15 mg , 45 mg
Quizartinib Pending FDA approval
Regorafenib Tab Stivarga , Nublexa®
® 40 mg
Ruxolitinib Tab Jakavi® 5 mg , 10 mg , 15 mg , 20 mg
Sorafenib Tab Nexavar ® 200 mg , 400 mg
Sunitinib Cap Sutent ® 12.5 mg , 25 mg , 50 mg
Trametinib Tab Mekinist® 0.5 mg , 2 mg
Vandetanib Tab Caprelsa ® 300 mg
Nintedanib Cap Ofev , Vargatef
® ® 100 mg , 150 mg
Zanubrutinib Cap Brukinsa® 80 mg
Ziv-Aflibercept Vial Zaltrap ® 100 mg , 200 mg
Cyclin Dependent Kinase inhibitor antineoplastics
Abemaciclib Tab Verzenio® 100 mg , 150 mg , 200 mg
Palbociclib Cap Ibrance ® 75 mg , 125 mg
Ribociclib Tab Kisqali ® 200 mg
BRAF Kinase inhibitor antineoplastics
Dabrafenib Cap Tafinlar® 50 mg , 75 mg
Encorafenib Cap Braftovi ® 50 mg , 75 mg
Vemurafenib Tab Zelboraf® 240 mg
mTOR Kinase inhibitor antineoplastics
Everolimus Tab Afinitor® 5 mg , 10 mg
Tab Zortress® 0.25 mg , 0.5 mg
Temsirolimus Vial Torisel ® 25 mg/ml
G. Histone deacetylase inhibitors

1. The Histone deacetylase inhibitors are a new class of cytostatic agents that inhibit the
proliferation of tumor cells by inducing cell cycle arrest, differentiation and/or apoptosis;
Histone deacetylase inhibitors exert their anti-tumor effects via the induction of expression
changes of oncogenes or tumor suppressor, through modulating the acetylation/deactylation of
histones and/or non-histone proteins such as transcription factors.
2. Several compounds act on the Histone deacetylate system, these include:
➢ Romidepsin (which is obtained naturally from Chromobacterium Violaceum bacterium,
and acts by blocking Histone deacetylase enzymes; thus, inducing apoptosis.
➢ Vorinostat, Belinostat, Entinostat and Mocetinostat (which are synthetic Histone
deacetylase inhibitors).

Romidepsin Vial Istodax ® 10 mg
Vorinostat Cap Zolinza ® 100 mg
Belinostat Vial Beleodaq ® 500 mg
Entinostat
Mocetinostat
Note: Nobel Prize in Physiology or Medicine 2018

The 2018 Nobel Prize in Physiology or Medicine was awarded to James P. Allison and Tasuku
Honjo “for their discovery of cancer therapy by inhibition of negative immune regulation”.
Their pioneering work on the CTLA4 and PD1 immune checkpoints revealed that these pathways
act as so-called ‘brakes’ on the immune system, and showed that inhibition of these checkpoint
pathways allows T cells to more effectively eradicate cancer cells. This research laid the
foundation for the clinical development of immune checkpoint inhibitors, which have
dramatically improved outcomes for many people with cancer.
References
4- Lippincott’s Pharmacology, 7th Ed.

TOXICOLOGY
Chapter Seventeen: Toxicology
17.1- General care 17.6- Monograph that Summarize
Toxicology
17.2- Techniques for reducing the
Toxicological effects
A. Prevention of absorption
B. Active elimination
C. Hemodialysis
D. Alkalization of the urine
E. Removal from the GIT
17.3- Intoxications
1. Acute Intoxication of Ethyl Alcohol
2. Acute Intoxication of Methyl Alcohol
(Methanol), Ethylene Glycol
3. Methemoglobinemia
4. Cocaine intoxication
5. Organophosphorous Poisoning
6. Inhaled Carbon Monoxide
7. Tear Gas intoxication
8. Cyanide Poisoning
9. Poisonous Bites
a. Supportive measures
b. Scorpion Bites
c. Snake Bites
d. Insect stings
17.4- Toxicity with Drugs

A. Anticoagulants
B. Atropine
C. Paracetamol
D. Salicylates (Aspirin and NSAIDs)
E. Benzodiazepines
F. Antidepressants
G. Opiates (opioids)
H. Digoxin
I. Beta-blockers
J. Calcium-channel blockers
K. Theophylline
L. Amphetamine and Related Drugs
M. Phenothiazines and Related Drugs
N. Iron salts
17.5- Chelation Agents

Sam’s Guide: Chapter 17 – Toxicology
Chapter Seventeen: Toxicology
Patients who have features of poisoning should generally be admitted to hospital, and Patients
who have taken poisons with delayed action should also be admitted, even if they appear well,
Delayed-action poisons include aspirin, iron, Paracetamol, tricyclic antidepressants,
(Diphenoxylate + atropine); the effects of modified-release preparations are also delayed.
17.1- General care

It is often impossible to be certain of the identity of the poison and the size of the dose.
- Respiration
Respiration is often impaired in unconscious patients, an obstructed airway requires immediate
attention, and an oropharyngeal or nasopharyngeal airway may be useful in patients with
reduced consciousness to prevent obstruction, provided ventilation is adequate.
Intubation and ventilation should be considered in patients whose airway cannot be protected
or who have respiratory acidosis because of inadequate ventilation.
Most poisons that impair consciousness also depress respiration, assisted ventilation (either
mouth-to-mouth or using a bag-valve-mask device) may be needed.
Oxygen is not a substitute for adequate ventilation, although it should be given in the highest
concentration possible in poisoning with carbon monoxide and irritant gases.
- Blood pressure
Hypotension is common in severe poisoning with central nervous system depressants.
A systolic blood pressure of less than 70 mmHg may lead to irreversible brain damage or
renal tubular necrosis, Hypotension should be corrected initially by raising the foot of the bed
and administration of an infusion of either sodium chloride or a colloid.
Fluid depletion without hypotension is common after prolonged coma and after aspirin
poisoning due to vomiting, sweating, and hyperpnoea.
- Heart
Cardiac conduction defects and arrhythmias can occur in acute poisoning, notably with tricyclic
antidepressants, some antipsychotics, and some antihistamines.
Arrhythmias often respond to correction of underlying hypoxia, acidosis, or other biochemical
abnormalities, but ventricular arrhythmias that causes serious hypotension require treatment,
Supraventricular arrhythmias are seldom life-threatening and drug treatment is best
withheld until the patient reaches hospital.
- Body temperature
Hypothermia may develop in patients of any age who have been deeply unconscious for some
hours, particularly following overdose with barbiturates or Phenothiazines. It may be missed
unless core temperature is measured using a low-reading rectal thermometer.
Hyperthermia can develop in patients taking CNS stimulants; children and the elderly are also at
risk when taking therapeutic doses of drugs with Antimuscarinic properties. Hyperthermia is
initially managed by removing all unnecessary clothing and using a fan. Sponging with tepid
water will promote evaporation, both hypothermia and hyperthermia require urgent
hospitalization for assessment and supportive treatment.
- Convulsions
Single short-lived convulsions (lasting less than 5 minutes) do not require treatment. If
convulsions are protracted or recur frequently, lorazepam 4 mg or diazepam (preferably as
emulsion) 10 mg should be given by slow intravenous injection into a large vein.
Benzodiazepines should not be given by the intramuscular route for convulsions. If the I.V.
route is not readily available, midazolam [unlicensed use] can be given by the buccal route
or diazepam can be administered as a rectal solution.
17.2- Techniques for reducing the Toxicological effects
A) Prevention of absorption:
By using Activated Charcoal, when given by mouth; it can bind many poisons in the gastro-
intestinal system, thereby reducing their absorption, the sooner it is given the more effective
it is, but it may still be effective up to 1 hour after ingestion of the poison.
➢ Dose: in adults 50 gm initially then 50 gm every 4 hours, Vomiting should be treated
(e.g. with an antiemetic drug) since it may reduce the efficacy of charcoal treatment.
➢ In cases of intolerance, the dose may be reduced and the frequency increased (e.g. 25
gm every 2 hours or 12.5 g every hour) but this may compromise efficacy.
➢ In children under 12 years of age, activated charcoal is given in a dose of 1 gm/kg (max.
50 gm) every 4 hours; the dose may be reduced and the frequency increased if not
tolerated.
Activated Charcoal Granules Carbomix® 50 gm/pack
Oral Susp. Charcodote® 1 gm/5 ml (100 ml)
B) Active elimination:
Repeated doses of activated charcoal by mouth enhance the elimination of some drugs after
they have been absorbed; repeated doses are given after over dosage with: Carbamazepine,
Dapsone, Phenobarbital, Quinine and Theophylline.
C) Hemodialysis
Generally used for ethylene glycol, lithium, methanol, phenobarbital, salicylates, and sodium
valproate. And for severe cases of hyperkalemia.
D) Alkalization of the urine: (for acidic drugs such as salicylates)
E) Removal from the gastro-intestinal tract:

➢ By Gastric lavage, it’s used for substances that cannot be removed effectively by other
means, it may occasionally be considered in patients who have ingested drugs that are not
adsorbed by charcoal (such as iron or lithium).
- It should be considered only if a life-threatening amount has been ingested within the
previous hour.
- It should be carried out only if the airway can be protected adequately.
- It is contraindicated if a corrosive substance or a petroleum distillate is ingested.
➢ By Induction of emesis, (e.g. with Ipecacuanha) is not recommended because there is no

evidence that it affects absorption and it may increase the risk of aspiration.
o Dose: 15 to 30 mL followed by 3 to 4 glasses of water.
o May repeat dose within 20 min if vomiting does not occur.
Ipecacuanha Syrup Ipecac® 30 ml
➢ By Whole bowel irrigation (by means of a bowel cleansing preparation), it has been used in
poisoning with certain modified-release or enteric-coated formulations.

17.3- Intoxications:
1) Acute Intoxication of Ethyl Alcohol
Treatment:
- Stomach wash
- Mild cases: observation until recovery
- Severe cases:
➢ Circulatory collapse: plasma expanders + positive Inotropics.
➢ Hemodialysis is indicated in severe cases not responding to above treatment.
- Put on ventilator if signs of respiratory depressions persist in severe cases.
➢ Nikethamide Amp (a CNS stimulant which mainly affects the respiratory cycle as a
Respiratory stimulant) I.V. repeated as necessary
- Glucose 20 % 500 ml to correct hypoglycemia and ketoacidosis
- Add insulin if the patient is diabetic
- Sod bicarbonate 1.4% or 5% 500 ml to correct lactic acidosis
- Thiamine 25 mg Amp I.V daily. (Given to prevent Wernicke syndrome).
Nikethamide Amp Coramina® 375 mg/1.5 ml , 500 mg/2 ml
Thiamine Tab , Cap Vit B1® 50 mg , 100 mg
Inj. (amp) 25 mg/ml , 100 mg/ml
2) Acute Intoxication of Methyl Alcohol (Methanol), Ethylene Glycol

Treatment:
- Stomach wash and Warm the patient.
- Sodium bicarbonate infusion (for acidosis): 5% 500 ml bottle.
Antidote:
- Fomepizole is the treatment of choice for Ethylene glycol and Methanol poisoning.
➢ LD 15 mg/kg I.V infusion over 30 min, then 10 mg/kg I.V every 12 hr. for 4 doses, then 15
mg/kg every 12 hr.
- Ethyl alcohol which should be given early (inhibits alcohol dehydrogenase which converts
methyl alcohol to its toxic metabolites).
➢ 50 gm orally followed by 8 to 10 gm/hr. I.V. to produce blood Concentration of 1-2 gm/L
➢ OR: 60 gm orally followed by 9 gm/15 minute (1 gm = 5 ml 20 % ethyl alcohol)
- Folinic acid 30 mg vial I.V. every 6 hours to protect against ocular toxicity.
- Pyridoxine, Thiamine I.V for Ethylene Glycol.
- Hemodialysis: for severe cases – Ethanol 1-2 gm added to 1 liter of dialysis fluid.
Fomepizole Inj. Solu. Antizol® 1.5 gm/1.5 ml
Folinic acid Inj. Solu Leucovorin® 50 mg/ml
3) Methemoglobinemia
Drug (aniline, Dapsone) or chemical-induced Methemoglobinemia should be treated with
Methylthioninium chloride (Methylene blue) if the methemoglobin concentration is 30% or
higher, or if symptoms of tissue hypoxia are present despite oxygen therapy, Methylthioninium
chloride reduces the ferric iron of methemoglobin back to the ferrous iron of hemoglobin.
In high doses, Methylthioninium can itself cause Methemoglobinemia.
➢ Dose: 1–2 mg/kg, repeated after 30–60 minutes if necessary, (max. cumulative dose per
course 7 mg/kg.
Methylene Blue Inj. Proveblue® 5 mg/ml (10 ml amp)
4) Cocaine intoxication
Symptoms: causing agitation, dilated pupils, tachycardia, hypertension, hallucinations,
hyperthermia, hypertonia and hyperreflexia; cardiac effects include chest pain, myocardial
infarction, and arrhythmias.
Treatment:
- Maintain airways - Put to ventilator if necessary.
- cooling measures for hyperthermia
- Convulsions: Diazepam Amp 10 mg I.V + Phenytoin Amp may be added
- Propranolol 1 mg Amp: 2-4 Amp I.V to control tachyarrhythmia
Diazepam Amp Valium® 10 mg
Phenytoin Amp Epantuin® 50 mg/ml
Propranolol Amp Inderal® 1 mg/ml
5) Organophosphorus Poisoning
Symptoms:
Mild: Nausea, Vomiting, abdominal pain, Dizziness, irritability, hyper salivation and Bradycardia
Severe: Flaccid paralysis, including ocular and respiratory, pulmonary edema and copious
secretions from mouth, Convulsions, Cyanosis, Hyperglycemia.
Treatment:
➢ Remove contaminated clothes & wash skin by soap and water to prevent further
absorption from skin and Give the following:
B. Atropine (blocks receptors and reverse the Antimuscarinic effects): 2 mg (2 Amp) I.V at
once, Repeat the same dose every 5- 10 minutes until signs of atropine side effects appear:
dry mouth, dilatation of pupils – heart rate 70 to 80 bpm.
C. Palidoxime (Cholinesterase reactivator, to improve muscle tone): 1 gm vial, indicated in
moderate to severe cases: 2 vials diluted with 10 – 15 ml water and given by slow I.V,
Improvement in muscle power expected within 30 minutes
➢ Exact dose 30 mg/kg over 20 minutes, followed by 8 mg/kg/hour
➢ Continued until the patient has not required Atropine for 12 hours.
➢ Repeat if necessary, in severe cases: 1-2 doses.
➢ Maximum dose = 12 gm I.V. or I.M/ 24 hr.
➢ Supportive measures:
➢ Convulsions: Diazepam Amp 10 mg I.V or I.M
➢ Pulmonary edema: Oxygen inhalation – put to ventilator.
Atropine Tab Atreza® 0.4 mg
Amp AtroPen® 1 mg/ml
Palidoxime Inj. powder Protopam® 1 gm/vial
6) Inhaled Carbon Monoxide

Carbon monoxide poisoning is usually due to inhalation of smoke, car exhaust, or fumes caused
by blocked flues or incomplete combustion of fuel gases in confined spaces.
Treatment:
- Pure oxygen inhalation (100%)
- Put on ventilator if necessary
- Packed red cell transfusion
- Mannitol 10-20% + Dexamethasone 8 mg I.V if cerebral edema is suspected.
7) Tear Gas intoxication
Also called CS spray, which is used for riot control, irritates the eyes (hence ‘tear gas’) and the
respiratory tract, which may lead to respiratory complications.
Treatment:
Symptoms normally settle spontaneously within 15 minutes.
- If symptoms persist, the patient should be removed to a well-ventilated area
- The exposed skin washed with soap and water after removal of contaminated clothing.
- The Eye should be treated by irrigating the eyes with physiological saline (or water if
saline is not available).
8) Cyanide Poisoning
Treatment:
- Cardio-respiratory support, as necessary
- Oxygen should be administered to patients with cyanide poisoning (Pure oxygen).
- The choice of antidote depends on the severity of poisoning.
- Dicobalt Edetate is the antidote of choice when there is a strong clinical suspicion of
severe cyanide poisoning, But Dicobalt Edetate itself is toxic, associated with
anaphylactic reactions, and is potentially fatal if administered in the absence of
cyanide poisoning.
- Regimen of sodium nitrite followed by sodium thiosulfate is an alternative if Dicobalt
Edetate is not available.
Antidote:
➢ Kelocyanor® (Dicobalt Edetate) is the antidote of choice: 20 ml amp (300 mg) I.V over 1
min followed by 50 ml glucose 50%. Repeated if necessary.
➢ Sodium nitrate: 10 ml Amp I.V over 3 min followed by sodium thiosulphate 25 ml 50%
given over 10 min. if Dicobalt Edetate is not available.
➢ Amyl nitrate vitrille inhalation: (Amp crushed)/12 sec for 2-3 min until the antidote is
available.
➢ Hydroxocobalamine (Cyanokit®) can be considered for use in victims of smoke
inhalation who show signs of significant cyanide poisoning.
Dicobalt Edetate Amp Kelocyanor® 15 mg/ml (20 ml amp)
Sodium nitrate Amp Sodium nitrate® 30 mg/ml (10 ml amp)
Sodium thiosulphate Amp Sodium thiosulphate® 500 mg/mL
Amyl nitrate vitrille Amp (inhale) Amyl nitrate® 0.3 ml
Hydroxocobalamin Inj. Powder Cyanokit® 5 gm/vial
9) Poisonous Bites:
A) Supportive measures for Bites (Snake and Scorpion)
- Pain: Tramadol amp, if still persistent Pethidine 50 mg amp
- Nausea/Vomiting: Largactil® 50 mg amp I.V
- Shock: plasma or Dextran + Positive Inotropics (Norepinephrine 0.1 % Amp or
Dobutamine infusion) + Hydrocortisone inj. I.V up to 200 mg.
- Bleeding tendency: Fresh blood or Plasma.

B) Scorpion Bites
Symptoms:
- Local: pain, swelling and tender enlargement of regional lymph nodes.
- Systemic: Ranging from early anaphylactic symptoms (transient hypotension with
syncope, angioedema, urticaria, abdominal colic, diarrhea, and vomiting), with later
persistent or recurrent hypotension, ECG abnormalities, spontaneous systemic bleeding,
coagulopathy, adult respiratory distress syndrome, and acute renal failure.
Treatment:
A. Lidocaine 2%: 2 ml injected at the site of the bite (immediate relief of pain).
B. Early anaphylactic symptoms should be treated with Adrenaline (epinephrine)
C. To delay absorption of the poison: Press firmly on site of bite, and Immobilize limb with
a splint.
D. Antidote: Anti-scorpion serum Vial (Anascorp®):
- 3 vials added to 50-100 ml 0.9% Normal Saline and infused I.V slowly over 10 min.
- From 3 to 10 vials may be required to neutralize the poison.
- Hypersensitivity reactions are very common: One Amp adrenaline may be given S.C as
prophylaxis, if reactions appear another amp of adrenaline + 2 amp 100 mg hydrocortisone
added to solution.
C) Snake Bites
Symptoms:
- Local: pain, swelling and tender enlargement of regional lymph nodes.
- Systemic: Ranging from early anaphylactic symptoms (transient hypotension with
syncope, angioedema, urticaria, abdominal colic, diarrhea, and vomiting), with later
persistent or recurrent hypotension, ECG abnormalities, spontaneous systemic bleeding,
coagulopathy, adult respiratory distress syndrome, and acute renal failure.
Treatment:
A. Lidocaine 2%: 2 ml injected at the site of the bite (immediate relief of pain).
B. Early anaphylactic symptoms should be treated with Adrenaline (epinephrine)
C. To delay absorption of the poison: Press firmly on site of bite, and Immobilize limb with
a splint.
D. Antidote:
- Anti-snake venom (Favirept®): 10 ml amp, Start with 2 Amp added to 250 ml 0.9% Normal
Saline – 5% Glucose and infused I.V slowly over 10 min.
- From 2 to 10 Amp may be required to neutralize the poison.
- Hypersensitivity reactions are very common: One Amp adrenaline may be given S.C as
prophylaxis, if reactions appear another amp of adrenaline + 2 amp 100 mg hydrocortisone
added to solution.
D) Insect stings
Stings from ants, wasps, hornets, and bees cause local pain and swelling but seldom cause
severe direct toxicity unless many stings are inflicted at the same time.
Treatment:
- Anaphylactic reactions require immediate treatment with I.M Adrenaline (epinephrine)
- A short course of an oral antihistamine or a topical corticosteroid may help to reduce
inflammation and relieve itching.
- A vaccine containing extracts of bee and wasp venom can be used to reduce the risk of
anaphylaxis and systemic reactions in patients with systemic hypersensitivity to bee or
wasp stings.

17.4- Toxicity with Drugs
A) Anticoagulants
Treatment:
- Stop drugs given
- Oral anticoagulants: Vit. K amp 10 - 50 mg I.V slowly.
- Heparin antidote: Protamine Sulphate 50 mg I.V Slowly.
Vit. K Amp Phytonadione® 2 mg/ml , 10 mg/ml
Tab 100 mcg , 5 mg
Protamine Sulphate I.V Solu. Protamine® 10 mg/ml (10 ml amp)
B) Atropine intoxication
Treatment:
- Follow stomach lavage with sodium Sulphate 30 g in 200 ml water.
- Fever and hyperthermia: apply cold water and ice bags.
- If Severe tachycardia: Neostigmine 2.5 mg I.V. very slowly over 10 min with ECG monitoring.

Neostigmine Inj. Solu. Prostigmin® , Bloxiverz® 0.5 mg/ml , 1 mg/ml , 2.5 mg/ml
Tab 15 mg
C) Paracetamol
The Main fear is liver necrosis, N-Acetylcysteine and Methionine protect the liver if given in 10
-12 hrs., Liver damage is maximal 3-4 days after Paracetamol overdose and may lead to
encephalopathy, hemorrhage, hypoglycemia, cerebral edema, and death.
➢ Hepatotoxicity may occur after a single ingestion of more than 150 mg/kg Paracetamol
taken in less than 1 hour.
Treatment:
- Acetylcysteine (also called Cysteamine) is given in a total dose (based on patient
weight) that is divided into 3 consecutive I.V infusions over a total of 21 hours.
o 1st dose: loading dose 150 mg/kg, infused in 1 hour with 200 ml D5W.
o 2nd dose: 50 mg/kg, in 500 ml D5W over 4 hours.
o 3rd dose: 100 mg/kg in 1000 ml D5W over 16 hours.
o Maybe administered orally, as 140 mg/kg loading dose, then 70 mg/kg every 4
hours for 17 doses.
- Hepsan® (acetyl methionine) Amp/4 hours, Repeat for 4 doses.
- Methionine 250 mg tab: 10 Tab (2.5 gm) ingested/4 hours for 12 hrs.)
Acetylcysteine Inj. Solu. Parvolex® 200 mg/ml (10 ml amp)
Acetyl Methionine Amp Hepsan® 10 ml amp
Methionine Tab Methon ® 250 mg

D) Salicylates (Aspirin and NSAIDs)
Symptoms: Hyperventilation, Tinnitus, deafness, Vasodilatation and Sweating.
Treatment:
- Stomach Wash: in all cases (mild and severe) even after the lapse of several hours.
Mild cases:
- High intake of oral fluids + activated charcoal and Observe for 12 – 24 hours
Severe cases: When serum salicylates is greater than 50 mg/dl (in adults), 30 mg/dl (in children)
- Forced alkaline diuresis to reach urine PH more than 8
- 50 gm Activated charcoal (charcoal or ultracarbon) 0.25 gm tab every 4 hrs.
- Convulsions: Diazepam 10 gm Amp
- Vit. K 10 mg I.V to prevent hypoprothrombinemia.
Very severe: when plasma-salicylate concentration exceeds 70 mg/dl, with failure of the above-
mentioned measures or development of cerebral edema or renal failure = peritoneal dialysis or
hemodialysis.
E) Benzodiazepines
Symptoms: Drowsiness, Weakness, ataxia, Respiratory depression, nystagmus, Hypotension,
hypothermia and Coma
Treatment:
- Activated charcoal can be given within 1 hour of ingesting.
- Stomach wash in all cases
Mild cases: Recovery without specific treatment, discharge after a short period of obs.
Severe cases:
- Oxygen in high concentrations
- Insert an endotracheal tube (allows suction of mucus) + ready to connect to a mechanical
ventilator if cyanosis is not relived.
- Hypotension: raise foot of bed + Dopamine Amp I.V Infusion
Antidote: Flumazenil 0.5 mg Amp given in increasing doses of 0.2 – 0.3 – 0.5 mg at 1 min
intervals until a good response is obtained or a total dose of 3 to 5 mg is given.
➢ VIP Note: Flumazenil can be hazardous, particularly in mixed overdoses involving
tricyclic antidepressants or in benzodiazepine-dependent patients. Flumazenil may
prevent the need for ventilation, particularly in patients with severe respiratory
disorders; thus, it should be used on expert advice only.
Flumazenil Amp Romazicon® 0.1 mg/ml (5 ml amp)
F) Antidepressants
Symptoms:
- Anti-cholinergic manifestations: fever, Mydriasis flushing, retention of urine, decreased
bowel motility
- CNS manifestation: restlessness, myoclonus, confusion, convulsions, coma.
- Cardiac manifestation: A-V blockade, cardiac arrhythmias
- Delirium with confusion, agitation, and visual and auditory hallucinations are common
during recovery.
Treatment: (Essentially supportive measures)
- Stomach wash is followed by activated charcoal with cathartics / 2-4 hours.
- CNS manifestation: Neostigmine Amp 2 mg I.V very slowly over 2 minutes.
- Convulsions: Diazepam 10 mg Amp , or Lorazepam 1 mg amp
- Cardiac manifestation :Arrhythmias = Lignocaine infusion.
- Hypotension = Dopamine infusion
- Hemodialysis has no effect because of the large Vd of these drugs.
G) Opiates (opioids) Intoxication
Symptoms: Drowsiness, Respiratory depression and Pin-point pupil.
Also has cardio-toxic effects which may require treatment with sodium bicarbonate, or
magnesium sulfate, or both; arrhythmias may occur for up to 12 hours.
Treatment: Antidote:
A. Naloxone:
➢ 1 to 3 Amp (0.8 mg amp) I.V every 5 minutes until evident of clinical response or until 12
Amp (9.6 mg) has been given, Effect lasts 1-4 hrs.
➢ Do not exceed 10 mg.
➢ Repeat within 1 to 4 hours if signs of toxicity (papillary constriction, depression of
respiration) still persist.
B. Naltrexone:
It’s approved only for opioid dependence and Alcohol dependence (not used in Opioids toxicity).
Naloxone Amp Narcan® 400 mcg/ml (2 ml amp)
Amp Prenoxad® 1 mg/ml (2 ml amp)
Auto-Inj. Evzio® 0.4 mg/0.4 ml
H) Digoxin
Mild cases: Nausea + Ectopic beats
- Potassium Chloride orally: Potassium syrup: 1 teaspoonful x 3 day or slow Potassium
tab for 2 days.
More severe cases: Persistent vomiting, confusion, heart block (all degrees) or arrhythmia (all
types), vision disturbances
Potassium changes:
➢ Hyperkalemia occurs with acute intoxication
➢ Hypokalemia is common with chronic intoxication
Treatment:
- Discontinue drug
-If there is hyperkalemia:
- 500 ml glucose 25 % + insulin soluble 30 Units
- Kayexalate® (sodium polystyrene) A Cation-Exchange Resin, (it act by enhancing
excretion of potassium ions), dose 15 gm orally 1-4 times daily, or 30-50 gm rectally.
- If there is hypokalemia:
- KCL 0.2% in 5 % dextrose (500 ml) infused over 1 hour with continuous ECG monitoring,
stop drip immediately if sinus rhythm is restored, or if peaking of T waves returns to
normal.
- Repeat if necessary up to 1 gm potassium chloride.
- Severe cases of Digoxin Toxicity:
➢ Digoxin antibodies 40 mg vials: Empiric dosing for acute poisoning 10 -20 vials in both
adults and children, Empiric dosing for chronic poisoning adults 3-6 vials, while children
1-2 vials only.
➢ Propranolol 1 mg Amp I.V (to counteracts ectopic beats and tachycardia), Repeated if
necessary
➢ Atropine 1 mg Amp I.V (to counteract bradycardia).
Sodium Polystyrene Oral powder Kayexalate® 453.6 gm (total)
Rectal Susp. 15 gm/60 ml
Digoxin antibodies Vail (Solu.) DigiBind® 38 mg , 40 mg
I) Beta-blockers
Symptoms: light headedness, dizziness, and possibly syncope as a result of bradycardia and
hypotension; heart failure may be precipitated or exacerbated. Propranolol over dosage in
particular may cause coma and convulsions.
Treatment:
- Bradycardia: I.V Inj. of Atropine (3 mg for an adult, 40 mcg/kg (max. 3 mg) for a child).
- Convulsions: Diazepam 10 mg Amp , or Lorazepam 1 mg amp
- Insulin 30 units and 5% glucose 500 ml infusion may be required in the management
of hypotension and myocardial failure.
- Glucagon 2-10 mg in glucose 5% (with precautions to protect the airway in case of
vomiting) followed by an I.V infusion of 50 mcg/kg/hour.
Glucagon Vial (powder) GlucaGen® 1mg/vial
J) Calcium-channel blockers
Symptoms: nausea, vomiting, dizziness, agitation, confusion, and coma in severe poisoning.
Metabolic acidosis and hyperglycemia may occur.
Treatment:
- Activated charcoal should be considered if the patient presents within 1 hour, repeated
doses of activated charcoal are considered for a modified-release preparation.
- Calcium chloride inj. or Calcium gluconate inj.
- Atropine is given to correct symptomatic bradycardia.
- Insulin 30 units and 5% glucose 500 ml infusion may be required.
- Glucagon 2-10 mg in glucose 5% (with precautions to protect the airway in case of
vomiting) followed by an I.V infusion of 50 mcg/kg/hour.
K) Theophylline
Symptoms: vomiting (which may be severe and intractable), agitation, restlessness, dilated
pupils, sinus tachycardia, and hyperglycemia.
More serious effects are hematemesis, convulsions, and supraventricular and ventricular
arrhythmias. Severe hypokalemia may develop rapidly.
Treatment:
- Repeated doses of activated charcoal can be used to eliminate theophylline even if more
than 1 hour has elapsed after ingestion.
- Ondansetron as an antiemetic.
- Hypokalemia is corrected by I.V infusion of Potassium Chloride (KCL) and may be so
severe as to require 60 mmol/hour (high doses require ECG monitoring).
- Convulsions should be controlled by I.V administration of Lorazepam or Diazepam.
- If the patient does not suffer from asthma, a short-acting beta-blocker can be
administered I.V to reverse severe tachycardia, hypokalemia, and hyperglycemia.
L) Amphetamine and Related Drugs

Symptoms:
- Moderate: wakefulness, excessive activity, paranoia, hallucinations, hypertension,
Insomnia and Hallucinations.
- Severe: exhaustion, convulsions, hyperthermia, and coma.
Treatment:
a. The early stages can be controlled by Diazepam or Lorazepam
b. Largactil® (Chlorpromazine) + Inderal® (Propranolol) 1 mg Amp
c. In severe Cases: Epantuin® (phenytoin) Amp + ice packs + artificial ventilator may be
needed, also acid diuresis to help excretion.
M) Phenothiazines and related drugs
Symptoms: Hypotension, hypothermia, sinus tachycardia, and arrhythmias may complicate
poisoning. Dystonic reactions can occur with therapeutic doses (particularly with
Prochlorperazine and Trifluoperazine), and convulsions may occur in severe cases.
Treatment:
- Arrhythmias may respond to correction of hypoxia, acidosis.
- Dystonic reactions are rapidly abolished by injection of drugs such as Procyclidine or
Diazepam 10 mg amp.
N) Iron salts
Symptom: nausea, vomiting, abdominal pain, diarrhea, hematemesis, and rectal bleeding.
Hypotension and hepatocellular necrosis can occur later, Coma, shock, and metabolic acidosis
indicate severe poisoning.
Treatment:
- I.V. Deferoxamine given to chelate absorbed iron in excess of the expected iron binding
capacity, dose 15 mg/kg/hour, reduced after 4–6 hours; max 80 mg/kg in 24 hours.
Deferoxamine * Inj. powder Desferal® 500 mg , 2 gm (vial)
Desferiprone Tab, Oral Solu. Ferriprox® 500 mg (tab) , 100 mg/ml
Deferasirox Tab Exjade® 125 mg , 250 mg , 500 mg
Tab Jadenu® 90 mg , 180 mg , 360 mg
* Deferoxamine = Desferrioxamine, they are the same drug.
* Deferiprone = Desferiprone, they are the same drug.
17.5- Chelation Agents

Chelators are drugs that will form covalent bonds with cationic metals, the chelator-metal
complex is then excreted in urine, thereby greatly facilitating the excretion of the heavy metal.
Unfortunately, Chelators are not specific to heavy metals, and essential metals, such as zinc, often
can also be chelated, additionally, some Chelators have potentially serious adverse effects
themselves, and their use in treatment of heavy metal intoxication is undertaken only when the
benefits of chelation therapy outweigh the associated risks.
1. Dimercaprol used by itself to chelate mercury and arsenic and in combination with
Edetate calcium disodium to treat lead intoxication. It is not effective orally and is usually
given I.M., its use is limited by its capacity to increase blood pressure and heart rate.
2. Succimer (dimercaptosuccinic acid) is a derivative of Dimercaprol that is effective upon oral
administration, a second advantage of Succimer over Dimercaprol is the lack of increased
blood pressure and heart rate during treatment. Some elevation of serum levels of hepatic
enzymes can be observed with Succimer treatment; Succimer is currently approved for
treatment of lead intoxication, but may be effective in chelation of other metals as well.
3. Edetate calcium disodium is used primarily for treatment of lead intoxication, but it can
also be used for poisoning by other metals. It is not effective orally and is given I.V or I.M., it
can cause renal damage that is reversible upon cessation of the drug.
Dimercaprol Inj. Solu. BAL® 100 mg/ml
Succimer Cap Chemet® 100 mg
Edetate Calcium Disodium Inj. Solu Versenate® 200 mg/ml
Pentetate Zinc Trisodium Inj. Solu. Zn DTPA® 1gm/5 ml

17.6- Monograph that Summarize Toxicology

References:
1- Lippincott’s pharmacology 7 Ed .
3- Goldfrank’s Toxicological Emergencies, 10th Ed.
MISCELLANEOUS TOPICS
Chapter Eighteen: Miscellaneous Topics

1. I.V Anesthetics
2. Inhalational Anesthetics
3. Nitrous Oxide
4. Neuromuscular blocking drugs
a. Depolarizing Neuromuscular
Blockers
b. Non-Depolarizing Neuromuscular
Blockers
5. Drugs for reversal of neuromuscular
blockade
Third: Appetite stimulants
Fourth: Obesity and weight reducing

agents
Fifth: Vitamins, Medical Supplements

1. Minerals and Electrolytes
2. Vitamins
3. Multivitamin preparations

Sam’s Guide: Chapter 18 – Miscellaneous
Chapter Eighteen: Miscellaneous Topics
1. An average cigarette yields about 2 mg of absorbed nicotine, which act as a stimulant and
improves attention, high amounts (50–100 mg) can be very harmful.
2. The stimulant effect is the major contributing factor to the addictive properties of tobacco
smoking, it also causes feelings of relaxation, sharpness, calmness, and alertness.
3. It also reduces the appetite and raise the metabolism; thus, some smokers may lose weight.
➢ Nicotine is associated with cardiovascular disease, it increases blood pressure and heart
rate, and can also induce potentially atherogenic genes in human coronary artery endothelial
cells, it elevates serum cholesterol levels, supports clot formation, and aids in plaque
formation by enhancing vascular smooth muscle.
➢ Abrupt and sudden cessation of smoking has worst effects than smoking itself; thus, a
gradual cessation is always recommended.
4. Treatment approaches include: Nicotine replacement therapy (NRT), Bupropion, and
Varenicline are effective aids to smoking cessation.
➢ Nicotine replacement therapy should be started 2 weeks after a cardiovascular event (such
as acute coronary syndrome); sudden cessation of smoking cause CVS deteriorations.
5. Smoking cessation is the most important therapeutic intervention for COPD and Asthma.
A) Bupropion
1. Bupropion is an antidepressant drug, a weak norepinephrine dopamine reuptake inhibitor (1).
2. For smoking cessation, treatment should be started about 1 to 2 weeks before the patient
attempts to stop smoking, to allow steady-state blood levels of bupropion to be reached, and
normally continues for 7 to 12 weeks; if there is no significant progress towards smoking
abstinence by the seventh week, then therapy should be stopped.
3. Should not be prescribed for patients with epilepsy, (it lowers the seizure threshold).
B) Varenicline
1. Varenicline is a selective nicotinic receptor partial agonist that is used as an aid for smoking
cessation, Patients are advised to set a date to stop smoking and start Varenicline 1 to 2 weeks
before; Treatment is normally given for 12 weeks.
2. In patients who successfully stop smoking, a further 12 weeks of treatment has been
recommended to reduce the risk of relapse.
C) Nicotine replacement therapy (NRT)

1. The first-line pharmacological intervention is NRT.
2. NRT is available in numerous formulations: chewing gum, transdermal patches, inhalators, nasal
sprays, sublingual tablets, and lozenges.
3. Choice of formulation is based on patient preference, tolerance, and previous treatments:
a. The transdermal patch is easiest to use and compliance is greatest with this route but
local effects may be troublesome.
b. The gum has an unpleasant taste initially and some find the chewing action difficult.
c. The sublingual tablet may be useful for those who have difficulty chewing the gum.
d. The nasal spray has a fast onset of action but may cause local irritation.
e. The inhalator has the advantage of simulating cigarette smoking but may cause local
irritation of the mouth and throat.
f. The lozenges have the advantage that it can be sucked discreetly.
4. NRT for is usually continued for about 3 months before being withdrawn.
Bupropion Tab Wellbutrin , Zyban
® ® 150 mg , 300 mg
Varenicline Tab Champix , Chantix
® ® 0.5 mg , 1 mg
o Several types of drug are given together during general anesthesia, which usually contain 2 steps,
induced phase and maintenance phase.
➢ Anesthesia is induced with either a volatile drug given by inhalation or with an IV
administered drug.
➢ Anesthesia is maintained with an IV or inhalational anesthetic.
➢ Analgesics; usually short-acting opioids, are also used.
➢ Neuromuscular blocking drugs used in anesthesia are also known as muscle relaxants, by
specific blockade of the neuromuscular junction they enable light anesthesia to be used with
adequate relaxation of the muscles of the abdomen and diaphragm. They also relax the
vocal cords and allow the passage of a tracheal tube.
➢ Antimuscarinic drugs are used (less commonly nowadays) as pre-medications to dry
bronchial and salivary secretions which are increased by intubation, upper airway surgery,
or some inhalational anesthetics.
➢ Antimuscarinics are also used before or with Neostigmine to prevent bradycardia,
excessive salivation, and other muscarinic actions of Neostigmine, and also used to prevent
bradycardia and hypotension associated with drugs such as Propofol and Suxamethonium.
1) I.V Anesthetics
o May be used either to induce anesthesia or for maintenance of anesthesia throughout surgery,
they can cause apnea and hypotension, and so adequate resuscitative facilities must be available
when giving them to patients.
A) Propofol, can be used in adults and children, but it is not commonly used in neonates, it is
associated with rapid recovery and less hangover effect than other IV anesthetics, it causes
pain on I.V injection (which can be reduced by IV lidocaine).
➢ Onset of action is 30-40 seconds of IV injection, duration about 5-10 minutes.
➢ Has a direct anti-emetic effect.
➢ It Has a full recovery characteristics profile.
B) Thiopental sodium is a barbiturate that is used for induction of anesthesia, but has no
analgesic properties, dose related cardiovascular and respiratory depression can occur.
➢ Thiopental Along with Pancuronium and KCL, is used to execute prisoners by
lethal injection, (Cause death without pain).
C) Etomidate have a rapid recovery without a hangover effect, it causes less hypotension than
thiopental and Propofol during induction.
➢ Onset of action is 30-60 seconds of IV injection.
➢ Etomidate suppresses adrenocortical function, particularly during continuous
administration, thus it should not be used for maintenance of anesthesia.
➢ Has the most stable cardiovascular profile, associated with minimal CVS
depression, thus; preferred in patients with cardiovascular dysfunction.
D) Ketamine causes less hypotension than thiopental and Propofol during induction, it is used
mainly for pediatric anesthesia, the main disadvantage of ketamine is the high incidence
of hallucinations, nightmares, and other transient psychotic effects.
➢ Doesn’t cause respiratory depression, useful in asthmatic patient.
➢ Produce a dissociative stare (eyes are open but the patient doesn’t respond).
Etomidate Inj. Hypnomidate® 2 mg/ml (10 ml amp)
Ketamine Inj. Ketalar® 10 mg , 50 mg , 100 mg (per ml)
Propofol Inj. Diprivan® 1% (10 mg/ml) , 2% (20 mg/ml)
Fospropofol Inj. Lusedra® 35 mg/ml (30 ml Vial)
Thiopental sodium * Inj. powder Thiopental® 500 mg/vial
* Thiopental = Thiopentone, they are the same drug.
2) Inhalational Anesthetics
o These include gases and volatile liquids; Gaseous anesthetics require suitable equipment for
storage and administration; Volatile liquid anesthetics are administered using calibrated
vaporizers, using air, oxygen, or nitrous oxide-oxygen mixtures as the carrier gas, to prevent
hypoxia, the inspired gas mixture should contain a minimum of 25% oxygen at all times.
o Higher concentrations of oxygen (greater than 30%) are usually required during inhalational
anesthesia when nitrous oxide is being administered.
o Volatile liquid anesthetics can trigger malignant hyperthermia and are contra-indicated in
those susceptible to malignant hyperthermia; They can increase cerebrospinal pressure and
should be used with caution in those with raised intracranial pressure.
a. Isoflurane is the preferred inhalational anesthetic for use in obstetrics.
b. Desflurane have about one-fifth the potency of Isoflurane, it is not recommended for
induction of anesthesia as it is irritant to the upper respiratory tract.
c. Sevoflurane is more potent than Desflurane, and it is non-irritant and is therefore
often used for inhalational induction of anesthesia
Isoflurane Inhale Solu. Forane® 100 ml , 250 ml
Desflurane Inhale Solu. Suprane® 240 ml
Sevoflurane Inhale Solu. Ultane® 100%
Enflurane Inhale Solu. Ethrane®, CMPND 347® 125 ml , 250 ml
3) Nitrous Oxide (N20)

o Commonly Known as Laughing gas (due its euphoretic effect when inhaled), Nitrous oxide is
used for maintenance of anesthesia and in sub-anesthetic concentrations for analgesia.
o For anesthesia, nitrous oxide is commonly used in a concentration of 50-66% in oxygen as part
of a balanced technique in association with other inhalational or intravenous agents, for
analgesia (without loss of consciousness), a mixture of nitrous oxide and oxygen containing 50%
of each gas (Entonox®, Equanox®) is used.
o Nitrous oxide should not be given continuously for longer than 24 hours or more frequently
than every 4 days without close supervision and hematological monitoring (prolonged exposure
may cause megaloblastic anemia).
4) Neuromuscular blocking drugs

o These drugs block cholinergic transmission between motor nerve endings and the nicotinic
receptors on the neuromuscular endplate of skeletal muscle.
o They enable light anesthesia to be used with adequate relaxation of the muscles of the
abdomen and diaphragm, they also relax the vocal cords and allow passage of a tracheal tube.
o Classified into Depolarizing (Agonist) and Non-Depolarizing (Antagonist).
A) Depolarizing Neuromuscular Blockers:
o Succinylcholine (or Suxamethonium) is the only depolarizing muscle relaxant in use today, all
other family members are discontinued, it is more resistant to degradation by AChE, and can thus
more persistently depolarize the muscle fibers.
➢ Because of its rapid onset and short duration of action, succinylcholine is useful when
rapid endotracheal intubation is required during the induction of anesthesia.
➢ It is also used during electroconvulsive shock treatment.
➢ Can trigger malignant hyperthermia.
➢ Cause Hyperkalemia and Apnea.
Succinylcholine Amp Anectine ® 50 mg/ml (2 ml amp)
* Succinylcholine = Suxamethonium, they are the same drug.
B) Non-Depolarizing Neuromuscular Blockers
o These drugs compete with acetylcholine for receptor sites at the neuromuscular junction and
their action can be reversed with anticholinesterases such as Neostigmine, they have a slower
onset of action than Succinylcholine, they have no sedative or analgesic effects and are not
considered to trigger malignant hyperthermia.
o All have intermediate duration of action, except Pancuronium (has a long duration of action),
and Mivacurium (has a short duration of action).
1. Atracurium has a high cardiovascular side effects profile and it’s associated with
significant histamine release.
2. Cisatracurium is more potent and has a slightly longer duration of action than
Atracurium and provides greater cardiovascular stability because Cisatracurium lacks
histamine-releasing effects.
3. Rocuronium exerts an effect within 2 minutes and has the most rapid onset.
Note: Cisatracurium and Vecuronium are devoid of clinically significant cardiovascular effects
and are the agents of choice for patients with unstable cardiovascular profiles.
Atracurium Amp Tracrium ® 10 mg/ml (2.5 ml , 5 ml amp)
Vial 10 mg/ml (25 ml vial)
Cisatracurium Amp Nimbex ® 2 mg/ml (10 ml amp)
Vial Nimbex Forte ® 5 mg/ml (30 mlvial)
Mivacurium Amp Mivacron ® 2 mg/ml (5 ml , 10 ml amp)
Pancuronium Amp Pavulon® 2 mg/ml (2 ml amp)
Rocuronium Vial Esmeron ® 10 mg/ml (5 ml , 10 ml vial)
Vecuronium Vial (powder) Norcuron ® 10 mg/vial
Note: An important point to remember is that neuromuscular blocking agents have no known
effect on consciousness or pain threshold.
5) Drugs for reversal of neuromuscular blockade

There are 3 drugs available for this purpose: Neostigmine, Pyridostigmine and Sugammadex.
a. Neostigmine (Acetylcholinesterase inhibitor) is used specifically for reversal of non-
depolarizing (competitive) blockade. It acts within one minute of IV injection and its effects
last for 20 to 30 minutes; a second dose may then be necessary.
b. Pyridostigmine is a pro-drug of Neostigmine.
o Glycopyrronium or Atropine given before or with Neostigmine and Pyridostigmine
to prevent bradycardia, excessive salivation, and other muscarinic effects of those drugs.
c. Sugammadex (selective relaxing binding agent) can be used for rapid reversal of
neuromuscular blockade induced by Rocuronium or Vecuronium (used mainly for rapid
reversal of neuromuscular blockade in an emergency).
Neostigmine Inj. Solu. Prostigmin® , Bloxiverz® 0.5 mg/ml , 1 mg/ml , 2.5 mg/ml
Tab 15 mg
Pyridostigmine Inj. Solu. Mestinon® 5 mg/ml
Tab 60 mg , 180 mg (CR tab.)
Sugammadex Amp Bridion® 100 mg/ml (2 ml , 5 ml amp)
Neostigmine + Amp Glyco-Prostigmin® (2.5 mg + 500 mcg)/ml
Glycopyrronium (1 ml amp)
Third: Appetite stimulants
o There are several appetite stimulants available worldwide, only those below has a scientific
support as an appetite stimulant; all other claimed stimulants are not recommended to be
used, especially those herbal combinations or local made combinations
➢ Local made combinations can be very harmful since some contain a large amount of
Dexamethasone, Cyproheptadine and starch.
o Some tries to gain weight throw using Proteins and amino-acids formulas (which are made for
Body-Building Athletes) without going to the Gym or even training, such behavior can be harmful
since the body’s intake of energy is much more than its usage, and also those high protein
formulas tend to cause renal stones.
Available Appetite stimulants include:

1. Lysine is an essential amino-acid, which plays a role in appetite stimulation by contributing in
the pathway of the digestive enzymes, considered the best option for children.
➢ There are some Multivitamins combinations which contain Lysine in its components,
which makes them ideal for children growth support.
➢ Examples of those combinations: Vitan®, Predine®
2. Cyproheptadine, which is an antihistamine drug; has been used to increase weight, it’s not
recommended for routine use because of the anticholinergic side effects, including dizziness,
sedation, and dry mouth.
➢ It was approved for appetite stimulate in the 1960s, but in 1971, the U.S. FDA withdrew
approval for the use of (Cyproheptadine) as an appetite stimulant for children - and
approval for adult use was never given.
➢ The withdrawal was due to the American Medical Association reports that the effect of
Cyproheptadine on children is "inconsistent, transient, and quickly reversible on
withdrawal of the drug”, besides its side effects.
3. Pizotifen (an anti-migraine medication) is also used for appetite stimulation, it’s observed as
a side effect of Pizotifen, publication and studies of Pizotifen observes only that "a slight increase
in body weight is observed in some patients”
➢ Long term use will do more harm than good.
4. Dronabinol has been shown to increase weight in a small placebo control study of Alzheimer’s
patients, but its use is limited because of the risk of seizures, confusion, sleepiness, and euphoria.
➢ It’s also used as an anti-emetic for chemotherapy-induced Nausea and vomiting.

Lysine Tab ---------------- ---------------
Pizotifen Tab Sadnomigran , Mosegor 0.5 mg
® ®
Cyproheptadine Tab Periactin®, Ciptadine®, 4 mg

Cyprodad®, Nebor®
Syr. Cyprodine® , Citadine® 2 mg/5 ml
Dronabinol Tab Marinol® 2.5 mg , 5 mg , 10 mg
Cyproheptadine Alpha- Amp (for Dynamogen® 3 mg
Ketoglutarate + oral intake) + 1 gm
Arginine Aspartate

Fourth: Obesity and weight reducing agents
o Obesity is also defined as a BMI (body mass index) over 30 kg/m2, Patients with a BMI between
25 and 29.9 are considered overweight.
o There is a lot of weight reduction formulations found in our markets; none of them has a proven
or reliable clinical study to prove their efficacy and safety, so please; as a responsible pharmacist
don’t give these medications without being sure of their safety and benefits.
o Remember that weight reduction products have caused disasters in health and many
products of this category are withdrawn (see the table below).
The safest anti-obesity drug is Orlistat:

1. Orlistat is a gastric and pancreatic lipase inhibitor that limits the absorption of dietary fat, it
is used together with dietary modification in the management of obesity; (in patients with a
BMI of 30 kg/m2 or greater); it may also be used in overweight patients with a BMI of 27
kg/m2 or more if there are associated risk factors (such as type 2 DM, hypertension).
2. Orlistat is given in a usual dose of 120 mg orally three times daily, immediately before,
during, or up to 1 hour after meals. If a meal is missed or contains no fat, the dose should
be omitted, Orlistat therapy should be stopped if the patient does not lose at least 5% of
their body-weight during the first 12 weeks of therapy.
Other Agents include:

Table showing current anti-obesity drugs:


Fifth: Vitamins and Medical Supplements
1. Minerals and Electrolytes:
a. Calcium supplements
1. Calcium salts are used in the management of hypocalcemia and calcium deficiency states
resulting from dietary deficiency or ageing.
2. Intravenous calcium (calcium gluconate) salts are also used to reverse the toxic cardiac
effects of potassium in the emergency treatment of severe hyperkalemia (calcium act to
protect the heart from hyperkalemia).
3. Calcium SC inj. is used in cases of HCL acid burns (because it forms un-harmful CaCL salt).
4. Used in cases of hyper-Mg+
5. Used as antidote for overdose of Calcium Channel Blocker (CCBs).
6. Used for treatment in the neurotoxicity of Aminoglycosides.
7. Calcium carbonate or acetate are effective phosphate binders and are given orally (with
food) to reduce phosphate absorption from the gut in patients with hypophosphatemia;
this is particularly relevant to patients with chronic renal failure
8. Oral calcium supplements can also be used adjunct in the management of osteoporosis.
b. Phosphate-binding agents
1. Calcium-containing preparations are used as phosphate-binding agents in the management
of hypophosphatemia complicating renal failure.
2. Sevelamer hydrochloride and Sevelamer carbonate are both licensed for the treatment
of hypophosphatemia in patients on hemodialysis or peritoneal dialysis.
c. Potassium
1. Potassium salts are used for the prevention and treatment of hypokalemia.
2. An I.V. Potassium salt (KCL) may be required in severe acute hypokalemia.
3. When I.V. Potassium is added to I.V. fluid, it is important to mix thoroughly; if the solutions
are not mixed; a concentrated layer of potassium chloride may form (layering effect) owing
to differences in density; if such a mixture is administered it may have a serious effect.
d. Zinc
1. Zinc supplement is used for zinc deficiency.
2. Zinc supplements have been shown to reduce the incidence, intensity, or duration of
acute diarrhea in children in developing countries, (it enhances the absorption of water
and electrolytes).
➢ The WHO/UNICEF recommend that children with acute diarrhea also receive zinc (10
mg of elemental zinc/day for infants younger than 6 months; 20 mg of elemental zinc/day
for older infants and children) for 10 to 14 days.
3. Zinc prevents the absorption of copper in Wilson’s disease.
4. Zinc supplementation can cause a Copper deficiency.
e. Magnesium
1. Magnesium Deficiency will cause ringing in the ears or hearing loss, muscle cramps or
tremors, depression, abnormal heart function and kidney stones.
2. Sever Magnesium Deficiency can be treated by using a nebulizer filled with magnesium
Sulphate or magnesium chloride dissolved in water; Nebulizing has the advantage of taking
effect within minutes, relieving muscle pain, tension or breathing difficulties.
3. Magnesium is indicated for Emergency treatment of serious arrhythmias (torsade de
pointes); and in Severe acute asthma, and in the Prevention and treatment of seizures in pre-
eclampsia in pregnancy.
2. Vitamins:
a. Vitamin A:
1. Vitamin A, a fat-soluble vitamin, is essential for growth, for the development and maintenance
of epithelial tissue, and for vision.
2. Vitamin A is used in the treatment and prevention of vitamin A deficiency, Vitamin A has
also been used to treat various skin disorders including acne and psoriasis.
3. It has two forms Retinol and Beta-Carotene.
➢ 1 IU vitamin A equals 0.3 mcg Retinol, 0.6 mcg Beta-Carotene.
4. In view of evidence suggesting that high levels of vitamin A may cause birth defects
(teratogenic), women who are (or may become) pregnant are advised not to take vitamin
A supplements (except on the advice of a doctor); nor should they eat liver.
(The American College of Obstetricians and Gynecologists has recommended that women who
are pregnant or planning pregnancy should ensure that any vitamin supplements they take
contain a daily dose of vitamin A of no more than 5000 units, The Australian Adverse Drug
Reactions Advisory Committee has advised women in this category to avoid vitamin A
supplements and to not exceed the recommended daily allowance of 2500 units from all sources)
b. Vitamin B:
There are several type of vitamin B, which include the following:
Vitamin B Scientific name Uses
B1 Thiamine - Thiamine is used in the treatment and prevention of thiamine
deficiency (Beriberi).
B2 Riboflavin Riboflavin is used in the treatment and prevention of riboflavin
deficiency.
B3 Niacin Used for the treatment of hyperlipidemia.
B5 Pantothenic acid - Plays a role in synthesis and maintenance of Coenzyme A.
- Its deficiency causes depression.
- Also used as a dietary supplement.
B6 Pyridoxine - Pyridoxine is used in the treatment and prevention of pyridoxine
deficiency states (2).
- Prevention of isoniazid-induced neuropathy.
- Treatment of premenstrual syndrome.
- Maybe useful as an antiemetic.
B7 Biotin - Helping the body metabolize proteins, fats and carbohydrates
(or Vit H) - Helping the body process glucose
- It also contributes towards healthy nails, skin and hair. It is
therefore found in many cosmetic and health products for the skin
and hair, it cannot be absorbed through hair or skin.
B9 Folic acid - used as a supplementation for pregnancy to prevent Neural tube
defect.
- Also used in Megaloblastic anemia caused by folic deficiency.
B12 Cobalamins - Vitamin B12 is used in the treatment and prevention of vitamin
B12 deficiency.
- Treatment of B12- deficient Megaloblastic anemias.
- Useful in neuropathic pain.
c. Vitamin C: (Ascorbic acid)

Usually used in combination products for Common cold and Flu, but Claims that vitamin C
ameliorates colds or promotes wound healing have not been proved.
➢ Scurvy is an avitaminosis resulting from lack of vitamin C, since without this vitamin, collagen
made by the body is too unstable to perform its function.
➢ Scurvy leads to the formation of brown spots on the skin, spongy gums, and bleeding from all
mucous membranes.
d. Vitamin D:
1. A diet deficient in vitamin D in conjunction with inadequate sun exposure causes osteomalacia (or
rickets when it occurs in children), which is a softening of the bones.
2. The term Vitamin D is used for a range of compounds which possess the property of preventing or
curing rickets. They include Ergocalciferol (Calciferol, vitamin D2), Cholecalciferol (vitamin D3),
Alfacalcidol (1-α hydroxycholecalciferol), and Calcitriol (1, 25-dihydroxycholecalciferol)
3. Vitamin D requires hydroxylation by the kidney to its active form, therefore the hydroxylated
derivatives Alfacalcidol or Calcitriol should be prescribed if patients with severe renal
impairment require vitamin D therapy.
4. Preparations containing calcium with Vitamin D are available for the management of combined
calcium and vitamin D deficiency.
➢ 1 IU Vit. D = 0.025 mcg Cholecalciferol or Ergocalciferol.
5. Note: How to calculate the required Vit D3 dose for patients
➢ Use the following equation; (75 – lab test ng/ml) × (Age in yrs.) × (wt. in kg) = dose per month IU
➢ Divide by 30 = dose per day, divide by 4 = dose per week, given for at least 2 months.
6. Available in combination with Vit. A, as a topical product (emollient).
7. Vitamin D overdose causes hypercalcemia, which is a strong indication of vitamin D toxicity – this can
be noted with an increase in urination and thirst; If hypercalcemia is not treated, it results in excess
deposits of calcium in soft tissues and organs such as the kidneys, liver, and heart, resulting in pain
and organ damage including renal failure.
e. Vitamin E: (Tocopherol)
1. Vitamin E is used in the treatment and prevention of vitamin E deficiency.
2. It has an anti-Oxidant effect, and also plays a role in preventing oxidation of Vitamin A and C.
3. Can be used in Post Herpetic Neuralgia (off-label), Vitamin E has been tried for various other
conditions but there is little scientific evidence of its value.
4. Available as a topical product (emollient).
5. Regular consumption of more than 1,000 mg (1,500 IU) of Vitamin E per day may be cause
hypervitaminosis E
➢ Vitamin E can act as an anticoagulant, increasing the risk of bleeding.
➢ Hypervitaminosis E may also counteract vitamin K, leading to a vitamin K deficiency.
f. Vitamin K:
1. Vitamin K is necessary for the production of blood clotting factors.
2. Vitamin K compounds are used in the treatment and prevention of hemorrhage associated
with vitamin K deficiency.
3. The body also needs Vitamin K for controlling binding of calcium in bones and other tissues;
thus, it’s important in treating or preventing osteoporosis or osteomalacia.
4. Vitamin K is one of the treatments for bleeding events caused by overdose of the anticoagulant
drug warfarin.
5. Because vitamin K is fat soluble, patients with fat malabsorption, especially in biliary obstruction
or hepatic disease, may become deficient; Menadiol sodium phosphate is a water-soluble
synthetic vitamin K derivative that can be given orally to prevent vitamin K deficiency in
malabsorption syndromes.
➢ BUT Menadiol may be toxic by interfering with the function of glutathione.
3. Multivitamin preparations:
1. There are too many multivitamins combinations found in the market, so choose carefully.
2. It is generally considered that healthy persons eating a normal balanced diet should have no
need for vitamin supplementation.
3. Supplementation should concentrate on groups of people at risk of deficiency such as pregnant
and lactating women, who need calcium, folic acid, and iron; and certain groups who need vitamin
D; A multivitamin supplement might be considered for some groups such as the elderly and those
with reduced calorie intake.
Note 1:
The table below shows the normal range of the common electrolytes, with their causes of
elevation and decline:
Note 2: Signs of Nutritional deficiencies:

Note3: ECG and Electrolytes relationship:

There are several types of Milk inside our market, with different signs and symbols, some used
for babies and some for adults; below a list that explain their meanings:
No. Sign Used for (or meaning)
1 AC Anti-Colic (for spasm and gases)
2 Cesar For Cesarean Baby
3 Gentle Anti-Colic (for spasm and gases)
4 Soya Allergy form Cow products
5 LF Lactose Free
6 CT Constipation Treatment
7 Ensure Milk for Adults
8 Enure Plus Food supplement for Adults
9 Pedia Sure Food Supplement from 1 – 10 years
10 Promil For Babies from 6 – 12 months
11 Gloserna For Diabetic Adults
12 IT Improved Transfer (better absorption)
13 Comfort Anti-Colic (for spasm and gases)
14 HA Hypo - Allergic
15 PDF Post Delivery Formula
16 AR Anti-Regurgitation (Vomiting)
17 AD Anti-Diarrhea
18 Aniline Ca and Vit. D Supplement for Adults
19 HN25 High Nutrition Milk
20 Promise Food Supplement from 1 – 10 years

Sam’s Guide: Index
Index
(Bold Names indicates a must Know Drug)
1 Alendronic acid + Colecalciferol ....................................... 228

Alfacalcidol........................................................................ 230
1,25-dihydroxycholecalciferol ..........................................230 Alfatradiol .......................................................................... 370
Alfuzosin .............................................................. 80, 257, 258
2 Alglucosidase alfa .............................................................. 233
Alimemazine .................................................................. 17, 18
2-octyl cyanoacrylate .........................................................379 Alirocumab ........................................................................... 92
Aliskiren............................................................................... 72
Aliskiren + Amlodipine ........................................................ 72
A Aliskiren + Valsartan ........................................................... 72
Alitretinoin ................................................................. 367, 410
Abacavir ..............................................................................176 Allantoin ............................................................. 256, 360, 379
Abaloparatide .....................................................................229 Allantoin + Aloe Vera ......................................................... 379
Abarelix ...............................................................................220 Allopurinol ........................................................................ 308
Abatacept .................................................................... 306, 396 Allopurinol + Benzbromarone .......................................... 308
Abciximab ............................................................................96 Allyl-Estrenol ............................................................ 210, 211
Abemaciclib ........................................................................415 Almitrine .............................................................................. 26
Abiraterone ............................................................... 217, 412 Almotriptan ........................................................................ 297
Acalabrutinib ......................................................................414 Aloe Barbadensis extract..................................................... 47
Acarbose.............................................................................191 Aloe Vera ............................................................................ 379
Acebutolol ...................................................................... 75, 87 Alogliptin ............................................................................ 191
Aceclofenac ........................................................................278 Alosetron .............................................................................. 45
Acefylline ........................................................................ 12, 24 Alpha Hydroxy Acid......................................................... 373
Acemetacin ........................................................................278 Alpha-galactosidase ............................................................. 54
Acenocoumarol ..................................................................100 Alprazolam ........................................................................ 115
Acetazolamide ............................................... 63, 67, 323, 324 Alprazolam + Melatonin .................................................... 127
Acetic Acid ..........................................................................338 Alprostadil......................................................................... 265
Acetic Acid + HC .................................................................338 Alteplase ............................................................................ 102
Acetic Acid + Sorbic Acid ...................................................256 Altretamine ........................................................................ 406
Acetohydroxamic Acid. ...................................................272 Aluminum Chloride Hexahydrate .................................. 375
Acetyl Carnosine.................................................................334 Aluminum zirconium tetrachlorohydrix .......................... 375
Acetyl Hexapeptide-3 .........................................................373 Alverine ................................................................................ 46
Acetyl Methionine ..............................................................423 Alvimopan ............................................................................ 41
Acetylcysteine .................................................. 22, 24, 82, 423 Amantadine............................................................... 133, 171
Acipimox ...............................................................................93 Ambrisentan....................................................................... 108
Acitretin ..................................................................... 363, 367 Ambroxol .......................................................... 22, 23, 24, 346
Aclidinium ............................................................................10 Amcinonide ........................................................................ 358
Acrivastine .............................................................. 18, 21, 343 Amifampridine ................................................................... 313
Actinomycin D ....................................................................407 Amifostine .......................................................................... 410
Acyclovir ............................................................. 170, 330, 354 Amikacin .................................................................... 151, 335
Adalimumab ................................................ 53, 306, 364, 396 Amiloride ............................................................................. 66
Adapalene ..........................................................................366 Aminacrine ........................................................................ 338
Adefovir dipivoxil ..............................................................173 Amino salicylic acid ........................................................... 158
Adenosine.............................................................................88 Aminoacridine.................................................................... 344
Ado-Trastuzumab ..............................................................411 Aminocaproic acid ................................................... 103, 236
Aescin .......................................................................... 295, 309 Aminophylline ....................................................................... 12
Afatinib ...............................................................................414 Amiodarone......................................................................... 88
Aflibercept .........................................................................336 Amisulpride ........................................................................ 120
Agalsidase alfa ....................................................................232 Amitriptyline ............................................................. 124, 292
Agomelatine ......................................................................127 Amitriptyline + Chlordiazepoxide .................................. 127
Albendazole .......................................................................179 Amitriptyline + Perphenazine ........................................ 127
Albiglutide ..........................................................................200 Amlexanox .......................................................................... 344
Albumin ..............................................................................106 Amlodipine .......................................................................... 77
Albuterol................................................................................8 Amlodipine + Atenolol ......................................................... 78
Alcaftadine .................................................................... 19, 326 Amlodipine + Benazepril ..................................................... 78
Alclometasone ....................................................................357 Amlodipine + Lisinopril....................................................... 78
Alcloxa .................................................................................359 Amlodipine + Olmesartan ................................................... 78
Aldesleukin ................................................................. 401, 413 Amlodipine + Telmisartan .................................................. 78
Alectinib ..............................................................................414 Amlodipine + Valsartan ....................................................... 78
Alefacept .............................................................................364 Ammonium Chloride ........................................................... 22
Alemtuzumab ..................................................... 311, 396, 411 Amobarbital ....................................................................... 115
Alendronate .......................................................................228 Amodiaquine ...................................................................... 185
Amorolfine ..........................................................................168 Atropine ................................ 31, 43, 44, 46, 47, 425, 426, 433
Amoxapine ..........................................................................124 Attapulgite ............................................................................ 44
Amoxicillin ........................................................................146 Auranofin ................................................................... 306, 396
Amoxicillin + Flucloxacillin ...............................................146 Aurothiomalate Na ............................................................ 306
Amphotericin B ......................................................... 166, 335 Avanafil............................................................................... 263
Ampicillin ..........................................................................146 Avelumab ........................................................................... 411
Ampicillin + Cloxacillin ....................................................146 Avocado oil + Soybean oil.................................................. 309
Ampicillin + Sulbactam ......................................................146 Axitinib ............................................................................... 414
Amrinone...........................................................................106 Azacitidine.......................................................................... 409
Amyl nitrate vitrille ............................................................421 Azapentacene .................................................................... 334
Amylmetacresol .................................................................346 Azathioprine ....................................... 53, 305, 363, 393, 394
Anagliptin ...........................................................................191 Azelaic acid ............................................................... 366, 376
Anagrelide..................................................................... 96, 390 Azelastine .................................................... 19, 317, 326, 341
Anakinra .............................................................................306 Azilsartan ............................................................................. 70
Anastrozole ................................................................ 210, 413 Azithromycin............................................................. 152, 329
Ancestim .............................................................................391 Azosemide ............................................................................ 64
Andexanet alfa ....................................................................101 Aztreonam .......................................................................... 149
angiotensin II ........................................................................70
Anidulafungin .....................................................................166
Anise extract .........................................................................54 B
Anistreplase ........................................................................102
Anti-D Immune Globulin .................................................398 Bacitracin .................................................. 164, 329, 351, 381
Anti-D Immunoglobulin ..................................................237 Baclofen ............................................................................. 289
Anti-scorpion serum .......................................................422 Baloxavir ............................................................................ 171
Anti-snake venom ............................................................422 Balsalazide ........................................................................... 52
Antithymocyte globulin Equine ......................................398 Bambuterol ............................................................................ 8
Anti-Thymocyte globulin Equine ....................................395 Basiliximab ......................................................................... 396
Antithymocyte globulin Rabbit .........................................398 Bazedoxifene + Conjugated Estrogen ............................... 209
Anti-Thymocyte globulin Rabbit .......................................395 Becaplermin ....................................................................... 379
Apalutamide .......................................................................412 Beclomethasone ................................................... 9, 317, 341
Apixaban ............................................................................100 Beclomethasone + Formoterol ........................................... 9
Apomorphine......................................................................133 Beclomethasone + Salbutamol .............................................. 9
Apraclonidine .....................................................................324 Bedaquiline ........................................................................ 158
Apremilast .........................................................................363 Belatacept........................................................................... 396
Aprepitant..........................................................................136 Belimumab ................................................................. 306, 309
Aprotinin..................................................................... 103, 236 Belinostat ........................................................................... 416
Arachis Oil...........................................................................339 Bemiparin.......................................................................... 100
Arbutin ................................................................................376 Bempedoic acid .................................................................... 93
Ardeparin............................................................................100 Benazepril ............................................................................ 69
Arformoterol ..........................................................................8 Bendamustine .................................................................. 406
Argatroban..........................................................................100 Bendrofluazide .................................................................. 65
Arginine Aspartate ...........................................................434 Bendroflumethiazide ........................................................... 65
Argireline .................................................................. 373, 374 Benoxinate ......................................................................... 334
Aripiprazole.......................................................................120 Benoxinate + Fluorescein .................................................. 334
Armrodafinil .......................................................................139 Benperidol .......................................................................... 119
Arsenic trioxide ..................................................................410 Benproperine ....................................................................... 22
Artemether .........................................................................186 Benralizumab ....................................................................... 14
Artemether + Lumefantrine ..............................................186 Benzalkonium Chloride .................................................. 332
Artemisinin .........................................................................186 Benzbromarone ................................................................. 308
Artesunate ..........................................................................186 Benzhexol.......................................................................... 133
Artichoke leaf .....................................................................57 Benznidazole ...................................................................... 184
Ascorbic acid .....................................................................439 Benzocaine ........................................................................ 361
Asenapine ..........................................................................120 Benzoxonium ..................................................................... 346
Asparaginase ......................................................................410 Benzoyl peroxide .............................................................. 366
Aspirin .......................................................................... 96, 277 Benztropine........................................................................ 133
Aspirin + Clopidogrel ...........................................................97 Benzyl benzoate ............................................................... 355
Aspirin + Dipyridamole .......................................................97 Bepotastine .................................................................. 19, 326
Atazanavir...........................................................................176 Beractant ............................................................................. 27
Atenolol ................................................ 73, 74, 75, 78, 79, 298 Beraprost............................................................................ 108
Atezolizumab ......................................................................411 Besifloxacin ................................................................ 154, 329
Atomoxetine.......................................................................139 Beta Hydroxy Acid ........................................................... 373
Atopaxar ...............................................................................96 Beta Sitosterol .................................................................... 379
Atorvastatin.........................................................................90 Betahistine ................................................................ 136, 340
Atosiban .............................................................................234 Betaine........................................................................ 232, 379
Atovaquone................................................................. 182, 186 Betaine + Polyhexanide ..................................................... 379
Atovaquone + Proguanil ....................................................182 Betamethasone ........... 303, 317, 318, 319, 320, 327, 341, 344
Atracurium .........................................................................433 Betaxolol ................................................................ 74, 76, 323
Bethanechol ...................................................................... 260
Betrixaban ..........................................................................100 Cabergoline ........................ 133, 134, 223, 224, 250, 251, 267
Bevacizumab ............................................................. 335, 411 Cabotegravir....................................................................... 176
Bexarotene..........................................................................410 Cabozantinib ...................................................................... 414
Bezafibrate............................................................................91 Cadexomer iodine .............................................................. 379
Bicalutamide ..................................................... 217, 258, 412 Caffeine ...................................... 21, 22, 26, 139, 286, 290, 299
Bictegravir ..........................................................................176 Calamine ...................................................................... 19, 360
Bifonazole ...........................................................................168 Calcifediol ........................................................................... 230
Bilastine ................................................................................18 Calciferol ............................................................................ 230
Bimatoprost.......................................................................324 Calcipotriene ..................................................................... 363
Bimatoprost + Timolol .......................................................325 Calcipotriene + Betamethasone ..................................... 363
Biotin ..................................................................................439 Calcitonin salmon............................................................. 229
Biperiden ............................................................................133 Calcitriol ..................................................................... 230, 363
Bisacodyl .................................................................. 38, 39, 40 Calcium Dobesilate............................................................. 84
Bismuth subcitrate .............................................................37 Calcium Hydroxylapatite ............................................... 373
Bismuth subcitrate + Tetracycline ......................................37 Calfactant.............................................................................. 27
Bismuth subsalicylate ........................................................45 Camphor ..................................................................... 294, 295
Bisoprolol ....................................................................... 73, 75 Canagliflozin ..................................................................... 191
Bivalirudin ..........................................................................100 Canakinumab ............................................................. 308, 396
Bleomycin ..........................................................................407 Candesartan ........................................................................ 70
Blinatumomab ....................................................................411 Cangrelor .............................................................................. 96
Boceprevir ..........................................................................173 Cannabidiol ................................................................ 130, 301
Boric acid ...........................................................................331 Capecitabine ..................................................................... 409
Bortezomib .......................................................................414 Capreomycin ..................................................................... 158
Bosentan ............................................................................108 Capsicum ............................................................................ 295
Bosutinib .............................................................................414 Captopril .............................................................................. 69
Boswellia Extract................................................................303 Carbachol............................................................................ 325
Botulinum toxin A ..............................................................299 Carbamazepine......................................................... 129, 292
Botulism Immune Globulin................................................398 Carbamide Peroxide ........................................................ 339
Bremelanotide ....................................................................255 Carbetapentane.................................................................... 22
Brentuximab .....................................................................411 Carbetocin .......................................................................... 236
Brexpiprazole .....................................................................120 Carbimazole ...................................................................... 206
Brigatinib ............................................................................414 Carbinoxamine ............................................................. 17, 23
Brimonidine.......................................................................324 Carbocysteine........................................................... 22, 23, 24
Brimonidine + Brinzolamide .............................................325 Carbomer............................................................................ 333
Brimonidine + Timolol .....................................................325 Carbonyl Iron ..................................................................... 382
Brinzolamide ....................................................... 67, 324, 325 Carboplatin ....................................................................... 406
Brinzolamide + Timolol ...................................................325 Carboprost ................................................................. 213, 236
Brivaracetam ......................................................................130 Carboxymethylcellulose .................................................... 332
Brodalumab ........................................................................364 Carfilzomib ......................................................................... 414
Brolucizumab .....................................................................336 Carglumic acid.................................................................... 233
Bromazepam .....................................................................115 Cariprazine ......................................................................... 120
Bromfenac ..........................................................................327 Carisoprodol ..................................................................... 289
Bromhexine .............................................................. 22, 23, 24 Carmellose ........................................................................ 332
Bromocriptine ........... 133, 134, 199, 200, 223, 224, 250, 251 Carmustine ......................................................................... 406
Brompheniramine ................................................................17 Carteolol ................................................................ 74, 76, 323
Brotizolam ..........................................................................114 Carvedilol ................................................................ 73, 74, 75
Bucindolol .............................................................................75 Caspofungin ...................................................................... 166
Budesonide ...................................... 9, 53, 317, 320, 341, 358 Castor Oil ............................................................. 40, 236, 360
Budesonide + Formoterol ..................................................9 Catumaxomab .................................................................... 411
Buformin .............................................................................190 Cefaclor .............................................................................. 148
Bumetanide .........................................................................64 Cefadroxil .......................................................................... 147
Bumetanide + Amiloride ......................................................68 Cefalothin ........................................................................... 147
Buprenorphine ...................................................................285 Cefazolin ............................................................................. 147
Bupropion .................................................................. 126, 430 Cefdinir .............................................................................. 148
Buserelin .............................................................................219 Cefditoren........................................................................... 148
Buspirone ...........................................................................116 Cefepime ............................................................................ 148
Busulfan ..............................................................................406 Cefiderocol ......................................................................... 148
Butabarbital ........................................................................115 Cefixime ............................................................................. 148
Butamirate ...................................................................... 22, 24 Cefluprenam ....................................................................... 148
Butenafine .................................................................. 168, 352 Cefoperazone .................................................................... 148
Butoconazole ...................................................... 168, 169, 240 Cefoperazone + Sulbactam ................................................ 148
Butorphanol .............................................................. 285, 297 Cefotaxime ......................................................................... 148
Cefotetan ............................................................................ 148
Cefoxitin ............................................................................. 148
C Cefozopran ......................................................................... 148
Cefpirome ........................................................................... 148
C1 inhibitor .........................................................................400 Cefpodoxime ...................................................................... 148
Cabazitaxel..........................................................................408
Cefprozil .............................................................................148 Cinnarizine .................................................... 48, 49, 339, 340
Cefquinome.........................................................................148 Ciprofibrate .......................................................................... 91
Ceftaroline ..........................................................................148 Ciprofloxacin ..................................................... 154, 329, 338
Ceftazidime ................................................................ 148, 335 Cisapride .............................................................................. 49
Ceftazidime + Avibactam ...................................................148 Cisatracurium ................................................................... 433
Ceftibuten ...........................................................................148 Cisplatin ............................................................................ 406
Ceftizoxime .........................................................................148 Citalopram ................................................................ 123, 292
Ceftobiprole ........................................................................148 Citicoline ........................................................................... 139
Ceftolozane + Tazobactam .................................................148 Cladribine ........................................................................... 409
Ceftriaxone ........................................................................148 Clarithromycin.................................................................. 152
Cefuroxime .........................................................................148 Clemastine ..................................................................... 16, 17
Celadrin....................................................................... 295, 309 Clenbuterol ........................................................................ 216
Celecoxib ............................................................................281 Clevidipine ........................................................................... 77
Celecoxib + Orphenadrine .................................................282 Clidinum + Paracetamol ...................................................... 47
Celiprolol ..............................................................................75 Clindamycin .............................................. 155, 241, 351, 366
Cemiplimab .........................................................................411 Clioquinol .................................................................. 352, 353
Cenobamate ........................................................................130 Clobazam ............................................................................ 115
Cephalexin .........................................................................147 Clobetasol .................................................................. 353, 358
Cerebrolysin .....................................................................139 Clobutinol ............................................................................. 22
Cerena .................................................................................300 Clocortolone ....................................................................... 358
Ceritinib ..............................................................................414 Clofarabine ......................................................................... 409
Certolizumab ........................................................ 53, 306, 396 Clofazimine................................................................. 158, 159
Cetirizine .................................................. 16, 18, 22, 326, 343 Clomiphene................................................ 208, 209, 218, 251
Cetrimide .................................................................... 345, 359 Clomipramine ........................................................... 124, 292
Cetrimide + Benzalkonium ................................................359 Clonazepam ....................................................................... 115
Cetrimide + Dimeticone .....................................................359 Clonidine ...................................................... 79, 206, 298, 299
Cetrimide + Urea ................................................................359 Clopamide ............................................................................ 65
cetrimonium .....................................................................332 Cloperastine ......................................................................... 22
Cetrorelix ...........................................................................220 Clopidogrel .......................................................................... 96
Cetuximab ...........................................................................411 Clorazepate ........................................................................ 115
Cetylpyridinium Cl .............................................................345 Clotrimazole .............................................. 168, 169, 240, 344
Cevimeline ..........................................................................345 Clotrimazole + Lignocaine .............................................. 338
Chamomile Extract ....................................................... 55, 256 Clove Oil.............................................................................. 345
Charcoal ....................................................................... 37, 418 Clozapine ........................................................................... 120
Chenodeoxycholic ................................................................56 Cobalamins ....................................................................... 439
Chenodiol ..............................................................................56 Cobicistat ............................................................................ 177
Chloral hydrate .................................................................116 Cobimetinib ........................................................................ 414
Chlorambucil ....................................................................406 Cod Liver Oil ....................................................................... 302
Chloramphenicol....................................................... 163, 329 Codeine .............................................................................. 285
Chlorbutol ................................................................... 295, 338 Colchicine ................................................................... 274, 308
Chlordiazepoxide ..............................................................115 Colchicine + Allopurinol .................................................... 308
Chlordiazepoxide + Clidinum ..............................................47 Colchicine + Probenecid .................................................... 308
Chlorhexidine ............................................................. 345, 359 Colecalciferol...................................................................... 230
Chlorobutanol ........................................................... 332, 339 Colesevelam................................................................. 92, 200
Chlorocresol .......................................................................359 Colestipol .............................................................................. 92
Chloroquine ............................................................... 185, 305 Colistimethate .............................................................. 27, 163
Chlorothiazide ......................................................................65 Colistin ................................................................................ 338
Chlorpheniramine ................ 16, 17, 21, 22, 23, 24, 286, 328 Collagen .............................................................................. 302
Chlorpromazine .......................................................... 50, 118 Collagen Hydrolysate......................................................... 309
Chlorpropamide ...............................................................192 Collagen type II .................................................................. 303
Chlortalidone ......................................................................65 Collagenase ........................................................................ 379
Chlorthalidone ....................................................................65 Conivaptan ......................................................................... 222
Chlorthalidone + Triamterene.............................................68 Conjugated Estrogen........................................ 208, 209, 240
Chlorzoxazone ...................................................................289 Copper Gluconate ............................................................. 383
Cholestyramine ...................................................................92 Corifollitropin Alfa ..................................................... 219, 252
Chondroitin......................................................... 295, 302, 303 Corticorelin ........................................................................ 321
Choriogonadotropin Alfa ......................................... 219, 252 Corticotropin ...................................................................... 321
Chorionic gonadotropin........................................... 218, 252 Cranberry .......................................................................... 275
Chrysanthellum ..................................................................274 Crisaborole ................................................................. 358, 363
Ciclesonide.............................................................. 9, 317, 341 Crisantaspase ..................................................................... 410
Ciclopirox .................................................................... 168, 352 Crizanlizumab .................................................................... 387
Cidofovir .............................................................................171 Crizotinib ............................................................................ 414
Cilazapril ...............................................................................69 Crofelemer............................................................................ 45
Cilostazol........................................................................ 84, 96 Cromoglicate ......................................................... 13, 57, 341
Cilostazole ............................................................................84 Cromoglicic acid ................................................................ 13
Cimetidine ...................................................................... 35, 36 Cromoglycate ...................................................... 13, 327, 341
Cinacalcet ..........................................................................231 Cromolyn .............................................................. 13, 327, 341
Crotamiton................................................... 19, 354, 355, 360 Desferrioxamine .............................................................. 388
Cumin oil ...............................................................................55 Desflurane .......................................................................... 432
Curcuma Rhizomes extract..................................................57 Desipramine ............................................................... 124, 260
Curcumin ..............................................................................47 Desirudin ............................................................................ 100
cyanoacrylate .....................................................................379 Desloratidine .......................................................... 13, 16, 18
Cyanocobalamin ............................................... 292, 293, 384 Desmopressin.................................................... 221, 222, 261
Cyclobenzaprine .................................................................289 Desogestrel ................................................................ 211, 244
Cyclopentasiloxane ............................................................379 Desogestrel + EE .............................................................. 211
Cyclopenthiazide ..................................................................65 Desonide ............................................................................. 357
Cyclopenthiazide + Amiloride .............................................68 Desoximetasone ................................................................. 358
Cyclopentolate ...................................................................333 Desvenlafaxine ................................................................... 125
Cyclophosphamide ............................................. 306, 393, 406 Deutetrabenazine .............................................................. 313
Cycloserine .........................................................................158 Dexamethasone...........................303, 318, 319, 320, 327, 335
Cyclosporine ................................ 53, 306, 335, 363, 392, 393 Dexchlorpheniramine .................................................. 17, 22
Cyproheptadine........................................................... 17, 434 Dexibuprofen ..................................................................... 278
Cyproterone ............................................................... 217, 367 Dexketoprofen................................................................... 278
Cyproterone + Ethinyl Estradiol .....................................217 Dexlansoprazole ................................................................. 35
Cysteamine ........................................................ 231, 335, 376 Dexmethylphenidate ......................................................... 139
Cystine + B6 ........................................................................370 Dexpanthenol .................................................................... 360
Cytarabine .........................................................................409 Dexrazoxane....................................................................... 410
Cytidine ..............................................................................292 Dextran ............................................................................... 106
Cytomegalovirus Immune Globulin ..................................398 Dextran 70 .......................................................................... 332
Dextroamphetamine ....................................................... 139
Dextromethorphan .............................................................. 21
D Dextromethorphan + Quinidine........................................ 312
Dextropropoxyphene ....................................................... 285
Dabigartan ........................................................................100 Diacerein ............................................................................ 309
Dabrafenib ..........................................................................415 Diazepam................................................................... 115, 420
Dacarbazine ......................................................................406 Diazoxide ............................................................................ 202
Daclatasvir ..........................................................................173 Dibucaine............................................................................ 361
Daclizumab ................................................................. 311, 396 Dichlorobenzene ................................................................ 339
Dacomitinib ........................................................................414 Dichlorobenzyl alcohol ...................................................... 346
Dactinomycin......................................................................407 Diclofenac K+ ..................................................................... 278
Dalbavancin ........................................................................161 Diclofenac Na + Pridinol* .................................................. 287
Dalfampridine.....................................................................311 Diclofenac Na+ ........................................................... 278, 327
Dalteparin.................................................................. 100, 238 Diclofenac Na+ + Misoprostol ............................................ 280
Danaparoid .........................................................................100 Dicobalt edetate ................................................................. 421
Danazol ..............................................................................215 Dicyclomine ......................................................................... 46
Dandelion root ...................................................................57 Dicycloplatin ...................................................................... 406
Dantrolene ..........................................................................289 Dicycloverine ..................................................................... 46
Dapagliflozin .....................................................................191 Didanosine ......................................................................... 176
Dapoxetine ................................................. 123, 124, 266, 267 Dienogest ................................................................... 211, 244
Dapsone..............................................................................159 Dienogest + Estradiol....................................................... 211
Daptomycin .......................................................................163 Diethylamine Salicylate ..................................................... 295
Daratumumab ....................................................................411 Diethylcarbamazine........................................................... 179
Darbepoetin Alfa ................................................................388 Diethylstilbestrol ............................................................... 412
Darifenacin .........................................................................259 Difenoxin + Atropine ........................................................... 44
Darunavir ............................................................................176 Diflucortolone ................................................................... 353
Dasabuvir ............................................................................174 Difluprednate ............................................................. 319, 327
Dasatinib ...........................................................................414 Digitoxin ............................................................................... 88
Daunorubicin ......................................................................407 Digoxin ................................................................................. 88
Decitabine ...........................................................................409 Digoxin antibodies ............................................................. 425
Deferasirox ................................................................ 388, 427 Dihydroartemisinin ........................................................... 186
Deferoxamine ............................................................ 388, 427 Dihydro-Ergotamine ........................................................ 297
Defibrotide..........................................................................102 Dihydroxypropyltheophylline ............................................ 24
Deflazacort..........................................................................321 Diisopropyl ......................................................................... 356
Degarelix ..................................................................... 217, 412 Diloxanide Furoate........................................................... 181
Dehydroepiandrosterone ................................................216 Diloxanide Furoate + Metronidazole ............................ 181
Delafloxacin ........................................................................154 Diloxanide Furoate + Tinidazole ....................................... 181
Delapril .................................................................................69 Diltiazem ............................................................................. 77
Delavirdine .........................................................................176 Dimercaprol ....................................................................... 427
Demeclocycline ..................................................................150 Dimethicone ................................................... 47, 54, 242, 359
Denosumab ................................................................ 230, 411 Dimethyl Fumarate ............................................................ 311
Deprenyl ............................................................................133 Dimethylpolysiloxane ..................................................... 242
Dequalinium .......................................................................243 Dimeticone ........................................................................ 356
Dequalinium Chloride ........................................................346 Dimetindene .................................................................. 16, 17
Deserpidine ........................................................................109 Dinoprostone ..................................................... 213, 235, 236
Desferiprone ............................................................... 388, 427
Dinutuximab .......................................................................411 Eflornithine ................................................................ 184, 371
Dioctyl Sodium Sulpho-Succinate ...................................339 Eformoterol .......................................................................... 8
Diosmectite ...........................................................................44 Eicosapentaenoic acid ...................................................... 92
Diosmin + Hesperidin ..........................................................59 Elagolix ............................................................................... 220
Diphenhydramine ..........17, 19, 21, 22, 23, 24, 287, 330, 360 Elbasvir .............................................................................. 173
Diphenoxylate ............................................................... 43, 44 Eletriptan .......................................................................... 297
Diphenoxylate + Atropine ..................................................44 Elosulfase alfa .................................................................... 232
Diprophylline.......................................................................12 Elotuzumab ........................................................................ 411
Dipyridamole.......................................................................96 Eltrombopag ..................................................................... 389
Disopyramide ......................................................................87 Eluxadoline........................................................................... 45
Dithranol ..................................................................... 363, 371 Elvitegravir......................................................................... 176
Divalproex ..........................................................................129 Emedastine................................................................... 19, 326
Dobesilate ............................................................................84 Empagliflozin .................................................................... 191
Dobutamine .......................................................................106 Emtansine........................................................................... 412
Docetaxel ...........................................................................408 Emtricitabine ..................................................................... 176
Docosahexaenoic acid .......................................................92 Enalapril .............................................................................. 69
Docosanol ................................................................... 170, 354 Enalaprilat ............................................................................ 85
Docusate Na+ ........................................................................40 Encorafenib ........................................................................ 415
Dofetilide ..............................................................................88 Enflurane ............................................................................ 432
Dolasetron ..........................................................................136 Enfuvirtide ......................................................................... 176
Dolutegravir .......................................................................176 Enoxaparin ................................................................ 100, 238
Domperidone ................................... 36, 48, 49, 224, 239, 299 Enoximone ......................................................................... 106
Donepezil...........................................................................138 Enoxolone........................................................................... 346
Dopamine...........................................................................106 Entacapone......................................................................... 133
Doravirine ...........................................................................176 Entecavir............................................................................ 173
Doripenem ..........................................................................149 Entinostat ........................................................................... 416
Dornase Alfa .........................................................................27 Entrectinib ......................................................................... 414
Dorzolamide ........................................................ 67, 324, 325 Enzalutamide ............................................................. 217, 412
Dorzolamide + Timolol .............................................. 67, 325 Eperisone ........................................................................... 289
Dosulepin ............................................................................125 Epinastine..................................................................... 19, 326
Doxapram ............................................................................26 Epinephrine.......................................................... 57, 106, 107
Doxazosin ............................................................. 80, 257, 258 Epirubicin ........................................................................... 407
Doxepin .............................................................. 125, 260, 299 Eplerenone .......................................................................... 66
Doxercalciferol ...................................................................230 Epoetin Alfa ....................................................................... 388
Doxorubicin ......................................................................407 Epoetin Beta ....................................................................... 388
Doxycycline ........................................................................150 Epoetin Theta ..................................................................... 388
Doxylamine .................................................................. 17, 135 Epoetin Zeta ....................................................................... 388
Dried Ivy leaf extract ............................................................26 Epoprostenol.............................................................. 100, 108
Dronabinol .................................................................. 136, 434 Eprosartan .......................................................................... 70
Dronedarone .......................................................................88 Eptifibatide........................................................................... 96
Droperidol ..........................................................................136 Eptinezumab ...................................................................... 299
Drospirenone + EE ................................................... 211, 367 Eravacycline ....................................................................... 150
Drospirenone + Estradiol ..................................................212 Erdosteine ............................................................................ 22
Drotaverine .........................................................................46 Erenumab ........................................................................... 299
Droxidopa ...........................................................................104 Ergocalciferol.................................................................... 230
Dulaglutide ........................................................................200 Ergometrine ...................................................................... 236
Duloxetine .................................................. 125, 260, 292, 310 Ergometrine + Oxytocin .................................................... 236
Dupilumab .................................................................... 14, 364 Ergotamine........................................................................ 297
Durvalumab ........................................................................411 Ergotamine + Caffeine ..................................................... 299
Dutasteride ........................................................ 217, 257, 258 Eribulin ............................................................................... 408
Dutasteride + Tamsulosin ...............................................258 Erlotinib ............................................................................ 414
Dydrogesterone ........................................................ 210, 211 Ertapenem ......................................................................... 149
Dyphylline.............................................................................12 Ertugliflozin ....................................................................... 191
Erythromycin ............................................ 152, 329, 351, 366
Escitalopram ..................................................................... 123
E Esketamine ......................................................................... 127
Eslicarbazepine .................................................................. 129
Ebastine .................................................................... 13, 18, 22 Esmolol ............................................................. 76, 85, 87, 206
Eberconazole ............................................................. 168, 353 Esomeprazole.................................................. 32, 35, 36, 280
Ecallantide ..........................................................................400 Esomeprazole + Meloxicam ................................................ 36
Echothiophate ....................................................................325 Esomeprazole + Naproxen .................................................. 36
Econazole ........................................................... 168, 169, 240 Estazolam ........................................................................... 115
Edetate Calcium Disodium ................................................427 Estradiol .................................................................... 208, 240
Edetate Disodium.............................................................332 Estramustine ...................................................................... 406
Edoxaban ............................................................................100 Estriol ......................................................................... 208, 240
Efalizumab ..........................................................................364 Estropipate ................................................................. 208, 240
Efavirenz .............................................................................176 Eszopiclone ........................................................................ 116
Efinaconazole ............................................................. 168, 352
Etamsylate ................................................................. 103, 391 Fidaxomicin ........................................................................ 152
Etanercept .......................................................... 306, 364, 396 Filgrastim .......................................................................... 390
Etelcalcetide ......................................................................231 Fimasartan ........................................................................... 70
Ethacrynic acid .....................................................................64 Finafloxacin ........................................................................ 338
Ethambutol ................................................................ 157, 158 Finasteride ................................................ 217, 257, 258, 370
Ethambutol + Isoniazid ......................................................158 Fingolimod ........................................................................ 311
Ethanolamine .....................................................................391 fish Roe ............................................................................... 266
Ethionamide ......................................................................158 Flavocoxid + citrated zinc ................................................. 309
Ethosuximide .....................................................................129 Flavoxate ............................................................................ 259
Etidronate ...........................................................................228 Flecainide ............................................................................ 87
Etifoxine .............................................................................116 Flibanserin ......................................................................... 255
Etilefrine ............................................................................104 Floxuridine ......................................................................... 409
Etodolac..............................................................................278 Flubendazole ..................................................................... 179
Etofenamate ......................................................................278 Flucloxacillin ...................................................................... 146
Etomidate ................................................................... 226, 431 Fluconazole ............................................................... 166, 331
Etonogestrel ...................................................... 211, 246, 247 Fluconazole + Secnidazole................................................ 166
Etonogestrel + EE ...............................................................211 Fluconazole + Tinidazole................................................... 166
Etoposide ............................................................................408 Flucytosine ......................................................................... 166
Etoricoxib ...........................................................................281 Fludarabine ........................................................................ 409
Etoricoxib + Paracetamol ..................................................282 Fludrocortisone ........................................................ 104, 318
Etoricoxib + Pregabalin ...................................................282 Flumazenil .................................................................. 115, 424
Etoricoxib + Thiocolchicoside ...........................................282 Flunisolide .............................................................. 9, 317, 341
Etravirine ............................................................................176 Fluocinolone ...................................... 320, 352, 358, 363, 376
Etynodiol + EE ............................................................ 211, 244 Fluocinonide ...................................................................... 358
Eucalyptol ...........................................................................345 Fluorescein ......................................................................... 334
Eucalyptus oil .......................................................................26 Fluoride Na+ .............................................................. 345, 347
Eucalyptus Oil .....................................................................294 Fluorometholone ...................................................... 319, 327
Everolimus .................................................................. 393, 415 Fluorometholone + Cromoglycate ................................. 327
Evogliptin............................................................................191 Fluorouracil ........................................................ 363, 394, 409
Evolocumab ..........................................................................92 Fluoxetine .................................................................. 123, 292
Exemestane ................................................................ 210, 413 Fluoxetine + Olanzapine .................................................... 127
Exenatide ............................................................................200 Fluoxymesterone .............................................................. 216
Ezetimibe .............................................................................93 Flupenthixol ...................................................................... 119
Ezetimibe + Atorvastatin .....................................................93 Flupenthixol + Melitracen *............................................. 127
Ezetimibe + Simvastatin ......................................................93 Fluphenazine .................................................................... 118
Ezogabine ...........................................................................130 Flupirtine .......................................................................... 277
Fluprednidene.................................................................... 353
Flurandrenolide ................................................................. 358
F Flurazepam ........................................................................ 115
Flurbiprofen ...................................................... 278, 327, 346
Famciclovir ........................................................................170 Flutamide .......................................................... 217, 258, 412
Famotidine................................................................... 36, 280 Fluticasone .................................................... 9, 317, 341, 358
Famotidine + Ibuprofen .......................................................36 Fluticasone + Azelastine ................................................. 341
Fampridine ................................................................ 311, 313 Fluticasone + Formoterol ..................................................... 9
Febuxostat .........................................................................308 Fluticasone + Salmeterol .................................................... 9
Felbamate ...........................................................................130 Fluticasone + Vilanterol........................................................ 9
Felodipine ............................................................................77 Fluvastatin .......................................................................... 90
Felodipine + Enalapril ..........................................................78 Fluvoxamine ...................................................................... 123
Felodipine + Metoprolol ......................................................78 Folic Acid.................................................................... 385, 439
Felodipine + Ramipril ..........................................................78 Folic Acid + Iron ................................................................ 385
Fendiline ...............................................................................77 Folinic acid ................................................................ 410, 419
Fenofibrate ..........................................................................91 Follitropin Alfa.......................................................... 218, 252
Fenoldopam ................................................................. 85, 231 Follitropin Alfa + Lutropin Alfa ........................................ 252
Fenoprofen .........................................................................278 Follitropin Alfa + Lutropin Alfa ......................................... 219
Fenoterol .......................................................................... 8, 10 Follitropin Beta......................................................... 219, 252
Fentanil ...............................................................................285 Fomepizole ......................................................................... 419
Fentanyl .............................................................................285 Fomivirsen ......................................................................... 171
Fenticonazole ............................................................. 169, 240 Fondaparinux ................................................................... 100
Ferric Carboxymaltose.......................................................384 Formaldehyde ................................................................... 368
Ferric Gluconate................................................................384 Formestane ........................................................................ 210
Ferric Hydroxide Polymaltose Complex .........................382 Formoterol ........................................................................ 8, 9
Ferric pyrophosphate ........................................................384 Fosamprenavir ................................................................... 176
Ferrous Fumarate.............................................................382 Fosaprepitant ..................................................................... 136
Ferrous Gluconate ............................................................382 Foscarnet........................................................................... 335
Ferrous Sulphate...............................................................382 Foscarnet sodium .............................................................. 171
Ferumoxytol .......................................................................384 Fosfomycin ........................................................................ 155
Fesoterodine.......................................................................259 Fosinopril ............................................................................. 69
Fexofenadine ................................................................. 16, 18
Framycetin .........................................................................330 Glycopyrrolate + Formoterol .............................................. 10
Frangula ..............................................................................41 Glycopyrronium ............................................. 10, 37, 375, 433
Fremanezumab...................................................................299 Glycopyrronium+ Indacaterol ............................................ 10
Frovatriptan .......................................................................297 Glycyrrhiza Glabra ............................................................ 26
Fructo-oligosaccharide ......................................................41 Gold Na+ Thiomalate .......................................................... 396
FSH .............................................................................. 218, 252 Golimumab ................................................... 53, 306, 364, 396
Fulvestrant ................................................................ 209, 413 Gonadorelin................................................................ 219, 252
Furazolidone .....................................................................181 Goserelin ............................................................ 219, 258, 413
Furazolidone + Nifuroxime................................................242 Gosogliptin ......................................................................... 191
Furosemide ..........................................................................64 Gramicidin................................................................. 330, 353
Furosemide + Amiloride ......................................................68 Granisetron ....................................................................... 136
Furosemide + Spironolactone .............................................68 Grazoprevir ........................................................................ 173
Furosemide + Triamterene..................................................68 Green Aniseed ...................................................................... 54
Fusafungine ............................................................... 164, 351 Grepafloxacin ..................................................................... 154
Fusidic acid ................................................ 164, 329, 351, 381 Griseofulvin ....................................................................... 166
Fusidic acid + Betamethasone ........................................164 Guaiacolsulfonate ................................................................ 22
Fusidic acid + Hydrocortisone.........................................164 Guaifenesin.............................. 21, 22, 23, 24, 26, 79, 251, 309
Guanethidine ...................................................................... 109
Guanfacine ............................................................................ 79
G Guselkumab........................................................................ 364
Gabapentin ................................................................ 130, 292
Gabapentin + Tramadol .....................................................288 H
Galantamine........................................................................138
Galcanezumab ....................................................................299 Halcinonide ........................................................................ 358
Gallopamil .............................................................................77 Halfa bar extract ................................................................ 274
GammaCore .......................................................................300 Halobetasol ........................................................................ 358
Ganciclovir ......................................................... 171, 330, 335 Halofantrine ....................................................................... 185
Ganirelix..............................................................................220 Haloperidol ......................................................... 50, 118, 136
Gatifloxacin ................................................................. 154, 329 Haloxyl ................................................................................ 378
Gaultheria Oil......................................................................295 Hamamelis Virginiana ....................................................... 379
Gefitinib ..............................................................................414 hCG.............................................................................. 218, 252
Gemcitabine ......................................................................409 Hematin .............................................................................. 232
Gemeprost .......................................................... 213, 235, 236 Heme arginate .................................................................... 232
Gemfibrozil ..........................................................................91 hemodialysate .................................................................... 379
Gemifloxacin ......................................................................154 Heparin ...................................................................... 100, 238
Gemigliptin .........................................................................191 Heparin Na + Allantoin ..................................................... 379
Gemtuzumab .............................................................. 411, 412 Hepatitis B Immune Globulin ............................................ 398
Gentamycin ........................................................ 151, 329, 351 Heptaminol......................................................................... 104
Gentian Violet ....................................................................344 Hetastarch .......................................................................... 106
Gestodene + EE ......................................................... 211, 244 Hexamine ........................................................................... 274
Gilteritinib ..........................................................................414 Hexetidine .......................................................................... 345
Gimeracil .............................................................................409 Histamine dihydrochloride ............................................... 413
ginger root ..........................................................................303 Histrelin .............................................................................. 219
Ginkgo Biloba ............................................................. 266, 303 hMG............................................................................. 218, 252
Glabridin .............................................................................376 Homatropine ...................................................................... 333
Glatiramer ...........................................................................311 Hyaluronan ....................................................................... 304
Glecaprevir .........................................................................173 Hyaluronate ...................................................................... 304
Glibenclamide....................................................................190 Hyaluronic acid .................................................................. 332
Glibornuride .......................................................................190 Hyaluronic acid Na+ ........................................................... 243
Gliclazide............................................................................190 Hydralazine ................................................................... 79, 85
Glimepiride ........................................................................190 Hydrochlorothiazide .......................................................... 65
Glimepiride + Pioglitazone ................................................194 Hydrochlorothiazide + Amiloride ....................................... 68
Glimepiride + Rosiglitazone ..............................................194 Hydrochlorothiazide + Spironolactone .............................. 68
Glipizide .............................................................................190 Hydrochlorothiazide + Triamterene .................................. 68
Gliquidone ..........................................................................190 Hydrocodone...................................................................... 285
Glucagon .................................................................... 202, 426 Hydrocortisone ...........................353, 354, 357, 358, 361, 421
Glucarpidase .......................................................................410 Hydroflumethiazide ............................................................. 65
Glucosamine ....................................................... 295, 302, 303 Hydrogen Peroxide ........................................................... 359
Glutathione ........................................................................376 Hydromorphone ................................................................ 285
Gluteraldehyde ...................................................................368 Hydroquinone ................................................................... 376
Glyburide ............................................................................190 Hydroxocobalamin ........................................... 293, 384, 421
Glycerin .......................38, 39, 40, 67, 328, 332, 333, 334, 360 Hydroxyamphetamine ....................................................... 333
Glycerol ........................................................................ 40, 332 Hydroxycarbamide........................................................... 387
Glyceryl Guaiacolate.............................................................22 Hydroxychloroquine ................................ 185, 305, 306, 396
Glyceryl trinitrate ...............................................................82 Hydroxyprogesteron ................................................ 210, 211
Glyclopyramide ..................................................................190 Hydroxypropylmethylcellulose .................................... 332
Glycopyrrolate ......................................................................37 Hydroxyurea ..................................................................... 387
Hydroxyzine .........................................................................17 Iodoquinol .................................................................. 181, 352
Hylan polymers ..................................................................304 Ipecacuanha ....................................................................... 418
Hyoscine ................................................................. 46, 47, 333 Ipilimumab ......................................................................... 411
Hyoscine + Paracetamol ......................................................47 Ipragliflozin ........................................................................ 191
Hypochlorite .......................................................................359 Ipratropium ........................................................................ 10
Hypromellose .....................................................................332 Ipratropium + Fenoterol ................................................... 10
Ipratropium + Salbutamol ................................................ 10
Irbesartan ........................................................................... 70
I Irinotecan ........................................................................... 408
Iron dextran ...................................................................... 383
Ibalizumab ..........................................................................176 Iron Gluconate .................................................................. 383
Ibandronate.......................................................................228 Iron Isomaltoside ............................................................... 384
Ibrutinib ..............................................................................415 Iron Protein-succinylate.................................................. 382
Ibuprofen ...........................................................................278 Iron sucrose....................................................................... 383
Ibuprofen + Famotidine .....................................................280 Isavuconazole..................................................................... 166
Ibutilide.................................................................................88 Isavuconazonium ............................................................... 166
Icatibant ...................................................................... 391, 400 Isocarboxazid ..................................................................... 127
Icosapent ..............................................................................93 Isoconazole................................................................. 168, 353
Idarubicin ...........................................................................407 Isoflurane ........................................................................... 432
Idarucizumab .....................................................................101 Isoniazid .................................................................... 157, 158
Idebenone ...........................................................................139 Isopropyl Myristate ................................................... 355, 356
Idelalisib .............................................................................415 Isoproterenol ..................................................................... 106
Idoxuridine .........................................................................330 Isosorbide............................................................................. 67
Idrabiotaparinux ................................................................100 Isosorbide di nitrate .......................................................... 82
Idraparinux .........................................................................100 Isosorbide mono nitrate .................................................... 82
Idrocilamide .......................................................................294 Iso-Tretinoin ............................................................. 366, 367
Idursulfase ..........................................................................232 Isoxsuprine .......................................................................... 83
Ifosfamide..........................................................................406 Ispaghula husk ................................................................... 41
ILaprazole .............................................................................35 Ispaghula husk + Senna ...................................................... 41
Iloperidone .........................................................................120 Ispaghula husk + Plantago ovate + Senna ...................... 41
ILoprost ..............................................................................108 Isradipine ............................................................................. 77
Imatinib .............................................................................415 Itopride ................................................................................ 49
Imidapril ...............................................................................69 Itraconazole .............................................................. 166, 331
Imiglucerase ............................................................. 231, 232 Itraconazole + Secnidazole................................................ 166
Imipenem + Cilastatin ......................................................149 Ivabradine ........................................................................... 83
Imipramine ........................................................ 124, 260, 292 Ivacaftor ............................................................................... 27
Imiquimod .........................................................................369 Ivermectin ................................................................. 179, 355
Immune Globulin ..............................................................398 Ixabepilone ......................................................................... 408
Inamrinone .........................................................................106 Ixazomib ............................................................................. 414
Inclacumab .........................................................................387 Ixekizumab ......................................................................... 364
Indacaterol ...................................................................... 8, 10
Indapamide .........................................................................65
Indinavir .............................................................................176 J
Indomethacin .................................................... 278, 294, 327
Indoramin ..................................................................... 80, 258 Josamycin ........................................................................... 152
Infliximab..................................................... 53, 306, 364, 396
Inosine Pranobex ...............................................................170
Inositol Nicotinate ................................................................84 K
Inotuzumab ........................................................................412
Insulin Aspart .....................................................................197 K+ Iodide + Na+ Iodide ...................................................... 334
Insulin Degludec .................................................................198 K+ Permanganate ............................................................. 359
Insulin Detemir ..................................................................198 Kanamycin.......................................................................... 151
Insulin Glargine ..................................................................198 Kaolin + pectin .................................................................... 44
Insulin Glulisine..................................................................197 Ketamine ........................................................................... 431
Insulin Inhale ......................................................................199 Ketoconazole .............. 166, 168, 217, 226, 269, 352, 353, 361
Insulin Isophane .................................................................198 Ketoglutarate.................................................................... 434
Insulin Lente .......................................................................198 Ketoprofen ........................................... 36, 278, 280, 290, 294
Insulin Lispro .....................................................................197 Ketoprofen + Omeprazole ................................................. 280
Insulin NPH .........................................................................198 Ketorolac ................................................................... 279, 327
Interferon Alfa-2a...............................................................399 Ketotifen ...................................................................... 17, 326
Interferon Alfa-2b ..............................................................399 Kocamad P-Bettine ............................................................ 356
Interferon Alfacon-1 ..........................................................399 Kojic Acid .......................................................................... 375
Interferon Alfa-n3 ..............................................................399
Interferon Beta-1a..............................................................399 L
Interferon Beta-1b .............................................................399
Interferon Gamma 1b.........................................................399 L-5-Methyl-Tetrahydrofolate ........................................ 385
Inulin ....................................................................................41 Labetalol .................................................................. 74, 75, 85
iodochlorohydroxyquin ..................................................353
Lacidipine .............................................................................77 Liotrix ................................................................................. 205
Lacosamide .......................................................................130 Lipo Hydroxy Acid ........................................................... 373
Lactase enzyme ....................................................................54 Liquorice roots extract ........................................................ 57
lactic acid + Glycogen .........................................................243 Liraglutide......................................................................... 200
Lactitol .................................................................................41 lisdexamfetamine .............................................................. 139
Lactobacillus acidophilus ..................................................45 Lisinopril ............................................................................. 69
Lactobacillus bulgaricus ...................................................45 Lixisenatide ........................................................................ 200
Lactulose .................................................... 29, 38, 39, 41, 162 Lobeglitazone ..................................................................... 191
Lafutidine..............................................................................36 Lodoxamide ............................................................... 327, 341
Lamivudine ........................................................ 173, 176, 400 Lofepramine ....................................................................... 125
Lamotrigine .......................................................................130 Lomefloxacin ............................................................. 154, 329
Landiolol ...............................................................................75 Lomitapide ..................................................................... 92, 93
Laninamivir ........................................................................171 Lomustine........................................................................... 406
Lanreotide .................................................................. 223, 412 Loperamide ........................................................... 43, 44, 284
Lansoprazole ................................................................. 32, 35 Loperamide + Simethicone ................................................. 44
Lapatinib ...........................................................................415 Loprazolam ........................................................................ 114
Laronidase ..........................................................................232 Loratadine ....................................................... 16, 18, 22, 343
Lasmiditan ..........................................................................297 Lorazepam ........................................................................ 115
Latanoprost .......................................................................324 Lorlatinib ............................................................................ 415
Latanoprost + Timolol .....................................................325 Lormetazepam ................................................................... 114
Latanoprostene ..................................................................324 Lornoxicam ....................................................................... 279
Laureth Sulfate ...................................................................356 Losartan .............................................................................. 70
Ledipasvir ..........................................................................173 Loteprednol ....................................................... 319, 327, 330
Lefamulin ............................................................................163 Lovastatin ....................................................................... 90, 93
Leflunomide ............................................................... 305, 396 Loxapine ............................................................................ 119
lemon balm ...........................................................................55 Loxoprofen ........................................................................ 278
Lenalidomide ....................................................................413 Lubiprostone ........................................................................ 42
Lenograstim ......................................................................390 Lucinactant ........................................................................... 27
Lenvatinib ...........................................................................415 Luliconazole .............................................................. 168, 352
Lepirudin ............................................................................100 Lumacaftor + Ivacaftor ........................................................ 27
Lercanidipine ......................................................................77 Lumiracoxib ....................................................................... 281
Lesinurad ............................................................................308 Lurasidone ......................................................................... 120
Letermovir ..........................................................................171 Luspatercept ...................................................................... 387
Letrozole .................................................... 209, 210, 251, 413 Lusutrombopag.................................................................. 389
Leuprolide .......................................................... 219, 258, 413 Lutropin Alfa .............................................................. 219, 252
Levalbuterol ...........................................................................8 Lymecycline ....................................................................... 150
Levamisole .........................................................................179 Lynestrenol................................................................ 211, 244
Levetiracetam ...................................................................130 Lyophilized fish roe ........................................................... 266
Levobunolol ................................................................. 76, 323 Lysine ................................................................................. 434
Levocabastine ............................................................... 19, 326
Levocarnitine......................................................................232
Levocetirizine ................................................................ 16, 18 M
Levodopa + Benserazide .................................................133
Levodopa + Carbidopa ....................................................133 Macitentan.......................................................................... 108
Levodopa + Carbidopa + Entacapone ..........................133 Macrogol ........................................................................ 41, 42
Levofloxacin ............................................................... 154, 329 Mafenide ..................................................... 156, 164, 351, 381
Levofolinic acid ................................................................410 Magnesium Sulfate............................................................. 359
Levomepromazine .............................................................119 Malathion ................................................................... 355, 356
levoMilnacipran .................................................................125 Manganese Gluconate...................................................... 383
Levonorgestrel ................................... 211, 212, 244, 247, 248 Manidipine ........................................................................... 77
Levonorgestrel + EE.........................................................211 Mannitol ...................................................................... 67, 420
Levorphanol .......................................................................285 Maprotiline................................................................ 125, 292
levo-salbutamol....................................................................8 Maraviroc ........................................................................... 176
Levosimendan ...................................................................109 Mavacoxib .......................................................................... 281
Levosulpiride ........................................................................47 Mebendazole ..................................................................... 179
levothyroxine.....................................................................205 Mebeverine .................................................................... 46, 47
Lidocaine............................................................... 87, 334, 361 Mebeverine + Dimethicone ................................................. 47
Lidocaine + Fluocinolone .....................................................59 Mebeverine + Ispaghula ...................................................... 47
Lidocaine + Prilocaine......................................................267 Mebeverine + Sulpride ....................................................... 47
Lignocaine .........................................................................338 Mecamylamine ................................................................... 109
Linaclotide ............................................................................41 Mecasermin ........................................................................ 222
Linagliptin .........................................................................191 Meclizine .............................................................................. 49
Linagliptin + Empagliflozin.............................................194 Meclizine + B6 ...................................................................... 49
Lincomycin .........................................................................155 Meclofenoxate .................................................................... 139
Lindane ...............................................................................355 Medroxyprogesterone ..................... 207, 211, 212, 244, 246
Linezolid .............................................................................162 Mefenamic acid ................................................................. 278
Liothyronine ......................................................................205 Mefloquine ......................................................................... 186
Megestrol............................................................................ 211
Megestrol acetate ....................................................... 258, 413 Methylene Blue .................................................................. 419
Meglumine Antimoniate ....................................................183 Methylergometrine .......................................................... 236
Melarsoprol ........................................................................184 Methylfolate...................................................................... 385
Melatonin ................................................................... 116, 127 Methylnaltrexone................................................................. 41
Meloxicam ..........................................................................279 Methylphenidate ............................................................. 139
Meloxicam + Carisoprodol* ...............................................287 Methylprednisolone ................................................. 303, 318
Meloxicam + Esomeprazole ...............................................280 Methylsulfonylmethane .................................................... 302
Meloxicam + Gabapentin*..................................................287 Methyl-Testosterone ........................................................ 215
Meloxicam + Pridinol* .......................................................287 Methyl-Testosterone + Esterified Estrogens .................. 217
Melphalan ..........................................................................406 Metipranolol................................................................. 76, 323
Memantine ........................................................................138 Metoclopramide ................................................... 48, 49, 239
Memantine + Donepezil ....................................................138 Metolazone ........................................................................... 65
Menaquinone-7 .................................................................230 Metoprolol ....................................................... 73, 75, 87, 298
Menfegol .............................................................................246 Metronidazole ............................153, 160, 164, 180, 241, 344
Menotropin ................................................................ 218, 252 Metyrapone ........................................................................ 226
Menthol ....................................................................... 294, 345 Metyrosine ........................................................................... 81
Menthol + Menthyl isovalerate ........................................83 Mexiletine ............................................................................ 87
Mepacrine ...........................................................................181 Mg+ Sulphate ...................................................................... 14
Mepenzolate ........................................................................37 Mianserin ........................................................................... 125
Meperidine .........................................................................285 Micafungin .................................................................. 166, 331
Mepolizumab ........................................................................14 Miconazole ................................................ 168, 169, 240, 344
Meprobamate .....................................................................116 Miconazole + Hydrocortisone ........................................... 242
Mequinol .............................................................................376 Miconazole + Metronidazole ............................................. 242
Mequinol + Retinol .............................................................376 Miconazole + Nystatin ....................................................... 242
Mercaptamine ....................................................................232 Microlactin ......................................................................... 309
Mercaptopurine .......................................... 53, 393, 394, 409 Midazolam ......................................................................... 114
Meropenem ........................................................................149 Midodrine ........................................................................... 104
Mesalamine .........................................................................52 Midostaurin ...................................................................... 415
Mesna .................................................................................410 Mifamurtide ....................................................................... 413
Mesoridazine ......................................................................118 Mifepristone ............................................................... 213, 226
Mesterolone .......................................................................215 Miglitol ............................................................................... 191
Metafolin............................................................................385 Miglustat ..................................................................... 231, 232
Metaxalone .........................................................................289 Milk Thistle extract .............................................................. 57
Metenolon ..........................................................................216 Milnacipran ................................................................ 125, 310
Metformin .......................... 190, 191, 192, 194, 195, 249, 371 Milrinone ............................................................................ 106
Metformin + Alogliptin ......................................................194 Miltefosine.......................................................................... 183
Metformin + Canagliflozin .................................................194 Minocycline ........................................................................ 150
Metformin + Dapagliflozin .................................................194 Minoxidil .............................................................. 79, 370, 371
Metformin + Empagliflozin ................................................194 Mint extract .......................................................................... 54
Metformin + Glibenclamide .............................................194 Miocamycin ........................................................................ 152
Metformin + Glimepiride ................................................194 Mipomersen ......................................................................... 92
Metformin + Glipizide ........................................................194 Mirabegron......................................................................... 259
Metformin + Linagliptin .....................................................194 Mirtazapine ....................................................................... 126
Metformin + Pioglitazone ................................................194 Misoprostol ......................................... 37, 213, 235, 236, 280
Metformin + Repaglinide ...................................................194 Mitiglinide .......................................................................... 190
Metformin + Rosiglitazone ................................................194 Mitomycin ......................................................................... 407
Metformin + Saxagliptin ..................................................194 Mitotane ..................................................................... 226, 410
Metformin + Sitagliptin ...................................................194 Mitoxantrone ............................................................. 311, 407
Metformin + Vildagliptin .................................................194 Mivacurium ........................................................................ 433
Methadone .........................................................................285 Mizolastine ........................................................................... 18
Methamphetamine .............................................................139 Mocetinostat ...................................................................... 416
Methandrostenolone ........................................................216 Moclobemide ...................................................................... 127
Methazolamide ..................................................... 67, 323, 324 Modafinil ............................................................................ 139
Methenamine ......................................................................155 Moexipril.............................................................................. 69
Methimazole .......................................................................206 Mogamulizumab ................................................................ 411
Methionine..........................................................................423 Molsidomine ........................................................................ 83
Methocarbamol .................................................................289 Mometasone ........................... 9, 317, 341, 353, 358, 363, 376
Methotrexate ..................................................... 305, 394, 409 Mometasone + Formoterol.................................................... 9
Methoxsalen .......................................................................363 Monalazone ........................................................................ 246
Methoxy polyethylene glycol Epoetin Beta ....................388 Monobenzone .................................................................... 376
Methscopolamine .................................................................37 Montelukast ........................................................................ 13
Methsuximide .....................................................................130 Montelukast + Desloratidine ............................................ 13
Methyclothiazide .......................................................... 65, 109 Montelukast + Ebastine ....................................................... 13
Methyl Salicylate ........................................................ 294, 345 Morphine ........................................................................... 285
Methylcellulose ............................................... 38, 39, 41, 332 Morrhuate Na+ ................................................................... 391
Methylcobalamin ...................................................... 293, 384 Mosapride............................................................................ 49
Methyldopa ..........................................................................79 Moxidectin .......................................................................... 179
Moxifloxacin ......................................................................154 Nicotine ............................................................................. 430
Moxisylyte.............................................................................84 Nifedipine ............................................................................ 77
Moxonidine ..........................................................................79 Nifedipine + Atenolol ........................................................... 78
MSM ....................................................................................302 Nifuroxazide ...................................................................... 162
Mucopolysaccharide + Heparinoid .....................................59 Nifurtimox .......................................................................... 184
Mupirocin ................................................................... 164, 351 Nikethamide ....................................................................... 419
Muromonab-CD3 ................................................................395 Nilotinib ............................................................................ 415
Mycophenolate ..................................................................394 Nilutamide .................................................................. 217, 412
Myrtle oil...............................................................................26 Nimesulide......................................................................... 279
Nimodipine .......................................................................... 77
Nintedanib.................................................................... 27, 415
N Nisoldipine ........................................................................... 77
Nitazoxanide ..................................................................... 181
Na+ Picosulfate ............................................................... 40, 42 Nitisinone ........................................................................... 233
Nabilone ..............................................................................136 Nitrazepam......................................................................... 115
Nabumetone .......................................................................278 Nitrendipine + Enalapril...................................................... 78
N–Acetyl Carnosine ............................................................334 Nitrofurantoin .................................................................. 155
N-acetylcysteine ...................................................................25 Nitroglycerin ....................................................................... 85
Nadifloxacin............................................................... 164, 351 Nitroprusside ................................................................ 79, 85
Nadolol ........................................................... 74, 75, 206, 298 Nitrous Oxide ................................................................... 432
Nadroparin ........................................................................100 Nivolumab......................................................................... 411
Nafarelin .............................................................................219 Nizatidine ....................................................................... 35, 36
Naftidrofuryl .......................................................................84 Nonivamide ........................................................................ 295
Naftifine ...................................................................... 168, 352 Nonoxinol 9 ....................................................................... 246
Nalbuphine .........................................................................285 Nonoxinol 9 + Benzethonium Cl...................................... 246
Naldemedine ........................................................................41 Norelgestromin + EE ........................................................ 245
Nalidixic acid .....................................................................154 Norepinephrine ................................................................ 106
Nalmefene ...........................................................................295 Norethindrone ................................................................. 211
Naloxegol ..............................................................................41 Norethindrone + EE ................................................... 211, 244
Naloxone .................................................................... 295, 425 Norethindrone + Estradiol ........................................ 211, 212
Naloxone + Buprenorphine ...............................................295 Norethindrone + Mestranol ...................................... 211, 244
Naltrexone ................................................................. 295, 425 Norethisterone ......................................................... 211, 246
Nandrolone ........................................................................216 Norfloxacin ................................................................ 154, 329
Naphazoline......................................... 20, 328, 330, 333, 342 Norgestimate + EE ............................................................. 211
Naphazoline + Antazoline................................................328 Norgestimate + Estradiol .................................................. 212
Naphazoline + Chlorpheniramine ..................................328 Norgestrel + EE .......................................................... 211, 244
Naphazoline + Glycerin ....................................................328 Norgestrel + Estradiol ..................................................... 212
Naphazoline + Pheniramine............................................328 Nortriptyline .............................................................. 124, 260
Naphazoline + Sulfophenate ...........................................328 Nortriptyline + Fluphenazine ........................................ 127
Naproxen ............................................................................278 Noscapine ................................................................. 21, 22, 24
Naproxen + Esomeprazole ................................................280 Nystatin.............................................. 166, 168, 169, 240, 344
Naproxen + Misoprostol ....................................................280
Naratriptan .........................................................................297
Natalizumab.................................................. 53, 310, 311, 396 O
Natamycin ................................................................... 329, 331
Nateglinide ........................................................................190 Obinutuzumab ................................................................... 411
Nebivolol .................................................................. 73, 74, 75 Ocrelizumab ....................................................................... 311
Necitumumab .....................................................................411 Ocriplasmin ........................................................................ 336
Nedaplatin ..........................................................................406 Octreotide .................................................................... 45, 223
Nedocromil ........................................................... 13, 327, 341 Ofatumumab ...................................................................... 411
Nefazodone .........................................................................126 Ofloxacin ............................................................ 154, 329, 338
Nefopam.............................................................................277 Oil of Wintergreen ............................................................. 294
Nelarabine ..........................................................................409 Olanzapine ........................................................................ 120
Nelfinavir ............................................................................176 Olaparib .............................................................................. 410
Neomycin.................................................................... 151, 329 Olaratumab ........................................................................ 411
Neostigmine ....................................................... 313, 423, 433 Olmesartan ........................................................................... 70
Neostigmine + Glycopyrronium ........................................433 Olodaterol......................................................................... 8, 10
Nepafenac ..........................................................................327 Olopatadine......................................................... 19, 326, 341
Neratinib .............................................................................415 Olsalazine ............................................................................. 52
Nerivio Migra ....................................................................300 Omadacycline ..................................................................... 150
Nesiritide ............................................................................109 Omalizumab ....................................................................... 14
Netarsudil ...........................................................................325 Omapatrilat ........................................................................ 72
Netilmicin ...........................................................................151 Omarigliptin ....................................................................... 191
Nevirapine ..........................................................................176 Ombitasvir .......................................................................... 174
Niacin............................................................................ 93, 439 Omeprazole ..................................................... 32, 35, 36, 280
Nicardipine ..................................................................... 77, 85 Omeprazole + Aspirin .......................................................... 36
Niclosamide ........................................................................179 Omeprazole + Ketoprofen ................................................... 36
Nicorandil ............................................................................83 Ondansetron ..................................................................... 136
Opium tincture .....................................................................44 Pasireotide ......................................................... 223, 226, 412
Oprelvekin .................................................................. 389, 401 Pazopanib ......................................................................... 415
Oritavancin .........................................................................161 Pegaptanib.......................................................................... 336
Orlistat ...............................................................................435 Pegaspargase ..................................................................... 410
Ornidazole ................................................................. 160, 241 Pegfilgrastim ...................................................................... 390
Ornidazole + Cefixime ........................................................161 Peginesatide ....................................................................... 388
Ornidazole + Ciprofloxacin ..............................................161 Peg-Interferon Alfa-2a............................................. 174, 400
Ornidazole + Gatifloxacin ..................................................161 Peg-Interferon Alfa-2b .............................................. 174, 400
Ornidazole + Levofloxacin .................................................161 Pegloticase ......................................................................... 308
Ornidazole + Ofloxacin.......................................................161 Pegvisomant ....................................................................... 223
Orphenadrine ....................................................................289 Pembrolizumab ............................................................... 411
Oseltamivir ........................................................................171 Pemetrexed ........................................................................ 409
Osimertinib .........................................................................415 Pemirolast .................................................................. 327, 341
Ospemifene .........................................................................209 Penbutolol ............................................................................ 75
Oteracil................................................................................409 Penciclovir ................................................................. 170, 354
Otilonium .............................................................................46 Penicillamine.............................................................. 233, 305
Oxaliplatin .........................................................................406 Pentamidine ............................................................... 183, 184
Oxandrolone .............................................................. 215, 264 Pentazocine ........................................................................ 285
Oxaprozin ...........................................................................278 Pentetate Zinc Trisodium .................................................. 427
Oxazepam ...........................................................................114 Pentobarbital ..................................................................... 115
Oxcarbazepine ..................................................................129 Pentostatin ......................................................................... 409
Oxeladine ........................................................................ 22, 24 Pentoxifylline ...................................................................... 84
Oxerutins ..............................................................................84 Peppermint Oil ....................................................... 31, 46, 294
Oxiconazole................................................................ 168, 352 Peramivir............................................................................ 171
Oxide ...................................................................................360 Perampanel ........................................................................ 130
Oxitropium ...........................................................................10 Pergolide ............................................................................ 133
Oxomemazine .............................................. 17, 18, 23, 24, 26 Pericyazine ......................................................................... 119
Oxprenolol ...........................................................................75 Perindopril .......................................................................... 69
Oxybuprocaine ...................................................................334 Permanganate .................................................................. 359
Oxybuprocaine + Chlorhexidine ........................................334 Permethol ........................................................................... 345
Oxybuprocaine + Tetracaine .............................................334 Permethrin ............................................................... 355, 356
Oxybutynin.........................................................................259 Perphenazine ..................................................................... 118
oxychloro complex...........................................................332 Pertuzumab ........................................................................ 411
Oxycodone .................................................................. 285, 292 Pethidine............................................................................ 285
Oxymetazoline............................................. 20, 328, 342, 366 Petrolatum ......................................................................... 379
Oxymetholone....................................................................216 Pexidartinib ........................................................................ 415
Oxymorphone .....................................................................285 Phenazone ......................................................................... 338
Oxytetracycline .......................................................... 150, 353 Phenazone + Chlorbutol *................................................ 338
Oxytocin .............................................................................236 Phenazone + Lidocaine .................................................... 338
Ozenoxacin ................................................................. 164, 351 Phenazopyridine ................................................................ 275
Ozogamicin .........................................................................412 Phendimetrazine................................................................ 139
Phenelzine ......................................................................... 127
Phenformin ........................................................................ 190
P Phenindione ....................................................................... 100
Pheniramine ............................................................... 17, 328
Paclitaxel ...........................................................................408 Phenobarbital ................................................................... 115
Pacritinib ............................................................................415 Phenolsulphonate .............................................................. 330
Palbociclib .........................................................................415 Phenothrin ......................................................................... 356
Palidoxime ..........................................................................420 Phenoxybenzamine ............................................................. 81
Palifermin ...........................................................................410 Phentermine..................................................................... 139
Paliperidone ......................................................................120 Phentolamine ......................................................... 81, 85, 265
Palivizumab ........................................................................174 Phenylephrine........................ 20, 59, 106, 107, 260, 328, 343
Palonosetron ......................................................................136 phenylethylmalonamide ................................................ 115
Pamidronate .......................................................................228 Phenytoin........................................................... 130, 379, 420
Pancreatine ...........................................................................55 Phloroglucinol ...................................................................... 46
Pancuronium ......................................................................433 Pholcodine............................................................................ 22
Panitumumab .....................................................................411 Phyllanthus ........................................................................ 274
Panobinostat.......................................................................410 Pilocarpine ................................................................ 325, 345
Pantoprazole ..................................................... 32, 33, 35, 36 Pilocarpine + Timolol ........................................................ 325
Pantoprazole + Domperidone .............................................36 Pimavanserin ..................................................................... 120
Pantothenic acid ..............................................................439 Pimecrolimus .................................................... 363, 392, 393
Papaverine................................................................. 109, 265 Pimozide ............................................................................ 118
Paracetamol ......................................................................276 Pinaverium ........................................................................... 46
Parecoxib ............................................................................281 Pindolol ................................................................................ 75
Paricalcitol ..........................................................................230 Pioglitazone ...................................................................... 191
Paritaprevir ........................................................................174 Pipazethate............................................................... 22, 24, 26
Paromomycin .....................................................................181 Pipenzolate ........................................................................... 55
Paroxetine.................................................................. 123, 292
Pipenzolate + Phenobarbitone ............................................55 Primula rooy ........................................................................ 26
Piperacillin + Tazobactam ..............................................146 Probenecid ......................................................................... 308
Piperaquine ........................................................................186 Procainamide ....................................................................... 87
Piperazine ...........................................................................274 Procaine benzyl penicillin .................................................... 146
Piperonyl Butoxide ............................................................356 Procarbazine .................................................................... 406
Pipotiazine ..........................................................................121 Prochlorperazine ......................................... 48, 49, 118, 119
Piracetam ..........................................................................139 Procyclidine...................................................................... 133
Pirbuterol................................................................................8 Proflavine ........................................................................... 359
Pirenoxine...........................................................................334 Progesterone ..................................................................... 211
Pirenzepine ..........................................................................37 Proguanil ............................................................................ 186
Piretanide .............................................................................64 Promazine .......................................................................... 118
Pirfenidone ..........................................................................27 Promethazine ................................................. 17, 21, 23, 343
Piribedil ..............................................................................133 Propafenone ........................................................................ 87
Piroxicam ...........................................................................279 Propantheline ...................................................... 46, 259, 312
Pitavastatin ...........................................................................90 Proparacaine .................................................................... 334
Pivmecillinam .....................................................................149 Proparacaine + Fluorescein .............................................. 334
Pixantrone ..........................................................................407 Propiverine ........................................................................ 259
Pizotifen ............................................................. 298, 299, 434 Propofol ............................................................................. 431
Plazomicin ..........................................................................151 Propolis ............................................................................. 275
Plecanatide ...........................................................................41 Propranolol .................... 73, 87, 206, 298, 299, 420, 425, 426
Plerixafor ............................................................................391 Propylene Glycol ................................................................ 333
Podophyllotoxin ................................................................369 Propylhexedrine .......................................................... 20, 342
Policresulen ........................................................................243 Propylthiouracil ............................................................... 206
Policresulen + Cinchocaine ..................................................59 Protamine Sulfate .............................................................. 101
Polidocanol ................................................................ 368, 391 Protamine Sulphate ........................................................... 423
Polyacetic Acid .................................................................373 Protein-free hemodialysate .............................................. 379
Polycaprolactone .............................................................373 Prucalopride................................................................... 42, 49
Polycarbophil .......................................................................44 Pseudoephedrine ......................................................... 21, 260
Polyethylene Glycol 400 ....................................................332 Pulsante ............................................................................. 301
Polyhexamethylene .........................................................332 Pyrantel pamoate............................................................... 179
Polyhexanide ......................................................................379 Pyrazinamide ........................................................... 157, 158
Polymethylmethacrylate ................................................373 Pyrethrum Extract ............................................................. 356
Polymyxin B .......................................................................329 Pyridostigmine ......................................................... 313, 433
Polymyxin B + Bacitracin......................................... 164, 329 pyridoxine ........................................................... 49, 158, 439
Polymyxin B + Trimethoprim ............................................329 Pyrimethamine .................................................. 156, 182, 186
Polyquaternium-1............................................................332 Pyrimethamine + Sulfadoxine ................................... 156, 182
Polysaccharide Iron ...........................................................382 Pyrithione zinc .................................................................. 361
Polysiloxane........................................................................379 Pyritinol ............................................................................ 139
Polysiloxane + Silicon dioxide ...........................................379
Polythiazide .................................................................. 65, 109
Polyvinyl alcohol ................................................................332 Q
Polyvinyl alcohol + Povidone ............................................332
Pomalidomide ....................................................................413 Quazepam........................................................................... 115
Ponatinib.............................................................................415 Quetiapine ......................................................................... 120
Poractant Alfa .....................................................................27 Quinacrine .......................................................................... 181
Posaconazole ......................................................................166 Quinagolide ........................................................................ 224
Potassium Iodide ................................................................206 Quinapril .............................................................................. 69
Povidone-Iodine ................................................. 256, 359, 381 Quinethazone ....................................................................... 65
Pralatrexate ........................................................................409 Quinidine ...................................................................... 87, 186
Pramipexole ......................................................................133 Quinine ....................................................................... 186, 418
Pramlintide .........................................................................200 Quinupristin + Dalfopristin ............................................... 162
Pramoxine...........................................................................360 Quizartinib ......................................................................... 415
Pranlukast.............................................................................13
Prasugrel .............................................................................96 R
Pravastatin............................................................................90
Praziquantel .......................................................................179 Rabeprazole ............................................................ 32, 35, 36
Prazosin ....................................................................... 80, 258 Rabeprazole + Domperidone .......................................... 36
Prednicarbate .....................................................................358 Rabies Immune Globulin ................................................... 398
Prednisolone......................... 53, 59, 298, 316, 319, 327, 330 Racecadotril ........................................................................ 45
Prednisone .........................................................................318 Raloxifene ........................................................................... 209
Pregabalin ......................................................... 130, 292, 310 Raltegravir.......................................................................... 176
Pretomanid .........................................................................158 Raltitrexed .......................................................................... 410
Pridinol ...............................................................................289 Ramelteon ......................................................................... 116
Prifinium ..............................................................................46 Ramipril ............................................................................... 69
Prilocaine ...........................................................................361 Ramucirumab..................................................................... 411
Primaquine ................................................................. 184, 185 Ranibizumab ............................................................ 335, 336
Primidone ..........................................................................115 Ranitidine ...................................................................... 35, 36
Ranolazine ...........................................................................83
Rasagiline............................................................................133
S
Rasburicase ................................................................ 308, 410
Sacubitril ............................................................................. 72
Raxibacumab ......................................................................396
Safinamide .................................................................. 127, 133
Rebamipide...........................................................................37
Salbutamol ............................................................ 8, 9, 10, 24
Reboxetine .................................................................. 125, 127
Salicylic Acid ..................................................................... 363
Recombinant hMG ...................................................... 219, 252
Salicylic Acid + Zinc Oxide ................................................ 363
Recombinant human growth hormone ............................222
Salicylic Acid + Betamethasone ...................................... 363
Regorafenib ........................................................................415
Salicylic Acid + Dexamethasone ..................................... 363
Regular Insulin ...................................................................197
Salicylic acid + Lactic acid ............................................... 368
Relebactam........................................................................149
Salicylic Acid + Mometasone ........................................... 363
Relugolix .............................................................................220
Salmeterol ......................................................................... 8, 9
Remi-Fentanyl ...................................................................285
Saquinavir .......................................................................... 176
Renzapride............................................................................42
Sarecycline ......................................................................... 150
Repaglinide........................................................................190
Sargramostim ..................................................................... 390
Reserpine ................................................................... 109, 110
Saroglitazar ........................................................................ 191
Reslizumab ...........................................................................14
Saxagliptin ........................................................................ 191
Resorcinol ...........................................................................376
Saxagliptin + Dapagliflozin................................................ 194
Retapamulin ............................................................... 164, 351
Scion device ...................................................................... 301
Reteplase ............................................................................102
Scopolamine ........................................................ 46, 135, 333
Retigabine ...........................................................................130
Secnidazole................................................................ 160, 241
Retinaldehyde ..................................................................373
Secnidazole + Albendazole ................................................ 161
Retinol ........................................................................ 373, 376
Secnidazole + Fluconazole ................................................ 161
Retinyl Palmitate .............................................................373
Secnidazole + Itraconazole................................................ 161
Revefenacin ..........................................................................10
Secobarbital ....................................................................... 115
Reviparin ............................................................................100
Secukinumab..................................................................... 364
Rho(D) IG............................................................................398
Selegiline ................................................................... 127, 133
Rhubarb ................................................................................54
Selenium Sulphide ............................................................ 361
Ribavirin .................................................................... 173, 174
Selexipaq ............................................................................ 108
Ribociclib ...........................................................................415
Semaglutide ........................................................................ 200
Riboflavin ..........................................................................439
Senna .................................................................. 38, 39, 40, 41
Rifabutin ....................................................................... 37, 158
Sennosides ........................................................................... 40
Rifampicin ......................................................... 157, 158, 159
Serratiopeptidase .............................................................. 309
Rifampicin + Isoniazid .......................................................158
Sertaconazole ........................................................... 168, 353
Rifapentine .........................................................................158
Sertindole ........................................................................... 120
Rifaximin ...........................................................................162
Sertraline................................................................... 123, 267
Rilonacept ...........................................................................400
Sevelamer .................................................................. 231, 438
Rilpivirine ...........................................................................176
Sevoflurane ........................................................................ 432
Riluzole ...................................................................... 231, 313
Sildenafil ...................................................... 82, 108, 263, 312
Rimantadine .......................................................................171
Silicon dioxide .................................................................... 379
Rimegepant.........................................................................299
Silodosin ...................................................................... 80, 258
Rimexolone ................................................................. 319, 327
Silodosin + Tamsulosin ..................................................... 258
Riociguat .............................................................................108
Siltuximab .......................................................................... 411
Risedronate .......................................................................228
Silver Sulfadiazine.................................... 156, 164, 351, 381
Risperidone................................................................ 120, 121
Silymarin ............................................................................. 57
Ritonavir ..................................................................... 174, 176
Simeprevir .......................................................................... 173
Rituximab ........................................................... 306, 396, 411
Simethicone .............................................. 31, 44, 54, 55, 360
Rivaroxaban ......................................................................100
Simethicone + Silicon Dioxide ............................................. 54
Rivastigmine .....................................................................138
Simvastatin ..................................................... 89, 90, 93, 379
Rizatriptan ........................................................................297
Simvastatin + niacin ............................................................ 93
Rocuronium ........................................................................433
Siponimod .......................................................................... 311
Rofecoxib ............................................................................281
Sirolimus............................................................................ 393
Roflumilast ...........................................................................14
Sitagliptin .......................................................................... 191
Rolapitant ...........................................................................136
Sitaxentan ........................................................................... 108
Romidepsin .........................................................................416
Sitosterol ............................................................................ 379
Romiplostim .......................................................................389
Sodium Fluoride ........................................................ 345, 347
Ronacare AP .......................................................................374
Sodium Hyaluronate ................................................ 304, 332
Ropinirole ..........................................................................133
Sodium nitrate ................................................................. 421
Rose Hip ...................................................................... 302, 309
Sodium Oxybate ................................................................. 116
Rosiglitazone .....................................................................191
sodium perborate ............................................................ 332
Rosuvastatin........................................................................90
Sodium phenylbutyrate ..................................................... 233
Rotigotine ..........................................................................133
Sodium Polystyrene ........................................................... 425
Roxatidine .............................................................................36
Sodium stibogluconate .................................................... 183
Roxithromycin ....................................................................152
Sodium thiosulphate ....................................................... 421
Rufinamide .........................................................................130
Sofosbuvir .................................................................. 172, 173
Rupatadine ...........................................................................18
SofZia ................................................................................. 332
Ruxolitinib.........................................................................415
Solifenacin ......................................................................... 259
Somatropin ........................................................................222 Tedizolid ............................................................................. 162
Sorafenib ...........................................................................415 Tegafur ............................................................................... 409
Sorbitol ..................................................................... 22, 38, 41 Tegaseride ............................................................................ 42
Sotagliflozin ........................................................................191 Tegaserod ............................................................................. 42
Sotalol ....................................................................... 74, 76, 88 Teicoplanin........................................................................ 161
Sparfloxacin ........................................................................154 Telaprevir ........................................................................... 173
Spinosad..............................................................................355 Telavancin .......................................................................... 161
Spiramycin ......................................................... 152, 153, 182 Telbivudine ........................................................................ 173
Spiramycin + Metronidazole ...........................................182 Telithromycin .................................................................... 152
Spironolactone .................................. 63, 64, 66, 68, 217, 249 Telmisartan......................................................................... 70
Stanozolol ..........................................................................216 Telotristat ............................................................................. 45
Stavudine ............................................................................176 Temazepam ........................................................................ 115
Sterculia ............................................................. 38, 39, 41, 43 Temozolomide ................................................................. 406
Sterculia + Frangula...........................................................41 Temsirolimus ..................................................................... 415
Stiripentol ...........................................................................129 Tenapanor ............................................................................ 42
Streptokinase ....................................................................102 Tenatoprazole ...................................................................... 35
Streptomycin .....................................................................151 Tenecteplase ..................................................................... 102
Streptozocin .......................................................................406 Teneligliptin ....................................................................... 191
Strontium Ranelate ..........................................................230 Teniposide .......................................................................... 408
Succimer .............................................................................427 Tenofovir ................................................................... 173, 176
Succinylated gelatin ...........................................................106 Tenoxicam ......................................................................... 279
Succinylcholine ................................................................432 Terazosin ..................................................................... 80, 258
Sucralfate .............................................................................37 Terbinafine................................................................ 168, 353
Sugammadex ......................................................................433 Terbutaline ............................................................. 8, 24, 234
Sulbutiamine ......................................................................139 Terconazole ........................................................ 168, 169, 240
Sulconazole ................................................................. 168, 353 Terfenadine .................................................................. 18, 152
Sulfacetamide .....................................................................329 Teriflunomide .................................................................... 311
Sulfadiazine ................................................................ 156, 182 Teriparatide ...................................................................... 229
Sulfadoxine .........................................................................156 Terlipressin ........................................................................ 222
Sulfamethoxazole + Trimethoprim ................................156 Terpene mixture ................................................................ 275
Sulfamethoxypyrazine .......................................................186 Testosterone ..................................... 215, 217, 263, 264, 269
Sulfasalazine ............................................... 52, 156, 305, 306 Tetanus Immune Globulin ................................................. 398
Sulfinpyrazone ...................................................................308 Tetrabenazine................................................................... 313
Sulfisoxazole ............................................................... 156, 329 Tetracaine .................................................................. 334, 361
Sulfisoxazole + Erythromycin............................................156 Tetracosactide .................................................................. 321
Sulodexide ..........................................................................100 Tetracycline ...................................................... 150, 329, 351
Sulpiride ..............................................................................47 Tetradecyl Sulfate .............................................................. 391
Sulpride ..............................................................................118 Tetrahydrocannabinol....................................................... 301
Sulprostone......................................................... 213, 235, 236 Tetrahydrocannabinol + Cannabidiol .............................. 301
Sumatriptan ......................................................................297 Tetrahydrofolate ............................................................. 385
Sumatriptan + Naproxen ...................................................299 Tetrahydrozoline................................ 20, 328, 330, 333, 342
Sunitinib ............................................................................415 Tetrahydrozoline + Zinc Sulfate ..................................... 328
Suramin ...............................................................................184 Thalidomide ..................................................................... 413
Suvorexant ..........................................................................116 Theophylline ................................................... 12, 24, 26, 418
Suxamethonium ...............................................................432 Thiabendazole .................................................................. 179
synthetic human angiotensin II ...........................................70 Thiamine .................................................................... 419, 439
Thiocolchicoside ............................................................... 289
Thiopental .................................................................. 115, 431
T Thiopentone ..................................................................... 431
Thiophenicol ...................................................................... 163
Tacalcitol.............................................................................363 Thioridazine ....................................................................... 119
Tacrine ................................................................................138 thiosulphate ..................................................................... 421
Tacrolimus ......................................................... 363, 392, 393 Thiotepa ............................................................................. 406
Tadalafil ....................................................... 82, 108, 263, 312 Thiothixene ........................................................................ 119
Tafenoquine........................................................................186 Thonzonium ....................................................................... 338
Tafluprost ...........................................................................324 Thyme fluid extract ............................................................. 26
Talimogene Laherparepvec ...............................................413 Thymol................................................................................ 345
Tamoxifen .................................................................. 209, 413 Thymoxamine .................................................................... 84
Tamsulosin .......................................................... 80, 257, 258 Thyroglobulin .................................................................... 205
Tannate ................................................................................44 Thyrotropin Alfa ................................................................ 205
Tapentadol ..........................................................................285 Tiabendazole .................................................................... 179
Tar Extract .........................................................................363 Tiagabine ............................................................................ 130
Taurine ...............................................................................335 Tianeptine .......................................................................... 127
Tavaborole ..........................................................................168 Tiaprofenic acid................................................................ 278
Tazarotene................................................................. 363, 366 Tibolone ..................................................................... 208, 255
Tbo-filgrastim .....................................................................390 Ticagrelor ............................................................................ 96
Tebipenem ..........................................................................149 Ticarcillin + Clavulanic acid .............................................. 146
Tecovirimat ........................................................................170
Ticlopidine ...........................................................................96 Trimetazidine ............................................................... 83, 84
Tiemonium...........................................................................46 Trimethobenzamide .......................................................... 136
Tigecycline .........................................................................150 Trimethoprim ................................................................... 156
Tilisolol .................................................................................75 Trimethylglycine ................................................................ 232
Tiludronate .........................................................................228 Trimethylphloroglucinol ..................................................... 46
Timolol ........................................ 67, 73, 74, 76, 298, 323, 325 Trimipramine ..................................................................... 125
Tinidazole .......................... 160, 161, 166, 180, 181, 241, 242 Tripamide ............................................................................. 64
Tinidazole + Norfloxacin..................................................161 Triprolidine ..................................................... 17, 19, 21, 343
Tinzaparin ................................................................. 100, 238 Triptorelin ................................................................. 219, 413
Tioconazole......................................................... 168, 169, 240 Trolamine ......................................................................... 294
Tioconazole + Tinidazole ...................................................242 Troleandomycin ................................................................. 152
Tioguanine ..........................................................................409 Tromantadine .................................................................... 170
Tiotropium...........................................................................10 Tropicamide ...................................................................... 333
Tiotropium + Olodaterol ......................................................10 Trospium Chloride ........................................................... 259
Tipiracil ...............................................................................409 Trovafloxacin ..................................................................... 154
Tipranavir ...........................................................................176 Turmeric Extract ............................................................... 57
Tirofiban ...............................................................................96 Turpentine Oil .................................................................... 294
Tizanidine ..........................................................................289 Tyrothricin ......................................................................... 346
Tobramycin ............................................................... 151, 329
Tocilizumab ................................................................ 306, 396
Tofacitinib...........................................................................309 U
Tofisopam ..........................................................................116
Tofogliflozin........................................................................191 Ulipristal .................................................................... 213, 248
Tolazamide........................................................................192 Ultra-Lente ......................................................................... 198
Tolbutamide .....................................................................192 Umeclidinium + Vilanterol .................................................. 10
Tolcapone ...........................................................................133 Unoprostone ...................................................................... 324
Tolfenamic acid ..................................................................278 Urapidil ............................................................................... 109
Tolnaftate .................................................................. 168, 353 Urea .................................................................................... 359
Tolperisone ........................................................................289 Uridine ................................................................................ 292
Tolterodine ........................................................................259 Urofollitropin ............................................................ 218, 252
Tolvaptan ............................................................................222 Urokinase ........................................................................... 102
Topiramate ................................................................ 130, 299 Ursodeoxycholic Acid ....................................................... 56
Topotecan ...........................................................................408 Ursodiol ............................................................................... 56
Toremifene .........................................................................209 Ustekinumab ...................................................... 306, 364, 396
Torsemide ............................................................................64
Tositumomab .....................................................................411 V
Trabectedin ........................................................................410
Tramadol ................................................................... 285, 292 Vaborbactam ...................................................................... 149
Trametinib ..........................................................................415 Vaccinia Immune Globulin ................................................ 398
Trandolapril..........................................................................69 Valacyclovir ........................................................................ 170
Tranexamic acid ............................................... 103, 236, 389 Valbenazine ................................................................ 119, 313
Tranylcypromine................................................................127 Valdecoxib .......................................................................... 281
Trastuzumab.....................................................................411 Valganciclovir..................................................................... 171
Travaprost .........................................................................324 Valproic acid ..................................................................... 129
Travaprost + Timolol .........................................................325 Valsartan ............................................................................. 70
Trazodone ........................................................... 125, 126, 265 Vancomycin ............................................................... 161, 335
Trelagliptin .........................................................................191 Vandetanib ......................................................................... 415
Trenbolone ........................................................................216 Vardenafil.................................................................. 263, 267
Treosulfan ...........................................................................406 Varenicline ........................................................................ 430
Treprostinil.........................................................................108 Varicella Zoster Immune Globulin .................................... 398
Tretinoin ............................................................ 366, 376, 410 Vasopressin ................................................................ 222, 261
Triamcinolone ....................... 9, 303, 316, 335, 341, 353, 358 Vecuronium ........................................................................ 433
Triamterene ..........................................................................66 Vedolizumab ........................................................................ 53
Triazolam ............................................................................114 Velaglucerase ..................................................................... 232
Tribenosid + Lidocaine ........................................................59 Velcalcetide ...................................................................... 231
Trichlormethiazide ..............................................................65 Velosulin ............................................................................. 197
Trichloroacetic Acid ........................................................373 Velpatasvir ................................................................. 173, 174
Triclabendazole ..................................................................179 Vemurafenib ..................................................................... 415
Trientine ............................................................................231 Venetoclax .......................................................................... 410
Triethanolamine ...................................................... 294, 339 Venlafaxine................................................................ 125, 292
Trifarotene..........................................................................366 Verapamil ............................................................................ 77
Trifluoperazine + Isopropamide .........................................47 Verapamil + Trandolapril .................................................... 78
Trifluridine ......................................................... 170, 330, 409 Vernakalant .......................................................................... 88
Trihexyphenidyl .................................................................133 Verteporfin ......................................................................... 336
Trimebutine .........................................................................46 Vidarabine .......................................................................... 330
Trimeprazine ......................................................................18 Vigabatrin ......................................................................... 130
Trimetaphan .........................................................................85 Vilanterol .......................................................................... 9, 10
Vilazodone ..........................................................................127
Vildagliptin ........................................................................191
X
Vinblastine ........................................................................408
Xipamide............................................................................... 65
Vincamine ..................................................................... 84, 139
Xipamide + Triamterene ..................................................... 68
Vincristine .........................................................................408
Xylometazoline ........................................................... 20, 342
Vindesine ............................................................................408
Vinflunine ...........................................................................408
Vinorelbine .........................................................................408 Y
Vismodegib .........................................................................410
Vitamin A ...........................................................................439 Yohimbine .................................................................... 80, 265
Vitamin B ...........................................................................439
Vitamin C ...........................................................................439
Vitamin D ...........................................................................440 Z
Vitamin E ...........................................................................440
Vitamin K ................................................................... 423, 440 Zafrilucast ........................................................................... 13
Voglibose ............................................................................191 Zaleplon .............................................................................. 116
Vorapaxar ..................................................................... 96, 100 Zanamivir ........................................................................... 171
Voriconazole ......................................................................166 Zanubrutinib ...................................................................... 415
Vorinostat ...........................................................................416 Zidovudine ......................................................................... 176
Vorozole ..............................................................................210 Zileuton ................................................................................ 13
Vortioxetine ........................................................................127 Zinc Oxide + Castor Oil ..................................................... 360
Voxelotor ............................................................................387 Ziprasidone ........................................................................ 120
Voxilaprevir ........................................................................174 Ziv-Aflibercept ................................................................... 415
Zofenopril ............................................................................. 69
Zoledronic acid ................................................................. 228
W Zolmitriptan ...................................................................... 297
Zolpidem ............................................................................ 116
Warfarin ............................................................................100 Zonisamide ......................................................................... 130
Wintergreen Oil ..................................................................294 Zopiclone ........................................................................... 116
Zuclopenthixol .................................................................. 119
β (Βeta)
β-Sitosterol ......................................................................... 379
β-white ............................................................................... 376

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Self-Assessment Medication’s Guide

19. Index (drug categorization by alphabet)

2015 ‫) لسنة‬2483( ‫رقم اإليداع في دار الكتب والوثائق ببغداد‬

1.1-3. Anti-Muscarinic bronchodilators

1.1-4. Theophylline and Xanthine’s

1.1-6. Cromoglicate & Nedocromil

1.3- Cough preparations, Common

1.4- Respiratory Stimulants

1.5- Pulmonary Surfactant

4. What Can go wrong in the Respiratory tract?

8. Drug Delivery available for Respiratory tract

Self-Assessment Medications Guide 3.1 ed. Page | 4

Drugs used for Cough

Self-Assessment Medications Guide 3.1 ed. Page | 5

Teach the Patient

Self-Assessment Medications Guide 3.1 ed. Page | 6

Using a metered dose inhaler

Using a Breath actuated inhaler

Self-Assessment Medications Guide 3.1 ed. Page | 7

Note1: Combination products for Anti-Muscarinic bronchodilators:

Note: Nobel Prize in Physiology or Medicine 2019

Self-Assessment Medications Guide 3.1 ed. Page | 11

1.1.5 - Leukotriene Receptor Antagonists

Note: Combination products:

1.1.6 – Cromoglicate and Nedocromil

Note4: Salmeterol or Formoterol?

Note5: Again; Salmeterol or Formoterol or Tiotropium?

2nd and 3rd Generation Antihistamines:

Self-Assessment Medications Guide 3.1 ed. Page | 18

Note2: Topical Antihistamine

Note3: Other Antihistamines (As Nasal Sprays & Eye drops)

1.3 - Cough preparations, Common Cold and Flu

B) Common Cold and Flu:

C) Expectorants & Antitussive

Note: American College of Chest Physicians (ACCP) Recommendations

E) Herbal mixtures for Cough

1.4 – Respiratory Stimulants

1.6 – Drugs for Cystic Fibrosis

Part One: Introduction 2.9 - Drugs for Inflammatory bowel

2.7 - Anti-Emetics and Prokinetics

2.8 – Drugs for the treatment of

2. What Can go wrong in the Gastrointestinal tract?

Self-Assessment Medications Guide 3.1 ed. Page | 28

➢ Medications available include:

Self-Assessment Medications Guide 3.1 ed. Page | 29

2.2- Anti-Ulcer (Acid suppression) drugs

A. Proton pump inhibitors (PPIs)

B. Histamine-2 Receptor Antagonists (H2RAs)

D. Other GI ulcers related drugs:

3-Lubricant (stool softeners) Liquid paraffin 6-8 hours

5. Product selection guidelines

Self-Assessment Medications Guide 3.1 ed. Page | 38

E- Guanylate Cyclase-C agonists: This type of laxative changes stool consistency.

Self-Assessment Medications Guide 3.1 ed. Page | 40

Combination products: Stimulant Laxative + Bulk Laxative

C) Stool Softeners (No Longer Recommended)

D) Osmotic laxative drugs

E) Guanylate Cyclase-C agonists: