UR/CMHS

HUYE CAMPUS
MODULE: BMS
UNIT: GENERALPHARMACOLOGY
LEVEL:
ACADEMIC YEAR: 2019-2020
 
 
 
LEARNING OUTCOMES
A.11 Describe various routes of drug administration
A.12 Explain various ways of pharmacological process
B.4 Provide appropriate drugs related to micro-organisms
and parasitic diseases
D.3 Respect drug administration rules in provision of care
 UNIT4: PHARMACOLOGY I
4.1. General information
4.2. Pharmacokinetics
4.3. Pharmacodynamics
4.4. Medical prescription
4.5. Drug classifications
4.6. Antibiotics
4.7. Anti-parasitic drugs
4.8. Solutions, disinfectants and electrolytes
4.9. Analgesics and Anti-inflammatory and antipyretics
TEACHING /LEARNING STRATEGIES

Interactive lecture
Discussion groups
ASSESSMENT STRATEGY
Formative assessment:
Assignments
Group work
Test
Summative assessment: Final exam
RECOMMENDED READINGS

Bhardwaj,U., Bhardwaj,R.(2011). Biochemistry for nurses. India:

Pearson Education
Robert, LS. Janovy, J and Schimidt,P.(2004). Foundations of
Parasitology (7th Ed.). NewYork McGraw-Hill Science
Lehne,RA.(2012). Pharmacology for nursing care (8th Ed.). New
York: Saunders.
Van Leeuwen,A. And Poelhuis-Leth,D.(2011). Davis
comprehensive handbook of laboratory and diagnostic tests with
nursing implications (4th Ed.). Philadelphia: F.A.Davis.Co.
CHAPTER I. INTRODUCTION

Pharmacology is one of the cornerstones of the drug

discovery process. The medicinal chemist may
create the candidate compound, but the
pharmacologist is the one who tests it for
physiologic activity.
CONT.
A promising compound is investigated by many other
scientists including toxicologists, microbiologists,
clinicians, but only after the pharmacologist has
documented a potential therapeutic effect.
 CONT.

Etymologically, pharmacology is the science of drugs

(Greek pharmakos, medicine or drug; and logos, study).
In actual use, however, its meaning is limited to the
study of the actions of drugs.
 CONT.

Pharmacology studies the effects of drugs and how they

exert their effects. There is a distinction between what a
drug does and how it acts. Thus, amoxicillin cures a
strep throat, and cimetidine promotes the healing of
duodenal ulcers.

Pharmacology asks “How”? Amoxicillin inhibits the

synthesis of cell wall mucopeptide by the bacteria that
cause the infection, and cimetidine inhibits gastric acid
secretion by its antagonist action on histamine H2
receptors.
 I.1 HISTORY

Synthetic organic chemistry was born in 1828, when

Friedrich Wohler synthesized urea from inorganic
substances.
In the early 19th century, physiologists performed many
pharmacologic studies.
François Magendie studied the action of nux vomica (a
strychnine-containing plant drug) on dogs, and showed
that the spinal cord was the site of its convulsant action.
His work was presented to the Paris Academy in 1809.
CONT.

In 1842, Claude Bernard discovered that the arrow

poison curare acts at the neuromuscular
junction to interrupt the stimulation of muscle
by nerve impulses.
Pharmacology is held to have emerged as a
separate science only when the first university
chair was established.
CONT.

This occurred in 1847, when Rudolf Buchheim

was appointed professor of pharmacology at the
University of Dorpat in Estonia (then a part of
Russia)
Although Buchheim is credited with turning the
purely descriptive and empirical study of
medicines into an experimental science, his
reputation is overshadowed by that of his
student, Oswald Schmiedeberg
CONT.

Oswald Schmiedeberg (1838–1921) is generally

recognized as the founder of modern
pharmacology

Schmiedeberg obtained his medical doctorate in

1866 with a thesis on the measurement of
chloroform in blood
In 1872, he became professor of pharmacology at
the University of Strassburg, receiving generous
government support in the form of a magnificent
institute of pharmacology
 CONT.

In 1878, he published a classic text, Outline of

Pharmacology,
In his 46 years at Strassburg, Schmiedeberg trained
most of the men who became professors at other
German universities and in several foreign countries
He was largely responsible for the preeminence of the
German pharmaceutical industry up to World War II.
 CONT.

In the United States, the first chair in pharmacology

was established at the University of Michigan in
1890 under John Jacob Abel, an American who had
trained under Schmiedeberg.
Friedrich Serturner, the German pharmacist who
isolated the first alkaloid from opium in 1805,
administered a very large dose (100 mg) to himself
and three friends
 CONT.

All experienced the symptoms of severe opium

poisoning for several days. The alkaloid was named
morphine, for Morpheus, the Greek god of sleep.
Although humans are no longer used as laboratory
animals, they are essential in clinical pharmacology
Clinical trial is a process in which a medication or
other medical treatment is tested for its safety and
effectiveness, either in comparison to placebos or
existing treatments.
 CONT.

Potential drugs first have to be discovered, purified,

characterized,and tested in labs (in cell and animal
studies) before ever reaching clinical trials
Perhaps the first ever clinical trial was James Lind's
demonstration in 1753 that citrus fruits cure scurvy
In all, about 1,000 potential drugs are tested before just
one reaches the point of being tested in a clinical
trial
 CONT.

For example, a new cancer drug has, on average, at

least 6 years of research behind it before it even
makes it to clinical trials.
On average, about 8 years pass from the time a cancer
drug enters clinical trials until it is approved. Drugs
for other diseases have similar timelines.
About 400 cancer medicines were being tested in
clinical trials in 2005
 CONT.
I.2 DEFINITIONS AND SCOPE OF PHARMACOLOGY
 
A. Major divisions of pharmacology are:
1. Pharmacokinetics.
2. Pharmacodynamics.
B. Definitions of terms
Pharmacology: is defined as the study of the making,
ingredients, uses, and actions of drugs. Pharmacology
is also defined as science that deals with
origin/nature/chemistry/effects/use of drugs.
 
 
CONT.

Drugs: substances that are used to treat,

diagnose, or prevent disease.Frequently, we
use the terms drug and medication or medicine
interchangeably.
Medication: is used in reference to drugs used
as a treatment in the practice of medicine.
Medical pharmacology: branch of
pharmacology that studies the interactions
between drugs and the tissues of the human
body.
 CONT.

Pharmacy is a branch of pharmacology that deals with

identification, selection, preservation, combining,
analyzing, standardization, preparing, compounding
and dispensing of medicines for administration to the
patient.
It can also be defined as the art and science of
preparing and dispensing drugs and medicines.
A pharmacist prepares compounds and
dispenses medicines to the patient upon a
written order of a licensed medical practitioner.
 CONT.

The pharmacy can also be a retail shop where medicine

and other articles are sold.
Pharmacognosy is a branch of pharmacology that deals
with the sources of drugs derived from plants and
animals.
Pharmacokinetics is a term derived from the Greek
word 'kinesis' meaning a movement. It deals with the
time course of drug absorption, distribution,
metabolism and excretion. In other words, it means
"What the body does to the drug".
 CONT.
 

Pharmacodynamics (Greek word 'dynamics' means

force) is the study of physiological and biochemical
effects of drugs, mechanisms of action and the
relationship of the plasma concentration of the
drug with its response and the duration of action.
In other words, it means "What the drug does to
the body".
Chemotherapy deals with the use of
chemotherapeutic agents to inhibit or destroy
invading microbes, parasites or cancer cells with
minimal effect on healthy living tissues.
CONT.

Toxicology (Greek 'toxicon' means poison) is the

science of poisons. It deals with the adverse
effects of drugs and poisonous effects of various
chemicals (household, environmental, industrial or
homicidal).
It is also concerned with their source, chemical
composition, action, tests for detection and
antidotes. Clinical toxicology is the science of
detection, diagnosis and treatment of poisoning.
CONT.
Clinical pharmacology is a branch of pharmacology that
deals with the pharmacological effects of drugs in man.
It gives useful data about the potency, usefulness, doses
and toxicity of new drugs for their safe clinical use.
Experimental pharmacology aim is to specify the
therapeutic properties of new natural or synthetic
substances, by testing them systematically on different
living systems, using different techniques that are
specific to pharmacology or borrowed to physiology and
biology
Medicinal chemistry is the science of designing and
synthesis of a new drug.
 CONT.

Pharmacopoeia: It is an official code containing a

selected list of the established drugs and medicinal
preparations with descriptions of their physical
properties, identification, purity, potency and the
minimum standard required and the average dose
for adults.
Each country has its own pharmacopeia. For
example: British Pharmacopeia, United States
Pharmacopeia
 CONT.
Indication: A condition/disease for which a drug is expected to
have a beneficial effect or the most common use of a drug in
treating a condition.
E.g.: Bronchodilators in case of Asthma
Contraindication: Situation in which a drug should not be used
because it may do harm to the patient or have no effect at all.
E.g.: Patient with gastritis should not take NSAIDs
Tetracyclines are strictly contraindicated for pregnant mothers
CONT.
The dose : A specific quantity of a therapeutic drug or
agent taken at any one time or at specified intervals
It is the amount of drug taken at any one time. This can be
expressed as the weight of drug (e.g. 250 mg), volume of
drug solution (e.g. 10 mL, 2 drops), the number of
dosage forms (e.g. 1 capsule, 1 suppository) or some
other quantity (e.g. 2 puffs).
The dosage regimen: is the frequency at which the drug
doses are given. Examples include 2.5 mL twice a day,
one tablet three times a day, one injection every four
weeks.
I.3 NATURE/SOURCES OF DRUGS

Drugs are obtained from different sources:

Minerals: Liquid paraffin, magnesium sulfate, magnesium
trisilicate, kaolin, etc.
Animals: Insulin, thyroid extract, heparin and antitoxin
sera, etc.
Plants&Herbal: Morphine, digoxin, quinine, atropine,
castor oil, etc.
 CONT.
Synthetic source: Aspirin, sulphonamides, paracetamol,
zidovudine, pethidine, amodioaquine, doputamine etc.
Microorganisms: Penicillin, streptomycin and many other
antibiotics.
Genetic engineering: Human insulin, human growth
hormone, etc
Biotech: Erytropoitin (EPO)
 
I.4 PHARMACEUTICAL PROPERTIES OF DRUGS
 

A. DRUG CLASSIFICATION
 1. Legal definition of drug
 Natural or synthetic substance which,when taken
into a living body, affects its functioning or
structure, and is used in the diagnosis, mitigation,
treatment, or prevention of a disease or relief of
discomfort.Also called legal drug or medicine. A
legal or medicinal drug (E.g.: amphetamines),
however, can be harmful and addictive if misused.
2. DRUG CLASSES

Definition: A class of drugs is a group of drugs that have

similar characteristics; they may cure the same diseases,
have similar chemical structures or work in the same
way.
Medications can be classified in various ways, such as by
chemical properties, mode or route of administration,
biological system affected, or therapeutic effects. An
elaborate and widely used classification system is the
Anatomical Therapeutic Chemical Classification System
(ATC system). The World Health Organization keeps a
list of essential medicines. Thus, drugs can be classified
as antipyretics: reducing fever (pyrexia/pyresis),
analgesics: reducing pain,etc.
EXAMPLES:

Basing on body system, drugs may be classified as

follows:
Respiratory medications
Cardiac medications
Drugs of the digestive system
Nervous system medications, etc.
According to their function or use, they may be classified
in:
Nonsteroidal anti-inflammatory medications
Narcotic analgesics
Antidepressants, etc.
 CONT.
According to their chemical makeup (chemical properties), they
may be classified as follows:
Aminoglycosides
Estrogens
Opioids, etc.
Classification systems enable to readily identify the similarities
and differences among a large number of medications within
and outside of a particular classification.
CONT.
One of the best and most efficient ways to master
pharmacology is to become familiar with the
classifications of medications and then to focus on the
similarities and differences of medications within the
same classification
The drug can easily be classified into different ways
according to the classification system used. Thus,
Aspirin is classified as a salicylate when one bases on
Chemical class and as an analgesic when one bases on
Pharmacological class (therapeutic effect)
3. DRUG USES

Drugs can be used for any of the following purposes:

a. Symptomatic treatment i.e Analgesics like paracetamol
b. Prevention i.e vaccines
c. Diagnostic drugs i.e Contrast products
d. Curative i.e Antibiotics
e. Health maintenance or modifification, correctors i.e
Contraception
 B. TYPES OF DRUG NAMES/DRUG
NOMENCLATURE
A drug may be known for any of four names. These are names
assigned to the drug at different times in its development.
a. The Chemical name
It identifies the chemical structure of the drug. This is usually
the first name assigned to a drug when it is developed. It
actually identifies the atomic/molecular structure of the
dug.
b. The Generic name
It is often a shorter version of the chemical name. This name
is assigned to the drug before it is officially listed. It is an
abbreviated form of chemical name. U.S. Adopted Names
(USAN) Council.It is never capitalized.
CONT.
c. The Trade name
It is the name given to it by the manufacturer. A
particular drug may have several trade names,
depending on how many companies are producing and
marketing it. It is a Copyright ® and always capitalized.
d. The Official name
It is the name assigned to the drug by the United States
Pharmacopoeia or National Formulary. This indicates
that the drugs meet their requirements. The official
name is commonly the generic name followed by the
initials U.S.P. or N.F. Usually same as generic name.
E.G.
E.g.: Ethyl 1-methyl-4-phenylisonipecotate hydrochloride
(chemical name)
Meperidine hydrochloride (Generic name)
DEMEROL HYDROCHLORIDE ® (Trade name)
Meperidine hydrochloride, USP (Official name)
Note: The superscript ® is registered by the U.S. Patent Office
and approved by the FDA (Food and Drug Administration)
 
C. DRUG DOSAGE FORMS

C.1. DEFINITION OF DOSAGE FORM

Drugs are rarely administered in their original pure state.

They are converted into suitable formulations which are
called dosage forms. Every dosage form is a combination
of the drug and other non-drug components.
The non-dug components are known as “additives”. The
additives are used to give a particular shape to the
formulation, to increase its stability and also to increase its
palatability as well as to give more elegance to the
preparation.

 
C.2. REASONS OF CONVERTING DRUGS INTO
DOSAGE FORMS
 

Transformation of drug into different dosage forms is done

for the following reasons:
1. To protect the drug from oxidation (e.g. Vitamin C,
Ferrous sulfate), hydrolysis (aspirin) and reduction (e.g.
coated tablets, sealed ampoules).
2. To protect the drug from destructive effect of gastric
juice (HCl) of the stomach after oral administration (e.g.
enteric coated tablets).
3. To provide a safe and convenient delivery of accurate
dosage.
4. To conceal the bitter (e.g. chloramphenicol), salty or
obnoxious taste or odour of a drug substance (e.g.
capsules, coated tablets and flavoured syrups etc).
CONT.
5. To provide for the optimum drug action through
inhalation therapy (e.g. inhalation aerosols and
inhalants).
6. To provide for the drug into one of the body cavities
(e.g. rectal suppositories).
7. To provide for the maximum drug action from topical
administration sites (e.g. creams, ointments, ophthalmic
preparations and E.NT. [Ear, Nose and Throat]
preparation).
CONT.
8. To provide sustained release action through
controlled release mechanism (e.g sustained release
tablets, capsules and suspensions).
9. To provide liquid dosage form of the drugs soluble in
a suitable vehicle (e.g. solutions)
 
C.3. DIFFERENT TYPES OF DRUG DOSAGE
FORMS (DRUG PREPARATIONS)
 
 

1. SOLID
Capsules
Effervescent granules
Lozenges
Pessaries
Tablets: coated or uncoated
Suppositories (for vaginal use)
 
CONT.
2. SEMISOLID
Creams
Jellies
Suppositories (E.g.: Diclofenac suppository)
Ointments (E.g.: Tetracycline Ophthalmic ointments)
 
 
3. LIQUID
Aromatic water
Ear drops
Eye drops
Nasal drops (E.g.: Otrivin, normal saline)

 
CONT.
Suspensions
Gargles
Injections (E.g.: Gentamicin)
Lotions
Mouthwashes
Syrups

4. GAS
Aerosols
Inhalation
5. MISCELLANEOUS
Transdermal drug delivery systems
Implants
 
C.4. EXAMPLES OF DRUG DOSAGE FORMS

 TABLETS
Tablets are unit solid dosage form of medicament or
medicament without suitable diluents
 CAPSULE
A pill in the form of a small rounded gelatinous container
with medicine inside
 SUPPOSITORIES
Suppositories are special shaped solid dosage form of
medicament for insertion into body cavities other than
mouth (Usually in the rectum, vagina or urethra)
CREAMS
Creams are viscous liquid or semisolid emulsions intended for
application to the skin i.e. for external use.

JELLIES
Jellies are transparent or non-greasy semisolid preparations meant for
external application to the skin or mucous membrane. They are used
for medication or lubrication purposes
OINTMENTS
Ointments are the soft semisolid, greasy preparations meant for
external application onto the skin or mucous membrane (rectum and
nasal mucosa)
 CONT.
 
 

 PASTES

Pastes are semisolid preparations meant for external

application to the skin. They generally contain large
amount of finely powdered solids such as starch, zinc
oxide, calcium carbonate etc.
 
OPHTHALMIC OINTMENTS
Ophthalmic ointments are meant for application to the eye.
They should be sterile and free from irritation
 
CONT.
SYRUPS
Syrups are liquid oral preparations in which the vehicle is a concentrated aqueous
solution of sucrose or other sugar
If the syrup is clear it is called elixir and
If it is suspension it is called mixtures.
 AROMATIC WATER
 Aromatic waters are also known as medicated waters. They are dilute, usually
saturated, aqueous solutions of volatile oils (e.g. peppermint oil, cinnamon oil) or
volatile substances (e.g. camphor).
LINCTUSES
Linctuses are viscous, liquid, oral preparations that are usually prescribed for the
relief of cough
 GLYCERIN OR GLYCERITES
Glycerites are the viscous preparations in which the drug is dissolved in glycerin with
or without heating. They are generally used as antiseptic or anti-inflammatory
preparations
 
CONT.
LINIMENT
Liniments are liquid, semi-liquid or occasionally semi-solid preparations intended for
application on the skin.
They may be alcoholic or oily solutions or emulsions
LOTIONS
Lotions are liquid preparations for external application without friction.
They are either dabbed on the skin or applied on a suitable dressing and covered with
water proof material to reduce evaporation.
e.g. Copper and zinc sulfate lotion is used for impetigo
 
GELS
Gels are aqueous colloidal suspensions of the hydrated forms of insoluble medicaments
e.g. aluminium hydroxide gel, used as antacid
 
TINCTURES
These are alcoholic preparations containing the active principles of vegetable drugs.
 CONT.

SPIRITS
Spirits are alcoholic or hydroalcoholic solutions of volatile substances. Most are used as
flavouring agents but a few have medicinal value. E.g. Chloroform Spirit, Lemon Spirit,
Compound Orange Spirit
 INFUSIONS
(i) Fresh Infusions are made by extracting vegetable drugs for a short time with cold or boiling
water (cf. making of tea). They quickly deteriorate as a result of microbial contamination
and therefore must be used within 12 hours.
(ii) Concentrated infusions are made by cold extraction with 25 % alcohol. The alcohol
preserves the product for an indefinite period.
Dilution of 1 part of concentrated infusions with 10 parts of water gives a preparation
corresponding fresh infusion.
E.g. Concentrated Compound Gentian Infusion
concentrated Senega Infusion.
 
C.5. PARENTERAL PRODUCT PACKAGING

 
Ampoules:
Sterile
Sealed glass or plastic container
Contain a single liquid dose
Vials:
Glass or plastic container
Sterile liquid dose
Sealed with a rubber diaphragm
Either single or multiple dose
 
 
 
 
SOLID FORMS OF DRUGS/MEDICINE
Effervescent
Tabletstablets

Effervescent tablets
PILLS AND CAPSULES, SHWABLES TABLET
LIQUID FORM OF DRUG
 TO MANAGE PATIENTS’ DISEASES WITH MEDICINES

When selecting a pharmacological product always think of

HOW DOES THE DRUG GET THE SITE OF
ACTION? In quantity and in velocity of entering and
leaving
HOW DOES IT WORK IN THE BODY?
PHARMACOKINETI
CS
In onset of action and effects
PHARMACODYNAM HOW MAY IT HARM OR CAUSE INJURY?
IC In serious and tolerable side effects

TOXICOLOGY WHICH AMOUNT IS NEEDED AND FOR HOW LONG?

In patient’s compliance and outcomes
THERAPEUTIC
DETERMINANT OF PHARMACOTHERAPY OUTCOMES

Factors influencing pharmacologic response

Patient’s health state,
Patient’s genetic heritage,
• Drug-drug interaction,
• Food interaction,
Prescribing guidelines
• Adequacy
• Adherence / Compliance
 D. PRINCIPLES AND WAYS/ROUTES OF DRUG
 
ADMINISTRATION
1. ROUTES OF DRUG ADMINISTRATION
 
The main routes of drug administration are
Enteral: oral, sublingual, rectal
Parenteral: intravascular (intravenous), intramuscular,
subcutaneous, intrathecal (in CSF)
Others: inhalation, intranasal, topical (vaginal), transdermal
 
ENTERAL ROUTES
 
 

The drug is placed directly in the GI tract. The

enteral routes include the following:

Oral route: swallowing

Sublingual route: placed under the tongue
Rectal route:absorption through the rectum
 
 
 
Oral route (per orum/po )

Giving a drug by mouth is the most common route of

administration but it is also the most variable, and requires
the most complicated pathway to the tissues.Little absorption
occurs until the drug enters the small intestine.
 
Advantages:
 
Convenient: can be self-administered, pain free, easy to take
and possible recall in case of overdose
Absorption: takes place along the whole length of the GI tract
Cheap (economical): compared to most other parenteral routes
 
 CONT.
Disadvantages:
 Unpleasant taste of some drugs
Irritation to gastric mucosa: nausea and vomiting
Destruction of drugs by gastric acid and digestive juices
Sometimes inefficient: only part of the drug may be absorbed
Effect too slow for emergencies
Unable to use in unconscious patients or those who have had
GI surgery
First-pass effect: drugs absorbed orally are initially transported
to the liver via the portal vein
 
 
 
Sublingual route

Placement under the tongue allows the drug to diffuse

into the capillary network and therefore to enter the
systemic circulation directly.
When only small amounts of drugs are required to gain
access to the blood, the sublingual route may be very
satisfactory.
Drugs are absorbed from the mouth straight into the
systemic circulation without entering the portal system
and so escape first-pass metabolism by the liver.

E.g.: nitroglycerin to treat angina pectoris .

 ADVANTAGES
 Rapid absorption
Drug stability: because the stomach is bypassed,acid-
liability and gut-permeability is not important
Avoid first-pass effect
 Disadvantages:
 Inconvenient
Small doses
Unpleasant taste of some drugs
 
 

 
 Rectal route ( per rectum)

The rectal route way administration (RWA) is a way

of administering drugs into the rectum to be
absorbed by the rectum's blood vessels and into the
body's circulatory system which distributes the drug
to the body's organs and various systems where the
drug elicits its effects.
50% of the drainage of the rectal region bypasses the
portal circulation; thus the biotransformation of
drugs by the liver is minimized.
 
ADVANTAGES

Avoid destruction of the drug by intestinal enzymes

or by low pH in the stomach
Useful for unconscious patients (postoperative) and
children
Useful if patient is nauseous or vomiting
Good for drugs affecting the bowel such as
laxatives
Can be used for both local effects and systemic
effects
 
DISADVANTAGES

Irritating drugs are contraindicated

Erratic absorption of drugs
This route may be not well accepted
Contraindicated in immunocompromised patients
because trauma can lead to abscess formation
1.2 PARENTERAL ROUTES
 

Parenteral describes the introduction of nutrition,

a medication, or other substance into the body
via a route other than the gastro-intestinal tract,
especially via infusion, injection or implantation.
Parenteral nutrition refers to providing nutrition
via the veins.
CONT.
Parenteral administration is used for drugs that are poorly
absorbed from the gastrointestinal (GI) tract, and for
agents such as insulin that are unstable in the GI tract.
Parenteral administration is also used for treatment of
unconscious patients and under circumstances that
require a rapid onset of action.
The three major parenteral routes are
Intravascular (intravenous or intra-arterial)
Intramuscular
Subcutaneous
 
OTHER PARENTERAL ROUTES INCLUDE
  Intradermal, Intraosseous infusion (into the
bone marrow) is, in effect, an indirect
intravenous access because the bone marrow
drains directly into the venous system.
This route is occasionally used for drugs and fluids
in emergency medicine and pediatrics when
intravenous access is difficult.
  Intracerebral (into the brain parenchyma)
  Intraarticular, intraperitoneal, etc
 
 1.2.1 INTRAVASCULAR ROUTES
1.2.1.1 Intravenous route
Intravenous (IV) injection is the most common parenteral
route. For drugs that are not absorbed orally, there is
often no other choice.
ADVANTAGES

Rapid onset of action because the drug is injected

directly into the bloodstream
Useful in emergencies and in patients who are
unconscious
The drug avoids the GI tract and first-pass
metabolism by the liver
Smaller doses generally are required than the other
routes but cost is high
 
 
 
DISADVANTAGES

High concentration attained rapidly so that the

injected amount of drug cannot be recalled by
strategies such as emesis or binding to activated
charcoal
Risk of embolism (obstruction of blood vessel)
May introduce bacteria through contamination;
may also induce hemolysis
Pain at application site
No self administration facility
CONT.

1.2.1.2 Intra-artery route

Similar properties, advantages and disadvantages of intravascular route.
Intra-artery route is specially used when high drug concentration in
specific tissue is required than other tissue for: diagnostic purpose and
chemotherapy
1.2.2 Intramuscular route
 Drugs administered intramuscularly can be aqueous solutions or
specialized depot preparations; often a suspension of drug in a non-
aqueous vehicle, such as ethylene glycol or peanut oil.
Absorption of drugs in aqueous solution is fast, whereas that from depot
preparations is slow. Drug passes through capillary walls to enter the
blood stream.
 
  
 
 CONT.

Intramuscular (IM) route is preferred or indicated when:

 The client cannot swallow a drug
The client vomits or has a gastric suction
The drug action can be hampered or destroyed by GI secretions
Quicker action needed compared to oral route
The drug is irritating to GIT
The substance is irritating to subcutaneous tissues
Rapid drug action is desired
Amount of drug (to be injected) is more than what
subcutaneous tissues can absorb
 
ADVANTAGES OF INTRAMUSCULAR INJECTIONS
Medications are completely absorbed.
Absorption is quicker than subcutaneous route due to
increased vascularisation.
IM is a safer technique to use on thin patients.
IM is a safer technique to use with an agitated or
combative patient.
 
DISADVANTAGES OF INTRAMUSCULAR INJECTIONS

There is increased discomfort with an

intramuscular injection for some drugs (pain at
the injection site)
There is a risk of hitting a nerve, causing nerve
damage.
There is a risk that an abscess may form at the
injection site.
 
1.2.3 SUBCUTANEOUS ROUTE
Drug is injected beneath the skin and permeates capillary walls to
enter blood stream.
Absorption from the site of injection is dependent on local blood
flow. Concurrent administration of vasoconstrictor will slow
absorption.
For example, minute amount of epinephrine is sometimes used in
combination with a drug to restrict its area of action. Epinephrine
acts as alocal vasoconstrictor and decreases removal of a drug,
such as lidocaine (local anesthetic), from the site of
administration.
Examples of drugs given by this route are insulin and sodium
heparin, neither of which is absorbed orally, and both of which
should be absorbed slowly over many hours.
 
 
 
 
 1.2.4 OTHER PARENTERAL ROUTES
 
 

1.2.4.1 Intra-articular route

 
Injected directly into bone joints. E.g.: Hydrocortisone
 
1. 2.4.2 Intrathecal/lntraventricular route
 
It is sometimes necessary to introduce drugs directly into the cerebrospinal
fluid (CSF).The drug is injected into subarachnoid space of spinal cord
e.g. spinal anaesthetics
1.2.4.3 Intraperitonial: Injections given into the abdominal cavity e.g. infant
saline, glucose
 
 
 1.3 OTHER ROUTES/WAYS OF DRUG
 
ADMINISTRATION
1.3.1. Inhalation
Inhalation provides the rapid delivery of a drug across the
large surface area of the mucous membranes of the
respiratory tract and pulmonary epithelium, producing an
effect almost as rapidly as by intravenous injection.This route
of administration is used for drugs that are gases and volatile
agents (for example, some anesthetics), or those that can be
dispersed in an aerosol (for example, salbutamol also known
as ventolin)
The route is particularly effective and convenient for patients
with respiratory complaints (for example, asthma or chronic
obstructive pulmonary disease) as a drug is delivered directly
to the site of action and systemic side effects are minimized.
1.3.2 TOPICAL/LOCAL ROUTE

Topical application is used when a local effect of

the drug is desired. Used for most dermatologic
and ophthalmologic preparations. It is the same
case for vaginal route.
E.g.: Clotrimazole is applied as a cream to the skin
in the treatment of dermatophytosis.
Atropine is instilled directly into the eye to
dilate the pupil and permit measurement of
refractive errors
 
 VAGINAL WAY ADMINISTRATION

 
Vaginal medicines are topical agents prepared specifically for
insertion into a woman's vagina. They are compounded in the
form of a cream, foam, gel, tablet, or suppository, and are
absorbed through the vaginal mucosa.
Vaginal medicine in the form of a cream, foam, gel, or tablet
is administered using a specific applicator that is provided by
the manufacturer. Suppositories have the medicine suspended
in wax and are shaped like a small bullet. They are inserted
into the vagina with the index finger.
Vaginal medicines are most often administered at bedtime, as
the reclined position enhances medication absorption.
 
Vaginal delivery can be used for systemic as well as local
action.
Traditionally, vaginal delivery was restricted to locally
acting drugs such as: Antibacterial, anti-fungal, anti-
protozoal, anti-viral, spermicidal, labour-inducing agents,
prostaglandins and steroids.
But gradually, the potential for systemic delivery through
vagina was explored because of its large surface area, high
vascularity, and permeability to a wide range of compounds
including peptides and proteins.
It offers a favorable alternative to oral and parenteral route.
 
Vaginal medicines are most commonly used to
combat infection, inflammation, or dryness of the
vaginal mucosa. Other types of vaginal medicines
include spermicides (i.e., to prevent conception),
chemotherapy (i.e., for cancer treatment), and
aborticides (i.e., for inducing labor).
However, several drawbacks like cultural sensitivity,
personal hygiene, gender specificity, local irritation
and influence on sexual intercourse need to be
addressed during the design of a vaginal
formulation.
PRECAUTIONS

Vaginal tissue can be traumatized by the forceful

use of applicators or fingernails during medicine
administration, so medications should be
introduced into the vagina gently.
Patients should be encouraged to relax, as this
will decrease resistance to the mode of
insertion. One should not attempt to insert
vaginal medication when a patient is confused
and combative.
COMPLICATIONS
Tissue irritation or allergic reactions can result from vaginal
medications. If irritation, swelling, or redness of the
tissue is apparent, or if the patient complains of pain or
burning, the next dose of medicine should not be given
until the physician has been consulted
 1.3.3 Transdermal route
 This route of administration achieves systemic effects by
application of drugs to the skin, usually via a
transdermal patch.
The rate of absorption can vary markedly depending upon
the physical characteristics of the skin at the site of
application. This route is most often used for the
sustained delivery of drugs, such as the antianginal
drug, nitroglycerin.
ROLE OF NURSE AND MIDWIFE IN
ADMINISTRATION OF DRUGS
 It is the nurse’s and midwife’s responsibility to safely prepare
and give the drugs ordered by the physician. If not given
properly, medicines can be harmful or even fatal. Know the
following elements before administration of any drug:
the doses of the drug which are safe to administer
the dose of the drug which has been prescribed for the
patient
the method of administration
the drug's actions and expected effects
possible side effects (unintended effects).

 
CONT.

It is also important to know if a patient is allergic

to a drug. Ask your patient about any reactions
he/she had to drugs in the past.
For safe administration of drugs: give the right
dose of the right drug to the right patient in the
right route at the right time.
When giving medications, the nurse needs to be
aware of possible interactions between the
patient’s different drugs. Drug interactions can
sometimes harm the patient.
PATIENT’S RIGHTS

  Because of the risks involved in drug administration, patients

have the right to:
be informed of the name, purpose, action & potential side
effects of drugs
refuse a medication regardless of the consequences
receive labelled medications safely in accordance with the six
(6) rights
be adequately informed of the experimental nature of any drug
and sign a written consent
Not receive unnecessary medications
CONT.
The nurse is also responsible for ensuring that they have
the knowledge to ensure the correct administration of
drugs. This includes pharmacology, anatomy and
physiology, and legal issues.
Medication charts are legal documents and must be
completed accurately and unambiguously in order to
ensure that patient Medication Charts should be
written legibly in the prescriber’s own handwriting and
include:
CONT.
Patient’s surname, first name, medical record number
(MRN), ward/clinic
- If a patient ID label is used it must be affixed to every
medication chart and signed for verification by the
prescriber.
Prescriber’s printed name, signature and date of order: the
prescriber’s full signature and date of order must be
written for EACH DRUG ordered
Weight should be provided for any drug dosed by weight.
 CONT.

N.B. Each medication order must be legible, complete

and unambiguous so that the correct patient is
administered the correct drug at the appropriate
dose.
A nurse cannot administer the drug and a pharmacist
cannot dispense a drug to a patient unless all details
are correct and complete. Every registered nurse is
legally responsible for the correct administration of
drugs
 3. THE SIX RIGHTS OF MEDICATION
ADMINISTRATION
The midwife/nurse has to know the following six rights of
drug administration as well as the specific considerations
before administering any medication. These six rights are:
 1. Right Patient. Is this the right patient for the drug?
While there may be indications for giving a drug, there
may be a need of looking at contraindications such as
allergies; mental status; GI status; heart rate, etc.
2. Right Medication. Drugs come in similar ampoules,
nebulas or vials. Check the drug three times.
CONT.

First as you remove it from the kit, box, or cabinet; check

the name, dose and concentration; also check for expiry date
and fluid clarity.
Second, check again as you draw up the drug into the
syringe, pour into a nebulizer mask, or doling tablets to a
patient.
Third, immediately before administration, show the drug
container to your partner, asking for confirmation is a
further way to ensure the right drug is given. If uncertain,
do not administer. Syringes with left over drug must be
labeled with name, concentration.
CONT.
3. Right Dose. Double check your calculations, have your
partner or colleague also check when practical
4. Right Route. Make sure you administer through the right
way specifically because any mistake may cause harm to
client
5. Right Time. Most of the time nurses/midwives will give
drugs to patients on a schedule, drugs can also be given
in urgent or emergency situations.
CONT.
I n all cases, timing can still be important. Giving
Nitroglycerin sprays to a patient too rapidly can result in
the patient becoming hypotensive; in order to help lower
the threshold for defibrillation, epinephrine must be
repeated on time.
6. Right Documentation. As the nurse/midwife is required
to document vital signs, splinting, bleeding control etc.,
he/she must also document all drugs given in the field
and the patient’s response to them.
All other providers need to know what has been done for
the patient so they can continue to provide care.
SPECIAL POPULATION CONSIDERATIONS

 
 Pregnant patients
 Pediatric patients
 Geriatric patients
  
 
PREGNANT PATIENTS

 When the patient is a female of childbearing years, one

must consider the possibility that she is pregnant. The
treatment of pregnant patients means that you will be
treating two patients. Potential risks to the fetus by a drug,
must be outweighed by possible benefits to the mother by
the drug. Two pharmacological problems arise from
pregnancy: the potential for drugs to harm the fetus as well
as changes in the anatomy and physiology of the mother.
 
CONT.
The mother’s heart rate, cardiac output and her blood
volume all increase as she is entirely supporting the
fetus, as a result the onset and duration of action of many
drugs can be affected by this altered maternal
physiology.
The ingestion of teratogenic drugs in the first trimester
has the potential to deform, injure or to kill the fetus.
Drugs administered in the third trimester may cross the
placental barrier and harm the fetus. They may also be
communicated to a newborn during breastfeeding.
 
 PEDIATRIC PATIENTS

Small body mass, therefore, adjust dosages

Difficult coordinating inhalation of medicines
Reluctant to take medicines
ELDERLY: GERIATRIC PATIENTS

Multiple drugs/multiple illnesses

May not be sure as to why they take the medicines
As these special people take more medicines, there is a
greater chance of drug interactions
Slower metabolism of drugs due to aging
The nurse/midwife has to transport medicines with patient
CHAPTER II. PHARMACODYNAMICS
 II.1 INTRODUCTION

Pharmacodynamics is a description of the many different ways

that drugs affect the body.
When a drug is swallowed, ingested or absorbed through the skin,
in most cases it will enter the bloodstream and circulate
throughout the body interacting with a number of target sites.

In some cases a drug may act in only one specific part of the body,
depending on the properties and administration.
In other case, the interaction with the target site will usually
produce the desired effect, even though interaction with other
cells, organs and tissues may result in what we know as side
effects.
 
 
 CONT.

While some drugs act on many different tissues and organs,

others affect mainly a single organ or system.
Atropine is given to relax muscles in the gastrointestinal tract
but can also relax the muscles of the eye, respiratory tract and
decrease the secretions of the mucous glands and sweat glands.
On the other hand, Digitalis, which is given for heart failure,
works on the heart to increase its pumping efficiency. The
answer to how drugs know where to exert their effects lies in
how they interact with cells or enzymes.
 CONT.

In many cases a drug will bind to cells by means of receptors on

the surface of the cell. This allows the activity of the cell to be
influenced by chemicals like drugs or hormones that are located
outside the cell.
The specific configuration of the receptor allows only a drug
which fits precisely to attach to it.
Although some drugs attach only to one type of receptor, there
are others that can attach to several types of receptors
throughout the body.
For example, pain relieving drugs attach to the same receptors in
the brain as do endorphines.
CONT.

There is a class of drugs called agonists which activate

or stimulate their receptors to trigger a response that
will either increase or decrease the cell's function.
A second class of drugs called antagonist will block the
access or binding of agonists to their receptors.
CONT.
In some cases such as asthma, agonists and
antagonists are used in different but complimentary
approaches to treatment.
Another important target for drug action are enzymes.
Enzymes help transport vital chemicals, regulate the
rate of chemical reactions or serve other transport,
regulatory or structural functions. Drugs targeted at
enzymes are classified as inhibitors or inducers.
CONT.

Affinity: the mutual strength of the bond between

a drug and its target
Intrinsic activity: the measure of the drug's ability
to produce a pharmacologic effect when bound to
a receptor
Those are two drug properties that are important
to drug activity in the body.
CONT.

The potency of a drug refers to the amount of drug needed

to produce a given effect.
The efficacy of a drug refers to the potential maximum
therapeutic response which a drug can produce.
Drug tolerance refers to what occurs when the body
adapts to the continued presence of a drug.
CONT.

Drug tolerance is a term used to describe a

decreased response to a drug, requiring an
increase in dosage to achieve the desired effect.
Drug tolerance may develop when a patient
takes certain drugs, such as the narcotics and
tranquilizers, for a long time.
The individual who takes these drugs at home
increases the dose when the expected drug
effect does not occur.
CONT.

The development of drug tolerance is a sign of drug

dependence.
Drug tolerance may also occur in the hospitalized patient.
When the patient receives a narcotic for more than 10 to 14
days, the nurse suspects drug tolerance (and possibly drug
dependence). The patient may also begin to ask for the
drug at more frequent intervals
 
 
 
 
Drug abuse and drug dependence represent
different ends of the same disease process.
Drug abuse is an intense desire to obtain increasing
amounts of a particular substance or substances to
the exclusion of all other activities.
 Drug dependence is the body's physical need, or
addiction, to a specific agent
 
CONT.

Although many of the drugs that are currently being used were
discovered by experimental trial and observation, it is good to
note that no drugs are perfectly effective and completely safe.

Due to this, it is important that a doctor assess the drugs

benefits and risk with every situation that requires prescription
drug treatment.
 
 DRUG ABUSE AND DEPENDENCE

 Substance abuse is the overindulgence in

and dependence of a drug or other
chemical leading to effects that are
detrimental to the individual's physical and
mental health, or the welfare of others.
Substance abuse refers to the harmful or
hazardous use of psychoactive substances,
 
including alcohol and illicit drugs.
 
 
 
 
 
 
 
 
CONT.
Psychoactive substance use can lead to
dependence syndrome a cluster of behavioural,
cognitive, and physiological phenomena that
develop after repeated substance use and that
typically include a strong desire to take the drug,
difficulties in controlling its use,
persisting in its use despite harmful
consequences, a higher priority given to drug use
than to other activities and obligations, increased
tolerance, and sometimes a physical withdrawal
state.
 
 II.2 OTHER DEFINITIONS
 
a. Efficacy: Degree to which a drug is able to produce the desired
response
b. Potency: Amount of drug required to produce 50% of the maximal
response the drug is capable of inducing
c. Effective Concentration 50% (ED50): Concentration of the drug
which induces a specified clinical effect in 50% of subjects
d. Lethal Dose 50% (LD50): Concentration of the drug which induces
death in 50% of subjects.
e. Margin of Safety: Margin between the therapeutic and lethal doses of
a drug
CONT.
f. Dose-Response Relationship
Drug induced responses are not an “all or none” phenomenon
Increase in dose may:
 Increase therapeutic response
 Increase risk of toxicity
 
g. Median lethal dose: This is the dose (mg/kg), which would be expected to
kill one half of a population of the same species and strain.
h. Median effective dose: This is the dose (mg/kg), which produces a desired
response in 50 per cent of test population.
i. Therapeutic index (T.I): It is an approximate assessment of the safety of the
drug. It is the ratio of the median lethal dose and the median effective dose.
Also called as therapeutic window or safety.
Calculation: LD50/ED50
 
CONT.
N.B.: The larger the therapeutic index, the safer is the drug.
Penicillin has very high therapeutic index, while it is
much smaller for the digitalis preparation.
 A. Receptor and non-receptor mechanisms: Most of the
drugs act by interacting with a cellular component called
receptor. Some drugs act through simple physical or
chemical reactions without interacting with any receptor.
Receptors are protein molecules present either on the cell
surface or within the cell. E.g. adrenergic receptors,
cholinoceptors, insulin receptors, etc.
 
CONT.

The endogenous neurotransmitters, hormones, autacoids

and most of the drugs produce their effects by binding
with their specific receptors.
Aluminium hydroxide and magnesium trisilicate, which are
used in the treatment of peptic ulcer disease act by non-
receptor mechanism by neutralizing the gastric acid.
Many drugs are similar to or have similar chemical groups
to the naturally occurring chemicals and have the ability
to bind onto a receptor where one of two things can
happen: either the receptor will respond or it will be
blocked. A drug, which is able to fit onto a receptor, is
said to have affinity for that receptor.
 B. SITE OF DRUG ACTION

A drug may act:

(i) Extracellularly e.g: osmotic diuretics, plasma
expanders.
(ii) On the cell surface e.g.: digitalis, penicillin,
catecholamines
(iii) Inside the cell e.g.: anti-cancer drugs, steroid
hormones.
 C. Structural activity relationship
 
CONT.
The activity of a drug is intimately related to its chemical
structure. Knowledge about the chemical structure of a
drug is useful for:
(i) Synthesis of new compounds with more specific actions
and fewer adverse reactions
(ii) Synthesis of competitive antagonist and
(iii) Understanding the mechanism of drug action.
II.3 DRUG-RECEPTOR INTERACTIONS
 

Drugs typically exert their effects by interacting

with a macromolecule (receptor)
Drug-receptor interactions have been important in:
new drug development
therapeutic decisions
Major roles of receptors:
Determines quantitative relationships between drug
dose and pharmacological effect.
Determines drug action selectivity
Mediates antagonist (blocking) as well as agonist
(activating) effects
MOLECULAR CHARACTERISTICS OF RECEPTORS

Usually proteins, specifically regulatory proteins

mediating effects of:
neurotransmitters
autacoids (histamine, serotonin, endogenous
peptides, prostaglandins, leukotrienes)
hormones
CONT.

Some receptors are enzymes, may be inhibited or

occasionally activated by drugs
e.g. dihydrofolate reductase (receptor) versus
methotrexate(drug inhibitor)
Other receptors are transport proteins:
e.g. Na/K ATPase (receptor for digitalis glycosides
{digoxin (Lanoxin, Lanoxicaps), digitoxin(Crystodigin)}
Still other receptors are structural proteins:
Tubulin: receptor for certain anticancer drugs and anti-
inflammatory drugs
INTRACELLULAR RECEPTORS

lipid-soluble drugs, after crossing the cell

membrane barrier, interact with intracellular
receptors.
Example: nitric oxide (NO)
The agents below bind to DNA response
elements that control transcription:
thyroid hormone
corticosteroids
mineralocorticoids
sex steroids
vitamin D
CONT.

Drug antagonists bind either to the receptor

itself or to some components of the effector
mechanism to prevent the agonist action.
Antagonists themselves have no effect.
If the antagonist-mediated inhibition can be
overcome by increasing agonist concentration
ultimately reaching the same maximal effect,
the antagonist is termed competitive.
CONT.

Competitive inhibition is based on reversible

binding at receptor sites.
With competitive inhibition, the dose-effect
curve will be shifted to the right.
With competitive inhibition, the maximal drug
effect will not be affected.
CONT.

By contrast, a non-competitive antagonist will

prevent the agonist from producing a maximal
effect (and any agonist concentration)
If the antagonist binds at the active site and is a
reversible antagonist, the inhibition will be
competitive.
If the antagonist binds that the active site and is
an irreversible antagonist, the inhibition will be
noncompetitive.
CHAPTER III. PHARMACOKINETICS
 
A. INTRODUCTION
CONT.
 

Pharmacokinetics deals with the absorption, distribution,

metabolism and excretion (elimination) of drugs in the
body. Actually, the response of any given drug depends
on its concentration at the site of action.
After drug administration, the drug is absorbed and
passes into blood stream, then distributed in the body up
to the site of action and must be eliminated from the
body using a specific way of drug excretion.
 
B. DRUG ABSORPTION
 

1. Definition
Absorption is the process by which the drug enters in to the systemic
circulation from the site of administration through biological barrier. In
case of intravenous or intra-arterial administration the drug bypasses
absorption processes and it enters into the circulation directly.
Absorption can also be defined as the process by which a drug is made
available to the fluids of distribution of the body (e.g., blood, plasma,
serum, aqueous humor, lymph, etc.).
In the fasting state, most orally-administered drugs reach a maximum or
"peak" blood concentration within 1-2 hours. Intravenous (IV)
administration is the most rapid route of administration, with intra-nasal,
smoking (inhalation), sublingual (under the tongue), intra-muscular (IM),
subcutaneous (e.g., under the skin, SC or SQ), and percutaneous (through
the skin) being the next most rapid.
 
 1.BIOTRANSPORT OF DRUG

It is translocation of a solute from one side of the

biological barrier to the other.
 1. Structure of biological membrane
 The outer surface of the cell covered by a very thin
structure known as plasma membrane. It is composed
of lipid and protein molecules.
CONT.

The membrane proteins have many functions

like:
(a) Contributing structure to the membrane
(b) Acting as enzyme
(c) Acting as carrier for transport of substances
(d) Acting as receptors.
The plasma membrane is a semipermeable
membrane allowing certain chemical substances
to pass freely e.g. it allows water, glucose, etc.
but it won’t allow sucrose until it is converted
into glucose and fructose.
 
PASSAGE OF DRUG ACROSS MEMBRANE

 i) Simple diffusion: Movement of a solute through

a biological barrier from the phase of higher
concentration to phase of lower concentration.
No need of energy e.g. highly lipid soluble drugs.
ii) Filtration: Is the process by which water soluble
drug of relatively low molecular weight crosses
the plasma membrane through pores as a result
of hydrodynamic pressure gradient across the
membrane e.g. urea and ethylene glycol.
CONT.
iii) Facilitated diffusion: It means the passage of drug across
the biological membrane along the concentration gradient
by the protein carrier mediated system also called as carrier
mediated diffusion. It depends on number of carrier e.g.
tetracycline, pyrimidine.
iv) Active transport: The process by which drugs pass across
the biological membrane most often against their
concentration gradient with the help of carriers along with
the expenditure of energy e.g. alpha methyl dopa, levodopa,
5-fluoro-uracil, 5 bromouracil.
v) Endocytosis: It is the process by which the large molecules
are engulfed by the cell membrane and releases them
intracellularly e.g. protein, toxins (botulinum, diphtheria)
 
TYPES OF BIOTRANSFORMATION

The chemical reactions involved in biotransformation are

classified as phase-I and phase – II (conjugation)
reactions. In phase-I reaction the drug is converted to
more polar metabolite. If this metabolite is sufficiently
polar, then it will be excreted in urine. Some metabolites
may not be excreted and further metabolised by phase –
II reactions.
Phase-I: Oxidation, reduction and hydrolysis.
Phase-II: Glucuronidation, sulfate conjugation, acetylation,
glycine conjugation and methylation reactions.
   
2. BIOAVAILABILITY

It is the rate and amount of drug that is absorbed from a

given dosage form and reaches the systemic circulation
following non-vascular administration. When the drug is
given IV, the bioavailability is 100%.
It is important to know the way in which a drug is absorbed.
The route of administration largely determines the latent
period between administration and onset of action. Drugs
given by mouth may be inactive for the following reasons:
a) Enzymatic degradation of polypeptides within the lumen
of the gastrointestinal tract e.g.: insulin, ACTH, etc.
b) Inactivation by liver e.g. test
c) Poor absorption during first passage through the liver
before it reaches systemic circulation.
3. FACTORS AFFECTING DRUG ABSORPTION
AND BIOAVAILABILITY
a) Physico-chemical properties of drug
b) Nature of the dosage form
c) Physiological factors
d) Pharmacogenetic factors
e) Disease status.
 
A) PHYSICO-CHEMICAL PROPERTIES OF DRUG:

i) Physical state: Liquids are absorbed better than

solids and crystalloids absorbed better than
colloids.
ii) Lipid or water solubility: Drugs in aqueous
solution mix more readily than those in oily
solution. However at the cell surface, the lipid
soluble drugs penetrate into the cell more
rapidly than the water soluble drugs.
 
CONT.

iii) Ionization: Most of the drugs are

organic compounds. Unlike inorganic
compounds, the organic drugs are not
completely ionized in the fluid.
Unionized component is predominantly
lipid soluble and is absorbed rapidly and
an ionized is often water soluble
component which is absorbed poorly.
Most of the drugs are weak acids or
weak bases.
CONT.

It may be assumed for all practical purposes, that

the mucosal lining of the G.I.T is impermeable to
the ionized form of a weak organic acid or a weak
organic base. These drugs exist in two forms.
 Acidic drugs: rapidly absorbed from the stomach
e.g. salicylates and barbiturates.
Basic drugs: Not absorbed until they reach the
alkaline environment i.e. small intestine when
administered orally e.g. pethidine and ephedrine.
 
 B) DOSAGE FORMS:

i) Particle size: Small particle size is important for drug absorption.

Drugs given in a dispersed or emulsified state are absorbed better e.g.
vitamin D and vitamin A.
ii) Disintegration time and dissolution rate.
Disintegration time: The rate of break up of the tablet or capsule into
the drug granules.
Dissolution rate: The rate at which the drug goes into solution.
iii) Formulation: Usually substances like lactose, sucrose, starch and
calcium phosphate are used as inert diluents in formulating powders
or tablets. Fillers may not be totally inert but may affect the
absorption as well as stability of the medicament. Thus a faulty
formulation can render a useful drug totally useless therapeutically.
 
C) PHYSIOLOGICAL FACTORS:

i) Gastrointestinal transit time: Rapid absorption occurs

when the drug is given on empty stomach. However
certain irritant drugs like salicylates and iron preparations
are deliberately administred after food to minimize the
gastrointestinal irritation. But some times the presence of
food in the G.I tract aids the absorption of certain drugs
e.g. griseofulvin, propranolol and riboflavin.
ii) Presence of other agents: Vitamin C enhances the
absorption of iron from the G.I.T.
Calcium present in milk and in antacids forms insoluble
complexes with the tetracycline antibiotics and reduces
their absorption.
CONT.
iii) Area of the absorbing surface and local circulation: Drugs
can be absorbed better from the small intestine than from the
stomach because of the larger surface area of the former.
Increased vascular supply can increase the absorption.
iv) Enterohepatic cycling: Some drugs move in between
intestines and liver before they reach the site of action. This
increases the bioavailability e.g. phenolphthalein.
v) Metabolism of drug/first pass effect: Rapid degradation of a
drug by the liver during the first pass (propranolol) or by the
gut wall (isoprenaline) also affects the bioavailability.
Thus a drug though absorbed well when given orally may not
be effective because of its extensive first pass metabolism.
 
CONT.
d) Pharmacogenetic factors:

Individual variations occur due to the genetically mediated

reason in drug absorption and response.
e) Disease states:
Absorption and first pass metabolism may be affected in
conditions like malabsorption, thyrotoxicosis, achlorhydria
and liver cirrhosis.
 
4. BIOAVAILABILITY CURVES

Single dose bioavailability test involves an

analysis of plasma or serum concentration
of the drug at various time intervals after
its oral administration and plotting a
serum concentration time curve.
 
ADVERSE RX
1) Side effects: Side effects are in fact noxious pharmacological
effects produced with therapeutic dose of the drug. E.g: Dryness
of mouth with atropine which is troublesome in peptic ulcer
patients and useful when used as a preanaesthetic medication.
2) Allergic reactions: Most of the drugs and serum used in
therapeutics are capable of causing allergic or hypersensitive
reactions. These reactions may be mild or very severe like
anaphylaxis. When an individual has been sensitized to an antigen
(allergen), further contact with that antigen can sometimes lead to
tissue damaging reactions.
CONT.
3) Idiosyncratic reactions: The term idiosyncrasy means one’s peculiar
response to drugs. With the increasing knowledge of pharmacogenetics,
many idiosyncratic reactions have been found to be genetically
determined.
E.g: Drugs like primaquine, sulfonamides and dapsone may cause
haemolysis in patients with glucose -6-phosphate dehydrogenase
defeciency.
4) Teratogenic effect: Some drugs given in the first three months of
pregnancy may cause congenital abnormalities and are said to be
teratogenic. The best known example is thalidomide which results in
early easily recognizable abnormalities such as absent or grossly
abnormal limbs.
Other drugs with teratogenic potential are androgens, steroids,
anticonvulsants, antineoplastic drugs, cortisone, lithium, pencillamine,
tricyclic antidepressants and warfarin.
 
 
 C. DISTRIBUTION OF DRUGS

 1. Definition: Penetration of a drug to the sites of action

through the walls of blood vessels from the administered
site after absorption is called drug distribution.
Once a drug has been absorbed from the stomach and/or
intestines (GI Tract) into the blood, it is circulated to some
degree to all areas of the body to which there is blood flow.
During this is the process of distribution, organs with high
blood flow such as brain, heart, liver, etc. are the first to
accumulate drugs, while connective tissue and lesser
perfused organs are the last.
 CONT.
Many drugs are bound to plasma proteins such as albumin.
Since only drugs which are not bound are free to exert a
pharmacologic effect, the ratio of "free" to "bound" drug is
important in determining the onset and duration of action of
drugs.
Highly bound drugs are distributed less extensively throughout
the body and are slower to act. By virtue of their high
binding to plasma proteins, they also stay in the body for
longer periods of time because the binding sites act as a sort
of "reservoir" for the drug, releasing drug molecules slowly.
CONT.
Drugs distribute through various body fluid compartments
such as:
(a) Plasma
(b) Interstitial fluid compartment
(c) Trans-cellular compartment.
 
CONT.
2. Apparent Volume of distribution (VD): The volume into which the total amount of a
drug in the body would have to be uniformly distributed to provide the concentration
of the drug actually measured in the plasma. It is an apparent rather than real volume.
 3. Factors determining the rate of distribution of drugs:
 Protein binding of drug: A variable and other significant portion of absorbed drug may
become reversibly bound to plasma proteins.
 
The active concentration of the drug is that part which is not bound, because it is only this
fraction which is free to leave the plasma and site of action.
(a) Free drug leaves plasma to site of action
(b) Binding of drugs to plasma proteins assists absorption
(c) Protein binding acts as a temporary store of a drug and tends to prevent large
fluctuations in concentration of unbound drug in the body fluids
(d) Protein binding reduces diffusion of drug into the cell and thereby delays its
metabolic degradation e.g. high protein bound drug like phenylbutazone is long
acting.
Low protein bound drug like thiopental sodium is short acting.
TYPES OF BINDING PLASMA PROTEINS

Albumin
The albumin is the most abundant protein; it represents 50 to 60%. It is a single
polypeptide chain with the mass approximating 69.000 and composed of 610
amino acids (alternation of 20 amino acids).
Globulins 
Globulins are polypeptides of variable molar mass according to the class to which
they belong (, ,  ). They play a big role in immunity and the regulation of the
biologic activities.
1-Glycoprotein acid 
It is the smallest of the plasma proteins; its mass varies around 41.000. It is a very
soluble and very steady protein, because 41% of the molecule are constituted of
carbohydrates.
 
CONT.
Plasma concentration of drug (PC): It represents the drug that is bound to the
plasma proteins
(albumins and globulins) and the drug in free form. It is the free form of drug that is
distributed to the tissues and fluids and takes part in producing pharmacological
effects.
The concentration of free drug in plasma does not always remain in the same level
e.g.
i) After I.V. administration plasma concentration falls sharply
ii) After oral administration plasma concentration rises and falls gradually.
iii) After sublingual administration plasma concentration rises sharply and falls
gradually.
 
CONT.
Clearance: Volume of plasma cleared off the drug by metabolism and excretion per
unit time.
Protein binding reduces the amount of drug available for filtration at the glomeruli
and hence delays the excretion, thus the protein binding reduces the clearance.
 
Physiological barriers to distribution: There are some specialized barriers in the
body due to which the drug will not be distributed uniformly in all the tissues.
 
These barriers are:
a) Blood brain barrier (BBB) through which thiopental sodium
is easily crossed but not dopamine for example.
b) Placental barrier: which allows non-ionized drugs with high
lipid/water partition coefficient by a process of simple
diffusion to the foetus e.g. alcohol, morphine.
 
Affinity of drugs to certain organs: The concentration of a drug
in certain tissues after a single
dose may persist even when its plasma concentration is reduced
too low. Thus the hepatic concentration of mepacrine is more
than 200 times that of plasma level. Their concentration may
reach a very high level on chronic administration. Iodine is
similarly concentrated in the thyroid tissue.
CONT.

Many drugs are bound to plasma proteins such as

albumin. Since only drugs which are not bound are
free to exert a pharmacologic effect, the ratio of
"free" to "bound" drug is important in determining
the onset and duration of action of drugs.
CONT.

Highly bound drugs are distributed less extensively

throughout the body and are slower to act. By
virtue of their high binding to plasma proteins,
they also stay in the body for longer periods of
time because the binding sites act as a sort of
"reservoir" for the drug, releasing drug
molecules slowly.
3. FACTORS DETERMINING THE RATE OF
DISTRIBUTION OF DRUGS:
 

Protein binding of drug: A variable and other

significant portion of absorbed drug may
become reversibly bound to plasma proteins. The active
concentration of the drug is that part which is not
bound, because it is only this fraction which is free to
leave the plasma and site of action.
(a) Free drug leaves plasma to site of action
(b) Binding of drugs to plasma proteins assists
absorption
(c) Protein binding acts as a temporary store of a drug and
tends to prevent large fluctuations in concentration of
unbound drug in the body fluids
(d) Protein binding reduces diffusion of drug into the cell
and thereby delays its metabolic degradation e.g. high
protein bound drug like phenylbutazone is long acting.
Low protein bound drug like thiopental sodium is short
acting.
 
Plasma concentration of drug (PC): It represents the
drug that is bound to the plasma proteins
(albumins and globulins) and the drug in free form. It is
the free form of drug that is distributed to the tissues
and fluids and takes part in producing
pharmacological effects.
The concentration of free drug in plasma does not
always remain in the same level e.g.
i) After I.V. administration plasma concentration falls
sharply
ii) After oral administration plasma concentration rises
and falls gradually.
iii) After sublingual administration plasma
concentration rises sharply and falls gradually.
 
D. METABOLISM OF DRUGS

Drugs are chemical substances, which interact with

living organisms and produce some pharmacological
effects and then, they should be eliminated from the
body unchanged or by changing to some easily
excretable molecules. It means that drugs in the
blood and tissues must be inactivated and excreted
from the body.
This process is initiated by altering the chemical
structure of the drug in such a way as to promote its
excretion. The transformation of the drug molecule
into a chemically related substance that is more easily
excreted from the body is called metabolism,
biotransformation or detoxification.
In the case of ethanol, the alcohol molecule is
metabolized in the liver by the enzyme
alcohol dehydrogenase, to acetaldehyde
which causes dilatation of the blood vessels
and, after accumulation, is responsible for
the subsequent hangover which ensues. The
acetaldehyde is subsequently metabolized
by the enzyme aldehyde dehydrogenase to
acetate, a substance very similar to acetic
acid or vinegar.
Therapeutic agents like antibiotics and drugs used for the
treatment of high blood pressure, epilepsy (e.g.,
phenobarbital, Dilantin), pain (e.g., morphine, codeine),
anxiety (e.g., Valium, Xanax) are also metabolized to
chemically-related compounds called metabolites, which are
then excreted in the urine.
Note: Urine drug screens usually determine metabolites in
urine, not the original "parent" drug which was ingested or
taken. For example, if cocaine is snorted, smoked or
injected, a urine drug screen will most often detect the
cocaine metabolite benzoylecgonine in the urine, not
cocaine itself The process by which the body brings about
changes in drug molecule is referred as drug metabolism or
biotransformation.
 
Enzymes responsible for metabolism of drugs:
 
a) Microsomal enzymes: Present in the smooth
endoplasmic reticulum of the liver, kidney and
GIT e.g. glucuronyl transferase,
dehydrogenase, hydroxylase and cytochrome
P450
b) Non-microsomal enzymes: Present in the
cytoplasm, mitochondria of different organs.e.g.
esterases, amidase, hydrolase.
 
E. EXCRETION OF DRUGS

Excretion of drugs means the transportation of unaltered or altered

form of drug out of the body. Excretion can also be defined as the
process by which a drug is eliminated from the body.
The major processes of excretion include renal excretion, hepatobiliary
excretion and pulmonary excretion. The minor routes of excretion
are saliva, sweat, tears, breast milk, vaginal fluid, nails and hair.
However, the most common fluid in which to look for drugs is the
urine.
The rate of excretion influences the duration of action of drug. The
drug that is excreted slowly, the concentration of drug in the body is
maintained and the effects of the drug will continue for longer
period.
 
Different routes of drug excretion
 a) Renal excretion: A major part of excretion of
chemicals is metabolically unchanged or changed. The
excretion of drug by the kidney involves:
i) Glomerular filtration
ii) Active tubular secretion
iii) Passive tubular reabsorption.
The function of glomerular filtration and active tubular
secretion is to remove drug out of the body, while
tubular reabsorption tends to retain the drug.
 
b) Hepatobiliary excretion: the conjugated drugs are
excreted by hepatocytes in the bile. Excretion of drugs
through bile provides a back up pathway when renal
function is impaired.
After excretion of drug through bile into intestine, certain
amount of drug is reabsorbed into portal vein leading to an
enterohepatic cycling which can prolong the action of
drug.E.g.chloramphenicol; oral estrogens are secreted into
bile and largely reabsorbed and have long duration of
action.
Tetracylines which are excreted by biliary tract can be used
for treatment of biliary tract infection.
 
c) Gastrointestinal excretion: When a drug is administered orally, a part of the drug is not
absorbed and excreted in the faeces. The drugs which do not undergo enterohepatic cycle after
excretion into the bile are subsequently passed with stool e.g. aluminium hydroxide changes
the stool into white colour, ferrous sulfate changes the stool into black and rifampicin into
orange red.
 
d) Pulmonary excretion: Drugs that are readily vaporized, such as many inhalation anaesthetics
and alcohols are excreted through lungs. The rate of drug excretion through lung depends on
the volume of air exchange, depth of respiration, rate of pulmonary blood flow and the drug
concentration gradient.
 
e) Sweat: A number of drugs are excreted into the sweat either by simple diffusion or active
secretion e.g. rifampicin, metalloids like arsenic and other heavy metals.
 
f) Mammary excretion: Many drugs mostly weak basic drugs are accumulated into the
milk.Therefore lactating mothers should be cautious about the intake of these drugs because
they may enter into baby through breast milk and produce harmful effects in the
baby.E.g.ampicillin, aspirin, chlordiazepoxide, coffee, diazepam, furosemide, morphine,
streptomycin.
 
CLEARANCE OF A DRUG:

 
It is the volume of plasma cleared off the drug by metabolism (hepatic) and
excretion (renal) and other organs.
Total clearance will be calculated by Ct = Ch + Cr + C others
Ct = total clearance
Ch = hepatic clearance
Cr= Renal clearance
 
THEORETICAL PHARMACOKINETICS
 Information about the time course of drug absorption, distribution
and elimination (pharmacokinetics) can be expressed in mathematical
terms and has contributed to the understanding and planning of drug
regimens. Pharmacokinetic principles aid in the selection and
adjustment of drug-dose schedules.
 1. Half life
 Half life (t1/2) of a drug is the time taken for the concentration of
drug in the blood or plasma to decline to half of original value or the
amount of drug in the body to be reduced by 50%. It has two phases
namely half-life of distribution and half-life of elimination.
 A half-life value can be readily determined for most drugs by
administering a dose of the drug to a subject, taking blood samples at
various time intervals and then assaying the samples. For example if
a blood level of drug A is 8.6 mg/ml at 10 minutes and 4.3 mg/ml at 60
minutes, so the half – life of that drug is 50 minutes.
 
2. ORDER OF KINETICS

 
Drugs are used for the treatment of diseases but the modes of administration of drugs are
different. For example atenolol is administered once daily whereas paracetamol needs 3-4
times administration daily. Morphine is more effective in intramuscular route, and insulin is
in subcutaneous route. The mode of administration is designed on the basis of absorption,
distribution, metabolism and excretion (ADME) of drugs. Drugs usually follow two processes
for their pharmacokinetic behaviour in the body.These are first order and zero order
processes.
 
First order:
This is the most common process for many drugs. The rate at which absorption, distribution,
metabolism and excretion occur are proportional to the concentration of drugs i.e. constant
fraction of this drug in the body disappears in each equal interval of time.
 
Zero order kinetic:
It is independent of the amount of drug present at the particular sites of drug absorption or
elimination. Few drugs follow this process e.g. ethanol, phenytoin. Here constant amount of
the drug is eliminated in each equal interval of time. On repeated administration of drug
after certain stage it goes on accumulating in the body and leads to toxic reactions
 
3. STEADY STATE PLASMA CONCENTRATION

 
When a drug dose is given repeatedly over a given period, a steady state is eventually reached, at
which point the amount of drug absorbed is in equilibrium with that eliminated from the body.
 
Steady state is achieved after 4 to 5 half –lives for most of the drugs which follow first order
kinetics. For example a drug with half life of 6 hours will be expected to be at steady state after
more than 24 hours of administration. The pattern of drug accumulation during repeated
administration of drug at intervals equal to its elimination half-life.
 
For some drugs, the effects are difficult to measure, toxicity and lack of efficacy are both potential
dangers, and/or the therapeutic window is narrow. In these circumstances doses must be
adjusted carefully to a desired steady- state concentration by giving loading and maintenance
doses.
Loading dose: The loading dose is one or a series of doses that may be given at the onset of therapy
with the aim of achieving the target concentration rapidly.
Maintenance dose: To maintain the chosen steady-state or target concentration, the rate of drug
administration is adjusted such that the rate of input equals to rate of loss.
 
 
CHAPTER IV. DRUG SAFETY AND EFFECTIVENESS
  A. FACTORS MODIFYING DOSAGE AND ACTION OF DRUGS

 Individuals differ both in the degree and the

character of the response that a drug may elicit and
therefore the optimum dose of a drug which
produces the desired therapeutic effect varies from
person to person. The important factors which
influence the effect of a drug are:
 1. Drug intolerance: It is a quantitative deviation
from the anticipated response to a given dose of a
drug. Thus drug intolerance is inability of the
individual to tolerate a drug. It is also called
hypersusceptibility.
 
CONT.
2. Sex difference: Special care should be exercised when
drugs are administrated during menstruation, pregnancy
and lactation.
a) Menstruation: Drugs producing pelvic congestion should
be avoided during menstruation. E.g.: drastic purgatives.
 
b) Pregnancy: During pregnancy, the use of all drugs except
those essential to maintain pregnancy should be used with
caution. Drugs which may stimulate the uterine smooth
muscle are contraindicated during pregnancy. Further,
many drugs administered to mother are capable of crossing
the placenta and affecting the foetus.
CONT.
Most of drugs can produce teratogenicity when they are used
in pregnancy. Teratogenicity means congenital
malformation.These malformations may be severe, the reason
why before prescribing any drug, it is extremely needed to
know its contraindications as well as the physiological state of
the patient, especially women and girls of childbearing age.
 
i) Drugs known to produce teratogenicity e.g thalidomide,
cyclophosphamide, methotrexate, tetracyclines, phenytoin,
carbamazepine and progestogens.
ii) Drugs that may be teratogenic e.g Warfarin, lithium,
quinine, primaquine, trimethoprim, rifampicin, anaesthetic
agents.
 
 CONT.
c) Breast feeding: Nearly all agents received by mother are likely
to be found in her milk and could theoretically harm the infant.
Most of the lipid soluble drugs get into breast milk.
Therefore the drugs, which are excreted in the milk and harm
the infant health should be avoided by breast-feeding mothers
e.g. :
Sulphonamides
Tetracycline
Nalidixic Acid
Isoniazid
Diazepam
Lithium
Indomethacin
Aspirin Etc.
 
 CONT.

3. Body weight: The average dose is mentioned either in

terms of mg per kg body weight or as the total single dose for
an adult weighing between 50-100kg.
However, dose expressed in this fashion may not apply in
cases of excessively obese individuals or those suffering from
edema, or dehydration.
Nutritional factors can sometimes alter drug metabolizing
capacity and this should be kept in mind in malnourished
patients.
 
 CONT.
4. Age: The pharmacokinetics of many drugs changes with age.
Thus gastric emptying is prolonged and the gastric pH
fluctuates in neonates and infant, further the liver capacity to
metabolize drugs is low, renal function is less developed and
the proportion of body water is higher in the newborn and the
neonates.
Hence children may not react to all drugs in the same fashion
as young adults. With a few exceptions, drugs are more active
and more toxic in the new born than the adults.
 
 CONT.

The pediatric doses are expressed in terms of body weight

(mg/kg per dose or day) or in terms of body surface area
(mg/m2 per day). The body surface area can be calculated from
the height and weight of the child.
Like children, old people also present problems in dosage
adjustment and this may vary widely with different people. The
metabolism of drugs may diminish in the elderly and the renal
function declines with age.
Elderly are sensitive to the drugs like hypnotics, tranquilizers,
phenylbutazone, diazepam, pethidine, etc.
 
 CONT.

5. Disease state: Some antimicrobial agents penetrate the

cerebrospinal fluid well across the normal meninges while
other antimicrobials penetrate well only when the meninges
are inflamed (meningitis)
e.g. sulphonamides, metronidazole, chloramphenicol,
isoniazid and rifampicin penetrate well through the normal
meninges and other antimicrobial agents like benzyl
penicillin, ampicillin, tetracycline, streptomycin, gentamicin
and cephalosporin penetrate only when the meninges are
inflamed.
 
 CONT.

Acute or chronic liver diseases markedly modify the rate and extent of
biotransformation of drugs. The t1/2 of chlordiazepoxide and diazepam in
patients with liver cirrhosis is greatly increased with corresponding
prolongation of their effects.

Cardiac disease by limiting blood flow to the liver may impair disposition of
some drugs whose biotransformation is flow limited e.g. imipramine, isoniazid,
lignocaine, morphine and propranolol.

Similarly renal and pulmonary diseases may modify the biotransformation of

drugs like insulin or isoprenaline. Excretion of drug is impaired in chronic renal
disease.
 
 
CONT.

6. Pharmacogenetics: The science of pharmacogenetics is

concerned with the genetically mediated variations in drug
responses. Some examples of genetically mediated
variations are:
Acetylation and hydroxylation of drugs: The rate of
acetylation of INH, dapsone, hydralazine procainamide and
some sulfonamides is controlled by an autosomal recessive
gene and the dosage of these drugs depends up on the
acetylator status of individuals.
 
CONT.

 7) Drug interactions

It is usual for patients to receive a number of drugs at the same
time. It is a phenomenon which occurs when the effects of one
drug are modified by the prior or concurrent administration of
another drug(s).
CONT.

A drug interaction may result in beneficial or harmful

effects and may be classified into:
 a) Pharmaceutical drug interactions:
 Serious loss of potency can occur from incompatibility
between an infusion fluid and a drug that is added to it. For
example diazepam if added to infusion fluid there will be a
precipitate formation → loss of therapeutic effect.
 
CONT.
 8) Repeated administration and drug cumulation:
If a drug is excreted slowly, its administration may build
up a sufficiently high concentration in the body to
produce toxicity. E.g. digitalis, emetine.
To avoid cumulation:
a) One must know if a drug is eliminated slowly or rapidly
b) Stop the drug administration at the appearance of the
first warning symptoms
CONT.
c) Carefully select the form in which the drug is to be
administered.
d) Check liver and kidney function before and during drug
administration, as even an otherwise non-cumulative
drug would produce cumulation in the presence of
hepatic and renal damage.
 
 CONT.
9) Drug tolerance:
 When an unusually large dose of a drug is required to elicit an
effect ordinarily produced by the normal therapeutic dose of the
drug, the phenomenon is termed as drug tolerance.
 10) Emotional factors
 E.g.: Placebo response.
CONT.
An adverse drug reaction is defined as any response to a
drug that is noxious and unintended and that occurs at
doses used in man for prophylaxis, diagnosis or therapy
(WHO).
The adverse effects are:
1) Side effects
2) Allergic reactions
3) Idiosyncratic reactions and
4) Teratogenic effects.
 
 CONT.

1) Side effects: Side effects are in fact noxious pharmacological

effects produced with therapeutic dose of the drug.
E.g.: Dryness of mouth with atropine which is troublesome in
peptic ulcer patients and useful when used as a preanaesthetic
medication.
CONT.
2) Allergic reactions: Most of the drugs and serum used in
therapeutics are capable of causing allergic or
hypersensitive reactions.
These reactions may be mild or very severe like
anaphylaxis.
When an individual has been sensitized to an antigen
(allergen), further contact with that antigen can
sometimes lead to tissue damaging reactions.
 CONT.

3) Idiosyncratic reactions: The term idiosyncrasy means one’s

peculiar response to drugs. With the increasing knowledge of
pharmacogenetics, many idiosyncratic reactions have been found
to be genetically determined.
E.g: Drugs like primaquine, sulfonamides and dapsone may cause
haemolysis in patients with glucose -6-phosphate dehydrogenase
defeciency.
 
 
CONT.
4) Teratogenic effect: Some drugs given in the first three
months of pregnancy may cause congenital abnormalities
and are said to be teratogen.
The best known example is thalidomide which results in
early easily recognizable abnormalities such as absent or
grossly abnormal limbs.

Other drugs with teratogen potential are androgens,

steroids, anticonvulsants, antineoplastic drugs, cortisone,
lithium, penicillamine, tricyclic antidepressants and
warfarin.
CHAPTER V.DEVELOPMENT AND EVALUATION OF
NEW DRUGS
CONT.
Drug development comprises two steps.
a) Preclinical development and
b) Clinical development
 
a) Preclinical development: Synthesis of new chemical
entities is done as per research policy decision which is
based on:
Random synthesis
Structure activity relationship (SAR)
Biochemical and pharmacological insight and chance
finding.
 
CONT.
b) Clinical development: About one in 1000 NCEs reach this
stage. The steps to be studied in this stage include:
a) Pharmaceutical study
b) Pharmacological study
c) Clinical trial.
CONT.
Pharmaceutical study: covers stability of formulation and
compatibility of the NCEs with other tablet or infusion
ingredients.
Pharmacological study: includes further chronic
toxicological study in animal, initially animal, metabolic and
pharmacokinetic study.
CONT.
When studies in animals predict that a NCE may be useful
medicine i.e. effective and safe in relation to its benefits,
then the time has come to put it to the test in man i.e.
clinical trial.
Clinical Trial: Clinical trial is a means by which the efficacy
of drug is tested on human being. It may also give some
idea about the risk involved. It is divided into 4 phases.
With each phase, the safety and efficacy of the compound
are tested progressively.
 
 CONT.
Phase I: This is the first exposure of the new drug on man
which is usually conducted in healthy volunteers and which
is designed to test the tolerable dose, duration of action.
This phase is usually carried out in only one center on 20 to
50 subjects.
 Phase II: This phase comprises small scale trials on patients
used to determine dose level and establish that the
treatment offers some benefit. It usually involves 100-500
patients and is usually conducted in several centers.
Phase III: Full scale evaluation of treatment comparing it with
standard treatment is done in this phase. It involves
randomized control trials on 250 to 2000 patients and is done
in multiple centers.
CONT.

Information from all studies is received by the “Committee

of safety of medicines” (CSM). If the drug is satisfied by the
CSM, the product license is issued then the drug is
marketed.
Phase IV: It is also called as phase of post marketing
surveillance. Reports about efficacy and toxicity are
received from the medical practitioners and reviewed by
the committee of review of medicines. Renewal or
cancellation of the product license depends on the
comment of the review committee.
 
CHAPTER VI.MEDICAL PRESCRIPTION AND ITS
RULES
CONT.
 
A.INTRODUCTION
A prescription (℞) is a health-care program implemented by a
physician or other medical practitioner in the form of instructions that
govern the plan of care for an individual patient.

Prescriptions may include orders to be performed by a patient,

caretaker, nurse, pharmacist or other therapist. Commonly, the term
prescription is used to mean an order to take certain medications.
 CONT.

Prescriptions have legal implications, as they may indicate that

the prescriber takes responsibility for the clinical care of the
patient and in particular for monitoring efficacy and safety.

However, as medications have increasingly become

pre–packaged manufactured products and medical practice has
become more complex, the scope of meaning of the term
"prescription" has broadened to also include clinical
assessments, laboratory tests, and imaging studies relevant to
optimizing the safety or efficacy.
CONT.
Both pharmacists and prescribers are regulated
professionals in most jurisdictions. A prescription as a
communications mechanism between them is also regulated
and is a legal document.

Regulations may define what constitutes a prescription, the

contents and format of the prescription (including the size
of the piece of paper and how prescriptions are handled and
stored by the pharmacist).
Many jurisdictions will now allow faxed or phone
prescriptions containing the same information.
CONT.

Many brand name drugs have less expensive generic drug

substitutes that are therapeutically and biochemically
equivalent.
Prescriptions will also contain instructions on whether the
prescriber will allow the pharmacist to substitute a generic
version of the drug. This instruction is communicated in a
number of ways.
CONT.
In some jurisdictions, the preprinted prescription contains
two signature lines: one line has "dispense as written" printed
underneath the other line has "substitution permitted"
underneath.
CONT.

Some have a preprinted box "dispense as written" for the

prescriber to check off (but this is easily checked off by
anyone with access to the prescription).
Other jurisdictions the protocol is for the prescriber to
handwrite one of the following phrases: "dispense as
written", "DAW", "brand necessary", "do not substitute", "no
substitution", "medically necessary", "do not interchange".
CONT.

In other jurisdictions may they use completely different

languages, never mind a different formula of words. In
some jurisdictions, it may be a legal requirement to include
the age of child on the prescription.

For pediatric prescriptions some advise the inclusion of the

age of the child if the patient is less than twelve and the age
and months if less than five. (In general, including the age
on the prescription is helpful.) Adding the weight of the
child is also helpful.
 CONT.
Prescriptions often have a "label" box. When checked, the
pharmacist is instructed to label the medication.
When not checked, the patient only receives instructions for
taking the medication and no information about the
prescription itself.
Some prescribers further inform the patient and pharmacist
by providing the indicator for the medication i.e. what is being
treated.
 CONT.

This assists the pharmacist in checking for errors as many

common medications can be used for multiple medical
conditions.
Some prescriptions will specify whether and how many
"repeats" or "refills" are allowed, that is whether the patient
may obtain more of the same medication without getting a
new prescription from the medical practitioner.
CONT.

Regulations may restrict some types of drugs from being

refilled.
In group practices, the preprinted portion of the
prescription may contain multiple prescribers' names.
Prescribers typically circle themselves to indicate who is
prescribing or there may be a checkbox next to their name
 TYPES OF MEDICATION ORDERS

The health care practitioner prescribes medications in different ways,

depending on their purpose.
Medications can be prescribed as stat, single-dose, standing, and as
needed ( prn ) orders.
Stat Orders
A stat order is an order for a single dose of medication to be given
immediately. Stat drugs are often prescribed in emergency situations to
modify a serious physiological response; a stat dose of nitroglycerin may
be ordered for a client experiencing chest pain.
The nurse should assess and document the client’s response to all stat
medications.
 
 CONT.

Single-dose Orders
Single-dose orders are one-time medications or may require
the administration of drops or tablets over a short period of
time.
The nurse should administer single-dose orders only once,
either at a time specified by the health care practitioner or at
the earliest convenient time.
These drugs are often prescribed in preparation for a diagnostic
or therapeutic procedure for example, radiopaque tablets may
be administered in preparation for a gallbladder test, or a one-
time order may be given for a preoperative medication.
STANDING ORDERS

Standing orders are also referred to as scheduled orders

because they are administered routinely as specified until
the order is canceled by another order.
The standing orders stay in effect until the health care
practitioner discontinues or modifies the dosage or
frequency with another order or until a prescribed number
of days has elapsed as determined by agency policy.
The purpose of a standing medication order is to maintain
the desired blood level of the medication.
 
CONT.
prn Orders
A drug may be ordered on a prn (as needed) basis as
circumstances indicate. The drug is administered when, in
the nurse’s judgment, the client’s condition requires it.
Before administering a prn medication, the nurse must
thoroughly assess the client, using both objective and
subjective data in determining the appropriateness of
administering the medication.
This type of order is commonly written for analgesics,
antiemetic, and laxatives.
CONT.
The order written by the health care practitioner indicates
how frequently a prn medication can be given.
A nurse cannot administer a prn medication more
frequently than the order indicates without consulting with
the health care practitioner for a change in that order.
Examples of prn orders are meperidine (a narcotic
analgesic) 75 mg IM q3–4 hours prn incisional pain and
Tylenol 650 mg q4 hours prn headache.
CONT.

When the prn medication has been administered, the

nurse documents the assessment and the time of
administration.
In addition, the nurse is responsible for monitoring the
effectiveness of the medication and documenting the
effect in the client’s medical record.
The nurse administers the pain medication on the basis
of the assessment of the client’s pain and as specified in
the order.
 B.WHO CAN WRITE PRESCRIPTIONS (THAT MAY
LEGALLY BE FILLED WITH PRESCRIPTION-ONLY
ITEMS)?

Any jurisdiction that allows freedom of written communication

generally must therefore allow anybody to write a prescription
to anybody, in as much as the prescription itself is just written
advice.

Therefore "who can write prescriptions" will be explained below

as shorthand for "whose prescriptions may legally be filled with
items restricted to dispensing via the order of certain persons".
CONT.

National or legislation governs who can write a

prescription.In Rwanda, physicians have the broadest
prescriptive authority.
Many other healthcare professions also have some form of
prescriptive authority related to their area of practice.
Veterinarians, dentists, and podiatrists have prescribing
power.
All the country allows registered certified Nurse
practitioners prescription power with some limitations to
controlled substances.
CONT.
Both pharmacists and prescribers are regulated
professionals in most jurisdictions. A prescription as a
communications mechanism between them is also regulated
and is a legal document.
Regulations may define what constitutes a prescription, the
contents and format of the prescription including the size of
the piece of paper and how prescriptions are handled and
stored by the pharmacist.
Many jurisdictions will now allow faxed or phone
prescriptions containing the same information.
C. PARTS OF THE DRUG ORDER
 All orders should be written clearly and legibly, and the drug
order should contain seven main parts:
1. Identification of the client (name, age, sex..)
2. The date and time when the order is written
3. The name of the drug to be administered
4. The dosage
CONT.

5.The route by which it is to be administered and special

directives about its administration
6. The time of administration and frequency
7. The signature of the person writing the order, such as
the physician or advanced practice registered nurse
D.CONVENTIONS FOR AVOIDING AMBIGUITY

Not only the drug order and medical prescription should

have the above mentioned parts, should they also have the
full information in order to give all required details about
the order or prescription. Prescribers have developed
many conventions for prescription-writing, with the goal of
avoiding ambiguities or misinterpretation.
 CONT.

These include:
•Date medication dispensed
•Sequential number
•Client full identity
•Prescriber’s direction for usage including the frequency
and route of administration
•Prescriber’s name
•Name and address of the agency dispensing
•Name and strength of the drug dispensed
 E.1. UNIT AND CONVERSION

Sometimes, one may have to convert a quantity from one unit to

another.
Example:
500mg can be rewritten as 0.5g
300mg = 0.3g
0.5g = 500mg
750mcg = 0.75 mg
2500ml = 2.5l
0.025m = 25mm
0.05mg = 50 mcg
E.2. DOSAGE CALCULATIONS OF TABLETS

On a drug round, you may be given the total dose a patient

is to receive. The nurse and midwife's task will be to find
out the amount of drug in each tablet and then to calculate
how many tablets to give the patient.
EXAMPLE
X patient has to be given 120mg of Verapamil but the
tablets that are available have got only 40mg each. How
many tablets are required?
The number of tablets = Amount prescribed
Amount in each tablet
The prescription is the total quantity to be given or "what is
wanted".
In our example the answer would be 120mg/40mg =3
(what you want)
EXAMPLE TWO
The previous formula for tablets may also work here as
follows:
Number of measures = amount prescribed
Amount per measure
The measure is the unit amount of liquid. In this case it is
one milliliter.
EXAMPLE

Diclofenac injection is available as an ampule of 75mg/3

ml. This means that the concentration is 25 mg/ml or 75
mg/ 3 ml. Question: How much volume of liquid will the
client receive when the prescription is to give only 50
mg?
 CONT.
The answer is:
50mgx3ml/75mg=2ml
2 ml of Diclofenac

Sometimes the drug may be available in other

concentrations, such as 10mg/5ml.
This is often the case for syrup which is usually administered
by 5ml teaspoon or cup. The 5ml is the unit measure.
So the way to calculate the quantity is exactly as it was in the
previous example.
CONT.
Example: A syrup is available as 25mg/5ml and the patient
must be given 50mg. What volume will be given in
milliliters?
Answer: The amount prescribed is 50mg and the amount
per measure is 25mg so the number of measures is 2. Now
each measure is 5ml so the quantity to be given is 2 x 5 =
10ml.
25
CONT.
There is a formula which combines the two stages above to
calculate the volume rather than the number of measures:
Volume to be given = amount prescribed x unit volume
Amount per unit volume
In the above example, the volume to be given is 50 X 5
which is 10 (ml)
E.4. INTRAVENOUS DRIPS

The rate of flow of fluid down intravenous infusion

lines must be regulated and this is often controlled by
a device known as an infusion regulator.

The regulator measures precise volumes of liquid and

releases small droplets, each of exactly the same
volume, down the IV line (tube) at precise intervals.
CONT.

The infusion regulator has a keypad or thumb-wheel which

allows the operator to alter the flow of liquid. Some
regulators require setting the Flow Rate, which is measured
in Milliliters per Hour.

Others require setting the Drip Rate, measured in Drips per

Minute. This will be written on the machine itself.
To calculate the Flow Rate, this is simply the volume in ml
divided by the duration in hours.
 EXAMPLE

A patient requires 500ml IVI (Intravenous indirect) over twelve

hours. What is the flow rate?
Answer 500 divided by 12 is 41.66ml/hr. If you do not the facility
to enter decimals then round to the nearest whole number.
The answer would then be 42ml/hr.
CONT.

On some types of flow regulator, the size of each drop of

liquid given is governed by the internal mechanics of the
controller. It is fixed at the factory and cannot be altered.

This constant quantity gives rise to the "drop factor" which

is the number of drops which make up every milliliter of
fluid delivered. Two common sizes are 20 drops per ml and
15 drops per ml. A special pediatric infusion controller is
available which delivers 60 drops per ml.
CONT.
When drugs are in liquid form, the availability is given in
terms of the concentration of the solution or suspension.
As an example, gentamicin is almost always available as
80mg/2ml.

This means that 40 mg of gentamicin are dissolved in every

ml of liquid (because the whole ampule has got 2 ml and
80mg in these 2 ml). This means that the concentration of
gentamicin is 80 mg in 2 ml or 40 mg in 1 ml.
 MEDICAL PRESCRIPTION(EXAMPLE1 )
LE BON SAMARITAIN MEDICAL CLINIC DATE……………….
HUYE
NAME:
SURNAME:
AGE:
GENDER:
WEIGHT:
 
MEDICAL PRESCRIPTION
R/………………………………………………
R/……………………………………………….
 
STAMP &SIGNATURE OF PRESCRIBER
 
 
 
 
EXAMPLE 2
PRIMARY CARE ASSOCIATE
1234 Wellness Road · Resume Speed, Kansas · (913) 999-1212
 
 
Name
Priscilla Promiscuous
Date
3/18/98
 
Address
124 Red Light Lane
Age/Wt
______
 
 
Katzung B.G(1998).

BIBLIOGRAPH
Ben et al, (2009) Trounce’s clinical pharmacology for nurses,eighteenth
edition churchill Livingstone, pg 21, 147,301
Hardman GJ, et al.Goodman&Gilmans(1996) The pharmacological basis of
therapeutics. Ninth edition,McGraw-Hill,New York
Hawary MBEL, et al (1993).Handbook of pharmacology.The scientific book
centre, Volume 1 & 2, Cairo,.
 Satoskar R.S. et.al (1995) Pharmacology and Pharmacotherapeutics, Revised fourteenth Edition, popular prakashan Bombay,

CONT’’
Basic and clinical pharmacology. Seventh edition, Appelton & Lange,
Stanford, Lehne,RA.(2012).
Pharmacology for nursing care (8th Ed.). New York: Saunders.
Misbahuddin Mir et.al(1998) General principals of Pharmacology, fourth
edition, Books and allied (P) Ltd, Calcutta