Pharma Main Handout

TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY MAIN DIGITAL HANDOUT BY PEREYRA-BORLONGAN RPh, MD-MBA
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This handout is only valid for the Sept 2020 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.

Anti-Arrhythmic Drugs 29
Important Legal Information Diuretics 32
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Preparation Incorporated are duly protected by RA 8293 otherwise known as the Drugs used in the treatment of Dyslipidemia 35
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Histamine, Serotonin, Ergot Alkaloids 38
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NSAIDS, Acetaminophen, DMARDS and Drugs Used in 48
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The handouts/review materials must be treated with utmost confidentiality. It shall be the
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person whose name does not appear therein shall be prima facie evidence of violation of RA
8293. Topnotch review materials are updated every six (6) months based on the current Antiprotozoal drugs 64
trends and feedback. Please buy all recommended review books and other materials listed Anthelmintic drugs 67
below. Gastrointestinal Pharmacology 70
Toxicology 73
INSTRUCTIONS Management of Poisoned Patients 76
To scan QR codes on iPhone and iPad CNS Drugs
1. Launch the Camera app on your IOS device Sedative-Hypnotic Drugs 80
2. Point it at the QR code you want to scan
3. Look for the notification banner at the top Alcohols 81
of the screen and tap Antiseizure Drug 83
To scan QR codes on Android General Anesthetics 87
1. Install QR code reader from Play Store Local Anesthetics 89
2. Launch QR code app on your device Skeletal Muscle Relaxants 91
3. Point it at the QR code you want to scan
4. Tap browse website Drugs Used in Parkinsonism 93
Antipsychotic Agents and Lithium 95
Antidepressants 98
Approach to Topnotch Pharmacology Opioid Analgesics and Antagonists 101
• Please have the following Topnotch materials at hand: Drugs of Abuse 103
o Topnotch Main Handout will serve as your main reference material Endocrine Pharmacology: 104
• Please buy the following: Hypothalamic and Pituitary Hormones 104
(1) Katzung, Basic and Clinical Pharmacology 14th ed. 2018 Thyroid and Anti-thyroid drugs 106
(2) Goodman and Gilman’s The Pharmacological Basis of Therapeutics. Corticosteroids and Antagonists 108
13th ed. 2018 Gonadal Hormones and Inhibitors 110
• Pharmacology, like Biochemistry, is one of those subjects that seem very Pancreatic Hormones, Antidiabetic agents, Drugs 114
difficult at first, but is actually kayang-kaya. for Obesity and Glucagon
• It’s not that hard for the following reasons: Drugs that affect Bone and Mineral Homeostasis 118
o Most questions are of the recall-type Cancer Chemotherapy 120
o most of the answers to the questions that they ask can be found in the
recommended textbook (Katzung) This handout is only valid for the Sept 2020 PLE batch. This will be
o almost all questions revolve on the following themes: drug of choice, rendered obsolete for the next batch since we update our handouts
mechanism of action, indications, contraindications and adverse regularly.
effects.
• Most students who self-study usually just read pharma recall or
Lippincott. The pharma lecture and handout are based purely upon BASIC PRINCIPLES OF
Katzung Pharmacology and Goodman & Gilman.
SUPPLEMENT: PHARMACOLOGY
• Text in “Supplement” boxes is for additional information When you study the basic principles of pharmacology, make sure that you
• Letters after each drug signifies its FDA Pregnancy Category. If no read and understand the concepts. Not much will be asked from this part,
letter is found: NO FDA ASSIGNMENT YET. maybe 1-2 questions BUT your understanding of pharmacology is hinged
on understanding these principles. So make sure you understand the
concepts really well. Good luck in your pharma journey!
PHARMACOLOGY
Dr. Lopez
INTRODUCTION
By Maria Yña Eluisia T. Pereyra-Borlongan, RPh, DEFINITION OF TERMS
MD-MBA • DRUGS
Annotated by: o any substance that brings about a change in biologic function
Julianne Cristy B. Lopez, MD-MBA through its chemical actions
Maria Yña Eluisia T. Pereyra-Borlongan, RPh, MD-MBA • PHARMACODYNAMICS
Eric E. Calderon Jr., MD o actions of a drug on the body
o receptor interactions, dose-response phenomena, and
TOPIC PAGE mechanisms of therapeutic and toxic action
Basic Principles of Pharmacology 1 • PHARMACOKINETICS
Pharmacodynamics 5 o actions of the body on the drug
Pharmacokinetics 7 o concerned with
Drug Metabolism 8 § absorption
Drug Evaluation and Regulation 10
§ distribution
Autonomic Pharmacology 11
§ metabolism
Cholinoreceptor-Activating and Cholinesterase- 13
Inhibiting Drugs § elimination
Cholinoreceptor Blockers 15 MNEMONIC: Pharmacokinetics vs Pharmacodynamics
Adrenergic Pharmacology 17 pharmacoKineTics pharmacoDynaMics
Sympathomimetics 18 (Katawan → Tableta) (Drugs → Man)
Adrenoreceptor Blockers 20
Treatment of Glaucoma 21
Cardiovascular Drugs PHARMACOKINETICS vs.
Drugs for Hypertension 22 PHARMACODYNAMICS
Drugs Used in the Treatment of Angina Pectoris 26 https://qrs.ly/k7bllv5
Drugs Used in Heart Failure 28
TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY MAIN DIGITAL HANDOUT BY PEREYRA-BORLONGAN RPh, MD-MBA. Page 1 of 128
PHARMACOKINETIC PRINCIPLES WATER AND LIPID SOLUBILITY OF DRUGS

MOVEMENT OF DRUGS IN THE BODY • aqueous solubility is directly proportional to electrostatic
charge (ionization, polarity)
• drug molecules must travel from the site of administration to
o ionized and polar drugs are more water-soluble
the site of action
o increased aqueous solubility = increased clearance
SUPPLEMENT: NATURE OF DRUGS • lipid solubility is inversely proportional to electrostatic charge
• SIZE AND MOLECULAR WEIGHT (ionization, polarity)
o vary from MW 7 (lithium) to over MW 50,000 (alteplase, o non-ionized and non-polar drugs are more lipid-soluble
thrombolytic enzymes) o increased lipid solubility = increased capacity to cross
o majority have MW 100 to 1000 biological membranes = increased absorption
o <100 – rarely sufficiently selective in their actions There are 3 important dependent factors for permeation, namely:
o >1000 – poorly absorbed and poorly distributed 1) Solubility (through diffusion through lipid bilayer)
• DRUG-RECEPTOR BONDS 2) Concentration gradient (diffusion down a concentration gradient- only
o Arranged according to decreasing order of strength free unionized drug contribute to concentration gradient)
§ Covalent bonds 3) Surface area and vascularity: the larger the surface area and the
§ Electrostatic bonds: ionic bonds, hydrogen bonding, van greater the vascularity, the better the absorption of the drug Example:
Stomach vs. Intestine, Intramuscular vs. Subcutaneous route.
der Waals Dr. Calderon Jr.
§ Hydrophobic bonding
o strength of bond formed by drugs determines reversibility
of effects WEAK ACIDS AND BASES
§ Pralidoxime cannot reverse insecticide poisoning if the • many drugs are weak acids and weak bases
bonds formed by the poison have aged and become • dissociate into ionized and non-ionized forms
covalent • pH determines the fraction of drug molecules charged (ionized)
versus uncharged (non-ionized)
• predicted by Henderson-Hasselbach equation
WATER AND LIPID SOLUBILITY OF DRUGS
o relationship between pH, pKa (dissociation constant) and
PERMEATION is the movement of drug molecules into and within concentration of charged and uncharged forms
biologic environments
• aqueous diffusion
HENDERSON-HASSELBACH EQUATION
• lipid diffusion
[𝑈𝑛𝑝𝑟𝑜𝑡𝑜𝑛𝑎𝑡𝑒𝑑]
• transport by special carriers 𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔
• endocytosis, pinocytosis [𝑃𝑟𝑜𝑡𝑜𝑛𝑎𝑡𝑒𝑑]
[𝐴R ]
𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔
AQUEOUS DIFFUSION [𝐻𝐴]
[𝐵]
• passive movement of non-protein-bound drugs between the 𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔
blood and extravascular space through small water-filled pores [𝐵𝐻T ]
(exceptions: brain, testes, eye and placenta)
• affected by drug concentration and charge HENDERSON-HASSELBACH
• governed by Fick’s Law of Diffusion EQUATION
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LIPID DIFFUSION
• movement of drugs through lipid membranes separating body DISSOCIATION OF WEAK ACIDS
compartment, and from the ECF to the ICF
• most important limiting factor for permeation
• governed by Fick’s law of diffusion
• very important for the diffusion of weak acids and weak bases
• unprotonated (A-) form is more water-soluble and undergoes
TRANSPORT BY SPECIAL CARRIERS better clearance
• for drugs that do not readily cross through membranes may be • protonated (HA) form is more lipid soluble and more likely to
transported across barriers by mechanisms that carry similar cross biological membranes
endogenous substances DISSOCIATION OF WEAK BASES
o ions through Na+/K+ pump
o neurotransmitter through reuptake transporters
o metabolites such as glucose through GLUT
o carriers for foreign molecules or xenobiotics
• unprotonated (B) form is more lipid-soluble and more likely to
• NOT governed by Fick’s law of diffusion and is capacity-limited
cross biological membranes
• protonated (BH+) form is more water-soluble and undergoes
ENDOCYTOSIS AND PINOCYTOSIS
better clearance
• endocytosis: large drugs bind to receptors, are internalized and
released after vesicle breakdown (exocytosis is the reverse
process)
• small polar drugs combine with special proteins to form
complexes which undergo endocytosis
o vitamin B12 bound to intrinsic factor
o iron bound to transferrin
FICK’S LAW OF DIFFUSION

• predicts the rate of movement of molecules across a barrier
Titration curve for an acid of the type HA. The heavy dot in the center of the curve indicates the pKa 5.0.
Permeability Coefficient Modified Figure 2-4. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
𝑅𝐴𝑇𝐸 = (𝐶( − 𝐶+ ) × × 𝐴𝑟𝑒𝑎 MNEMONIC: pKa
Thickness
• pharmacologic implications “UP Above”
o absorption is faster in organs with larger SA (intestinal > Unprotonated >Protonated: above pKa
stomach)
o absorption is faster in organs with thinner membranes (lung >
skin) UP Above
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✔PRACTICE PROBLEMS SUBCUTANEOUS ROUTE

1. Aspirin is a weak organic acid with a pKa of 3.5. What percentage of • slower absorption than intramuscular route
a given dose will be in the lipid soluble form at a stomach pH of 2.5? o NO blood vessels in the subcutaneous space
[𝑈𝑛𝑝𝑟𝑜𝑡𝑜𝑛𝑎𝑡𝑒𝑑] • large volume doses are less feasible
𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔
[𝑃𝑟𝑜𝑡𝑜𝑛𝑎𝑡𝑒𝑑] • bypasses the first pass effect
[𝑈]
2.5 = 3.5 + 𝑙𝑜𝑔 • anticoagulants do NOT cause hematomas when administered via
[𝑃]
this route
[𝑈]
2.5 − 3.5 = 𝑙𝑜𝑔
[𝑃]
[𝑈] BUCCAL AND SUBLINGUAL ROUTE
−1 = 𝑙𝑜𝑔 • buccal: pouch between the gums and cheek
[𝑃]
[𝑈] • sublingual: under the tongue
10R( =
[𝑃] • direct absorption into the systemic venous circulation,
Unprotonated is 10-1 or 0.10 or 10% bypassing the first-pass effect
Protonated is 90%
Since aspirin is a weak acid, the more lipid soluble form is the CORRELATIONS: Anatomy – Sublingual drugs
protonated HA form. Hence, the final answer is 90%. Through which blood vessels do drugs administered SL pass
2. Atropine is a weak organic base with a pKa of 9.7. What percentage before reaching the heart?
of a given dose will be in the lipid soluble form at a pH of 7.7?
Lingual vein → internal jugular vein → brachiocephalic
(innominate) vein → superior vena cava → right atrium
ANSWER TO QUESTION 2
https://qrs.ly/49bllw1 RECTAL (SUPPOSITORY) ROUTE
• partial avoidance of the first-pass effect
• useful for large amounts of drugs with unpleasant tastes and for
SUPPLEMENT: Application of HH Equation patients who are vomiting
• excretion of a weak acid may be accelerated by alkalinizing CORRELATIONS: Anatomy – Rectal route
the urine with bicarbonate (HCO3-) Why is there only partial bypass of the first pass-effect on rectal
• excretion of a weak base may be accelerated by acidifying the administration?
urine with ammonium chloride (NH4Cl) and ascorbic acid Review the VENOUS DRAINAGE OF THE RECTUM.
Superior Rectal Vein: IMV → PV (first-pass)
DRUG ABSORPTION Middle Rectal Vein: IIV → IVC
ABSORPTION Inferior Rectal Vein: IPV → IIV → IVC
• transfer of a drug from its site of administration to the
bloodstream INHALATIONAL ROUTE
• affected by 3 major factors • offers delivery closest to the target in respiratory diseases
o route of administration • rapid absorption with minimal systemic effects
o blood flow • convenient for drugs that are gases at room temperature
o concentration (nitrous oxide, nitric oxide) or easily volatilized (anesthetics)
ROUTES OF DRUG ADMINISTRATION TOPICAL ROUTE

ORAL ROUTE • application to skin, mucous membranes of the eye, ear, nose,
• offers maximum convenience throat, airway, or vagina for local effect
• most common route of drug administration • absorption varies with the area of application and drug
• absorption is slow and less complete formulation
o gastric contents o increasing ability to retard evaporation
o first-pass effect o (more evaporation) tinctures > wet dressings > lotions > gels
§ a significant amount of the drug is metabolized in the gut > aerosols > powders > pastes > creams > foams > ointments
wall, portal circulation and liver before it reaches the (less evaporation)
systemic circulation • slowest route of drug administration
INTRAVENOUS ROUTE SUPPLEMENT: Topical Preparations
• instantaneous and complete absorption that bypasses first-pass Describe the utility of dermatologic drug preparations for skin
effect (100% bioavailability) inflammation.
• potentially more dangerous • Acute inflammation = drying agents
o high blood levels reached on rapid administration (tinctures, wet dressings, lotions)
o Inadvertent systemic introduction of bacteria through the IV • Chronic inflammation = lubricating agents
line (line sepsis) (creams, ointments)
o Difficult to reverse effects
INTRAMUSCULAR ROUTE TRANSDERMAL ROUTE
• absorption is faster and more complete than oral (higher • application to the skin for systemic effect
bioavailability) • absorption occurs very slowly but bypasses the first-pass effect
o bypasses first-pass effect SUPPLEMENT:
• large volumes may be delivered if drug is not too irritating (i.e. What routes of administration undergo significant First-Pass
5g of MgSO4) Effect? ORAL
• anticoagulants cannot be given by this route because they may Partially bypass? RECTAL
cause bleeding (hematomas) Completely bypass? IV, IM, SC, SL, INHALATIONAL, TOPICAL,
SUPPLEMENT: IM Injections to Buttocks TRANSDERMAL
Which quadrant of the buttocks is safest Which route of administration has the fastest absorption?
for IM drug administration? INHALATION
Take note that IV route does not involve absorption, with
• superolateral = safe extravascular administration, less than 100% of a dose may reach the
• superomedial = gluteus medius gait systemic circulation because of variations in bioavailability (how
• inferomedial = sciatica much does go into the blood?
Dr. Pereyra-Borlongan
DRUG DISTRIBUTION SPECIAL BARRIERS TO DISTRIBUTION

Placenta – most low molecular weight drugs cross the placental barrier
• Process wherein drug reversibly leaves the bloodstream and (although fetal blood vessel supply is lower than maternal)
enters the target organ Blood Brain Barrier – permeable only to lipid soluble or with low
• Depends on 4 major factors: molecular weight drug e.g. Lithium (has the lowest molecular weight)
o Size of the organ and Ethanol (though ionized (water-soluble) has a low molecular weight)
o Blood flow *The RULE IS IF THE DRUG CAN CROSS THE BLOOD BRAIN BARRIER,
IT CAN CROSS THE PLACENTA
o Solubility Dr. Calderon Jr.
o Protein Binding
SUPPLEMENT: Size of the Organ DRUG METABOLISM

• determines concentration gradient between blood and the METABOLISM
organ • drugs are chemically altered in the body
o skeletal muscles is very large organ • drugs may undergo 3 metabolic fates:
§ large doses are required to actually change the o termination of drug action
concentration gradient o drug activation
o the brain is a small and compact organ o elimination without metabolism
§ only a small amount of drugs is required to change
concentration gradients TERMINATION OF DRUG ACTION
• drugs are metabolized into biologically inactive derivatives
BLOOD FLOW • conversion to a metabolite is a form of elimination
• important determinant of the rate of drug uptake
• well-perfused organs will achieve high tissue concentrations DRUG ACTIVATION
sooner than poorly perfused tissues • prodrugs are metabolized in the body to become active
• concentration of drugs with rapid elimination will not • some drugs are metabolically active but still have active
significantly rise in poorly perfused tissues metabolites
• blood flow affects the rate of uptake of drug but not the amount o ex. Desmethyldiazepam – an active metabolite of Diazepam,
of drug in tissue equilibrium Chlordiazepoxide and Flurazepam, which extends the plasma
t½ to 60 hours or more
SOLUBILITY
• influences the concentration of the drug in the extracellular fluid ELIMINATION WITHOUT METABOLISM
surrounding blood vessels • some drugs are not modified by the body and continue to act
• most barriers in the body (BBB, placenta, glomerulus) are lipid- until they are excreted
barriers Let us correlate this to Biochemistry – Xenobiotics:
o non-ionized, non-polar drugs are more lipid-soluble and Do you remember the chapter of Xenobiotics in Harper’s? The two phases
undergo more extensive distribution of Metabolism: Phase I and Phase II
To simplify:
PROTEIN BINDING Phase I: the goal is to convert drugs to be water soluble, yet some drugs
• binding to macromolecules in blood or tissue will tend to are still active. It involves Reduction, Oxidation, Hydrolysis (ROH). This
phase gets slower in geriatric population.
increase the drug’s concentration in that compartment Phase II: the goal is to make the drug more water soluble and inactive. It
o acidic drugs are bound to albumin involves the process of Methylation, Glucuronidation, Acetylation and
o basic drugs are bound to orosomucoid and a1-acid Sulfation (MGAS). This phase remains active in geriatric population. We
glycoprotein consider this in giving drugs to elderly
• bound drugs CANNOT cross membranes and exert their effect Dr. Calderon Jr.
• only unbound drugs CAN cross membranes and exert their effect
o ONLY THE FREE (UNBOUND) DRUG CAN BE ABSORBED, DRUG ELIMINATION
DISTRIBUTED, METABOLIZED, EXCRETED AND EXERT ELIMINATION
PHARMACOLOGIC EFFECT • elimination: termination of drug action
o Examples: Phenytoin, Valproic acid • excretion: release of drugs or their metabolites in the urine,
stool, bile, exhaled air etc.
Apparent Volume of Distribution and Physical
SUPPLEMENT:
Volumes
• duration of drug action is determined by:
o dose administered
• determines concentration gradient between blood and the
o rate of elimination following the last dose
Volume of Distribution: relates the amount of drug in the
body to the concentration in the plasma. SUPPLEMENT: Elimination and Drug Metabolites
COMPARTMENT VOLUME (L/Kg) body weight • elimination of parent molecule does not terminate the drug’s
Plasma 0.04 action for drugs with active metabolites
Blood 0.08 • excretion is the mode of elimination for drugs that are not
Extracellular 0.20 metabolized
Total Body Water 0.60
Fat 0.2-0.35 FIRST-ORDER ELIMINATION
• rate of elimination is proportionate to the concentration
In normal condition, protein-binding capacity is much larger than is o concentration decreases exponentially over time
drug concentration and consequently the free fraction is generally
• characteristic half-life of elimination
constant.
o concentration decreases by 50% for every half-life
Many drugs bind to plasma proteins with an equilibrium between bound • most common type of elimination
and free. The most common protein where drugs bind is albumin. Is
albumin a receptor for a drug? No. Remember, that true receptor will give
a biologic response ZERO-ORDER ELIMINATION / SATURABLE / MICHAELIS-
MENTEN KINETICS
This concept is very important because of competition of drugs for
plasma-protein binding sites may increase the “free fraction” of the • rate of elimination is constant regardless of concentration
other enhancing the effects of the displayed o concentration decreases linearly over time
1. Sulfonamides and bilirubin in neonate → Hyperbilirubinemia • occurs when drugs have saturated their elimination mechanisms
2.Warfarin + Sulfonamides → Sulfonamide will displace Warfarin
increasing its free fraction. What could be its toxicity? Potential
bleeding
3. PTU vs. Methimazole in first trimester pregnancy. Choose PTU
because it is more protein-bound than Methimazole
Graded-Dose Response Curves
Figure 2-1. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
SUPPLEMENT:
• efficacy (Emax) and potency (EC50) are derived from this curve
MNEMONIC: Zero Order Kinetics
What drugs display zero order elimination kinetics? Definitions
WHAT PET Emax = Maximal effect achievable with increasing
Warfarin concentration of a drug
Heparin EC50 = Concentration of the drug wherein half of the maximal
Aspirin effect is achieved
Tolbutamide Bmax = Maximum percentage of receptors with increasing
Phenytoin concentration of a drug / maximal number of receptors bound
Ethanol Kd = Concentration wherein 50% of receptors is occupied
Theophylline
QUANTAL DOSE-RESPONSE RELATIONSHIPS
• minimum dose required to produce a specified response is
ZERO-ORDER KINETICS
determined in each member of a population
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• quantal dose-response curve
o fraction of the population that responds at each dose against
the log of the dose administered
✔PRACTICE PROBLEM
o median effective (ED50), median toxic (TD50) and median lethal
ELIMINATION KINETICS
(LD50) doses are derived
1. Which drug displays first-order elimination? Zero-order
• no attempt is made to determine maximal effect
elimination?
Quantal-Dose Response Curves
ANSWER TO
ELIMINATION KINETICS
QUESTION
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PHARMACODYNAMICS
RECEPTORS
• specific molecules in a biologic system with which drugs interact
to produce changes in the function of the system
• must be selective in their ligand-binding characteristics THERAPEUTIC INDEX
• must be modified when they bind an agonist to bring about
functional change
• most are proteins
RECEPTOR SITES OR RECOGNITION SITES

• specific binding region of the macromolecule
• high and selective affinity for the drug molecule
EFFECTORS
• translate the drug-receptor interaction into a change in cellular
activity
SUPPLEMENT:
• some receptors are also effectors
o a single molecule may incorporate both the drug binding
site and the effector mechanism
§ Examples: Tyrosine kinase receptor in insulin receptor
molecule, Na/K channel in nicotinic Ach receptor, Therapeutic Index and Therapeutic Window
Adenylyl cyclase • TI = TD50 / ED50
• Therapeutic Window: dose range between MEC and MTC
GRADED DOSE-RESPONSE RELATIONSHIPS
• dose-response curve EFFICACY
o response of a particular receptor-effector system measured • maximal efficacy or Emax
against increasing drug concentrations • maximal effect an agonist can produce if the dose is taken to very
o yields a sigmoid curve if plotted on a semilogarithmic axis high levels
Binding Affinity • determined mainly by the nature of the receptor and its
• fraction of receptors bound by a drug plotted against the log of associated effector system
the drug concentration • measured with graded dose-response curves NOT with quantal
• Kd is the concentration required to bind 50% of the receptors dose-response curves
o The smaller the Kd, the greater the affinity of a drug for its • partial agonists have lower maximal efficacy than full agonists
receptor
POTENCY ANTAGONISTS
• denotes the amount of drug needed to produce a given effect • do not provoke a biological response by themselves upon
• determined mainly by the affinity of the receptor for the drug binding to a receptor
• measurement • blocks or dampens drug response in the presence of an agonist
o in graded dose-response curves, it is the dose required to • classification
produced 50% of the maximal effect o competitive (reversible)
o in quantal dose-response curves, three potency variables are o non-competitive (irreversible)
measurable (ED50, TD50, LD50) o physiologic
o chemical
ANTAGONIST PART 1
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ANTAGONIST PART 2
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SUPPLEMENT: Spare Receptors

• are receptors that do not bind drug when the drug
concentration is sufficient to produce maximal effect
• they are present when Kd > EC50
• increase sensitivity to the agonist because the likelihood of
Drug-Receptor interaction increases directly proportional to
the number of receptors available
Let us correlate this to Biochemistry again.
• AFFINITY: is the ability to bind to a receptor; it is inversely First Aid for the USMLE Step 1 2020. p 234
proportional to Kd (drug concentration required to give ½ maximum Competitive or Reversible Antagonists
binding to receptor) (like Km)
o it is shown by the proximity of the curve to the Y-axis (if the curves • bind to receptors in a reversible way without activating the
are parallel) the nearer to the y axis, the greater the affinity (In the effector system
example above, we can say that A has more affinity compared to B) • shift Dose Response Curves (DRC) to the right (increased ED50)
• EFFICACY: like Vmax, shown by the maximal height reached by the curve but same maximal effect is reached
(in the example above, A=B=C in terms of efficacy) • effects overcome by adding more agonist
• POTENCY: shows relative doses of two or more agonists to produce the • Examples: β-blockers (Propranolol) and β-agonists
same magnitude of effect. Shown by the proximity of the respective (Isoproterenol)
curves to y-axis (provided the curves do not cross) e.g. in the above
example, we can say that A has the highest potency.
Dr. Calderon Jr. Non-competitive or Irreversible Antagonists
• causes downward shift of the DRC
FACTORS AFFECTING DOSE RESPONSE CURVES • no horizontal shift of DRC (ED50 unchanged) unless spare
FULL AGONISTS receptors are present
• not overcome by adding more agonist
• capable of fully activating the effector system when it binds to
• example: Norepinephrine and Phenoxybenzamine
the receptor
• high affinity for the activated receptor conformation
Physiologic Antagonists
• sufficiently high concentrations result in all the receptors
• binds to a different receptor, producing an effect opposite to that
achieving the activated state
produced by the drug it is antagonizing
• Examples: Histamine and Epinephrine, Propranolol and thyroid
PARTIAL AGONIST
hormone
• produces less than the full effect, even when it has saturated the
receptors Chemical Antagonists
• in the presence of an agonist, a partial agonist acts as an • interact directly with the drug being antagonized to remove it or
inhibitor / antagonist to prevent it from reaching its target
• does not depend on interaction with agonist receptors
FULL vs PARTIAL • examples: Dimercaprol for lead poisoning, Pralidoxime for
AGONISTS organophosphate poisoning
https://qrs.ly/27bllym SUPPLEMENT: Signaling Mechanisms
• Steroid-like transmembrane diffusion of the drug to bind to
intracellular receptor
• Membrane-spanning receptor effector enzyme
• Transmembrane receptors that alter activation by an
appropriate ligand
• Ligand-activated membrane ion channels
• G-protein coupled receptors / 7-transmembrane spanning
receptors
VARIATIONS IN DRUG RESPONSE

TOLERANCE
• continuous activation may lead to depletion of essential
substrates
• reversed by repletion of missing substrates
• EXAMPLE: depletion of thiol cofactors in nitroglycerin tolerance,
Figure 1-3. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
reversible with administration of glutathione
SUPPLEMENT: CLEARANCE
Downregulation • relates the rate of elimination to the plasma concentration
• Long term reduction in receptor number due to continuous • depends on the drug and the condition of the organs of
exposure to agonist elimination
Upregulation o for a drug that is very effectively extracted by an organ,
• Occurs when receptor activation is blocked for prolonged clearance is flow-limited
periods • for drugs eliminated with first-order kinetics, clearance is a
constant proportion
TACHYPHYLAXIS • for drugs eliminated with zero-order kinetics, clearance is a
• responsiveness diminishes rapidly after administration of a drug constant amount
• frequent or continuous exposure to agonists often results in • Most important pharmacokinetic parameter to be
short-term diminution of the receptor response considered in defining a rational steady state during dosage
e.g. Theophylline, Salbutamol. Nitrates, Dobutamine regimen
MMNEMONIC: Tachyphylaxis
What drugs display tachyphylaxis?
MEDical students Love to watch CNN in HD!
Metoclopramide Nitroglycerin
Ephedrine Nicotine
Dobutamine Hydralazine
LSD Desmopressin
Calcitonin
IDIOSYNCRATIC DRUG RESPONSE
• one that is infrequently observed in most patients
• EXAMPLES:
o aplastic anemia with chloramphenicol
o cataracts with allopurinol
PHARMACOKINETICS
When you study pharmacokinetics, the focus is understanding the
concepts and not memorizing the formulas. As long as you’re able to Figure 3-2. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
understand the spirit of the formula, then you’re okay. Does that make STEADY STATE
sense? If you’re preparing for the USMLE though, that’s a different story • condition in which the average total amount of drug in the body
as you will be asked to compute. does not change over multiple dosing intervals
Dr. Lopez
• rate of drug administration equals the rate of elimination

EFFECTIVE DRUG CONCENTRATION

• concentration of a drug at the receptor site • Reached in 4-5 half-lives of the drug
• except for topically applied agents, the concentration at the
HALF-LIFE
receptor site is usually proportional to the drug's concentration
𝟎. 𝟔𝟗𝟑 × 𝑽𝒐𝒍𝒖𝒎𝒆 𝒐𝒇 𝒅𝒊𝒔𝒕𝒓𝒊𝒃𝒖𝒕𝒊𝒐𝒏
in the plasma or whole blood at equilibrium 𝒕𝟏r =
𝟐 𝑪𝒍𝒆𝒂𝒓𝒂𝒏𝒄𝒆
APPARENT VOLUME OF DISTRIBUTION • constant for drugs following first-order kinetics
• volume at which drug would need to be uniformly distributed to • disease, age, and other variables usually alter clearance of a drug
produce an observed blood concentration much more than Vd
𝑨𝒎𝒐𝒖𝒏𝒕 𝒐𝒇 𝒅𝒓𝒖𝒈 𝒊𝒏 𝒕𝒉𝒆 𝒃𝒐𝒅𝒚
𝑽𝒅 = • half-life may not change despite a decreased clearance if the Vd
𝑷𝒍𝒂𝒔𝒎𝒂 𝒅𝒓𝒖𝒈 𝒄𝒐𝒏𝒄𝒆𝒏𝒕𝒓𝒂𝒕𝒊𝒐𝒏
decreases at the same time
• purely pharmacokinetic parameter with no direct physical
equivalent BIOAVAILABILITY
• can be altered by liver and kidney disease
• fraction of the administered dose that reaches the systemic
Volume of Distribution circulation
• drugs administered intravenously have 100% bioavailability
• reduced by incomplete absorption, first-pass metabolism, and
presystemic redistribution
• determined by computing the area under the plasma
concentration curve (AUC)
✔PRACTICE PROBLEMS
After oral administration of 500mg of Drug A, only 300mg were
absorbed into the patient’s systemic circulation. What is its
bioavailability?
BIOAVAILABILITY
ANSWER TO QUESTION
https://qrs.ly/bmbobnf
DOSAGE REGIMEN Cockcroft-Gault Equation

SUPPLEMENT: Dosage Regimen • to calculate the patient’s creatinine clearance, use the Cockcroft-
Gault equation
• plan for drug administration over a time period (𝟏𝟒𝟎 − 𝑨𝒈𝒆) × 𝑾𝒆𝒊𝒈𝒉𝒕𝒌𝒈
• results in the achievement of therapeutic levels of the drug in 𝑪𝒍𝑪𝒓 = (× 𝟎. 𝟖𝟓 𝒊𝒏 𝒇𝒆𝒎𝒂𝒍𝒆𝒔)
the blood without exceeding the minimum toxic 𝟕𝟐 × 𝑺𝒆𝒓𝒖𝒎 𝑪𝒓𝒆𝒂𝒕𝒊𝒏𝒊𝒏𝒆𝒎𝒈/𝒅𝑳
concentration SUPPLEMENT:
• based on knowledge of both the minimum therapeutic and Amount of drug in the body at any time is computed as:
minimum toxic concentrations for the drug, as well as its 𝑉Š × 𝑝𝑙𝑎𝑠𝑚𝑎 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛
clearance and Vd Steady State Concentration during the ff t½:
MAINTENANCE DOSE 1st t½ : 50%
𝑪𝒍𝒆𝒂𝒓𝒂𝒏𝒄𝒆 × 𝑫𝒆𝒔𝒊𝒓𝒆𝒅 𝒑𝒍𝒂𝒔𝒎𝒂 𝒄𝒐𝒏𝒄𝒆𝒏𝒕𝒓𝒂𝒕𝒊𝒐𝒏 2nd : 75%
𝑴𝒂𝒊𝒏𝒕𝒆𝒏𝒂𝒏𝒄𝒆 𝑫𝒐𝒔𝒆 = 3rd : 87.5%
𝑩𝒊𝒐𝒂𝒗𝒂𝒊𝒍𝒂𝒃𝒊𝒍𝒊𝒕𝒚
• equal to the rate of elimination at steady state 4th : 93.75%
• Vd is not involved in calculating MD
• important to maintain concentration above minimum DRUG METABOLISM
therapeutic level:
• metabolic pathways alter drug activity and their susceptibility to
o give large doses at long intervals
excretion
o smaller doses at more frequent intervals
• Two phases
o Phase 1 or Functionalization Reaction
LOADING DOSE
o Phase 2 or Conjugation Reaction
𝒅𝒆𝒔𝒊𝒓𝒆𝒅 𝑷𝒍𝒂𝒔𝒎𝒂 𝑪𝒐𝒏𝒄𝒆𝒏𝒕𝒓𝒂𝒕𝒊𝒐𝒏
𝑳𝒐𝒂𝒅𝒊𝒏𝒈 𝑫𝒐𝒔𝒆 = 𝑽𝒅 ×
𝑩𝒊𝒐𝒂𝒗𝒂𝒊𝒍𝒂𝒃𝒊𝒍𝒊𝒕𝒚
• if therapeutic concentration must be achieved rapidly and the
PHASE I REACTIONS
volume of distribution is large • convert the parent drug to a more polar (water-soluble) or more
• clearance is not involved in calculating LD reactive product by unmasking or inserting a polar functional
• if the LD is very large, dose should be given slowly to prevent group
toxicity • EXAMPLES: oxidation, reduction, deamination, hydrolysis
o due to excessively high plasma levels during the distribution Bottom line is Phase 1 reactions will usually yield SLIGHTLY polar, water
phase soluble metabolites and more often than not, can still be active.
Dr. Lopez
THERAPEUTIC WINDOW MNEMONICS: Phase I Reactions

• safe range between the minimum effective concentration and A HORDe of PHASE I REACTIONS
the minimum toxic concentration of a drug Hydrolysis Reduction
o minimum effective concentration usually determines the Oxidation Deamination
desired trough levels of a drug given intermittently
o minimum toxic concentration determines the permissible CYTOCHROME P450 ENZYMES
peak plasma concentration
• Also called mixed-function oxidases
• High concentrations in the smooth endoplasmic reticulum of the
liver
• Not highly selective in their substrates
• Approximately 75% are metabolized by: CYP3A4 or CYP2D6
Examples of Phase I Reactions
SUPPLEMENT: Adjustment of Dosage

• renal disease or reduced cardiac output often reduces the
clearance of drugs that depend on renal function
• impairment of hepatic clearance occurs when liver blood flow
is reduced Table 4-1 Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
o EXAMPLES: heart failure, severe cirrhosis, other forms of
liver failure
PHASE 2 REACTIONS
ADJUSTMENT OF DOSAGE IN RENAL IMPAIRMENT • Involve conjugation of subgroups to –OH, –NH2, and –SH
𝑪𝒓𝒆𝒂𝒕𝒊𝒏𝒊𝒏𝒆 𝑪𝒍𝒆𝒂𝒓𝒂𝒏𝒄𝒆 functions on the drug molecule
𝑪𝒐𝒓𝒓𝒆𝒄𝒕𝒆𝒅 𝑫𝒐𝒔𝒆 = 𝐴𝑣𝑒𝑟𝑎𝑔𝑒 𝐷𝑜𝑠𝑒 ×
𝟏𝟎𝟎 𝒎𝑳/𝒎𝒊𝒏 o makes the drug more polar and less lipid-soluble than the
• if a drug is cleared partly by the kidney and partly by other original drug molecule
routes, apply the equation only to the part of the dose that is o EXAMPLES: glucuronate, acetate, glutathione, glycine, sulfate,
eliminated by the kidney and methyl group
✔PRACTICE PROBLEMS • Phase II enzymes are not very selective
Corrected Dosage • Drugs may undergo Phase II metabolism before or after Phase I
A drug is 50% cleared by the kidney and 50% by the liver. Its Phase II reactions will usually yield VERY POLAR inactive metabolites.
normal dosage is 200 mg/d. What is the corrected dosage in a That’s why some drugs can bypass phase 1 reactions all together.
patient with a creatinine clearance of 20 mL/min? Another way to help with remembering what phase 2 reactions (although
they normally won’t ask it in the exams) is anything that is outside of the
HORDe mnemonic (Phase I reactions) is part of your Phase 2 reactions.
CORRECTED DOSAGE Dr. Lopez
FOR RENAL PATIENTS

https://qrs.ly/t5blm0z
Examples of Phase II Reactions MNEMONIC: CYTOCHROME P450 INHIBITORS
“Inhibitors Stop Cyber Kids from Eating GRApefruit QV”
Isoniazid Grapefruit Juice
Sulfonamides Ritonavir (on acute ingestion)
Cimetidine Amiodarone
Ketoconazole Quinidine
Erythromycin Valproic Acid
OTHER CYP450 INHIBITORS
Table 4-2. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 Allopurinol Chloramphenicol
SUPPLEMENT: Chlorpromazine Dicumarol
Sites of Drug Metabolism Disulfiram Ethanol (acute toxicity)
Itraconazole Nortriptyline
• LIVER (most important organ for drug metabolism) Oral contraceptives Phenylbutazone
• KIDNEYS Saquinavir Secobarbital
• TISSUE COMPARTMENTS Spironolactone Troleandromycin
o few drugs (e.g. esters) are metabolized in many tissues (e.g. *Phenylbutazone (inhibits the metabolism of phenytoin & tolbutamide)*
liver, blood, intestinal wall) because of the broad Suicide Inhibitors
distribution of their enzymes
• bind irreversibly to metabolizing enzymes
Drug Biotransformation
o EXAMPLES: ethinyl estradiol, norethindrone, spironolactone,
• most often due to genetic or drug-induced differences
secobarbital, allopurinol, fluroxene, PTU
• gender is important for only a few drugs
o first-pass metabolism of alcohol (M > F)
• primary determinant of clearance DRUG EVALUATION AND REGULATION
o variations must be considered carefully when designing or SUPPLEMENT: Animal Testing
modifying a dosage regimen • required before human studies begin
Genetic Factors • function of the proposed use and the urgency of the application
• drug-metabolizing systems differ among families or o drug proposed for non-systemic use requires less extensive
populations in genetically determined ways testing
• recent advances in genomic techniques allow screening for a o anti-cancer drugs and drugs proposed for use in AIDS require
huge variety of polymorphisms (pharmacogenomics) less evidence of safety
Examples in Pharmacogenomics
• HYDROLYSIS OF ESTERS
ACUTE TOXICITY
Succinylcholine metabolism by Pseudocholinesterase • required for all new drugs
• ACETYLATION OF AMINES • involve administration of single doses of the agent up to the
Fast and slow acetylation of Isoniazid, Hydralazine, and lethal level in at least 2 species (e.g., 1 rodent and 1 non-rodent).
Procainamide SUBACUTE AND CHRONIC TOXICITY
• OXIDATION
• required for most agents, especially those intended for chronic
Debrisoquin, Sparteine, Phenformin, Dextromethorphan,
use
Metoprolol, and Tricyclic antidepressants
• duration: 2–4 weeks (subacute) or 6–24 months (chronic), in at
ENZYME INDUCTION least 2 species
• results from increased synthesis of cytochrome P450 enzymes SUPPLEMENT: Pharmacologic Profile
and heme • description of all the pharmacologic effects
• several days are usually required to reach maximum induction o effects on cardiovascular function, gastrointestinal activity,
• most common strong inducers are Carbamazepine, respiration, renal function, and endocrine function, CNS
Phenobarbital, Phenytoin, and Rifampin • both graded and quantal dose-response data are gathered
REPRODUCTIVE TOXICITY
ENZYME INDUCTION • involves the study of the fertility effects of the candidate drug
https://qrs.ly/19blm2g and its teratogenic and mutagenic toxicity
• FDA uses a 5-level descriptive scale to summarize information
regarding the safety of drugs in pregnancy
MNEMONIC: CYTOCHROME P450 INDUCERS FDA Drug Categories
“Ethel Booba takes Phen-Phen CATEGORY DESCRIPTION
and Refuses Greasy Carb Shakes” Controlled studies in women fail to demonstrate risk to
Ethanol (Chronic ingestion) Griseofulvin the fetus in the 1st trimester (and there is no evidence of
A
Barbiturates exc. SECOBARBITAL Carbamazepine a risk in later trimesters), and the possibility of fetal
Phenytoin St. John’s Wort/Smoking harm appears remote
Either animal reproduction studies have not
Rifampicin
demonstrated a fetal risk but there are no controlled
OTHER ENZYME INDUCERS: studies in pregnant women, or animal reproduction
Glutethimide B studies have shown an adverse effect (other than a
Phenylbutazone decrease in fertility) that was not confirmed in
Ritonavir (on chronic or repeated administration) controlled studies in women in the 1st trimester (and
**SECOBARBITAL is an INHIBITOR ** there is no evidence of a risk in later trimesters
** Phenylbutazone (induces the metabolism of Aminopyrine, Either studies in animals have revealed adverse effects
Cortisol, Digitoxin) ** on the fetus (teratogenic or embryocidal or other) and
there are no controlled studies in women, or studies in
C
ENZYME INHIBITION women and animal are not available. Drugs should be
• most significant inhibitors are Amiodarone, Cimetidine, given only when the potential benefit justifies the
Furanocoumarins present in grapefruit juice, azole antifungals, potential risk to the fetus.
There is positive evidence of human fetal risk, but the
and the HIV protease inhibitor ritonavir
benefits from use in pregnant women may be acceptable
• metabolism may be decreased by reduction in blood flow to the D despite the risk (e.g. if the drug is needed in a life-
metabolizing organ threatening situation or for a serious disease for which
o EXAMPLE: Propranolol reduces hepatic blood flow safer drugs cannot be used or are ineffective)
Studies in animals or human beings have demonstrated
fetal abnormalities or there is evidence of fetal risk
ENZYME INHIBITION based on human experience or both, and the risk of the
X
https://qrs.ly/6vblm2y use of the drug in pregnant women clearly outweighs
any possible benefit. The drug is contraindicated in
women who are or may become pregnant.
SUPPLEMENT: Drugs and Pregnancy CLINICAL TRIAL
• requires approval by institutional committees that monitor the
ethical (informed consent, patient safety) and scientific aspects
(study design, statistical power) of the proposed tests
INVESTIGATIONAL NEW DRUG (IND)
• includes all the preclinical data collected up to the time of
submission and the detailed proposal for clinical trials
NEW DRUG APPLICATION (NDA)
• constitutes the request for approval of general marketing of the
new agent for prescription use and includes all the results of
preclinical and clinical testing
TERATOGENESIS PHASE 1 TRIAL
• induction of developmental defects in the somatic tissues of the • careful evaluation of the dose-response relationship and
fetus pharmacokinetics among normal human volunteers (25–100
• studied by treating pregnant female animals of at least 2 species usually, only 20-50 for chemotherapeutic and other toxic drugs)
at selected times during early pregnancy when organogenesis is o EXCEPT in cancer and highly toxic agents (volunteer patients
known to take place with target disease)
o EXAMPLES: thalidomide, isotretinoin, valproic acid, ethanol, • acute effects of the agent are studied over a broad range of
glucocorticoids, warfarin, lithium, and androgens dosages
COMMON TERATOGENS PHASE 2 TRIAL
• evaluation of a drug in a moderate number of patients (e.g. 100–
200) with the target disease
• placebo or positive control drug is included in a single-blind or
double-blind design
• under carefully controlled conditions with close monitoring
usually in a hospital ward
• determine whether the agent has the desired efficacy at doses
that are tolerated by sick patients
PHASE 3 TRIAL
• large design involving many patients, including those
considered as “special population” (1000–5000)
• would be done by many clinicians in different
centers/hospitals/countries
• include placebo and positive controls in a double-blind
crossover design
• explore further the spectrum of beneficial actions of the new
drug, to compare it with older therapies, and to discover
infrequent toxicities not seen in Phase 2
• large amounts of data are collected
• usually very expensive
PHASE 4 TRIAL
• post-marketing surveillance phase
• detects toxicities that occur very infrequently
• findings reported early enough to prevent major therapeutic
disasters
MUTAGENESIS
• induction of changes in the genetic material of animals of any age
and therefore induction of heritable abnormalities
o EXAMPLES: aflatoxin, cancer chemotherapeutic drugs, and
other agents that bind to DNA
SUPPLEMENT:
Ames Test
• standard in vitro test for mutagenicity
• uses a special strain of Salmonella that naturally depends on
specific nutrients Figure 1-6. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
• loss of this dependence signals a mutation BIOEQUIVALENCE

Dominant Lethal Test • two related drugs are bioequivalent if they show comparable
• in vivo mutagenicity test carried out in mice bioavailability and similar times to achieve peak blood
• male animals are exposed to the test substance before mating concentrations
• abnormalities in the results of subsequent mating signal a • used in determining safety and efficacy of generic drugs
mutation in the male's germ cells SUPPLEMENT:
Drug Patents
CARCINOGENESIS • usually submitted around the time that a new drug enters
• induction of malignant characteristics in cells animal testing
• difficult and expensive to study • right to market the drug without competition from other
• high degree of correlation between mutagenicity in the Ames firms for a period of 20 years
test and carcinogenicity in some animal tests • after expiration of patent, any company may apply to the FDA
o EXAMPLES: coal tar, aflatoxin, nitrosamines, urethane, vinyl for permission to market a generic version of the same drug
chloride, polycyclic aromatic hydrocarbons in tobacco smoke o must demonstrate that their generic drug molecule is
(benzo-α-pyrene) bioequivalent
Orphan Drug ORGAN SYMPATHETIC PARASYMPATHETIC
• drug for a rare disease (one affecting fewer than 200,000 Eye
people) Iris radial muscle Mydriases (a1) No effect
• often neglected because the sales of an effective agent for an Iris circular No effect Miosis (M3)
uncommon ailment might not pay the costs of development muscle Relaxes (b) Contraction (M3) for
Ciliary muscle near vision or
accomodation
AUTONOMIC PHARMACOLOGY Heart
One of the most important topics to understand wholeheartedly for the SA node Tachycardia (b1 > Bradycardia (M2)
boards and for the general practice of medicine is the section on Contractility b2) Decreased (atria) (M2)
Autonomics. Always an all-time favorite. A tip in studying this section, Increased (b1 > b2)
understand the system of physiology and pathology in order to clinically Blood vessels
correlate and understand this section well. In this ordeal, it is essential to
Skin, splanchnic Vasoconstriction No effect
know the target organ, the messenger system (more of biochemistry) and
the response.
vessels (a1>a2)

Dr. Calderon Jr.
Autonomic Nervous System Skeletal muscle Vasodilation (b2 No effect

• major involuntary, unconscious, automatic portion of the vessels and less
nervous system importantly,
• concerned primarily with visceral functions (i.e. cardiac output, M3**)
blood flow distribution, digestion) Endothelium of Synthetizes and
• major divisions: vessels in heart, releases EDRF
o Parasympathetic ANS (PANS) brain and viscera (M3,M5)
o Sympathetic ANS (SANS) Bronchiolar Bronchodilation Bronchoconstriction
A good simplistic way to remember the difference between smooth muscle (b2) (M3)
parasympathetic and sympathetic nervous system is this. For the Gastrointestinal
sympathetic system, that is the system that is working during a “FIGHT tract
vs. FLIGHT response” (i.e. You’re a zookeeper who is in charge of feeding Smooth muscle Relaxation (a2, Contraction (M3)
hungry lions and suddenly, you locked yourself in the cage with them by walls b2)
accident. MAKAKAISIP KA BA NUN?). For the parasympathetic nervous
system, on the other hand, the theme for it is “REST and DIGEST”. All
Smooth muscle Contraction (a1) Relaxation (M3)
vegetative/constitutive functions are under the wing of the
parasympathetic nervous system.
sphincters
Dr. Lopez
• Enteric nervous system (ENS) Secretion Increased (M3)

o Primarily controlled by the ANS Genitourinary
o consists of myenteric plexus (plexus of Auerbach) and tract
submucous plexus (plexus of Meissner) Bladder wall Relaxation (b2) Contraction (M3)
(detrusor)
Trigone and Contraction (a1) Relaxation (M3)

bladder
sphincter
Uterus, pregnant Relaxation (b2) Contraction (M3)-

not sensitive
Penis, Seminal Ejaculation (a) Erection (M)

vesicles Hence Shoot; S for Hence Point, P for
Sympathetic parasympathetic
Dr. Lopez Dr. Lopez
Glands
(sweat, salivary, Increased secretion
No effect
lacrimal, (M)
nasopharyngeal)
Skin
Pilomotor Contracts (a) No effect
smooth muscle
Eccrine sweat Increases (M) No effect
glands remember, its
sympathetic but
mediated by Ach
OVERVIEW OF ANS Dr. Lopez
https://qrs.ly/gjblm3c Apocrine (stress) Increases (a) No effect
sweat glands
Liver Gluconeogenesis No effect
(b2, a)
Glycogenolysis No effect
(b2, a)
Fat cells Lipolysis (b3) No effect
Kidney Renin release No effect
(b1)
** Vascular smooth muscle in skeletal muscle has sympathetic cholinergic
dilator fibers
Correlate this table with your knowledge of autonomic physiology. This
serves as a review. As you can see, this table above that tabulates the
different organ systems with the corresponding sympathetic and
parasympathetic effects is a MUST REMEMBER guys. The goal is for you
MNEMONIC PLASMA (for parasympathetic nervous system)
to reconstruct this table from memory and be able to teach it to someone
Parasympathetic NS, Long preganglionic fibers, Acetylcholine, else. WHY? Because if you memorize this table, remembering the
Short postganglionic fibers, Acetylcholine different autonomic drugs will be a breeze. Muscarinic agonist,
antagonist. Beta agonist, alpha antagonist. DIBA nakakalito? vesicle membrane) and triggers FUSION of the vesicle membrane with the
Memorizing this table will give you the ability to predict the drug effect terminal membrane and opening of pore into the synapse. What
EASILY. As long as you know their mechanism of action and drug class, Botulinum toxin does it doesn’t allow fusion to happen, hence there is no
you’re good to go. release of Ach to the synaptic cleft.
Dr. Lopez
To help in remembering, remember this. When we talk about your alpha
1 receptor, regardless of location, when you STIMULATE it, it will always STEP 4 – TERMINATION
lead to CONTRACTION/CONSTRICTION. Whether it be found in the iris
• degradation of ACh into choline and acetate by
radial muscle, abdominal smooth wall or sphincter. When you talk about
your beta 2 receptor, regardless of location, when you STIMULATE it, it acetylcholinesterase (AChE)
will always lead to RELAXATION/DILATION. o inhibited by INDIRECT-ACTING CHOLINOMIMETICS
Also, when you talk about the difference between Beta 1 and beta 2, (Carbamates & Organophosphates)
remember that you only have 1 HEART (hence beta 1) and 2 LUNGS
(hence beta 2) TEST YOURSELF: Cholinergic transmission and drugs that
Dr. Lopez block each step (FILL IN THE BLANKS)
SUPPLEMENT: MNEMONIC: Point and Shoot PROCESS DRUGS THAT BLOCK EACH STEP
Point (Erection) = Parasympathetic NS Synthesis
Shoot (Ejaculation) = Sympathetic NS Storage
Release
Termination
CHOLINERGIC PHARMACOLOGY
ACETYLCHOLINE CHOLINERGIC
• primary transmitter in all autonomic ganglia and at the synapses PHARMACOLOGY
between parasympathetic postganglionic neurons and their AND QUIZ
effector cells https://qrs.ly/biblm4y
• primary transmitter at the somatic (voluntary) skeletal muscle
neuromuscular junction
SUPPLEMENT: Acetylcholinesterase (AChE)
• is an enzyme found in the postsynaptic membrane of
neuromuscular junctions that hydrolyzes Ach into choline
and acetic acid and thus terminates action of Ach
• Half-life: fraction of a second (very short)
• Butyrylcholinesterase (found in the liver) and
pseudocholinesterase (found in the plasma) are also
cholinesterases with lower specificity for Ach
Question: What drugs are metabolized by your Butyrylcholinesterase
/pseudocholinesterase?
Answer: Succinylcholine (the only DEPOLARIZING neuromuscular
blocker), Mivacurium (short acting NON-depolarizing neuromuscular
blocker)

Dr. Lopez
Cholinergic Drug Effects

• not very useful for systemic therapy because their effects are
not sufficiently selective
o PANS and SANS ganglia and somatic neuromuscular
junctions all may be blocked
• botulinum toxin is a very large molecule and diffuses very
slowly
o injection for relatively selective local effects
CHOLINORECEPTORS
Figure 6-2a. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
RECEPTOR RESULT OF LIGAND
TYPICAL LOCATION
NAME BINDING
STEP 1 – SYNTHESIS IP3 and DAG,
M1 Nerves
• ACh is synthesized from acetyl CoA and choline by the enzyme intracellular Ca2+
choline acetyltransferase (ChAT) Opening of K+
Myocardium, nerves,
o choline transport inhibited by Hemicholinium M2 channels, inhibition
smooth muscles
On a side note, CHT is a Na+/Choline symporter, as you can see in the of cAMP production
picture, it transports choline and Na in the same direction. Also, please Exocrine glands,
don’t confuse the drug Hemicholinium with Hexamathonium. vessels (Smooth IP3 and DAG,
M3
Hexamethonium is a GANGLION BLOCKER which you will encounter later muscle, intracellular Ca2+
as you proceed with your notes. Same first 2 letters sila but different endothelium)
drugs, different actions. The examiners love tricking you with sounds inhibition of cAMP
like/looks like drugs so now you know of their style. M4 CNS
Dr. Lopez
production
STEP 2 – STORAGE IP3 and DAG,
M5 CNS
intracellular Ca2+
• ACh is actively transported into vesicles for storage by vesicle-
Skeletal muscle Opening of Na+ and
associated transporter (VAT) NN neuromuscular K+ channels,
o inhibited by Vesamicol junction depolarization
Opening of Na+ and
STEP 3 – RELEASE Neuronal type,
NM K+ channels,
ganglion
• entry of calcium triggers interaction among SNARE proteins depolarization
(VAMPs and SNAPs) Important to correlate this table with your PHYSIO knowledge.
o Botulinum toxin alter synaptobrevins to prevent release of Remember the receptor, their locations, their mechanisms and secondary
ACh through the enzymatic removal of 2 amino acids from one messengers. An example of how examiners will test you is by asking this
or more of the fusion proteins (example lang eto guys): what is the secondary messenger involved in
Physiologic release of Ach is triggered by this calcium influx so this is an stimulation of your M2 receptor? Answer is decrease in cAMP (as opposed
important event. Based on your physio, this occurs when the action to increase in IP3 that can be seen with M1 and M3 activation. So, you now
potential reaches the terminal and triggers sufficient influx of calcium. know the different ways they can ask about this table
Dr. Lopez
Calcium, then, will interact with VAMP (specifically synaptotagmin on the
CHOLINOCEPTOR-ACTIVATING AND PILOCARPINE [C]

Class Cholinomimetic (direct-acting, muscarinic)
CHOLINESTERASE-INHIBITING DRUGS SimD CEVIMELINE [C] (M3 selective)
Activates muscarinic (M3) receptors in ciliary muscle
(causing contraction of ciliary body to facilitate
aqueous humor outflow and diminish its rate of
secretion) and salivary glands (increasing salivation)
Remember Muscarinic agonists instilled in the eye cause
MOA CONTRACTION of smooth muscle of iris sphincter resulting
to miosis and accommodation → the iris is pulled away from
the angle of the anterior chamber → trabecular meshwork
at the base of the ciliary muscle is OPENED → net result:
both effects facilitate aqueous humor outflow

Dr. Lopez
Uses Glaucoma, Sjögren syndrome, Sicca syndrome

Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
Miosis, Blurring of vision (due to cyclospasm),
The term Cholinomimetics, stems from the fact that these drugs, mimic Increased salivation, Hypertension
the action of Acetylcholine. Some cholinomemtics can be DIRECT Hypertension is an Interesting exception to the rule for
ACTING, meaning, they bind and activate CHOLINORECEPTORS (either SE pilocarpine (vasodilation is seen in Ach, carbachol and
muscarinic or nicotinic) or INDIRECT ACTING, meaning, they inhibit the bethanechol). But for Pilocarpine, hypertension maybe seen
termination of Ach by inhibiting the enzyme that metabolizes it. It’s after a brief period of hypotension due to the activation of
called indirect acting, because the drugs don’t act on the receptor per se sympathetic postganglionic M1 receptors
Dr. Lopez
but the final result is an increase in the levels of Ach, which will result in

a cholinomimetic action. In general, your cholinomimetics exhibit Good lipid solubility compared to choline esters
PST
PARASYMPATHOMIMETIC effects. Used as miotic
Cholinoreceptors or cholinergic receptors, on the other hand, are KEY LEARNING POINTS Sjögren Syndrome
receptors that respond to both Ach. Cholinergic muscarinic receptors What is Sjögren Syndrome?
respond specifically to the prototypical alkaloid, muscarine and
Cholinergic nicotonic receptors, on the other hand, respond to the drug
An autoimmune disorder characterized by triad of
Nicotine. • Xerostomia (Dry Mouth)
Dr. Lopez • Xerophthalmia (Dry Eyes)
• Rheumatoid Arthritis
DIRECT-ACTING CHOLINOMIMETICS
SUPPLEMENT: ACETYLCHOLINE [C] DIRECT-ACTING CHOLINOMIMETICS, NICOTINIC
Class Cholinomimetic (direct-acting, muscarinic) NICOTINE [C]
Similar Methacholine (no Nicotinic action, resistant to SimD VARENICLINE [C], LOBELINE
drugs AChE, just like carbachol and bethanechol) Class Cholinomimetic (direct-acting, nicotinic)
Act on both M and N receptors. Activates M1-M3 MOA Activates nicotinic Ach receptors (Nn and Nm)
MOA
receptors in all peripheral tissues. Uses Smoking Cessation
Uses Miotic during ocular surgery Generalized ganglionic stimulation (hypertension,
CNS stimulation, miosis, cyclospasm, SE
tachycardia, nausea, vomiting, diarrhea)
bronchoconstriction, excessive GI and GU Did you know that the fatal dose for nicotine is 40mg, found
smooth muscle contraction, increased secretory in 2 regular cigarettes? The reason why we don’t die from
SE
activity of sweat gland, airways etc., vasodilation smoking 2 cigarettes is that nicotine is destroyed as side
(arises from M3 activation and requires an intact stream smoke. But try eating your cigarettes… Okay,
endothelium – Nitric oxide mediated) PLEASE DON’T. Overdose can lead to convulsions, paralysis
and coma.
Results to increased secretion, smooth muscle
contraction (except in vascular smooth muscles Where does the addictive property of nicotine lie? Nicotine
Notes where it causes relaxation) and changes in heart in the CNS is associated with a greater release of dopamine
in the mesolimbic system. This results in a mild
rate; very short-lived duration of action: 5-30sec, alerting/addictive potential of Nicotine. Lesson? Stick to
rapidly hydrolyzed by AChE Notes smoking your cigarettes. Don’t eat them.

Dr. Lopez
BETHANECHOL [C] Nicotine activates ALL autonomic post ganglionic

Class Cholinomimetic (direct-acting, muscarinic) neurons (both sympathetic and parasympathetic,
Carbachol (act on both muscarinic and nicotinic hence producing generalized ganglionic stimulation)
SimD and skeletal muscle neuromuscular end plates. Able to
action)
Activates muscarinic (M1-M3) receptors. Act on M enter the CNS and activate NN receptors ; DOA: 1-6h
MOA only
receptors only
Bladder and bowel atony (post-surgery or spinal Varenicline: Selective partial agonist at nicotinic
Uses
cord injury), Congenital megacolon receptors; DOA 12-24h
Cyclospasm, Diarrhea, Urinary urgency, Vasodilation
SE
(similar MOA with Ach), Reflex tachycardia, Sweating MUSCARINIC TOXICITY
• Both carbachol and bethanechol are carbamic acid esters • This is seen in overdosage of muscarinic agonists and certain
and are resistant to hydrolysis of AChE, hence their longer types of mushrooms (genus: Inocybe)
duration of action, compared to Ach
• Treatment: Atropine (Cholinergic antagonist)
• Carbachol is used for glaucoma, used as miotic.
• Neostigmine (an indirect acting cholinomimetic) is also
• CNS stimulation
another drug useful for bladder and bowel atony. • EYE: miosis, spasm of accommodation
Notes
• Before administration of cholinomimetics, you must be • LUNGS: bronchoconstriction
certain that your patient doesn’t have mechanical • GIT/GUT: excessive gastrointestinal and genitourinary smooth
obstruction to outflow. Because administration of muscle activity
cholinomimetics in a patient with bladder and bowel • Increased secretory activity (sweat glands, airway,
atony will worsen obstruction.
Dr. Lopez
gastrointestinal tract, lacrimal glands)
• Vasodilation
SUPPLEMENT: MNEMONICS – Bethanechol Notice that the symptoms of muscarinic poisoning is essentially the same
with organophosphate poisoning minus symptoms of nicotinic excess
B = Bethanechol = Bowel & Bladder Atony which you will see with organophosphates (MOA of organophosphates:
long acting acetylcholinesterase inhibitor or indirect acting
cholinomimetic).
Dr. Lopez
NICOTINIC TOXICITY CORRELATIONS: Myasthenia Gravis
• largely due to the nonspecific ganglionic stimulation What is myasthenia gravis?
Remember sympathetic, parasympathetic and neuromuscular junctions An autoimmune destruction of nicotinic ACh receptors,
are ALL affected)
Dr. Lopez
characterized by:
• blockade of neuromuscular end plate depolarization • fluctuating muscle
o leading to fasciculations and paralysis • weakness
• CNS toxicity: stimulation (convulsions) followed by CNS • ocular symptoms
depression • bulbar symptoms
• Treatment: symptom directed (atropine for muscarinic excess, • proximal muscle weakness
diazepam and anticonvulsants for CNS stimulation, mechanical Q: Myasthenia gravis patients are sensitive to which drug class, that
ventilation if with neuromuscular blockade) when given, may actually worsen their condition?
A: Nondepolarizing neuromuscular blockers (because the mechanism
of the disease and its MOA are similar), Aminoglycoside antibiotics
INDIRECT-ACTING CHOLINOMIMETICS (because these drugs interfere with neuromuscular transmission)
Dr. Lopez
MOA of Indirect-Acting Cholinomimetics
• bind to cholinesterase and undergo prompt hydrolysis SUPPLEMENT:
Differentiate myasthenic crisis
o alcohol portion released from cholinergic crisis
o acidic portion retained and released slowly MYASTHENIC CRISIS
§ prevents the binding and hydrolysis of endogenous • acute worsening of symptoms due to infection, stress or
acetylcholine UNDERmedication
§ amplify acetylcholine effects wherever Ach is released CHOLINERGIC CRISIS
• no significant actions at uninnervated sites where ACh is not • excessive activation of cholinoceptors (skeletal muscle
normally released weakness and parasympathetic signs) due to
In simple terms, your indirect acting cholinomimetics act by raising Ach
OVERmedication
concentrations in the synaptic cleft by inhibiting the action of the enzyme
that metabolizes Ach. Hence, the term acetylcholinesterase inhibitors How does EDROPHONIUM differentiate myasthenic crisis from
provide better insight to the MOA of these drugs. Personally, I like to call cholinergic crisis?
them using that term, instead of indirect acting cholinomimetics. • IMPROVES muscle strength in myasthenic crisis
Dr. Lopez
• WEAKENS muscle strength in cholinergic crisis

EDROPHONIUM [C]
Class Cholinomimetic (indirect-acting) [Alcohol] RIVASTIGMINE [B]
Inhibits acetylcholinesterase. Amplifies endogenously SimD GALANTAMINE [B], DONEPEZIL [C], TACRINE [C]
MOA
released acetylcholine. Class Cholinomimetic (indirect-acting)
Myasthenia gravis (diagnosis – Tensilon test), Inhibits acetylcholinesterase. Amplifies endogenously
MOA
Differentiation of cholinergic crisis and myasthenic released acetylcholine.
Uses
crisis (see note below for explanation) , Reversal of neuromuscular Uses Alzheimer’s disease
blockade Miosis, Salivation, Nausea, Vomiting, Diarrhea,
Miosis, Salivation, Nausea, Vomiting, Diarrhea, SE
SE Bradycardia
Bradycardia Rivastigmine is available as transdermal patch
PST IV, very short lived DOA: 5-15min Donepezil is combined with Memantine (NMDA
PST antagonist) for Alzheimer’s dementia
NEOSTIGMINE [C] ** Donepezil is often asked in the exams. Please keep it
PYRIDOSTIGMINE [C], PHYSOSTIGMINE [C], close to your ♥**
SimD AMBENONIUM [C], DEMECARIUM [CARBAMATES]
Most students get confused with the drugs used for Alzheimer disease vs.
[C], ECHOTHIOPHATE [ORGANOPHOSPHATE] [C] the ones used for Parkinson disease (maybe because both are CNS
Class Cholinomimetic (indirect-acting) pathologies). In solving this, remember that the primary pathology in
Inhibits acetylcholinesterase. Amplifies endogenously Parkinson is dopamine deficiency. So, the drugs’ MOA should aim to
MOA
released acetylcholine. increase dopamine for Parkinson. For Alzheimer, the MOA of some of the
Myasthenia gravis (treatment), Reversal of drugs used for this condition is aimed at increasing Ach levels. Two very
nondepolarizing neuromuscular blockade different drug classes and mechanisms. Don’t get confused.
Dr. Lopez
Uses (Neostigmine), Glaucoma (physostigmine,
echothiophate, demecarium), Bladder and Bowel MNEMONIC: Organophosphate Poisoning
atony (Neostigmine) What are the signs and symptoms of organophosphate
Miosis, Salivation, Nausea, Vomiting, Diarrhea, poisoning? DUMBBELSS
SE Diarrhea Excitation (skeletal muscle and CNS)
Bradycardia
Muscarinic effects are blocked by ATROPINE Urination Lacrimation
Neostigmine: poor lipid solubility, oral. DOA: 30 min-2 Miosis Sweating
hours Bronchospasm Salivation
Pyridostigmine: poor lipid solubility, oral. DOA: 4-8 hours Bradycardia
Echothiophate: moderate lipid solubility. DOA: 2-7 days
Notes Physostigmine: good lipid solubility: able to enter the CNS SUPPLEMENT: Other Drugs for Alzheimer’s Dementia
because of its tertiary amine structure, DOA: 4-8h (All other MEMANTINE [B] NMDA receptor blocker; used for
indirect acting cholinomimetics are quaternary ammonium moderate to severe Dementia
compounds; therefore, they cannot cross the blood brain
barrier) TREATMENT OF ORGANOPHOSPHATE POISONING
Dr. Lopez
ATROPINE [C]
QUIZ TIME! Class Cholinergic antagonist (muscarinic)
Q: What is the Drug of choice for bowel and bladder atony whose MOA is
MOA Competitively blocks ALL muscarinic receptors
a nonselective muscarinic agonist?
A: Bethanechol Mydriatic, Cycloplegic, Antidote for organophosphate
Uses poisoning (first choice), Bradycardia, Hypersalivation,
Q: When reversing the effects of non-depolarizing neuromuscular
blockers with neostigmine or edrophonium, why do we need to co-
Decrease airway secretion during general anesthesia
administer ATROPINE? Tachycardia, Mydriasis, Cycloplegia, Skin flushing,
A: To counteract the bradycardia associated with giving an indirect SE Delirium, Hallucinations, Urinary retention,
acting cholinomimetic Constipation
Dr. Lopez Addresses only MUSCARINIC symptoms, No effect on the
SUPPLEMENT: OTHER ORGANOPHOSPHATES nicotinic signs of toxicity.
Notorious for causing hyperthermia in susceptible
Malathion (Scabicide) and Parathion (Insecticide): high lipid Notes
patients (because Atropine suppresses thermoregulatory
solubility, DOA: 7-30 days sweating).
Sarin, Tabun, Soman: Nerve Gases Dr. Lopez
Direct acting Muscarinic Agonist: cholinomimetics big responses are as BENZTROPINE [C]
follows: SimD BIPERIDEN [C], TRIHEXYPHENIDYL [C]
1) a decrease in heart rate Class Cholinergic antagonist (muscarinic)
2) increase in secretion and Competitively blocks all muscarinic receptors.
3) increase in smooth muscle contraction (e.g. diarrhea and urinary MOA Restores neurotransmitter balance in the basal
incontinence)
ganglia.
Direct acting Muscarinic Agonist: cholinomimetics directly act on the Uses Parkinson’s disease
receptor of effector cells (do not require acetylcholinesterase nor
Blurring of vision, Dry eyes, Constipation, Dry mouth,
INNERVATION) SE
Urinary retention
Acetylcholinesterase inhibitors: Indirect-acing cholinomimetics The tremors associated with Parkinson disease is a result of
• they will not reach the blood vessels (they purely act on innervation) RELATIVE EXCESS of cholinergic activity due to the
• they also stimulate nicotinic receptors deficiency of dopaminergic activity in the basal-ganglia
Dr. Calderon Jr.

Notes striatum system. Hence the role of your cholinergic

PRALIDOXIME [C] antagonists in improving tremors. It is important to note
Class Cholinesterase regenerator, Antidote that your cholinergic antagonists reduce tremors more
Binds phosphorus of organophosphate. Breaks than bradykinesia or rigidity
MOA organophosphate bond with cholinesterase. Dr. Lopez
(Regenerates active acetylcholinesterase)

Antidote for early stage cholinesterase inhibitor MNEMONICS Muscarinic Antagonists for Parkinsonism
poisoning (organophosphate poisoning and nerve gas “Tri (try) to Park your BENZ, BIP (beep) here.”
Uses
poisoning) ; can relieve skeletal muscle and endplate • TRIhexyphenidyl
block • BENZtropine
SE Muscle weakness • BIPeriden
Addresses BOTH Nicotinic and Muscarinic symptoms. • PARK is for Parkinson’s disease
Must be administered before 6-8 hours of organophosphate
Notes bond with cholinesterase occurs (before the bond has AGED
or turned covalent, which is a stronger bond); has oxime MUSCARINIC ANTAGONISTS
group which has high affinity for phosphorus FOR PARKINSON DISEASE
Dr. Lopez https://qrs.ly/6qbln3y
If you notice, your cholinomimetics have similar side effects. So, the
strategy here is don’t memorize the side effects specific to the drug.
Memorize it as a drug class and tie it with the table you’ve memorized
from page 11. So now, I’m sure you see the value in memorizing that IPRATROPIUM [B]
table. TIOTROPIUM [B], UMECLIDINIUM [C],
SimD
Dr. Lopez GLYCOYRRONIUM [B]
Class M receptor antagonist
CHOLINOCEPTOR BLOCKERS Blocks muscarinic receptors in bronchial smooth
MOA muscle. Prevents vagal-stimulated
bronchoconstriction
Uses Acute Asthma, COPD
Dry mouth, blurred vision etc. (Anti-cholinergic
SE
effects)
• Less toxic than beta-agonists (LESS TACHYCARDIA
→ LESS ARRHYTHMIA) in patients with COPD
• Tiotropium and Aclidinium have longer DOA than
SUPPLEMENT: Atropine Ipratropium. Both bind to M1-M3 receptors with
• prototype nonselective muscarinic blocker equal affinity but dissociate most rapidly from M2
• found in Atropa belladonna receptors.
MNEMONIC – Cycloplegia and Mydriasis • Ipratropium given as aerosol has little systemic
C = Cycloplegia = Ciliary muscle paralysis = loss of Notes effects
Accommodation • Has no effect on the chronic inflammation aspect of
Mydriasis = Dilate (or you dilate your mouth when you say Bronchial asthma
mydriasis) • Glycopyrronium does not cross the BBB, and
consequently has none to few central effects. It may
ATROPINE [C] be used as a monotherapy as maintenance for COPD.
It may also be used as an anti-spasmodic and reduce
HOMATROPINE [C], CYCLOPENTOLATE [C],
SimD salivation with some anesthetics
TROPICAMIDE [C]
Class Cholinergic antagonist (muscarinic)
KEY LEARNING POINTS Ipratropium in COPD
MOA Competitively blocks ALL muscarinic receptors
Mydriatic : resulting from unopposed sympathetic dilator Why is ipratropium the preferred bronchodilator in patients
activity with comorbid COPD and heart disease?
Cycloplegic: due to weakened contraction of ciliary muscle, • less likely to cause tachycardia and cardiac arrhythmias
resulting in loss of ability to accommodate; hence an
Uses atropinized eye cannot focus for near vision SCOPOLAMINE [C]
Dr. Lopez
Class Cholinergic antagonist (muscarinic)

Antidote for organophosphate poisoning (first choice,

addresses muscarinic excess), Bradycardia, Competitively blocks ALL muscarinic receptors.
Hypersalivation MOA Additional MOA: Antagonizes histamine and
Tachycardia, Mydriasis, Cycloplegia, Skin flushing, serotonin.
Delirium, Hallucinations, Minimal stimulant effect in Motion sickness, decrease acid secretion in GIT,
SE Uses
the brain, “Sandy eyes” (Dry eyes due to reduced Nausea and Vomiting
lacrimal secretion) Drowsiness, Amnesia, Sedation, Blurring of vision, Dry
SE
it’s a tertiary amine that readily crosses blood brain barrier eyes, Constipation, Dry mouth, Urinary retention
(just like your physostigmine, which is an indirect acting Applied as a transdermal patch for motion sickness
Notes
cholinomimetic) Other name of scopolamine is hyoscine
Dr. Lopez Notes Scopolamine has the highest propensity to cause CNS
symptoms compared to all the other anticholinergics
Dr. Lopez
DICYCLOMINE [B] HEXAMETHONIUM [D]
Class Cholinergic antagonist (muscarinic) SimD TRIMETHAPHAN, [D] MECAMYLAMINE [C]
SimD HYOSCYAMINE [B], GLYCOPYRROLATE [B] Class Cholinergic antagonist (nicotinic)
MOA Competitively blocks M3 receptors. MOA Competitively blocks Nn nicotinic ACh receptors
Uses IBS, minor diarrhea, decrease acid secretion in GIT Uses Hypertension (obsolete), Hypertensive emergencies
Tachycardia, confusion, urinary retention, increased Postural Hypotension, Dry mouth, Blurred vision,
SE SE
IOP Constipation, Sexual dysfunction, Tachycardia
Structurally, these drugs are quaternary amines, hence Differentiate your Hexamethonium from Hemicholinium.
their actions remain on the periphery (unlike tertiary What’s the MOA of Hemicholinium again? Write in the
amines ex. Atropine, scopolamine that can cross the BBB blank below:
Notes and act centrally) Notes

Dr. Lopez
Available PO and IV forms, relatively short t½ (6hrs) ________________________________________________________________

Another Name: Dicycloverine Dr. Lopez
SUPPLEMENT: OXYBUTYNIN [B] How to predict the effect of ganglion blockers?

Class Cholinergic antagonist (muscarinic) First, figure out the predominant autonomic tone for the organ
concerned.
DARIFENACIN [C], SOLIFENACIN [C],
SimD TOLTERADINE [C], TROSPIUM [C], Pupils: Predominantly parasympathetic
IMIDAFENACIN [X] Blood vessels: Predominantly sympathetic
Cardiac (Contractility and heart rate): Predominantly parasympathetic
Slightly blocks M3 receptors. Reduces Detrusor
MOA So, if you administer ganglion blocking agents to these organs with intact
muscle tone
Uses Urge incontinence, Post-operative spasms autonomic innervation, the result will be as follows:
Tachycardia, constipation, xerostomia, increased Pupils → moderately DILATED (hence blurred vision)
SE Blood Vessels → Vasodilated (hence the severe orthostatic hypotension
IOP
observed in these agents)
Notes Available as patch (may cause pruritus)
Cardiac → tachycardia
Simple right?
ATROPINE TOXICITY Dr. Lopez
• Atropine fever (hyperthermia)

• Atropine flush (cutaneous vasodilation) NEUROMUSCULAR BLOCKERS
• Decreased secretions • important for producing complete skeletal muscle relaxation in
• Tachycardia surgery
• Arrhythmias (intraventricular conduction block) • classification
• Constipation o NONDEPOLARIZING (Tubocurarine, Pancuronium,
• Blurred vision Atracurium, Vecuronium)
• CNS toxicity o DEPOLARIZING (Succinylcholine)
• Treatment: Symptomatic MNEMONIC: Depolarizing Neuromuscular Blocker
o Temperature control: use of cooling blankets Kapag nakapagDEPOsit ka sa toilet, SUCCess yun!
o Seizure control: Diazepam (DEPOlarizing = SUCCinylcholine)
o Physostigmine You only have to remember one depolarizing agent, and that is
Atropine fever or hyperthermia is largely due to the inhibition of succinylcholine. The rest are nondepolarizing agents. Simplifies your
sweating. memorization right? There is an entire section discussing your
A more specific term if the symptoms are primarily CNS in nature is neuromuscular blockers in the CNS portion so stay tight.
Dr. Lopez
CENTRAL ANTICHOLINERGIC SYNDROME and can be caused by OD of
other anticholinergic, most notorious is scopolamine
ADRENERGIC PHARMACOLOGY
Dr. Lopez
MNEMONIC: Atropine Toxicity

NOREPINEPHRINE
• HOT as a hare (hyperthermia)
• DRY as a bone (decreased secretion) • primary transmitter at the sympathetic postganglionic neuron-
• RED as a beet (cutaneous vasodilation) effector cell synapses in most tissues
• BLIND as a bat (cycloplegia) o EXCEPTIONS:
§ eccrine sweat glands
• MAD as a hatter (CNS toxicity)
§ vasodilator sympathetic fibers in skeletal muscle
• it is the immediate precursor of epinephrine
CONTRAINDICATIONS TO MUSCARINIC
SUPPLEMENT: MNEMONIC: Dopamine/Norepinephrine
BLOCKERS
• cautious use in infants (since they are sensitive to the Dopamine vasoDILATES renal blood vessels while
hyperthermic effects of atropine) Norepinephrine vasCONSTRICTS them
• acute angle-closure glaucoma (since mydriasis can block the
normal drainage of aqueous humor)
• benign prostatic hyperplasia (can precipitate further urinary
retention already present in this subgroup because muscarinic
antagonists will relax smooth muscle of the ureters and bladder
wall)
GANGLION BLOCKERS
• competitive pharmacologic antagonists at nicotinic
acetylcholine receptors of both sympathetic and
parasympathetic autonomic ganglia
Differentiate this with your neuromuscular blocking agents which act on
nicotinic acetylcholine receptors found at the neuromuscular junctions.
Same types of receptors but different locations
Dr. Lopez
• first successful agents for the treatment of hypertension but

were abandoned
o adverse effects of ganglion blockade in hypertension are so
severe
o lack of selectivity confers broad range of undesirable effects,
hence limiting its use Figure 6-2b. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
STEP 1 – SYNTHESIS Remember, the theme of alpha 1 receptor is when stimulated, regardless
• tyrosine is hydroxylated by tyrosine hydroxylase to DOPA of location, is contraction.
Dr. Lopez
o inhibited by Metyrosine
ALPHA-2 (a2) ADRENERGIC EFFECTS

• DOPA is decarboxylated to dopamine
Tissue Actions
• Dopamine is hydroxylated to norepinephrine
Adrenergic and cholinergic
INHIBIT transmitter release
Tyrosine hydroxylase catalyzes the rate limiting step of catecholamine terminals
synthesis. Platelets Stimulates aggregation
Dr. Lopez
Some vascular smooth muscle Contracts
Fat cells Inhibits lipolysis
STEP 2 – STORAGE Pancreatic B cells Inhibits insulin release
• norepinephrine and dopamine are transported into vesicles eyes Increase outflow of aqueous humor
o inactivated by monoamine oxidase in the cytoplasm
o Monoamine oxidase inhibitors (MAOi) increase stores of NE
and dopamine ALPHA-2 RECEPTORS
• The transfer of DOPA into vesicles is BLOCKED by the drug https://qrs.ly/gwblnid
Reserpine
BETA-1 (b1) ADRENERGIC EFFECTS
STEP 3 – RELEASE (CALCIUM DEPENDENT)
• entry of calcium triggers interaction among SNARE proteins
(VAMPs and SNAPs)
o inhibited by Guanethidine
o promoted by Amphetamines and Tyramine
BETA-2 (b2) ADRENERGIC EFFECTS
Release of NE via these agents is calcium INDEPENDENT.
Dr. Lopez
STEP 4 – TERMINATION
• diffusion and reuptake via NET and DAT in synaptic cleft
o inhibited by Cocaine and TCAs
• metabolized by MAO and COMT into metanephrines and VMA
o inhibited by MAOi and COMTi
SITES OF AUTONOMIC DRUG ACTION

MNEMONIC: Beta receptors
You have 1 heart and 2 lungs
b1 is for the heart, b2 is for the lungs
Beta receptors are more sensitive than alpha receptors.
Beta 1 blocker decreases renin release in the management of
hypertension.
Beta 2 receptors are found in all blood vessels mostly are not innervated.
Who cannot reach beta 2 receptors? Neurotransmitters e.g.
Norepinephrine
Clinical correlation:
During a fight or flight response, there is a surge of norepinephrine. What
are the effects of norepinephrine during fight or flight response? What is
You should be able to recreate this table from memory.
Dr. Lopez
the role of epinephrine during this stage?
Norepinephrine will cause alpha 1 stimulation → vasoconstriction. If
SUPPLEMENT: Drug Effects on Adrenergic Transmission there is too much vasoconstriction there would be no blood supply to the
• used in treatment of several diseases (pheochromocytoma, critical organs just like the heart, brain and skeletal muscle. Epinephrine
hypertension) plays a role in vasodilation to give blood supply to these organs.
o block sympathetic but NOT parasympathetic functions Remember that epinephrine can act on the beta 2 receptors causing
vasodilation → decrease in total peripheral resistance → decrease in
• other drugs promote catecholamine release diastolic blood pressure → decrease in afterload and also smooth muscle
o predictably cause sympathomimetic effects relaxation.
Norepinephrine can never ever decrease the blood pressure because it has
ADRENOCEPTORS no Beta 2 effect.
Dr. Calderon Jr.
• describes receptors that respond to catecholamines (NE, EPI and

MISCELLANEOUS ADRENERGIC EFFECTS

DOPA) Beta-3 (b3) Adrenergic Effects
Dopamine-1 (D1) Adrenergic Effects

Tissue Actions
Renal, mesenteric, coronary, Renal: vasodilation, increased
cerebral vascular beds Na+ excretion inducing
natriuresis and diuresis
Dopamine-2 (D2) Adrenergic Effects

Tissue Actions
Presynaptic nerve terminals à Vasodilation
inhibits adenyl cyclase and NE
Alpha-1 (α1) Adrenergic Effects release
Pituitary gland, emetic center, Can explain nausea and
medulla, kidney vomiting when D2 receptors are
stimulated
SYMPATHOMIMETICS DOPAMINE [C]

Class Sympathomimetic (non-selective, direct-acting)
Activates a, b and D1 adrenergic receptors.
a1: vasoconstriction, increases BP, increase
MOA pulmonary vascular resistance
b1: increased HR, conduction and contractility
D1: vasodilation in splanchnic and renal blood vessels
Cardiogenic Shock, Acute Heart failure (especially if
accompanied with severe hypotension)
Dopamine is best used for patients with decreased
contractility, low systemic blood pressure and low urine
Uses output (ex. Cardiopulmonary bypass or chronic heart
failure). It is UNIQUE among the catecholamines in being
able to simultaneously INCREASE myocardial contractility,
GFR, excretion of Na and urine output)
Dr. Lopez
SE Cardiovascular disturbance, Arrhythmias

Inactive per orem ; do not enter CNS significantly; short
DOA; very effective in renal failure associated with shock
MOA of Sympathomimetics L-dopa (immediate precursor of dopamine), the first line
Notes drug for Parkinson, readily crosses the blood brain barrier
• direct activation of adrenoceptors
Dopamine is NOT the preferred inotropic agent with
• indirect activation by increasing concentration of available pulmonary hypertension or right ventricular dysfunction
catecholamines in the synapse Dr. Lopez
o release of stored catecholamines
DOSE-DEPENDENT ACTIONS OF DOPAMINE
o inhibition of reuptake
• LOW DOSE (0.5 to 3 mcg/kg/min)
EPINEPHRINE [C] o Stimulates D1 and D2 receptors
Sympathomimetic (non-selective, direct-acting) o Leading to vasodilation, decreased arterial blood pressure and
Class
Other names: adrenaline increased renal and splanchnic blood flow (natriuresis and
Activates a and b adrenergic receptors. diuresis will occur)
a1: vasoconstriction (predominantly in the cutaneous, • MEDIUM DOSE (3-10 mcg/kg/min)
splanchnic & renal vascular beds) causing increases BP o Stimulates β1 receptors
more apparent at higher dose of epi infusion o Results in increased cardiac output (by increasing
b1: increased HR, conduction (by accelerating the rate chronotropy and contractility)
of spontaneous phase 4 depolarization) and • HIGH DOSE (>10 mcg/kg/min)
MOA
contractility, increased liver glycogenolysis (can o Stimulates α1 receptors
explain perioperative hyperglycemia) o Leads to arterial and venous vasoconstriction, increased
b2: bronchodilation, vasodilation in skeletal muscle BV systemic vascular resistance, increased blood pressure and
(can explain fall in total peripheral resistance seen with therefore, increased cardiac output
lower doses of epi infusion) o Reflex bradycardia may be seen at this point
b1 = b2 > a Dopamine acts like Norepinephrine in high doses.
Dr. Lopez
Severe Asthma, COPD, Hemostasis
Added to local anesthetic solutions to decrease systemic ISOPROTERENOL [C]

Uses absorption hence prolonging the duration of anesthetic and Class Sympathomimetic (beta-nonselective)
contributes to a bloodless surgical field Non-selectively activates b adrenergic receptors.

Dr. Lopez
b1: increased HR, conduction and contractility
Hypertension, Tachycardia, Ischemia, Hyperglycemia, b2: bronchodilation, vasodilation
SE Mydriasis (due to alpha 1 activation), arrhythmias
(MOST arrhythmogenic) Its action leads to a fall in mean arterial pressure as
MOA
contributed by a fall in diastolic blood pressure and
Functions as a hormone (secreted by the adrenal medulla)
systemic vascular resistance. This offsets the possible
Inactive per orem (significant first pass effect) hence its
increase in systolic blood pressure contributed by increase
formulations are available as SQ, IV and IM; do not enter
in cardiac output due to B1 stimulation.
Notes CNS significantly because it is purely lipid INsoluble Dr. Lopez
(remember what we’ve discussed in the basics?) ; short

Asthma (adjunct to your Beta 2 agonist), Drug for

DOA ; can cross the placenta (may cause fetal anoxia)
Dr. Lopez Uses sustained increases in HR (during pacemaker
insertion for bradydysrhtmia)
NOREPINEPHRINE [C]
SE Cardiovascular disturbance, Arrhythmias
Sympathomimetic (non-selective, direct-acting)
Class First of all, just because a drug ends with an -ol, doesn’t
Other names: noradrenaline, levarterenol mean it’s a Beta blocker (think propranolol, esmolol,
Activates a and b adrenergic receptors. metoprolol). Isoproterenol is an exception to that rule. It is
a1: intense vasoconstriction in ALL vascular beds a non-selective beta agonist, NOT A BETA BLOCKER
MOA (except coronaries), increases BP Pearl: Avoid Isoproterenol for patients with coronary artery
b1: increased HR, conduction and contractility disease. Why? If given to patients with CAD, Isoproterenol
won’t induce a compensatory baroreceptor mediated reflex
a > b1 >> b2 (almost negligible) Notes
slowing of the HR (because mean arterial pressure is not
First line treatment for refractory hypotension in increased which is a trigger for reflex bradycardia to occur).
Uses
severe sepsis, Cardiogenic shock (last resort) Therefore, tachycardia in the setting of a CAD patient will
Extreme vasospasm, Tissue necrosis (when worsen the existing coronary problem of the patient
extravasation occurs, hence better to use a central Isoproterenol is a synthetic catecholamine, not readily
line), Ischemia and decreased end organ taken up into nerve endings
hypoperfusion (due to intense vasoconstriction), Dr. Lopez
SE
Arrhythmias (less chance compared to epi), Infarction,
Reflex bradycardia, Metabolic acidosis (due to intense SELECTIVE ALPHA-1 (α1) AGONISTS
peripheral vasoconstriction decreasing tissue blood PHENYLEPHRINE [C]
flow) PSEUDOEPHEDRINE [B], OXYMETAZOLINE [C],
Unlike epinephrine, norepinephrine has minimal metabolic
SimD TETRAHYDROZOLINE [C], MIDODRINE [C],
effects.
Dr. Lopez NAPHAZOLINE [C], XYLOMETAZOLINE [C]
Notes Compensatory vagal reflexes tend to overcome the Class Sympathomimetic (alpha1-selective)

direct positive chronotropic effects; Inactive per orem; Selectively activates a1 adrenergic receptors.
MOA
do not enter CNS significantly ; short DOA a1: vasoconstriction, increases BP
Nasal Decongestant, Mydriatic, Drug-induced METHYLDOPA [B]
Uses hypotension, Orthostatic hypotension, Spinal GUANFACINE [B], GUANABENZ [C],
SimD
anesthesia induced hypotension DEXMEDETOMIDINE [C], TIZANIDINE [C]
Rebound nasal congestion (Rhinitis Class Sympathomimetic (alpha2-selective)
SE medicamentosa), Stroke, Myocardial infarction, Activates a2 adrenergic receptors.
piloerection, urinary retention, Reflex bradycardia MOA a2: decreases central sympathetic outflow (by
• Ocular administration causes mydriasis WITHOUT lowering peripheral vascular resistance)
cycloplegia; also used intranasally to produce local Pre-eclampsia, Gestational hypertension,
vasoconstriction as a decongestant Uses “Conscious sedation” (Dexmedetomidine), muscle
• Phentolamine is the DOC for Alpha-1 agonist relaxant (Tizanidine)
overdose Sedation (most common undesirable SE), Hemolytic
• Avoid Pseudoephedrine in the 1st trimester because Anemia (positive Coombs test), Lactation (due to
it may be associated with possible risk of SE increased prolactin secretion), CNS effects (mental
gastroschisis depression, vertigo, nightmares, impaired mental
• No available data on oxymetazoline topical use in concentration)
Notes pregnant women to inform a drug-associated risk for
APRACLONIDINE [C]
major birth defects or miscarriage
SimD BRIMONIDINE [B]
• Midodrine is a drug used for the treatment of
Class Sympathomimetic (alpha2-selective)
orthostatic hypertension
Activates a2 adrenergic receptors.
For episodes of hypotension, Phenylephrine is useful for MOA
a2: decreases secretion of aqueous humor
patients with coronary artery disease and aortic stenosis
because it increases coronary perfusion pressure without Uses Glaucoma
chronotropic side effects (tachycardia) seen in other Blurring of vision, Dry mouth, hyperemia and
SE
sympathomimetics pruritus, eye discomfort
Dr. Lopez
SELECTIVE BETA-1 (b1) AGONISTS

SUPPLEMENT: HORNER’s SYNDROME DOBUTAMINE [B]
• A unilateral condition that results from interruption of Class Sympathomimetic (beta1-selective)
sympathetic nerves to the face. Activates b1 adrenergic receptors.
MOA
• Symptoms include vasodilation, ptosis, miosis and loss of b1: increases HR and contractility
sweating on the affected side Acute heart failure, Cardiogenic shock, Cardiac stress
testing
MNEMONIC: PAM is Horny (P- Ptosis, A - Anhidrosis or loss Uses Pharmacologic agent to induce ischemia in the
of sweating and M- Miosis) myocardium.

Dr. Lopez
Can be caused by a preganglionic or postganglionic lesion. Tachycardia, Arrhythmias, Tachyphylaxis,

How to differentiate? Hypertension, Eosinophilic myocarditis, Premature
SE
• If lesion is POSTGANGLIONIC (lesions results in ventricular beats, Angina, Dyspnea, Fever, Headache,
degeneration of adrenergic nerve endings and loss of stored Nausea
catecholamines from them), indirect acting Exists as a 50:50 racemic mixture of 2 stereoisomers
(-) enantiomer is a a1 agonist
sympathomimetics will NOT DILATE the abnormally
(+) enantiomer is a competitive antagonist at a1 and a
constricted pupil (because catecholamines have been lost strong agonist at b1>b2
from the nerve endings in the iris) but PHENYLEPHRINE (α1 Notes
Dobutamine effect on alpha receptors increases at higher
agonist) will. dose, which explains why peripheral resistance doesn’t
• If lesion is PREGANGLIONIC (leaves the postganglionic decrease significantly with dobutamine use
neuron INTACT), a NORMAL response (dilation) is seen with Dr. Lopez
BOTH types of drugs

SELECTIVE BETA2 (b2) AGONISTS
SELECTIVE ALPHA-2 (α2) AGONISTS ALBUTEROL/SALBUTAMOL [C]
CLONIDINE [C] SimD TERBUTALINE [C], RITODRINE [B], ISOXUPRINE [C]
Class Sympathomimetic (alpha 2-selective) Class Sympathomimetic (beta2-selective)
Activates beta2-receptors in bronchial smooth muscle
Activates a2 adrenergic receptors. MOA
→ bronchodilation.
a2: decreases central sympathetic outflow →
MOA Acute asthma attacks (DOC), Tocolysis for preterm
INHIBITION of sympathetic tone and reduced blood Uses
labor (terbutaline, ritodrine, Isoxuprine)
pressure
Uses Hypertension, Cancer pain, Opioid withdrawal Tachycardia, Tremors, Nervousness, Restlessness,
Sedation (common), Rebound hypertension (due to SE Arrhythmias when used excessively, Loss of
SE responsiveness (tolerance),
abrupt discontinuation), Dry mouth (common)
BP lowering effect of clonidine results from reduction of May precipitate arrhythmias in patient with
cardiac output due to decreased HR and relaxation of concurrent COPD and heart disease; Rapid
capacitance vessels and peripheral vascular resistance Notes development of tolerance; Isoxuprine may also be
Taper use prior to discontinuation to avoid rebound
used as a vasodilator in Raynaud’s phenomenon ;
hypertension Isoxuprine can cause maternal pulmonary edema
If rebound hypertension occurs, administer Phentolamine Clinical Applications of
SUPPLEMENT:
(reversible alpha antagonist) Sympathomimetics
When taken per orem, there is initial increase in BP then will
Notes go down once the drug enters the CNS
If Clonidine is given to patients with pure autonomic
failure, clonidine may INCREASE BP because the central
sympatholytic effect of clonidine becomes irrelevant
whereas peripheral vasoconstriction remains intact
Drug interaction with TCA: TCAs can reduce the
antihypertensive effect of clonidine (due to alpha blocking
effects of TCAs)
Dr. Lopez
SUPPLEMENT: OTHER SYMPATHOMIMETICS KEY LEARNING POINTS:

PHENYLPROPANOLAMINE [C] Alpha-1 Selectivity
• Act mainly by causing release of NE, but also has direct What is the pharmacologic advantage of a1 selectivity?
agonist activity at some adrenergic receptors. It activates A Reflex Tachycardia is LESS common and less severe
and B adrenergic receptors in the respiratory mucosa à
vasoconstriction and reduction in nasal secretions, tissue Settings where alpha selectivity is best used for
hyperemia, edema and nasal congestion; most commonly hypertension treatment
used as a nasal vasoconstrictor and an appetite suppressant ; a-adrenoreceptor antagonists are most useful when increased
may indirectly stimulate B receptors producing tachycardia blood pressure reflects excess circulating concentrations of a
and positive inotropic effect; Used with CAUTION because agonists (ex. Pheochromocytoma, overdosage of sympatho-
this may precipitate Hemorrhagic Stroke, especially among mimetics or clonidine withdrawal)
women MNEMONIC: Isoproterenol
ISOproterenol is NOT a beta blocker.
ADRENOCEPTOR BLOCKERS It is a nonselective beta agonist.
I SOrry! Akala ko beta blocker ka!
SUPPLEMENT: Selective Alpha-2 (a2) Blockers
YOHIMBINE
Class Adrenergic antagonist
MOA Selective a2 antagonist
Uses Orthostatic hypotension, Male erectile dysfunction
Increased skeletal muscle activity, tremors,
SE
tachycardia, hypertension, rhinorrhea, paresthesia
Yohimbine can greatly elevate BP if administered
Notes
to patients receiving NE-transport blocking drugs
NONSELECTIVE BETA BLOCKERS
PROPRANOLOL [C]
NON-SELECTIVE ALPHA BLOCKERS PINDOLOL [B], TIMOLOL [C], LABETALOL [C],
PHENOXYBENZAMINE [C] CARVEDILOL, [C, D in 2nd & 3rd trim] NADOLOL [C],
Class Adrenergic antagonist (alpha-nonselective) SimD
LEVOBUNOLOL [C], METIPRANOLOL [C], CARTEOLOL
Irreversibly blocks a adrenergic receptors (a1>a2) by [C], SOTALOL
MOA
forming a covalent bond with the receptors Class Adrenergic antagonist (beta-nonselective)
Uses Pheochromocytoma (pre-surgical) Blocks b1 and b2 receptors. Blocks sympathetic effects
MOA
Orthostatic hypotension, Reflex tachycardia, on heart and BP. Reduces renin release.
SE
Gastrointestinal irritation, myocardial ischemia Angina prophylaxis, Hypertension, Arrhythmias,
Phenoxybenzamine also blocks histamine (H1), Ach and Migraine, Performance anxiety, Hyperthyroidism /
serotonin receptors. Uses
Thyroid storm (Propranolol), Glaucoma, Esophageal
Notes Its reduction of BP is greatest when sympathetic tone is high varices (Propranolol)
(ex. Pheochromocytoma, upright posture, reduced Blood Bronchospasm, AV block, Heart failure, CNS sedation,
volume) Erectile dysfunction, increased VLDL and decreased
Dr. Lopez SE
HDL, Bradycardia (Most common cardiac SE),
Increased plasma potassium
PHENTOLAMINE [C], TOLAZOLINE [C]
Masks symptoms of hypoglycemia in diabetics
Class Adrenergic antagonist (alpha-nonselective)
MOA Reversibly blocks a adrenergic receptors (a1=a2). Carvedilol and Labetalol has combined a and b blockade
(may be used in pheochromocytoma)
Pheochromocytoma (pre-surgical), Antidote to a1
Uses agonist overdose, Rebound Hypertension, reversal IUGR, small placentas and congenital abnormalities have
been reported with Propranolol uses, but no adequate and
of local anesthetics in soft tissue sites
well-controlled studies conducted
Orthostatic hypotension, Reflex tachycardia,
SE Sotalol lacks local anesthetic action and has marked class
Gastrointestinal irritation
III antiarrhythmic effects
Phentolamine has minor inhibitory effects at serotonin
receptors and agonist effects at muscarinic, H1 and H2 Beta blockers are used for the treatment for
Notes hyperthyroidism by blocking the sympathomimetic effects
receptors.
Dr. Lopez Notes of thyroid hormones and inhibition of peripheral conversion
of thyroxine to triiodothyronine (more active form)
SELECTIVE ALPHA-1 (a1) BLOCKERS Interaction with verapamil (calcium antagonist): severe
hypotension, bradycardia, heart failure and cardiac
PRAZOSIN [C] conduction abnormalities. Setting: Susceptible patient
DOXAZOSIN [C], TERAZOSIN [C], TAMSULOSIN [B], taking a topical ophthalmic beta blocker with oral
SimD
SILODOSIN [B], ALFUZOSIN [B] verapamil.
Class Adrenergic antagonist (alpha1-selective) Propranolol: High first pass effect, highly protein bound
MOA Selectively blocks a1 adrenergic receptors Principal Contraindication to beta antagonist use:
Uses Benign prostatic hyperplasia, Hypertension preexisting atrioventricular heart block or cardiac failure
First dose orthostatic hypotension, Reflex tachycardia NOT caused by tachycardia
(less chance compared to non-selective a antagonists), Dr. Lopez
SE
Dizziness, Drowsiness, Headache, Weakness, Asthenia, BETA-BLOCKERS IN DIABETIC PATIENTS
Nausea, Edema, Increased HDL (Prazosin) • Beta blockers can mask premonitory symptoms of hypoglycemia
Tamsulosin is most selective for prostatic smooth from insulin overdosage (tachycardia, tremor, anxiety)
muscle; Doxazosin, Tamsulosin, Silodosin and • impaired hepatic mobilization of glucose
Alfuzosin are not indicated for use in females or for the
treatment of hypertension BETA BLOCKERS IN CARDIAC PATIENTS
Notes Oral tamsulosin may precipitate Intraoperative Floppy Iris • Timolol (non-selective), Propranolol (non-selective) and
Syndrome (IFIS) in patients undergoing cataract surgery. Metoprolol (b1 selective) prolongs survival in patients with
This is characterized by billowing of flaccid iris, propensity myocardial infarction
for iris prolapse and progressive intraoperative pupillary • Metoprolol (b1 selective), Bisoprolol (b1 selective) and
constriction
Dr. Lopez
Carvedilol (a/b antagonist) are effective in reducing mortality
in selected patients with chronic heart failure
EFFECTS NOT RELATED TO BETA BLOCKADE Though there is b1 (cardio-selective) blocker, in clinical practice we shy
Intrinsic Sympathomimetic Activity away from its use in the above condition. Remember, that selectivity is a
matter of dose and is different in the body
• Partial agonist activity
• Effective for hypertension and angina and ideal because they’re MNEMONICS:
less likely to cause bradycardia and abnormalities in plasma • All beta 1 blockers are with “-olol”
• All beta 1 blockers starting from A to M are cardioselective
lipids • All beta. Blockers name that start in P are nonselective
• Advantage in treating patients with asthma because these drugs Dr. Calderon Jr.
are less likely to cause bronchospasm
• Acebutolol, Pindolol, Carteolol, Labetolol, Celiprolol, TREATMENT FOR GLAUCOMA
Penbutolol, Bopindolol, Oxprenolol
Complex Organ Control: The Eye
Local Anesthetic Activity
• Also known as “membrane-stabilizing activity” • reciprocal control of the PUPIL
WHAT THE HECK does membrane stabilization mean? Membrane o SANS (pupillary dilator muscle)
stabilization means inhibition of action potential propagation across the o PANS (pupillary constrictor)
cell membrane similar to Na channel blockers that are class I anti- • CILIARY MUSCLE (controls accommodation)
arrhythmics) o PANS (primary control of muscarinic receptors)
Dr. Lopez
o insignificant contributions from the SANS
• disadvantage when beta-blockers are used topically in the eye • CILIARY EPITHELIUM
o decreases protective reflexes o important receptors with permissive effect on aqueous humor
o increases the risk of corneal ulceration secretion
• absent from timolol and Betaxolol making them useful in
glaucoma
Both beta and alpha antagonists
• Nebivolol
• Carvedilol
• Labetolol
MNEMONIC: Nadolol
NADOLOL = NAsa DOLO ang half-life= longest half-life
SELECTIVE BETA 1 (b1) BLOCKERS

ATENOLOL [D]
BETAXOLOL [C], ESMOLOL [C, D in 2nd & 3rd trim],
ACEBUTOLOL [B, D in 2nd & 3rd trim], METOPROLOL
SimD
[C], ALPRENOLOL, NEBIVOLOL [C], BISOPROLOL [C],
CELIPROLOL
Class Adrenergic antagonist (beta1-selective)
Selectively blocks b1 receptors. Blocks sympathetic
MOA
effects on heart and BP. Figure 6-9. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
Angina, Hypertension, Heart failure, Supraventricular FLOW OF AQUEOUS HUMOR
Uses
tachycardia (Esmolol only) Ciliary body ® posterior chamber ® anterior chamber angle ®
Bronchospasm (less chance), AV block, Heart failure, pupil ® anterior chamber ® trabecular meshwork ® canal of
SE CNS sedation, Erectile dysfunction, increased VLDL Schlemm ® uveoscleral veins
and decreased HDL, Increased plasma potassium
Beta 1 selective agents are also termed as cardio-selective
drugs (because 75% of beta receptors in the myocardium Types of Glaucoma
are beta 1 receptors) OPEN ANGLE CLOSED ANGLE
Beta 1 selective agents are better suited for patients with Chronic • Associated with a shallow anterior
asthma or restrictive airway disease (less chance of condition chamber
bronchospasm)
• A dilated iris can OCCLUDE outflow
Also, better suited for patients with essential hypertension drainage pathway between the cornea and
as these drugs lack inhibition of peripheral beta 2 receptors ciliary body → acute and painful increases
that produce vasodilation
in pressure
Notes Principal Contraindication to beta antagonist use: Treatment:
preexisting atrioventricular heart block or cardiac failure Treatment: Iridectomy
Pharmacologic
NOT caused by tachycardia
Masks symptoms of hypoglycemia in diabetics Pharmacologic Treatment of Glaucoma is two pronged:
Esmolol has shortest half-life 1. REDUCTION of aqueous humor Production
Betaxolol may also be used as ophthalmic solution for 2. ENHANCEMENT of aqueous humor OUTFLOW
glaucoma
Use of cardio-selective BB Atenolol during pregnancy has DRUG CLASS EXAMPLES MECHANISM
been shown to lower birthweights and impair fetal growth. TIMOLOL
Dr. Lopez (nonselective)
MNEMONIC: Esmolol LEVOBUNOLOL
ESMOLOL = ESMOL (small) lang ang half-life = shortest half- (nonselective)
life CARTEOLOL (non-
Beta antagonists
selective) Decreased
b1 blockers can be used in the management of hypertension. You decrease METIPRANOLOL (non- production of
the heart rate, stroke volume and cardiac output. Hence, oxygen demand selective) aqueous
is decreased. Patients with MI, HPN and angina (except Prinzmetal
BETAXOLOL (b1 humor from
variant we use nitrates) benefit from b1 blocker
selective) ciliary
The ultimate concern for b1 blockers is AV nodal blockade. Glucagon is the Osmotic agents Mannitol epithelium
known antidote
Brimonidine,
b1 blockers are also used in the management of open angle glaucoma (by a2 antagonists
Apraclonidine
decreasing aqueous humor production of the ciliary body) Carbonic
Beta blockers must be avoided in patients with asthma, diabetes mellitus Acetazolamide,
anhydrase
and peripheral vascular diseases Dorzolamide
inhibitors
Pilocarpine (Non Ciliary muscle
selective muscarinic contraction,
agonist), opening of
Cholinomimetics Physostigmine & trabecular
Echothiopate meshwork →
(Acetylcholinesterase increased
inhibitor) outflow
Increased
Prostaglandin Latanoprost, outflow
analogue Brimatoprost through canal
of Schlemm
Increased
Non selective a outflow via
Epinephrine
agonists uveoscleral
veins
Please do not neglect this table. Glaucoma is often asked in the exam.
Please know their specific MOAs. Their favorite question to ask is on
latanoprost and pilocarpine.
Dr. Lopez
CARDIOVASCULAR DRUGS
DRUGS FOR HYPERTENSION
JNC 7
JNC 8
AHA OCTOBER 2017 GUIDELINES
BLOOD PRESSURE
https://qrs.ly/a5blnj4
KEY LEARNING POINTS: Target BP • So for diuretics that cause K+ wasting, they are expected
What is the blood pressure goal in hypertensive patients with to cause HYPOkalemic Metabolic ALKALOSIS since H+ is
(JNC7) (JNC8) also lost in the urine. While for K+ sparing diuretics, since
you retain K+, you will also retain H+, leading to
• no comorbidities? < 140/90 • <150/90 HYPERkalemic metabolic ACIDOSIS. The mechanism of
• diabetes mellitus? < 130/80 • <140/90 acidosis caused by Carbonic Anhydrase inhibitors will be
• chronic kidney disease? < 130/80 • <140/90 further discussed in the diuretics chapter.
• Mechanism on how it causes Hypercalcemia and its
SUPPLEMENT: HYPERTENSION IN PREGNANCY
mechanism for Nephrogenic DI will be given during the
• NO CLEAR CONSENSUS ON THE MANAGEMENT OF MILD TO pearls. Reabsorption of Ca caused by Thiazides greatly
MODERATE HTN IN PREGNANCY. Nevertheless, drugs that helps in patients with renal Ca stones or Hypercalciuria.
have been listed as acceptable oral antihypertensive agents in Dr. Pereyra-Borlongan
pregnant women are as follows:

o Methyldopa FUROSEMIDE [C]
o Labetalol BUMETANIDE [C], TORSEMIDE, ETHACRYNIC ACID
SimD
o Nifedipine [B]
• Methyldopa is a drug of first choice. It does not alter maternal Class Loop diuretic
cardiac output or blood flow to the kidneys or uterus Inhibit Na/K/2Cl transporter in thick ascending limb
• The combined alpha and beta blockade of labetalol makes it a MOA of loop of Henle. Cause powerful diuresis and
peripheral vasodilator which has been shown to be effective increased Ca excretion.
in pre-eclamptic and non-proteinuric hypertension in Heart failure, Pulmonary edema, Hypertension,
Uses
pregnancy. However, because the safety record of labetalol in Hypercalcemia, Acute renal failure, Anion overdose
pregnancy in not well established as that of methyldopa, Hypokalemic metabolic alkalosis, Potassium wasting,
labetalol should be considered a 2nd line agent for pregnant SE Dehydration, Ototoxicity, Sulfa allergy, Hyperuricemia,
women with chronic hypertension requiring long-term drug Hypomagnesemia, Nephritis, Hypocalcemia
therapy. Ethacrynic acid is a loop diuretic that is not a sulfur-
• Oral CCBs have been shown to reduce maternal blood derivative, and therefore, can be given to Px with
pressure in pregnant women, but little is known about the sulfur allergy
effects of long-term administration in the 1st trimester. • TOXICITIES of LOOP DIURETICS? OH-DANG!
Among the CCBs, Nifedipine has been the best studied and has O-totoxicity
been used extensively in later pregnancy. H-ypokalemia
• Oral HYDRALAZINE is effective as monotherapy or as add-on D-ehydration
to methyldopa in chronic hypertension in pregnancy. In A-llergy to sulfa
general, hydralazine often requires combination therapy with N-ephritis
Notes
a sympatholytic agent (Methyldopa or BB) to help attenuate G-out
the reflex tachycardia associated with hydralazine • Very effective in edematous and states of fluid overload.
• Inhibition of a different isoform of NKCC1 in the inner is
• ACEi and ARBs are NOT recommended during pregnancy thought to be responsible for the ototoxicity that is rarely
• Diuretics are also avoided since it can reduce maternal seen with high dose IV loop diuretics
plasma volume and can cause electrolyte disturbance • Hypercalciuria may cause nephrocalcinosis
• Mechanism on how it causes Hypocalcemia and how it
can be used for Hypercalcemia will be given during the
DIURETICS pearls
Diuretics lower BP by decreasing volume and a direct vascular effect that Dr. Pereyra-Borlongan
is not yet fully understood.
SYMPATHOPLEGICS

HYDROCHLOROTHIAZIDE [B]
CHLORTHALIDONE [B], INDAPAMIDE [B], Decrease venous return, decrease HR, decrease contractile force, decrease
SimD cardiac output, decrease TPR
METOLAZONE [B]
Class Thiazide diuretic
Inhibit Na+/Cl- transporter in distal convoluted tubule.
MOA Cause moderate diuresis and reduced excretion of
calcium
Hypertension (first line), Heart failure, Hypercalciuria,
Uses
Renal calcium stones, Nephrogenic diabetes insipidus
Hypokalemic metabolic alkalosis, Dilutional
hyponatremia, Potassium wasting, Hyperglycemia,
SE
Hyperlipidemia, Hyperuricemia, Hypercalcemia Sulfa
allergy
Metolazone appears in cord blood and crosses
placenta and may cause hypokalemia, hyponatremia,
hypoglycemia, jaundice and thrombocytopenia.
• TOXICITIES OF THIAZIDES: HYPER-GLUC
G-lycemia
L-ipidemia
U-ricemia Modified from Figure 11-2. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
C-alcemia 1. CNS SYMPATHETIC OUTFLOW BLOCKERS
** Don’t ever forget thissss!
• Less effective in edematous states compared to Loop
CLONIDINE [C]
diuretics. Class Sympathetic Outflow Blocker
Notes • For diuretics remember that they can cause acid-base Activates a2 adrenergic receptors → decreases central
MOA
imbalances, both acidosis and alkalosis. sympathetic outflow
Uses Hypertension, Cancer pain, Opioid withdrawal
SE Sedation, Rebound hypertension, Dry mouth
DIURETICS
Taper use prior to discontinuation to avoid rebound
https://qrs.ly/m6blnj7
hypertension (Antidote: Phentolamine); readily enters
the CNS
• Always remember that “Where Na+ goes, water follows” When a2 receptors are stimulated, it causes a decrease in
and “Where Na+ goes, HCO3- follows too” (This will be Notes the outflow of the vasoconstrictor neurotransmitter
useful also for explaining acidosis caused by Carbonic Norepinephrine, hence decreasing the SVR
Anhydrase inhibitors). Major SE: Sedation. Kaya ask your patient how they will go
• Also remember that “Where K+ goes, H+ follows” home. Dapat may kasama baka mabangga :))
METHYLDOPA [B] PROPRANOLOL [C]
Class Sympathetic Outflow Blocker PINDOLOL [B], TIMOLOL [C], LABETALOL [C], CARVEDILOL,
Activates a2 adrenergic receptors → decreases central [C, D in 2nd & 3rd trim] NADOLOL [C], LEVOBUNOLOL [C],
MOA SimD METIPRANOLOL [C],
sympathetic outflow
BETAXOLOL [C], BISOPROLOL [C], NEBIVOLOL [C]
Uses Pre-eclampsia
Class
Adrenergic antagonist (beta-nonselective)
Sedation, Hemolytic anemia (Positive Coombs Test)
Blocks b1 and b2 receptors. Blocks sympathetic effects
Most commonly used maintenance meds for hypertension MOA
during pregnancy on heart and BP. Reduces renin release.
SE Positives Coombs test/Hemolytic anemia always comes out Angina prophylaxis, Hypertension, Arrhythmias,
of the PLE. It is usually asked as: What drug causes Uses Migraine, Performance anxiety, Hyperthyroidism,
HEMOLYTIC ANEMIA as an IDIOSYNCRATIC REACTION? Glaucoma
Bronchospasm, AV block, Heart failure, CNS sedation,
SE
Erectile dysfunction
2. GANGLION BLOCKERS Masks symptoms of hypoglycemia in diabetics
HEXAMETHONIUM [D] Carvedilol and Labetalol has combined a and b
SimD TRIMETHAPHAN [D], MECAMYLAMINE [C] blockade (may be used in pheochromocytoma) ; IUGR,
Class Ganglion blocker small placentas and congenital abnormalities have
MOA Competitively blocks Nn nicotinic ACh receptors been reported with Propranolol uses, but no adequate
Uses Hypertension (obsolete), Hypertensive emergencies and well-controlled studies conducted ; Metipranolol
Postural Hypotension, Dry mouth, Blurred vision, Notes is used as an ophthalmic drop for glaucoma
Constipation, Sexual dysfunction • Used as maintenance for Angina and post-
Not used anymore due to serious side effects. Since Nn STEMI/NSTEMI cases to decrease heart rate and thus
receptors are found in both Sympathetic nervous system decrease myocardial oxygen demand
SE (SNS) and Parasympathetic nervous system (PNS), • Used in Chronic heart failure to regular HR but NOT acute
blockade of both may be observed. heart failure for it may further depress the heart
Try to check the different side effects and see what • Mnemonic on BBs will be given during the pearls
autonomic nervous system is being inhibited (SNS or PNS?)
Dr. Pereyra-Borlongan KEY LEARNING POINTS: Pheochromocytoma
What drugs are used to control blood pressure in
3. NERVE TERMINAL BLOCKERS pheochromocytoma?
Phenoxybenzamine, Phentolamine or Labetalol
NOREPINEPHRINE SYNTHESIS,
STORAGE, RELEASE,
VASODILATORS
REUPTAKE, METABOLISM
https://qrs.ly/75bk4u2 1. OLDER ORAL VASODILATORS
• 5 general MOA for vasodilators:
RESERPINE [C] 1. Alter intracellular Ca2+: Hydralazine
Class Nerve terminal blocker 2. Opening of K+ channels → Hyperpolarization: Minoxidil
Irreversibly blocks the vesicular monoamine 3. Increase in NO (nitric oxide) → Inc. in cGMP → vasodilation:
MOA Nitroprusside, Nitrates (di yan magkagroup ha)
transporter (VMAT)
4. Ca2+ Channel Blockade: CCBs
Uses Hypertension (obsolete)
5. D1 receptor agonism: Fenoldopam
Sedation, Severe psychiatric depression, Suicidal
SE • Take note that ALL VASODILATORS have 1 COMMON SE: REFLEX
ideation TACHYCARDIA (due to a decrease in BP caused by vasodilation. The
Avoid in Px with history of depression tachycardia happens as a compensatory mechanism of your body to
Notes Not used anymore due to psychiatric side effects prevent hypotension)
See YouTube Video: 2:34min
Dr. Pereyra-Borlongan HYDRALAZINE [C]
Class Vasodilator
GUANETHIDINE [C] Alters intracellular Ca2+ metabolism. Relaxes
SimD GUANADREL [B] MOA arteriolar smooth muscle, causing vasodilation →
Class Nerve terminal blocker Decreases afterload
Inhibit vesicular release of NE from the presynaptic Hypertension, Heart failure (in combination with
MOA Uses
neuron ISDN), Pre-eclampsia
Uses Hypertension (obsolete) Edema, Reflex Tachycardia, Myocardial ischemia,
SE
Sedation, Severe psychiatric depression, Suicidal Drug-induced lupus
SE
ideation Combination treatment with ISDN for heart failure is
Avoid in Px with history of depression more effective than ACEIs in blacks
Not used anymore due to psychiatric side effects Notes Used in hypertensive urgencies among pregnant patients
Notes Emphasis on the Drug-induced lupus pls. Common PLE
See YouTube Video: 2:54min
Dr. Pereyra-Borlongan question.
4. ADRENERGIC BLOCKERS MNEMONIC: Drug-Induced Lupus
PRAZOSIN [C] What medications may cause drug-induced lupus?

“It’s HIPP to have LUPUS!”
DOXAZOSIN [C], TERAZOSIN [C], TAMSULOSIN [B],
SimD Hydralazine Procainamide
SILODOSIN [B], ALFUZOSIN [B]
Isoniazid Penicillamine
Class Adrenergic antagonist (alpha1-selective)
MINOXIDIL [C]
MOA Selectively blocks a1 adrenergic receptors
SimD DIAZOXIDE [C]
Uses Benign prostatic hyperplasia, Hypertension
Class Vasodilator
First dose orthostatic hypotension, Reflex tachycardia
SE (less chance), Dizziness, Drowsiness, Headache, Opens K+ channels in vascular smooth muscle, causing
MOA
Weakness, Asthenia, Nausea, Edema hyperpolarization, muscle relaxation and vasodilation
Tamsulosin is most selective for prostatic smooth Uses Hypertension, Alopecia
Edema, Reflex tachycardia, Angina, Pericarditis,
muscle; Doxazosin, Tamsulosin, Silodosin and
SE Pulmonary hypertension, Hypertrichosis, Hirsutism, Salt
Alfuzosin are not indicated for use in females or for the
and water retention
treatment of hypertension; Doxazosin and Terazosin
Notes Require concomitant use of diuretics and BBs to block
has longer duration of action than prazosin compensatory responses
Given at bedtime to prevent orthostatic hypotension Notes Has oral and topical preparations for hair growth J Yeyyy
“Start Low, Go Slow” Nagpapasalamat ang mga Aloe Vera :))
Dr. Pereyra-Borlongan Dr. Pereyra-Borlongan
HOW DOES MINOXIDIL CAUSE EXCESSIVE FENOLDOPAM [B]

SUPPLEMENT: Class Dopamine agonist (D1 receptor)
HAIR GROWTH?
Minoxidil stimulates hair follicles (telogen phase) to Causes arteriolar vasodilation of the afferent and
MOA
differentiate into growth follicles (anagen phase) efferent arterioles. Increases renal blood flow.
Uses Hypertensive emergency
SE Hypotension, Hypokalemia
2. CALCIUM CHANNEL BLOCKERS Short duration of action: 10mins
VERAPAMIL [C] Not commonly used due to its very short t½ Not commonly
Notes
SimD DILTIAZEM [C] available.
Class Non-dihydropyridine calcium channel blocker Dr. Pereyra-Borlongan
Block voltage-gated L-type calcium channels SUPPLEMENT: Malignant Hypertension

MOA
(Cardiac > Vascular) • accelerated form of severe hypertension associated with
Angina, Hypertension, Supraventricular tachycardia, rising blood pressure and rapidly progressing end-organ
Uses
Migraine damage
Constipation, Pretibial edema, Nausea, Flushing, • MANAGEMENT
SE Dizziness, Gingival hyperplasia, Heart failure, AV o powerful vasodilators (nitroprusside, fenoldopam, or
block, Sinus node depression diazoxide) combined with diuretics (furosemide) and beta-
Excessive cardiac depression may occur blockers to lower BP to 140–160/90–110
• Diltiazem does NOT cause gingival hyperplasia,
VERAPAMIL DOES
• Never used in Acute Heart Failure because it may further ANGIOTENSIN ANTAGONISTS
Notes depress the heart
• Since they are more cardio-selective than
Dihydropyridine CCBs, they are the ones used for
arrhythmia
• Common SE: constipation and edema
MNEMONIC: Drugs that can cause Gingival Hyperplasia

“NapaCa-Pangit ng gingiVa mo”
Nifedipine
Cyclosporine
Phenytoin
Verapamil
NIFEDIPINE [C]
AMLODIPINE [C], FELODIPINE [C], NICARDIPINE [C],
NISOLDIPINE [C], CLEVIDIPINE [C], ISRADIPINE [C],
SimD
LEVAMLODIPINE [D], LACIDIPINE [C],
LERCANIDIPINE [C],
Class Dihydropyridine calcium channel blocker
Block voltage-gated L-type calcium channels
MOA
(Vascular > Cardiac) Figure 11-3. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
Uses Angina, Hypertension

Constipation, Pretibial edema, Nausea, Flushing, 1. ACE INHIBITORS
SE Most common SE of this group: cough and angioedema
Dizziness
Greater vasodilator effect than cardio-depressant
CAPTOPRIL [C, D in 2nd & 3rd trim]

effect
ENALAPRIL [D], BENAZEPRIL [D], FOSINOPRIL [D],
• Since they are more vasoselective than non-
dihydropyridines, they are more of vasodilators
LISINOPRIL [D], QUINAPRIL [D], RAMIPRIL [D],
SimD
compared to the two. So they are the ones more used for TRANDOLAPRIL [D], MOEXIPRIL [D], PERINDOPRIL
hypertension [D], IMIDAPRIL
Notes • This group is not used for arrhythmia. Since they are Class Angiotensin converting enzyme (ACE)-inhibitor
potent vasodilators, they may cause reflex tachycardia, Inhibits ACE and formation of Angiotensin II.
hence, they have pro-arrhythmogenic effect MOA
Decreases aldosterone secretion
• Common SE: constipation and edema Hypertension, Heart Failure, Post-myocardial
• Other dihydropyridine CCBs cause gingival hyperplasia Uses
infarction, Diabetic nephropathy
too! I’ve seen several Amlodipine-induced gingival
hyperplasia J Cough, Taste disturbance, Angioedema, Hypotension,
SE
Dr. Pereyra-Borlongan Teratogen, Hyperkalemia
• Slows ventricular remodeling and increases survival
3. PARENTERAL VASODILATORS in heart failure.
NITROPRUSSIDE [C] • Delays progression of diabetic nephropathy
Class Vasodilator • Use of drugs that act on the RAAS during the 2nd & 3rd
trim reduces renal function and increases fetal and
Relaxes venous and arteriolar smooth muscle by
MOA neonatal morbidity and death.
increasing NO → ↑ cGMP → smooth muscle relaxation
• Discontinue as soon as pregnancy is detected (fetal
Hypertensive emergency, Acute heart failure,
Uses hypotension, neonatal skull hypoplasia, anuria, renal
Cardiogenic shock, Controlled hypotension
failure, renal dysplasia).
SE Hypotension, Headache, Cyanide Toxicity
Notes • Captopril has a short half-life, necessitating 2-4x a
Not commonly used because it is very light sensitive,
day administration
has short Duration of action; given as continuous
• May further decrease GFR in Px with Renal Artery
infusion
Stenosis because of dilation of the Efferent
• The most effective vasodilator there is! Why? Because it is
both an ARTERIOLAR vasodilator and a VENOdilator! arterioles.
Notes • May be combined with diuretics for patients
It can vasodilate virtually all your blood vessels.
• But due to its very sensitive and “high maintenance” necessitating multiple drugs for control of blood
nature, it is not commonly used (but in advanced pressure.
countries meron sila nito, galing!). • Should not be given in patients experiencing AKI (Acute
Kidney Injury) and Hyperkalemia.
• Never combine ACEi and ARBs together (Increased Fetal harm may occur when given during pregnancy.
adverse reaction since they have the same effect on the Use of drugs that act on the RAAS during the 2nd & 3rd
RAAS pathway and possible increased incidence of trim reduces renal function and increases fetal and
cancer) Notes neonatal morbidity and death.
• 5-20% of patients experience dry cough. Remedy:
May be combined with diuretics or CCBs for patients
decrease dose or shift to ARBs
• Do not give to patients with bilateral Renal Artery
necessitating multiple drugs for control of blood
stenosis since ACEi can decrease the GFR of the stenotic pressure.
kidney (due to removal of angiotensin II-induced renal MNEMONIC: Renin Antagonists
vasoconstriction)
“Alis ka Renin!”
• Usually withheld in patients who are CKD stage 4 already
because use of ACEi and ARBs may result in significant Aliskeren inhibits Renin action, therefore preventing
worsening of kidney function, while another study has conversion of Angiotensinogen to Angiotensin I.
suggested that discontinuing these agents in patients
with advanced CKD may improve renal function.
Dr. Pereyra-Borlongan DRUGS USED IN THE TREATMENT OF
ANGINA PECTORIS
KEY LEARNING POINTS ACE-inhibitors
SUPPLEMENT:
Why are patients with diabetic nephropathy treated with ACE-
Atherosclerotic Angina
inhibitors?
• angina of effort or classic angina
• ACE inhibitors decrease albumin excretion and slow
• associated with atheromatous plaques that partially occlude
progression from micro- to macroalbuminuria
1 or more coronary arteries
(renoprotective effect)
• constitutes about 90% of angina cases
Vasospastic Angina
2. ANGIOTENSIN RECEPTOR BLOCKERS
• rest angina, variant angina, or Prinzmetal angina
LOSARTAN [D]
• responsible for less than 10% of cases
CANDESARTAN [C in 1st trim, D in 2nd & 3rd trim],
• involves reversible spasm of coronaries, usually at the site of
VALSARTAN [D], IRBESARTAN [C in 1st trim, D in 2nd &
an atherosclerotic plaque
3rd trim], EPROSARTAN [C in 1st trim, D in 2nd & 3rd
SimD • may deteriorate into unstable angina
trim], TELMISARTAN [C in 1st trim, D in 2nd & 3rd trim],
AZILSARTAN [D], OLMESARTAN [C in 1st trim, D in 2nd Unstable Angina
& 3rd trim], VALSARTAN [D] • unstable/crescendo angina, acute coronary syndrome
Class Angiotensin receptor blocker (ARB) • increased frequency and severity of attacks that result from a
Blocks Angiotensin (AT1 receptors) in vascular smooth combination of atherosclerotic plaques, platelet aggregation
MOA muscle and adrenal cortex. Decreases aldosterone and vasospasm
secretion. • immediate precursor of a myocardial infarction
Uses Hypertension, Heart Failure, Diabetic nephropathy THERAPEUTIC STRATEGIES IN ANGINA
Hypotension, Teratogen, Hyperkalemia,
SE • defect that causes anginal pain is inadequate coronary oxygen
Hypoglycemia, Anemia, diarrhea
delivery relative to the myocardial oxygen requirement
• Slows ventricular remodeling and increases survival • can be corrected in 2 ways:
in heart failure o increasing oxygen delivery
• Delays progression of diabetic nephropathy o reducing oxygen requirement
• ARBS are as effective as ACEi but has less cough You decrease myocardial oxygen demand by decreasing the heart rate
• Use of drugs that act on the RAAS during the 2nd & 3rd You increase oxygen delivery by vasodilatation
trim reduces renal function and increases fetal and Dr. Pereyra-Borlongan
neonatal morbidity and death

• Discontinue as soon as pregnancy is detected (fetal
hypotension, neonatal skull hypoplasia, anuria, renal
Notes
failure, renal dysplasia).
• May be combined with diuretics or CCBs for patients
necessitating multiple drugs for control of blood
pressure.
• 1.6-6.6% of Px may experience cough as well.
• Has lower rates of cough and angioedema but higher
rates of hypotension
• May joke sana ako dito e, pero sa pearls na lang
hahahaha :))
KEY LEARNING POINTS Hyperkalemia

Why do patients taking angiotensin antagonists (ACEis/ARBs)
develop hyperkalemia? Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
• ACE-Is/ARBs reduce aldosterone levels and cause potassium

retention VASODILATORS
Effects of electrolyte imbalance on ECG: 1. NITRATES
• HyperKalemia: peaked T-waves AMYL NITRITE [C, X for angina]
• HypoKalemia: T-wave inversion
Class Ultrashort-acting nitrate
• HyperCalcemia: decreased PR-interval
• HypoCalcemia: increased PR-interval Releases nitric oxide (NO), increases cGMP (cyclic
Dr. Pereyra-Borlongan MOA guanosine monophosphate), and relaxes smooth
muscle, especially vascular
3. RENIN ANTAGONISTS Uses Cyanide poisoning
ALISKIREN [D] Reflex tachycardia, Orthostatic hypotension,
SE
Class Renin antagonist Headache, Methemoglobinemia
Inhibits renin. Prevents conversion of ROA: Inhalational
MOA • Part of the Lilly Cyanide Kit as short acting nitrite to
angiotensinogen to angiotensin I.
cause oxidation of Fe2+ in Hemoglobin to Fe3+ in
Uses Hypertension Notes methemoglobin
Headache, diarrhea, cough, rash, hyperkalemia, • Treatment for Methemoglobinemia? Low dose Methylene
SE increase in serum creatinine, renal impairment, blue J
angioedema Dr. Pereyra-Borlongan
KEY LEARNING POINTS Cyanide DILTIAZEM [C]

Class Non-dihydropyridine calcium channel blocker
Which portion of the electron transport chain is affected
by cyanide? Block voltage-gated L-type calcium channels
MOA
(cardiac > vascular)
• Complex IV (cytochrome oxidase) of the Electron Transport
Chain Angina, Hypertension, Supraventricular tachycardia,
Uses
What is the antidote for cyanide poisoning? Vasospasm, Raynaud’s phenomenon
• Lilly Cyanide Kit: inhaled amyl nitrite + IV sodium nitrite + IV Constipation, Pretibial edema, Nausea, Flushing,
sodium thiosulfate SE Dizziness, Heart failure, AV block, Sinus node
depression
SUPPLEMENT: Monday Disease Drug enters breast milk
• due to occupational exposure to nitrates Notes DOC for Prinzmetal Angina
• alternating development of tolerance (during the work week) Dr. Pereyra-Borlongan
and loss of tolerance (over the weekend) every Monday

KEY LEARNING POINTS Calcium Channel Blockers
Nitrates cause vasodilation → Increased ICP → headache

Dr. Pereyra-Borlongan Why is calcium-dependent neurotransmission or hormone
NITROGLYCERIN [C] release not affected by CCBs?
ISOSORBIDE DINITRATE [C], • CCBs block L-type calcium channels
SimD
ISOSORBIDE MONONITRATE [C] • other functions use N-, P-, and R-types
Class Short-acting nitrate What drugs can cause gingival hyperplasia?
Releases nitric oxide (NO), increases cGMP (cyclic NapaCa-Pangit ng gingiVa mo!
MOA guanosine monophosphate), and relaxes smooth Nifedipine Phenytoin
muscle, especially vascular Cyclosporine Verapamil
Uses Angina, Acute Coronary Syndromes
Reflex tachycardia, Orthostatic hypotension,
SE
Headache, Tolerance (transdermal) BETA BLOCKERS
Dangerous hypotension with PDE inhibitors such as PROPRANOLOL [C]
Sildenafil PINDOLOL [B], TIMOLOL [C], LABETALOL [C],
First Pass effect is ~90% (NTG) SimD CARVEDILOL [C, D in 2nd & 3rd trim], NADOLOL [C],
NTG also decrease platelet aggregation LEVOBUNOLOL [C], METIPRANOLOL [C]
• Nitrates increase cGMP. Sildenafil also increases cGMP Class Adrenergic antagonist (beta-nonselective)
Notes (by inhibiting its degradation). This could lead to a very Blocks b1 and b2 receptors. Blocks sympathetic effects
dangerous hypotension MOA
on heart and BP. Reduces renin release.
• Nitrates are more of a venodilator than an arteriolar Angina prophylaxis, Hypertension, Arrhythmias,
vasodilator
Uses Migraine, Performance anxiety, Hyperthyroidism,
• ISMN: M for matagal since it has longer half-life. And M
for Matibay since it does not undergo first pass effect Glaucoma
Dr. Pereyra-Borlongan Excessive B blockade: Bronchospasm, AV block, Heart
SE
failure, CNS sedation, Erectile dysfunction
Notes Masks symptoms of hypoglycemia in diabetics
SUPPLEMENT: Effects of Drug Combinations
KEY LEARNING POINTS: Nitrate-Induced Headache

Why do patients taking nitrates usually experience throbbing
headaches?
• due to meningeal blood vessel vasodilation
SUPPLEMENT: METABOLISM MODIFIERS

2. CALCIUM CHANNEL BLOCKERS
Metabolism modifiers decrease myocardial oxygen demand in general
NIFEDIPINE [C] since they try make use of pathways that utilize less ATP, hence, less
AMLODIPINE [C], FELODIPINE [C], NICARDIPINE [C], amount of work for the myocardium.
SimD
NISOLDIPINE [C], CLEVIDIPINE [C], ISRADIPINE [C]
Class Dihydropyridine calcium channel blocker TRIMETAZIDINE [C]

Block voltage-gated L-type calcium channels Class Cytoprotective agent, Metabolism modifier
MOA Inhibit Beta oxidation of fatty acid by inhibiting 3-
(Vascular > Cardiac)
Uses Angina, Hypertension ketoacyl-CoA thiolase which enhances glucose
MOA
Constipation, Pretibial edema, Nausea, Flushing, oxidation. Prevent decrease in ATP in ischemic /
SE hypoxic states.
Dizziness
Greater vasodilator effect that cardio-depressant Uses Angina pectoris, Tinnitus, Dizziness
Notes SE EPS, gait instability, restless leg syndrome
effect
Interacts with MAO inhibitors
VERAPAMIL [C] Notes Known Brand name is VASTAREL
Class Non-dihydropyridine calcium channel blocker Dr. Pereyra-Borlongan
Block voltage-gated L-type calcium channels
MOA RANOLAZINE [C]
(cardiac > vascular)
Class Metabolism modifier
Angina, Hypertension, Supraventricular tachycardia,
Uses Reduces a late, prolonged Na+ current in myocardial
Migraine
cells → decreased intracellular Na+ → increase Ca2+
Constipation, Pretibial edema, Nausea, Flushing,
MOA expulsion via Na+-Ca2+ exchanger → decrease
SE Dizziness, Gingival hyperplasia, Heart failure, AV
intracellular Ca2+ → decrease cardiac force and
block, Sinus node depression
work. May also modify fatty acid oxidation
Notes excessive cardiac depression may occur
Uses Prophylaxis of angina hospitalizations in the treatment group (patients with

SE QT prolongation, nausea, constipation, dizziness heart failure and sinus rhythm) but no reduction in
CYP3A4 inhibitors increase Ranolazine mortality or improvement in QOL. Generally, digoxin is
Notes now relegated as therapy for patients who remain
concentration and DOA
profoundly symptomatic despite optimal
IVABRADINE neurohormonal blockade and adequate volume
Class Metabolism modifier control.
In funny Na current in SA node, decreases
MOA hyperpolarization-induces inward pacemaker
current → decrease HR and cardiac work MOA OF DIGOXIN
Uses Prophylaxis of angina, Hear Failure https://qrs.ly/ipbk9z4
Bradycardia, Hypertension, Atrial Fibrillation
SE Very effective in decreasing heart rate without
decreasing the blood pressure J The most common ECG change seen in Digoxin toxicity is
Premature Ventricular Contractions (PVCs)
DRUGS USED IN HEART FAILURE MNEMONIC: Narrow Therapeutic Index

What drugs have narrow therapeutic index?
WALA na Cyang PaPa! VasTeD na!
Warfarin Phenobarbital
Aminoglycosides Phenytoin
Lithium Vancomycin
Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 Amphotericin B Theophylline
SUPPLEMENT: Pathophysiology of Congestive Heart Failure Carbamazepine Digoxin
• fundamental physiologic defect is decrease in cardiac
output relative to the needs of the body SUPPLEMENT: Digitalis Toxicity
• frequently associated with chronic hypertension, valvular • increased by hypokalemia, hypomagnesemia, and
disease, coronary artery disease, and cardiomyopathies hypercalcemia
o loop diuretics and thiazides may significantly reduce serum
THERAPEUTIC STRATEGIES FOR CHF
potassium and precipitate digitalis toxicity
• removal of retained salt and water with diuretics o digitalis-induced vomiting may deplete serum magnesium
• reduction of afterload and salt and water retention by means of and similarly facilitate toxicity
ACE inhibitors
There is more digitalis toxicity when given concomitantly with
• reduction of excessive sympathetic stimulation by means of diuretic especially Thiazides since it can cause all three: HypoK,
beta-blockers HypoMg and HyperCa
• reduction of preload or afterload with vasodilators Dr. Pereyra-Borlongan
• direct augmentation of depressed cardiac contractility with

positive inotropic drugs TREATMENT OF DIGITALIS TOXICITY
• Correction of potassium/magnesium deficiency
CURRENT CLINICAL EVIDENCE FOR CHF • Antiarrhythmic drugs
• ACUTE HEART FAILURE o drug of choice is LIDOCAINE
o should be treated with a loop diuretic o electronic pacemaker may be required in severe cases
o if very severe, use prompt-acting positive inotropes (beta- • Digoxin antibodies
agonists or PDE inhibitors) and vasodilators o digoxin antibodies (Fab fragments; Digibind)
• CHRONIC HEART FAILURE o may save patients who would otherwise die
o treated with diuretics (often loop plus spironolactone) plus If digoxin antibodies are not available, Bile Acid binding resins can be
an ACE inhibitor and, if tolerated, a beta-blocker given as a substitute (pls see topic on Drugs for Dyslipidemia. Examples
o digitalis may be helpful if systolic dysfunction is prominent include: Colestipol, Cholestyramine). Since these agents all substances
KEY LEARNING POINTS Heart Failure that look like cholesterol (meaning they also have the CPPP ring), then
they can also bind Digoxin since digoxin is also a sterol. (All glycosides are
Which type of heart failure presents with: sterol derivatives)
• Orthopnea, PND, Pulmonary Congestion? Dr. Pereyra-Borlongan
Left-sided heart failure

• Hepatomegaly, Edema, Engorged Neck Veins? OTHER DRUGS FOR CHF
Right-sided heart failure DIURETICS
It is important to take note that among patients with acute heart failure, • First-line therapy for both systolic and diastolic failure
the most important strategy is to unload the overloaded heart by diuresis, • FUROSEMIDE for immediate reduction of the pulmonary
and to decrease HR to decrease the amount of work that the myocardium
congestion and severe edema associated with acute heart failure
does.
Dr. Pereyra-Borlongan • SPIRONOLACTONE and EPLERENONE have significant long-
term benefits and can reduce mortality in chronic failure

DIGOXIN [C]
SimD DIGITOXIN [C]
Class Cardiac glycoside ANGIOTENSIN ANTAGONISTS
Inhibits Na+/K+ ATPase; Increases intracellular Ca2+, • reduce aldosterone secretion, salt and water retention and
MOA
increasing cardiac contractility vascular resistance
Uses Heart failure, Nodal arrhythmias • decrease ventricular remodeling (cardioprotective)
Narrow therapeutic index • reduce morbidity and mortality in chronic heart failure
SE
Arrhythmias, Vomiting, Diarrhea, Visual changes • first-line drugs for chronic heart failure
Reduced clearance with quinidine, amiodarone, • ARBs have the same benefits as ACE-inhibitors
cyclosporine, diltiazem and verapamil
Arrhythmogenesis increased by hypokalemia, BETA-1-SELECTIVE SYMPATHOMIMETICS
hypomagnesemia and hypercalcemia. Digitalis • DOBUTAMINE (b1-selective) and DOPAMINE are useful in acute
glycosides exert a mild inotropic effect, attenuate heart failure
Notes
carotid sinus baroreceptor activity and are sympatho- • not appropriate for chronic failure because of tolerance, lack of
inhibitory. These effects decrease serum oral efficacy and significant arrhythmogenic effects
norepinephrine levels, plasma renin levels, and
Tachyphylaxis is a common problem with Dobutamine.
possibly aldosterone levels. The DIG trial Dr. Pereyra-Borlongan
demonstrated a reduction in heart failure
BETA-BLOCKERS
• CARVEDILOL, LABETALOL, BISOPROLOL, NEBIVOLOL and SINGH-VAUGHAN WILLIAMS CLASSIFICATION
METOPROLOL reduce progression of chronic heart failure • based loosely on the channel or receptor affected
• beta-blockers are not of value in acute failure and may be o CLASS 1. Sodium channel blockers
detrimental if systolic dysfunction is marked o CLASS 2. Beta-adrenoceptor blockers
No value in Acute Heart Failure o CLASS 3. Potassium channel blockers
o CLASS 4. Calcium channel blockers

PHOSPHODIESTERASE INHIBITORS
• EXAMPLES: INAMRINONE, MILRINONE Always Remember: ALL ANTI-ARRHYTHMICS ARE PRO-ARRHYTHMICS.
They may cure you of a certain kind of arrhythmia, but they may cause
• MECHANISM OF ACTION:
you to have a different kind of arrhythmia.
o increase cAMP by inhibiting its breakdown by Dr. Pereyra-Borlongan
phosphodiesterase; increase intracellular Ca2+, vasodilation
• should not be used in chronic failure because they increase
CLASS 1 ANTIARRHYTHMICS
morbidity and mortality
• have local anesthetic activity
VASODILATORS • act on Phase 0 (zero) of cardiac action potential
• NITROPRUSSIDE or NITROGLYCERIN for acute severe failure • further subdivided based on their effects on AP duration
with congestion o Group 1A drugs prolong the AP duration
• Dramatically effective in CHF due to increased afterload (e.g. o Group 1B drugs shorten the AP duration
continuing hypertension in an individual who has just had an o Group 1C drugs have no effect on AP duration
infarct)
MOA OF GROUP 1 ANTIARRHYTHMICS
• HYDRALAZINE and ISOSORBIDE DINITRATE have been shown
to reduce mortality in African Americans • all group 1 drugs slow or block conduction in ischemic and
• Calcium channel blockers are of no value in CHF depolarized cells and slow or abolish abnormal pacemakers
NESIRITIDE (BNP analog, increases cGMP) may be used for acute • most selective agents (group 1B) have significant effects on
decompensated failure but has not been shown to reduce mortality. sodium channels in ischemic tissue, but negligible effects on
Dr. Pereyra-Borlongan normal cells
MNEMONIC: Survival in CHF • use dependent or state dependent in their action
What drugs have been shown to improve survival in cases of o selectively depress tissues that are frequently depolarizing
heart failure? o selectively depress tissues that are relatively depolarized
ABA! Buhay ka pa! during rest
ACE inhibitors • amiodarone has class 1A activity
Beta-blockers KEY LEARNING POINTS: CLASS 1 Antiarrhythmics
Aldosterone Antagonists What are the effects of class I antiarrhythmics on action
These 3 drugs are the main stay treatment for chronic heart failure: potential duration?
ACEi/ARBs, Beta Blockers, and Spironolactone. • Class IA: prolongs AP duration
• Class IB: shortens AP duration
SUPPLEMENT: OTHER DRUGS FOR HEART FAILURE • Class IC: no effect on AP duration
an antihypertensive drug used in combination
with Valsartan for Heart Failure. It is prodrug
that is activated to Sacubitrilat, which inhibits
the enzyme Neprilysin (responsible for the
SACUBITRIL degradation of atrial and brain natriuretic
peptide – two BP lowering peptides that work
mainly by reducing blood volume. This enzyme
also degrades Bradykinin – an inflammatory
mediator exerting potent vasodilatory action
There is a combination therapy of Sacubitril with Valsartan (Brand
Names include Entresto and Vymada) that has been proven to
improve ejection fraction among patients with chronic heart failure
with reduced EF.
ANTIARRHYTHMIC DRUGS
SUPPLEMENT:
Arrhythmogenic Mechanisms
• ABNORMAL AUTOMATICITY
o pacemaker activity that originates anywhere other than in
the sinoatrial node
• ABNORMAL CONDUCTION
o conduction of an impulse that does not follow the defined
path or reenters tissue previously excited
Torsades de Pointes
• often induced by antiarrhythmics and other drugs that
change the shape of the action potential and prolong the QT
interval
• ECG morphology
o polymorphic ventricular tachycardia, often displaying
waxing and waning QRS amplitude
• associated with long QT syndrome
o heritable abnormal prolongation of the QT interval caused
by mutations in the IK or INa channel proteins
Take note of the different parts of the action potential and see what • Lidocaine is the least cardiotoxic among
electrolytes goes in. Each part of the action potential also corresponds to conventional anti-arrhythmics
portions of an ECG tracing. A detailed explanation is surely given in your
• Lidocaine is never given PO due to significant first
physiology handout.
Dr. Pereyra-Borlongan pass effect
• For phenytoin, an increased incidence of major
CLASS 1A ANTIARRHYTHMICS malformations (e.g. orofacial clefts, cardiac defects,
fetal hydantoin syndrome etc.) and cognitive defects
PROCAINAMIDE [C]
has been reported for pregnant women who use it
Class Class 1A antiarrhythmic
for epilepsy. It is also secreted in the human milk
Use- and state-dependent block of INa channels; some Mexiletine is used for neuropathic pain
block of IK channels. Slowed conduction velocity and Phenytoin as we know is also used as an anti-convulsant
MOA
pacemaker activity; prolonged action potential Dr. Pereyra-Borlongan
duration and refractory period MNEMONIC: Class 1B Antiarrhythmics

Atrial and ventricular arrhythmias, especially after
Uses Class 1B:
myocardial infarction I Buy Mexican Taco’s from Lily
SE Arrhythmias, Hypotension, Lupus-like syndrome 1B: Mexiletine, Tocainide, Lidocaine
Hyperkalemia exacerbates cardiac toxicity 1B Is Best post MI
Crosses into breast milk
Notes What are the drugs that can cause agranulocytosis?
Short duration of action: 2-3hours only Agranulocytosis! CCCAPPIT Me!
Clozapine Phenylbutazone
Co-trimoxazole PTU
DISOPYRAMIDE [C] Colchicine Indomethacin
Class Class 1A antiarrhythmic Aminopyrine Tocainide
Use- and state-dependent block of INa channels; some Methimazole
block of IK channels. Slowed conduction velocity and
MOA
pacemaker activity; prolonged action potential CLASS 1C ANTIARRHYTHMICS
duration and refractory period MOA OF GROUP 1C ANTIARRHYTHMICS
Uses Atrial and ventricular arrhythmias
• powerful depressants of sodium current
Arrhythmias, Hypotension, Marked antimuscarinic
SE • can markedly slow conduction velocity in atrial and ventricular
effects, Heart failure
cells
Hyperkalemia exacerbates cardiac toxicity
Notes • ECG effects
Crosses into breast milk
o no effect on ventricular AP duration or the QT interval
o increases the QRS duration
QUINIDINE [C]
Class Class 1A antiarrhythmic Class 1C is the most arrhythmogenic among the class1 anti-arrhythmics
that’s why they’re only used for refractory arrhythmias (especially that
Use- and state-dependent block of INa channels; some
they have propensity to increase QRS duration. Normal is < 3 small
block of IK channels. Slowed conduction velocity and squares)
MOA
pacemaker activity; prolonged action potential
duration and refractory period FLECAINIDE [C]
Uses Atrial and ventricular arrhythmias, Malaria SimD PROPAFENONE [C], ENCAINIDE [B], MORICIZINE [B]
Arrhythmias (torsades), Hypotension, Cinchonism Class Class 1C antiarrhythmic
SE (headache, vertigo, tinnitus), Cardiac depression, GI Selective use and state-dependent block of INa; slowed
upset, Autoimmune reactions (ITP) MOA
conduction velocity and pacemaker activity
Hyperkalemia exacerbates cardiac toxicity Uses Refractory arrhythmias
Reduces clearance of digoxin Increased arrhythmias (proarrhythmic effect), CNS
Notes SE
Crosses into breast milk. excitation
Use with extreme caution to Pregnant Px Hyperkalemia exacerbates cardiac toxicity.
MNEMONIC: Class 1A Antiarrhythmics Notes Contraindicated for post-MI arrhythmias.
Class 1A: Enters breast milk
I Am the Queen Who Proclaimed Diso’s pyramid MNEMONIC: Class 1C Antiarrhythmics
Quinidine, Procainamide, Disopyramide Class 1C: Chicken ay Pagkain For Enrico
SUPPLEMENT: Treatment of Class 1A Overdose 1C: Propafenone, Flecainide, Encainide
• Sodium Lactate to reverse drug-induced arrhythmias 1C Is Contraindicated post MI
• Pressor sympathomimetics to reverse drug-induced Summary of the Clinical Uses of Class 1
SUPPLEMENT:
hypotension if indicated Antiarrhythmics
• Class 1A
CLASS 1B ANTIARRHYTHMICS o all types of arrhythmias
MOA OF GROUP 1B ANTIARRHYTHMICS o arrhythmias in acute phase of myocardial infarction
o Procainamide and Amiodarone for WPW
• reduces AP duration
• Class 1B
• slows recovery of sodium channels from inactivation leading to o acute ventricular arrhythmias, especially post-MI
prolonged ERP o atrial arrhythmias due to digitalis
• selectively affects ischemic or depolarized Purkinje and • Class 1C
ventricular tissue o refractory arrhythmias
o because these agents have little effect on normal cardiac cells,
they have little effect on the ECG
LIDOCAINE [B]
CLASS 2 ANTIARRHYTHMICS
SimD MEXILETINE [C], TOCAINIDE [C], PHENYTOIN [D] MOA OF CLASS 2 ANTIARRHYTHMICS
Class Class 1B antiarrhythmic • primarily cardiac beta-adrenoceptor blockade and reduction in
Highly selective use and state-dependent INa block; cAMP
MOA o reduction of both sodium and calcium currents
minimal effect in normal tissue; no effect on IK
DOC for ventricular arrhythmias post-myocardial o suppression of abnormal pacemakers
Uses • AV node is particularly sensitive to blockers
infarction, Digoxin-induced arrhythmias
CNS stimulation, Cardiovascular depression, o PR interval is usually prolonged
SE • Act on Phase 4
Arrhythmias, Allergy, Agranulocytosis (Tocainide)
• Only affect ischemic tissue • Sotalol and Amiodarone also have group 2 effects
Notes
• Hyperkalemia exacerbates cardiac toxicity
PROPRANOLOL [C] AMIODARONE [X]
SimD METOPROLOL [C], TIMOLOL [C] SimD DRONEDARONE [X], VERNAKALANT
Class Class 2 antiarrhythmic Class Class 3 antiarrhythmic
MOA Block of beta-receptors; slowed pacemaker activity Strong IK block produces marked prolongation of
Post-MI prophylaxis against sudden death, action potential and refractory period. Group 1 activity
Uses MOA
Thyrotoxicosis slows conduction velocity; groups 2 and 4 activity
Bronchospasm, Cardiac depression, AV block, confer additional antiarrhythmic activity
SE
Hypotension Refractory arrhythmias, Used off-label in many
Uses
In CHF, reduces progression and decreases incidence arrhythmias
of potentially fatal arrhythmias Microcrystalline deposits in cornea and skin, Thyroid
Notes Sotalol is a beta-blocker anti-arrhythmic that has Class SE dysfunction (hyper- or hypo-), Paresthesia, Tremor,
3 properties. Pulmonary fibrosis
Metoprolol and Timolol is concentrated in breast milk Most efficacious of all antiarrhythmic drugs
ESMOLOL [C, D in 2nd & 3rd trim] Has the longest t½
Class Class 2 antiarrhythmic Can cause fetal harm (cardiac, thyroid,
neurodevelopmental, neurological and growth defects
Selective block of beta-1 receptors; slowed pacemaker
MOA in neonates)
activity
Acute perioperative and thyrotoxic arrhythmias, Notes Amiodarone is the most effective since it can do all MOA of
Uses class 1 to 4. However, it is also the most toxic and has the
Supraventricular tachycardia
most numerous side effects. Its effect on the thyroid
Bronchospasm, Cardiac depression, AV block, hormone levels is explained in the video below.
SE Hypotension Dronedarone is less toxic but less effective than
Used especially in Thyrotoxic arrhythmias Amiodarone. It is used in Afib and Atrial flutter
KEY LEARNING POINTS: Beta-Blockers KEY LEARNING POINTS: Amiodarone Toxicity

What are the major subgroups of beta-blockers? AMIODARONE TOXICITY
Pulmonary fibrosis Thyroid dysfunction
Paresthesia Corneal deposits
Tremors Skin deposits
AMIODARONE
https://qrs.ly/v9blniy
Mnemonics for the different groups of BB will be given during the pearls CLASS 4 ANTIARRHYTHMICS
J MOA OF CLASS 4 ANTIARRHYTHMICS
• effective in arrhythmias that must traverse calcium-dependent
cardiac tissue (e.g. the AV node)
CLASS 3 ANTIARRHYTHMICS • cause a state- and use-dependent selective depression of calcium
MOA OF CLASS 3 ANTIARRHYTHMICS currents
• act on Phase 3 • AV conduction velocity is decreased and effective refractory
• hallmark is prolongation of the AP duration period increased
o caused by blockade of IK potassium channels that are • ECG morphology
responsible for the repolarization of the AP o PR interval is consistently increased
o results in an increase in ERP and reduces the ability of the KEY LEARNING POINTS: Dihydropyridine CCBs
heart to respond to rapid tachycardias Why are dihydropyridine calcium channel blockers not useful
• ECG morphology as antiarrhythmics?
o increase in QT interval • dihydropyridine CCBs evoke compensatory sympathetic
Like Class 1C anti-arrhythmics, this group is also highly arrhythmogenic, discharge which facilitates arrhythmias rather than
hence used for refractory arrhythmias also. With high propensity to terminating them
cause Torsades As previously mentioned, dihydropyridine CCBs can cause reflex
Remember this group as AIDS tachycardia and are pro-arrhythmogenic.
A-miodarone Dr. Pereyra-Borlongan
I-butilde
D-ofetilide VERAPAMIL [C]
S-otalol Class Non-dihydropyridine calcium channel blocker
block voltage-gated L-type calcium channels
MOA

DOFETILIDE [C] (cardiac > vascular)

SimD IBUTILIDE [C] Angina, Hypertension, Supraventricular tachycardia,
Class Class 3 antiarrhythmic Uses
Migraine
Selective IK block; prolonged action potential & QT Constipation, Pretibial edema, Nausea, Flushing,
MOA
interval SE Dizziness, Gingival hyperplasia, Heart failure, AV
Uses Treatment and prophylaxis of atrial fibrillation block, Sinus node depression
SE Torsades de pointes Excessive cardiac depression may occur
Notes
Should be avoided in Ventricular tachycardia
SOTALOL [B]
Class Class 3 antiarrhythmic DILTIAZEM [C]
MOA IK block and beta-adrenoceptor block Class Non-dihydropyridine calcium channel blocker
Ventricular arrhythmias, Atrial fibrillation, block voltage-gated L-type calcium channels
Uses MOA
Supraventricular tachycardia (cardiac > vascular)
Dose-related torsade de pointes, Excessive beta- Angina, Hypertension, Supraventricular tachycardia,
SE Uses
blockade (sinus bradycardia, asthma) Vasospasm, Raynaud’s phenomenon
Drug present in breast milk, do not nurse while taking Constipation, Pretibial edema, Nausea, Flushing,
Sotalol is really a BB. That’s why it has -alol. That’s why it SE Dizziness, Heart failure, AV block, Sinus node
Notes also has Class 2 effects. But its more dominant effect is in depression
the K channel. That’s why it is grouped under Class 3. Drug enters breast milk
Notes
Should be avoided in Ventricular tachycardia
Summary of the Effects of Antiarrhythmic Drugs CARBONIC ANHYDRASE INHIBITORS
SUPPLEMENT: Proximal Convoluted Tubule
• carries out isosmotic reabsorption of amino acids, glucose,
and numerous cations
o major site for sodium chloride and sodium bicarbonate
reabsorption (60-70%)
• site of uric acid transport
• site of action of carbonic anhydrase inhibitors
MISCELLANEOUS ANTIARRHYTHMICS
ADENOSINE [C]
Class Miscellaneous antiarrhythmic
Increase in diastolic IK of AV node that causes marked
MOA
hyperpolarization and conduction block; reduced ICa
AV nodal arrhythmias, DOC for paroxysmal
Uses
supraventricular tachycardia
SE Flushing, Hypotension, Transient chest pain, Dyspnea
Only used in the ER setting
Has a very short t½ of 15sec
Notes Adenosine also occurs naturally in the body as a potent
bronchoconstrictor and so this drug may also induce such
effect
Dr. Pereyra-Borlongan ACETAZOLAMIDE [C]
SUPPLEMENT: DORZOLAMIDE [C], BRINZOLAMIDE [C],
SimD
DICHLORPHENAMIDE [C], METHAZOLAMIDE [C]
Potassium Ion
Class Carbonic anhydrase inhibitor
• MOA: depresses ectopic pacemakers, including those caused
by digitalis toxicity Inhibits carbonic anhydrase. In proximal tubule, in
glaucoma, secretion of aqueous humor is reduced, and
• when treating arrhythmias, serum potassium should be MOA
in mountain sickness, metabolic acidosis increases
measured and normalized if abnormal
respiration
o hypokalemia is associated with an increased incidence of
arrhythmias, especially in patients receiving digitalis Uses Glaucoma, Mountain Sickness, Edema with alkalosis
o excessive potassium levels depress conduction and can Drowsiness, Paresthesia, Sulfa allergy, Renal calcium
cause reentry arrhythmias SE stones, Potassium wasting, Hyperchloremic metabolic
Magnesium Ion acidosis, Hepatic encephalopathy in cirrhotic patients
• MOA: poorly understood, possible increase in Na+/K+ Acetazolamide enters breast milk
ATPase activity, slows the rate of SA node impulse formation Diuresis is self-limiting after 2-3 days
in the myocardium and prolongs conduction time. Notes These agents cause acidosis since they force HCO3- out of the
• similar depressant effects as potassium on digitalis-induced urine. And so, you lose your bases, leading to acidosis
arrhythmias
• effective in some cases of TORSADES DE POINTES
Sudden and large increase in Mg may cause severe respiratory
paralysis
DIURETICS
These agents interfere with the reabsorption of HCO3-. HCO3- is
reabsorbed in the proximal tubule and requires the activity of carbonic
anhydrase. HCO3- reabsorption takes place in a circuitous way.
Intracellularly carbonic anhydrase (CA in the diagram) converts H2O and
CO2 to carbonic acid (H2CO3). H2CO3 dissociates into H+ and HCO3-.
The HCO3- is transported across the basolateral membrane. H+ is secreted
into the tubular lumen in exchange for Na+. The H+ combines with a
filtered HCO3- (using CA) to form H2CO3 which immediately dissociates
into H2O and CO2 that is reabsorbed. Therefore, a filtered bicarbonate is
reabsorbed for every H+ secreted. Carbonic anhydrase inhibitors, by
blocking the enzyme, prevent the reabsorption of NaHCO3- and hence
diuresis occurs.
MNEMONIC: Metabolic Acidosis

ACIDazolamide causes ACIDosis
What are the causes of HAGMA? NAGMA
Methanol Hyperalimentation
Uremia Acetazolamide
DKA RTA
Paraldehyde Diarrhea
Isoniazid, Iron Ureteral diversion
Lactic Acid Pancreatic fistula
Ethanol, Ethylene glycol
Salicylates
HYDROCHLOROTHIAZIDE [B]
CHLORTHALIDONE [B], INDAPAMIDE [B],
LOOP DIURETICS METOLAZONE [B], BENDROFLUMETHIAZIDE [C],
SUPPLEMENT: Thick Ascending Limb of the Loop of Henle SimD HYDROFLUMETHIAZIDE [D], METHYLCLOTHIAZIDE
• responsible for a significant percentage of sodium chloride [B], POLYTHIAZIDE [D], QUINETHAZONE [C],
reabsorption via the Na+/K+/2Cl– transporter TRICHLORMETHIAZIDE [B]
• site of action of loop diuretics Class Thiazide diuretic
• site of Calcium and Magnesium reabsorption Inhibit Na+/Cl- transporter in distal convoluted tubule.
• prostaglandins are important in maintaining glomerular MOA Cause moderate diuresis and reduced excretion of
filtration calcium.
• NSAIDs decrease the efficacy of loop diuretics Hypertension, Heart failure, Hypercalciuria, Renal
Uses
calcium stones, Nephrogenic diabetes insipidus
Hypokalemic metabolic alkalosis, Dilutional
hyponatremia, Potassium wasting, Hyperglycemia,
SE
Hyperlipidemia, Hyperuricemia, Hypercalcemia, Sulfa
allergy
Synergistic effect with loop diuretics
Notes
Efficacy decreased by NSAIDs
MNEMONIC: Thiazide diuretics
Hyper GLUC
HyperGlycemia HyperUricemia
HyperLipidemia HyperCalcemia
Thiazide diuretics will cause hyperpolarization of ATP dependent K
channels (pancreatic beta cells and blood vessel. Pancreatic beta cell
hyperpolarization means no insulin release. Therefore, hyperglycemia
follows. DM patients should be a concern.
Dr. Calderon Jr.
FUROSEMIDE [C]
BUMETANIDE [C], TORSEMIDE [C], POTASSIUM-SPARING DIURETICS
SimD SUPPLEMENT: Cortical Collecting Ducts
ETHACRYNIC ACID [B]
Class Loop diuretic • last tubular site of sodium reabsorption
Inhibit Na+/K+/2Cl- transporter in thick ascending o responsible for reabsorbing 2–5% of the total filtered Na+
MOA limb of loop of Henle. Cause powerful diuresis and • under the influence of aldosterone, reabsorption of sodium
increased Ca2+ excretion. occurs via channels
Heart failure, Pulmonary edema, Hypertension, o accompanied by an equivalent loss of potassium or
Uses hydrogen ions
Hypercalcemia, Acute renal failure, Anion overdose
Hypokalemic metabolic alkalosis, Potassium wasting, • primary site of acidification of the urine
SE Dehydration, Ototoxicity, Sulfa allergy, Hyperuricemia, • last site of potassium excretion
Hypocalcemia, Hypomagnesemia, Nephritis o sites of action of the potassium-sparing diuretics
Synergistic ototoxicity with aminoglycosides
Efficacy decreased by NSAIDs SPIRONOLACTONE [C]
Efficacy is decreased by NSAIDs because NSAIDs inhibit SimD EPLERENONE [B]
Notes Prostaglandin production. PGs vasodilate the afferent Class Potassium-sparing diuretic (aldosterone antagonist)
arteriole. If it is inhibited, then the vasodilating effect will Steroid inhibitors of cytoplasmic aldosterone receptor
be gone decreasing now the GFR. MOA
in cortical collecting ducts. Reduce K excretion.
Hyperaldosteronism, Hypertension, Heart failure,
SUPPLEMENT: MNEMONICS – Loop Diuretic Toxicities Uses
Hypokalemia
What are the adverse effects associated with loop diuretics? Hyperkalemia, gynecomastia (spironolactone only),
OH DANG! SE Impotence, Benign prostatic hyperplasia,
Ototoxicity Allergy to sulfa Hyperchloremic metabolic acidosis
Hypokalemia Nephritis Eplerenone reduces progression of DM nephropathy
Dehydration Gout and reduces mortality post-MI
Spironolactone acts not only on mineralocorticoid
receptors but also on other STEROID receptors such as sex
THIAZIDE DIURETICS hormone receptors. This explains the side effect
Notes
SUPPLEMENT: Distal Convoluted Tubule gynecomastia. Such effects have NOT been reported with
• actively pumps sodium and chloride out of the lumen of the eplerenone because it is much more selective than
spironolactone for the mineralocorticoid receptor, being
nephron via the Na+/Cl– carrier
virtually inactive on androgen or progesterone receptors.
• site of action of thiazide diuretics Dr. Pereyra-Borlongan
• responsible for approximately 5–8% of sodium reabsorption
Spironolactone is beneficial to patient with CHF. It helps in the
• calcium is also reabsorbed in this segment under the control management of cardiac remodeling.
of PTH (parathyroid hormone) Dr. Calderon Jr.
AMILORIDE [B] VASOPRESSIN [C]
SimD TRIAMTERENE [C] SimD DESMOPRESSIN [B], TERLIPRESSIN
Class Potassium-sparing diuretic (Na blocker) Class ADH agonist (Anti-diuretic Hormone)
Inhibitor of ENaC epithelial sodium channels in Agonists at V1 and V2 ADH receptors. Activate
MOA cortical collecting duct, reduces Na reabsorption and K MOA insertion of aquaporin water channels in collecting
excretion tubule. Vasoconstriction.
Uses Hypokalemia Central diabetes insipidus, Nocturnal enuresis,
Uses
Hyperkalemia, Acute renal failure (with Hemophilia, von Willebrand’s disease
SE
indomethacin), Kidney stones, Metabolic acidosis SE Hyponatremia, Hypertension
Notes Should never be given with potassium supplements Increases the factor VIII activity of patients with mild
hemophilia A or von Willebrand disease
MNEMONIC: Potassium-Sparing Diuretics Terlipressin: not recommended during pregnancy as it
The K STAEs (stays) with K sparing diuretics! Notes has been shown to cause uterine contractions and
Spironolactone increased uterine pressure in early pregnancy and
Triamterene may decrease uterine blood flow. It may have harmful
Amiloride effects on pregnancy and fetus
Eplerenone
CONIVAPTAN [C]
Which drugs can cause GYNECOMASTIA? TOLVAPTAN [C], LIXIVAPTAN,
Some Drugs Create Awesome Knockers SimD
DEMECLOCYCLINE [D], LITHIUM [D]
Spironolactone Alcohol Class ADH antagonist
Digoxin Ketoconazole MOA Antagonist at V1a & V2 receptors
Cimetidine Uses SIADH, Hyponatremia
Infusion site reactions, Hyperkalemia, Nephrogenic
OSMOTIC DIURETICS diabetes insipidus, Renal failure (lithium,
SE
MOA OF OSMOTIC DIURETICS demeclocycline), Bone and teeth abnormalities
(demeclocycline)
• remains in the lumen and "holds" water by virtue of its osmotic Central pontine myelinosis may occur with rapid
effect Notes correction of hyponatremia
• reabsorption of water is also reduced in the descending limb of Lixivaptan is considered an Orphan Drug
the loop of Henle and the collecting tubule
The two tables below are included to aid you in memorizing your
diuretics. Please make a blank table on your own and try to answer it J
MANNITOL [C]
Diuretics are frequently asked in the PLE so please take them by heart <3
SimD GLYCERIN [C], ISOSORBIDE [C], UREA[C]
Class Osmotic diuretic QUICK MEMORY TIPS:
Osmotically retains water in tubule by reducing PARAMETERS ELECTROLYTE CHANGES
reabsorption in proximal tubule, descending limb of Increased (all diuretics); serum NaCl may
MOA Urine Na
+
Henle's loop, and collecting ducts; in the periphery, decrease as a result
mannitol extracts water from cells Increased (all except K sparing diuretics); serum
Rhabdomyolysis, Hemolysis, Increased intracranial Urine K+
Uses K may decrease as a result
pressure, Acute glaucoma Increased in loop diuretics: decreased serum Ca
Transient volume expansion (hyponatremia, Urine
Decreased in thiazide diuretics: increased serum
SE pulmonary edema; followed by hypernatremia), Ca2+
Ca
Headache, Nausea, Vomiting, Dehydration Decreased (acidemia): carbonic anhydrase
Notes used to maintain high urine flow inhibitors – decreased HCO3 reabsorption
K-sparing diuretics – aldosterone blockade
Blood pH
ADH AGONIST / ANTAGONIST prevents K secretion and H secretion,
SUPPLEMENT: Medullary Collecting Duct Increased (alkalemia): both loop diuretics and
thiazides
• reabsorption of water occurs under the control of antidiuretic
hormone (ADH)
• site of action of ADH agonists and antagonists
SUMMARY TABLE
DRUG MECHANISM OF ACTION URINARY ELECTROLYTES BLOOD PH
Acetazolamide • Inhibition of Carbonic Anhydrase in PCT • ↑ Na, K, HCO3 • Acidosis
Furosemide • Inhibition of Na/K/Cl co-transporter in TAL • ↑ Na, K, Ca, Mg, Cl • Alkalosis
• ↑ Na, K, Cl
Hydrochlorothiazide • Inhibition of Na/Cl co-transporter in DCT • Alkalosis
• ↓ Ca
• ↓ K
Spironolactone • Blocks Na channels, blocks Aldosterone in collecting tubule • Acidosis
• ↑ Na (small)
SUPPLEMENT: OTHER CARDIOVASCULAR DRUGS treatment option in CV diseases such as
Dual endothelin receptor antagonist used in Peripheral Arterial Cardiovascular diseases,
BOSENTAN the treatment of pulmonary artery chronic heart failure, stable angina especially
[X] hypertension; teratogen; do NOT use in when Diabetes is also present.
hepatically impaired patients A sympatholytic antihypertensive drug, acts
Propionyl-L-Carnitine (PLC) is a naturally as an a1-adrenoceptor antagonist and 5HT1A
occurring derivative of carnitine that plays receptor agonist. Unlike some other a1
URAPIDIL
an important role in the metabolism of both antagonist, this does NOT elicit reflex
carbohydrates and lipids, leading to an tachycardia (may be related to its weak b1
increase in ATP generation. It also has a antagonistic activity)
L-
potent antiradical effect and may protect
CARNITINE
cells from oxidative damage. It has PERIPHERAL VASODILATORS & CEREBRAL
[B] SUPPLEMENT:
ACTIVATORS
demonstrated protective effects in cardiac
and endothelial dysfunction (prevent Stabilizes cell membranes and reduces
progression of atherosclerosis and improve free radicals, may stimulate release of
cardiometabolic alterations that frequently CITICOLINE
dopamine neurotransmitters in the brain,
accompany insulin resistance); a potential by activating the central cholinergic
system, may activate the central STATINS / HMG-COA REDUCTASE INHIBITORS

cholinergic system (thus may be useful for MOA OF STATINS
Alzheimer Disease; it also increases ACTH.
• inhibition of hepatic cholesterol synthesis contributes a small
TSH, GH and LH; proposed for use in
amount to drug effect
traumatic brain injuries, stroke, vascular
• greater cholesterol-lowering effect derived from the
dementia, Parkinson’s disease and brain
compensatory response of the liver
aging
o increased number of high-affinity LDL receptors, which clear
B2-adrenoceptor agonist that causes direct
LDL and VLDL remnants from the blood
relaxation of uterine and vascular smooth
• direct anti-atherosclerotic effects
muscle; used in the treatment of
premature labor and as vasodilator for • prevent bone loss
ISOXUPRINE cerebral vascular insufficiency and
[C] Raynaud’s phenomenon; may increase the SIMVASTATIN [X]
HR and cause changes in BP and irritate ATORVASTATIN [X], ROSUVASTATIN [X],
GIT; use with caution if combined with SimD FLUVASTATIN [X], PRAVASTATIN, [X] LOVASTATIN
other drugs such as sedatives and [X], PITAVASTATIN [X]
anesthetics reversible competitive inhibitor of HMG-COA
Class
An anti-histamine and CCB; promotes reductase
cerebral blood flow (used ito treat cerebral Inhibits rate-limiting enzyme in cholesterol
apoplexy, post-trauma cerebral symptoms biosynthesis. Increased hepatic cholesterol uptake.
MOA
CINNARIZINE and cerebral arteriosclerosis). However, it Increased high-affinity LDL receptors. Decreased LDL
[C] is more commonly prescribed for nausea levels. Also causes modest reduction in triglycerides
and vomiting due to motion sickness, Hypercholesterolemia (high LDL), Acute coronary
chemotherapy, vertigo or Meniere’s Uses syndromes / Atherosclerotic vascular disease
disease (primary and secondary prevention), Ischemic stroke
Hepatotoxicity, Myopathy, Rhabdomyolysis,
SE
Gastrointestinal distress, Teratogen
DRUGS USED IN THE TREATMENT OF • Increased risk of myopathy and rhabdomyolysis
DYSLIPIDEMIA when used with fibrates
• Given before bedtime because cholesterol synthesis
predominantly occurs at night
• This group of drugs is contraindicated for use in
pregnant women since safety in pregnant women
has not be established and there is no apparent
benefit of lipid-lowering drugs during pregnancy.
• These drugs decrease cholesterol synthesis and
Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 possibly the synthesis of other biologically active
Notes
SUPPLEMENT: Hyperlipoproteinemia substances derived from cholesterol
Pathogenesis of Hyperlipoproteinemia • Simvastatin and lovastatin are prodrugs, all the rest
• premature atherosclerosis is strongly associated with are in their active form already
elevated concentrations of lipoproteins • Rosuvastatin, Atorvastatin and Simvastatin have
o elevated level of low-density lipoproteins (LDL) greater maximal effect than other statins
o depressed level of high-density lipoproteins (HDL) • If given together with resins give at least 1hr before
o hypertriglyceridemia or 4hrs after resin administration (resins decrease
• hyperchylomicronemia is associated with a high incidence of the absorption of statins)
acute pancreatitis • Has CYP450 dependent metabolism (Drug levels
Treatment Strategies: DIET adversely affected by CYP inhibitors)
• cholesterol and saturated fats are the primary dietary factors
that contribute to elevated plasma lipoproteins KEY LEARNING POINTS: Statins in CAD
• dietary measures constitute the first method of management Why are statins used in the management of coronary artery
o may be sufficient to reduce lipoprotein levels to a safe range disease?
• Alcohol raises triglyceride and VLDL levels • for stabilization of atherosclerotic plaques
o should be avoided by patients with hypertriglyceridemia
Treatment Strategies: DRUGS BILE ACID BINDING RESINS
• choice of drug is based on the lipid abnormality MOA OF RESINS
• drugs most effective at lowering LDL cholesterol • over 90% of bile acids are reabsorbed and returned to the liver
o statins, resins, ezetimibe, niacin for reuse (enterohepatic recirculation)
• drugs most effective at lowering triglyceride and VLDL and • resins bind bile acids and prevent their intestinal absorption
raising HDL o divert hepatic cholesterol to synthesis of new bile acids
o niacin, fibrates o reduce amount of cholesterol in a tightly regulated pool
o compensatory increase in high-affinity LDL receptors
increases LDL removal
• modest reduction in LDL cholesterol but have little effect on HDL
or triglycerides
CHOLESTYRAMINE [C]
SimD COLESEVELAM [B], COLESTIPOL [C]
Class Bile acid-binding resin
Binds bile acids, preventing their reabsorption and
increasing cholesterol utilization for replacement →
MOA
Upregulates LDL receptors → Modestly lowers LDL
levels.
Hypercholesterolemia (high LDL), Pruritus in
Uses
cholestasis, Digitalis toxicity
Constipation, Bloating, Gritty taste, Steatorrhea,
SE
Gallstones (rare), Malabsorption (vitamin K)
• Increases TGs and VLDL in patients with high TGs MNEMONIC: Cutaneous Flushing
Treat constipation with fiber supplements/psyllium What are the drugs that cause flushing?
• Avoid in patients with diverticulitis V-A-N-C
• Interferes with the absorption of some drugs and Vancomycin Niacin
Notes vitamins Adenosine Calcium channel blockers
• Should be taken with meals
• Non-absorbable polymers that bind bile acids and
similar steroids in the intestines preventing their FIBRATES
reabsorption MOA OF FIBRATES
MNEMONIC: • ligands for the peroxisome proliferator-activated receptor-alpha
Ang Cholet, Colet, Colet mo! (PPAR-a) protein
o increased synthesis by adipose tissue of lipoprotein lipase
Sabi nang you should BAR this from people with HIGH TGs!
Cholestyramine, Colestipol and Colesevelam are Bile Acid § enhances clearance of triglycerides
Resins (BAR). Don’t use in people with HIGH TGs! • in the liver, fibrates stimulate fatty acid oxidation
o limits supply of triglycerides and decreases VLDL synthesis
• decrease expression of apoC-III
CHOLESTEROL ABSORPTION BLOCKERS o impedes the clearance of VLDL
MOA OF EZETIMIBE o increases the expression of apoA-I and apoA-II, which in turn
• converted in the liver to the active glucuronide form increases HDL levels
• inhibits NPC1L1 transporter (a specific transport process in • little or no effect on LDL concentrations
jejunal enterocyte) that mediates gastrointestinal uptake of
cholesterol and phytosterols GEMFIBROZIL [C]
• prevents absorption of dietary cholesterol and cholesterol that SimD FENOFIBRATE [C], BEZAFIBRATE [C]
is excreted in bile Class Fibric acid derivative
o reduces cholesterol in tightly regulated hepatic pool Activates PPAR-a and increases expression of
o compensatory increase in the synthesis of high-affinity LDL lipoprotein lipase and apolipoproteins (apoA-I, apoA-
MOA
receptors increases the removal of LDL II). Lowers triglycerides. Decreases secretion of VLDL.
EZETIMIBE [C] Increases HDL.
Class Sterol absorption blocker DOC for Hypertriglyceridemia, Hypercholesterolemia
Uses
Selective inhibitor of the NPC1L1 transporter, (low HDL, high LDL), Fat redistribution syndrome
decreasing intestinal absorption of cholesterol and Nausea, Rashes, Leukopenia, Hemoconcentration,
SE
MOA other phytosterols → Decreases cholesterol hepatic Increased risk of cholesterol gallstones
pool, increases hepatic LDL receptors → Decreases Increased risk of myopathy and rhabdomyolysis when
LDL and phytosterols used with statins
Uses Hypercholesterolemia (high LDL), Phytosterolemia Avoided in patients with hepatic or renal dysfunction
SE Hepatotoxicity (increased with statin use), Myositis Notes May increase LDL in patients with familial combined
hyperlipoproteinemia
Synergistic LDL-lowering effect with statins
Higher risk of gallstone formation if given together
Notes May be given as combination therapy with statins
with resins
Considered a prodrug
SITOSTEROL MNEMONIC: Fibrates
Class Sterol absorption blocker FULL
Cholesterol analog, takes the place of dietary and Fibrates Upregulate Lipoprotein Lipase
MOA biliary cholesterol, decreasing intestinal absorption of
cholesterol and other phytosterols. CORRELATIONS: Biochemistry – Lipoproteinemias
Uses Hypercholesterolemia (high LDL), Phytosterolemia
Which antihyperlipidemic drugs are indicated for the
Gastrointestinal upset, Bloating, Impotence (rare),
SE inherited lipoproteinemias?
Coronary events
NIACIN
MOA of Niacin
• multiple mechanisms of actions in various tissues
o inhibits lipolysis by hormone sensitive lipase
o in the liver, niacin reduces VLDL synthesis
o in adipose tissue, niacin reduces hormone-sensitive lipase
activity, decreases plasma fatty acid and triglyceride levels
o in capillary endothelial cells, niacin causes increased clearance
of VLDL by lipoprotein lipase
o niacin reduces the catabolic rate for HDL
o decreases circulating fibrinogen, increases tPA activity
• net effect on lipid profile
o most effective agent for increasing HDL levels
o reduces LDL cholesterol, triglycerides and VLDL
NIACIN [A, C if given in doses exceeding RDA] SUPPLEMENT:
Class Vitamin, Antihyperlipidemic drug Combination Therapy
Decreases catabolism of apoA-I. Decreases VLDL • all patients with hyperlipidemia are treated first with dietary
MOA synthesis and secretion from the liver. Decreases LDL modification
cholesterol concentrations. Increases HDL cholesterol • certain drug combinations provide advantages whereas
Uses Hypercholesterolemia (low HDL, high LDL/ VLDL) others present specific challenges
Flushing, Pruritus, Rashes, Acanthosis nigricans, Synergistic Antihyperlipidemic Combinations
Gastrointestinal irritation, Hepatotoxicity (mild),
SE
Hyperuricemia, Impaired glucose tolerance,
Arrhythmias, Amblyopia
Aspirin pre-treatment reduces flushing
Avoid in patients with peptic ulcer disease
Notes Potentiates effects of antihypertensives (vasodilators,
ganglion blockers)
Decreases fibrinogen and increases t-PA
Disadvantageous Antihyperlipidemic Combinations enzyme Q. Blockage of this will also affect the Na-K ATPase activity
affecting the resting membrane potential, sodium is maintained in the
cell. Review cell membrane physiology, where sodium goes, water follows
→ the cell will swell presenting as myalgia
Niacin is proven to increase the level of HDL by way of preventing its
degradation.
Harmless flushing associated to niacin intake is addressed by Naproxen
200 mg or Aspirin
Bile Acid Resins bind bile preventing it to be absorbed in the terminal
ileum to undergo enterohepatic cycling. Preventing bile from being
reabsorbed, forced the liver utilize the LDL from the periphery to create
cholesterol. Hence, there is upregulation of the LDL receptor with the net
effect of decreased LDL level. Because we need bile to emulsify fat,
preventing bile reabsorption will result to Vitamin A,D,E,K malabsorption
and steatorrhea
Ezetimibe works by preventing the chylomicron (from the food) to
contribute to endogenous cholesterol synthesis by the liver and in the
same manner this forces the liver to upregulate LDL receptors and utilize
LDL from the periphery.
Fenofibrates (Gemfibrozil) works in a different way as compared to the
above-mentioned mechanism. It does not cause upregulation of LDL
receptors. Fenofibrates rather stimulate the activity of the endothelial
Lipoprotein Lipase. Increasing the activity of lipoprotein lipase, promotes
the cleaving of the VLDL become LDL. The fatty acids (triglycerides) are
deposited in the adipose tissue. Thus, fenofibrates are the drug of choice
for hypertriglyceridemia. However, side effects include weight gain and
cholelithiasis.
Remember, the 5 F’s of cholelithiasis? Fat , Female, Forty, Fertile, Fair.
Fenofibrate is the 6th F.
Dr. Calderon Jr.
SUPPLEMENT: OTHER ANTI-DYSLIPIDEMIC

DRUGS ON SMOOTH MUSCLES
An anti-oxidant which can inhibit the HISTAMINE, SEROTONIN
oxidation of LDL and lowers the level of AND THE ERGOT ALKALOIDS
cholesterol in the bloodstream by increasing
the rate of LCL catabolism in the final
metabolic pathway for cholesterol
Histamine, Serotonin
elimination from the body. Additionally, it and Ergot Part 1
PROBUCOL https://qrs.ly/g6boajo
may inhibit early stages of cholesterol
[B]
biosynthesis and slightly inhibit dietary
cholesterol absorption. May also inhibit the
oxidation and tissue deposition of LDL, Histamine, Serotonin
thereby inhibiting atherogenesis; Used to
and Ergot Part 2
lower LDL and HDL cholesterol, yet has little
https://qrs.ly/e8boak3
effect on serum TG or VLDL
The study of drugs used for dyslipidemia is best supported with the
knowledge of endogenous lipoprotein synthesis pathway. Knowing this
and inserting the different anti dyslipidemic medication in each pathway
will enable you to understand this topic with ease
AUTACOIDS
• endogenous molecules with powerful pharmacologic effects that
do not fall into traditional autonomic groups
• histamine and serotonin are the most important amine
autacoids
HISTAMINERGIC AGENTS
SUPPLEMENT:
Histamine
• formed from the amino acid histidine
Figure 35-1. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018. • metabolized by the enzymes monoamine oxidase and
In a nutshell… diamine oxidase
Statins work by blocking the rate limiting enzyme HMG-CoA reductase • excess production detected by measurement of imidazole
depriving the liver with cholesterol and forcing it to increase the LDL
receptors to utilize the LDL from the periphery. The net result is decrease
acetic acid in the urine
level of LDL. Statins also work by preventing VLDL transport from the • important pathophysiologic roles
liver to the blood vessel. o seasonal rhinitis (hay fever), urticaria, and angioedema
It is essential to have a baseline ALT AST prior statins, because it can lead
o control of acid secretion in the stomach
to elevated transaminases. Triple Response of Lewis (wheal, flush and flare)
• classic demonstration of histamine effect
Clinical correlation: Biochemistry:
What is the biochemical basis of myalgia in Statins intake? • mediated mainly by H1 and H2 receptors
• involves a small red spot at the center of an intradermal
Statins block mevalonic acid which is essential to farnesysl
pyrophosphate, a part of the electron transport chain specifically Co- injection of histamine surrounded by a red edematous wheal
HISTAMINE RECEPTORS AND EFFECTS CIMETIDINE [B]
SimD RANITIDINE [B], FAMOTIDINE [B], NIZATIDINE [C]
Class H2-receptor antagonist
MOA Competitive pharmacologic block of H2 receptors
Peptic ulcer disease, Zollinger-Ellison syndrome,
Uses
Gastroesophageal reflux
CYP450 inhibitor and antiandrogen effects like
SE gynecomastia (cimetidine only), Decreased hepatic
flow (cimetidine)
Used in the ICU setting to prevent gastric erosion and
hemorrhage
Usual half-life: 1-3h
Notes
SUPPLEMENT: H1 Receptor Antagonists Reduction of nocturnal acid secretion in gastric and
duodenal ulcer, accelerate healing and prevent
• Diminish or abolish the major actions of histamine in the body
recurrences
by competitive, reversible blockade of histamine H1-receptor
sites on tissues First generation antihistamines are used for allergies and they cause
sedation and muscarinic blockade because they cross the blood brain
• Used primarily for the alleviation of conditions such as
barrier
urticarial rashes and nasal allergy that are characterised by
type I hypersensitivity Second generation antihistamines do not cross the blood brain barrier,
their sole indication is for allergy. They cause no sedation
• Are of value in preventing urticaria and are used to treat Dr. Calderon Jr.
urticarial rashes and mild angioedema
• Common SE: Sedation
SEROTONERGIC AGENTS
• Should not be given to neonates because they are more
susceptible to antimuscarinic effects SUPPLEMENT: Serotonin (5 Hydroxytryptamine or 5-HT)
• Possess antimuscarinic, adrenaline-antagonising, serotonin • produced from the amino acid tryptophan
antagonising, and local anaesthetic effects. Some have • metabolized by monoamine oxidase
calcium-channel blocking activity • excess production in the body detected by 5-hydroxyindole
• Sedating antihistamines may enhance the sedative effects of acetic acid (5-HIAA) in the urine
CNS depressants including alcohol, barbiturates, hypnotics, • physiologic roles
opioid analgesics, anxiolytic sedatives, and antipsychotics o neurotransmitter in CNS and enteric nervous system
• All are PO but can be given topical (nose and eyes) o local hormone that modulates gastrointestinal activity
• Negligible effect on H2 receptors
SEROTONIN RECEPTORS AND EFFECTS
DIPHENHYDRAMINE [B]
BROMPHENIRAMINE [C], CHLORPHENIRAMINE [B],
CYCLIZINE [B], MECLIZINE [B], BUCLIZINE [C],
CARBINOXAMINE [C], DIMEHYDRINATE [B],
SimD
HYDROXYZINE [C], PROMETHAZINE [C],
CYPROHEPTADINE [B], CLEMASTINE [B],
TRIPELENNAMINE [B]
Class H1-receptor antagonists (first generation)
Competitive pharmacologic block of peripheral and
MOA CNS H1 receptors plus a- and M-receptor block. Anti-
motion sickness effect.
Hay fever, Angioedema, Motion sickness, Insomnia,
Uses Dystonia, Anti-emetic (Promethazine), for Serotonin
Syndrome (Cyproheptadine) SUMATRIPTAN [C]
Drowsiness, Blurred vision, Dry mouth, Urinary ALMOTRIPTAN [C], ELETRIPTAN [C],
SE
retention, Anorexia, Orthostatic hypotension SimD FROVATRIPTAN [C], NARATRIPTAN [C] ,
• More likely to block autonomic receptors, also has a1 RIZATRIPTAN [C], ZOLMITRIPTAN [C]
blocking and local anesthetic effect Class 5-HT1D-receptor agonists
• Cyclizine (more anti-motion sickness action less 5-HT1D agonist. Causes vasoconstriction. Modulates
MOA
Notes sedative and autonomic effects) neurotransmitter release.
• Promethazine (less anti-motion sickness, more Uses DOC for acute migraine, Cluster headache
sedative and autonomic effects) Paresthesia, Dizziness, Chest pain, Coronary
SE
• Usual half-life: 4-12h vasospasm, Injection site reaction
If a drug contains PHEN on its name it is lipid soluble. Examples All are per orem only except for Sumatriptan which
acetaminophen, phenytoin, chloramphenicol. These can cross the blood Notes can also be given intranasally, transdermal and IV
brain barrier. All has 2-27hrs DOA except for sumatriptan DOA: 2-4h

Dr. Calderon Jr.
CETIRIZINE [B] ONDANSETRON [B]

LORATADINE [B], FEXOFENADINE [C], GRANISETRON [B], DOLASETRON [B],
DESLORATADINE [C], LEVOCETIRIZINE [B], SimD
SimD PALONOSETRON [B], ALOSETRON [B]
TERFENADINE [C], ASTEMIZOLE [C], EBASTINE, Class 5-HT3-receptor antagonist
AZELASTINE [C], BILASTINE, RUPATADINE [B] Pharmacologic antagonist. Blocks chemoreceptor
Class H1-receptor antagonists (second generation) MOA trigger zone and enteric nervous system 5-HT3
Competitive pharmacologic block of peripheral H1 receptors
MOA receptors. No autonomic or anti-motion sickness Chemotherapy and postoperative vomiting, Irritable
effects. Uses
bowel disease (Alosetron only)
Uses Hay fever, Angioedema, Urticaria Diarrhea, Headache, Malaise, QRS and QT prolongation
SE None SE
(Dolasetron only), Constipation (Alosetron only)
Fatal arrhythmias from interaction between
azoles/erythromycin and Terfenadine/Astemizole
Notes
No sedation and antimuscarinic effects
Usual half-life: 12-24h
ERGOT ALKALOIDS PROSTAGLANDINS AND OTHER EICOSANOIDS

SUPPLEMENT: Ergot Alkaloids
• complex molecules are produced by a fungus found in wet or PROSTAGLANDIN
spoiled grain AND EICOSANOIDS
o responsible for the epidemics of "St. Anthony's fire" https://qrs.ly/yhboaj5
(ergotism) described during the Middle Ages
• most are partial agonists at alpha receptors and 5HT
receptors but some are potent agonist at dopamine receptors
• Classification
o VASOSELECTIVE
o UTEROSELECTIVE Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
Are you familiar with the history of ergotoxicosis during the medieval EICOSANOIDS
age? There is an association of bewitchment and suffering but the actual • important group of endogenous fatty acid derivatives that are
cause is ingestion of bread infected with fungus. How about St. Anthony’s produced from arachidonic acid
fire?
Dr. Calderon Jr.
• major families of eicosanoids include
o straight-chain derivatives (leukotrienes)

ERGOTAMINE [X]
SimD DIHYDROERGOTAMINE [X], METHYSERGIDE [X] o cyclic derivatives (prostacyclin, prostaglandins, and
Class 5-HT2-receptor antagonist (vasoselective) thromboxane)
Partial agonist at a and 5-HT2 receptors, some have
MOA
potent agonist effect at Dopamine receptors
Uses Migraine, Cluster headache
Gastrointestinal upset, Vasospasm, Gangrene, Uterine
SE
spasm, Retroperitoneal fibrosis (methysergide only)
Antidote is Nitroprusside
Can cause epinephrine reversal due to partial agonist
Notes effect on alpha receptors (REMEMBER: All partial
agonist will act as antagonist in the presence of a full
agonist)
ERGONOVINE [C]
SimD METHYLERGONOVINE [C]
Class 5-HT2-receptor antagonist (uteroselective)
Partial agonist at a and 5-HT2 receptors, some have
MOA
potent agonist effect at Dopamine receptors Figure 18-1. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
Uses Postpartum bleeding, Migraine

CYCLOOXYGENASE ISOFORMS
Gastrointestinal upset (Nausea, Vomiting, Diarrhea),
SE • CYCLOOXYGENASE-1 (COX-1)
Uterine spasm, Abortion
The uterus becomes more sensitive to ergots during o found in many tissues
pregnancy, produce very powerful and long-lasting o important for a variety of normal physiologic processes
contraction leading to decreased bleeding • CYCLOOXYGENASE-2 (COX-2)
Notes o found primarily in inflammatory cells
Never give before delivery of placenta
Methylergometrine/Methylerobasin (another name of o major role in tissue injury (e.g. inflammation)
Methylergonovine) is a homolog of ergonovine o synthesis of prostacyclin in the vascular endothelium and of
prostaglandins important in renal function
SUPPLEMENT: DRUGS USED FOR VERTIGO EFFECTS OF IMPORTANT EICOSANOIDS
Strong antagonist of H3 receptor
(leads to increased levels of
neurotransmitters histamine,
acetylcholine, norepinephrine,
serotonin and GABA) and a weak
BETAHISTINE [D] agonist of H1 receptor (causes local
vasodilation and increased
permeability in the inner ear); used
for balance disorders or to alleviate
vertigo symptoms associated with
Meniere’s disease
An anti-histamine and CCB;
promotes cerebral blood flow MISOPROSTOL [X]
(used ito treat cerebral apoplexy, SimD GEMEPROST [B]
post-trauma cerebral symptoms and Class Prostaglandin E1 analog
CINNARIZINE [C] cerebral arteriosclerosis); Activates EP receptors. Causes increased HCO3- and
more commonly prescribed for MOA
mucus secretion in stomach. Uterine contraction
nausea and vomiting due to motion Peptic Ulcer Disease, Prevention of NSAID-induced
sickness, chemotherapy, vertigo or Uses
gastric mucosal injury, abortifacient
Meniere’s disease Abdominal pain, Diarrhea, Uterine cramping,
1st generation antihistamine used SE
DIMENHYDRINATE Miscarriage, Teratogenic effect (Moebius sequence)
for nausea, vomiting and dizziness Misoprostol's intended use is for NSAID-induced
[B]
caused by motion sickness gastritis
Notes
May also be used together with Mifepristone or
SUPPLEMENT: DRUGS USED FOR MIGRAINE Methotrexate as safe abortifacient
Selective Calcium Entry blocker with
calmodulin binding properties and H1
FLUNARIZINE antagonistic activity; effective in the
[C] prophylaxis of migraine, occlusive
peripheral vascular disease, vertigo, and
as adjuvant for epilepsy
ALPROSTADIL [C] BRONCHODILATORS AND OTHER DRUGS
Class Prostaglandin E1 analog
Activates EP receptors, causes vascular smooth muscle USED IN ASTHMA
MOA
relaxation and vasodilation
Maintenance of patent ductus arteriosus (PDA),
Uses DRUGS USE IN ASTHMA
Erectile dysfunction
https://qrs.ly/opboakd
Apnea, Hypotension, Arrhythmia, Priapism,
SE
Lightheadedness
Given as injection into the cavernosa for erectile SUPPLEMENT: ASTHMA
Notes
dysfunction
• characterized by airway inflammation and episodic,
reversible bronchospasm
MNEMONIC: Alprostadil
• Major risk factor of asthma: atopy
Prostaglandin E1 (Alprostadil) Pathophysiology of Asthma
E1 (iwan) mong bukas ang ductus • bronchoconstriction caused by release of several mediators
maintains patency of PDA from IgE-sensitized mast cells
• chemotactic mediators attract inflammatory cells to the
DINOPROSTONE [C] airways, leading to chronic inflammation
SimD SULPROSTONE • results in marked bronchial hyperreactivity, partially
Class Prostaglandin E2 analog mediated by vagal reflexes
Low concentrations contract, higher concentrations
MOA relax uterine and cervical smooth muscle, soften cervix
at term before induction with oxytocin
Uses Induction of labor (Cervical ripening), Abortifacient
SE Cramping, Fetal trauma
Approved abortifacient in the 2nd trimester
Notes Although effective in inducing labor, it produces more
SE than other oxytocics
SUPPLEMENT:
CARBOPROST [C] Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
BIMATOPROST[C], TRAVOPROST [C], STRATEGIES OF ASTHMA THERAPY
SimD
UNOPROSTONE [C] • acute attacks of bronchospasm (relievers)
Class Prostaglandin F2a analog o use bronchodilators or relievers
MOA Activates FP receptors o short-acting b2 agonists
Control of postpartum hemorrhage, for refractory o muscarinic antagonists
Uses
postpartum bleeding, abortifacient o methylxanthines
SE Vomiting, diarrhea, transient bronchoconstriction o intravenous corticosteroids
• long-term prevention and prophylaxis (controllers)
EPOPROSTENOL [B] o use anti-inflammatory drugs or controllers
SimD BERAPROST, ILOPROST [C], TREPROSTINIL [B] o corticosteroids
Class Prostaglandin I2 analog o long-acting b2 agonists
Activates IP receptors. Causes vasodilation. Reduces o mast cell stabilizers
MOA o anti-IgE antibodies
platelet aggregation
Pulmonary hypertension, Reduces platelet o leukotriene antagonists
Uses
aggregation in dialysis machines
SE Hypotension, Flushing, Headache
LATANOPROST [C]
BIMATOPROST [C], TRAVOPROST [C], UNOPROSTONE
SimD
[C]
Class Prostaglandin F2a analog
Activates FP receptors. Increases outflow of aqueous
MOA
humor, reduces intraocular pressure
Uses Glaucoma
Alters color of the iris, causing permanent eye color
SE
change
May cause vomiting, diarrhea, transient
Notes
bronchoconstriction if given systemically
Everything with a “prost” can be a concern for pregnancy. It might cause
premature uterine contraction
ALBUTEROL / SALBUTAMOL [C]
Dr. Calderon Jr.
LEVALBUTEROL [C], TERBUTALINE [C],
OTHER DRUGS USED FOR ERECTILE
SUPPLEMENT: SimD METAPROTERENOL [C], PIRBUTEROL [C],
DYSFUNCTION
PROCATEROL, FENOTEROL [B], BITOLTEROL [C]
SILDENAFIL [B]
Class b2-selective agonist (short-acting)
SimD TADALAFIL [B], VARDENAFIL [B]
Activates b2-receptors in bronchial smooth muscle.
Class Phosphodiesterase 5 inhibitor MOA
Causes bronchodilation.
Inhibits PDE5 which degrades cGMP to inactive
MOA Uses Acute asthma attacks (drug of choice)
GMP → vasodilation
Tachycardia, Tremors, Nervousness, Restlessness,
Erectile dysfunction, Pulmonary Arterial
Uses SE Arrhythmias when used excessively, Loss of
Hypertension, Raynaud’s Phenomenon
responsiveness (tolerance, tachyphylaxis)
Headache, flushing, priapism, hearing loss, optic
SE May precipitate arrhythmias in patient with
neuropathy
concurrent COPD and heart disease
Do not take with Nitrates (ISDN, ISMN, NTG) Usual DOA: 2-4hrs
Notes Notes
because it may lead to fatal hypotension All are given inhalational, Salbutamol and terbutaline
is also available PO
Terbutaline can also be given IV
SALMETEROL [C] CROMOLYN [B]
FORMOTEROL [C], CLENETEROL, BAMBUTEROL [C], SimD NEDOCROMIL [B], LODOXAMIDE [B]
SimD ARFORMOTEROL [C], VILANTEROL [C], Class Mast cell stabilizer
INDACATEROL [C], OLODATEROL [C] Prevents calcium influx and stabilizes mast cells →
Class b2-selective agonist (long-acting) MOA preventing degranulation and release of histamine,
Activates b2-receptors in bronchial smooth muscle. leukotrienes and other mediators
MOA Causes bronchodilation. Potentiation of corticosteroid Asthma prophylaxis,
action. Uses Allergies (ophthalmic, nasopharyngeal,
Uses Asthma prophylaxis (not for acute relief) gastrointestinal)
Tachycardia, Tremors, Nervousness, Restlessness, SE Cough, Airway irritation
SE Arrhythmias when used excessively, Loss of No bronchodilator action but can prevent
responsiveness (tolerance, tachyphylaxis) bronchoconstriction caused by antigens (both in the
Increase asthma mortality when used alone; early and late BA responses)
May precipitate arrhythmias Unusually insoluble chemicals so rarely used
Usual DOA: 12hrs Notes May be given as ophthalmic solution for allergic
Notes conjunctivitis
Vilanterol, Indacaterol and Olodaterol are Ultra Long-
acting LABAs. They have a 24-hour activity for once May also be given (Off-label) for Food allergy and IBD
daily treatment for COPD and Asthma Not normally used because it can induce cough
MNEMONIC: Long-Acting SABAs
“FAB C VIOS” FLUTICASONE [C]
Formoterol BECLOMETHASONE [C], BUDESONIDE [B if inhaled],
Arformoterol SimD CICLESONIDE [C], FLUNISOLIDE [C], MOMETASONE
Bambuterol [C], TRIAMCINOLONE [C]
Cleneterol Class Corticosteroid
Vilanterol Inhibitor of phospholipase A2. Reduces expression of
MOA
Indacaterol cyclooxygenase
Olodaterol Asthma prophylaxis (drug of choice), COPD, Allergic
Salmeterol rhinitis, first line treatment for moderate to severe BA,
Uses COPD, Allergic rhinitis, also used as anti-inflammatory
IPRATROPIUM [B] for other conditions such as auto-immune diseases
TIOTROPIUM [C], UMECLIDINIUM [C], and cancer, also for immune suppression
SimD
GLYCOYRRONIUM [B] Oropharyngeal candidiasis, Minimal systemic steroid
Class Muscarinic receptor antagonist SE toxicity (e.g. adrenal suppression), Mild growth
Blocks muscarinic receptors in bronchial smooth retardation
MOA muscle. Prevents vagal-stimulated Inhibit synthesis of arachidonic acid by inhibiting
bronchoconstriction Phospholipase A2, reduces expression of COX and LT,
Uses Acute Asthma, COPD increases responsiveness of Beta receptors in the
Dry mouth, blurred vision etc. airway, bind to intracellular receptors and activate
SE
(Anti-cholinergic effects) Glucocorticoid response elements in the nucleus
• Less toxic than b-agonists in patients with COPD Notes leading to synthesis of substances that prevent full
• Tiotropium and Umeclidinium have longer DOA than expression of inflammation and allergy
Ipratropium For status asthmaticus: use IV prednisolone or
• Ipratropium given as aerosol has little systemic hydrocortisone
effects Prednisolone is the active metabolite of prednisone
• Has no effect on the chronic inflammation aspect of Ciclesonide has lowest systemic steroid toxicity
Bronchial Asthma
Notes • Glycopyrronium does not cross the BBB, and ZILEUTON [C]
consequently has none to few central effects. It may Class Leukotriene synthesis (Lipooxygenase) inhibitor
be used as a monotherapy as maintenance for COPD. Inhibitor of 5-lipoxygenase. Reduces synthesis of
It may also be used as an anti-spasmodic and reduce MOA leukotrienes. Prevents airway inflammation and
salivation with some anesthetics bronchoconstriction.
TRIPLE TREATMENT FOR COPD-ASTHMA OVERLAP: Asthma prophylaxis, Exercise-, Antigen- and Aspirin-
LAMA + LABA + Inhaled ICS
Uses
induced bronchospasm
Flulike syndrome, Headache, Drowsiness, Dyspepsia,
SE
THEOPHYLLINE [C] Hepatitis, Elevation of liver enzymes
AMINOPHYLLINE [C], PENTOXIFYLLINE [C], No bronchodilator actions
SimD
DOXOFYLLINE [B] Not recommended for acute BA attack
Class Methylxanthine Notes The Lukasts gained more popularity because this group of
Phosphodiesterase inhibition. Adenosine receptor LT inhibitors can cause transaminitis
MOA Dr. Pereyra-Borlongan
antagonist. Causes bronchodilation
Asthma (prophylactic against nocturnal attacks)
Uses MONTELUKAST [B]
Intermittent claudication (pentoxifylline only)
SimD ZAFIRLUKAST [B], PRANLUKAST [B]
CNS stimulation (Insomnia, seizure, Anorexia),
SE Class Leukotriene receptor antagonist
Cardiac stimulation (Arrhythmias), Tremors,
increased BP, diuresis, increased GI motility Blocks cysteinyl leukotriene-1 receptor for
MOA leukotrienes C4, D4 and E4. Prevents airway
• Antidote in overdosage is Beta blockers
inflammation and bronchoconstriction.
• Higher clearance in adolescents and smokers
Asthma prophylaxis, Exercise-, Antigen- and Aspirin-
• Narrow therapeutic window Uses
induced bronchospasm
• Usual DOA: 12hrs
Gastrointestinal upset, Insomnia, Neuropsychiatric
• Causes bronchodilation and increased strength of SE
effects, Churg-Strauss syndrome (rare)
Notes contraction of diaphragm
No bronchodilator actions
Very effective in Asthma, however, is not frequently used Notes
anymore due to serious adverse effects. Not recommended for acute BA attack
If you are going to notice, all effects of Theophylline is the
same as coffee. For they are both Methylxanthine, including
also Theobromine from chocolate. J
OMALIZUMAB [B]
Class Anti-IgE antibody
Binds IgE antibodies on mast cells. Reduces reaction to
MOA
inhaled antigen.
Prophylaxis of severe, refractory asthma not
Uses
responsive to all other drugs
Fever, Angioedema, Anaphylactic reactions, Idiopathic
SE severe thrombocytopenia, nasopharyngitis, upper
abdominal pain
Binds IgE antibodies on sensitized mast cells and
prevents activation by BA triggers and subsequent
Notes release of inflammatory mediators
Humanized murine monoclonal antibody, very
expensive and only administered IV
GUIAFENESIN [C]
Class Expectorant
may act as an irritant to gastric vagal receptors, and
MOA recruit efferent parasympathetic reflexes that cause
glandular exocytosis of a less viscous mucus mixture
Uses Cough
Drowsiness, Incomplete or Infrequent Bowel
Movements, Inducing of a Relaxed Easy State, Stomach
SE
Cramps, dizziness or headache, a rash, or. nausea,
vomiting, or stomach upset
Notes Are often emetics (ipecac, guaifenesin)
ANTITUSSIVES
• Used for dry painful cough of neoplasia or pleural disease;
Irritative cough in inflammation of the respiratory tract
(epiglottitis); in hemoptysis
• DO NOT suppress in bacterial lung infections, asthma,
bronchiectasis (suppurating bronchial inflammation) or
chronic bronchitis where antitussives can cause harmful
sputum thickening & retention
DEXTROMETHORPHAN [C]
SimD CODEINE [C]
Class Centrally acting antitussive, opioid antitussive
decreased sensitivity of the medullary/ CNS cough
MOA centers to peripheral stimuli and decreased mucosal
secretion
Uses Cough
Decreases secretions in the bronchioles, thickens
SE sputum & inhibits ciliary activity, reducing clearance of
The major risk factor for asthma is atopy. thickened sputum, Constipation
The management of asthma depends on two important factors: Morphine may be effective but indicated only in
bronchodilation and smooth muscle relaxation.
intractable cough from bronchial carcinoma ;
Short-acting Beta 2 agonists are the first line reliever in intermittent
Notes Dextromethorphan has no addictive potential, no
asthma
Long-acting Beta 2 agonists are used as maintenance medications and analgesic effect, produces less constipation and
they are never used alone. They are commonly combined with in inhaled inhibition of mucociliary clearance
corticosteroids BUTAMIRATE CITRATE [C]
MNEMONIC: All long-acting beta 2 agonist has M in their names with Class Centrally acting antitussive, NON-opioid antitussive
the exception of Cleneterol MOA act through receptors in the brainstem to inhibit cough
Dr. Calderon Jr.
Uses Cough
SUPPLEMENT DRUGS USED FOR COUGH Somnolence, nausea, vomiting, diarrhea, dizziness and
N-ACETYLCYSTEINE [B] SE
hypotension
CARBOCISTEINE [C], AMBROXOL [C], BROMHEXINE Centrally acting antitussive but is neither chemically or
SimD Notes
[A], ERDOSTEINE pharmacologically related to opioids
Class Mucolytic
LEVODROPROPIZINE [D]
decrease sputum activity ; Usually derivatives of
Class Peripherally acting antitussive
cysteine; reduce disulfide bridges that bind
MOA Non-opioid drug with a peripheral action by inhibiting
glycoproteins to other proteins such as albumin; Also
MOA the afferent pathways that generate the cough reflex
act as antioxidants & may reduce airway inflammation
(modulates C-fiber activity)
Uses Cough (available as IV, PO, IM and inhalational forms
Uses Cough
Chest tightness, Disagreeable odor, Drowsiness, Fever,
Nausea, vomiting, heartburn, diarrhea, fatigue,
Hemoptysis, Increased volume of bronchial secretions,
SE SE weakness, drowsiness, dizziness, headache,
Irritation of tracheal or bronchial tract, Nausea,
palpitations
Rhinorrhea, Stomatitis, Vomiting
Orally available drugs are well-tolerated; but of little Does not cause side effects such as constipation or
Notes Notes respiratory depression which can be produced by
benefit in acute respiratory condition
opioid antitussive
N-acetylcysteine is also used in the management of acetaminophen
toxicity to prevent fulminant hepatitis. It is used as if to resurrect the SUPPLEMENT: OTHER DRUGS USED FOR COUGH
reduced form of glutathione that works as antioxidant to counteract Inhibits PDE III and inhibits Ca2+ entry (acts as
the reactive metabolite of acetaminophen known as NAPQ1 (free CCB), which partly explain its bronchodilatory
radical) effect; Considered a potent anti-inflammatory
Dr. Calderon Jr.
Vitex
negundo agent and acts via inhibition of COX2 without
(Lagundi) much interfering COX1 pathways; traditionally
used in hyperactive respiratory disorder, has
medicinal importance in asthma
AGENTS USED IN ANEMIAS AND Iron content of some oral Iron preparations (% w/w)
Fe carbonate / Carbonyl Iron 100%
HEMATOPOIETIC GROWTH FACTORS Fe fumarate 33%
Fe sulfate, dried 30%
DRUGS USED Fe sulfate, hydrated 20%
FOR ANEMIA PART 1 Ferric ammonium sulfate 18%
https://qrs.ly/vaboakz Fe gluconate 12%
Acute Iron Intoxication and
SUPPLEMENT:
DRUGS USED Hemochromatosis
FOR ANEMIA PART 2 Acute Iron Intoxication
https://qrs.ly/e4boakq • most common in children
• usually occurs as a result of accidental ingestion of iron
supplementation tablets
• CLINICAL MANIFESTATIONS
o necrotizing gastroenteritis, shock, metabolic acidosis,
coma, death
• TREATMENT
o removal of unabsorbed tablets from the gut
o correction of acid-base and electrolyte abnormalities
o parenteral administration of DEFEROXAMINE, which
chelates circulating iron
Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 Hemochromatosis
This topic in agents used in anemias and hematopoietic growth factor will • state of chronic iron overload that damages the organs that
be highly appreciated with the inclusion of hematology physiology and store excess iron (heart, liver, pancreas)
the study of different kinds of anemia: normocytic, microcytic and • Triad: CIRRHOSIS, DIABETES MELLITUS, SKIN
macrocytic. The B vitamins will also be appreciated as an adjunct to their PIGMENTATION
correlation in biochemistry • OCCURRENCE
Dr. Calderon Jr.
o persons with an inherited abnormality of iron absorption
o persons who receive frequent transfusions for treatment of
SUPPLEMENT: Iron and Iron Deficiency Anemia
hemolytic disorders (e.g. thalassemia major)
Iron and Vitamin Deficiency Anemias
• TREATMENT
• microcytic hypochromic anemia caused by iron deficiency is o phlebotomy
the most common type of anemia o chronic administration of DEFEROXAMINE or
o Laboratory picture: ↓ Iron, ↓ Ferritin, ↑ TIBC DEFERASIROX
• megaloblastic anemias are caused by a deficiency of vitamin
B12 or folic acid DEFEROXAMINE [C]
o pernicious anemia is the most common type SimD DEFERASIROX [B], DEFERIPRONE [D]
§ caused by a defect in the synthesis of intrinsic factor or by Class Heavy metal chelator
surgical removal of that part of the stomach that secretes MOA Chelates excess iron
intrinsic factor Acute iron poisoning, Hemochromatosis not
Uses
adequately treated by phlebotomy
Role of Iron Hypotension, ARDS, Neurotoxicity, Increased
SE
• essential metallic component of heme susceptibility to infections
• distribution of iron in the body Deferoxamine is used for acute intoxication (IV form),
o mostly contained in hemoglobin Notes while Deferasirox and Deferiprone are for chronic
o bound to Transferrin, a transport protein (Oral)
o bound to Ferritin, a storage protein SUPPLEMENT: Vitamin B12
• situations where iron deficiency occurs
Role of Vitamin B12
o in women because of menstrual blood loss
• cobalt-containing molecule
o in vegetarians or malnourished persons because of
inadequate dietary iron intake • cofactor in the transfer of 1-carbon units, a step necessary for
o children and pregnant women have increased iron the synthesis of DNA
requirements • deficiency of either vitamin B12 or folic acid usually manifests
o the unexplained presence of iron-deficiency anemia in any as megaloblastic anemia
adult (with the possible exception of a premenopausal, • vitamin B12 deficiency (NOT folic acid deficiency) causes
multiparous woman) mandates a thorough endoscopic neurologic defects
and/or radiographic visualization of the entire large bowel
CORRELATIONS: What are the neurologic manifestations
of Vitamin B12 deficiency?
FERROUS SULFATE [A]
Ataxic gait, impaired position and vibratory sense, spasticity
oral: FERROUS GLUCONATE [A], FERROUS
FUMARATE [A], FERROUS CARBONATE [A]
SimD Pharmacokinetics of Vitamin B12
parenteral: IRON DEXTRAN [A], SODIUM FERRIC
• produced only by bacteria
GLUCONATE COMPLEX [A], IRON SUCROSE [A]
• absorbed in the distal ileum in the presence of intrinsic factor
Class Hematopoietic growth factor
• plasma transport is accomplished by binding to
Required for the biosynthesis of heme and heme-
transcobalamin II
MOA containing proteins, including hemoglobin and
myoglobin • stored in the liver in large amounts (5-year supply)
Uses Iron deficiency anemia, Iron supplementation • 2 available forms: cyanocobalamin and hydroxocobalamin
Black stools (may obscure acute GI loss)
Pharmacodynamics of Vitamin B12
Acute overdose: necrotizing gastroenteritis,
abdominal pain, bloody diarrhea, shock, lethargy, • essential in 2 reactions
SE o conversion of methylmalonyl-coenzyme A (CoA) to
dyspnea
Chronic iron overload: hemochromatosis, organ succinyl-CoA
failure (heart, liver, pancreas etc.), death o conversion of homocysteine to methionine
• linked to folic acid metabolism and synthesis of
The best way to give iron is through oral preparation added with ascorbic deoxythymidylate (dTMP), a precursor required for DNA
acid for better absorption.
Dr. Calderon Jr.
synthesis
Vitamin B12 Deficiency FOLIC ACID [A]
• folates accumulate as N5-methyltetrahydrofolate FOLACIN (PTEROYLGLUTAMIC ACID) [A], FOLINIC
SimD
• supply of tetrahydrofolate is depleted ACID/LEUCOVORIN [C], L-METHYLFOLATE [A]
• production of red blood cells slows Class Hematopoietic growth factor
• administration of folic acid to patients with vitamin B12 Precursor of an essential donor of methyl groups used
deficiency helps refill the tetrahydrofolate pool and partially MOA for synthesis of amino acids, purines, and
or fully corrects the anemia deoxynucleotide.
• exogenous folic acid does not correct the neurologic defects Megaloblastic anemia, Prevention of neural tube
of vitamin B12 deficiency Uses defects (spina bifida), Prevention of coronary artery
disease
SE No significant toxicity
Folic acid is not toxic in overdose but large amounts
can partially compensate for Vit B12 deficiency and put
people with unrecognized B12 deficiency at risk of
Notes
neurologic consequences of Vit B12 deficiency (which
are not compensated by folic acid)
Only modest amounts are stored in the body
Recombinant Hematopoietic Growth Factors

• glycoprotein hormones that regulate the differentiation and
maturation of stem cells within the bone marrow
• approved for treatment of patients with blood cell deficiencies
EPOETIN ALFA [C]

DARBEPOETIN ALFA [C], METHOXY POLYETHYLENE
SimD
GLYCOL-EPOETIN BETA [C]
Class Hematopoietic growth factor
Agonist of erythropoietin receptors expressed by red
MOA
Figure 33-2. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018. cell progenitors
CYANOCOBALAMIN [C] Anemia especially associated with chronic renal
SimD HYDROXOCOBALAMIN [C], METHYLCOBALAMIN [C] failure, HIV infection, cancer, and prematurity, for
Uses
Class Hematopoietic growth factor prevention of the need for transfusion in patients
Cofactor required for essential enzymatic reactions undergoing certain types of elective surgery.
MOA that form tetrahydrofolate, convert homocysteine to SE Hypertension, Thrombosis, Pure red cell aplasia
methionine, and metabolize methylmalonyl-CoA Hemoglobin levels should be maintained <12 g/dL
Vitamin B12 deficiency, Megaloblastic anemia Performance-enhancing drug in athletes (prohibited
Uses use)
(pernicious anemia, gastric resection) Notes
SE No significant toxicity Darbepoetin is once a week administration, while
Parenteral form is required for pernicious anemia and Methoxy Polyethylene Glycol- Epoetin Beta is 1-2x per
other malabsorption syndrome month administration
Hydroxocobalamin has a longer t½ than Can you recall what is the main stimulus for EPO release in the kidney?
Notes Hypoxia-inducible factor 1.
cyanocobalamin
Dr. Calderon Jr.
Has a storage of up to 5yrs in the liver
FILGRASTIM (G-CSF)
Mecobalamin is the shorter term for Methylcobalamin
SARGRAMOSTIM (GM-CSF) [C], PEGFILGRASTIM [C],
SimD
PLERIXAFOR [D], LENOGRASTIM [C]
SUPPLEMENT: Folic Acid
Class Myeloid growth factor
Role of Folic Acid
Binds receptors on myeloid progenitors and
• required for normal DNA synthesis
stimulates cell maturation and proliferation.
• deficiency usually presents as megaloblastic anemia MOA
Accelerates neutrophil recovery and reduces
• deficiency of folic acid during pregnancy increases the risk of incidence of infection.
neural tube defects in the fetus Neutropenia associated with chemotherapy,
myelodysplasia, and aplastic anemia
Uses
Mobilization of peripheral blood cells in preparation
for hematopoietic stem cell transplantation
SE Bone pain (arthralgia), Fever, Edema, Splenic rupture
Pegfilgrastim has longer t½
Notes What are your granulocytes? Basophils, Eosinophils,
Neutrophils (BEN)
Dr. Calderon Jr.
OPRELVEKIN (IL-11) [C]

THROMBOPOIETIN [C], ELTROMBOPAG [C],
SimD
ROMIPLASTIM [C]
Class Megakaryocyte growth factor
Recombinant form of an endogenous cytokine;
MOA
activates IL-11 receptors.
Secondary prevention of thrombocytopenia in
Uses patients undergoing cytotoxic chemotherapy for non-
myeloid cancers
Fatigue, Headache, Dizziness, Anemia, Fluid
Modified from Figure 46-1. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
SE accumulation in the lungs, Transient atrial
arrhythmias
Pharmacokinetics of Folic Acid Notes given SC OD
• readily absorbed by the proximal jejunum
• only modest amounts are stored in the body
• decrease in dietary intake within 1-6 months is followed by
megaloblastic anemia
OTHER DRUGS FOR HEMATOLOGIC 2nd step: Platelet plug formation (primary hemostasis)
SUPPLEMENT:
DISORDERS • Exposed subendothelial collagen is highly thrombogenic
Small-molecule thrombopoietin (TPO)- • Platelet adhesion
receptor agonist that interacts with o mediated by vWF (essential for binding subendothelial
human TPO receptor transmembrane collagen to platelets) by GpIb receptor in the platelet
domain of human TPO-receptor & surface
initiates signaling cascades that induce • Platelet release reaction
proliferation & differentiation of o Adenosine diphosphate (ADP): platelet aggregation
megakaryocytes from bone marrow o Thromboxane A2 (TXA2): platelet activator and powerful
ELTROMBOPAG
progenitor cells ; used for Indicated for vasoconstrictor
treatment of thrombocytopenia in o Serotonin: platelet aggregation and vasoconstriction
adults and pediatric patients ≥6 yr with • Platelet aggregation → platelet plug
chronic immune (idiopathic)
thrombocytopenia (ITP) with 3rd step: Formation of clot via coagulation
insufficient response to corticosteroids, • 2 coagulation pathways
immunoglobulins, or splenectomy o intrinsic pathway: PTT Factor V, VIII, IX,X,XI, XII,
A hematopoietic stem cell mobilizer. prothrombin, Fibrinogen
Blocks binding of stromal cell-derived o extrinsic pathway: PT V,VII, X, prothrombin, fibrinogen
factor-1-alpha, found on bone marrow • net result of coagulation pathways: prothrombin activator
stromal cells, to the CXC chemokine (rate limiting factor causing blood coagulation)
receptor 4 (CXCR4). The inhibition
results in the mobilization of progenitor 4th step: fibrous Organization
and hematopoietic stem cells from the Fibrin mesh stabilize your platelet plug
PLERIXAFOR
bone marrow into peripheral blood;
Used for Mobilization of Hematopoietic
Stem Cells to Peripheral Blood for
Collection and Subsequent Autologous
Transplantation in Patients with Non-
Hodgkin Lymphoma (NHL) & Multiple
Myeloma
Fusion antibody-peptide that is a
thrombopoietin receptor agonist;
stimulates proliferation, differentiation,
ROMIPLOSTIM
and activity of monocytes, neutrophils,
eosinophils, and macrophages ; Used for
Thrombocytopenia
Given with a peripheral blood smear showing macrocytic red blood cells,
how can you clinically differentiate Folic acid deficiency vs. B12 deficiency?
The patient with macrocytic anemia with B12 deficiency will present
irreversible neurologic damage plus anemia. The Folic acid deficiency
patient will present with anemia alone.
What is the role of B12 deficiency in this neurologic manifestation?
According to Katzung, neurologic manifestation is associated with Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
methionine deficiency. Vitamin B12 also is essential for myelin and fatty
acid synthesis. ANTIPLATELET DRUGS
Dr. Calderon Jr.
• Arterial thrombosis is the most common cause of acute
myocardial infarction (MI), ischemic stroke, and limb gangrene
DRUGS USED IN COAGULATION DISORDERS • Predominance of platelets in arterial thrombi
SUPPLEMENT: Hemostasis
Mechanisms of hemostasis: ASPIRIN (ACETYSALICYLIC ACID, ASA) [C, D in 3rd trim]
1. Vasoconstriction SimD SALSALATE [C], SODIUM SALICYLATE
2. Platelet plug formation Antiplatelet drug, Anti-inflammatory drug ; COX
3. Formation of clot via blood coagulation Class
inhibitor
4. Fibrous Organization Nonselective, irreversible COX 1&2 inhibitor. Reduces
MOA platelet production of thromboxane A2, a potent
stimulator of platelet aggregation.
Prevention of arterial thrombosis (MI, TIA, CVD),
Uses Inflammatory disorders (rheumatic fever, Kawasaki
disease, juvenile rheumatoid arthritis)
Gastrointestinal toxicity, Nephrotoxicity, Tinnitus,
Hypersensitivity, Hyperventilation, HAGMA, Increased
SE
bleeding time, Nephrotoxicity (AKI and Interstitial
Nephritis)
Toxic dose (150 mg/kg); Lethal dose (500 mg/kg)
Uncoupler of oxidative phosphorylation
Associated with Reye syndrome in children
Do not use as NSAID for gout
Notes TRIFLUSAL is a Salicylic acid derivative
Aspirin Doses:
LOW Dose <160 Antiplatelet
Figure 37-1. Hall JE. Guyton and Hall Textbook of Medical Physiology. 13th ed. 2016 INTERMEDIATE Dose 160-1200mg Antipyretic, Analgesic
1st step: Vasoconstriction: HIGH Dose >1200mg Anti-inflammatory
• Local autacoid factors from traumatized tissues and platelets Dr. Pereyra-Borlongan
o Thromboxane A2 (TXA2): platelet activator and powerful A baby dose of aspirin 80 mg is enough for antiplatelet activity to prevent
vasoconstrictor thrombotic effects like TIA and MI. High doses of 3 to 5 grams serve as
o Endothelin: a potent endothelium derived vasoconstrictor anti-inflammatory drug.
• Local myogenic spasm Dr. Calderon Jr.
• Nervous reflexes
KEY LEARNING POINTS: Aspirin Toxicity As part of ACS regimen, a loading dose of 300 mg Clopidogrel can reduce
How many 500 mg Aspirin tablets must be ingested to platelet activity by 80% within 5 hours of administration.
produce toxicity? death?
Dr. Calderon Jr.
Toxic dose = 150 mg/kg DIPYRIDAMOLE [B]

150 mg/kg x 70 kg / 500 mg/tab = 21 tabs SimD CILOSTAZOL [C]
lethal dose = 500 mg/kg Class Antiplatelet drug; PDE inhibitor
500 mg/kg x 70 kg / 500 mg/tab = 70 tabs Inhibits phosphodiesterase III and increases cAMP in
What is the triad of aspirin hypersensitivity? MOA platelets and blood vessels. Inhibits platelet
SAMTER TRIAD aggregation and causes vasodilation.
• Asthma Prevention of thromboembolic complications of
• Aspirin sensitivity cardiac valve replacement, Secondary prevention of
Uses
• Nasal polyps ischemic stroke (with aspirin), Intermittent
ASPIRIN INTOXICATION claudication (cilostazol only)
• increased respiratory drive leads to hyperventilation and SE Headache (because it is a vasodilator), Palpitations
respiratory alkalosis Dipyridamole, by itself, has little or no benefit
• uncoupling of oxidative phosphorylation leads to increased Additional MOA: inhibit uptake of adenosine by
anaerobic metabolism via lactic acidosis and high-anion gap endothelial cells and RBC, thus increasing adenosine
metabolic acidosis Notes levels leading to inhibition of platelet aggregation ;
What is the expected acid-base abnormality in salicylate Cilostazol is contraindicated in heart failure
poisoning? Cilostazol used only in refractory intermittent claudication
in patients with PAD.
• Respiratory Alkalosis with HAGMA Dr. Pereyra-Borlongan
What is the difference between in presentation of aspirin
intoxication in children and adults? Usually anticoagulant is added with dipyridamole. Example in cases of
patient prosthetic heart valves.
• ADULTS = mixed acid-base disorder (Respiratory Alkalosis Dr. Calderon Jr.
with HAGMA)
• CHILDREN = pure acid-base disorder (HAGMA)
What is the difference between an inhibitor and an
ANTICOAGULANTS
uncoupler of oxidative phosphorylation? • mainly for the prevention and treatment of venous thrombosis
• INHIBITORS: completely halt ETC (pulmonary embolism, deep vein thrombosis)
• UNCOUPLERS: dissipate proton gradient without • drugs which inhibit the formation of fibrin clots
interrupting ETC • 2 major types of anticoagulants:
o indirect thrombin inhibitors: heparin, enoxaparin (LMWH),
CLINICAL CORRELATION: SURGERY coumarin derivatives (warfarin),
We often advise patient taking aspirin to stop medication intake for 7 to
10 days prior surgery. Is this advice proven safe? Will it not predispose
o direct thrombin inhibitors: Lepirudin
the patient to prothrombotic effects like stroke or myocardial infarction When to use anticoagulants? When to use antiplatelets? Aren’t they just
because you asked him or her to stop the medicine for a while? the same clot? As a general concept, we deal with the source and the
composition of the clot. Arterial source is platelet rich we call it white
The answer to this question is Yes it is safe. Remember, the half-life of thrombi. We prefer to give antiplatelet. Venous source is fibrin-rich and
platelets is around 7-10 days and aspirin molecule irreversibly and called red thrombi, we give anticoagulants.
covalently bind to that platelet for the rest of its life until reaching its
Dr. Calderon Jr.
graveyard (the spleen). COMPARISON OF HEPARIN AND WARFARIN
Dr. Calderon Jr.
CLINICAL CORRELATION: Aspirin in Uric Acid Elimination

Why is aspirin is not used anymore in management of gout
In low to moderate dose (Aspirin (being a weak acid just like your
furosemide, thiazide) can compete with Uric acid for elimination →
Hyperuricemia
High dose: decrease tubular reabsorption (because now in a high dose is
now nephrotoxic! Thus, uric acid is not absorbed it now URICOSURIC
Both spectrum has no clinical benefit.

Dr. Calderon Jr.
ABCIXIMAB [C]
SimD EPTIFIBATIDE [B], TIROFIBAN [B]
Class Antiplatelet drug ; GPIIa/IIIa inhibitor
Inhibits platelet aggregation by interfering with
MOA
GPIIb/IIIa binding to fibrinogen and other ligands
Used during PCI to prevent thrombosis, Adjunct to
Uses thrombolysis, Acute Coronary Syndromes (unstable
angina, NSTEMI)
SE Bleeding, Thrombocytopenia
Notes Prevents vessel restenosis, reinfarction and death
CLOPIDOGREL [B]
SimD TICLOPIDINE [B], PRASUGREL [B], TICAGRELOR [C]
Class Antiplatelet drug (Thienopyridine): ADP inhibitor
Irreversibly inhibits binding of ADP to platelet
MOA
receptors, reducing platelet aggregation
Prevention and treatment of arterial thrombosis
Uses (stroke, TIA, unstable angina), Prevention of
restenosis after PCI, Acute coronary syndromes
Bleeding, Nausea, Dyspepsia, Hematologic
SE (neutropenia, Leukopenia, Thrombotic
thrombocytopenic purpura (Ticlopidine)
GI & Hematologic SE are more common with
ticlopidine
Additive effects with aspirin MNEMONIC: PT/PTT
Notes TICAGRELOR specifically inhibits ADP subtype P2Y. IN What laboratory tests will you request to assess the extrinsic
contrast to another antiplatelet drug, it has a binding and intrinsic coagulation pathways?
site different from ADP, making it an allosteric PiTT = PTT for intrinsic pathway
antagonist PeT = PT for extrinsic pathway
HEPARIN [C] Chronic anticoagulation (DVT, atrial fibrillation, valve
Uses
Class Anticoagulant (indirect thrombin inhibitor) replacement) EXCEPT in pregnancy
Activates antithrombin III (inactivates thrombin or Bleeding, Warfarin-induced skin necrosis (for patients
MOA Factor IIa, Factor IXa & Factor Xa by forming stable SE with protein C & S deficiencies), Teratogen (bone
complexes with them) defects, hemorrhage)
Deep venous thrombosis, Pulmonary embolism, Monitor effects with PT
Myocardial infarction, Unstable angina, Adjuvant to Antidote is VITAMIN K (slow) or FFP (fast)
percutaneous coronary intervention (PCI) and Notes Narrow therapeutic window
thrombolytics, Atrial fibrillation, DOC for Active ingredient in most rat poisons
Uses
anticoagulation during pregnancy, given with Highly protein-bound
thrombolytics for revascularization procedures, given
with GPIIb-IIIa inhibitors for angioplasty and stent
placement
Bleeding, Heparin-induced thrombocytopenia,
SE
Osteoporosis with chronic use
Monitor with aPTT KEY LEARNING POINTS: Anticoagulant Overlap
Antidote is Protamine Sulfate In patients requiring anticoagulation, why is an overlap
Notes Administered IV or SC between heparin and warfarin usually done?
SULODEXIDE: A Heparinoid consisting of 80% • warfarin’s effect requires elimination of preformed clotting
Heparin and 20% dermatan sulfate factors (8 - 60h)
• to bypass the initial prothrombotic effect of warfarin (skin
ENOXAPARIN [B] necrosis)
DALTEPARIN [B], TINZAPARIN [B], DANAPAROID [B],
SimD
FONDAPARINUX [B], NADROPARIN [B] Drug Interactions of Warfarin
Class Anticoagulant (indirect thrombin inhibitor) • cytochrome P450-inducers increase clearance and reduce the
Binds and potentiates effect of antithrombin III on anticoagulant effect of a given dose
MOA
factor Xa (more selective). Less effect on thrombin. • cytochrome P450-inhibitors reduce clearance and increase
Deep venous thrombosis, Pulmonary embolism, the anticoagulant effect of a given dose
Myocardial infarction, Unstable angina, Adjuvant to
Uses Heparin-Induced Thrombocytopenia happens in 15% of patient. The
percutaneous coronary intervention (PCI) and pathogenesis is through opsonization of the heparin-platelet complex. In
thrombolytics, Atrial fibrillation immunology, large molecules are immunogenic. Hence, in some cases,
SE Bleeding, Less risk of thrombocytopenia because heparin is a large molecule it is immunogenic promoting its own
Does NOT require aPTT monitoring phagocytosis leading to a decrease number of platelet. The key here is to
Protamine sulfate is only partially effective in replace heparin with a Low molecular weight heparin just like
Notes reversing effects Fondaparinux.
Advantage over regular heparin is higher Warfarin-Skin Necrosis: This happens when you initially give warfarin
bioavailability and t½; Fondaparinux is given SC OD to patient. Remember the difference between warfarin and heparin and
their effects on their respective factors. Warfarin works in X, IX, VII,
Protein C and S. I want you to remember protein C and S as “brake fluids”
LEPIRUDIN [B]
of coagulation. Heparin works on the already activated factors.
DESIRUDIN[C], BIVALIRUDIN [B], ARGATROBAN [B], Imagine you give initial warfarin to your patient; will it address activated
SimD
DABIGATRAN [C] factors? No, but will it work against protein C and S (the break fluids)?
Class Anticoagulant (direct thrombin inhibitor) Yes. So, what is left is a state if pro-coagulation. Hence, skin necrosis.
Binds to thrombin's active site and inhibits its How to prevent this? You must start first with Heparin to address the
MOA activated factors and gradually introduce warfarin. This is the process of
enzymatic action
Anticoagulation in patients with heparin-induced Heparin-Warfarin bridging.
Dr. Calderon Jr.
Uses thrombocytopenia (HIT), Percutaneous coronary
MNEMONIC: P450 INDUCERS AND INHIBITORS
angioplasty (with aspirin)
Bleeding, Effect-prolonging antibodies, Anaphylactic CYTOCHROME P450 INDUCERS
SE Ethel Booba takes Phen-Phen
reactions
Monitor effect with aPTT and Refuses Greasy Carb Shakes
No reversal agents exist Ethanol Griseofulvin
Used with caution for patients with renal insufficiency Barbiturates Carbamazepine
Dabigatran is PO while all the rest are parenteral Phenytoin St. John’s Wort / Smoking
Notes Rifampicin
Bivalirudin also inhibits platelet activation
IDARUCIZUMAB is a monoclonal antibody used for
reversal of Dabigatran toxicity (needs dose adjustment CYTOCHROME P450 INHIBITORS
for renally impaired patients) Inhibitors Stop Cyber Kids from Eating GRApefruit QV
Isoniazid Grapefruit Juice
RIVAROXABAN [C] Sulfonamides Ritonavir
SimD APIXABAN [B] Cimetidine Amiodarone
Ketoconazole Quinidine
Class Oral Direct Factor Xa inhibitor
Erythromycin Valproic Acid
MOA Inhibit Factor Xa in the final common pathway
Prevention of Venous thromboembolism, Prevention
Uses PROTAMINE SULFATE [C]
of stroke in patients with Atrial Fibrillation
Class Antidote
SE Bleeding, Dizziness, Diarrhea, Edema, Epistaxis
Have rapid onset of action and shorter half-lives than Chemical antagonist of heparin. Reverses excessive
MOA
warfarin anticlotting activity of unfractionated heparin.
Notes Do not require monitoring. No antidotes Uses Heparin overdosage
Used esp. after hip or knee surgery Hypotension, Bradycardia, Flushing, Hypersensitivity,
SE
Dose adjustment needed in renally impaired patients Dyspnea
Notes Partially reverses effects of LMWHs
WARFARIN [X]
SimD DICUMAROL, ANISINDIONE
Class Anticoagulant
Inhibits vitamin K epoxide reductase (responsible for
MOA γ-carboxylation of the vitamin K-dependent clotting
(factors II, VII, IX, X, Protein C & Protein S)
FIBRINOLYTIC DRUGS DESMOPRESSIN [B]

SimD VASOPRESSIN [C], TERLIPRESSIN
• mainly for the treatment of acute myocardial infarction,
Class ADH agonist
ischemic stroke and massive pulmonary embolism
MOA Vasopressin V2 receptor agonist
Hemophilia A, von Willebrand’s disease, Central
Uses
diabetes insipidus
SE Headaches, Flushing, Nausea, Hyponatremia, Seizures
Increases the factor VIII activity of patients with mild
Notes
hemophilia A or von Willebrand disease
SUPPLEMENT: APROTININ [B]

Class Serine Protease Inhibitor ; Antiplasmin drug
Inhibits plasmin and plasmin-streptokinase
MOA complex in patients who have received
Streptokinase.
Uses Post-op or Intra-Op bleeding
Increased risk of renal failure, heart attack and
SE
stroke
May reduce bleeding by as much as 50% (in many
Notes types of surgeries)
Removed from the market in 2007 due to mortality
ALTEPLASE [C] OTHER DRUGS USED FOR COAGULATION

ANISTREPLASE [C], RETEPLASE [C], STREPTOKINASE SUPPLEMENT:
SimD DISORDERS
[C], TENECTEPLASE [C], UROKINASE [B] • Antihemophilic factor
Class Thrombolytic • Anti-inhibitor coagulant complex
Tissue plasminogen activator analog. Converts • Anti-thrombin III
MOA plasminogen to plasmin, which degrades the fibrin and • Factor VIIa, VIII, IX complex
fibrinogen, causing thrombolysis • Somatostatin: Tx of intestinal and pancreatic fistulae,
Acute myocardial infarction, Ischemic stroke, excessive secretion from endocrine tumors of the GIT, acute
Uses
Pulmonary embolism severe GI hemorrhage, endoscopic retrograde cholangio-
Bleeding, Cerebral hemorrhage, Reperfusion pancreatography
SE
arrhythmias
Loss of effectiveness (on 2nd use) and allergic reactions
may be observed with streptokinase NSAIDS, ACETAMINOPHEN, DMARDS AND
Antidote is AMINOCAPROIC ACID DRUGS USED IN GOUT
Tx should be done within 6 hrs, better if within 3hrs
Notes
Streptokinase forms a complex with endogenous
plasminogen, thus catalyzing the conversion of
plasminogen to plasmin
tPA is selective for fibrin-bound plasminogen
SUPPLEMENT: Contraindications to Thrombolysis
• history of cerebrovascular hemorrhage at any time
• non-hemorrhagic stroke or other cerebrovascular event Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
within the past year

• marked hypertension (>180/110 mmHg) at any time during SUPPLEMENT: Inflammation
the acute presentation • complex response to cell injury that primarily occurs in
• suspicion of aortic dissection vascularized connective tissue and often involves the immune
• active internal bleeding (excluding menses) response
• mediators of inflammation function to eliminate the cause of
cell injury and clear away debris, in preparation for tissue
PROTHROMBOTICS
repair
TRANEXAMIC ACID [B] • causes pain and tissue damage
Class Aminocaproic Acid; Antiplasmin drug
Competitively inhibits plasminogen activation by
MOA NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
inhibiting tPA
Prevention and treatment of acute bleeding episodes Classification of NSAIDs
in patients with high risk of bleeding (hemophilia, • SALICYLATES
Uses
intracranial aneurysms, menstrual, obstetric, o Aspirin
thrombolytics, postoperative) • NONSELECTIVE NSAIDs
SE Thrombosis, Hypotension, Myopathy, Diarrhea o Ibuprofen, Indomethacin, Ketorolac, Piroxicam
Contraindicated in disseminated intravascular • COX-2 SELECTIVE
Notes
coagulation (DIC) o Celecoxib, Etoricoxib, Parecoxib
VITAMIN K1 (PHYTONADIONE) [C]
Common NSAID Toxicities
VITAMIN K2 (MENAQUINONE)
SimD VITAMIN K3 (MENADIONE) • CNS: headaches, tinnitus, dizziness
PHYTOMENADIONE • CVS: hypertension, edema, heart failure
Class Endogenous vitamin, Antidote • GIT: abdominal pain, dysplasia, nausea, vomiting, ulcers,
Increases supply of reduced vitamin K, which is bleeding
MOA required for synthesis of functional vitamin K- • HEMATOLOGIC: thrombocytopenia, neutropenia, aplastic
dependent clotting and anticlotting factors anemia
Vitamin K deficiency, Antidote to warfarin, Prevention • HEPATIC: abnormal liver function tests, liver failure
Uses • PULMONARY: asthma
of hemorrhagic diatheses in newborns
Severe infusion reaction when administered too fast • RASHES: all types, pruritus
SE • RENAL: renal insufficiency, renal failure, hyperkalemia,
(dyspnea, chest and back pain)
Vitamin K3 (menadione) should NEVER be used in proteinuria
Notes
therapeutics (ineffective)
ASPIRIN (ACETYSALICYLIC ACID, ASA) [C, D I 3rd trim] • Ibuprofen and Indomethacin can be used to close
SALSALATE, SODIUM SALICYLATE, CHOLINE PDA
SimD
SALICYLATE, MAGNESIUM SALICYLATE • Ibuprofen and naproxen have moderate
Class Antiplatelet drug, NSAID (Non-selective) effectiveness
Nonselective, irreversible COX 1&2 inhibitor. Reduces • Ibuprofen is relatively safe but with short half-life of
MOA platelet production of thromboxane A2, a potent 2hrs
stimulator of platelet aggregation. • Naproxen and Piroxicam have longer half-lives
Prevention of arterial thrombosis (MI, TIA, CVD), • NSAIDs may interfere with ASA's antithrombotic
Uses Inflammatory disorders (rheumatic fever, Kawasaki action
disease, juvenile rheumatoid arthritis)
Gastrointestinal toxicity, Nephrotoxicity, Tinnitus, KETOROLAC [C, D in >30weeks AOG]
SE
Hypersensitivity, Hyperventilation, HAGMA SimD DEXKETOPROFEN [B]
Uncoupler of oxidative phosphorylation Class Intravenous NSAID (nonselective)
Associated with Reye’s syndrome in children Nonselective reversible COX-1 and COX-2 inhibitor.
Prevents uric acid excretion (don’t use in gout) MOA
Inhibits prostaglandin synthesis.
Notes Low doses undergo first order kinetics while high Post-surgical analgesic control (moderate to severe,
doses undergo zero order reaction Uses short-term), mainly used for analgesia not for anti-
Long term use reduces the risk of colon cancer inflammatory effect
(unknown/not well understood mechanism) High risk for gastrointestinal toxicity and
SE
nephrotoxicity, Allergic reactions
DOSAGE RANGES OF ASPIRIN Use generally restricted to 72 hours only (due to GI
• low range (<300 mg/d) and renal damage)
o effective in reducing platelet aggregation Notes Intravenous NSAID
o follows first-order elimination kinetics Ketorolac has significant analgesic effect but not anti-
• intermediate doses (300–2400 mg/d) inflammatory effect
o antipyretic and analgesic effects An effective replacement for morphine in post-surgical patient reducing
• high doses (2400–4000 mg/d) opioid requirement by 25-50%. It has no anti-inflammatory effect.
o anti-inflammatory effects
Dr. Calderon Jr.
o follows zero-order elimination kinetics INDOMETHACIN [C]

SUPPLEMENT: Aspirin Overdose Class NSAID (nonselective)
Nonselective reversible COX-1 and COX-2 inhibitor.
• DOSAGE MOA
Inhibits prostaglandin synthesis.
o toxic dose: 150 mg/kg (21 Aspirin 500mg tabs)
Anti-inflammatory (gout, arthritis, ankylosing
o lethal dose: 30g (60 Aspirin 500mg tabs) Uses
spondylitis), Closure of patent ductus arteriosus
• CLINICAL PRESENTATION
Gastrointestinal toxicity, Pancreatitis, Nephrotoxicity,
o HAGMA, dehydration, hyperthermia, collapse, coma
SE Serious hematologic reactions (aplastic anemia,
• TREATMENT
thrombocytopenia), BM suppression
o no specific antidote
Inhibits COX1 > COX2
o supportive management
Notes Indomethacin has greater anti-inflammatory effect
o activated charcoal / gastric lavage
compared to other NSAIDs
o alkalinize the urine with bicarbonate
Indomethacin has largely replaced colchicine in the management of
gouty arthritis
NSAIDS CHEMICAL GROUPING:
Dr. Calderon Jr.
• Salicylates: Aspirin, Diflunisal, Methyl Salicylate CELECOXIB [C, D in >30weeks AOG]

• Propionic Acid derivative: Ibuprofen, Naproxen, Fenoprofen, ETORICOXIB [C in 1st & 2nd trim, D in 3rd trim],
SimD
Carprofen, Ketoprofen, Dexketoprofen, Oxaprozin PARECOXIB [X in 3rd trim], ROFECOXIB, VALDECOXIB
• Pyrrolealkanoic acid derivative: Tolmetin Class NSAID (Highly COX-2 selective)
• Phenylalkanoic acid derivative: Flurbiprofen Selective COX-2 inhibitor. Inhibits prostaglandin
MOA
• Indole and Indene derivative: Indomethacin synthesis.
• Pyrazolone derivative: Phenylbutazone, Oxyphenbutazone Uses Analgesia, Antipyretic, Anti-inflammatory
• Phenylacetic acid derivative: Diclofenac, Alclofenac, Sulindac Gastrointestinal bleeding (reduced risk),
• Fenamate derivative: Meclofenamic acid, Mefenamic acid, SE Nephrotoxicity, Myocardial infarction and Stroke
Diclofenac (rofecoxib and valdecoxib only), rash
• Oxicam derivative: Piroxicam, Meloxicam, Tenoxicam Coxibs are 10-20x COX2 > COX1
• Naphthylacetic acid prodrug: Nabumetone 50% less GI SE compared to Non-selective NSAIDs
• Sulfoxide: Sulindac Rofecoxib and Valdecoxib withdrawn due to increased
Notes
incidence of thrombosis
IBUPROFEN [C, D in >30weeks AOG] MELOXICAM is a PREFERENTIALLY COX2 selective
DICLOFENAC [C], DIFLUNISAL [C], ETODOLAC [C], inhibitor
FENOPROFEN [D], FLURBIPROFEN [C], KETOPROFEN
[C], NABUMETONE [C], NAPROXEN [C], OXAPROZIN PARACETAMOL
SimD [C], PIROXICAM [C], SULINDAC [C], TOLMETIN [C], PARACETAMOL (ACETAMINOPHEN) [B]
MEFANAMIC ACID [C], BROMFENAC [C], SimD PHENACETIN [B]
MECLOFENAMATE [C], SUPROFEN [C], Class Analgesic (COX-3 inhibitor)
ACECLOFENAC [C in 1st & 2nd trim, D in 3rd trim] Selectively inhibits COX-3. Weak COX-1 and COX-2
Class NSAID (nonselective) MOA
inhibitor. Inhibits prostaglandin synthesis.
Nonselective reversible COX-1 and COX-2 inhibitor. Uses Analgesia (mild), Antipyretic
MOA
Inhibits prostaglandin synthesis. Hepatotoxicity, Renal papillary necrosis and
Analgesia (musculoskeletal, headache, SE Interstitial nephritis (phenacetin only),
Uses
dysmenorrhea), Antipyretic, Anti-inflammatory Methemoglobinemia, Hemolytic anemia
Gastrointestinal bleeding (less than aspirin), Increased hepatotoxicity with alcohol use
SE Nephrotoxicity (AKI and Interstitial Nephritis), Preferred antipyretic in children (does NOT cause
Hypersensitivity reaction Notes Reye’s syndrome)
• Long-term use reduces the risk of colon cancer Antidote is N-acetylcysteine
• Misoprostol prevents NSAID-induced gastritis t½ is only 2-3h
Notes
• NSAIDs (in general) may cause premature closure of
Ductus Arteriosus
SUPPLEMENT: Paracetamol Overdose AZATHIOPRINE [D]
Mechanism of Paracetamol Overdose Class DMARD
• oxidation to a cytotoxic intermediate called N-acetyl-p- Forms 6-Thioguanine, suppressing inosinic acid
benzoquinoneimine (NAPQI) by phase I cytochrome P450 MOA synthesis, B-cell and T-cell function, immunoglobulin
enzymes (CYP2E1) production, and interleukin-2 secretion
• occurs if substrates for phase II conjugation reactions Rheumatoid arthritis, Psoriatic arthritis, Reactive
Uses
(acetate and glucuronide) are lacking arthritis, Polymyositis, SLE, Behçet disease
• centrilobular region (zone III) is preferentially involved Bone marrow suppression, Increased risk of
because it is the area of greatest concentration of CYP2E1 SE infections, Increased incidence of lymphoma, Fever,
• antidote is N-acetylcysteine (NAC), a sulfhydryl donor Rash, Hepatotoxicity, Allergic reactions
Stages of Paracetamol Overdose Cannot give Allopurinol with azathioprine (allopurinol
reduces xanthine oxide catabolism of purine analogs,
Notes
increasing 6-thioguanine nucleotides, leading to
severe leukopenia)
CHLOROQUINE [C]
SimD HYDROXYCHLOROQUINE [C]
Class DMARD, Anti-malarial
Suppression of T-lymphocyte responses to mitogens,
decreased leukocyte chemotaxis, Stabilization of
MOA
lysosomal enzymes, Inhibition of DNA and RNA
synthesis, Trapping of free radicals
Uses Rheumatoid arthritis, SLE, Sjögren syndrome, Malaria
Paracetamol Overdose Ocular toxicity, Dyspepsia, Nausea, Vomiting,
SE
• DOSAGE Abdominal pain, Rashes, Nightmares
o toxic dose: 150mg/kg (21 Paracetamol 500 mg tabs)
o lethal dose: 15g (30 Paracetamol 500 mg tabs) CYCLOPHOSPHAMIDE [D]
• TREATMENT Class DMARD, Cancer Chemotherapeutic Drug
o antidote is N-acetylcysteine Forms phosphoramide mustard, which cross-links
o supportive management MOA DNA to prevent cell replication. Suppresses T-cell and
o gastric decontamination with activated charcoal B-cell function
Rheumatoid arthritis, SLE, vasculitis, Wegener's
Uses
DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS granulomatosis, Severe rheumatic diseases
Bone marrow suppression, Hemorrhagic cystitis,
(DMARDs) SE Hepatotoxicity, Alopecia, SIADH, Cardiac dysfunction,
SUPPLEMENT: Rheumatoid arthritis Pulmonary toxicity
• chronic inflammatory disease of unknown etiology marked Notes Rescue agent is MESNA
by a symmetric, peripheral polyarthritis.
• It is the most common form of chronic inflammatory arthritis CYCLOSPORINE [C]
Disease-Modifying Anti-Rheumatic Drugs (DMARDs) Class DMARD
• heterogeneous group of agents with anti-inflammatory actions Inhibits interleukin-1 and interleukin-2 receptor
used in several connective tissue diseases MOA production and secondarily inhibits macrophage–T-
• cause slowing or even reversal of joint damage cell interaction and T-cell responsiveness
• may take 6 weeks to 6 months for their benefits to become Rheumatoid arthritis, SLE, Polymyositis,
apparent Uses Dermatomyositis, Wegener's granulomatosis, Juvenile
rheumatoid arthritis, Tissue transplantation
METHOTREXATE [X] Nephrotoxicity, Hypertension, Hyperkalemia,
SE
Class DMARD, Cancer Chemotherapeutic Drug Hepatotoxicity, Gingival hyperplasia, Hirsutism
Inhibits AICAR transformylase and thymidylate MNEMONIC: Gingival Hyperplasia
MOA synthetase, with secondary effects on What drugs can cause gingival hyperplasia?
polymorphonuclear chemotaxis NapaCa-Pangit ng gingiVa mo!
Rheumatoid arthritis, SLE, JRA, Psoriatic arthritis, Nifedipine Phenytoin
Ankylosing spondylitis, Polymyositis, Cyclosporine Verapamil
Uses
Dermatomyositis, Wegener's granulomatosis, Giant
MYCOPHENOLATE MOFETIL [D]
cell arteritis, Vasculitis
Class DMARD
Nausea, Mucosal ulcers, Hepatotoxicity,
SE Active product (mycophenolic acid) inhibits inosine
Hypersensitivity, Pseudolymphomatous reaction
monophosphate dehydrogenase (important enzyme in
DMARD of first choice to treat rheumatoid arthritis MOA
Notes the guanine nucleotide synthesis) and inhibits T-cell
Rescue agent is Leucovorin (folinic acid)
lymphocyte proliferation
SLE nephritis, Vasculitis, Wegener’s granulomatosis,
INFLIXIMAB [B] Uses
Rheumatoid arthritis
ADALIMUMAB [B], ETANERCEPT [B],
SimD Gastrointestinal disturbances, Headache,
CERTOLIZUMAB [B], GOLIMUMAB [B]
SE Hypertension, Reversible myelosuppression
Class DMARD
(neutropenia)
Binds to TNF-a and prevents it from activating TNF-a
MOA Mycophenolic acid is the least toxic for SLE nephritis.
receptor
Dr. Calderon Jr.
Crohn’s disease, Rheumatoid arthritis, Other

Uses SULFASALAZINE [B, D if used for prolonged periods or near term]

rheumatic diseases Class DMARD
Bacterial infections (URTIs), Reactivation of latent Active metabolite (sulfapyridine) inhibits the release
tuberculosis, Lymphoma, Demyelination, Reactivation MOA
of inflammatory cytokines
SE of hepatitis B, Autoantibody formation (ANA, anti-
Rheumatoid arthritis, Inflammatory bowel disease,
dsDNA), Infusion reactions, hepatoxicity, Uses
JRA, Ankylosing spondylitis
hematotoxicity, cardiotoxicity
Nausea, Vomiting, Headache, Rash, Hemolytic anemia,
Synergistic effects with methotrexate
Methemoglobinemia, Neutropenia,
Crosses placenta SE
Notes Thrombocytopenia, Pulmonary toxicity, Autoantibody
This group of drugs has insufficient studies proving
formation (anti-dsDNA), Reversible infertility in men
their safety among pregnant Px
SUPPLEMENT: OTHER IMMUNOMODULATORS
ABATACEPT [C] A sphingosine-1-phosphate receptor
FINGOLIMOD
Class Co-stimulation modulator modulator; used for multiple sclerosis
Inhibits the activation of T Cells by binding to CD80 A monoclonal antibody against IL-17;
MOA
and CD86 on the APC SECUKINUMAB used for psoriasis and ankylosing
For moderate to severe Rheumatoid Arthritis spondylitis
Uses (monotherapy or in combination with other A monoclonal antibody against IL-2; used
DMARDs) BASILIXIMAB to prevent rejection during organ
Increased risk of infection (esp. URTI), transplantation
SE
Hypersensitivity reaction, Infusion-related reaction A monoclonal antibody against IL-12 and
Concomitant use with TNF-a blocker is not USTEKINUMAB IL-23; used for Crohn’s disease and
Notes recommended due to increased incidence of psoriasis
serious infection.
DRUGS FOR THE TREATMENT OF GOUT
LEFLUNOMIDE [X] SUPPLEMENT: Gout
Class Non-biologic DMARD • increased serum concentrations of uric acid
Its active metabolite inhibits Dihydroorotate • acute attacks involve joint inflammation initiated by
dehydrogenase → decreased synthesis of precipitation of uric acid crystals
MOA ribonucleotide and arrest of stimulated cells in the TREATMENT STRATEGIES FOR GOUT
G1 phase of cell growth. Inhibits T cell proliferation • reducing inflammation during acute attacks
and production of autoantibodies by B cells. • accelerating renal excretion of uric acid with uricosuric drugs
Uses Rheumatoid Arthritis • reducing the conversion of purines to uric acid by xanthine
Diarrhea, Elevation of liver enzymes, Mild alopecia, oxidase
SE Weight Gain, Increased blood pressure,
COLCHICINE [C]
Leukopenia, Thrombocytopenia
Class Antigout drug (microtubule assembly inhibitor)
Converted to its active metabolite in the intestines
(A77-1726) Inhibits microtubule assembly and LTB4 production
Notes MOA leading to decreased macrophage migration and
Considered as effective as Methotrexate in
phagocytosis
Rheumatoid Arthritis
Uses Gout, Familial Mediterranean fever
RITUXIMAB [C] Diarrhea, Nausea, Vomiting, Abdominal pain, Hepatic
Class Monoclonal antibody necrosis, Acute renal failure, Disseminated
SE intravascular coagulation, Seizures, Hair loss, Bone
Depletes B cells by cell-mediated and complement-
marrow depression (aplastic anemia), Peripheral
dependent cytotoxicity and stimulation of cell
neuritis, Myopathy
MOA apoptosis → reduced inflammation by decreasing
diarrhea is the adverse effect which signals toxicity
the presentation of antigens to T lymphocytes and Notes
from colchicine
inhibits secretion of cytokine
Moderate to Severe Rheumatoid Arthritis (with SUPPLEMENT: NSAIDs in Gout
Uses Methotrexate) in patients with an inadequate • In addition to inhibiting prostaglandin synthase, indomethacin
response to TNF-a. and other NSAIDs also inhibit urate crystal phagocytosis
Rash, Increased risk of infection, Cardiovascular • Aspirin is not used due to its renal retention of uric acid at low
SE doses
events
• Indomethacin is commonly used in the initial treatment of gout
TOCILIZUMAB [C] as the replacement for colchicine
Class Monoclonal Antibody PROBENECID [B]
Binds to IL-6 → decreased T cell activation and SimD SULFINPYRAZONE [C]
MOA
inflammatory process Class Antigout drug (uricosuric agent)
Moderate to Severe Rheumatoid Arthritis in Compete with uric acid for reabsorption in the
Uses MOA
patients with an inadequate response to TNF-a. proximal tubules. Increase uric acid excretion.
URTI, Headache, Hypertension, Elevated liver Uses Gout
enzymes, Neutropenia, Thrombocytopenia, Gastrointestinal irritation, Rashes, Nephrotic
SE
Tuberculosis, Fungal Viral and other Opportunistic SE syndrome (probenecid only), Aplastic anemia, Sulfa
infections Allergy
Screening for Tuberculosis should be done prior to May precipitate acute gout during early phase of drug
Notes beginning Tocilizumab action (prevent by co-administering with colchicine or
Do not use in patients with Diverticulitis indomethacin)
Inhibit secretion of other weak acids (e.g. penicillin,
OTHER DMARDs: Notes
methotrexate)
-see chapter on endocrine May be given together with antimicrobial agents
GLUCOCORTICOIDS pharmacology- (particularly Penicillins) to prolong therapeutic effect
Gold compounds MOA is not well by inhibiting renal tubular secretion of antibiotics
understood. Auranofin has a low
GOLD COMPOUNDS: A required minimum 30 ml/min GFR is important before starting
incidence of serious toxicity but the
GOLD SODIUM Probenecid. Other uricosuric agents are Fenofibrate and Losartan as
overall frequency of SE (rash, example.
THIOMALATE [C]
diarrhea) is higher with Auranofin Dr. Calderon Jr.
(Auranofin),
than any other DMARD. Its utility ALLOPURINOL [C]

AUROTHIOGLUCOSE
therefore is limited by low efficacy Class Antigout drug (xanthine oxidase inhibitor)
and poor tolerability Active metabolite (alloxanthine) irreversibly inhibits
Reduces number of T lymphocytes, MOA
Xanthine Oxidase and lowers production of uric acid
inhibits macrophage function, 1st line treatment for chronic gout, Tumor lysis
PENICILLAMINE [D] decreases IL-1, decreases Uses
syndrome
rheumatoid factor and prevents Gastrointestinal upset, Rash, Peripheral neuritis,
collagen from cross-linking SE Vasculitis, Bone marrow dysfunction, Aplastic anemia,
Janus Kinase inhibitor (JAK); used Cataracts
TOFACITINIB
for RA Inhibits metabolism of mercaptopurine and azathioprine
Withheld for 1–2 weeks after an acute episode of gouty
Notes
arthritis (co-administered with colchicine or
indomethacin to avoid an acute attack)
• BACTERIOSTATIC
o inhibits microbial growth but requires host defense
mechanisms to eradicate the infection
o does not kill bacteria
MNEMONIC: Bactericidal VS Bacteriostatic Antibiotics

What antibiotics are BACTERICIDAL?
Very Finely Proficient At Murder!
Vancomycin Aminoglycosides
Fluoroquinolones Metronidazole
Penicillins
What antibiotics are BACTERIOSTATIC?

Figure 36-7. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018. We’re ECSTaTiC about bacteriostatics.
FEBUXOSTAT [C] Erythromycin Trimethoprim
Class Antigout drug (xanthine oxidase inhibitor) Clindamycin Tetracycline
Nonpurine reversible inhibitor of xanthine oxidase Sulfamethoxazole Chloramphenicol
MOA (more selective than allopurinol). Lowers production
of uric acid. MINIMUM INHIBITORY CONCENTRATION
Chronic gout, Tumor lysis syndrome, Allopurinol • lowest concentration of antimicrobial drug capable of inhibiting
Uses
intolerance growth of an organism in a defined growth medium
Liver function abnormalities, Headache,
SE Gastrointestinal upset, rash, liver dysfunction
SUPPLEMENT: Antibacterial Therapy
(Febuxostat)
Withheld for 1–2 weeks after an acute episode of gouty • EMPIRIC THERAPY
arthritis (co-administered with colchicine or o initiation of drug treatment before identification of a
indomethacin to avoid an acute attack) specific pathogen
Notes Febuxostat is a newer non-purine inhibitor of • ANTIMICROBIAL PROPHYLAXIS
Xanthine Oxidase o use of antimicrobial drugs to decrease the risk of infection
Febuxostat is more effective than Allopurinol
ANTIBACTERIAL AGENTS
SUPPLEMENT: OTHER DRUGS FOR GOUT BACTERIAL CELL WALL SYNTHESIS INHIBITORS
A novel urate-lowering recombinant
PENICILLINS
mammalian Urate Oxidase enzyme
PEGLOTICASE MOA OF BETA-LACTAM ANTIBIOTICS
(an enzyme absent in humans which
converts uric acid to allantoin) • binds to penicillin-binding proteins (PBPs) located in the
IL-1 Pathway Inhibitor ; Used for bacterial cytoplasmic membrane
ANAKINRA, acute gout in patients with • inhibits the transpeptidation reaction that cross-links the linear
CANAKINUMAB, contraindication to, or who are peptidoglycan chain constituents of the cell wall
RILONACEPT refractory to traditional; therapies • activates autolytic enzymes that cause lesions in the bacterial
like NSAIDs and/or Colchicine cell wall
• Bactericidal
Prostaglandin has two important roles: protection of the gastric mucosa
by HCO3- production and maintenance of glomerular filtration by way of
• Excreted unchanged in the urine
dilation of afferent arteriole. Hence, in general, NSAIDS as inhibitors of • Capable of entering the blood brain barrier
prostaglandin synthesis will have 2 common side effects: gastritis and
decrease in GFR. PENICILLIN RESISTANCE
• enzymatic hydrolysis of beta-lactam ring by formation of beta-
The management of gout has 3 strategies
lactamases (penicillinases)
1) reducing inflammation during acute attacks
2)accelerating renal excretion of uric acid with uricosuric drugs
o EXAMPLE: Staphylococcus aureus
3) reducing the conversion of purines to uric acid by xanthine oxidase o Beta-Lactamase Inhibitors (Clavulanic Acid, Sulbactam,
Dr. Calderon Jr. Tazobactam) prevent inactivation
• structural change in target PBPs
o EXAMPLES: MRSA, Pneumococci, Enterococci
ANTIBIOTIC AGENTS • changes in the porin structures in outer cell wall impeding
OVERVIEW access of Penicillins to PBPs
A tip to study antibiotics is to pair it well with Microbiology and o EXAMPLE: Pseudomonas aeruginosa
Parasitology. Just in any concept, I would recommend you see the whole
picture first then try to see the specific details. Study it “from the outside NATURAL PENICILLIN
going to the inside,” starting from the cell wall going to the inside protein
synthesis, nucleic acid synthesis and DNA synthesis PENICILLIN G [B]
SimD PENICILLIN V [B]
• Cell wall synthesis inhibitors → Penicillins, Cephalosporins,
Monobactam, Carbapenem, Vancomycin Class Penicillin (Narrow spectrum)
• Protein synthesis inhibitors: ATCELLS → Aminoglycosides, Binds to penicillin-binding proteins. Inhibits
MOA
Tetracyclines, Chloramphenicol, Erythromycin (Macrolides), transpeptidation in bacterial cell walls.
Lincosamides (Clindamycin), Linezolid, Streptogramins DOC for syphilis, for streptococcal, pneumococcal,
• Nucleic acid synthesis inhibitors → Trimethoprim, Sulfamethoxazole Uses
meningococcal, G+ bacilli, spirochete infection
• DNA synthesis inhibitors → Rifampin, Fluroquinolones Hypersensitivity, Complete cross-allergenicity with
All Cell wall synthesis inhibitors are bactericidal. SE other Penicillins, Gastrointestinal disturbances,
All protein synthesis inhibitors are bacteriostatic except Aminoglycosides, seizures
Streptogramins and Chloramphenicol to the following bugs: Hemophilus Renal tubular reabsorption inhibited by probenecid
influenzae, Streptococcus pneumoniae, Neisseria and Bacteroides
Inactivated by beta-lactamase (penicillinase)
TMP alone is static, SMX alone is static. TMP-SMX is cidal
Dr. Calderon Jr. Benzathine Penicillin & Procaine Penicillin: long-
Notes acting intramuscular preparations
TYPES OF ANTIBIOTIC AGENTS Given IM but Pen V can be given PO
• BACTERICIDAL Increased activity against enterococci when given
o can eradicate an infection in the absence of host defense together with aminoglycosides
mechanisms
o kills bacteria
ISOXAZOLYL PENICILLIN (ANTI-STAPHYLOCCAL) CEPHALOSPORINS

METHICILLIN [B] ** Bactericidal; mostly IV; all have renal excretion
NAFCILLIN [B], OXACILLIN [B], CLOXACILLIN [B], EXCEPT Cefoperazone and Ceftriaxone **
SimD CEFAZOLIN [B]
DICLOXACILLIN [B]
Class Penicillin (Very-Narrow spectrum) CEFADROXIL [B], CEPHALEXIN [B], CEPHALOTHIN,
SimD
Binds to penicillin-binding proteins. Inhibits [B] CEPHAPIRIN [B], CEPHRADINE [B]
MOA Class Cephalosporin (First Generation)
transpeptidation in bacterial cell walls.
Uses Staphylococcal infections Binds to penicillin-binding proteins. Inhibits
MOA
Hypersensitivity, Complete cross-allergenicity with transpeptidation in bacterial cell walls.
other Penicillins, Gastrointestinal disturbances, Surgical prophylaxis, Bone infections, Infections due to
SE gram-positive cocci (Staphylococci and common
Interstitial nephritis (methicillin), Neutropenia
(nafcillin) Uses Streptococci), Escherichia coli and Klebsiella
Resistant to inactivation by beta-lactamase pneumoniae, Skin and soft tissue infections, Urinary
Notes (penicillinase) Tract infections
Biliary clearance Hypersensitivity, Cross-allergenicity (partial with
SE Penicillins, complete with cephalosporins), Injection
AMINO PENICILLIN site reactions, Phlebitis, GI upset
Increases nephrotoxicity of aminoglycosides
(EXTENDED SPECTRUM PENICILLIN)
Do not cross the BBB
AMPICILLIN Notes
Minimal activity against G- cocci, enterococci, MRSA
SimD AMOXICILLIN and most G- rods
Class Penicillin (Extended spectrum)
MNEMONIC: First Generation Cephalosporins
Binds to penicillin-binding proteins. Inhibits
MOA Which microbes are covered by the spectrum of activity of
Infections due to enterococci, Listeria monocytogenes, first generation cephalosporins?
Uses Escherichia coli, Proteus mirabilis, Haemophilus FIRST GENERATION CEPHALOSORINS
influenzae and Moraxella catarrhalis (HELPSE) PEcK FIRST
Hypersensitivity, Cross-allergenicity, GI upset, Proteus mirabilis
SE Escherichia coli
Pseudomembranous colitis and Rash (ampicillin)
Inactivated by beta-lactamase (penicillinase) Klebsiella pneumoniae
Enhanced effect when used with beta-lactamase How do you remember first generation cephalosporins?
Notes inhibitors (clavulanic acid, sulbactam) FIRST GENERATION CEPHALOSPORINS
Synergistic effect with aminoglycosides FADer, help me FAZ my PHarmacology boards!
Ampicillin undergoes enterohepatic recirculation CeFADroxil CePHalothin CePHradine
CeFAZolin CePHapirin CePHalexin
MNEMONICS: Ampicillin/Amoxicillin CEFACLOR [B - all]
• AMPicillin = AMPed up penicillin CEFAMANDOLE, CEFMETAZOLE, CEFONICID,
• amOxicillin = greater Oral bioavailability SimD CEFUROXIME, CEFPROZIL, CEFORANIDE, CEFOXITIN,
CEFOTETAN, LORACARBEF
Describe the antimicrobial coverage of extended Class Cephalosporin (Second Generation)
spectrum Penicillins (HELPSE):
Binds to penicillin-binding proteins. Inhibits
Amoxicillin HELPS kill Enterococci MOA
Haemophilus influenzae Proteus mirabilis
Escherichia coli Salmonella sp. Added coverage for infections due to Haemophilus,
Uses Enterobacter and Neisseria
Listeria monocytogenes Enterococci
Hypersensitivity, Cross-allergenicity (partial with
Penicillins, complete with cephalosporins), Injection
ANTIPSEUDOMONAL PENICILLIN SE
site reactions, Phlebitis, GI upset, Disulfiram reaction
PIPERACILLIN [B] (cefamandole, cefotetan)
SimD TICARCILLIN [B], CARBENICILLIN [B] Increases nephrotoxicity of aminoglycosides
Class Penicillin (Antipseudomonal) Do not cross the BBB
Binds to penicillin-binding proteins. Inhibits Slight less activity against G+ but extended G- activity
MOA
transpeptidation in bacterial cell walls. Cefuroxime has improved action against
Greater activity against G(-) infections. Infections due Notes pneumococcus and H. influenza
Uses
to Pseudomonas, Enterobacter and Klebsiella Cefotetan and Cefoxitin have good activity against B.
Hypersensitivity, Complete cross-allergenicity with fragilis and thus are used for abdominal and pelvic
SE
other Penicillins, Gastrointestinal disturbances infections
Inactivated by beta-lactamase (penicillinase) ALL ARE PREGNANCY CATEGORY B
Enhanced effect when used with beta-lactamase
MNEMONIC: Second Generation Cephalosporins
Notes inhibitors (clavulanic acid, tazobactam)
Synergistic with aminoglycosides against Which microbes are covered by the spectrum of activity of
Pseudomonas second generation cephalosporins?
SECOND GENERATION CEPHALOSORINS
HEN PEcKS
MNEMONIC: Antipseudomonal Penicillins
Haemophilus influenzae Proteus mirabilis
TCP: Takes Care of Pseudomonas Enterobacter aerogenes Escherichia coli
Ticarcillin Carbenicillin Piperacillin Neisseria spp. Klebsiella pneumoniae
PSEUDOMONAS is actually a mnemonic AHA. What are the diseases Serratia marcescens
associated with Pseudomonas? Pneumonia, Sepsis, Ecthyma How do you remember second generation cephalosporins?
gangrenosum, UTI, DM, Otitis externa, Mucopolysaccharidoses – Cystic
SECOND GENERATION CEPHALOSPORINS
Fibrosis, Osteomyelitis, Nosocomial infection (HAP and VAP) Skin
infection (in burns and hot tub folliculitis) In a FAMily gathering, you see your
Dr. Calderon Jr. FOXy cousin wearing a FUR coat and drinking TEA.
CeFAMandole, CeFOXitin,
CeFURoxime, CefoTEtan
SECOND GENERATION CEPHALOSPORINS
FAC! LORA the PROfessional AZhOLE is still on the FONe.
CeFAClor, LORAcarbef, CefPROzil,
CefmetAZOLE, CeFONicid
CEFOPERAZONE [B] Wide coverage against gram-positive and gram-
CEFOTAXIME, CEFTAZIDIME, CEFTIZOXIME, Uses negative bacteria. For serious infections such as
CEFTRIAXONE, CEFIXIME, CEFPODOXIME PROXETIL, pneumonia and sepsis
SimD
CEFDINIR, CEFDITOREN PIVOXIL, CEFTIBUTEN, Hypersensitivity, Cross-allergenicity (partial with
MOXALACTAM SE Penicillins), GI upset, CNS toxicity (confusion,
Class Cephalosporin (Third Generation) encephalopathy, seizures)
Binds to penicillin-binding proteins. Inhibits • Reserved for serious life-threatening infections
MOA
transpeptidation in bacterial cell walls. • Cilastatin inhibits renal metabolism (Hydrolysis) of
Decreased gram-positive coverage. Increased gram- imipenem by Dihydropeptidase
negative activity (Pseudomonas, Bacteroides), against • Given IV
Uses • Low susceptibility to B-lactamases
Providencia, Serratia, Neisseria, Haemophilus; DOC for
gonorrhea (Ceftriaxone and Cefixime) • Active against Pseudomonas and Acinetobacter EXCEPT
Notes
Hypersensitivity, Cross-allergenicity (partial with Ertapenem
SE Penicillins, complete with cephalosporins), GI upset, • Imipenem given with Cilastatin which acts as
Disulfiram reaction (Cefoperazone) Dihydropeptidase enzyme inhibitor
• Partial cross-allergenicity with Penicillins
• Synergistic effect with aminoglycosides
• Ertapenem has longer t½ but less active against
• All have renal excretion EXCEPT Cefoperazone and Enterococci and Pseudomonas
Ceftriaxone
• All can penetrate the BBB EXCEPT Cefoperazone and AZTREONAM [B]
Cefixime Class Monobactam
• Ceftriaxone and Cefotaxime are the most active Binds to penicillin-binding proteins. Inhibits
MOA
Cephalosporins against Penicillin-resistant transpeptidation in bacterial cell walls.
Notes Infections resistant to beta-lactamases produced by
Streptococcus pneumoniae
• Ceftizoxime is commonly used against Bacteroides Uses gram-negative rods, including Klebsiella,
• Should be reserved against serious infection EXCEPT Pseudomonas and Serratia
ceftriaxone and cefixime ; Ceftriaxone has very good Gastrointestinal upset, Superinfection, Vertigo,
SE
CNS penetration Headache, Hepatotoxicity, Skin rash
• Ceftazidime has very good action on Pseudomonas Resistant to beta-lactamase
• ALL ARE PREGNANCY CATEGORY B No cross-allergenicity with Penicillins
No activity against gram-positive bacteria or
Can I ask you a practical question? Kapag nagka-Pseudomonas ka ba
Notes anaerobes
magastos ba? Diba ma ICU ka! Hehe magastos yun. Kailangan mo ba ng
maraming PERA, kailangan mo ba ng cefoPERAzone?! AHA! Eh sosyal ka Given IV
ayaw mo ng pera, sabi mo dapat you have many DIMES so you want Synergistic with AG
ceftaziDIME!!! AHA! Kailangan din ba malakas lakas ka? Magtratraining Renal excretion
ka parang TRIathlete aha pwede ba ang CefTRIAxone! Aha ayos ba? Aztreonam is the silver bullet. It is design for gram negative rods.
Again, cefoPERAzone, ceftaziDIME and ceftriaxone. These 3rd gen Pseudomonas is a gram negative rod.
cephalosphorins have anti-pseudomonal property. AHA! Pero si Dr. Calderon Jr.
Ceftriaxone ay case to case basis. Only “some” cases are sensitive to
Ceftriaxone. Kaya hindi lahat kayang maging triathlete. AHA!

Dr. Calderon Jr. MISCELLANEOUS
CEFEPIME [B] CLAVULANIC ACID [B]
SimD CEFTAROLINE [B], CEFPIROME [B] SimD SULBACTAM [B], TAZOBACTAM [B]
Class Cephalosporin (Fourth Generation) Class Beta-lactamase inhibitor
Binds to penicillin-binding proteins. Inhibits Inhibits inactivation of Penicillins by bacterial beta-
MOA MOA
transpeptidation in bacterial cell walls. lactamase (penicillinase)
Wide coverage against gram-positive and gram- Infections against beta-lactamase producing
Uses Uses
negative bacteria, MRSA (Ceftaroline) gonococci, streptococci, E. coli and H. influenzae
Hypersensitivity, Cross-allergenicity (partial with SE Hypersensitivity, Cholestatic jaundice
SE
Penicillins, complete with cephalosporins), GI upset Usual combinations include Amoxicillin-Clavulanate,
Resistant to beta-lactamase. Broad G(-) activity Ampicillin-Sulbactam, Piperacillin-Tazobactam
In some sources, Ceftaroline belongs to the 5th Most active against plasmid encoded B lactamases
Notes
generation of Cephalosporin (Gonococci, Streptococci, E coli and H. Influenzae)
More resistant to beta-lactamase produced by Not good inhibitor of inducible chromosomal B
Notes lactamases (Enterobacter, Pseudomonas, Serratia)
Enterobacter, Haemophilus, Neisseria and
Pneumococcal VANCOMYCIN [C if parenteral, B if per orem]
Has improved stability to chromosomal lactamase TEICOPLANIN [B], DALBAVANCIN [C[, TELAVANCIN
Ceftaroline used for MRSA SimD
[C]
MNEMONIC: Anti-Pseudomonal Cephalosporins Class Glycopeptide
ANTI-PSEUDOMONAL CEPHALOSPORINS Inhibits cell wall synthesis by binding to the D-Ala-D-
Ceftazidime Cefepime Cefoperazone Ala terminus of nascent peptidoglycan → inhibit
MOA
transglycosylation → prevent elongation and cross-
SUPPLEMENT: CEFTOLOZANE
linking of peptidoglycan chain
A novel Cephalosporin, usually combined Serious infections caused by drug-resistant gram-
with Tazobactam, used for the treatment Uses positive organisms (MRSA), sepsis, endocarditis &
of complicated urinary tract and meningitis, Pseudomembranous colitis
intraabdominal infections; very good Red Man syndrome, Nephrotoxicity, Ototoxicity, Chills,
CEFTOLOZANE SE
activity against Gram negative organisms Fever, Phlebitis
[B]
including Pseudomonas aeruginosa, •
Reserved for serious life-threatening infections
most extended-spectrum-B-lactamase- •
Treat red man syndrome by slowing the rate of infusion
producing organisms and some •
Use oral formulation for Pseudomembranous colitis
anaerobes •
Narrow spectrum
•
VRSA and VRE are due to D-Ala-D-Lactate formation
OTHER BETA LACTAM ANTIBIOTICS •
Teicoplanin and Telavancin are not absorbed in the GIT
Notes
thus used for bacterial enterocolitis, they are also
IMIPENEM-CILASTATIN [C]
eliminated unchanged in the urine
SimD ERTAPENEM [B], MEROPENEM [B], DORIPENEM [B] • Decrease dose for renally impaired patients
Class Carbapenem • Dalbavancin has very long t½ (6-11 days) which
Binds to penicillin-binding proteins. Inhibits permits once-weekly dosing and is more active than
MOA
transpeptidation in bacterial cell walls. Vancomycin
SUPPLEMENT: MNEMONICS – Drugs of Last Resort CHLORAMPHENICOL [C]

Class Protein synthesis inhibitor (broad spectrum)
Which antibiotics are considered drugs of last resort?
I AM your Last Shot at Victory Inhibits transpeptidation (catalyzed by peptidyl
MOA
Imipenem Linezolid transferase) at 50S subunit. Bacteriostatic.
Amikacin Streptogramins Meningitis (Streptococcus pneumoniae, Haemophilus
Meropenem Vancomycin Uses influenzae, Neisseria meningitidis), Backup for
Salmonella, Rickettsia and Bacteroides
Gastrointestinal disturbance, Aplastic anemia
BACITRACIN [C]
SE (idiosyncratic), Gray baby syndrome, dose-related
Class Peptide antibiotic
anemia
Interferes with a late stage in cell wall synthesis in
MOA • Inhibits hepatic drug-metabolizing enzymes causing
gram-positive organisms
many drug interactions
Uses Infections due to gram-positive bacteria
• given PO and IV
SE Nephrotoxicity
• Able to cross the placenta and BBB
Reserved for topical use only due to marked
Notes • Inhibits hepatic drug-metabolizing enzymes causing
nephrotoxicity
Notes many drug interactions
• Resistance is due to the formation of
CYCLOSERINE [C]
acetyltransferase that inactivates drug
Blocks incorporation of D-Ala into the pentapeptide
MOA • Usually used as topical agent
side chain of the peptidoglycan
• Chloramphenicol Palmitate and Chloramphenicol Na
Uses Drug-resistant tuberculosis (2nd line drug)
Succinate
SE Neurotoxicity (tremors, seizures, psychosis)
Notes Only used as a second-line agent in TB Chloramphenicol is a bacteriostatic antibiotic but is bactericidal to the
following bugs: Hemophilus influenza, Neisseria, Bacteroides and
Streptococcus pneumoniae.
SUPPLEMENT: DAPTOMYCIN [B] Dr. Calderon Jr.
Binds to cell membrane causing depolarization and

MOA
rapid cell death SUPPLEMENT: Gray Baby Syndrome
Infections caused by G(+) bacteria including sepsis • characterized by decreased red blood cells, cyanosis and
Uses
and endocarditis cardiovascular collapse
SE Myopathy • characteristic ashen gray skin
More rapidly bactericidal than Vancomycin • premature neonates are deficient in hepatic
Inactivated by pulmonary surfactants so cannot be glucuronosyltransferase
used against pneumonia • very sensitive to doses of chloramphenicol
Notes Monitor Creatine Phosphokinase weekly to check
Glucuronidation is the way to metabolize chloramphenicol. Infants have
for severity of myopathy
immature liver thus low level of hepatic glucoronosyl transferase to
NOT Bactericidal (only destabilizes bacterial cell metabolize chloramphenicol as seen in Gray Baby syndrome.
membrane) Dr. Calderon Jr.
SUPPLEMENT: OTHER DRUGS ACTING ON CELLWALL TETRACYCLINE [D -ALL]

Inactivates the enzyme UDP-N- DOXYCYCLINE, MINOCYCLINE, TIGECYCLINE,
SimD
acetylglucosamine-3- DEMECLOCYCLINE, LYMECYCLINE
enolpyruvyltransferase which is Class Tetracycline
important in peptidoglycan synthesis MOA Binds 30S ribosomal subunit. Bacteriostatic.
(very early stage of bacterial cell wall Infections caused by M. pneumoniae, Chlamydia,
FOSFOMYCIN synthesis) → prevents formation of N- Rickettsia and Vibrio, Peptic ulcer disease, Lyme
[B] acetylmuramic acid (a peptidoglycan Uses disease, Malaria prophylaxis, Amebiasis, SIADH
precursor molecule); for uncomplicated (demeclocycline), Acne, CAP and bronchitis
UTI; safe for pregnant patients; renal (Doxycycline)
excretion; resistance emerges rapidly; GI disturbance, Teratogen (tooth enamel
synergistic with Beta lactam and dysplasia/discoloration), Hepatotoxicity,
SE
quinolones Nephrotoxicity, Photosensitivity, reversible
Vestibulotoxicity (especially Minocycline)
• Divalent cations impair oral absorption (minimal for
BACTERIAL PROTEIN SYNTHESIS INHIBITORS
Doxycycline)
MNEMONIC: Protein Synthesis Inhibitors
• Tigecycline has the broadest spectrum and has the
“AT CELLS” longest t½ (30-36hrs)
Aminoglycosides • Do not drink with milk (decreased absorption with
Tetracyclines divalent cations like calcium)
Chloramphenicol • High Vd, cross the placenta, enterohepatic recycling
Erythromycin (Macrolides) • All are excreted renally EXCEPT Doxycycline (bile)
Lincosamides (Clindamycin) Notes
• Resistance is due to development of efflux pumps for
Linezolid
active extrusion of tetracyclines and the formation of
Streptogramins
ribosomal protection proteins that interfere with
All bacterial protein synthesis inhibitors are bacteriostatic except tetracycline binding (but not present with
Aminoglycosides, Streptogramins, and Chloramphenicol to the following Tigecycline EXCEPT in Proteus and Pseudomonas)
bugs: Hemophilus, Neisseria, Bacteroides and Streptococcus pneumoniae. • Tigecycline is given IV only and is unaffected by
Dr. Calderon Jr.
common tetracycline resistance mechanisms
• GROUP PREGNANCY CATEGORY: D
I read this as TEETHracycline. It causes yellow teeth.
Dr. Calderon Jr.
MNEMONIC: Tetracycline
T = TeTracyclines
Block aTTachment of T-RNA to acceptor site
Teeth-racycline = tooth enamel dysplasia / discoloration
ERYTHROMYCIN [B] AMINOGLYCOSIDES
AZITHROMYCIN [B], CLARITHROMYCIN [C],
SimD Modes of Antibacterial Action
TELITHROMYCIN [C], ROXITHROMYCIN [B]
Class Macrolide • CONCENTRATION-DEPENDENT KILLING ACTION
o as the plasma level is increased above the MIC, an
MOA Binds 50S ribosomal subunit. Bacteriostatic.
increasing proportion of bacteria are killed and at a more
Community-acquired pneumonia, Pertussis,
Uses rapid rate
Diphtheria, Chlamydial infections
o EXAMPLE: aminoglycosides
Gastrointestinal upset, Cholestatic hepatitis,
• TIME-DEPENDENT KILLING ACTION
SE Hepatotoxicity, QT prolongation, Drug interactions,
• efficacy is directly related to time above MIC
rare fulminant hepatic failure (Telithromycin)
o efficacy independent of concentration once the MIC has
• All macrolides inhibit CYP450 EXCEPT Azithromycin
been reached
• Azithromycin has highest Vd and slowest elimination o EXAMPLES: Penicillins, cephalosporins
• Telithromycin is used for macrolide-resistance Post-antibiotic Effect
• Good oral bioavailability but azithromycin • seen in aminoglycosides
absorption is impeded by food • killing action continues when their plasma levels have
Notes • Half-lives: Erythromycin (2hrs), Clarithromycin
declined below measurable levels
(6hrs), Azithromycin (24-48hrs) • greater efficacy when administered as single large dose
• Resistance is due to development of efflux pumps • toxicity depends on a critical plasma concentration and on the
and production of methylase enzyme time such a level is exceeded
• Cross-resistance among macrolides: complete or o shorter with single large dose than multiple small doses
partial resistance with drugs acting on the 50S § basis for once-daily aminoglycoside dosing protocols
Azithromycin has a good pharmacokinetic profile. It is neither an
Aminoglycosides are bactericidal because of misreading. Try to apply a
inhibitor or inducer of general substrate. Azithromycin has a tremendous
concept of stop codon, that is how you compare the effect of
4 day half-life and has a high volume of distribution. It is greater in tissue
aminoglycosides. As a large sugar, aminoglycosides will occupy a large
macrophage than the plasma level.
Dr. Calderon Jr.
space in P site that will cause misreading.
Dr. Calderon Jr.

CLINDAMYCIN [B]
PHARMACOKINETICS OF AMINOGLYCOSIDES
SimD LINCOMYCIN [C]
Class Lincosamides • not absorbed after oral administration
o must be given IM or intravenously for systemic effect
MOA Binds 50S subunit. Bacteriostatic.
• limited tissue penetration
Skin and soft tissue infection, Anaerobic infections,
o do not readily cross the blood-brain barrier
Backup drug against gram-positive cocci, Endocarditis
Uses • glomerular filtration is the major mode of excretion
prophylaxis (penicillin-allergy), PCP pneumonia,
Toxoplasmosis o plasma levels greatly affected by changes in renal function
Gastrointestinal disturbance, Skin rash, Neutropenia, • Amikacin has the narrowest therapeutic window among
SE Hepatic dysfunction, Pseudomembranous colitis (C. aminoglycosides
difficile overgrowth) • Mostly given parenterally
Cross-resistance between clindamycin and macrolides • GROUP PREGNANCY CATEGORY: D
is common MOA OF AMINOGLYCOSIDES
Resistance is due to methylation of binding sites and • bactericidal inhibitors of protein synthesis
Notes
enzymatic inactivation • aminoglycoside transport can be enhanced by cell wall synthesis
G(-) aerobes are resistant because of poor penetration inhibitors (synergistic effect)
through the outer membrane • require oxygen for uptake
o ineffective against anaerobes
MNEMONIC: Clindamycin VS Metronidazole • bind to the 30S ribosomal subunit and interfere with protein
• CLINDAMYCIN for anaerobic infections ABOVE the synthesis:
diaphragm. o block formation of the initiation complex
• METRONIDAZOLE for anaerobic infections BELOW the o cause misreading of the code on the mRNA template
diaphragm. o inhibit translocation
RESISTANCE TO AMINOGLYCOSIDES
QUINUPRISTIN-DALFOPRISTIN [B] • plasmid-mediated formation of inactivating enzymes (group
Class Streptogramin transferases)
MOA Binds 50S subunit. Bactericidal. o AMIKACIN is often resistant to many enzymes that inactivate
Infections caused by drug-resistant gram-positive other aminoglycosides
Uses cocci such as Staphylococci and E. faecium (MRSA, • resistance to STREPTOMYCIN develops due to changes in the
VRSA, VRE) ribosomal binding site
Injection site reactions, severe Arthralgia-myalgia MNEMONIC: Aminoglycosides
SE
syndrome AminOglycosides require O2 for transport.
Inhibits CYP450 enzymes, causing multiple drug They won’t work under anaerobic conditions.
Notes
interactions
MNEMONICS – Aminoglycosides
LINEZOLID [C] Mean GNATS canNOT kill anaerobes.
SimD TEDIZOLID [C] Gentamicin Nephrotoxicity
Neomycin Ototoxicity
Class Oxazolidinone
Amikacin Teratogen
Binds to the 23S ribosomal RNA of 50S subunit.
MOA Tobramycin
Bacteriostatic.
Streptomycin
Infections caused by drug-resistant gram-positive
Uses cocci such as Staphylococci and Enterococcus (MRSA, GENTAMICIN [D]
VRSA, VRE), Listeria, Corynebacteria SimD TOBRAMYCIN [B if ophthalmic drop]
Bone marrow suppression, Thrombocytopenia, Class Aminoglycoside
Neutropenia, Serotonin syndrome (when given Inhibit protein synthesis by binding to 30S subunit.
SE MOA
together with serotonergic drugs such as SSRIs), Bactericidal.
Neuropathy, Optic neuritis Infections caused by aerobic gram-negative bacteria
Resistance is due to decreased affinity of drug to (E. coli, Enterobacter, Klebsiella, Proteus, Providencia,
Notes
binding site Uses Pseudomonas, Serratia), Endocarditis (caused by
staphylococci, streptococci and enterococci), Ocular
infections
Nephrotoxicity (reversible), Ototoxicity (irreversible), TOXICITIES OF AMINOGLYCOSIDES
SE
Neuromuscular blockade • OTOTOXICITY
• SYNERGISTIC effect with cell wall synthesis (Beta o MOST OTOTOXIC: kanamycin, amikacin
Lactam and Vancomycin) inhibitors due to o MOST VESTIBULOTOXIC: tobramycin, gentamicin
enhancement of transport to the inside of the o cumulative ototoxicity when used with loop diuretics
bacterial cell • NEPHROTOXICITY
• AG are given IM or IV only o acute tubular necrosis
• Have concentration dependent killing o MOST NEPHROTOXIC: tobramycin, gentamicin
• Are not capable of penetrating the blood brain § Toxicities of Aminoglycosides
barrier • NEUROMUSCULAR BLOCKADE
• Low tissue penetration o curare-like effect (nondepolarizing NMJ block) reversible with
Notes • Mechanism of resistance of AG: plasmid-mediated calcium and neostigmine
formation of inactivating enzymes "group • SKIN REACTIONS
transferase" → catalyze the acetylation of amine o commonly from Neomycin and Streptomycin
functions and the transfer of phosphoryl or adenylyl SUPPLEMENT: OTHER PROTEIN SYNTHESIS INHIBITOR
groups to the oxygen atoms of the hydroxyl groups
Inhibits translocation process during
of AG FUSIDIC ACID
protein synthesis; an antibiotic isolated
• Gentamicin and tobramycin are the most or Na
from the fermentation broth of Fusidium
vestibulotoxic and nephrotoxic FUSIDATE
coccineum; used as topical antimicrobial
• Gentamicin and Tobramycin are the most (Group:
against most common skin pathogens
vestibulotoxic and nephrotoxic aminoglycosides Fusidane)
including S. aureus
AMIKACIN [D]
Class Aminoglycoside
Inhibit protein synthesis by binding to 30S subunit.
NUCLEIC ACID SYNTHESIS INHIBITORS
MOA
Bactericidal.
Infections caused by aerobic gram-negative bacteria
(E. coli, Enterobacter, Klebsiella, Proteus, Providencia,
Uses
Pseudomonas, Serratia), Multi Drug-Resistant
Tuberculosis (2nd line drug)
Nephrotoxicity (reversible), Ototoxicity (irreversible),
SE
Neuromuscular blockade
Synergistic effect with beta-lactam antibiotics
Notes
Least resistance but narrowest therapeutic window
STREPTOMYCIN [D]
Class Aminoglycoside
Inhibit protein synthesis by binding to 30S subunit. ANTIFOLATE DRUGS
MOA
Bactericidal.
SUPPLEMENT:
Tuberculosis, Tularemia, Bubonic plague, Brucellosis,
Uses Sulfonamides
Enterococcal endocarditis
Hypersensitivity, Nephrotoxicity (reversible), • weakly acidic compounds that have a common chemical
Ototoxicity (vestibulotoxic, irreversible), nucleus resembling p-aminobenzoic acid (PABA)
SE • solubility may be decreased in acidic urine
Neuromuscular blockade, Teratogen (congenital
deafness), Injection site reactions o combination of 3 separate sulfonamides (triple sulfa) to
Synergistic effect with beta-lactam antibiotics reduce the likelihood that any one drug will precipitate
Administered intramuscularly
Has widespread resistance • Classification
Notes For Streptomycin, resistance is due to changes in the Intermediate
Short Acting Long Acting
ribosomal binding site Acting
If given together with Pens can be used for Sulfacytine Sulfadiazine Sulfadoxine
enterococcal endocarditis, TB plague and tularemia Sulfisoxazole Sulfamethoxazole * Pyrimethamine
Sulfamethizole Sulfapyridine
NEOMYCIN
* Trimethoprim
SimD KANAMYCIN, PAROMOMYCIN
Class Aminoglycoside Trimethoprim
Inhibit protein synthesis by binding to 30S subunit. • structurally similar to folic acid
MOA
Bactericidal.
• weak base that is trapped in acidic environments
Skin infections, Bowel preparation for elective surgery
• reaches high concentrations in prostatic and vaginal fluids
Uses (to decrease aerobic flora), Hepatic encephalopathy,
Visceral leishmaniasis (paromomycin)
MOA OF ANTIFOLATES
Hypersensitivity, Nephrotoxicity (reversible),
SE • SULFONAMIDES
Ototoxicity (irreversible), Neuromuscular blockade
Limited to topical and oral use (Neomycin) o bacteriostatic inhibitors of folic acid synthesis
Reverse neuromuscular blockade with calcium o competitive inhibitors of dihydropteroate synthase
Notes o selective toxicity of sulfonamides results from the inability of
gluconate and neostigmine
Kanamycin is most ototoxic mammalian cells to synthesize folic acid
o must use preformed folic acid that is present in the diet
SPECTINOMYCIN • TRIMETHOPRIM (intermediate acting)
Class Aminoglycoside o selective inhibitor of bacterial dihydrofolate reductase
Inhibit protein synthesis by binding to 30S subunit. o bacterial dihydrofolate reductase is 4–5x more sensitive to
MOA
Bactericidal. inhibition by trimethoprim
Drug-resistant gonorrhea, Gonorrhea in penicillin- • TRIMETHOPRIM PLUS SULFAMETHOXAZOLE
Uses
allergic patients o when the 2 drugs are used in combination, antimicrobial
Nephrotoxicity (reversible), Ototoxicity (irreversible), synergy results from the sequential blockade of folate
SE
Neuromuscular blockade, Anemia synthesis
No cross-resistance with other drugs used in o drug combination is bactericidal
Notes gonorrhea
Given Intramuscularly
TOXICITY OF SULFONAMIDES
• HYPERSENSITIVITY
o spectrum: EM, SJS/TEN, PAN, exfoliative dermatitis
o most common drug triggers
o cross-allergenicity should be assumed
• GASTROINTESTINAL DISTRESS
o nausea, vomiting, diarrhea and mild hepatic dysfunction
• HEMATOTOXICITY
o granulocytopenia, thrombocytopenia, aplastic anemia
o cause acute hemolysis in G6PD deficient patients
o Toxicity of Sulfonamides
• NEPHROTOXICITY
o crystalluria, hematuria
• DRUG INTERACTIONS
o displace protein binding affecting levels of warfarin and
methotrexate
o displace bilirubin binding sites leading to kernicterus
SUPPLEMENT: Kernicterus
Figure 46-1. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 • caused by increased levels of unconjugated bilirubin
• due to immaturity of fetal blood brain barrier
SUPPLEMENT: Resistance to Antifolate Drugs
• histopathology
• plasmid-mediated and results from: o bilirubin deposits in subcortical nuclei and basal ganglia
o decreased intracellular accumulation of the drugs • clinical presentation
o increased production of PABA by bacteria o hypo/hypertonia, lethargy, high-pitched cry, opisthotonos
o decrease in the sensitivity of dihydropteroate synthase to
sulfonamides
QUINOLONES
SILVER SULFADIAZINE [B]
As you increase in the generation there is a greater coverage for gram
SimD MAFENIDE ACETATE [C] positive organisms
Class Sulfonamide Dr. Calderon Jr.
MOA Inhibit dihydropteroate synthase. Bacteriostatic.

Uses Burn infections MOA OF QUINOLONES
GI upset, Acute hemolysis in G6PD deficiency, • interfere with bacterial DNA synthesis by inhibiting:
Nephrotoxicity, Hypersensitivity (assume cross- o Topoisomerase II (DNA Gyrase) in gram-negative organisms
SE
hypersensitivity, SJS/TEN), Hematotoxicity, Drug § prevents relaxation of supercoiled DNA
interactions, Kernicterus o Topoisomerase IV in gram-positive organisms
Notes Displaces protein binding of other drugs/bilirubin § interferes with the separation of replicated chromosomal
Correlation to surgery: Mafenide Acetate can cause Metabolic Acidosis DNA during cell division
and can penetrate the eschar. • usually bactericidal against susceptible organisms
In the silver sulfadiazine formula, it is the silver that is bactericidal. • exhibit post antibiotic effect
Remember, sulfa drug alone is static. Combining two drugs will make it • should not be taken with other preparations containing cations
bactericidal. (should be taken 2 hours before or 4 hours after any product
According to Schwartz, in case of severe burns and you try to utilize containing cations)
intravenous antibacterials it can promote further fungal growth.

Dr. Calderon Jr. • may damage growing cartilage and cause arthropathy
CO-TRIMOXAZOLE [D]
Class Sulfonamide SUPPLEMENT: Quinolones
Sequential blockade of dihydropteroate synthase RESISTANCE TO FLUOROQUINOLONES
MOA (Sulfamethoxazole) and dihydrofolate reductase • decreased intracellular accumulation of the drug via the
(Trimethoprim). Bactericidal. production of efflux pumps
Urinary tract, respiratory, ear and sinus infections • changes in porin structure
(Haemophilus, Moraxella, Aeromonas), P. jiroveci • changes in the sensitivity of the target enzymes via point
Uses
pneumonia, Toxoplasmosis, Nocardiosis, Cholera mutations in the antibiotic binding regions
(backup), Typhoid fever, Shigellosis
GI upset, Acute hemolysis in G6PD deficiency, CLASSIFICATION OF FLUOROQUINOLONES
Nephrotoxicity, Hypersensitivity (assume cross- • 1ST GENERATION
SE
hypersensitivity, SJS/TEN), Hematotoxicity, Drug o Nalidixic acid, Cinoxacin, Rosoxacin, Oxolinic acid
interactions, Kernicterus • 2ND GENERATION
• Displaces protein binding of other drugs/bilirubin o Ciprofloxacin, Ofloxacin, Norfloxacin, Lomefloxacin,
• Low solubility in acidic urine causing formation of Enoxacin
stones • 3RD GENERATION
• Resistance is due to plasmin-mediated (decreased o Levofloxacin, Gemifloxacin, Moxifloxacin, Sparfloxacin,
intracellular accumulation of the drug, increased Grepafloxacin, Gatifloxacin, Pazufloxacin, Tosufloxacin,
Notes production of PABA by bacteria, decreased Balofloxacin
sensitivity of dihydropteroate synthetase to sulfas • 4TH GENERATION
and production of dihydrofolate reductase that has o Trovafloxacin, Alatrofloxacin, Prulifloxacin, Clinafloxacin
decreased affinity for the drug
• Sulfonamides are formulated in a 5:1 ratio with ANTIMICROBIAL SPECTRUM OF FLUOROQUINOLONES
trimethoprim • 1st Generation: urinary tract infections
SUPPLEMENT: Other Sulfonamides and Antifolate Drugs: • 2nd Generation: gram negatives, gonococci, gram positive cocci
• Sulfisoxazole : only for lower UTI and Mycoplasma
• Sulfadiazine-Pyrimethamine: DOC for Toxoplasmosis • 3rd Generation: less gram negative and more gram positive
• Sulfadoxine-Pyrimethamine: 2nd line agent for Malaria activity, streptococci and enterococci
• Trimethoprim: used for lower UTI, may be safely given to • 4th Generation: broad spectrum, including anaerobes
patients with sulfonamide allergy o with increasing generation, increasing gram positive activity
• Pyrimethamine: co-administered with Leucovorin to limit o unlike cephalosporins where increasing generation leads to
bone marrow toxicity increasing gram negative activity
CIPROFLOXACIN [C] TROVAFLOXACIN [C]
OFLOXACIN [C], NORFLOXACIN[C], LOMEFLOXACIN ALATROFLOXACIN [C], PRULIFLOXACIN,
SimD SimD
[C], ENOXACIN [C] CLINAFLOXACIN
Class Fluoroquinolone (2nd Generation) Class Fluoroquinolone (4th Generation)
Inhibits DNA replication by binding to DNA gyrase and Inhibits DNA replication by binding to DNA gyrase and
MOA MOA
topoisomerase IV. Bactericidal. topoisomerase IV. Bactericidal.
Urinary tract infections and GIT infections (gram- Broad spectrum activity (gram-negatives, gram-
Uses
negative rods (such as Shigella, Salmonella, ETEC & positives), Enhanced activity against anaerobes
Campylobacter), gonococci, gram positive cocci), Gastrointestinal distress, CNS effects (dizziness,
Uses Atypical pneumonia, Tuberculosis (2nd line drug), SE headache), Tendinitis, QTc prolongation,
Infection of soft tissue, bones and joints; Intra- Hepatotoxicity (trovafloxacin)
abdominal MDR organisms (such as Pseudomonas and Avoid use in young children and pregnant women
Enterobacter) Notes Enhance toxicity of methylxanthines (theophylline)
Gastrointestinal distress, CNS effects (dizziness, Widest spectrum of activity among fluoroquinolones
SE headache), insomnia, skin rash, abnormal LFTs,
Tendonitis and Tendon rupture MISCELLANEOUS
• Avoid use in young children and pregnant women
METRONIDAZOLE [B]
• Enhance toxicity of methylxanthines (theophylline)
SimD TINIDAZOLE [C], SECNIDAZOLE [C]
• Ciprofloxacin is the most active agent against Gram
Class Nitroimidazole, Antiprotozoal
Negative organisms esp. Pseudomonas
Reactive reduction by ferredoxin forming free radicals
• General properties of quinolones: good oral MOA
Notes that disrupt electron transport chain. Bactericidal.
bioavailability, high Vd, t½ 3-8hrs, absorption is
Anaerobic or mixed intra-abdominal infections,
impeded by antacids, elimination is via kidneys by
Vaginitis (Trichomonas, Gardnerella),
tubular secretion (may compete with probenecid for Uses
Pseudomembranous colitis, Brain abscess, Protozoal
excretion) EXCEPT for MOXIFLOXACIN
infections
• Norfloxacin does not achieve adequate plasma levels
Gastrointestinal irritation, Metallic taste, Headache,
for use in systemic infections
SE Dark urine, Leukopenia, Dizziness, Ataxia,
Neuropathy, Seizures, Disulfiram reaction
LEVOFLOXACIN [C]
DOC for amoebiasis, giardiasis and
SPARFLOXACIN [C], MOXIFLOXACIN [C], Notes
Pseudomembranous colitis
SimD GEMIFLOXACIN [C], PAZUFLOXACIN, TOSUFLOXACIN,
BALOFLOXACIN
NITROFURANTOIN [B, CI at term]
Class Fluoroquinolone (3rd Generation)
Class Nitrofuran
Inhibits DNA replication by binding to DNA gyrase and
MOA Forms multiple reactive intermediates when acted
topoisomerase IV. Bactericidal.
MOA upon by bacterial nitrofuran reductase → disrupt
Lung infections caused gram-positive cocci, Atypical
protein, RNA and DNA synthesis. Bactericidal.
Uses pneumonia (Chlamydia, Mycoplasma), Tuberculosis
Uncomplicated Urinary tract infections (EXCEPT
(2nd line drug) Uses
Proteus and Pseudomonas)
Gastrointestinal distress, CNS effects (dizziness,
SE Anorexia, Nausea, Vomiting, Skin rashes, Pulmonary
headache), Tendinitis, QTc prolongation
SE infiltrates, Phototoxicity, Neuropathies, Hemolysis in
• Avoid use in young children and pregnant women
patients with G6PD deficiency
• Enhance toxicity of methylxanthines (theophylline)
Proteus and Pseudomonas are resistant
• Grepafloxacin withdrawn due to severe Notes
Contraindicated in Renal insufficiency
cardiotoxicity (arrhythmias), Gatifloxacin has also
been withdrawn due to Diabetes mellitus SUPPLEMENT:
• Moxifloxacin has hepatic clearance → lower urinary
MUPIROCIN [B]
levels, so use in UTI is not recommended
Class Topical anti-infective. Pseudomonic Acid
• High resistance especially for C. jejuni, gonococci, G+
cocci like MRSA, Pseudomonas and Serratia Inhibits Staphylococcal isoleucyl tRNA synthetase.
MOA
Bactericidal.
• Are used as alternative to Ceftriaxone and Cefixime
in gonorrhea Gram positive cocci including methicillin-
Uses susceptible and MRSA, for minor skin infections
• Ofloxacin can be used against C. trachomatis
such as Impetigo
• "Respiratory Quinolones"
Epistaxis, Stinging or burning sensation on the skin,
• Moxifloxacin and Gemifloxacin are the newest SE
mild skin rash, headache
members of this family and are considered to have
Only used topically (available as intranasal
Notes the broadest spectrum of activity with increased
ointment)
activity against anaerobes ang atypical agents
Do not used over large infected areas such as
• FQ elimination is via kidneys by tubular secretion
decubitus ulcers or open surgical wounds (may lead
(may compete with probenecid for excretion) Notes
to resistance)
EXCEPT Moxifloxacin
Single OD dose can prevent recurrent UTI
• NEVER use moxifloxacin in UTI
Acidification of urine enhances activity
• Levofloxacin is used in CAP caused by Chlamydia, Adjust dose in renal patients
Mycoplasma and Legionella
• Gemifloxacin, Levofloxacin and Moxifloxacin can POLYMYXIN B [C]
prolong QT
SimD POLYMYXIN E [C]
• Levofloxacin has superior activity against G(+)
Class Polymyxins. Cationic detergents
bacteria including S. pneumoniae ; All have relatively
Attach to and disrupt bacterial cell membrane, bind
long t½ permitting once daily dosing MOA
and inactivate endotoxin. Bactericidal.
• Oral absorption is impaired by cations
Gram-negative bacteria. For salvage therapy of
• Gatifloxacin can cause hyperglycemia in DM Px and
Uses Acinetobacter, Enterobacteriaceae and
hypoglycemia in patients also receiving OHA and
Pseudomonas aeruginosa
was withdrawn from the market in 2006 (USA)
Eosinophilia, fever, Nephrotoxicity, Neurotoxicity,
SE
Rash, Urticaria
Proteus and Neisseria are resistant
Notes
For Topical use only (to limit toxicity)
FIDAXOMICIN [B] MNEMONIC Isoniazid
Class Macrocyclic, Narrow-spectrum • INH Injures Neurons and Hepatocytes
Inhibits bacterial protein synthesis by binding to
MOA the sigma subunit of RNA polymerase. RIFAMPICIN (RIFAMPIN) [C]
Bacteriostatic. SimD RIFABUTIN [B], RIFAPENTINE [C], RIFAXIMIN [C]
Gram positive bacteria only, C. difficile colitis in Class Antimycobacterial (rifamycin)
Uses
adults Inhibits DNA-dependent RNA polymerase → inhibits
Nausea, Vomiting, Abdominal pain, GI bleeding, MOA
SE RNA production. Bactericidal.
Anemia, Neutropenia Tuberculosis (active, latent), Atypical Mycobacterial
Granted Orphan Drug Status for C. difficile in Infections, Leprosy, Prophylaxis for meningococcal
Notes Uses
children and staphylococcal carrier states, Drug-resistant
infections (MRSA, PRSP)
Red-orange Body Fluids, Light chain proteinuria,
SE Skin rash, Thrombocytopenia, Nephritis,
Hepatotoxicity, Flulike Syndrome, Anemia, Cholestasis
• Also considered a FIRST LINE AGENT for PTB
• Potent CYP450 inducer
• Rapid development of resistance if used alone
• Delays the emergence of resistance to dapsone
• RIFAXIMIN is a Rifampin derivative that is not
absorbed in the GIT, and so is used for the prevention
of hepatic encephalopathy, for treatment of
traveler’s diarrhea, (off-label use: for IBS and
Pseudomembranous colitis)
Notes • Resistance is due to changes of drug sensitivity of the
polymerase enzyme
• Undergoes enterohepatic recirculation
• Orange-colored metabolites
• Rifabutin is equally effective as anti-mycobacterial
Harrison’s Principles of Internal Medicine. 20th ed. 2018 agent with less drug interaction and it is the
preferred anti-TB for AIDS patients
ANTIMYCOBACTERIAL DRUGS • Rifaximin is not absorbed in the GIT and is used for
traveler's diarrhea
• Best taken 1 hour before or 2 hours after meals
MNEMONIC: Rifampicin
The Rs of Rifampicin
RNA polymerase inhibitor
Red-orange body fluids
Rapid development of resistance
Revs up cytochrome P450 (inducer)
PYRAZINAMIDE [C]
Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 Class Antimycobacterial (pyrazine derivative)
SUPPLEMENT: Drug Therapy for Mycobacterial Infections Unknown. Converted to active pyrazinoic acid under
acidic conditions of macrophage lysosomes.
• chemotherapy is complicated by numerous factors MOA
Bacteriostatic but can be bactericidal on actively
o limited information about mechanisms of drug action
dividing mycobacteria.
o development of resistance
Uses Tuberculosis (active)
o intracellular location of mycobacteria
o chronic nature of mycobacterial disease Hepatotoxicity, Non-gouty polyarthralgia,
o patient compliance SE Asymptomatic hyperuricemia, Myalgia, GIT irritation,
Rash, Porphyria, Photosensitivity
• chemotherapy always involves the use of drug combinations
to delay the emergence of resistance and to enhance efficacy • Also known as “sterilizing agent” used during the
first 2 months of therapy
• Most hepatotoxic anti-TB drug
DRUGS USED IN TUBERCULOSIS • Require metabolic conversion via pyrazinamidases
ISONIAZID [C] Notes in MTb
Class Antimycobacterial (nicotinic acid derivative) • Resistance is via mutation in pncA gene which codes
MOA Inhibits mycolic acid synthesis. Bactericidal. for pyrazinamidases and increased efflux systems
Uses Tuberculosis (active, latent, prophylaxis) • Decrease dose in hepatic and renal patients
Hepatitis, Neurotoxicity (seizures, neuritis, • Take with meals
SE insomnia), Acute hemolysis in G6PD deficiency, Drug-
MNEMONIC: Hepatotoxicity of Anti-TB Drugs
induced lupus, Drug interactions
Which anti-TB drugs are hepatotoxic?
• Most important drug used in tuberculosis (FIRST
ISO a Red PYRe!
LINE AGENT)
(I saw a red fire!)
• Prevent neurotoxicity by co-administering
Isoniazid < Rifampin < Pyrazinamide
Pyridoxine (Vitamin B6)
• Liver metabolism by acetylation (Filipinos are fast ETHAMBUTOL [B]
acetylators) Class Antimycobacterial (butanol derivative)
• Potent CYP450 inhibitor Inhibits arabinosyl transferases involved in the
Notes • Less Active against other Mycobacteria MOA synthesis of arabinogalactan in mycobacterial cell
• Structural congener of pyridoxine wall. Bacteriostatic.
• High level resistance due to deletion of KatG gene Tuberculosis (active), atypical mycobacterial
Uses
which codes for catalase-peroxidase enzyme infections
involved in bioactivation of INH, low level resistance Visual disturbances (decreased visual acuity, red-
due to deletion of inhA gene which encodes the green color blindness, retrobulbar neuritis, retinal
SE
target enzyme which is an acyl protein reductase damage), Headache, Confusion, Hyperuricemia,
• Best taken 1 hour before or 2 hours after meals Peripheral neuritis
Perform baseline ophthalmologic examination before ANTIFUNGAL AGENTS
starting antimycobacterial therapy
Resistance is due to mutation in emb gene
Notes
Dose adjustment if needed in renal patients
Always used in combination with other drugs for TB
Take with meals
STREPTOMYCIN [D]
Class Antimycobacterial (aminoglycoside)
Inhibit protein synthesis by binding to S12 ribosomal Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
MOA
subunit. Bactericidal.
Tuberculosis (for Drug-resistant strains), Tularemia,
Uses
Bubonic plague, Brucellosis
Hypersensitivity, Nephrotoxicity (reversible),
Ototoxicity (vestibulotoxic, irreversible),
SE
Neuromuscular blockade, Teratogen (congenital
deafness), Injection site reactions
Synergistic effect with beta-lactam antibiotics
Notes
Administered intramuscularly
SUPPLEMENT: Alternative Antimycobacterial Drugs

• AMIKACIN
o streptomycin-resistant or multidrug-resistant
mycobacterial strains
• CIPROFLOXACIN, OFLOXACIN
o active against strains of M. tuberculosis resistant to first-
line agents
• ETHIONAMIDE DRUGS FOR SYSTEMIC FUNGAL INFECTIONS
o no cross-resistance with INH
AMPHOTERICIN B [B]
o SE: severe gastrointestinal irritation and neurotoxicity
Class Antifungal (polyene)
• P-AMINOSALICYLIC ACID (PAS)
o rarely used because primary resistance is common Binds to ergosterol in fungal cell membranes, forming
MOA
o SE: gastrointestinal irritation, peptic ulcers, artificial pores. Fungicidal.
hypersensitivity reactions, effects on kidney, liver, and Systemic fungal infections (Aspergillus, Blastomyces,
Uses
thyroid function Candida albicans, Cryptococcus, Histoplasma, Mucor)
• CAPREOMYCIN Infusion reactions (chills, fever, muscle spasms,
o SE: ototoxicity, renal dysfunction SE hypotension), Nephrotoxicity (Renal Tubular Acidosis
with magnesium and potassium wasting)
• CYCLOSERINE
o SE: peripheral neuropathy, CNS dysfunction • Control infusion reactions by slowing rate of
infusion and premedication with antihistamines
• Additive nephrotoxicity with other nephrotoxic
DRUGS USED IN LEPROSY drugs (aminoglycosides)
DAPSONE [C] • LIPID FORMULATIONS: Ambisome, Amphotec,
SimD ACEDAPSONE [C] Abelcet
Class Antimycobacterial (sulfone) • Highly lipid soluble, poorly absorbed in the GIT
MOA Inhibition of folic acid synthesis. Bacteriostatic. • High Vd except in the CNS with a t½ of 2 weeks
Notes
Uses Leprosy, PCP pneumonia (backup) • Resistance is due to decreased level of ergosterol or
Gastrointestinal irritation, Fever, Skin rashes, change in membrane structure
SE Methemoglobinemia, Acute hemolysis in patients with • Has the WIDEST antifungal spectrum
G6PD deficiency Amphotericin B read as AmPOREtericin B cause pore
Most active drug against M. leprae formation and has poor oral bioavailability. A great
Usually used in combination with rifampicin and systemic antifungal but this cannot be use in fungal
Notes clofazimine meningitis. It cannot cross the blood brain barrier. Use
flucytosine for a fungal meningitis.
Acedapsone is a repository form of dapsone which has Dr. Calderon Jr.
drug action that can last for several months
FLUCYTOSINE [C]
CLOFAZIMINE [C] Class Antifungal (pyrimidine antimetabolite)
Class Antimycobacterial (phenazine dye) Accumulated in fungal cells by the action of permease
MOA and converted by cytosine deaminase to 5-FU, which
MOA Binds to guanine bases in bacterial DNA. Bactericidal.
inhibits thimidylate synthase. Fungistatic.
Uses Leprosy (sulfone-resistance)
Cryptococcosis, Systemic candidal infections,
SE Gastrointestinal irritation, Skin discoloration (ranging Uses
Chromoblastomycosis
from orange to red brown to nearly black)
SE Myelosuppression, Alopecia, Hepatotoxicity
Selective toxicity occurs because mammalian cells
DRUGS USED FOR ATYPICAL MYCOBACTERIA have low levels of permease and deaminase
• PROPHYLAXIS Decrease dose in renal patients
o Clarithromycin or Azithromycin with or without Rifabutin in Notes Resistance is due to decreased activity of fungal
patients with CD4 counts less than 50/L permease and deaminase
• TREATMENT Has synergistic effect when given with Amphotericin B
o azithromycin or clarithromycin with ethambutol and rifabutin and Triazoles.
KETOCONAZOLE [C]
Class Antifungal (azole)
Inhibit fungal P450-dependent enzymes blocking
MOA
ergosterol synthesis. Fungistatic.
Uses Chronic mucocutaneous candidiasis, Dermatophytosis
Gastrointestinal disturbances (vomiting, diarrhea),
SE
Rash, Hepatotoxicity, Drug interactions
Narrow antifungal spectrum TERBINAFINE [B]
Potent CYP450 inhibitor (Affect Phase I metabolism) SimD BUTENAFINE, NAFTIFINE
Limited to topical use because of systemic toxicity Class Antifungal (Allylamine)
Interferes with Steroid hormone synthesis Interfere with ergosterol synthesis by inhibiting fungal
Notes MOA
Resistance is due to changes in the sensitivity of target squalene oxidase. Fungicidal.
enzyme Uses Dermatophytosis, Onychomycosis
Ketoconazole is rarely used due to drug interactions Gastrointestinal upset, Rash, Headache, Taste
and narrow spectrum SE
disturbances, Hepatotoxicity
Accumulates in keratin
FLUCONAZOLE [D] Notes Given PO and topical
SimD VORICONAZOLE, POSACONAZOLE More effective than griseofulvin in onychomycosis
Class Antifungal (azole) – had good CNS penetrability
Inhibit fungal P450-dependent enzymes blocking TOPICAL DRUGS FOR
MOA
ergosterol synthesis. Fungistatic.
SUPERFICIAL FUNGAL INFECTIONS
Candidiasis (esophageal, oropharyngeal,
Uses vulvovaginitis), Coccidioidomycosis, Cryptococcal NYSTATIN [C]
meningitis (treatment and prophylaxis) SimD NATAMYCIN
Gastrointestinal disturbances (vomiting, diarrhea), Class Antifungal (polyene)
SE Binds to ergosterol in fungal cell membranes, forming
Rash, Hepatotoxicity MOA
Alternative to Amphotericin B in the treatment of C. artificial pores. Fungicidal.
neoformans Uses Candidiasis (Oropharyngeal, Esophageal, Vaginal)
As effective as Amphotericin B in candidemia SE Nephrotoxicity (severe)
Notes Posaconazole - BROADEST spectrum triazole (the only Minimal mucocutaneous absorption
Notes
azole with activity against Rhizopus sp. Available as a swish and swallow preparation
(mucormycosis)
Potent CYP450 inhibitor CLOTRIMAZOLE [C]
MICONAZOLE, KETOCONAZOLE, BUTOCONAZOLE,
ITRACONAZOLE [C] SimD ECONAZOLE, SULCONAZOLE, OXICONAZOLE,
Class Antifungal (azole) TERCONAZOLE, TIOCONAZOLE
Inhibit fungal P450-dependent enzymes blocking Class Antifungal (azole)
MOA Inhibit fungal P450-dependent enzymes blocking
ergosterol synthesis. Fungistatic. MOA
Blastomycosis, Sporotrichosis, Dermatophytosis, ergosterol synthesis. Fungistatic.
Chromoblastomycosis, Alternative for infections due Mucocutaneous candidiasis, Dermatophytosis,
Uses Uses
to Aspergillus, Coccidioides, Cryptococcus and Seborrheic dermatitis, Pityriasis versicolor
Histoplasma, Candida SE None significant when administered topically
Gastrointestinal disturbances (vomiting, diarrhea), Notes Limited to topical use because of systemic toxicity
SE
Rash, Hepatotoxicity
Much more selective for fungal cells than Ketoconazole ANTIVIRAL CHEMOTHERAPY AND
but with poor entry intro CNS
Notes
May also be used for subcutaneous PROPHYLAXIS
chromoblastomycosis
CASPOFUNGIN [C]
SimD ANIDULAFUNGIN, MICAFUNGIN
Class Antifungal (echinocandin)
Inhibits b-glucan synthase decreasing fungal cell wall
MOA
synthesis
Disseminated and mucocutaneous candidiasis, Salvage
Uses
therapy for invasive aspergillosis
Headache, Gastrointestinal distress, Fever, Rash,
SE
Flushing (histamine release), Elevated liver enzymes
All are given IV
Notes Micafungin can increase levels of cyclosporine and
tacrolimus
SYSTEMIC DRUGS FOR SUPERFICIAL MYCOSES Let us create and appreciate the whole picture of antiviral drugs to
appreciate its totality. In general, antiviral drugs are prodrugs (except
GRISEOFULVIN [X] NNRTI and Foscarnet which do not need phosphorylation). Antiviral
Class Antifungal from Penicillium griseofulvum drugs (except NNRTI and Foscarnet) need phosphorylation three times.
Interferes with microtubule function. Inhibits The first step is committed by the virus itself and the next two by humans.
MOA synthesis and polymerization of nucleic acids. Once activated, it can now render its function. As a concept, I want you
Fungistatic. to remember that antiviral drugs that need phosphorylation will cause
bone marrow suppression (neutropenia, anemia and depletion in
Uses Dermatophytosis platelets) as a side effect because they are incorporated in the DNA except
Headache, Mental confusion, Gastrointestinal Acyclovir. Question, where can you find the dormant stage of HSV? Diba
SE irritation, Photosensitivity, Hepatotoxicity, Disulfiram sa dorsal root ganglion at hindi sa bone marrow. Another one, how about
reaction, Drug interactions Ganciclovir saan natin ginagamit? Diba sa CMV. Nasaan ang CMV? CMV
Accumulates in keratin infects mononuclear cells. Nasaan ba ang mononuclear cells, diba nasa
Potent CYP450 Inducer bone marrow? Doc, my patient has CMV and he cannot tolerate the bone
Contraindicated in porphyria marrow suppression of Ganciclovir, what should I give? Give Foscarnet
an NNRTI which is not incorporated in the DNA. Therefore, no bone
Notes Given PO marrow suppression. See for yourself look at the similarities of these
Absorption is increased by intake of fatty meal medications.
Resistance is due to decreased transport of drug into Dr. Calderon Jr.
the fungal cell wall

Pronounce this as “greasyfulvin” it is best absorbed with greasy foods J
Dr. Calderon Jr.
FOSCARNET [C]
Class Antiviral (pyrophosphate analog)
Inhibits viral RNA polymerase, DNA polymerase, and
MOA HIV reverse transcriptase. Binds to pyrophosphate
binding site.
CMV retinitis, Acyclovir-resistance, HSV infection in
Uses
patients with AIDS
Nephrotoxicity, Electrolyte abnormalities
SE (hypocalcemia), Genitourinary ulceration, CNS effects
(headache, hallucinations, seizures)
Active against strains of HSV with absent thymidine
kinase activity
Does not require phosphorylation for antiviral activity
Notes
Resistance is due to mutations in DNA polymerase
gene
Dose adjustment in renal patients
DRUGS FOR HERPES This is an NNRTI therefore not incorporated in the DNA. It directly
ACYCLOVIR [B] attacks the DNA polymerase. Can you see bone marrow suppression as
side effect? Wala! AHA!
VALACYCLOVIR, PENCICLOVIR, FAMCICLOVIR,
SimD Dr. Calderon Jr.
DOCOSANOL, TRIFLURIDINE
Class Antiviral (anti-herpes)
Activated by viral thymidine kinase (TK) to forms that
DRUGS FOR HIV
MOA HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART)
inhibit viral DNA polymerase
Uses Infections due to HSV-1, HSV-2, VZV • initiation of treatment with 3 or more anti-retroviral drugs, if
Nausea, Diarrhea, Headache, Delirium, Tremor, possible, before symptoms appear
SE • usually 2 NRTIs plus 1 protease inhibitor
Seizures, Hypotension, Nephrotoxicity (crystalluria)
• No activity against strains of HSV with absent The concept of antiretroviral therapy has the same goal just like
Thymidine Kinase activity antibiotics. We combine different type of drugs to achieve synergism and
• DOCOSANOL inhibits fusion between the HSV combat possible resistance
Dr. Calderon Jr.
envelope and plasma membranes
ZIDOVUDINE [C]
• TRIFLURIDINE is a fluorinated pyrimidine
ABACAVIR, DIDANOSINE, EMTRICITABINE,
nucleoside SimD LAMIVUDINE, STAVUDINE, TENOFOVIR,
• VALOMACICLOVIR is an investigational agent which ZALCITABINE
acts as an inhibitor of viral DNA polymerase for Class Nucleoside Reverse Transcriptase Inhibitor
shingles and EBV
Inhibit HIV reverse transcriptase after
Notes • Given PO, topical and IV MOA
phosphorylation by cellular enzymes
• Dose adjustment in renal patients
HIV infection, Prevention of maternal-fetal HIV
• Resistance is due to changes in viral DNA Uses
transmission
polymerase Lactic Acidosis with hepatic steatosis
• Valacyclovir is a prodrug that is converted to Zidovudine: Bone marrow suppression
Acyclovir and reached plasma levels 3-5x (longer t½) SE Abacavir: Hypersensitivity
more than acyclovir Didanosine: Pancreatitis
• Penciclovir does not cause chain termination Stavudine, Zalcitabine: Peripheral neuropathy
• Famciclovir is a prodrug which is converted to
Abacavir, Emtricitabine, Lamivudine and Tenofovir are safe for pregnant
Penciclovir in vivo Dr. Calderon Jr.

This is an “ovir” but take a look there is no bone marrow suppression. DELAVIRDINE
Recall, HSV is dormant in the dorsal root ganglion not in the bone SimD EFAVIRENZ, ETRAVIRINE, NEVIRAPINE, RILPIVIRINE
marrow. Class Non-nucleoside Reverse Transcriptase Inhibitor
Dr. Calderon Jr.
Inhibit HIV reverse transcriptase. No phosphorylation

GANCICLOVIR [C] MOA

SimD VALGANCICLOVIR required.
Class Antiviral (anti-CMV) Uses HIV infection
Inhibits viral DNA polymerase, causing chain Delavirdine, Nevirapine: Rash, Increased AST/ALT
MOA SE Efavirenz: Teratogenicity
termination.
Uses Infections due to CMV, HSV-1, HSV-2, VZV Etravirine: Increased cholesterol, triglycerides
Leukopenia, Thrombocytopenia, Mucositis, Can you see signs of bone marrow suppression with NNRTI? None because
SE these are not incorporated in the DNA.
Hepatotoxicity, Seizures, Neutropenia
Dr. Calderon Jr.
No activity against strains of HSV with absent
thymidine kinase activity MNEMONIC: NNRTIs (Non-Nucleoside RT inhibitors)
Given as IV or intraocular implant (for CMV retinitis) “Never Ever Deliver Nucleosides”
CMV resistance is due to mutation in viral DNA Nevirapine Efavirenz / Etravirine Delavirdine
Notes
polymerase and in the genes that code for the
activating viral phosphotransferase INDINAVIR [C]
Valganciclovir is a prodrug of ganciclovir with AMPRENAVIR, ATAZANAVIR, DARUNAVIR,
increased oral bioavailability INDINAVIR, LOPINAVIR, NELFINAVIR, RITONAVIR,
SimD
CIDOFOVIR [C] SAQUINAVIR, TIPRANAVIR, FOSAMPRENAVIR,
Class Antiviral (anti-CMV) BOCEPREVIR, TELAPRIVIR
Inhibits viral DNA polymerase, causing chain Class Protease inhibitor
MOA MOA Inhibit viral protein processing
termination.
CMV retinitis, Mucocutaneous HSV infections, Uses HIV infection
Uses Acyclovir-resistance, Ganciclovir-resistance, Genital Hyperlipidemia, Fat redistribution, Hyperglycemia,
warts, Molluscum contagiosum Insulin resistance
SE Nephrotoxicity Atazanavir, Fosamprenavir, Lopinavir, Nelfinavir,
Active against strains of HSV with absent thymidine SE Saquinavir: GI distress and diarrhea
kinase activity Atazanavir: Peripheral neuropathy
Notes Amprenavir: Rash
Resistance is due to mutation in DNA polymerase
Dose adjustment in renal patients Indinavir: Hyperbilirubinemia and nephrolithiasis
MNEMONIC: Protease Inhibitors LAMIVUDINE [C]
NAVIR (never) TEASE a proTEASE. ADEFOVIR DIPIVOXIL, ENTECAVIR, TELBIVUDINE,
SimD
All protease inhibitors end with –navir. TENOFOVIR, CLEVUDINE
Class Antiviral (anti-hepatitis B)
Analogy to protease inhibitors, think of pro-insulin and insulin. Which one
do you need? Insulin. There is a C-peptide between pro-insulin and insulin MOA Inhibits HBV DNA polymerase
and you need a protease to liberate the insulin. Just like C-peptide, think Uses Hepatitis B infection, HIV infection (lamivudine)
of a peptide that links an immature virus to mature form. If you prevent Adefovir: Lactic acidosis, Renal and hepatic toxicity
the cleavage by giving a protease inhibitor, you are left with an immature
SE
Entecavir: Headache, Dizziness, Fatigue, Nausea
non-infectious particle. That is how protease inhibitors work, they Co-infection between HBV and HIV may increase the
prevent the cleavage. Notes
Dr. Calderon Jr.
risk of pancreatitis with lamivudine use
SUPPLEMENT: Drugs for HIV: ENTRY INHIBITORS RIBAVIRIN [X]
ENFUVIRTIDE Class Antiviral
Class Fusion inhibitor Inhibits guanosine triphosphate formation. Prevents
Binds to gp41 subunit of viral envelope MOA capping of viral mRNA. Blocks RNA-dependent RNA
MOA glycoprotein, preventing fusion of viral and cellular polymerases.
membranes Uses HCV infection, RSV infection
Uses HIV infection Hemolytic anemia, Conjunctival and bronchial
SE
Injection site reactions, Hypersensitivity, Increased irritation, Teratogen
SE Early intravenous administration of ribavirin
incidence of bacterial pneumonia
Notes No cross-resistance with other anti-HIV drugs decreases mortality in viral hemorrhagic fevers
Notes
OTHER DRUGS FOR RSV: Pavilizumab (monoclonal
MARAVIROC antibody against RSV antigen)
Class CCR5 receptor antagonist
SUPPLEMENT: MISCELLANEOUS ANTIVIRALS:
Blocks viral attachment via transmembrane
MOA an immune response modifier effective for
chemokine receptor CCR5 IMIQUIMOD
Uses HIV infection external genital and perianal warts
Cough, Diarrhea, Muscle and joint pain, Increased Licensed for the treatment of cell-mediated
SE INOSINE immune deficiencies associated with viral
hepatic transaminases
Notes Minimal cross-resistance with other anti-HIV drugs
ACEDOBEN infections; used for genital warts, herpes
DIMEPRANOL virus infection, subacute sclerosing
OTHER ANTI-HIV panencephalitis and other conditions
Integrase inhibitor (an enzyme essential A nucleotide prodrug that undergoes
for replication of HIV) leading to metabolism to the active uridine analog
RALTEGRAVIR inhibition of strand transfer ; DI: avoid SOFOSBUVIR triphosphate, an inhibitor of Hepatitis C
using rifampicin concomitantly (lowered virus RNA-dependent polymerase; used for
blood levels) Hepatitis C
DRUGS FOR INFLUENZA ANTIPROTOZOAL DRUGS

AMANTADINE [C]
SimD RIMANTADINE
Class Antiviral (anti-influenza)
Inhibit early step replication and prevent uncoating by
MOA
binding to M2 proton channels
Uses Influenza A only
GI irritation, Dizziness, Cerebellar dysfunction (ataxia,
SE
dysarthria), Livedo reticularis
Virtually obsolete in terms of usage
Notes
Amantadine is also used in treating Parkinsonism
MNEMONICS: Amantadine ANTIMALARIAL DRUGS
A man to dine takes off his coat SUPPLEMENT:
(Amantadine prevents uncoating)
• TISSUE SCHIZONTICIDES
Amantadine: for influenza A and rubellA , o kill schizonts in the liver
causes problems with the cerebellA o EXAMPLE: primaquine, atovaquone
OSELTAMIVIR [C] • BLOOD SCHIZONTICIDES
SimD ZANAMIVIR, PERAMIVIR o kill these parasitic forms only in the erythrocyte
Class Antiviral (anti-influenza) o EXAMPLES: chloroquine, quinine mefloquine, atovaquone,
Inhibits Neuraminidase. Decreases release of progeny pyrimethamine, doxycycline, halofantrine, artemisinin
MOA • GAMETOCIDES
virus.
Uses Influenza A and B, Shortens duration of symptoms o kills gametocides in human blood
Oseltamivir: Gastrointestinal effects o EXAMPLES: primaquine
SE • SPORONTICIDES
Zanamivir: Bronchospasm in asthmatics
OSELTAMIVIR: Presently the drugs of choice for o prevent sporogony and multiplication in the mosquito
Notes o EXAMPLES: proguanil, pyrimethamine
influenza (including H1N1)
CHLOROQUINE [C]
DRUGS FOR HBV AND HCV SimD HYDROXYCHLOROQUINE, AMODIAQUINE,
PIPERAQUINE
INTERFERON-a [X]
Class Antimalarial, Disease-Modifying Anti-Rheumatic Drug
Class Interferon
MOA Prevents polymerization of heme into Hemozoin.
Degrades viral RNA via activation of host cell RNAase
MOA Blood schizonticide.
(ribonuclease)
Uses Malaria (non-falciparum, chloroquine-sensitive),
HBV infection, HCV infection, Kaposi sarcoma, Genital
Uses Chemoprophylaxis (chloroquine-sensitive areas),
warts
Rheumatoid arthritis, Amebic liver abscess
Alopecia, Myalgia, Depression, Flu-like syndrome,
SE SE GI irritation, Skin rash, Headaches, Peripheral
Thyroid dysfunction, Hearing loss
neuropathies, Myocardial depression, Retinal damage,
Contraindications include autoimmune disease,
Notes Auditory impairment, Psychosis, QT prolongation
history of cardiac arrhythmias and pregnancy
Notes May precipitate porphyria
QUININE [C] HALOFANTRINE [C]
SimD QUINIDINE GLUCONATE SimD LUMEFANTRINE
Class Antimalarial Class Antimalarial
Complexes with DNA to prevent strand separation. MOA Unknown. Blood schizonticide.
MOA Blocks DNA replication and transcription. Blood Malaria (chloroquine-resistance), Severe falciparum
Uses
schizonticide. malaria (quinidine)
Malaria (chloroquine-resistance), Severe falciparum Abdominal pain, Diarrhea, Vomiting, Cough, Rash,
Uses
malaria (quinidine) Headache, Pruritus, Elevated liver enzymes,
SE
Cinchonism (headache, tinnitus, vertigo), Hemolysis Cardiotoxicity (prolongs PR and QT interval),
SE
in G6PD deficiency, Blackwater fever Teratogen
Quinine is commonly used with doxycycline or Lumefantrine used in combination with artemether
Notes
Notes clindamycin to limit toxicities (Co-Artem)
DOC for malaria in pregnant patients
SUPPLEMENT: Blackwater Fever ARTEMISININ
ARTESUNATE, ARTEMETHER,
• severe complication of P. falciparum malaria SimD
DIHYDROARTEMISININ
• characterized by intravascular hemolysis, massive
Class Antimalarial
hemoglobinuria and acute renal failure
Forms toxic free radicals in malarial food vacuole.
• rare and sometimes fatal complication in quinine-sensitized MOA
Blood schizonticide.
persons
Uses Malaria (uncomplicated falciparum, quinine-resistant)
MEFLOQUINE [B] SE Nausea, Vomiting, Diarrhea
Class Antimalarial Artemether-Lumefantrine (Co-Artem) is the drug of
MOA Unknown. Blood schizonticide. choice for uncomplicated falciparum malaria in the
Chemoprophylaxis (chloroquine-resistant areas), Philippines
Uses Alternative to quinine in acute attacks of falciparum Artemisinin-based combination therapy is current the
malaria first line of malaria treatment recommended by the
Notes
GI distress, Skin rash, Headache, Dizziness, WHO for children, adults and pregnant women in
SE Cardiac conduction defects, Psychiatric disorders second or third trimester. Due to potential
(psychosis), Neurologic symptoms, Seizures embryotoxicity of artemisinins identified in animal
studies, artemisinins are not considered safe for use in
PRIMAQUINE first trimester of pregnancy.
Class Antimalarial SUPPLEMENT:
Forms electron-transferring redox compounds that CLINICAL
MOA act as cellular oxidants. Tissue schizonticide. DRUG OF CHOICE / ALTERNATIVE
SETTING
Gametocide.
Chloroquine-
Malaria (radical cure of P. vivax, P. ovale), Terminal
Uses sensitive P. Chloroquine
prophylaxis (vivax, ovale), PCP pneumonia falciparum
GI distress, Pruritus, Headaches, Methemoglobinemia,
SE P. vivax and P.
Hemolysis in G6PD deficient patients Chloroquine then Primaquine
ovale
Should be used with a blood schizonticide
Uncomplicated Artemether + Lumefantrine (CoArtem) /
Notes Eradicates hypnozoites in the liver, preventing
Chloroquine- Malarone or Mefloquine or Quinine
malarial relapse resistant P. Sulfate + Clindamycin or other
falciparum Artemisinin-based combination regimen
ATOVAQUONE-PROGUANIL [C]
Artesunate then Doxycycline or
Class Antimalarial Severe or
Clindamycin or CoArtem ; Quinidine
Atovaquone disrupts mitochondrial electron Complicated P.
gluconate / Artemether or Quinine
MOA transport. Blood and tissue schizonticide. falciparum
dihydrochloride
Proguanil inhibits folate synthesis. Sporonticide.
Treatment and chemoprophylaxis (chloroquine-
Uses
resistant P. falciparum) – all stages
Abdominal pain, Nausea, Vomiting, Diarrhea,
SE
Headache, Rash, Increased liver enzymes
SULFADOXINE-PYRIMETHAMINE [C]
Class Antimalarial (antifolate)
Sequential blockade of folic acid synthesis. Blood
MOA
schizonticide. Sporonticide (pyrimethamine).
Uses Malaria (chlorine-resistant P. falciparum)
Skin rashes, GI distress, Hemolysis, Kidney damage,
SE Drug interactions, Folic acid deficiency
(pyrimethamine)
Competition for plasma protein binding sites with
Notes other drugs
Pyrimethamine is a long-acting folate antagonist
DOXYCYCLINE [D]
Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
Class Antimalarial, Tetracycline antibiotic SUPPLEMENT: Malaria Chemoprophylaxis
MOA Impairs progeny of malarial apicoplast genes,
• for CHLOROQUINE-SENSITIVE areas:
resulting in abnormal cell division. Blood
o CHLOROQUINE 500 mg/tab, 1 tab weekly
schizonticide.
Uses Chemoprophylaxis (Multidrug-resistant) • for CHLOROQUINE-RESISTANT areas:
o MEFLOQUINE 250 mg/tab, 1 tab weekly
SE GI disturbance, Teratogen (tooth enamel
o MALARONE (Atovaquone 250 mg/Proguanil 100 mg)/tab,
dysplasia/discoloration), Hepatotoxicity,
1 tab daily
Nephrotoxicity, Photosensitivity, Vestibulotoxicity
• for MULTIDRUG-RESISTANT areas:
Notes Do NOT drink with milk (decreased absorption)
Common side effect is a headache without organic lesion
o DOXYCYCLINE 100 mg/tab, 1 tab daily
that is Pseudotumor cerebri. • for P. vivax and P. ovale
Dr. Calderon Jr. o PRIMAQUINE 30mg daily for 2 weeks (for hypnozoites)
SUPPLEMENT: OTHER DRUGS FOR MALARIA NITAZOXANIDE [B]

Class Antiprotozoal
Also known as Quinacrine and Atabrine;
MEPACRINE MOA Reactive reduction by ferredoxin forming free
used in the treatment and prevention of
(Group: radicals that disrupt electron transport chain. Tissue
malaria; may also be used as an
Acridine) amebicide.
immunomodulatory agent
Uses Metronidazole-resistant amebiasis, Giardiasis,
DRUGS FOR AMEBIASIS Cryptosporidiosis (drug of choice)
SUPPLEMENT: SE Gastrointestinal distress
• TISSUE AMEBICIDES
o act on organisms in the bowel wall and the liver DRUGS FOR PNEUMOCYSTOSIS AND
o EXAMPLES: chloroquine, emetines, metronidazole, TOXOPLASMOSIS
tinidazole CO-TRIMOXAZOLE [C]
• LUMINAL AMEBICIDES Class Sulfonamide, Antiprotozoal
o act only in the lumen of the bowel Sequential blockade of dihydropteroate synthase
o EXAMPLES: diloxanide furoate, iodoquinol, paromomycin MOA (sulfamethoxazole) and dihydrofolate reductase
Mnemonic for luminal amebicide is DIP. We DIP in the lumen. (Diloxanide, (trimethoprim)
Iodoquinol,, Paromomycin) Prophylaxis and treatment of pneumocystosis (drug of
Uses
Dr. Calderon Jr.
choice), Prophylaxis (T. gondii, I. belli)
GI upset, Acute hemolysis in G6PD deficiency,
Nephrotoxicity, Hypersensitivity (assume cross-
SE
hypersensitivity, SJS/TEN), Hematotoxicity, Drug
interactions, Kernicterus
Displaces protein binding of other drugs/bilirubin
Notes
Recommended at CD4 count < 200
SUPPLEMENT: PENTAMIDINE
Class Antiprotozoal
MOA Unknown. Probably inhibits glycolysis or interferes
DILOXANIDE FUROATE with nucleic acid metabolism.
Class Antiprotozoal Uses Prophylaxis and treatment of pneumocystosis
MOA Unknown. Luminal amebicide. (backup), Trypanosomiasis
Asymptomatic cyst carriers of E. histolytica SE Respiratory stimulation followed by depression,
Uses
(drug of choice) Hypotension, Hypoglycemia, Anemia, Neutropenia,
SE Flatulence, Nausea, Abdominal cramps Hepatitis, Pancreatitis
SUPPLEMENT: EMETINE Notes Administered by nasal spray (aerosol)
SimD DEHYDROEMETINE
Class Antiprotozoal SULFADIAZINE-PYRIMETHAMINE [C]
Inhibit proteins synthesis. Blocks ribosomal SimD PYRIMETHAMINE + CLINDAMYCIN
MOA movement along messenger RNA. Tissue Class Antiprotozoal
amebicide. Sequential blockade of dihydropteroate synthase
Backup drug for severe intestinal and MOA (sulfadiazine) and dihydrofolate reductase
Uses
extraintestinal amebiasis (pyrimethamine)
Gastrointestinal distress, Muscle weakness, Prophylaxis and treatment of Toxoplasmosis (drug of
Uses
SE Cardiovascular dysfunction (arrhythmias and choice)
congestive heart failure) Gastric irritation, Glossitis, Neurologic symptoms
Reserved only for situations when metronidazole (headache, insomnia, tremors, seizures),
Notes
cannot be used SE Hematotoxicity (megaloblastic anemia,
thrombocytopenia), Pseudomembranous colitis
IODOQUINOL [C]
(clindamycin)
Class Antiprotozoal
MOA Unknown. Luminal amebicide.
Uses Mild-to-severe intestinal amebiasis DRUGS FOR TRYPANOSOMIASIS
Gastrointestinal distress, Thyroid enlargement, Skin
SE reactions due to iodine toxicity, Neurotoxicity
(peripheral neuropathy, visual dysfunction)
Notes Usually used in combination with metronidazole
METRONIDAZOLE [B] African trypanosomiasis will cause sleeping sickness. American
SimD TINIDAZOLE [C], SECNIDAZOLE [C] trypanosomiasis will not because America never sleeps. AHA!
Dr. Calderon Jr.
Class Antiprotozoal, Antibiotic
Reactive reduction by ferredoxin forming free radicals SUPPLEMENT: PENTAMIDINE
MOA that disrupt electron transport chain. Tissue Class Antiprotozoal
amebicide. Unknown. Probably inhibits glycolysis or interferes
MOA
Severe intestinal and extraintestinal amebiasis (drug with nucleic acid metabolism.
of choice), Trichomoniasis, Giardiasis, Bacterial African sleeping sickness (hemolymphatic stages),
Uses Uses Prophylaxis for pneumocystosis, Kala-azar
vaginosis, Anaerobic infections (B. fragilis, C. difficile),
Peptic ulcer disease (visceral leishmaniasis)
Gastrointestinal irritation, Metallic taste, Headache, Respiratory stimulation followed by depression,
SE Dark urine, Leukopenia, Dizziness, Ataxia, SE Hypotension, Hypoglycemia, Anemia, Neutropenia,
Neuropathy, Seizures, Disulfiram reaction Hepatitis, Pancreatitis
Notes Does not cross the blood brain barrier
PAROMOMYCIN [C]
Class Antiprotozoal, Aminoglycoside SURAMIN
Inhibits protein synthesis. Binds to 16S ribosomal Class Antiprotozoal
MOA
subunit. Luminal amebicide. Unknown. Probably inhibits glycolysis or interferes
MOA
Asymptomatic cyst carriers (backup), Intestinal with nucleic acid metabolism.
Uses
amebiasis, Cryptosporidiosis African sleeping sickness (Hemolympahtic stages),
Uses
SE Headaches, Dizziness, Rashes, Arthralgia Onchocerciasis (backup)
Fatigue, Nausea, Vomiting, Seizures, Shock Read Leishmaniasis as Leshbianiasis. Give STIBOgluconate
Dr. Calderon Jr.
Fever, Rash, Headache, Paresthesia, Neuropathies,
SE TREATMENT OF
Renal abnormalities (proteinuria), Chronic diarrhea, SUPPLEMENT:
Hemolytic anemia, Agranulocytosis OTHER PROTOZOAL INFECTIONS
Does not cross the blood brain barrier DRUG OF CHOICE /
Notes ORGANISM
Used in combination with melarsoprol ALTERNATIVE
EFLORNITHINE Clindamycin or Quinine /
Babesia sp.
Class Antiprotozoal Atovaquone or Azithromycin
MOA Suicide inhibitor of ornithine decarboxylase Balantidium Coli Tetracycline / Metronidazole
Advanced West African sleeping sickness (drug of Cryptosporidium sp. Paromomycin / Azithromycin
Uses Cyclospora
choice) TMP-SMX
Diarrhea, Vomiting, Anemia, Thrombocytopenia, cayetanensis
SE Dientamoeba Iodoquinol / Tetracycline or
Leukopenia, Seizures
Crosses the blood brain barrier fragilis Paromomycin
Notes Metronidazole or Tinidazole /
Considerably less toxic than melarsoprol Giardia lamblia
Furazolidone or Albendazole
MELARSOPROL TMP-SMX / Pyrimethamine or
Isospora belli
Class Antiprotozoal Folinic Acid
Organic arsenical. Inhibits enzyme sulfhydryl groups Microsporidia Albendazole
MOA Sodium stibogluconate /
in trypanosomes.
Uses African sleeping sickness (drug of choice) Meglumine or Pentamidine or
Leishmania
SE Gastrointestinal irritation, Reactive encephalopathy Amphotericin or Miltefosine or
Paromomycin
Crosses the blood brain barrier
Notes Administered intramuscularly TMP-SMX / Pentamidine or TMP-
Pneumocystis
Usually administered with suramin Dapsone or Clindamycin +
jirovecii
Primaquine or Atovaquone
NIFURTIMOX Pyrimethamine + Clindamycin +
Folinic acid or Spiramycin /
Class Antiprotozoal Toxoplasma gondii
Pyrimethamine + Sulfadiazine +
MOA Inhibits trypanothione reductase
Folinic acid
Chagas disease (drug of choice), African sleeping
Uses Trichomonas
sickness (backup), Mucocutaneous leishmaniasis Metronidazole or Tinidazole
vaginalis
Nausea, Vomiting, Abdominal pain, Fever, Rash,
SE Trypanosoma cruzi Nifurtimox or Benznidazole
Restlessness, Insomnia, Neuropathies, Seizures
Notes Does not cross the blood brain barrier
ANTIHELMINTHIC DRUGS
SODIUM STIBOGLUCONATE
MEGLUMINE ANTIMONATE, AMPHOTERICIN,
SimD
MILTEFOSINE
Class Antiprotozoal
Unknown. Probably inhibits glycolysis or interferes
MOA
with nucleic acid metabolism.
Uses Leishmaniasis (drug of choice except in India)
Gastrointestinal symptoms, Fever, Headache,
SE Myalgias, Arthralgias, Rash, Sterile abscesses,
Cardiotoxicity (T-wave changes, QT prolongation)
Alternative drugs include:
Visceral (kala-azar): pentamidine, miltefosine
Notes
Cutaneous: fluconazole, metronidazole
Mucocutaneous: amphotericin B
DRUGS ACTIVE AGAINST NEMATODES
DRUGS FOR THE TREATMENT OF HELMINTHIC INFECTIONS (NEMATODES)

Table 53-1. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
ALBENDAZOLE [C] DIETHYLCARBAMAZINE
Class Antihelminthic Class Antihelminthic
MOA Inhibits microtubule assembly. Larvicidal and ovicidal. Immobilizes microfilariae (by an unknown
Ascariasis, Hookworm, Pinworm, Hydatid disease MOA mechanism) and alters their surface structure → more
(drug of choice), Whipworm infections, Cutaneous & susceptible to host defense mechanisms
Uses Visceral Larva migrans, Cysticercosis (larval stages of Filariasis (drug of choice), Eye worm disease (drug of
Uses
T. solium), Angiostrongylus cantonensis, Capillaria choice), Onchocerciasis (backup)
philippinensis Headache, Malaise, Weakness, Anorexia, Filarial fever
Reversible leukopenia, Alopecia, Elevation of liver SE (fever, rashes, ocular damage, joint and muscle pain,
SE
function tests, Bone marrow suppression lymphangitis)
Improved penetration (>Praziquantel) of the May cause Mazzotti reaction when used for
Notes subarachnoid space in Neurocysticersosis onchocerciasis
Notes
Should not be given to patients with Cirrhosis DOXYCYCLINE has also shown significant activity
MEBENDAZOLE [C] against W. bancrofti
Class Antihelminthic IVERMECTIN [C]
Selectively inhibits microtubule synthesis and glucose Class Antihelminthic
MOA
uptake in nematodes. Ovicidal. Intensifies GABA-mediated neurotransmission in
MOA
Whipworm infections (drug of choice), Trichinosis, nematodes. Immobilizes parasites.
Uses
Visceral larval migrans (backup), Ascariasis, Pinworm Strongyloidiasis (drug of choice), Onchocerciasis,
Uses
Gastrointestinal irritation, Agranulocytosis, Alopecia, Cutaneous larva migrans, Filariasis (back up)
SE
Elevated liver enzymes Mazzoti reaction (fever, headache, dizziness, rashes,
THIABENDAZOLE [C] SE pruritus, tachycardia, hypotension, pain in joints,
Class Antihelminthic muscles and lymph glands), corneal opacities
Contraindicated in pregnancy and children < 5y/o
Selectively inhibits microtubule synthesis and glucose
Notes Avoid concomitant use of Ivermectin with other drugs
MOA uptake in nematodes. Inhibits fumarate reductase.
that enhance GABA activity (Barbiturates, BZDs etc.)
Ovicidal.
Uses Trichinosis (drug of choice), Strongyloidiasis (backup) PYRANTEL PAMOATE [C]
Gastrointestinal irritation, Headache, Dizziness, Class Antihelminthic
Drowsiness, Leukopenia, Hematuria, Hypersensitivity Stimulates nicotinic receptors at NMJ of nematodes.
MOA
SE reactions (SJS), Hepatotoxicity (intrahepatic Causes depolarization-induced paralysis.
cholestasis, liver failure), Reactions caused by dying Ascaris, Hookworm and Pinworm infections (drug of
Uses
parasites choice), Trichostrongylus sp.
Notes Contraindicated in pregnancy SE GI distress, Headache, Weakness
Wide activity against nematodes killing adult worms
Notes in the colon but not the eggs
Contraindicated in patients with hepatic dysfunction
DRUGS ACTIVE AGAINST TREMATODES AND CESTODES
DRUGS FOR THE TREATMENT OF HELMINTHIC INFECTIONS (TREMATODES AND CESTODES)

Table 53-1. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
PRAZIQUANTEL [B] SUPPLEMENT: NICLOSAMIDE
Class Antihelminthic
Class Antihelminthic
Increases membrane permeability to calcium →
Uncouples oxidative phosphorylation or by
MOA paralysis. Causes muscle paralysis, vacuolization and MOA
activating ATPases
death.
Alternative drug for cestode infections (Taenia,
Drug of choice for trematodes (Schistosoma,
Uses Diphyllobothrium, Hymenolepsis, Dipylidium,
Paragonimus, Clonorchis, Opisthorchis, Fasciolopsis,
Uses Fasciolopsis, Heterophyes)
Heterophyes) and cestodes (Taenia,
SE Gastrointestinal distress, Headache, Rash, Fever
Diphyllobothrium, Hymenolepsis)
Kills scolices and cestode segments but has no effect
Headache, Dizziness, Nausea, Malaise, drowsiness, GI
SE on ova
upset, arthralgia, myalgia, pruritus, skin rash, Notes
Contraindicated in ocular cysticercosis (may cause
Avoid ethanol consumption for 48h upon drug
irreparable eye damage) administration
Notes Used with corticosteroids in treating neurocysticercosis
May be used as an adjunct to Albendazole in Hydatid disease
SUPPLEMENT: MISCELLANEOUS ANTHELMINTICS Chlamydia
an organophosphate compound, an C. trachomatis Tetracycline, Azithromycin
alternative treatment for S. C. pneumoniae Tetracycline, Erythromycin
METRIFONATE haematobium; MOA is via cholinesterase C. psittaci Tetracycline
inhibition → paralysis ; SE: cholinergic Spirochetes
symptoms (DUMBBELS); CI in pregnancy Borrelia recurrentis Doxycycline
alternative to Praziquantel for S. Borrelia
mansoni; SE: fever, orange-red Doxycycline, Ceftriaxone
burgdorferi
discoloration of urine, proteinuria, Leptospira sp. Penicillin
OXAMNIQUINE
microscopic hematuria, seizures, Treponema sp. Penicillin
dizziness and drowsiness (no driving for Fungi
24 hrs) Aspergillus sp Voriconazole
alternative for ascariasis ; MOA: blocking Blastomyces sp Amphotericin B
ACh at the myoneural junction →
Candida sp Amphotericin B, Echinocandin
expulsion via normal peristalsis;
PIPERAZINE Cryptococcus Amphotericin B + Flucytosine
Contraindicated in pregnancy, impaired
Coccidioides
renal or hepatic function or with a history Amphotericin B
immitis
of epilepsy or chronic neurologic disease
alternative to triclabendazole for the Histoplasma
Amphotericin B
capsulatum
treatment of fascioliasis and
BITHIONOL Mucoraceae
paragonimiasis, SE: GI upset, skin rash ; Amphotericin B
do not use in Px <8y.o. (Rhizopus)
Sporothrix schenkii Amphotericin B
EMPIRIC ANTIMICROBIAL THERAPY BASED
SUPPLEMENT: EMPIRIC ANTIMICROBIAL THERAPT BASED
ON MICROBIOLOGIC ETIOLOGY SUPPLEMENT:
ON SITE OF INFECTION
GNC – gram negative cocci GPC – gram positive cocci
GNR – gram negative rods GPR – gram positive rods Bacterial Endocarditis
Vancomycin + Gentamicin
GNC (Aerobic) (Acute)
Moraxella TMP-SMX, 2nd or 3rd gen Bacterial Endocarditis
Penicillin + Gentamicin
catarrhalis Cephalosporin (Subacute)
Neisseria gonorrhea Ceftriaxone, Cefixime Septic arthritis (Child) Ceftriaxone
N. meningitides Pen G Septic arthritis (Adult) Cefazolin
GNR (Aerobic) Acute OM, Sinusitis Amoxicillin
E.coli, Klebsiella, Penicillinase-resistant
1st or 2nd gen Ceph, TMP-SMX Cellulitis penicillin, 1st gen
Proteus
Enterobacter, Cephalosporin
Citrobacter, TMP-SMX, Quinolone, Carbapenem Ampicillin + 3rd gen
Meningitis (Neonate)
Serratia Cephalosporin
Shigella Quinolone Ceftriaxone or Cefotaxime +
Meningitis (Child)
Salmonella Quinolone, Ceftriaxone Vancomycin
Campylobacter Meningitis (Adult) Ceftriaxone, Cefotaxime
Erythromycin or Azithromycin Metronidazole + 3rd gen
jejuni
Doxycycline + Rifampicin or Peritonitis Cephalosporin , Piperacillin-
Brucella sp. Tazobactam
Aminoglycoside
H. pylori PPI + Amoxicillin + Clarithromycin Ampicillin + 3rd gen
Pneumonia (Neonate)
Vibrio sp. Tetracycline Cephalosporin
Pseudomonas Antipseudomonal Pen + Ceftriaxone , Cefuroxime,
Pneumonia (Child)
aeruginosa Aminoglycoside Cefotaxime
Legionella sp. Azithromycin or Quinolone Macrolide, Amoxicillin,
GPC (Aerobic) Adult (CAP) Tetracycline, Quinolone
(respiratory)
S. pneumoniae Penicillin
Vancomycin + 3rd gen
S. pyogenes Penicillin, Clindamycin
Cephalosporin or Piperacillin-
S. agalactiae Penicillin ± Aminoglycoside Septicemia
Tazobactam or
Viridans
Penicillin Imipenem/Meropenem
Streptococcus
S. aureus Penicillinase-resistant Pen RECOMMENDATION FOR NON-SURGICAL
SUPPLEMENT:
MRSA Vancomycin ANTIMICROBIAL PROPHYLAXIS
Enterococcus Penicillin ± Aminoglycoside Anthrax Ciprofloxacin or Doxycycline
GPR (Aerobic) Cholera Tetracycline
Bacillus sp. Vancomycin Diphtheria Penicillin or Erythromycin
Listeria sp. Ampicillin ± Aminoglycoside Endocarditis Amoxicillin or Clindamycin
Nocardia sp. Sulfadiazine, TMP-SMX Genital Herpes
Acyclovir
Anaerobic Bacteria Simplex
GP (Clostridium, Perinatal HSV2 Acyclovir
Peptococcus, Group B Strep Ampicillin or Penicillin
Penicillin, Clindamycin
Actinomyces, Hib Rifampicin
Peptostreptococcus) Tenofovir / Emtricitabine ±
HIV
Clostridium difficile Metronidazole Lopinavir/Ritonavir
Bacteroides fragilis Metronidazole Influenza A & B Oseltamivir
Metronidazole, Clindamycin, Malaria Chloroquine
Fusobacterium
Penicillin Meningococcal Rifampicin, Ciprofloxacin or
Mycobacteria infection Ceftriaxone
M. tuberculosis HRZE Mycobacterium Azithromycin, Clarithromycin or
M. leprae Dapsone + Rifampicin ± Clofazimine avium complex Rifabutin
Mycoplasma Otitis Media Amoxicillin
Tetracycline, Erythromycin
pneumoniae Pertussis Azithromycin
Plague Tetracycline
Pneumococcemia Penicillin Correlation to Internal Medicine: PPIs are far more superior than H2
Pneumocystis blockers in acid control. H2 receptor antagonists are used as adjunct to
jirovecii TMP-SMX, Dapsone or Atovaquone nocturnal control of acid
Dr. Calderon Jr.
pneumonia
OMEPRAZOLE [C]
Rheumatic Fever Benzathine penicillin
LANSOPRAZOLE [B], RABEPRAZOLE [C],
Toxoplasmosis TMP-SMX SimD
PANTOPRAZOLE [B], ESOMEPRAZOLE [C]
Tuberculosis INH, Rifampin or PZE
Class Proton pump inhibitor
UTI TMP-SMX
Irreversible blockade of H+/K+ ATPase in active gastric
MOA parietal cells. Long-lasting reduction of meal-
GASTROINTESTINAL PHARMACOLOGY stimulated and nocturnal acid secretion.
Peptic ulcer disease (DOC), Zollinger-Ellison
Uses
syndrome, Gastroesophageal reflux, Dyspepsia, SJS
• Diarrhea, Headache, Abdominal pain, Malabsorption
(Vit B12, Ca, Fe, Zn), Infections (respiratory, enteric),
Hypergastrinemia, Atrophic gastritis, Fractures of
the hip and spine
• PPIs should be taken before meals, ideally 30mins to
1 hour before breakfast
• May interfere with absorption of drugs where gastric
pH is an important determinant of their
bioavailability (e.g. Ketoconazole, Ampicillin,
Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 SE Ferrous salts, Digoxin)
• Use with caution in Hepatically-impaired (Omep,
DRUGS USED IN PEPTIC ULCER DISEASE Esomep, Panto) and Renally-impaired (Omep,
SUPPLEMENT: Panto) patients
Peptic Ulcer Disease • PPIs are possibly associated with Clostridium
• chronic most often solitary lesions that occur in any portion difficile-associated diarrhea
of the gastrointestinal tract exposed to the aggressive action • Daily long-term use (more than 3yrs) may lead to
of acid-peptic juices malabsorption or deficiency of Vit B12
• at least 98% occur either in the first portion of the duodenum Since parietal cells also secrete intrinsic factor, there can be
or in the stomach Vit B12 deficiency
MAGNESIUM-ALUMINUM HYDROXIDE [C] Amongst the PPI, pantoprazole has the least drug-drug interaction.
SimD CALCIUM CARBONATE, SODIUM BICARBONATE Correlation to Internal Medicine: Why do we give PPIs for bleeding PUD?
Class Antacid According to Harrison’s, we have 3 important reasons 1). To maintain the
Neutralize stomach acid by reacting with protons in stability of the clot 2). To maintain an intragastric pH of 6 and 3) to
MOA reduce mortality. AHA!
the lumen of the gut
Dr. Calderon Jr.
Uses Peptic ulcer disease
SUCRALFATE [B]
Sodium bicarbonate: belching, metabolic alkalosis,
Class Mucosal protective agent
fluid retention
SE Binds to injured tissue and forms a protective covering
Calcium carbonate: hypercalcemia, renal insufficiency,
MOA over ulcer beds. Accelerates healing of peptic ulcers
metabolic alkalosis (milk-alkali syndrome)
and reduces recurrence rate.
• Impairs absorption of tetracyclines,
Uses Peptic ulcer disease
fluoroquinolones, itraconazole and iron
SE None
• Caution in giving to Px with Renal Insufficiency
Highly insoluble, requiring frequent dosing
• Impairs absorption of tetracyclines, Caution in chronic renal impairment
fluoroquinolones, itraconazole and iron → should Coats the ulcer bed to protect it from the stomach acid →
not be given within 2 hours with these drugs Notes healing.
Notes • When used regularly in large doses needed to
Needs frequent dosing since it will be washed away when
significantly raise the stomach pH, antacids, you drink or eat.
decrease recurrence rate of peptic ulcers Dr. Pereyra-Borlongan
• Aluminum and Magnesium are always given
MISOPROSTOL [X]
together to cancel out each other's adverse effect
Class Mucosal protective agent
• Avoid in renally impaired patients
Activates EP receptors. Causes increased HCO3 and
• DOA: 1-2 hours MOA
mucus secretion in stomach. Uterine contraction.
MNEMONICS: Maalox Peptic ulcer disease, Prevention of NSAID-induced
Uses
MAGnesium hydroxide causes diarrhea gastric mucosal injury, Abortifacient
MAGtatae ka! Abdominal pain, Diarrhea, Uterine cramping,
ALUMinum hydroxide causes constipation Miscarriage
Ayaw LUMabas! SE Activates PGE1 receptor which decreases acid secretion and
CIMETIDINE [B] increases mucus secretion in the stomach
SimD RANITIDINE, FAMOTIDINE, NIZATIDINE Dr. Pereyra-Borlongan
Class H2-receptor antagonist BISMUTH SALICYLATE [C, D in 3rd trim]

MOA Competitive pharmacologic block of H2 receptors Class Mucosal protective agent
Peptic ulcer disease, Zollinger-Ellison syndrome, Forms a protective coating on ulcerated tissue.
Uses
Gastroesophageal reflux, Dyspepsia Stimulates mucosal protective mechanisms, direct
MOA
Gynecomastia (cimetidine only), Diarrhea, Headache, antimicrobial effects and sequestration of
Fatigue, Myalgias, Constipation, Nosocomial enterotoxins.
SE
pneumonia, Mental status changes, Bradycardia, Uses Peptic ulcer disease, Dyspepsia, Infectious diarrhea
Hypotension, Blood dyscrasias Black stools, Darkening of tongue, Encephalopathy
Cimetidine is a potent inhibitor of CYP450 SE
(ataxia, headaches, confusion, seizures)
Highly-effective in suppressing Nocturnal acid Reduces stool frequency and liquidity in infectious
secretion but only modest effect on meal-stimulated diarrhea
Notes secretion Notes This drug has dual activity. It acts as mucosal protective
Ranitidine: Adjust doses for Renally impaired patients agent. And due to its heavy metal component (Bismuth), it
May be used for pregnant patients. Yayyy J has a direct bactericidal effect on H. pylori J
LACTULOSE [B]
MAGNESIUM OXIDE, SORBITOL, MAGNESIUM
SimD CITRATE, SODIUM PHOSPHATE, POLYETHYLENE
GLYCOL
Class Laxative (osmotic)
Soluble but nonabsorbable compounds that result in
MOA increased stool liquidity due to an obligate increase in
fecal fluid
Constipation, Hepatic encephalopathy (lactulose),
Uses
Preparation for endoscopy (polyethylene glycol)
Diarrhea, Flatus, Abdominal cramps, Electrolyte
SE abnormalities (hyperphosphatemia, hypocalcemia,
hypernatremia, hypokalemia, hypermagnesemia)
BISACODYL [B]
SimD ALOE, SENNA, CASCARA, CASTOR OIL
Class Laxative (stimulant/cathartic)
Unknown. Directly stimulate enteric nervous system
MOA
Mnemonics on how to remember your regimen will be given during the
and colonic electrolyte and fluid secretion.
pearls J Uses Constipation
Dr. Pereyra-Borlongan Diarrhea, Melanosis coli (anthraquinone-containing
SE
laxatives like Senna)
DRUGS THAT PROMOTE UPPER GI MOTILITY SUPPLEMENT: Melanosis Coli
METOCLOPRAMIDE [B] • benign disorder of colonic pigmentation
SimD DOMPERIDONE [C], ERYTHROMYCIN [B] • due to accumulation of brown lipofuscin pigments in
Class Prokinetic agent macrophages
Metoclopramide and domperidone block D2 receptors. • usually result from intake of anthraquinone-containing
MOA Erythromycin stimulates motilin receptors. Increases laxatives (e.g. Senna)
gastric emptying and intestinal motility.
Antiemetic for post-operative / chemotherapy
Uses
vomiting, Diabetic Gastroparesis (drug of choice)
ANTIDIARRHEAL AGENTS
Parkinsonism, Extrapyramidal effects, DIPHENOXYLATE [C]
SE LOPERAMIDE, KAOLIN + PECTIN, COLLOIDAL
Hyperprolactinemia SimD
Notes Domperidone does not cross the BBB (less toxic) BISMUTH, DIFENOXIN
Class Antidiarrheal agent
Correlation to Surgery: Erythromycin is used in bowel preparation prior
Activates opioid receptors in enteric nervous system.
surgery because it binds to the motilin receptor. Diarrhea is a common MOA
side effect of macrolides. Slows motility with negligible CNS effects.
Dr. Calderon Jr. Uses Diarrhea (nonspecific, noninfectious)
SE Drowsiness, Nausea, Paralytic ileus
LAXATIVES Do not use in children less than 4 years of age
SUPPLEMENT: Laxative (increased chance of causing paralytic ileus)
Notes
Reverse ileus by administering Bethanechol
• substance that increases the probability of a bowel movement Difenoxin is the principal metabolite of Diphenoxylate
by several mechanisms:
o irritant or stimulant action on the bowel wall
o bulk-forming action on the stool that evokes reflex ANTIEMETICS
contraction of the bowel ONDANSETRON [B]
o softening action on hard or impacted stool GRANISETRON, DOLASETRON, PALONOSETRON,
SimD
o lubricating action that eases passage of stool through the ALOSETRON, TROPISETRON
rectum Class 5-HT3-receptor antagonist
PSYLLIUM [B] Blocks chemoreceptor trigger zone and enteric
MOA
METHYLCELLULOSE, POLYCARBOPHIL, nervous system 5-HT3 receptors.
SimD Uses Vomiting (post-chemotherapy, postoperative)
MALTODEXTRIN
Class Laxative (bulk-forming) Headache, Dizziness, Constipation, QRS and QT
Indigestible, hydrophilic colloids that absorb water, prolongation (dolasetron only)
SE 5HT3 receptors are found in the CTZ (Chemoreceptor
MOA forming a bulky, emollient gel that distends the colon
and promotes peristalsis trigger zone) on the floor of the 4th ventricle of the brain.
Uses Constipation
Diarrhea The process of vomiting has an interplay of factors. Activating D2 receptor
in the area postrema triggers vomiting, substance P binding neurokinin
Increases the bulk of your stool so that the colon will be can cause pain-induced vomiting, we may give Aprepitant in this case.
SE distended. It will signal the enteric nervous system to Stimulation of the cholinergic receptor in the auditory canal can cause
activate peristalsis for defecation. motion sickness, we can give an anticholinergic Scopolamine and the
famous 5HT3 receptor antagonist in the area postrema Ondansetron for
DOCUSATE [C] post-operative and chemotherapy-induced vomiting. Many drugs can
SimD GLYCERINE SUPPOSITORY, MINERAL OIL cross the area postrema because it is devoid of the blood brain barrier.
Dr. Calderon Jr.
Class Laxative (stool-softening)
Soften stool material, permitting water and lipids to
MOA
penetrate DRUGS USED IN INFLAMMATORY BOWEL DISEASE
Uses Constipation MESALAMINE (5-ASA) [C]
Diarrhea, Aspiration (lipid pneumonitis), BALSALAZIDE, OLSALAZINE, SULFASALAZINE,
SimD
Malabsorption of fat-soluble vitamins (A, D, E, K) MESALAZINE
Class Immunomodulator
These lipid penetrate the stool in its creases → lipid will
SE soften stool → breaks stool into smaller pieces Unknown. Probably inhibits production of eicosanoid
MOA
Usually given to patients after MI so that they don’t have to inflammatory mediators.
do Valsalva when defecating J Uses Inflammatory bowel disease (mild to moderate)
Gastrointestinal upset, Headaches, Arthralgias,
DOCUSATE dinukot ang poops AHA! SE Myalgias, Bone marrow suppression, Malaise,
Dr. Calderon Jr. Hypersensitivity reactions (severe)
Not useful for treating acute flare-ups of disease Selective 5HT4 agonist used for chronic
Used only for mild CONTROLLED cases. Flareups should be PRUCALOPRIDE constipation and intestinal pseudo-
Notes given immunosuppressants such as corticosteroids, TNF obstruction
antagonists, Cyclosporine etc. An anti-muscarinic and Calcium
Channel Blocker (shown to inhibit L-
OTILONIUM
type and T-type calcium channels) used
BROMIDE
to reliever spasmodic pain of the gut,
especially in IBS
Antispasmodic and acts by increasing
the intracellular level of cAMP in the
TIROPRAMIDE
smooth muscular cell and binding of
Ca2+ ions to the sarcoplasmic reticulum.
Increases the availability of endogenous
opioids (enkephalins) by inhibiting
membrane-bound enkephalinase. The
enkephalins in turn mediate their effect
through delta receptor activation that
induces a selective increase in the
Chloride absorption by inhibiting
RACECADOTRIL adenylate cyclase; Unlike other opioid
medications used to treat diarrhea
which reduce intestinal motility,
Racecadotril has an antisecretory effect
– it reduces the secretion of water and
electrolyte into the intestine; reduces
TNF ANTAGONIST: ADALIMUMAB, CERTOLIZUMAB, both the frequency and duration of
INFLIXIMAB acute diarrhea
CORTICOSTEROIDS: BUDESONIDE, HYDROCORTISONE, A probiotic; has been found to produce
METHYLPREDNISOLONE antimicrobial substances that are active
BACILLUS
against gram positive bacteria including
CLAUSII
Staphylococcus aureus, Enterococcus
BILE ACID THERAPY FOR GALLSTONE faecium and Clostridium difficile
URSODIOL (URSODEOXYCHOLIC ACID) A broad-spectrum intestinal anti-
Class Bile Acid NIFUROXAZIDE
infectious agent used for acute diarrhea
Decreases the cholesterol content of bile by reducing Hepatoprotectant; MOA is not yet well
cholesterol secretion; appears to stabilize hepatocyte understood but there are some
canalicular membranes possibly through a reduction proposals:
MOA
in the concentration of other endogenous bile acids or • as antioxidant, scavenger and regulator
through inhibition of immune-mediated hepatocyte of intracellular content of glutathione
destruction. • as cell membrane stabilizers and
Dissolution of small cholesterol gallstones in Px with permeability regulators that prevent
symptomatic gallbladder disease who refuse surgery hepatotoxic agents from entering
or are poor surgical candidates, for prevention of hepatocytes
Uses gallstones in obese Px undergoing rapid weight loss • as promoters of ribosomal RNA
therapy, reduces liver function abnormalities and synthesis, stimulating liver regeneration
improve liver histology in early-stage primary biliary and
SILYMARIN • as inhibitor of the transformation of
cirrhosis
None. Diarrhea is rare stellate hepatocytes into myofibroblasts,
SE Chenodeoxycholate (predecessor) has been associated the process responsible for the
with hepatotoxicity deposition of collagen fibers leading to
cirrhosis.
Anti-inflammatory and anti-
SUPPLEMENT: MISCELLANEOUS GI DRUGS
carcinogenic properties have also been
An amino acid derivative of quinolinone documented; is able to neutralize the
that is used for mucosal protection, hepatotoxicity of several agents,
healing of gastroduodenal ulcers, and including Amanita phalloides, ethanol,
REBAMIPIDE treatment of gastritis; Works by paracetamol and carbon tetrachloride
enhancing mucosal defense scavenging in animal models
free radicals and temporarily activating ROWACHOLÒ Increases biliary secretion, relieves
genes encoding for COX-2 – menthol, spasms of the bile ducts, enhances
A prokinetic benzamide derivative menthone, metabolic liver function and reduces
unlike metoclopramide or alpha pinene, biliary stasis; can also inhibit HMG-CoA
domperidone; inhibit dopamine and beta pinene, reductase enzyme leading to reduced
ITOPRIDE acetylcholine esterase enzyme and have borneol, cholesterol production (maintaining the
gastrokinetic effect; for functional camphene, bile above the saturation level, assisting
dyspepsia and gastroparesis; take cineol and olive dissolution of gallstones and preventing
before meals oil precipitation of further stones)
Changes surface tension of gas bubbles L-ORNITHINE
and causes collapse of foam bubbles, Used for hepatic encephalopathy
SIMETHICONE ASPARTATE
thus allowing easier passage of gas and
preventing gas pockets in GIT ANORECTAL PREPARATIONS
A gastroprokinetic agent that acts as a Potent venotropic drug used in the
selective 5HT4 agonist. Its major active treatment of venous insufficiency;
metabolite, known as M1, additionally increases venous tone, improves lymph
acts 5HT3 antagonist, which accelerates DAFLONÒ
MOSAPRIDE drainage and protects microcirculation;
gastric emptying throughout the whole (Diosmin +
the flavonoids contained in Daflon has
GIT; used for the treatment of gastritis, Hesperidin)
been demonstrated to restrain lysosome
GERD, functional dyspepsia and IBS; enzymes and interfere with enzymes
taken 1-2hrs before meals involved in the flow of arachidonic acid
which causes inflammation. → decreases SULFUR DIOXIDE

synthesis of PGE2 and TXA2 by the CHARACTERISTICS
macrophage. It also demonstrated an • colorless, irritating gas from combustion of fossil fuels
antioxidant activity. All these effects result • forms sulfurous acid on contact with mucous membranes
to the reduction of the pericapillary
permeability and an increase in the EFFECTS
capillary resistance to blood extravasation
• conjunctival and bronchial irritation (bronchospasm)
in the interstitium.
• heavy exposure may lead to delayed pulmonary edema
Policresulen arrests bleeding by
• chronic low-level exposure may aggravate cardiopulmonary
coagulating blood protein and inducing the
disease
muscle fiber of small blood vessels to
contract. The coagulating properties and
TREATMENT
FAKTUÒ acidic pH brings about the antimicrobial
• removal from exposure to SO2
(Policresulen action against E.coli, Staphylococci sp.,
+ Streptococci sp., Pseudomonas aeruginosa, • relief of irritation and inflammation
Cinchocaine) Proteus vulgaris, Candida and other
bacteria. Thus, the wound is protected NITROGEN OXIDES
against infection; Cinchocaine has local CHARACTERISTICS
anesthetic action which relieved pain and • brownish irritant gas formed in fires and silage on farms
itching
EFFECTS
TOXICOLOGY • deep lung irritation and pulmonary edema
• irritation of the eyes, nose and throat
• branch of pharmacology that encompasses the deleterious
effects of chemicals on biologic systems TREATMENT
• no specific treatment is available
TOXIC CHEMICALS IN THE ENVIRONMENT • measures to reduce inflammation and pulmonary edema
SUPPLEMENT: Environmental vs. Occupational Toxicology
Environmental Toxicology OZONE
• area of toxicology that deals with the effects of agents found CHARACTERISTICS
in the environment • bluish irritant gas produced in air and water purification devices
and in electrical fields
Occupational Toxicology
• area of toxicology that deals with the toxic effects of chemicals EFFECTS
found in the workplace
• irritation and dryness of the mucous membranes
• pulmonary function impaired at higher concentrations
• chronic exposure leads to bronchitis, bronchiolitis, pulmonary
fibrosis and emphysema
TREATMENT
• no specific treatment is available
• measures that reduce inflammation and pulmonary edema
Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 SOLVENTS
SUPPLEMENT: Solvents
Classification of Air Pollutants ALIPHATIC HYDROCARBONS
• CARBON MONOXIDE (50%)
• REPRESENTATIVE AGENTS
• SULFUR OXIDES (18%) o halogenated solvents such as carbon tetrachloride,
• HYDROCARBONS (12%) chloroform and trichloroethylene
• PARTICULATE MATTER (e.g. smoke particles, 10%) • EFFECTS
• NITROGEN OXIDES (6%) o CNS depression (nausea, vertigo, locomotor disturbances,
headache, coma)
CARBON MONOXIDE o chronic exposure leads to hepatotoxicity and
CHARACTERISTICS nephrotoxicity
• odorless, colorless gas that competes avidly with oxygen for o long-term exposure to tetrachloroethylene or to
hemoglobin trichloroethane has caused peripheral neuropathy
• affinity of CO for hemoglobin is more than 200-fold greater than • TREATMENT
that of oxygen o removal from exposure and CNS supportive measures
• threshold limit values of CO:
o for an 8-h workday is 25 parts per million (ppm) AROMATIC HYDROCARBONS
o in heavy traffic, the concentration of CO may exceed 100 ppm • REPRESENTATIVE AGENTS
o benzene, toluene, xylene
EFFECTS • EFFECTS
• headache, confusion, decreased visual acuity, cherry red skin, o CNS depression with ataxia and coma
tachycardia, syncope, coma, seizures, death o long-term exposure to benzene is associated with
• collapse and syncope occur when approximately 40% of hematotoxicity (thrombocytopenia, aplastic anemia,
hemoglobin has been converted to carboxyhemoglobin pancytopenia) and hematologic cancers (leukemia)
• prolonged hypoxia can result in irreversible damage to the brain • TREATMENT
and the myocardium o removal from exposure and CNS supportive measures
TREATMENT
• removal of the source of CO and 100% oxygen
• Hyperbaric oxygen accelerates the clearance of CO
PESTICIDES ENVIRONMENTAL POLLUTANTS

Classification of Pesticides POLYCHLORINATED BIPHENYLS
• CHLORINATED HYDROCARBONS • SOURCE
o DDT and its analogs o used extensively in manufacturing electrical equipment
• ACETYLCHOLINESTERASE INHIBITORS • EFFECTS
o carbamates, organophosphates o most common effect is dermatotoxicity (acne, erythema,
• BOTANICAL AGENTS folliculitis, hyperkeratosis)
o nicotine, rotenone, pyrethrum alkaloids o mild increases in plasma triglycerides
o elevated liver enzymes
CHLORINATED HYDROCARBONS DIOXINS
• CHARACTERISTICS • SOURCE
o persistent, poorly metabolized, lipophilic chemicals that o unwanted by-products of the chemical industry
exhibit significant bioaccumulation o chemically stable and highly resistant to environmental
• EFFECTS degradation
o tremors and seizures in acute toxicity • EFFECTS
o chronic exposure increases risk of infertility and breast, brain o most common signs of toxicity are dermatitis and chloracne
and testicular cancer (cystic acneiform lesions that typically form on the face and
• TREATMENT upper body)
o no specific treatment is available o carcinogenic and teratogenic effects in humans
ASBESTOS
CHOLINESTERASE INHIBITORS • SOURCE
• REPRESENTATIVE AGENTS o formerly used widely in manufacturing and building
o carbamates (e.g. aldicarb, carbaryl) • EFFECTS
o organophosphates (e.g. dichlorvos, malathion, parathion) o fibrotic lung disorder (asbestosis) characterized by shortness
• EFFECTS of breath
o DUMBBELSS mnemonic for clinical manifestations o associated with several cancers including lung cancer,
o most common cause of death is respiratory failure mesothelioma and cancers of the gastrointestinal tract
o chronic exposure causes delayed neurotoxicity with axonal
degeneration HEAVY METALS AND CHELATORS
• TREATMENT
o atropine plus pralidoxime
o mechanical ventilation may be necessary
MNEMONIC: Organophosphate Poisoning
What are the signs and symptoms of organophosphate
poisoning?
DUMBBELSS
Diarrhea Excitation (skeletal muscle and CNS)
Urination Lacrimation
Miosis Sweating Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
Bronchospasm Salivation Chelating Agent / Chelator
Bradycardia • a molecule with 2 or more electronegative groups that can form
BOTANICAL INSECTICIDES stable coordinate complexes with multivalent cationic metal
• NICOTINE atoms
o causes excitation followed by paralysis of ganglionic, CNS, and • EXAMPLES: dimercaprol, succimer, EDTA, penicillamine,
neuromuscular transmission deferoxamine
• ROTENONE
o causes gastrointestinal distress when ingested LEAD POISONING
o conjunctivitis and dermatitis after direct contact
ACUTE INORGANIC LEAD POISONING
• PYRETHRUM
o causes contact dermatitis • SETTING
o large quantities may cause CNS excitation (including seizures) o industrial exposures (usually via the inhalation of dust)
and peripheral neurotoxicity o children who have ingested large quantities of chips or flakes
of lead-containing paint (PICA)
• PRESENTATION
HERBICIDES o acute abdominal colic (lead colic) and CNS changes (acute
CHLOROPHENOXY ACIDS encephalopathy)
• includes 2,4-dichlorophenoxyacetic acid and 2,4,5- o high mortality rate
trichlorophenoxyacetic acid (Agent Orange) • TREATMENT
• causes muscle hypotonia and coma o prompt chelation therapy is mandatory
• long-term exposure increases risk of non-Hodgkin's lymphoma
CHRONIC INORGANIC LEAD POISONING (PLUMBISM)
GLYPHOSATE • PRESENTATION
• most widely used herbicide in the world o peripheral neuropathy (wrist-drop), anorexia, anemia, tremor,
• causes significant eye and skin irritation weight loss, gastrointestinal symptoms
• no specific treatment is available o in children, growth retardation, neurocognitive deficits,
• CHARACTERISTICS developmental delay
o Paraquat is a bipyridyl herbicide used extensively to kill weeds • TREATMENT
on farms and for highway maintenance o removal from the source of exposure
• EFFECTS o chelation therapy
o initial effect is gastrointestinal irritation with hematemesis § oral SUCCIMER in outpatients
and bloody stools § EDTA ± DIMERCAPROL in severe cases
o progressive pulmonary impairment (pulmonary fibrosis) o dietary modification (high dietary calcium)
• TREATMENT
o no antidote is available
o gastric lavage and dialysis (less than 50% survival)
ORGANIC LEAD POISONING ORGANIC MERCURY POISONING

• SETTING • SETTING
o usually due to tetraethyl lead or tetramethyl lead contained in o consumption of fish or grains containing methylmercury
antiknock gasoline additives • PRESENTATION
• PRESENTATION o Minamata disease (cerebral palsy, deafness, blindness, mental
o hallucinations, headache, irritability, convulsions, coma retardation)
• TREATMENT • TREATMENT
o decontamination, seizure control o uncertain benefits from chelation therapy
ARSENIC IRON POISONING

• widely used in industrial processes • SETTING
• released during burning of coal o ingestion of ferrous sulfate tablets
• toxicity is entirely due to the trivalent form • PRESENTATION
o vomiting, gastrointestinal bleeding, lethargy, gray cyanosis
ACUTE ARSENIC POISONING o severe gastrointestinal necrosis, pneumonitis, jaundice,
seizures, coma
• PRESENTATION
o chronic excessive intake leads to hemosiderosis or
o severe gastrointestinal discomfort, vomiting, rice-water stools,
hemochromatosis
dehydration, shock
• TREATMENT
o sweet, garlicky odor in breath and the stools
o DEFEROXAMINE is the chelating agent of choice
• TREATMENT
o supportive therapy to replace water and electrolytes
DIMERCAPROL
o chelation therapy with DIMERCAPROL
Class Chelator
CHRONIC ARSENIC POISONING Chelates arsenic and mercury, forming water-soluble
• PRESENTATION MOA
complexes that are excreted in urine
o hair loss, bone marrow depression and anemia, chronic nausea Acute arsenic poisoning, Acute mercury poisoning,
and gastrointestinal disturbances Uses
Chronic lead poisoning (severe)
o transverse bands in nails (Mee’s lines) Transient hypertension, Tachycardia, Headache,
o skin changes (raindrop hyperpigmentation, milk and roses Nausea and vomiting, Paresthesia, Fever, Injection site
complexion, hyperkeratosis) SE
reactions (pain, hematomas), Thrombocytopenia,
o arsenic is a known carcinogen Increased prothrombin time
• TREATMENT Co-administered with EDTA in severe chronic lead
o DIMERCAPROL therapy Notes
poisoning
ARSINE GAS SUCCIMER

• SETTING Class Chelator
o occupational hazard formed during the refinement and Chelates lead, forming water-soluble complexes that
MOA
processing of certain metals used in semiconductors are excreted in urine.
• PRESENTATION Uses Lead poisoning (oral treatment)
o headache, dyspnea, weakness, vomiting, abdominal pain Gastrointestinal distress, CNS effects, Skin rash,
SE
o massive hemolysis (jaundice, hemoglobinuria) leading to Elevation of liver enzymes
pigment overload and renal failure Administered at blood lead concentrations greater
Notes
• TREATMENT than 45 mcg/dL
o exchange transfusion, vigorous hydration, hemodialysis
o chelators are of no clinical value SUPPLEMENT: UNITHIOL
Class Chelator
MERCURY MOA
Chelates arsenic and mercury, forming water-
• SOURCES soluble complexes that are excreted in urine
o mercury-containing materials in dental laboratories Acute severe arsenic poisoning, Acute severe
Uses
o manufacturing of wood preservatives, insecticides and mercury poisoning, Lead poisoning
batteries Dermatological reactions (mild), Vasodilation,
SE
o organic mercury compounds are used as seed dressings and Hypotension

fungicides
PENICILLAMINE
ACUTE INORGANIC MERCURY POISONING Class Chelator, Disease-Modifying Anti-Rheumatic Drug
• SETTING Chelates copper, forming water-soluble complexes
MOA
o inhalation of inorganic elemental mercury that are excreted in urine
• PRESENTATION Copper poisoning, Wilson's disease, Adjunctive
o chest pain, shortness of breath, nausea and vomiting, kidney Uses therapy in gold, arsenic and lead intoxication,
damage, gastroenteritis, CNS damage Rheumatoid arthritis
o life-threatening hemorrhagic gastroenteritis followed by renal Nephrotoxicity with proteinuria, Pancytopenia,
failure SE Autoimmune dysfunction (drug-induced lupus,
• TREATMENT hemolytic anemia)
o intensive supportive care
o prompt chelation with oral SUCCIMER or IM DIMERCAPROL EDETATE CALCIUM DISODIUM (EDTA)
Class Chelator
Chelates lead, forming water-soluble complexes that
CHRONIC INORGANIC MERCURY POISONING MOA
are excreted in urine
• SETTING Uses Chronic lead poisoning (severe)
o inhalation of mercury vapor
Hypocalcemia, Nephrotoxicity (renal tubular
• PRESENTATION SE
necrosis), ECG changes
o loosening of gums and teeth, gastrointestinal disturbances,
Co-administered with dimercaprol in severe chronic
and neurologic and behavioral changes (ERETHISM)
lead poisoning
• TREATMENT Notes
To prevent dangerous hypocalcemia, EDTA is given as
o chelation therapy with SUCCIMER and UNITHIOL the calcium disodium salt
o dimercaprol should not be used
§ may redistribute mercury to the CNS
DEFEROXAMINE • KEY INTERVENTIONS
SimD DEFERASIROX, DEFERIPRONE o correct acidosis and fluid and electrolyte imbalance
Class Chelator o alkaline diuresis or hemodialysis to aid elimination
Chelates iron, forming water-soluble complexes that MNEMONIC: Aspirin Poisoning C-H-A-F-S
MOA
are excreted in urine C-H-A-F-S
Acute iron poisoning, Iron overload states Coma
Uses
(thalassemia, myelodysplastic syndrome) Hyperventilation
Skin reactions (blushing, erythema, urticaria), Acidosis (HAGMA)
Neurotoxicity (e.g. retinal degeneration), Fever
SE Hepatotoxicity, Nephrotoxicity, Coagulopathies, Seizures
Hypotension, ARDS, Increased susceptibility to
infections
SEDATIVE-HYPNOTICS
• CLINICAL FEATURES
MANAGEMENT OF THE POISONED PATIENT o disinhibition initially, later lethargy, stupor, coma
COMMON POISONING SYNDROMES o nystagmus, decreased muscle tone, hypothermia
ANTIMUSCARINIC DRUGS o small pupils, hypotension, decreased bowel sounds in severe
overdose
• KEY INTERVENTIONS
o delirium, hallucinations, seizures, coma, tachycardia,
o airway and respiratory support
hypertension, hyperthermia, mydriasis, decreased bowel
o avoid fluid overload
sounds, urinary retention
o consider flumazenil for benzodiazepine overdose
o use hot as a hare mnemonic
• KEY INTERVENTIONS MNEMONIC: Sedative-Hypnotic Poisoning
o control hyperthermia Hot Hot Hot DeCisioN!
o physostigmine may be helpful, but not for tricyclic overdose Hypothermia Disinhibition
Hypotension Coma
MNEMONIC: Antimuscarinic Poisoning Hypoactive BS Nystagmus
• HOT as a hare (hyperthermia)
• DRY as a bone (decreased secretion) STIMULANTS
• RED as a beet (cutaneous vasodilation) • CLINICAL FEATURES
• BLIND as a bat (cycloplegia) o agitation, anxiety, seizures
• MAD as a hatter (CNS toxicity) o hypertension, tachycardia, arrhythmias
o mydriasis, vertical and horizontal nystagmus with PCP.
CHOLINOMIMETIC DRUGS o skin warm and sweaty, hyperthermia, increased muscle tone,
(ORGANOPHOSPHATE POISONING) possible rhabdomyolysis
o control seizures, hypertension and hyperthermia
o anxiety, agitation, seizures, coma, bradycardia or tachycardia,
pinpoint pupils, salivation, sweating, hyperactive bowel,
muscle fasciculations, paralysis TRICYCLIC ANTIDEPRESSANTS
o use DUMBBELSS mnemonic • CLINICAL FEATURES
• KEY INTERVENTIONS o antimuscarinic effects
o support respiration o use 3 Cs mnemonic
o treat with atropine and pralidoxime • KEY INTERVENTIONS
o decontaminate o control seizures
o correct acidosis and cardiotoxicity with sodium bicarbonate
MNEMONIC: Organophosphate Poisoning o give norepinephrine for hypotension
What are the signs and symptoms of organophosphate o control hyperthermia
poisoning? MNEMONIC: TCA Overdose
DUMBBELSS 3 Cs of TCA Overdose
Diarrhea Excitation (skeletal muscle and CNS) Coma
Urination Lacrimation Convulsions
Miosis Sweating Cardiotoxicity
Bronchospasm Salivation
Bradycardia OSMOLAR GAP
• difference between the measured serum osmolarity and
OPIOIDS predicted osmolarity
• CLINICAL FEATURES • Osm (calculated) = 2Na + Glu/18 + BUN/3
o lethargy, sedation, coma, bradycardia, hypotension, • Osmolar Gap = Osm (measured) – Osm (calculated)
hypoventilation, pinpoint pupils, cool skin, decreased bowel • gap is normally zero
sounds, flaccid muscles • increased osmolar gap is produced by intoxicants of low
o use PCR mnemonic molecular weight such as ethanol, methanol and ethylene glycol
o administer naloxone Cause of increased
KEY LEARNING POINTS
Stool Osmolar Gap
MNEMONIC: Opioid Overdose Methanol Isopropyl alcohol
P-C-R Ethanol Ethylene glycol
Pupillary constriction Diuretics
Comatose state
Respiratory depression SUPPLEMENT: Anion Gap
• difference between the sum of the measured serum
SALICYLATES concentrations of the 2 primary cations and 2 primary anions
• Anion Gap = (Na+ + K+) – (Cl- + HCO3-)
o confusion, lethargy, coma, seizures, hyperventilation, • gap is normally 12–16 mEq/L
hyperthermia, dehydration, hypokalemia, anion gap metabolic • high anion gap is produced by cyanide, ethanol, ethylene
acidosis glycol, ibuprofen, isoniazid, iron, methanol, phenelzine,
o use CHAFS mnemonic salicylates, tranylcypromine, valproic acid and verapamil
SERUM POTASSIUM SUPPLEMENT: Herbal Medicines
• myocardial function is critically dependent on serum potassium COMMON SCIENTIFIC INDICATIONS
level NAME NAME
• drugs that cause hyperkalemia Cough, colds, fever,
Lagundi Vitex negundo
o beta-adrenoceptor blockers, digitalis (in suicidal overdose), asthma
fluoride, lithium and potassium-sparing diuretics Pain, cough, colds,
Yerba Clinopodium
• drugs associated with hypokalemia nausea, dizziness,
Buena douglasii
o barium, beta-adrenoceptor agonists, methylxanthines, most pruritus
diuretics and toluene Blumea Hypertension, kidney
Sambong
balsamifera stones
DECONTAMINATION Tsaang Carmona
Gastroenteritis
• removal of any unabsorbed poison from the skin or gubat retusa
gastrointestinal tract Niyog- Quisqualis Anti-helminthic,
• strategies for decontamination include: niyogan indica headache
o removal of clothing Akapulko Cassia alata Antifungal
o adsorption using activated charcoal Ulasimang Peperonia Gout, rheumatic pains,
o gastric lavage to remove noncorrosive bato pellucida boils, abscesses
o inducing vomiting (emesis) by administering syrup of ipecac Lowers blood
o whole bowel irrigation with a balanced polyethylene-glycol Bawang Alium sativum cholesterol levels,
o cathartics decrease absorption and hasten removal of toxins antiseptic
SUPPLEMENT: Utility of Activated Charcoal Momordica Lowers blood sugar
Ampalaya
EFFECTIVE for NOT EFFECTIVE for charantia levels, fertility regulation
Psidium
• Amitriptyline • Iron Guava Antidiarrheal, antiseptic
guajava
• Barbiturate • Lithium
• Carbamazepine • Potassium BOTANICAL
• Digitalis • Alcohols COMMON INTENDED USE
SUPPLEMENT
• Glycosides • Cyanide Decrease duration and intensity of cold
Echinacea
• Phencyclidine • Corrosive symptoms
• Propoxyphene • Acids Ephedra (Ma Treatment of respiratory ailments such as
Huang) bronchitis and asthma, and a CNS stimulant
• Theophylline • Solvents
For cholesterol lowering and
• Tricyclic antidepressants Garlic
atherosclerosis
• Valproic acid Treatment for intermittent claudication,
Ginkgo
and cerebral insufficiency and dementia
ENHANCEMENT OF ELIMINATION Ginseng
Improvement of physical and mental
• manipulation of urine pH to accelerate renal excretion of weak performance
Limitation of hepatic injury and as an
acids and bases Milk thistle
antidote to Amanita mushroom poisoning
• hemodialysis Improvement in symptoms of benign
• a patient's blood is pumped through a column containing a Saw palmetto
prostatic hyperplasia
semipermeable membrane that allows the removal of many St. John’s Wort Treatment of mild to moderate depression
toxic compounds Improvement of ischemic heart disease and
Coenzyme Q10
SUPPLEMENT: Utility of Hemodialysis for Parkinson disease
Reduction of pain associated with
EFFECTIVE for NOT EFFECTIVE for Glucosamine
osteoarthritis
• Carbamazepine • Amphetamines Decrease jet lag symptoms and as a sleep
Melatonin
• Ethylene glycol • Antidepressants aid
• Lithium • Antipsychotic drugs DRUGS TO AVOID IN
• Methanol • Benzodiazepines SUPPLEMENT:
G6PD DEFICIENT PATIENTS
• Metformin • Calcium channel blockers AMINO ACIDS Arginine
• Phenobarbital • Digoxin Acetanilide
• Salicylate • Metoprolol Aspirin
• Theophylline • Propranolol NSAIDs
• Valproic acid

• Opioids Aminophenazone
ANTIDOTES Metamizole
ANTIDOTE POISON ANALGESICS Phenazone
Phenylbutazone
Acetylcysteine Acetaminophen
Tiaprofenic Acid
Atropine Cholinesterase inhibitors
Paracetamol
Bicarbonate Quinidine, TCAs
Phenacetin
Calcium Fluoride, CCBs Phenazopyridine
Deferoxamine Iron Trivalent Antimony
Digoxin antibodies ANTHELMINTICS Compounds
Digoxin
(Digibind) Stibophen
Caffeine, Theophylline, Chloramphenicol
Esmolol
sympathomimetics Nitrofuran
Ethanol Methanol, Ethylene glycol Furazolidone
Flumazenil Benzodiazepines, Zolpidem Nitrofural
Fomepizole Methanol, Ethylene glycol Nitrofurantoin
Glucagon Beta-adrenoceptor blockers Quinolones
Glucose Hypoglycemics Ciprofloxacin
ANTIBIOTICS
Hydroxocobalamin Cyanide Levofloxacin
Naloxone Opioids analgesics Moxifloxacin
Oxygen Carbon monoxide Nalidixic Acid
Physostigmine Muscarinic receptor blockers Norfloxacin
Pralidoxime Organophosphates Ofloxacin
Protamine sulfate Heparin Sulfonamides
Vitamin K, FFP Warfarin Sulfacetamide
Sulfadiazine
Sulfadimidine
Sulfadoxine
Sulfafurazole
Sulfaguanidine
Sulfamerazine
Sulfamethoxazole
Sulfamethoxypyridazine
Sulfanilamide
Sulfapyridine
Trimethoprim Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
ANTICONVULSANTS Phenytoin SUPPLEMENT: Definition of Terms

ANTIDIABETICS Glibenclamide • SEDATIVES (ANXIOLYTICS)
ANTIDOTES Dimercaprol o drugs that reduce anxiety and exert a calming effect
Acetazolamide o degree of CNS depression should be the minimum
ANTIGLAUCOMA Brinzolamide consistent with therapeutic efficacy
Dorzolamide • HYPNOTICS
Antazoline o drugs that produce drowsiness and encourage the onset
ANTIHISTAMINES Diphenhydramine and maintenance of a state of sleep
Tripelennamine o involve more pronounced CNS depression than sedation
Chloroquine
Mepacrine
Pamaquine
Primaquine
ANTIMALARIALS
Proguanil
Pyrimethamine
Quinidine
Quinine
ANTIMETHEMOGLOBINEMIC
Methylthioninium Cl
AGENTS
Dapsone
ANTIMYCOBACTERIALS Isoniazid
Streptomycin
ANTINEOPLASTIC AGENTS Doxorubicin
Levodopa
ANTIPARKINSONISM AGENTS
Trihexyphenidyl
Procainamide
CARDIAC DRUGS
Quinidine
DIAGNOSTIC AGENT FOR
Tolonium Cl Figure 22-2. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
CANCER
Colchicine The linear red slope for barbiturates, shows that with increasing dose
GOUT PREPARATIONS higher than needed for hypnosis, can potentially lead to general
Probenicid
anesthesia. At even higher doses, it may lead to depression of respiratory
SULFONAMIDE-CONTAINING and vasomotor centers in the medulla, leading to coma and death. For
Sulfasalazine
ANTI-INFLAMMATORY benzodiazepines, it is apparent based on the graph that there is a “ceiling”
Menadiol Sodium Sulfate effect. Therefore, benzos require a proportionately greater dose (if
Menadione possible) to achieve CNS depression more profound than hypnosis, hence
VITAMIN K SUBSTANCES Menadione Sodium a better safety profile.
Dr. Lopez
Bisulfite
Phytomenadione Appreciating the dose response curve above, we can see that
VITAMINS Ascorbic Acid Benzodiazepines plateau. Benzodiazepines are not GABA-mimetic
compared to Alcohol and barbiturates. Benzodiazepine works with the
Aminobenzoic acid physiologic amount of GABA in the brain. cognizant of this, with proper
Mesalazine dose it is less likely to cause medullary depression and coma. GABAA
Fava Beans (Broad receptor.
Beans) Dr. Calderon Jr.
Henna dyes used for • site of actions for your benzodiazepines, barbiturates and other
tattoo & hair related drugs (i.e. Zolpidem, Zaleplon, Eszopiclone)
Naphthalene (pure) This is different from GABAB receptor, of which the agonist is the drug
Rasburicase Baclofen).
Trinitrotoluene Dr. Lopez
OTHERS • functions as a chloride ion channel, which is activated by the
Some Traditional
Chinese Medicine inhibitory neurotransmitter GABA
Berberine
Cattle Gallstone
Bezoar
Chimonanthus flower
Honeysuckle
Pearl Powder
Bear Gall
CNS DRUGS
SEDATIVE-HYPNOTIC DRUGS
SEDATIVE HYPNOTICS
https://qrs.ly/qcboaj7
So that the photo above will make sense. You have to remember that your skeletal muscle relaxation, seizure disorders
Benzodiazepines don’t activate GABAA receptors directly. Instead, they (Clonazepam), status epilepticus (Lorazepam),
bind to a specific site, separate from the site where GABA binds to (BZ site: tranquilizers, Bipolar disorder (Clonazepam),
between g and a subunits as you can see on the image) then act myoclonic and infantile spasm (Clonazepam)
allosterically to ENHANCE affinity of receptors for GABA (the inhibitory
neurotransmitter) → this will lead to INCREASED FREQUENCY OF Anterograde amnesia, Decreased psychomotor skills,
OPENING OF CHLORIDE CHANNEL (MOA of benzos) → based on your SE Unwanted daytime sedation, Respiratory depression,
basic knowledge of physio, it will lead to increased chloride conductance Tolerance, Dependence liability
which will lead to HYPERpolarization of postsynaptic membrane making Additive CNS depression with ethanol, antihistamines,
your postsynaptic neurons are MORE RESISTANT to excitation resulting antipsychotics, opioids and TCAs
to overall CNS depression. GETS????? High dose BZD and Barbs may suppress seizure but at
On the other hand, barbiturates, facilitate action of GABA at multiple sites the expense of marked sedation EXCEPT Clonazepam
of the receptor, increasing the duration of opening of the chloride gated and Phenobarbital
channel (MOA of barbs). Barbiturates also depress actions of glutamic Notes Use lower doses in the elderly when used for insomnia
acid (excitatory neurotransmitter) and high concentrations, appear to be Minor tranquilizers should be avoided in the 1st trim
GABAmimetic. This is the reason why barbiturates can have more
pronounced CNS depressant effects compared to benzos at increasing
due to increased risk of congenital malformations
doses. Remember, comparing the 2, benzos have a greater margin of Maternal use shortly before delivery is associated with
safety compared to your barbs. floppy infant syndrome. Prenatal BZD exposure
Dr. Lopez slightly increases oral cleft risk
MNEMONICS: MOA of benzo vs barbiturates KEY LEARNING POINTS Sleep Disturbance from BZDs
FREnzodiazepine : FREquency What abnormal sleep pattern results from the use of
BarbiDURATes : DURATion benzodiazepines?
Decreased REM sleep
BENZOS VS. BARBITURATES DIAZEPAM [D]

https://qrs.ly/s9blnij CHLORAZEPATE, CHLORDIAZEPOXIDE [D],
SimD
FLURAZEPAM [X], QUAZEPAM [D], FLUNITRAZEPAM
Major inhibitory neurotransmitters? GABA, Glycine Class Benzodiazepine (long-acting)
Major excitatory neurotransmitters? Glutamate Binds GABAA receptor subunits to increase frequency
MOA of chloride channel opening; membrane
hyperpolarization
BENZODIAZEPINES For anxiety disorders, insomnia (Flurazepam),
What are the 5 principle pharmacologic effects skeletal muscle relaxation (e.g. cerebral palsy -
of your benzodiazepines? Diazepam), seizure disorders, tranquilizers, status
1. Anxiolysis Uses
epilepticus (Diazepam), adjunct to anesthesia
2. Sedation and hypnosis (Diazepam), alcohol withdrawal (Diazepam and
3. Anticonvulsant actions Chlordiazepoxide)
4. Spinal cord mediated skeletal muscle relaxation Anterograde amnesia, decreased psychomotor skills
5. Anterograde amnesia (especially Diazepam and Flurazepam), Unwanted
Anterograde amnesia: This effect is very specific to benzodiazepines. SE daytime sedation, Respiratory depression, Tolerance,
So, your different benzos just exhibit varying degrees of this various Dependence liability, rebound insomnia or anxiety,
pharmacologic functions. Painful on injection (diazepam)
Dr. Lopez

Diazepam: MOST effective drug for stopping status

MIDAZOLAM [D] epilepticus attacks as per mother Katzung
BROTIZOLAM, TRIAZOLAM [X], OXAZEPAM [D], Dr. Lopez
SimD
ETIZOLAM Additive CNS depression with ethanol

Class Benzodiazepine (short-acting) Flunitrazepam is used as a date-rape drug
Binds GABAA receptor subunits to increase frequency Decreased REM sleep
MOA of chloride channel opening; membrane Notes Use lower doses in the elderly when used for insomnia
hyperpolarization Minor tranquilizers should be avoided in the 1st trim
Acute anxiety, Panic attacks, Anesthesia induction, due to increased risk of congenital malformations.
Uses Preoperative sedation (especially Midazolam), Maternal use shortly before delivery is associated with
Insomnia (Triazolam) floppy infant syndrome. Prenatal BZD exposure
Anterograde amnesia, decreased psychomotor skills, slightly increases oral cleft risk
SE Unwanted daytime sedation, Tolerance, Dependence
liability, Rebound insomnia/anxiety SUPPLEMENT: Clinical Uses of Benzodiazepines
• Additive CNS depression with ethanol, PREFERRED
CLINICAL USE
antihistamines, antipsychotics, opioids and TCA BENZODIAZEPINE
• Use lower doses in the elderly when used for Anticonvulsant maintenance Clonazepam
insomnia Status epilepticus Lorazepam, Diazepam
• Minor tranquilizers should be avoided in the 1st trim Skeletal muscle relaxation
Diazepam
due to increased risk of congenital malformations. (e.g. cerebral palsy)
Notes
Maternal use shortly before delivery is associated Panic Disorders, Phobia Alprazolam, Clonazepam
with floppy infant syndrome. Prenatal BZD exposure Estazolam, Flurazepam,
slightly increases oral cleft risk Insomnia
Triazolam
• Rapid tissue redistribution (NOT rapid elimination) Anesthesia induction Midazolam, Diazepam
accounts for the short duration of action of this Bipolar disorder Clonazepam
agents Chlordiazepoxide,
Alcohol withdrawal
Diazepam
LORAZEPAM [D]
ALPRAZOLAM [D], ESTAZOLAM [X], CLONAZEPAM MNEMONICS: Chlordiazepoxide
SimD [D], LORMETAZEPAM, NITRAZEPAM, TEMAZEPAM Which benzodiazepine has the longest half-life?
[X] Chlordiazepoxide has longest half-life (36-200 hours) and the
Class Benzodiazepine (intermediate-acting) longest spelling (many letters).
Binds GABAA receptor subunits to increase frequency
MOA of chloride channel opening; membrane Which drugs are considered date-rape drugs?
hyperpolarization • Alcohol (most common)
For anxiety disorders even panic disorders • Flunitrazepam (rohypnol)
Uses • Gamma-hydroxybutyrate (GHB)
(Alprazolam and Clonazepam), insomnia (Estazolam),
SUPPLEMENT: Benzodiazepine Overdose Potent inducer of CYP450 enzymes (true for all
barbiturates)
• DOSAGE
Thiopental has highest lipid solubility (hence rapid
o toxic dose is 1000x the therapeutic dose
entry into the brain <1min and rapid awakening)
o In the elderly, be careful when you’re giving your
benzodiazepines! The overdose of benzos is the most Thiopental used to be the induction agent of choice in
common cause of reversible confusion and amnesia. anesthesia before the discovery of propofol. We will get to
propofol shortly.
Remember the adage: start low, go slow. Dr. Lopez

PENTOBARBITAL [D]
o slurred speech, ataxia, altered (decreased) mental status, SECOBARBITAL [D], AMOBARBITAL [D], BUTALBITAL
respiratory depression SimD
[C], BUTABARBITAL [D], TALBUTAL, APROBARBITAL
• TREATMENT Class Barbiturate (intermediate-acting)
o antidote is flumazenil, a BZD receptor antagonist Bind to GABAA receptor sites (distinct from
o activated charcoal is useless benzodiazepines); increases duration of chloride
MOA channel opening; block glutamic acid
FLUMAZENIL neurotransmission, at high doses can block NA
Class Antidote (benzodiazepine antagonist) channels
Competitive Antagonist at benzodiazepine sites on For insomnia and preoperative sedation
MOA Uses
GABA-A receptor (Secobarbital)
Uses Benzodiazepine overdose Extension of CNS depressant actions, Tolerance,
Agitation, confusion, and precipitates benzodiazepine Dependence liability (greater than benzodiazepines)
SE withdrawal for those with benzodiazepine
SE Contraindication: patients with a history of acute
dependence
intermittent porphyria, variegate porphyria,
Seizures and arrhythmias may occur when
hereditary porphyria and symptomatic porphyria
administered in patient who took both TCAs and
(because barbiturates enhance porphyrin synthesis)
benzodiazepines
Notes Notes Additive CNS depression with ethanol
Don’t forget flumazenil. They like asking about this. How?
What is the DOC for benzodiazepine overdose? A: flumazenil PHENOBARBITAL [D]
Dr. Lopez SimD MEPHOBARBITAL [D], PRIMIDONE [D]
Class Barbiturate (long-acting)
BARBITURATES Bind to GABAA receptor sites (distinct from
SUPPLEMENT: Barbiturates
benzodiazepines); increases duration of chloride
MOA channel opening; block glutamic acid
Structure – activity relationship of barbiturates
neurotransmission, at high doses can block NA
channels
Insomnia, Seizure disorders (phenobarbital), Status
Uses epilepticus (phenobarbital), Hyperbilirubinemias
(Gilbert’s syndrome)
Extension of CNS depressant actions, severe
respiratory and cardiovascular depression, Tolerance,
Dependence liability (greater than benzodiazepines)
SE Contraindication: patients with a history of acute
intermittent porphyria, variegate porphyria,
hereditary porphyria and symptomatic porphyria
Warning: Super good to know. Read only if you want a deeper (because barbiturates enhance porphyrin synthesis)
understanding • Additive CNS depression with ethanol
• Potent inducer of CYP450 enzymes (True for all
• Barbituric acid: the parent compound where all clinically barbiturates)
useful barbiturates came from • Phenobarbital may be excreted unchanged in the
• Pentobarbital and secobarbital (oxybarbiturates): have an urine
Oxygen at the second position Notes • High dose BZD and Barbs may suppress seizure but
• Thiopental and Thiamylal (thiobarbiturates): replacement at the expenses of marked sedation EXCEPT
of the oxygen with sulfur → sulfur makes it more lipid soluble Clonazepam and Phenobarbital
and have a greater hypnotic potency Barbiturates, particularly phenobarbital, is considered the
• Phenobarbital: has a phenyl group at fifth position → DOC for seizures in infants
increases anticonvulsant, but not hypnotic potency Dr. Lopez
• Methohexital: Methyl group on the nitrogen increases CORRELATION: Biochemistry - Porphyria

hypnotic potency but lowers seizure threshold and causes What enzyme is deficient in acute intermittent porphyria?
myoclonus on anesthesia induction HMB Synthase
Remember this contraindication with barbiturate use. They love
THIOPENTAL [C]
asking this in the exams. Just to reiterate, barbiturates (if they will ask
SimD METHOHEXITAL, THIAMYLAL about a specific barbiturate, its usually phenobarbital) may increase
Class Barbiturate (ultrashort-acting) porphyrin synthesis by induction of hepatic d-aminolevulinic acid
Bind to GABAA receptor sites (distinct from synthase (ALA -synthase). This can precipitate symptoms of acute
benzodiazepines); increases duration of chloride intermittent porphyria.
MOA channel opening; block glutamic acid Dr. Lopez
neurotransmission, at high doses can block NA What is the most catastrophic symptom of sedative-hypnotic
channels withdrawal?
Rebound Suicide
Anesthesia induction, Increased ICP, Seizure induction
Uses for epileptic patients undergoing temporal lobe
resection (Methohexital) NEWER HYPNOTICS
Extension of CNS depressant actions, Tolerance, ZOLPIDEM [C]
Dependence liability (greater than benzodiazepines) SimD ZALEPLON [C], ESZOPICLONE [C]
Contraindication: patients with a history of acute Class Imidazopyridine
SE
intermittent porphyria, variegate porphyria, Bind selectively to a subgroup of GABAA receptors,
hereditary porphyria and symptomatic porphyria acting like benzodiazepines to enhance membrane
(because barbiturates enhance porphyrin synthesis) MOA
hyperpolarization, only interact with GABAA receptors
Notes Additive CNS depression with ethanol with alpha-1 subunit
For insomnia and sleep disorder esp. when sleep onset ALCOHOLS
Uses
is delayed
Modest day-after psychomotor depression, Few
SE amnestic effects, Tolerance, Dependence liability (less
than benzodiazepines)
• Effects reversed with FLUMAZENIL
• Lack anti-convulsant, anti-anxiety and muscle
relaxant effects
• Very rapid onset of action
Notes • May decreased REM sleep
• Rebound insomnia on withdrawal from chronic use Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
• Increasing use due to rapid onset with minimal So, know let’s discuss your favorite drug to abuse - ALCOHOL (Miss nyo
effects on the sleep pattern and cause less daytime na ba to go drinking this ECQ?)
Dr. Lopez
cognitive impairment as compared to BZD
MNEMONIC Zolpidem
zzZZzzZZzzZZzz (sleep)
Zolpidem, Zaleplon = Zleep disorders
BUSPIRONE [B]
Class Anxiolytic drug
MOA Partial agonist at 5HT1A and D2 agonist
Uses Generalized anxiety disorder
Nonspecific chest pain, tachycardia, palpitations,
dizziness, nervousness, tinnitus, gastrointestinal
SE
distress, paresthesia, dose-dependent pupillary
constriction
No anticonvulsant
No muscle relaxant properties
Minimal CNS depressant effects
Minimal abuse liability
Minimal tolerance and withdrawal
Slow onset of action (>1week) – hence not for acute 2 MAJOR PATHWAYS FOR ALCOHOL METABOLISM
anxiety I would like you to remember that all alcohol can cause metabolic
Metabolized by CYP3A4 acidosis and can cause CNS depression. Three alcohol of the essence
Safe for pregnant patients should be remembered. Ethylene glycol (antifreeze) and Wood alcohol
Differentiate all 4 drugs. Students always confuse these (methanol) are associated with acute intoxication. It is either you will die
Notes drugs with one another: Buspirone vs Buprenorphine vs or will have grave side effects (Ethylene glycol can cause acute tubular
Benztropine vs Biperiden necrosis and Methadone can cause blindness. Our favorite ethanol is a
favorite question in biochemistry, pathology, and pharmacology. I highly
Buspirone: anxiolytic drug, MOA: partial 5HT1A agonist suggest you integrate alcohol with these subjects.)
Buprenorphine: MOA: agonist-antagonist at opioid Dr. Calderon Jr.
receptors
SUPPLEMENT: Alcohol Metabolism
Benztropine and Biperiden: Remember Tri to Park your
Benz, Bip here? MOA: Anticholinergic used for the treatment Alcohol Dehydrogenase Pathway
of Parkinson’s disease • ALCOHOL DEHYDROGENASE (ADH) catalyzes the
Don’t confused these drugs just because they start with the conversion of alcohol to acetaldehyde
same letter!!! • cytosolic, NAD+-dependent enzyme
Dr. Lopez
• found mainly in the liver and gut
• accounts for the metabolism of low to moderate doses of
SUPPLEMENT: RAMELTEON [C] ethanol
Class Anxiolytic drug: Melatonin Receptor Agonist • Women demonstrate less activity of a stomach ADH than
MOA Activates melatonin receptors (MT1 and MT2 men, with resulting higher blood alcohol levels after oral
receptors) in the suprachiasmatic nuclei in the CNS administration of a similar dose. The generally higher fat and
--> decreased latency of sleep onset blood ratio in women also contributes to the increased effect
Uses Insomnia of ethanol.
SE Dizziness, fatigue, decreased testosterone, • because of the limited supply of the coenzyme NAD+, the
increased prolactin reaction has zero-order kinetics
Notes Minimal rebound insomnia or withdrawal o fixed capacity for ethanol metabolism of 7–10 g/h
symptoms What does 7-10 g of alcohol look like? It is equivalent to 1 bottle of 330
Minimal abuse liability ml of beer, 1 glass of wine (assuming the glass is around 100 ml in
Metabolized by CYP450 (increased levels in the volume) or 1 shot of hard liquor (30 ml of 80 proof to be exact). If you
presence of CYP1A2 or CYP2D6 inhibitors) stick to drinking either of this amount every hour, good chance that
you won’t get drunk (not accounting for the interindividual
differences in alcohol metabolism of course). But try doubling the
MNEMONIC: Buspirone
amount – i.e. 3 bottles of beer every hour, or 5 shots of tequila every
Buspirone for Busy People (Always Anxious) hour, because you are going over the fixed amount of alcohol your
BuSPirone like your BenzodiaZaPine body can process per unit time (Remember it follows zero order
kinetics), then expect you’ll get tipsy then eventually drunk in no time!
Dr. Lopez
SUPPLEMENT: OTHER SEDATIVE-HYPNOTICS
Why is there lactic acidosis and hypoglycemia?

A 1st generation antihistamine that acts Increased metabolism → increase NADH:NAD+ ratio → diverts
HYDROXYZINE as an alternative to Benzodiazepines as pyruvate to lactate & OAA to malate
an anxiolytic After math: inhibits gluconeogenesis and stimulates FA
synthesis
Consequence: hypoglycemia and hepatic fatty change
(hepatocellular steatosis)
Overproduction of lactate → acidosis
Depletion of OAA shuts down the TCA cycle, shunts acetyl-CoA
into ketone production
Breakdown of excess malate increases NADPH and thus FA • GASTROINTESTINAL SYSTEM
synthesis o irritation, inflammation, bleeding and scarring of gut wall
o absorption defects and exacerbation of nutritional deficiencies
o increased risk of pancreatitis
• CENTRAL NERVOUS SYSTEM
o peripheral neuropathy (described as generalized, symmetric)
is the most common neurologic abnormality in chronic
alcoholics
• ENDOCRINE SYSTEM
o gynecomastia, testicular atrophy and salt retention due to
altered steroid metabolism in the cirrhotic liver
• CARDIOVASCULAR SYSTEM
Microsomal Ethanol Oxidizing System (MEOS) o increased incidence of hypertension, anemia and dilated
• responsible for ethanol metabolism at blood levels higher cardiomyopathy
than 100 mg/dL o binge drinking can cause arrhythmias
• MEOS is the system that’s induced during chronic ethanol o ingestion of modest quantities of ethanol (10–15 g/day) raises
consumption HDL levels and may protect against CAD
o induces cytochrome P450 enzyme synthesis and MEOS • FETAL ALCOHOL SYNDROME
activity o Mental retardation (most common)
o development of tolerance to ethanol o growth deficiencies
• acetaldehyde is rapidly metabolized to acetate by ALDEHYDE o microcephaly
DEHYDROGENASE (ADH) o characteristic underdevelopment of midface region
o inhibited by disulfiram, metronidazole, oral hypoglycemics, o associated with heavy consumption of alcohol during the first
and some cephalosporins trimester of pregnancy
o genetic deficiency of aldehyde dehydrogenase in Asians • NEOPLASIA
“Oriental flush” – higher tendency for east Asians (Chinese in o increased incidence of neoplastic diseases in GIT
particular) to get drunk faster is due to the genetic deficiency in the o small increase in the risk of breast cancer
activity of ALDH which results to a noxious reaction when consuming • IMMUNE SYSTEM
alcohol (due to the high acetaldehyde concentration)
Dr. Lopez
o enhances inflammation in the liver and pancreas
o inhibits immune function in other tissues
ACUTE EFFECTS OF ETHANOL o heavy use predisposes to infectious pneumonia
• CNS EFFECTS
o sedation, loss of inhibition, impaired judgment, slurred speech, ALCOHOL INTOXICATION VS. ALCOHOL
ataxia WITHDRAWAL
As you can see with the effects enumerated above, alcohol is a CNS WERNICKE –KORSAKOFF SYNDROME
depressant. Much like your benzos and barbiturates, and with a good
• ataxia, confusion, paralysis of the extraocular muscles
reason. If you look at the MOA of alcohol, it actually has a stimulating
effect on GABA pathways and a negative effect on GLUTAMATE pathways, • seen in intoxication states
the resultant effect is CNS depression. • Associated with thiamine deficiency (Vitamin B1)
Have you ever experienced “BLACKOUTS” (i.e. periods of memory loss that • Rarely seen in the absence of alcoholism
occurs with high levels of alcohol intoxication). I’m sure anyone who has • Ocular signs and ataxia improve with thiamine administration
ever been drunk in their lives has experienced this – there’s a particular • Left with a disabling chronic memory disordered known as
segment of your drinking binge night that you’ve forgotten and you can’t Korsakoff’s psychosis (irreversible memory loss)
recreate after you’ve been sober. How do these blackouts occur? These
blackouts are a result of inhibition of NMDA activation (since ethanol MNEMONIC: Wernicke-Korsakoff Syndrome
inhibits the ability of glutamate to open the cation associated with NMDA
receptors). Interestingly, an IV anesthetic, ketamine, also works via Weird ACO
NMDA antagonism. More on ketamine in the next segments. Wernicke-Korsakoff Syndrome:
Dr. Lopez Ataxia, Confusion, Ophthalmoplegia
• EFFECTS ON OTHER ORGAN SYSTEMS
o slight cardiac depression, vasodilation, hypothermia, uterine What changes in the brain are seen in Wernicke-Korsakoff
muscle relaxation syndrome?
hemorrhagic necrosis of the mamillary bodies
Blood Alcohol Concentration (BAC)
• Treatment:
o maintenance of vital signs
o prevention of aspiration after vomiting
o intravenous dextrose – for hypoglycemia
o thiamine administration to protect against Wernicke-
Korsakoff syndrome
o correction of electrolyte imbalance and hydration – since
patients maybe dehydrated and vomiting
Correlation to Biochemistry: Before giving glucose in a patient with
CHRONIC EFFECTS OF ETHANOL hypoglycemia, we must restore the dehydrogenase enzyme necessary for
carbohydrate metabolism, do give thiamine to resurrect the level of
• TOLERANCE AND DEPENDENCE dehydrogenase. Otherwise, it will just cause more osmotic pull in the cell.
o result of CNS adaptation and increased ethanol metabolism Dr. Calderon Jr.
Case in point: A chronic alcoholic may appear sober or only slightly

intoxicated with a blood level of 300-400, whereas this level on a non- DELIRIUM TREMENS
tolerant or normal individual may present with marked intoxication or
• seen in chronic alcoholics when forced to reduce or discontinue
even coma!
Dr. Lopez alcohol
o cross-tolerance with benzodiazepines and barbiturates • a withdrawal syndrome (characteristic of motor agitation,
o marked psychological and physical dependence anxiety, insomnia and reduction of seizure threshold)
• LIVER DISEASE
o most common complication of chronic alcohol abuse
o reduced gluconeogenesis leads to hypoglycemia
o progressive loss of liver function (reversible fatty liver to
irreversible hepatitis, cirrhosis and liver failure)
o increased severity in females and those with hepatitis B and C
MNEMONICS: Disulfiram Reaction
What drugs can cause disulfiram reaction?
Clara took the Pre-Medical Test in the PM
Chlorpropamide Procarbazine
Cefo Perazone Metronidazole
Mandole
Tetan
MNEMONIC:
DRUGS THAT CAUSE
DISULFIRAM REACTION
https://qrs.ly/6rblnis
Figure 23-2. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018. SUPPLEMENT: ACAMPROSATE
Tremors, anxiety, insomnia is seen 6-8 hours from time of last alcoholic MOA Weak NMDA antagonist and GABAA receptor
consumptions. Frank seizures and hallucinations are expected in 1-5 days activator
from time of last intake. This will eventually culminate in delirium Uses alcohol dependence
tremens, which is characterized by delirium, agitation, autonomic
SE Nausea, vomiting, diarrhea (GI)
instability, low grade fever and diaphoresis.
Dr. Lopez
SUPPLEMENT: Other Alcohols

MNEMONIC: Delirium Tremens METHANOL
H-A-D 48 • Methanol is metabolized by ADH to formaldehyde, which is
Hallucinations Delirium then oxidized to formic acid (toxic)
Autonomic instability 48-72 hours post-discontinuation • SOURCES
o wood alcohol, windshield cleaners, “canned heat,”
• Treatment of Delirium Tremens: commercial solvents, photocopier toner
o substituting a long-acting sedative-hypnotic drug as a • CLINICAL MANIFESTATIONS
replacement for alcohol and then gradually reducing o visual dysfunction, gastrointestinal distress, shortness of
("tapering") the dose of the long-acting drug. breath, loss of consciousness, coma
§ DOC is long-acting benzodiazepine (e.g. diazepam, o accumulation of formaldehyde and formic acid causes
chlordiazepoxide) severe acidosis, retinal damage, and blindness
§ short-acting benzodiazepine with less complex metabolism Treatment of Methanol Poisoning
(e.g. lorazepam) is preferred in patients with compromised • ETHANOL
liver function o retards formation of formaldehyde
o acts as a preferred substrate for alcohol dehydrogenase
PHARMACOLOGIC MANAGEMENT o competitively inhibits the oxidation of methanol
OF CHRONIC ALCOHOLISM • FOMEPIZOLE
o inhibitor of alcohol dehydrogenase
NALTREXONE [C]
SimD NALOXONE [C], NALMEFENE [B], ALVIMOPAN [B], ETHYLENE GLYCOL
METHYLNALTREXONE [B]
• SOURCES
Class Opioid antagonist (systemic and long acting)
o industrial exposure (by inhalation or skin absorption)
MOA Competitively blocks µ, d and k receptors. Rapidly o self-administration (e.g. by drinking antifreeze products)
reverses effects of opioid agonists. • CLINICAL MANIFESTATIONS
Uses Opioid and alcohol dependence (naltrexone only) o severe acidosis and renal damage
SE Pruritus, Nausea, Vomiting, Hepatotoxic o due to accumulation of oxalic acid
Notes Precipitates abstinence syndrome in patients with
opioid dependence Treatment of Ethylene Glycol Poisoning
Naltrexone reduces craving in alcohol, nicotine and • ETHANOL
opioid dependence o competes for oxidation by alcohol dehydrogenase
Naltrexone & Nalmefene have longer DOA • FOMEPIZOLE
Naloxone and Nalmefene is IV (DOA: 12-24 hrs) while o slows or prevents formation of oxalic acid
Naltrexone is PO (DOA: 48h)
Alvimopan & Methylnaltrexone have poor CNS
penetrability → antagonize peripheral effects such as
constipation
Remember:
Naloxone is DOC for opioid overdose vs Naltrexone is DOC
for opioid dependence and chronic alcoholism. Don’t
confuse the two. Same drug class and MOA. Different
indications
Don’t combine with disulfiram because both drugs are
hepatotoxic
Dr. Lopez
DISULFIRAM
MOA Aldehyde dehydrogenase inhibition
Uses Alcohol dependence
SE Nausea, headache, flushing and hypotension
Drug interactions: decreases metabolism of Diazepam,
Phenytoin, Oral anticoagulants and isoniazid Figure 23-2. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
Notes Disulfiram is absorbed rapidly (peak effect is 12
hours) but eliminated slowly (action may persist for
days)
ANTISEIZURE DRUGS
ANTISEIZURE MEDICATIONS
https://qrs.ly/qjboal5
SUPPLEMENT: Seizures
Seizures
• finite episodes of brain dysfunction resulting from abnormal
discharge of cerebral neurons Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
• classification based on seizure characteristics
o simple or complex As you can see from the photo above, drugs used for both primary and
o partial, generalized or partial with secondary secondary generalized tonic clonic seizures is the same and is used for
generalization partial seizures. Making memorization easier. But for the other types of
CLASSIFICATION OF SEIZURE TYPES: generalized seizures, it is determined by their specific subtype.
Dr. Lopez
•Simple partial seizures

Tips for study of antiseizure medications: A possible question could be the
•Complex partial seizures
Partial •partial seizures secondarily
side effects which are not dose dependent and are associated with
(FOCAL) immunogenic response. In my opinion, the most important could be the
generalized
oldest drugs Valproic acid, Phenytoin, and Carbamazepine.
seizures Dr. Calderon Jr.
•GTC Antiseizure Drug

•Absence Na+ Ca2+ K+ GABA Glutamate Others
(AED)
•Tonic NE,
Phenytoin • ° ° °
Ach
Generalized •Atonic
•Clonic and myoclonic seizures Carbamazepine • °
Seizure
•infantile spasms Valproic acid • ° ° °
Phenobarbital ° ° • °
Ethosuximide • °
Benzodiazepine •
Types of Seizures
Gabapentin • °
• SIMPLE PARTIAL SEIZURES Lamotrigine • ° °
o Characterized by minimal spread of abnormal discharge Levetiracetam • • • SV2A
such that consciousness and awareness is preserved Topiramate • • • •
(patient can describe in full detail the attack)
This is a table tabulating the different MOAs of your antiseizure drugs.
o manifested variously as convulsive jerking, paresthesia,
The one in • represents the major MOA and the one in ° represents the
psychic symptoms (altered sensory perception, illusions, minor MOA. Basis for this table is Katzung and Goodman and Gilman.
hallucinations, affect changes) and autonomic dysfunction Dr. Lopez
• COMPLEX PARTIAL SEIZURES

o Localized discharge → becomes more widespread (usually
bilateral)
o impaired consciousness
o usually arise from temporal lobe (susceptible to hypoxia or
infection)
o demonstrate automatisms (fragment of integrated motor
behavior ex. lip smacking, swallowing, scratching, walking
about) of which the patient has no memory
• GENERALIZED TONIC-CLONIC SEIZURES (GRAND MAL)

o tonic phase (less than 1 min) involves abrupt loss of
consciousness, muscle rigidity and respiration arrest
o clonic phase (2–3 min) involves jerking of body muscles,
with lip or tongue biting, and fecal and urinary incontinence
• ABSENCE SEIZURES (PETIT MAL)

o impaired consciousness (often abrupt onset and brief) Big picture of the mechanism of seizure drugs falls under any of the 3
o automatisms, loss of postural tone, or enuresis categories:
o begin in childhood and usually cease by age 20 yrs 1. enhancement of GABAergic (INHIBITORY) Transmission
2. Diminution of excitatory (usually GLUTAMATERGIC) transmission
3. Modification of ionic conductance (Na, K, Ca, etc.) and presynaptic
• MYOCLONIC SEIZURES
transmitter release (SV2A)
o Sudden, brief, shock-like contractions of musculature So, when you study this table, make sure you think of this 3 overarching
(myoclonic jerks) principles for easier memorization (unfortunately guys, I know it’s a lot
of memory work). They do ask 1-2 questions on MOA of seizure drugs. So,
• ATONIC SEIZURES if you care about that, yes. You have to memorize. But one thing they love
o Sudden loss of postural tone asking about, as is true with all the other drugs, is their side effects. So, I
want you to put extra emphasis on that.
Dr. Lopez
• INFANTILE SPASMS
o Epileptic syndrome
o 90% of patients have their first attack before the age of 1
• STATUS EPILEPTICUS
o series of seizures (usually tonic-clonic) without recovery of
consciousness between attacks
o life-threatening emergency
TRADITIONAL ANTISEIZURE DRUGS

PHENYTOIN [D]
SimD FOSYPHENYTOIN, MEPHENYTOIN, ETHOTOIN [D]
Class Anticonvulsant drug (hydantoin)
Major: Blocks voltage-gated Na+ channels
Use dependent effect of Phenytoin: It prolongs that
MOA inactivated state of Na+ channels; also inhibits generation
rapidly repetitive action potentials characteristic of
neurons).

Dr. Lopez
DOC for generalized tonic-clonic seizures, DOC for

Uses partial seizures, status epilepticus, arrhythmias
(Group 1B Action), migraine
Nystagmus (early), Diplopia and Ataxia (most
common), Gingival Hyperplasia (favorite to ask in the
SE boards), Hirsutism, Anemias, Peripheral neuropathy,
Osteoporosis, Teratogen (fetal hydantoin syndrome),
abnormalities in Vit D metabolism
Other MOA of phenytoin: also alters K+, Ca2+ (inhibition of
influx), Glutamate (decrease release), GABA (enhance
release)
Potent inducer of CYP450 enzymes (remember Phen-phen
SOME ANTISEIZURE DRUGS ENHANCE in our inducer mnemonics?)
GABA SYNAPTIC TRANSMISSION Metabolism is NON-LINEAR (elimination shift from 1st
Figure 17-3. Brunton LL. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. 2018
order to zero order at moderate to high dose levels), hence
As described in the previous section, the GABAA receptor is a target of your serum monitoring is necessary
numerous CNS depressants. In the presence of GABA, your primary Notes Fosphenytion is a water-soluble prodrug of phenytoin
inhibitory neurotransmitter, the GABAA receptor opens, allowing an Phenytoin is preferred in prolonged therapy for status
influx of Cl-, which in turn increases membrane polarization. There are epilepticus because it is less sedating
numerous ways to enhance GABA transmission, as indicated in the blue 90% is Highly protein bound
text which represent our ASD (anti-seizure drugs). Some drugs, like Phenytoin is NOT sedating at therapeutic doses (only at
Vigabatrin and Valproate, act by reducing metabolism of GABA. Others, very HIGH levels)
like your Benzos and barbiturates, act on the receptor itself. Others like Phenytoin has an affinity for thyroid binding globulin (can
tiagabine, act by inhibiting its reuptake (action on GAT-1). Gabapentin, interfere with thyroid function)
acts presynaptically to promote GABA release Dr. Lopez
Dr. Lopez
FETAL HYDANTOIN SYNDROME

(TERATOGENIC EFFECT OF PHENYTOIN)
• Wide set eyes
• upturned nose
• mild midfacial hypoplasia / broad mandible
• long upper lip with thin vermilion border
• lower distal digital hypoplasia
SUPPLEMENT: REVIEW!
Let’s review PROTEIN BINDING (a basic pharmacokinetic
principle) and use PHENYTOIN as an example.
REMEMBER:
• Medications that compete for protein-binding sites of
highly BOUND drug (example: PHENYTOIN) can
ANTISEIZURE DRUG-ENHANCED DISPLACE the bound drug → INCREASES in pharmacologic
NA+ CHANNEL INACTIVATION active phenytoin (examples: phenylbutazone, thyroxine,
Figure 17-2. Brunton LL. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. 2018 salicylates)
What’s happening here is they prolong the inactivation of the Na
• Since ALBUMIN is the principal binding protein for acidic
channels, reducing the ability of the neurons to fire at high frequencies.
The text in blue are the different ASDs that work via this mechanism.
drugs (phenytoin is a weak acid), HYPOALBUMINEMIA (as
Dr. Lopez can be seen in renal, hepatic disease, malnutrition) can result
in INCREASED plasma concentrations of phenytoin
CARBAMAZEPINE [D]
SimD OXCARBAZEPINE [C], ESLICARBAZEPINE
Anticonvulsant drug (tricyclic)
Structurally, Carbamazepine is related to Tricyclic
Class antidepressant imipramine. Also, of note, the spatial
conformation of phenytoin and carbamazepine are very
similar.

Dr. Lopez
Blocks voltage-gated Na channels

Since it is structurally similar to phenytoin, its MOA is also
similar (it slows the rate of recovery of Na+ channels from
MOA inactivation and inhibits high frequency repetitive firing of
neurons). It also has an effect on potentiation of voltage
gated K current
Dr. Lopez
ANTISEIZURE DRUG-INDUCED REDUCTION OF CURRENT

DOC for trigeminal neuralgia, DOC for generalized

THROUGH T-TYPE CA2+ CHANNEL
Figure 17-4. Brunton LL. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. 2018 Uses tonic-clonic seizures, DOC for partial seizures, Manic
Drugs like ethosuximide and valproic acid, both being DOC for absence phase (bipolar disorder)
seizures, reduce calcium influx through Thalamic-type (T-type) Ca2+ Diplopia and ataxia (Most common – just like phenytoin),
channels → REDUCES the pace-maker current that underlies thalamic cognitive dysfunction, drowsiness, ataxia, blood
rhythm dyscrasias (i.e. aplastic anemia and agranulocytosis, both
Dr. Lopez SE idiosyncratic reactions), Stevens-Johnson syndrome,
erythematous rash (most common idiosyncratic
reaction), teratogen (spina bifida and craniofacial
anomalies), hyponatremia (Oxcarbazepine)
Potent CYP450 inducer GABAPENTIN [C]
Can cause auto-induction (induce its own metabolism) SimD PREGABALIN [C]
Notes
Oxcarbazepine has less drug interactions Class Anticonvulsant drug (GABA analogue)
Also, highly protein bound (75%) Blocks Ca2+ channels. Decrease glutamate release.
VALPROIC ACID [D for seizure or BPD, X for migraine] Inhibits neuronal discharge from seizure foci.
MOA On the contrary, despite its structural similarity with GABA,
SimD SODIUM VALPROATE
it’s MOA doesn’t directly act on GABA receptors
Class Anticonvulsant drug (branched-chain fatty acid) Dr. Lopez
Blocks high-frequency firing of neurons (similar to

Partial seizures, Neuropathic pain (postherpetic

MOA phenytoin and carbamazepine) via Na channel, Blocks Uses neuralgia) – first line, Migraine, Fibromyalgia
NMDA, Increases GABA levels (Pregabalin)
DOC for bipolar disorder (acute mania), DOC for SE Dizziness, Sedation, Ataxia, Nystagmus, Tremor
generalized tonic-clonic seizures and absence seizure Eliminated in the kidneys in their unchanged form
(especially if with GTC component), partial seizures, Structural analogues of GABA but does not activate
Uses myoclonic seizures, migraine prophylaxis
GABA receptor directly
Consider valproic acid as a broad spectrum anti-seizure Notes Also have the same effect on Ca currents like
drug. Ethosuximide
Dr. Lopez
Pregabalin is also manufactured as a combination drug

GI upset (Most common, in the form of nausea, vomiting,

anorexia), Drowsiness (more so if combined with other with Methylcobalamin for neuropathic pain
SE drugs), Fine Tremor (at high doses), Alopecia, Weight
gain, Hepatotoxicity (Idiosyncratic reaction esp. in LAMOTRIGINE [C]
infants), Teratogen (neural tube defects, spina bifida) SimD ZONISAMIDE [C]
CYP450 INHIBITOR (unlike some of its AED relatives which Class Anticonvulsant drug (phenyltriazine)
Notes are more often than not, INDUCERS) Blocks Na and Ca channels, decreases glutamate,
Highly protein bound (90%) MOA
Dr. Lopez Zonisamide only blocks Na channels
Generalized tonic-clonic seizures, DOC for Partial
PHENOBARBITAL [D]
Uses seizures, Myoclonic seizures, Absence seizures,
SimD PRIMIDONE [D] Bipolar disorder
Class Anticonvulsant drug (barbiturate) Dizziness, ataxia, nausea, rash, headache, SJS / TEN
Bind to GABAA receptor sites (distinct from SE
(lamotrigine), severe skin reaction (Zonisamide)
benzodiazepines); also has actions on Na (limits Primarily undergoes glucuronidation reaction
MOA
sustained repetitive firing in neurons), Ca and Lamotrigine may be used for acute manic phase and as
glutamate Notes prophylaxis in the depressive phase
Generalized tonic-clonic seizures, Partial seizures, Zonisamide may also cause cognitive impairment,
Uses
Status epilepticus, Insomnia, Hyperbilirubinemia confusion and poor concentration
Sedation (most frequent unwanted SE), Extension of CNS
depressant actions, Tolerance, Dependence liability
SE LEVETIRACETAM [C]
(greater than benzodiazepines), Acute intermittent
porphyria Class Anticonvulsant drug (piracetam)
Do not use phenobarbital for absence, atonic and infantile Selectively binds synaptic vesicular protein SV2A →
spasms. It may worsen these seizure types. selectively inhibiting hypersynchronization of
MOA
Barbiturates, particularly phenobarbital, is the DOC for epileptiform burst firing; Modifies synaptic release of
Notes
infants (Katzung) glutamate and GABA. Inhibits Ca channels also
Potent inducer of CYP450 enzymes Generalized tonic-clonic seizures, Partial seizures,
Dr. Lopez Uses
Juvenile myoclonic epilepsy
ETHOSUXIMIDE [C] Ataxia, Asthenia, Dizziness, Sedation, Weakness,
SimD PHENSUXIMIDE, METHSUXIMIDE [C] SE
Irritability, Hallucinations, Psychosis
Class Anticonvulsant drug (cyclic ureide) Drug interactions are minimal (neither an
MOA Decreases Ca2+ currents (T-type) in thalamus inducer/inhibitor). It is not metabolized by CYP450
Uses Absence seizures (DOC) Notes enzymes. This is more of an exception to the rule because
most ASD are either inducers or inhibitors
GI complaints (MC; ex. Nausea, vomiting, anorexia),
SE Lethargy, Headache, Behavioral changes (euphoria)
Dr. Lopez
Ethosuximide reduces low threshold T-type Ca2+ currents in

TOPIRAMATE [D]
the thalamic neurons and inhibition of T-type currents
Notes likely is the mechanism by which ethosuximide inhibits SimD FELBAMATE [C]
absence seizures Class Anticonvulsant drug (monosaccharide derivative)
Dr. Lopez Multiple actions on synaptic function, probably via
DIAZEPAM [D] actions on phosphorylation (Na, K, Ca, GABA, AMPA-
SimD LORAZEPAM [D], CLORAZEPATE MOA glutamate, carbonic anhydrase); Felbamate also
Class Anticonvulsant drug (benzodiazepine) facilitate the inhibitory actions of GABA but its exact
Binds GABAA receptor subunits to increase frequency MOA is still unknown
MOA of chloride channel opening; membrane Generalized tonic-clonic seizures, Absence seizures,
hyperpolarization Partial seizures, Lennox-Gastaut syndrome, West
Uses
Uses Status epilepticus syndrome, Migraine; Felbamate is only for severe
Anterograde amnesia, Painful on injection, Decreased refractory seizure states
psychomotor skills, Unwanted daytime sedation, Drowsiness, Dizziness, Ataxia, Psychomotor slowing,
SE Memory impairment, Paresthesia, Weight loss, Acute
Respiratory depression, Tolerance, Dependence
liability myopia, Glaucoma, Urolithiasis (because of weak
SE
carbonic anhydrase effect); Felbamate causes hepatic
CLONAZEPAM [D] failure and hematotoxicity (can cause ITP, aplastic
Class Anticonvulsant drug (benzodiazepine) anemia)
SimD CLOBAZAM [C] Topiramate is a weak inhibitor of carbonic anhydrase
Binds GABAA receptor subunits to increase frequency Antiseizure drug with the greatest number of mechanisms
MOA of chloride channel opening; membrane of action
hyperpolarization Undergo both hepatic and renal metabolism
Notes Topiramate can also block Na channels, activate a
Absence seizures (second line), Myoclonic seizures,
Uses hyperpolarizing K+ current and potentiate action of GABA
Infantile spasms, Lennox-Gaustat syndrome and block glutamate receptor (particularly AMPA receptor)
Anterograde amnesia, Decreased psychomotor skills, Felbamate may also block glutamate receptors
SE Sedation (prominent), Respiratory depression, Dr. Lopez
Tolerance, Dependence liability

SUPPLEMENT: OTHER ANTICONVULSANTS Stages of Anesthesia (Guedel’s signs):
Depresses CNS, blocks peripheral
neuromuscular transmission →
MAGNESIUM
anticonvulsant effect; decreases amount
SULFATE
of acetylcholine released at the end-plate
by motor nerve impulse
Enhances K channel opening; Adjunctive
treatment for partial seizures; SE:
RETIGABINE
dizziness, somnolence, confusion,
blurred vision
Prolongs inactivation of VG Na channels;
Adjunctive treatment of Lennox-Gastaut
RUFINAMIDE
Syndrome; SE: somnolence, pyrexia,
diarrhea, vomiting
Irreversibly inhibits GABA-transaminase
(GABA-T) which terminates the action of
VIGABATRIN GABA; For GTC seizure, partial seizures Your goal as an anesthesiologist when preparing someone for surgery is
to transition them from stage 1 to stage 3 smoothly and maintain them
and infantile spasms; SE: drowsiness, on stage 3.
dizziness, psychosis, visual field loss Dr. Lopez
Inhibits GABA transporter (GAT-1) in
neurons and glia thus inhibiting its
reuptake, leading to prolongation of
TIAGABINE
GABA effects; For partial seizures; SE:
nervousness, dizziness, depression,
asthenia or weakness
Enhances slow inactivation of Na
channels, blocks effect of neurotrophins;
LACOSAMIDE
For GTC seizure, Partial seizure; SE: Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
dizziness, HA, nausea
AMPA receptor antagonist; used for
partial and GTC seizures; the drug has a INHALATIONAL ANESTHETICS
black box warning that the drug may Inhalational Anesthetics
PERAMPANEL • include nitrous oxide, halothane, desflurane, enflurane,
cause serious psychiatric and behavioral
changes (may cause homicidal or suicidal isoflurane, sevoflurane, and methoxyflurane
thoughts) • partial pressure or "tension” is a measure of concentration of
inhaled anesthetics
CLINICAL USES OF ANTISEIZURE DRUGS o standard pressure of the total inhaled mixture is atmospheric
pressure (760 mm Hg at sea level)
o 50% nitrous oxide in the inhaled air would have a partial
pressure of 380 mm Hg
Minimum Alveolar Anesthetic Concentration (MAC)

• best measure of potency of inhaled anesthetics
• a 1.0 MAC as the partial pressure of an inhalational anesthetic in
the alveoli of the lungs is 50% of the population of non-relaxed
patients remained immobile at the time of surgical skin incision
(standardized painful stimulus)
For comparison, to attain surgical anesthesia (to be more specific, 95%
of your patients will remain immobile to a standardized painful stimulus,
which is skin incision),the suggested value is to maintain your patients at
1.3-1.5 MAC. On the other hand, Ablation of implicit and explicit memory
happens at lower MAC values, around 0.2-0.4 MAC.
Dr. Lopez
• when several anesthetic agents are used simultaneously, their

OTHER CLINICAL USES OF ANTISEIZURE DRUGS MAC values are additive
• BIPOLAR AFFECTIVE DISORDERS: valproic acid (first-line for
Properties of Inhaled Anesthetics
mania), carbamazepine, lamotrigine
• TRIGEMINAL NEURALGIA: carbamazepine (DOC),
oxcarbazepine
• NEUROPATHIC PAIN (POSTHERPETIC NEURALGIA):
gabapentin, pregabalin
• MIGRAINE: gabapentin, phenytoin, topiramate
GENERAL ANESTHETICS
SUPPLEMENT:
General Anesthesia
• A neurophysiologic state characterized by unconsciousness,
analgesia, amnesia, skeletal muscle relaxation, and loss of
reflexes
• An ideal anesthetic should induce rapid, smooth loss of
The MAC values tabulated here are at volume % (unit) a 1.0 MAC value,
consciousness, be rapidly reversible upon discontinuation
which only ensures that your patients won’t move 50% of the time when
and possess a wide margin of safety. you perform a surgical incision. BUT you don’t want to leave it to chance
(a toss coin) to say whether your patients are really fully anesthetized
when you do your surgical incision right? So, let’s take the more
commonly used gas, sevoflurane, as an example. If you want to use
sevoflurane as your maintenance drug for anesthesia, you want to use a
surgical MAC dose which is set at 1.3-1.5 MAC (remember you don’t want
them to move 95% of the time when they cut your patient open right?).
So hence you increase sevoflurane volume concentration % to 2.6-3% (1.0 • Lowest potency (highest MAC) and least cardiotoxicity
MAC for sevoflurane is 2% therefore 1.3-1.5 MAC is 2.6-3 vol%). among inhalational anesthetics
MAC is a measure of potency of your inhaled anesthetics. Therefore, the • Prolonged exposure to nitrous oxide decreases
higher the MAC, the less potent the inhaled anesthetic is. The lower the methionine synthase activity
MAC, the more potent the inhaled anesthetic is. • CNS effect of Nitrous oxide: only inhaled anesthetic that
INCREASES cerebral blood flow and hence INCREASE ICP
Partition coefficient or blood:gas partition coefficient is a measure of
due to activation of sympathetic nervous system
solubility of an inhaled anesthetic for the blood compared with that of
• Cardiac effect of Nitrous oxide: minimal circulatory
inspired gas. In simple terms, it determines the speed of induction (how
depressant (only at high doses) because it activates the
fast you’ll be able to put the patient to sleep) and speed of recovery (how
SNS
soon will the patient wake up the minute you turn off the gas). And the
• Do not use nitrous oxide in the ff groups: middle ear
rule is, the lower the blood:gas partition coefficient, the faster the rate of
surgeries, brain surgeries, bowel surgeries due to
induction/ recovery will be. Examples of these types of gas will be nitrous
expansion of air filled cavities in non-compliant spaces
oxide and desflurane. On the other hand, if the blood:gas partition Dr. Lopez
coefficient is HIGH (example: Halothane) induction will be slower and
rate of recovery will be longer. DESFLURANE
Dr. Lopez Class General anesthetic (inhalational)
SUPPLEMENT: Effects of Inhaled Anesthetics MOA Facilitate GABA-mediated inhibition; block brain
CNS EFFECTS: variable effects depending on MAC levels NMDA and ACh-N receptors
• 0.5 MAC: reduction in cerebral metabolic rate is greater than Uses General anesthesia
vasodilation → cerebral blood flow is decreased SE Bronchospasm (pulmonary irritant), Peripheral
• 1.5 MAC: vasodilation is greater than reduction in cerebral vasodilation
metabolic rate → cerebral blood flow is increased Notes • Desflurane is contraindicated for patients with asthma
o Undesirable for patients with increased ICP (remember and hyperreactive airways
Monroe-Kelly Doctrine?) ex. Brain tumor, ICH and head • Desflurane cannot be used as an agent for induction
because of its pungency and ability to cause
injury bronchospasm
• 1.0 MAC: the effects are balanced and CBF is unchanged • In terms of its PK, desflurane has a low blood:gas
• EXCEPTION: Nitrous OXIDE (see below) partition coefficient, which allows fast induction and
PHYSIO CORRELATION: effect on hyperventilation on ICP prompt awakening
Hyperventilation to decrease PaCO2 → cerebral • Desflurane is unique amongst all inhaled anesthetics in
vasoconstriction → decrease in cerebral blood flow → reduction that it requires a special heated and pressurized
vaporizer because at normal room temperature,
in ICP
desflurane would boil
CARDIOVASCULAR EFFECTS Dr. Lopez
• ALL inhaled anesthetic depress normal cardiac contractility
SEVOFLURANE [B]
→ decrease mean arterial pressure via different mechanisms
Class General anesthetic (inhalational)
o Halothane and enflurane: via myocardial depression
(reduce cardiac output, no change in SVR) Facilitate GABA-mediated inhibition; block brain
MOA
o Isoflurane, Desflurane and sevoflurane: via vasodilation NMDA and ACh-N receptors
(cardiac output is preserved); hence these agents are best Uses General anesthesia
for patients with heart failure Peripheral vasodilation, Renal insufficiency (due to
SE
o EXCEPTION: Nitrous Oxide (see below) Compound A formation), bronchodilation
• Inhaled anesthetics have variable effect on baroreceptor Described as sweet smelling
reflex Compound A formation causes proximal tubular necrosis in
rats (only a theoretical possibility in humans)
o Desflurane and isoflurane: less depression of Notes Best to use sevoflurane for inhalational induction and
baroreceptor reflex → may increase HR on fall of mean induction of asthmatic patients (has the most
arterial pressure bronchodilation effect)
o Halothane, enflurane and sevoflurane: depressed Dr. Lopez
baroreceptor reflex → little effect on heart rate ISOFLURANE [C]

• Inhaled anesthetics reduce myocardial oxygen consumption Class General anesthetic (inhalational)
RESPIRATORY EFFECTS Facilitate GABA-mediated inhibition; block brain
• ALL inhaled anesthetics have BRONCHODILATING MOA
NMDA and ACh-N receptors
properties except Uses General anesthesia
o DESFLURANE (and ISOFLURANE to a lesser extent) – can Catecholamine-induced arrhythmias, Peripheral
cause airway irritability and hence is unsuitable for SE vasodilation, Bronchodilation, Coronary steal
induction syndrome
o Preferred for bronchodilation is sevoflurane and halothane, Coronary steal syndrome, the preferential redistribution
both sweet smelling of blood from ischemic areas to non-ischemic areas, is a
• Characteristic effect on tidal volume and RR: ¯ tidal volume Notes
theoretical possibility for isoflurane use
& RR (resulting in a rapid, shallow breathing) Dr. Lopez
• Inhaled anesthetics INCREASE apneic threshold and ENFLURANE

decrease ventilatory response to hypoxia Class General anesthetic (inhalational)
• ALL inhaled anesthetics produce varying degrees of carbon Facilitate GABA-mediated inhibition; block brain
monoxide from interaction with strong bases in DRY carbon MOA
dioxide absorbers Uses General anesthesia
o Desflurane produces the MOST CO out of all the inhaled Spike-and-wave activity in EEG, muscle twitching,
anesthetics breath-holding, myocardial depression, renal
SE
NITROUS OXIDE insufficiency (due to inorganic fluoride ions),
Class General anesthetic (inhalational) decreased cardiac output, bronchodilation
Facilitate GABA-mediated inhibition; block brain Notes Has pungent odor which limits its use
MOA
NMDA and ACh-N receptors HALOTHANE
Anesthesia for minor surgery and dental procedures, Class General anesthetic (inhalational)
Uses
Balanced anesthesia for major surgery Facilitate GABA-mediated inhibition; block brain
Megaloblastic anemia on prolonged exposure, MOA
Euphoria (laughing gas), bronchodilation, Expansion Uses General anesthesia
SE
of air-filled cavity to NONCOMPLIANT spaces, Catecholamine-induced arrhythmias, Myocardial
diffusion hypoxia depression (direct myocardial depressant effect),
• Nitrous oxide is never used as a SOLE anesthetic agents. SE
Halothane Hepatitis (immune mediated response
Notes It is usually combined with other inhaled local anesthetics characterized by eosinophilia), Bronchodilation
for a more balanced effect
Halothane, amongst all inhaled anesthetics, has the highest KETAMINE [B]
propensity to cause HEPATITIS (via free radical formation General anesthetic (intravenous)
Notes or immune mediated responses) Class Phencyclidine derivative (drug of abuse; a powerful
Halothane is stored in amber colored bottles and thymol is hallucinogen)
added as a preservative to prevent oxidative decomposition
Dr. Lopez MOA NMDA antagonist, weak GABAA modulation
Dissociative anesthesia (analgesia, amnesia and
Uses
METHOXYFLURANE catatonia but with retained consciousness)
Class General anesthetic (inhalational) Cardiovascular stimulation, Hypertension, Increased
Facilitate GABA-mediated inhibition; block brain intracranial pressure, Lacrimation and salivation
MOA SE (pretreatment with anticholinergics), Emergence
delirium (Post-op effects: disorientation, hallucination,
Uses General anesthesia
excitation)
SE Renal insufficiency (due to Fluorine release)
• Dissociative anesthesia seen in ketamine is characterized
Highest potency and lowest MAC among inhalational by thalamocortical dissociation apparent in EEG
Notes
anesthetics (very slow onset and recovery) • Ketamine produces potent analgesia with little
respiratory depression (it is a bronchodilator) making it
MALIGNANT HYPERTHERMIA ideal for asthmatic patients
• Genetic disorder of susceptible individuals upon exposure to • The sympathetic stimulation effect of ketamine can be
Notes traced to its ability to block the reuptake of
volatile anesthetics and succinylcholine
catecholamines “cocaine-like” effect. This ability also
• Signs and symptoms: muscle rigidity, hyperthermia, rapid onset makes it an ideal induction agent of choice for acutely
of tachycardia, hypercapnia, hyperkalemia and metabolic hypovolemic patients
acidosis • You can reduce emergence delirium by pretreatment with
• Pathophysiology: Mutation in the ryanodine receptor (calcium benzodiazepines
release channel in the SR) of the skeletal muscle that results to Dr. Lopez
uncontrolled release of Ca2+ from the sarcoplasmic reticulum

• Caffeine-Halothane contracture test: most reliable test to ETOMIDATE [C]
establish susceptibility General anesthetic (intravenous)
Class
• Treatment: Dantrolene Imidazole derivative
MOA Modulates GABAA receptors containing b3 subunits
Don’t forget MH and its treatment. It’s a fave question in the boards!
General anesthesia (especially in patients with limited
Dr. Lopez
Uses
cardiac or respiratory reserve)
Pain on injection, Myoclonus, Postoperative nausea
INTRAVENOUS ANESTHETICS SE
and vomiting, Adrenocortical suppression
THIOPENTAL [C] • Etomidate, unlike other IV anesthetics, has minimal
SimD METHOHEXITAL, THIAMYLAL effects on CV and respiratory functions upon induction.
General anesthetic (intravenous) HENCE, it can be used as an induction agent of choice for
Class
Barbiturate (ultrashort-acting) unstable patients or those with minimal
Bind to GABAA receptor sites (distinct from cardiopulmonary reserve
MOA benzodiazepines); increases duration of chloride Notes • Etomidate’s propensity to cause adrenocortical
channel opening suppression limits its use. This can be apparent in a single
IV induction dose.
Anesthesia induction (old), Increased ICP ,
Uses • Etomidate does not have analgesic properties
identification of epileptic foci (Methohexital only) • Short DOA
Extension of CNS depressant actions, Tolerance, Dr. Lopez
Dependence liability (greater than benzodiazepines),

Acute intermittent porphyria, Accidental Intra-arterial FENTANYL [C, D of prolonged use or at term]
SE
injection can lead to gangrene (Tx: sympathetic block MORPHINE [C, D of prolonged use or at term],
like stellate ganglion block, injection of local anesthetic SimD
ALFENTANIL, REMIFENTANIL
lidocaine) General anesthetic (intravenous)
• Barbiturates do not produce analgesia, can rather cause
Class
Opioid analgesic
hyperalgesia Interact with µ (mu), d (sigma) and k (kappa)
• Barbiturates are potent cerebral vasoconstrictors → MOA
receptors for endogenous opioid peptides
useful for patients with increased ICP
• Patients claim to experience a garlic and onion taste after
Uses Analgesia
Notes administration Respiratory depression, chest wall rigidity (which may
SE cause impaired ventilation) and constipation
• Do not mix with acidic drugs (neuromuscular blockers) →
can cause precipitates • Antidote is NALOXONE (DOC)/NALTREXONE
• Additive CNS depression with ethanol • Neuroleptanesthesia (analgesia + amnesia) happens
• Potent inducer of CYP450 enzymes when Fentanyl, Droperidol and Nitrous oxide are given
Dr. Lopez together
Notes • Faster recovery: remifentanil
MIDAZOLAM [D] • These drugs have fast onset of action
BROTIZOLAM, TRIAZOLAM, OXAZEPAM, ETIZOLAM, Fentanyl is used mainly as part of anesthesia induction to
SimD
LORAZEPAM block the cardio-stimulatory response to intubation
Dr. Lopez
General anesthetic (intravenous)
Class
Benzodiazepine (short-acting)
PROPOFOL [B]
Binds GABAA receptor subunits to increase frequency
MOA of chloride channel opening; membrane SimD FOSPROPOFOL [B]
hyperpolarization Class General anesthetic (intravenous)
Acute anxiety, Panic attacks, Anesthesia induction, MOA Potentiates GABAA receptors, Blocks Na channels
Uses IV anesthetic induction of choice, General anesthesia,
Preoperative sedation Uses
Anterograde amnesia, Decreased psychomotor skills, Sedation for ICU patients and outpatient procedures
SE Unwanted daytime sedation, Dependence liability, Bradycardia, vasodilation, Hypotension, negative
Postoperative respiratory depression inotropism, pain at injection site, Profound apnea,
SE
Additive CNS depression with ethanol paresthesia in the perianal region (Fospropofol),
Antidote is FLUMAZENIL Propofol Infusion syndrome
Notes Midazolam is a usual adjunct with inhalational • Called the “Milk of Amnesia”
anesthetics and IV opioids, has a slow onset but longer • Contains egg lecithin
DOA Notes • Metabisulfite (an agent to prolong shelf life) can cause
allergic reactions to asthmatic patients and patients with
sulfa allergies
• Propofol causes less “hangover” effect (without any Since LA are weak bases (pKa around 7.5-9), making the pH of the
residual CNS effects) → patients claim they had the best solution more basic (Adding bicarbonate) will increase the concentration
sleep of their lives of the uncharged form. This is employed as a strategy to hasten onset of
• Propofol is ideal because it has a prompt recovery (short block
context sensitive t½) / short duration of action (8-10 Dr. Lopez
minutes) due to REDISTRIBUTION from brain (target o once inside the axon, the ionized (charged) form of the drug is
organ) to less well perfused areas (skeletal muscle) the more effective blocking entity (see explanation below why
• REMEMBER: Zero analgesic properties LA is not useful for I&D of abscesses)
• Propofol has an antiemetic action
• Alternative General anesthetic maintenance for patients
susceptible to malignant hyperthermia
• Fospropofol is the water-soluble prodrug form of propofol
but with slower onset and recovery
Dr. Lopez
SUPPLEMENT: KEY LEARNING POINT:

PROPOFOL INFUSION SYNDROME
• Seen in prolonged high dose infusions (>75ug/kg/min) for
longer than 24 hours
• Cardinal feature: metabolic (lactic) acidosis
TRIVIA – Death of Michael Jackson Figure 26-1. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
MICHAEL JACKSON (1958-2009) KEY LEARNING POINTS Abscesses

immediate COD: acute propofol intoxication Why should you NOT inject local anesthetics into an abscess
contributory factors: drug interactions (lorazepam, during I & D?
midazolam, diazepam) Lidocaine won’t work in an acidic environment (below
pKa = charged form will predominate. Will not be able to
SUPPLEMENT: OTHER ANESTHETICS
cross the cell membrane and exert its action
a novel sedative-analgesic agent,
an alpha-2 adrenoceptor agonist. • blockade of Na+ channels is both state-dependent and use-
Alpha2 receptor agonists decrease dependent
sympathetic tone with attenuation o state-dependent: activated > inactivated > resting
DEXMEDETOMIDINE o use-dependent: rapidly firing fibers are usually blocked before
of the neuroendocrine and
hemodynamic responses to slowly firing fibers
anesthesia and surgery and cause • relationship of local anesthesia with electrolytes
sedation and analgesia o hyperkalemia enhances local anesthetic activity
o hypercalcemia antagonizes local anesthetic activity
Mnemonic for IV Anesthetics lifted from USMLE: the mighty King
Proposes to Oprah: Thiopental Midazolam, Ketamine, Propofol and LOCAL ANESTHESTIC SYSTEMIC TOXICITY
SUPPLEMENT:
Opioids. (LAST)
Dr. Calderon Jr.
• adverse systemic effects following INADVERTENT
INTRAVASCULAR injection or ABSORPTION of LA from site of
LOCAL ANESTHETICS administration
SUPPLEMENT: A good example of this is giving your FULL dose of labor analgesia to
Local Anesthesia an expecting parturient without doing an epidural test dose (3 ml of
• Refers to a loss of sensation in a limited region of the body dilute LA with 1:200,000 epinephrine mixture) or giving it nonetheless
despite a bloody tap (indicating that you’ve punctured an epidural
accompanied by muscle paralysis and sympathetic blockade. vein which has a direct connection to the systemic circulation
• Recovery from clinically relevant local anesthetics should be Dr. Lopez
spontaneous, predictable and without residual effects • CNS EFFECTS
o Initial symptom of circumoral and tongue numbness and
metallic taste
o light-headedness or sedation, restlessness, nystagmus,
generalized tonic-clonic seizures, respiratory and
cardiovascular depression
• CARDIOVASCULAR EFFECTS
o Most local anesthetics have intrinsic vasodilator quality
EXCEPT cocaine, mepivacaine and ropivacaine
MNEMONICS:
o use with caution in patients with preexisting cardiovascular
MNEMONICS – Local Anesthetics disease because they may develop heart block and
How will you distinguish whether local anesthetics are esters arrhythmias
or amides?
ESTERS have only 1 i in their names.
KEY LEARNING POINT
Tetracaine, Procaine, Benzocaine
AMIDES have 2 i’s in their names. Q: What is the treatment to LAST?
Bupivacaine, Ropivacaine, Lidocaine • Treatment should be instituted during earliest sign of toxicity
As long as you know how to count, you can get this right! • Ensure oxygenation (supplemental Oxygen) and ventilation
MNEMONICS – Half Life of Local Anesthetics (control airway if necessary)
Which local anesthetics have the shortest and longest half- • Treat seizures with benzodiazepines
lives? • ANTIDOTE: INTRALIPID
PROCAINE = shortest half-life (1-2 mins) • Avoid propofol (only if hemodynamically stable), beta
A PRO finishes the race fastest. blockers and calcium channel blockers
ROPIVACAINE = longest half-life (4.2 hrs)
At the end of the long ROPe. ESTER LOCAL ANESTHETICS
MOA OF LOCAL ANESTHETICS PROCAINE
SimD NOVOCAINE, CHOLOROPROCAINE [C]
• block voltage-gated Na+ channels, reducing influx of Na+, thereby
preventing depolarization Class Local anesthetic (ester)
• most are weak bases that undergo dissociation Blockade of Na channels slows, then prevents axon
MOA
o more lipid-soluble (nonionized, uncharged) form reaches potential propagation
effective intracellular concentrations more rapidly (uncharged Local anesthesia, Extravasation complications from
Uses venipuncture, Inadvertent intraarterial injections.
means it’s able to cross membranes, important for cell
penetration) Used for very short procedures
Light-headedness, Sedation, Restlessness, Nystagmus, Transient Neurologic Symptoms vs.
KEY LEARNING POINT:
SE Seizures, Respiratory and cardiovascular depression, Cauda Equina syndrome
Antibody formation What is TNS?
Shortest half-life among local anesthetics • Type of neural tissue toxicity produced by LA
Notes
May also be given with epinephrine • Manifests as moderate to severe pain in the lower back,
buttocks and posterior thighs that appears 6-36 hours after
BENZOCAINE [C] complete recovery from an uneventful single shot spinal
SimD BUTAMBEN anesthesia
Class Local anesthetic (ester) • Incidence is greatest following lidocaine injection (about
Blockade of Na channels slows, then prevents axon 30%) making lidocaine fall out of favor for its use in spinal
MOA
potential propagation anesthesia
Uses Local anesthesia, Topical anesthesia What is cauda equina syndrome?
Light-headedness, Sedation, Restlessness, Nystagmus, • This occurs when diffuse injury across the lumbosacral
Seizures, Respiratory and cardiovascular depression, plexus occurs producing varying degrees of sensory
SE anesthesia, bowel and bladder sphincter dysfunction and
Skin irritation, Antibody formation,
Methemoglobinemia (rare but serious SE) paraplegia
Benzocaine is unique in the sense that it is a weak acid, • If pharmacologically caused, it is associated with use of
hence it exist predominantly in the non-ionized form at hyperbaric 5% lidocaine when given via continuous spinal
physiologic pH. anesthesia (hence the use of indwelling catheters for spinal
Notes
Dr. Lopez
anesthesia is not practiced anymore)
Use cautiously when treating sunburns or large areas
of skin PRILOCAINE [C]
Limited for Topical use only SimD MEPIVACAINE [C]
Class Local anesthetic (amide)
COCAINE [C, X if non-medical use] Blockade of Na channels slows, then prevents axon
MOA
Class Local anesthetic (ester), Drug of abuse potential propagation
Blockade of Na channels slows, then prevents axon Local anesthesia, Dental anesthesia, Component of
Uses
MOA potential propagation. Intrinsic sympathomimetic EMLA
activity. Causes vasoconstriction. Light-headedness, Sedation, Restlessness, Nystagmus,
Local anesthesia, Topical anesthesia. Used for SE Seizures, Respiratory and cardiovascular depression,
Uses surgeries involving the ear, nose, and throat Methemoglobinemia
procedures Administer methylene blue if patient develops
Notes
Light-headedness, Sedation, Restlessness, Nystagmus, methemoglobinemia
Seizures, Respiratory and cardiovascular depression, BUPIVACAINE [C]
SE Antibody formation, Abuse liability, Severe SimD LEVOBUPIVACAINE
hypertension, Cerebral hemorrhage, Cardiac
Class Local anesthetic (amide)
arrhythmias, Myocardial infarction, Stroke
Blockade of Na channels slows, then prevents axon
With intrinsic sympathomimetic activity so it does MOA
potential propagation
NOT need an alpha agonist (like epinephrine) to limit
Local anesthesia, Epidural anesthesia, Intrathecal
its systemic absorption Uses
anesthesia
Notes Causes mood elevation due to action on dopamine
Light-headedness, Sedation, Restlessness, Nystagmus,
receptor
Seizures, Respiratory and cardiovascular depression,
All local anesthetics are vasodilators EXCEPT cocaine SE
Severe cardiovascular toxicity, Hypotension,
Topical use only
Arrhythmias
Most cardiotoxic out of all the LA
TETRACAINE [C]
Use with caution in pregnant women and patients with
Class Local anesthetic (ester)
cardiac disease (may cause heart block, arrhythmia
Blockade of Na channels slows, then prevents axon
MOA and hypotension)
Notes Contraindicated in intravenous regional anesthesia
Local anesthesia, Spinal anesthesia, Epidural Treat cardiotoxicity with INTRALIPID/LIPOSOMAL
Uses
anesthesia, Topical ophthalmic anesthesia FORMS (fat emulsion used in TPN)
Light-headedness, Sedation, Restlessness, Nystagmus, Longer DOA than Lidocaine but not given topically or
SE Seizures, Respiratory and cardiovascular depression, IV
Antibody formation
Used primarily for spinal anesthesia (2-3hrs) ROPIVACAINE [C]
Notes Also available as Ophthalmic solution Class Local anesthetic (amide)
Long acting ester LA Blockade of Na channels slows, then prevents axon
MOA
Uses Local anesthesia, Epidural anesthesia
AMIDE LOCAL ANESTHETICS Light-headedness, Sedation, Restlessness, Nystagmus,
LIDOCAINE [B] SE Seizures, Respiratory and cardiovascular depression,
Class Local anesthetic (amide) Cardiotoxicity
Blockade of Na channels slows, then prevents axon Ropivacaine is an S(-) enantiomer of bupivacaine,
MOA
potential propagation rendering it less cardiotoxic to bupivacaine
Infiltration of Local anesthesia, Antiarrhythmic (group Longest half-life among local anesthetics
Uses 1B activity; used post-MI and for digitalis toxicity), Notes
Contraindicated in intravenous regional anesthesia
Component of EMLA Treat cardiotoxicity with INTRALIPID/LIPOSOMAL
Light-headedness, Sedation, Restlessness, Nystagmus, FORMS (fat emulsion used in TPN)
Seizures, Respiratory and cardiovascular depression,
SE KEY LEARNING POINT: EMLA
Transient Neurological symptoms, Cauda equina
syndrome What are the components of EMLA?
Routes: topical, IV, infiltration, spinal, epidural, minor • EMLA stands for Eutectic Mixture of Local Anesthetics
and major peripheral blocks • It is a formulation of 2.5% lidocaine and 2.5% prilocaine,
Given with epinephrine to decrease systemic which permits anesthetic penetration of the keratinized layer
Notes of the skin, producing localized numbness
absorption
PROPARACAINE is another local anesthetic commonly You’re probably wondering why the formulation of EMLA is here? It
used in ophthalmic preparations was actually asked one time in the boards. So, if ever it gets asked
again, at least now.. you know!
Dr. Lopez
SKELETAL MUSCLE RELAXANTS Skeletal muscle relaxation during intubation and

Uses
general anesthesia
SUPPLEMENT: Skeletal Muscle Relaxants
Respiratory paralysis, Apnea, Histamine release
• neuromuscular blocking drugs are used to produce muscle SE
(moderate)
paralysis to facilitate surgery or assisted ventilation Reverse effects with NEOSTIGMINE
• spasmolytic drugs are used to reduce abnormally elevated Metabolized by pseudocholinesterase (just like
tone caused by neurologic or muscle end plate disease Notes
succinylcholine)
Short DOA (10-20mins)
ATRACURIUM [C]
SimD CISATRACURIUM [B]
Nondepolarizing neuromuscular blocker
Class
ISOQUINOLINE
Duration intermediate-acting (45 minutes)
Competitive antagonists at skeletal muscle
MOA
nicotinic acetylcholine receptors
Skeletal muscle relaxation during intubation and
general anesthesia. Relaxation of respiratory
Uses
muscled to facilitate mechanical ventilation in the
TYPES OF NEUROMUSCULAR BLOCKADE
ICU setting
• DEPOLARIZING BLOCKADE Respiratory paralysis, Apnea, Seizures, Histamine
o neuromuscular paralysis that results from persistent SE
release, Bronchospasm
depolarization of the end plate (e.g. by succinylcholine) • Reverse effects with NEOSTIGMINE
• NONDEPOLARIZING OR STABILIZING BLOCKADE • Both atracurium and Cisatracurium undergo
o Competitive antagonists at the acetylcholine receptor of the Hoffman elimination (rapid spontaneous
end plate (e.g. by tubocurarine) breakdown) yielding Laudanosine (seizure causing)
o Increasing doses of Ach can reverse the effect of • Atracurium undergoes ester hydrolysis; whilst
nondepolarizing neuromuscular blocker (i.e. use of Cisatracurium undergoes additionally renal
neostigmine or an indirect acting cholinomimetic) metabolism
Notes • Cisatracurium have less histamine release compared
to atracurium
• Atracurium and Cisatracurium are ideal for hepatic
patients
• Cisatracurium, vecuronium and rocuronium are
NMBs considered as DOC for hemodynamically
compromised patients (less chances for histamine
release causing hypotension)
Dr. Lopez
VECURONIUM [C]
Class
AminoSTEROID
Duration Intermediate-acting (25-40 minutes)
Competitive antagonists at skeletal muscle
MOA
Uses
general anesthesia
SE Respiratory paralysis, Apnea
Reverse effects with NEOSTIGMINE/Suggamadex (less)
Undergoes elimination in bile
Cisatracurium, vecuronium and rocuronium are NMBs
Notes considered as DOC for hemodynamically compromised
patients (less chances for histamine release causing
hypotension)
Dr. Lopez
INTERACTIONS OF DRUGS WITH THE ACETYLCHOLINE

RECEPTOR ON THE END PLATE CHANNEL ROCURONIUM [C]
Figure 27-5. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018. Nondepolarizing neuromuscular blocker
Class
AminoSTEROID
NONDEPOLARIZING NEUROMUSCULAR BLOCKERS Duration Intermediate-acting (36-73 minutes)
TUBOCURARINE [C] - prototype Competitive antagonists at skeletal muscle
MOA
Nondepolarizing neuromuscular blocker nicotinic acetylcholine receptors.
Class Skeletal muscle relaxation during intubation and
Natural alkaloid Uses
Duration Long acting (80 minutes) general anesthesia
Competitive antagonists at skeletal muscle SE Respiratory paralysis, Apnea, Hypersensitivity
MOA • Reverse effects with NEOSTIGMINE
• SUGAMMADEX is a novel reversal agent specifically
Active ingredient of curare (an arrow poison that
for rocuronium (but can also reverse vecuronium and
Uses produced skeletal muscle paralysis when shot at pancuronium to a lesser extent
animals) • Useful in patients with renal impairment
Respiratory paralysis, Prolonged apnea, Ganglion • Cisatracurium, vecuronium and rocuronium are
SE block (hypotension), Histamine release Notes NMBs considered as DOC for hemodynamically
(moderate) with hypotension, Recurarization compromised patients (less chances for histamine
Notes Reverse effects with Neostigmine release causing hypotension)
• Has a rapid onset time (60-120 sec) if dose is
increased to 1.2 mg/kg (x2 intubating dose) → make
MIVACURIUM [C]
it act like succinylcholine (useful for rapid sequence
Nondepolarizing neuromuscular blocker induction)
Class
ISOQUINOLINE Dr. Lopez
Duration Short acting (15-21 minutes) Do you still recall the types of antagonism? Suggamadex is a chemical
Competitive antagonists at skeletal muscle antagonist to rocuronium
MOA
nicotinic acetylcholine receptors Dr. Calderon Jr.
PANCURONIUM [C] CENTRALLY ACTING SPASMOLYTIC DRUGS
Class BACLOFEN [C]
aminoSTEROID
Class Centrally Acting Spasmolytic Drug
Duration Long acting (85-100 minutes)
GABAB agonist. Facilitates spinal inhibition of motor
Competitive antagonists at skeletal muscle MOA
neurons
MOA nicotinic acetylcholine receptors. Moderate block
Severe spasticity due to cerebral palsy, multiple
on cardiac muscarinic receptors. Uses
sclerosis, stroke
Sedation. Weakness. Dizziness. Confusion. Nausea,
Uses general anesthesia, Euthanasia, Lethal injection, SE
Headache
Strychnine poisoning
Respiratory paralysis, Apnea, Tachycardia (has
SUPPLEMENT:
SE atropine like effects), Hypertension,
Recurarization ORPHENADRINE
Reverse effects with NEOSTIGMINE CHLORPHENESIN, METHOCARBAMOL,
Notes SimD
Mechanism for elimination is renal CYCLOBENZAPRINE
Class Centrally Acting Spasmolytic Drug
SUPPLEMENT: APPLICATIONS – Lethal Injection Poorly understood inhibition of muscle stretch
MOA
What are the drugs used in lethal injection? reflex
• Thiopental (5 g) Uses Acute spasm due to muscle injury. Inflammation
• Pancuronium (100 mg) SE Strong antimuscarinic effects
• Potassium chloride (100 mEq)
DIAZEPAM
Class Centrally Acting Spasmolytic Drug. GABA agonist
DEPOLARIZING NEUROMUSCULAR BLOCKERS MOA Facilitates GABAergic transmission in CNS
Phases of Depolarizing Blockade Chronic spasm due to cerebral palsy, stroke, spinal
Uses
• PHASE I (DEPOLARIZATION) cord injury, acute spasm due to muscle injury
o membrane depolarizes w/ initial electric discharge Anterograde amnesia, Decreased psychomotor
o transient fasciculations followed by flaccid paralysis SE skills, Unwanted daytime sedation, Respiratory
• PHASE II (DESENSITIZATION) depression, Tolerance, Dependence liability
o membrane repolarizes but receptor is desensitized to the
effects of acetylcholine TIZANIDINE
Centrally Acting Spasmolytic Drug. Adrenoceptor
SUCCINYLCHOLINE [C] Class
agonist
Depolarizing neuromuscular blocker MOA a2 adrenoceptor agonist in the spinal cord
Class Short acting Spasm due to multiple sclerosis, stroke,
Duration: 6-11 minutes, onset: 60-90 seconds Uses
amyotrophic lateral sclerosis
Agonist at ACh-N receptors causing initial twitch then SE Weakness, Sedation, Hypotension
persistent depolarization. Initial depolarization causes
MOA transient contractions, followed by prolonged flaccid
paralysis. Depolarization is then followed by DIRECT-ACTING MUSCLE RELAXANT
repolarization that is also accompanied by paralysis DANTROLENE [C]
Skeletal muscle relaxation during intubation and Class Direct-acting muscle relaxant
Uses general anesthesia, NMB of choice for rapid sequence Block RyR1 Ca2+-release channels in the sarcoplasmic
MOA
induction reticulum of the skeletal muscle
Post-operative muscle pain, Hyperkalemia (0.5 mEq/L Malignant Hyperthermia, Spasm due to cerebral palsy,
Uses
increase), Increased intragastric pressure leading to spinal cord injury& multiple sclerosis
SE
regurgitation (aspiration), Increased intraocular SE Muscle weakness
pressure, Malignant hyperthermia, Arrhythmia
In terms of structure, Sux is 2 Ach molecules linked side to SUPPLEMENT: OTHER MUSCLE RELAXANT
Notes side. Metabolized by pseudocholinesterase (just like
Antispasmodic drug which relaxes both
mivacurium)
skeletal and vascular smooth muscles and
Dr. Lopez
EPERISONE
reduces myotonia, improves circulation and
MALIGNANT HYPERTHERMIA suppresses pain reflex.
• rare interaction of succinylcholine (and possibly tubocurarine)
with inhaled anesthetics (halothane) DRUGS USED IN PARKINSONISM
• potentially life-threatening condition characterized by massive
calcium release from the sarcoplasmic reticulum of skeletal
muscle
• early sign: contraction of jaw muscles (trismus)
• TREATMENT: Dantrolene
KEY LEARNING POINT: DIBUCAINE NUMBER

Dibucaine number Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
• Measure of ability of a patient to metabolize

Correlation to Pathology: It has been established that Parkinson disease
succinylcholine/mivacurium; reflects the quality of
is secondary to loss of dopaminergic neurons in the nigrostriatal pathway
cholinesterase enzyme and excess cholinergic activity. It presents with the classic triad of
• NMB induced by succinylcholine or mivacurium can be bradykinesia, resting tremors and dystonia. We have 4 ways to address
significantly PROLONGED if a certain individual possesses an this pathology here are as follows:
abnormal genetic variant of pseudocholinesterase 1. Increase level of levodopa
• Interpretation of dibucaine number 2. Dopamine agonist
• Normal: 70 → block lasts less than 11 minutes 3. Increase availability by inhibiting degrading enzymes and
4. Curb the cholinergic excess.
• Heterozygous atypical: 40-60 → block lasts less than an hour The first three will address bradykinesia and number 4 will address
• Homozygous atypical: less than 30 → block lasts around 4-8 dystonia and resting tremors.
hours Dr. Calderon Jr.
SUPPLEMENT: Parkinson Disease LEVODOPA-CARBIDOPA [C]
• also known as paralysis agitans Class Anti-parkinsonism drug (dopamine precursor)
• neurodegenerative disease caused by degeneration of Levodopa – dopamine precursor.
dopaminergic neurons in the substantia nigra MOA Carbidopa – inhibits peripheral metabolism via dopa
• progressive neurologic disease characterized by shuffling decarboxylase.
gait, stooped posture, resting tremor, speech impediments, Uses DOC for Parkinson disease
movement difficulties and an eventual slowing of mental GI disturbance (anorexia, nausea and vomiting),
processes and dementia Arrhythmia, Dyskinesia (choreoathetosis), Behavioral
• The pathological hallmark of PD is the loss of the pigmented, SE changes (anxiety, agitation, confusion, delusion), On-
dopaminergic neurons of the substantia nigra pars off phenomena, Wearing-off phenomena, Postural
compacta, with the appearance of intracellular inclusions hypotension, tachycardia,
known as Lewy bodies. • GI disturbance is due to the peripheral dopamine effects
• The principal component of the Lewy bodies is aggregated α- on the GI system
synuclein • PHENOTHIAZINE (antipsychotics largely used as
antiemetics) SHOULD BE AVOIDED when taking L-dopa
• Treatment strategy: because it may exacerbate PD
o Restore dopaminergic activity in the basal ganglia via • Contraindicated in patients with history of psychosis
dopamine precursors / dopamine agonists / drugs that • Arrhythmia is due to the increased dopamine
inhibit its metabolism Notes peripherally
o Restore balance between cholinergic and dopaminergic • Behavioral changes may be treated with ATYPICAL
neural circuitry, hence the value of your antimuscarinic Antipsychotics (low affinity for D2 receptors such as
agents clozapine, quetiapine, olanzapine, etc.)
• Hypertensive crisis occurs when used with monoamine
oxidase inhibitors
• Use with COMT inhibitors to prolong duration of effect
Dr. Lopez
SEQUENCE OF NEURONS INVOLVED IN PARKINSONISM

As you can see from the photo above, what happens in parkinsonism
is there is loss of dopaminergic neurons, as shown by the dotted red
line (70-80% loss for it to be clinically significant), which is
responsible for inhibiting excitatory cholinergic output from the
striatum.
Dr. Lopez
MNEMONICS – Parkinson Disease

What are the primary signs of Parkinson Disease?
PARKINSON DISEASE: It’s a TRAP!
Tremor Akinesia
Rigidity Postural instability
DRUG-INDUCED PARKINSONISM
• occurrence of reversible Parkinsonian symptoms in patients
taking the following drugs:
o Typical antipsychotic drugs (MOA: Dopamine antagonist)
o RESERPINE (MOA: depletes catecholamine stores)
o MPTP (methylphenyltetrahydropyridine) (MOA: protoxin
damaging dopaminergic neurons)
FATE OF ORALLY ADMINISTERED LEVODOPA AND THE
EFFECT OF CARBIDOPA
If levodopa is given ALONE, majority of it will be converted peripherally

to dopamine and it won’t reach the site where it matters, the brain. In
order for the drug to be effective, it has to be able to cross the BBB and be
centrally converted to dopamine. Seen above are 2 scenarios: one with
levodopa alone and the other with carbidopa. As you can see, with the
combination of levodopa and carbidopa, peripheral metabolism of
levodopa is reduced, more dopa is available for entry to the brain.
Dr. Lopez
Problems encountered with levodopa

SUPPLEMENT:
treatment
• As treatment is continued, patients eventually become less
responsive to L-dopa
• Begins to diminish after 3-4 years of therapy
• ON-OFF PHENOMENA (unrelated to timing of doses)
o alternating periods of improved mobility and akinesia,
occurring over a few hours to days during treatment
• WEARING-OFF PHENOMENA (related to timing of doses)
o deterioration of drug effect in between medication doses
(off periods are characterized with marked akinesia which
PHARMACOLOGIC STRATEGIES FOR DOPAMINERGIC
alternate with few hours of on periods characterized by
THERAPY OF PARKINSON’S DISEASE
Figure 28-5. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018. improved mobility )
Always refer to this figure when individual drugs are discussed o due to progressive destruction of nigrostriatal neurons that
Dr. Lopez occurs with disease progression
BROMOCRIPTINE [B] Since they are SELECTIVE MAO B inhibitors, these drugs do
SimD PERGOLIDE [B], CABERGOLINE [B], PIRIBEDIL not exhibit the “CHEESE EFFECT” (i.e. hypertensive crisis
Anti-parkinsonism drug (dopamine agonist) seen with ingestion of tyramine rich food such as cheese
Class whilst taking a NON SELECTIVE MAO inhibitor). Remember
Ergot derivatives
that.
Partial agonist at dopamine D2 receptors in brain, D2
MOA Dr. Lopez
agonism leads to inhibition of prolactin release Selegiline is converted to an amphetamine metabolite. It is prudent to
Parkinson’s disease, Levodopa intolerance, know this not to misidentify a patient using amphetamine.
Uses
Hyperprolactinemia
Dr. Calderon Jr.
Anorexia, nausea, vomiting, dyskinesia, postural ENTACAPONE [C]

hypotension, behavioral changes, erythromelalgia SimD TOLCAPONE [C]
SE
(Bromocriptine), pulmonary infiltrate Class Anti-parkinsonism drug (COMT inhibitor)
(Bromocriptine) Block L-dopa metabolism by inhibiting catechol-O-
Piribedil can also act as a D3 agonist and A2 adrenergic methyltransferase in periphery (both) and CNS
MOA
antagonist. It is particularly used for the alleviation of (tolcapone only). Net result: Prolongs response to
Notes
tremors. It has also been used for circulatory disorders levodopa.
such as intermittent claudication Parkinson’s disease (wearing-off phenomena), as
Uses
PRAMIPEXOLE [C] adjunct to levodopa
SimD ROPINIROLE [C] Dyskinesias, Gastrointestinal distress, Postural
Anti-parkinsonism drug (dopamine agonist) Hypotension, Sleep disturbance, Orange urine,
Class SE Hepatotoxicity (tolcapone only), Neuroleptic
Non-Ergot
Partial agonist at dopamine D2 (pramipexole) and D3 malignant syndrome, Rhabdomyolysis, Nausea,
MOA Confusion
receptors (ropinirole) in brain.
Since inhibition of dopa-decarboxylase upregulates other
Parkinson disease (addresses affective symptoms of
Uses pathways of levo dopa metabolism (COMT pathway),
PD), Restless legs syndrome, On-Off phenomenon inhibitors of COMT will improve therapeutic response to
Anorexia, Nausea, Vomiting, Dyskinesias, Postural levo dopa treatment by diminishing its peripheral
hypotension, Behavioral changes, Confusion, Notes metabolism (particularly its conversion to 3-OMD by COMT
SE
Compulsive gambling, Hypersexuality, Overeating, pathway)
Uncontrollable tendency to fall asleep Remember, Entacapone only acts in the periphery while
The impulse control disorders arising from the use of these Tolcapone acts both in the periphery and CNS.
Dr. Lopez
drugs is attributed to the activation of D2/D3 receptors in
the mesolimbic pathways of the brain. Such symptoms
abate with discontinuance of use. AMANTADINE [C]
Dr. Lopez Class Anti-parkinsonism drug, Anti-influenza (antiviral)
• Contraindicated in patients with active peptic ulcer Potentiate dopaminergic function by influencing the
Notes disease, psychotic illness, or recent myocardial synthesis, release, or reuptake of dopamine.
infarction MOA
Antagonizes the effects of adenosine at adenosine A2A
• Behavioral changes are more prominent compared receptors
to levodopa Uses Parkinson disease, Influenza
• Decrease dose in renal dysfunction Behavioral changes (restlessness, agitation, insomnia,
• Neuroprotective hallucination, acute toxic psychosis), Livedo
SE
• Ropinirole is metabolized by CYP1A2 reticularis, Gastrointestinal disturbances, Urinary
On a clinical standpoint, if we are to use a dopamine agonist, we prefer to retention, Postural hypotension, Peripheral edema
use the non-ergots because of lesser side effect and they have an anti- May improve bradykinesia, rigidity and tremor
Notes
oxidant property compared to ergot dopamine agonist. We may utilize Has anti-muscarinic action
the direct agonist to cases of prolactinoma or acromegaly. These ergots
can manifest with enhance side effects. MNEMONIC Livedo Reticularis

Dr. Calderon Jr. What drugs can cause livedo reticularis? A man reads FHM
APOMORPHINE [C] and GQ!
Class Anti-parkinsonism drug (dopamine agonist) Amantadine Gemcitabine
Agonist at dopamine D2 receptors. Antagonist at 5-HT Hydroxyurea Quinidine
MOA
and alpha adrenoceptors. Minocycline
Rescue treatment for off-periods of Parkinson’s
BENZTROPINE
Uses disease (temporary relief), Alcoholism, Opiate
SimD BIPERIDEN [C], TRIHEXYPHENIDYL, PROCYCLIDINE
addiction, Erectile dysfunction, Alzheimer’s disease
Profound Hypotension, Loss of consciousness, QT Class Antiparkinsonism drug (anticholinergic)
SE prolongation, Severe nausea, Dyskinesias, Decrease the excitatory actions of cholinergic neurons
Drowsiness, Sweating MOA on cells in the striatum by blocking muscarinic
Use only when other dopamine agonists and COMT receptors
inhibitors have failed As adjunct for Parkinson’s disease and Extrapyramidal
Notes Uses
Premedicate with TRIMETHOBENZAMIDE to prevent symptoms caused by antipsychotics
severe nausea Drowsiness, Inattention, Confusion, Delusions,
SE Hallucinations, Atropine-like effects (urinary
SELEGILINE [C] retention, constipation, dry mouth)
SimD RASAGILINE [C] Remember the mnemonic of your anti muscarinic agents
Class Anti-parkinsonism drug (MAO type B inhibitor) used for Parkinson disease: TRI (TRIhexiphenydyl) to PARK
Selective inhibitors of monoamine oxidase type B → (drugs for PARKinsons) your BENZ (BENZtropine), BIP
MOA decreased degradation of dopamine. Increases (BIPeriden) here.
response to levodopa/carbidopa. Notes
Dr. Lopez
Improve tremor and rigidity, with little effect on

Adjunct for waning effect treatment to levodopa for
bradykinesia
Uses Parkinson’s disease, wearing off or on-and-off
Exacerbate tardive dyskinesias that result from
phenomenon
prolonged use of antipsychotic drugs
Insomnia, Mood changes, Dyskinesias,
SE
Gastrointestinal distress, Hypotension
SUPPLEMENT: OTHER DRUGS FOR PARKINSON’S DISEASE
Combination with meperidine causes agitation,
delirium and death (fatal reaction) Dopamine agonist; used for Parkinson’s
Serotonin syndrome occurs when used with SSRIs, disease and Restless Leg Syndrome;
Notes TCA and Meperidine ROTIGOTINE formulated as a once-daily transdermal
Higher doses of selective MAO-B inhibitors can also patch which provides a slow and constant
inhibit MAO-A receptor supply of the drug over 24 hours
SUPPLEMENT: DRUGS FOR HUNTINGTON’S DISEASE • ATYPICAL ANTIPSYCHOTICS
Deplete amine transmitters o MOA: Block 5HT2A receptors > D2 receptors
especially Dopamine from nerve o HETEROCYCLICS (clozapine, loxapine, olanzapine,
endings by reversibly inhibiting risperidone, quetiapine, ziprasidone, aripiprazole)
human vesicular monoamine o Atypical antipsychotics address both positive and
TETRABENAZINE, negative effects of schizophrenia
transporter type 2 (VMAT2)
RESERPINE o Atypicals have a lesser propensity to cause EPS compared to
resulting in decreased uptake of
monoamines; reduces chorea its typical counterparts, but has a higher propensity in causing
severity; SE: hypotension, sedation, metabolic derangements (weight gain, endocrine problems)
depression, diarrhea SUPPLEMENT: Dopamine
SUPPLEMENT: DRUGS FOR TOURETTE’S SYNDROME Dopamine Hypothesis
• schizophrenia is caused by a relative excess of dopamine in
Block central D2 receptors, reduce
specific neuronal tracts in the brain
vocal and motor tic frequency &
HALOPERIDOL, severity ; SE: parkinsonism and other o many antipsychotic drugs block brain dopamine receptors
PIMOZIDE dyskinesias, sedation, blurred vision, (especially D2 receptors)
o dopamine agonist drugs (e.g. amphetamine, levodopa)
dry mouth, GI disturbance, Pimozide
may cause arrhythmia exacerbate schizophrenia
• not fully satisfactory because antipsychotic drugs are only
partly effective in most patients
ANTIPSYCHOTIC AGENTS AND LITHIUM Dopamine Receptors
• five different dopamine receptors (D1–D5) grouped into 2
separate families:
o D1 receptor family: D1,D4, D5
o D2 receptor family: D2 and D3
• D2 receptors are found presynaptically and postsynaptically
in the caudate putamen, nucleus accumbens, cerebral cortex
and hypothalamus
o target of action of TYPICAL antipsychotics
o higher chance of blocking POSITIVE SYMPTOMS of
schizophrenia (hence the immediate quieting capability of
typical antipsychotics)
o this happens at the expense if HIGHER chances of EPS
(usually occurs at blockade of 80% and more)
Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 Dopaminergic Tracts
Correlation to Psychiatry: Schizophrenia means split personality. It was • MESOLIMBIC-MESOCORTICAL pathway: cell bodies in
established that the pathology behind this is the excess activity of the ventral tegmentum to limbic system and neocortex
dopaminergic neuron in the mesolimbic and mesocortical pathway. We o regulating mentation and mood
have to broad categories for signs and symptoms of psychosis: soft or o where most of the antipsychotic actions of dopamine
negative and hard or positive. antagonists lie
Hard symptoms/ Positive (HIDES) • NIGROSTRIATAL pathway: from substantia nigra to dorsal
Hallucination, Illusion, Delusion, Excitement and Suspiciousness. striatum
For negative signs, think of social depression (anhedonia, avolition, o Responsible for coordination of voluntary movement
anergia)
o Blockade of D2 receptors in this pathway is responsible for
We have two categories for antipsychotics: Typical/traditional drugs extrapyramidal symptoms
address the positive symptoms and are associated with extrapyramidal • TUBEROINFUNDIBULAR pathway: arises from the arcuate
effects (think of pseudoparkinsonism) and atypical/newer drugs address
nuclei and periventricular neurons and release dopamine
both hard and soft signs and are less associated with EPS
Dr. Calderon Jr. into the peripheral circulation
o control of prolactin release

CLASSIFICATION OF ANTIPSYCHOTICS
• TYPICAL (CLASSICAL) ANTIPSYCHOTICS Remember from physiology: Dopamine released by these neurons
o MOA: Block more D2 receptors > 5HT2A receptors physiologically INHIBITS prolactin secretion from the anterior
o Different classes: PHENOTHIAZINES (chlorpromazine, pituitary. This explains why to varying degrees, both typical and
atypical antipsychotics will have, as side effect, symptoms of
thioridazine, fluphenazine), THIOXANTHENES (thiothixene)
hyperprolactinemia (amenorrhea, galactorrhea and impotence)
and BUTYROPHENONES (haloperidol) Dr. Lopez
o Addresses positive symptoms (Hallucinations) of • MEDULLARY-PERIVENTRICULAR pathway: consists of
schizophrenia but not much effect on negative symptoms neurons in the motor nucleus of vagus nerve with ill-defined
(emotional blunting, social withdrawal, lack of motivation) projections
o High potency typical antipsychotics (i.e. Haloperidol, o eating behavior
droperidol): higher chances of causing extrapyramidal • INCERTOHYPOTHALAMIC pathway: forms connections
symptoms (EPS) from the medial zona icerta to the hypothalamus and
o Low potency typical antipsychotics (i.e. Thioridizine, amygdala
Chlorpromazine): lower chances of causing EPS, more likely to o anticipatory motivational phase of copulatory behavior
cause sedation and postural hypotension (due to alpha
receptor blockade)
TOXICITIES OF ANTIPSYCHOTICS
SUPPLEMENT: OTHER DRUGS FOR PARKINSON’S DISEASE
DISORDER TIMING CHARACTERISTIC Tx
4hrs- Retrocollis, opisthotonos, oculogyric
Acute Dystonia Diphenhydramine
4days crisis
4days- Tremor, rigidity, akinesia, postural
Parkinsonism Benztropine
4mos instability
4mos-
Rabbit Syndrome Perioral tremor Benztropine
4yrs
Tardive Dyskinesia Repetitive involuntary movement
supersensitvity of the postjunctional DA receptors in the CNS 4mo-4yr (tongue protrusion, lip None
leading to relative decrease in cholinergic activity smacking/pursing)
Restlessness, pacing, sitting up and Decrease Dose,
Akathisia Any time
down Diphenhydramine
Withdraw drug,
Neuroleptic Malignant Syndrome Fever, Encephalopathy, Vitals
Any time dantrolene, diazepam,
extreme sensitivity to EPS effects of antipsychotics unstable, Elevated CPK, Rigidity
dopamine agonists
When studying each individual drugs, try to relate it with the respective receptor binding profile for each drug at the side notes aspect of your handout to get
a better sense of the adverse effects associated with the individual drugs.
Dr. Lopez
TYPICAL ANTIPSYCHOTICS HALOPERIDOL [C]

** may also be used for pruritus and as sedatives ** SimD DROPERIDOL [C]
Typical antipsychotics are derived from phenothiazines Class Typical antipsychotic (butyrophenone)

Dr. Calderon Jr. MOA Block of D2 receptors ≫ 5-HT2 receptors
CHLORPROMAZINE [C] Schizophrenia and other psychotic disorders, BPD
THIOTHEXENE [C] (Thioxanthene), FLUPENTIXOL Uses (Manic phase), Huntington's disease, Tourette's
SimD (Thioxantene), PROMETHAZINE, PROCHLORPERAZINE syndrome
[C], LEVOMEPROMAZINE Extrapyramidal dysfunction (major, D2), Tardive
Class Typical antipsychotic (Phenothiazine) dyskinesia (D2), Hyperprolactinemia (D2 in
MOA Block of D2 receptors ≫ 5-HT2 receptors SE
tuberoinfundibular pathway), Neuroleptic Malignant
Schizophrenia and other psychotic disorders, Manic syndrome
Uses phase of BPD, antiemetic (Promethazine and Specific Receptor antagonism binding profile:
prochlorperazine only)
D2 > a1 > D4 > 5HT2A > D1 > H1
Postural hypotension (a) , Marked sedation (H1),
Extrapyramidal dysfunction (D2), Tardive dyskinesia Haloperidol causes the most extrapyramidal symptoms of
(D2), Hyperprolactinemia (D2 in tuberoinfundibular Notes all typical anti-psychotics
SE Weakest autonomic effects
pathway), Failure of ejaculation (a), Corneal and lens
Least sedating among typical antipsychotics
deposits, Neuroleptic malignant syndrome, Contact
Some a-blockade but minimal M receptor blockade
dermatitis, (a) Dr. Lopez
Specific Receptor antagonism binding profile:
Haloperidol (Haldol) is a major tranquilizer given intramuscularly. It has
a1 > 5HT2A > D2 = D1 the highest potential for EPS and neuroleptic malignant syndrome.
Remember: Histamine antagonism accounts for relief of Dr. Calderon Jr.
pruritus and sedating effect
NOTES Chlorpromazine: Prototype of all antipsychotics ATYPICAL ANTIPSYCHOTICS
Levomepromazine blocks a variety of receptors including ** atypicals may be used for mania and psychotic symptoms in Alzheimer's dementia
adrenergic dopamine, histamine, muscarinic and and Parkinson disease **
serotonin receptors CLOZAPINE [B]
Dr. Lopez
Class Atypical antipsychotic (Dibenzodiazepine)
THIORIDAZINE [C] MOA Block of 5-HT2 receptors ≫ D2 receptors
FLUPHENAZINE [C], PERPHENAZINE [C], Schizophrenia (DOC for refractory and suicidal
Uses
SimD schizophrenia) and other psychotic disorders
TRIFLUOPERAZINE [C]
Extrapyramidal dysfunction (less),
Class Typical antipsychotic (Piperdine)
Hyperprolactinemia (less), Postural hypotension,
MOA Block of D2 receptors ≫ 5-HT2 receptors
SE Weight gain, Hyperglycemia (diabetes mellitus),
Uses Schizophrenia and other psychotic disorders
Hyperlipidemia, Myocarditis, Agranulocytosis,
Extrapyramidal dysfunction (D2), Tardive dyskinesia Seizures, Ileus, Hypersalivation (sialorrhea)
(D2), Hyperprolactinemia (D2 in tuberoinfundibular
pathway), Anticholinergic effects, Failure of
D4 = a1 > 5HT2A > D2 = D1
SE ejaculation (a), Postural hypotension (a), Retinal
• Clozapine is the prototype of your atypicals
deposits (Thioridazine), Cardiotoxicity (QT • Relapse after discontinuation is rapid and severe
prolongation – arrhythmias - Thioridazine), decreased • Clozapine and Olanzapine has the highest tendency to
seizure threshold cause weight gain amongst your atypicals
Thioridazine and Ziprasidone has quinidine like actions • Only antipsychotic that reduces the risk of suicide
(prolongation of QT interval) • Reserved for treatment of schizophrenia not amenable to
Thioridazine has the strongest autonomic effects Notes other drugs
The only antipsychotic with fatal overdose • With some M receptor, histamine and a-blockade
Notes Fluphenazine and Trifluoperazine have very significant • Agranulocytosis and seizures are feared complications
Parkinson-like effect • Because of the risk of agranulocytosis, patients receiving
Fluphenazine has less sedation compared to other anti- clozapine must have weekly blood counts for 6 months of
psychotics treatment
Dr. Lopez
• Quetiapine and Clozapine are amongst the atypicals that
is LEAST LIKELY to cause tardive dyskinesia
MNEMONIC: Ocular complications of antipsychotics Dr. Lopez
Chlorpropamide = Corneal and lens deposit Clozapine is not associated with EPS because it blocks the D2C receptor
ThioRidazine = Retinal deposit (mesocortical mesolimbic area) not the D2A (nigrostriatal pathway).
Thioridazine has the most muscarinic blockade therefore has the least However, it is cumbersome to use this because of the potential life-
EPS amongst the typical antipsychotics threatening agranulocytosis which requires the patient to have weekly
Dr. Calderon Jr. CBC. Cognizant of this, other atypical antipsychotics were born. J
Dr. Calderon Jr.
OLANZAPINE [C] ZIPRASIDONE [C]
Class Atypical antipsychotic (Thienobenzodiazepine) Class Atypical antipsychotic (dihydroindolone)
MOA Block of 5-HT2 receptors ≫ D2 receptors MOA Block of 5-HT2 receptors ≫ D2 receptors
Schizophrenia and other psychotic disorders, Bipolar Schizophrenia and other psychotic disorders, Bipolar
Uses Uses
disorder, Anorexia nervosa, Depression disorder (acute mania)
Extrapyramidal dysfunction (less), Extrapyramidal dysfunction (less), Postural
SE
Hyperprolactinemia (less), Postural hypotension, hypotension, QT prolongation (TDP)
SE
Weight gain, Hyperglycemia (diabetes mellitus), • Thioridazine and Ziprasidone has quinidine like actions
Hyperlipidemia, Agranulocytosis (prolongation of QT interval)
Specific Receptor antagonism binding profile: • Ziprasidone has the greatest risk for QT prolongation
5HT2A > H1 > D4 > D2 > a1 > D1 (and hence don’t combine with drugs that will have the
same effect i.e. thioridazine, class I and 3
• Olanzapine, Quetiapine and Aripiprazole cause MINIMAL
antiarrhythmics)
or NO increases in prolactin and has a reduced risk of EPS
Notes • No atropine-like effects
Notes (reflected by minimal D2 antagonism)
• Little or no tendency to cause hyperglycemia,
• Clozapine and Olanzapine has the highest tendency to
hyperprolactinemia or weight gain
cause weight gain amongst your atypicals
• Increased mortality in elderly patients with dementia-
• With some histamine and M receptor-blockade
related psychosis
• Safe in Pregnancy
Dr. Lopez • With some histamine and a-blockade
Dr. Lopez
Mnemonic for Olanzapine: “Kapag ikaw ay napasobra sa ZAPINE ZAPINE
ikaw ay magakaka weight gain” AHA ARIPIPRAZOLE [C]
Dr. Calderon Jr. Class Atypical antipsychotic (Dihydrocarbostyril)
MNEMINICS: Olanzapine and clozapine MOA Partial agonist at the D2 receptor
“O” Schizophrenia and other psychotic disorders, Bipolar
Olanzapine and clOzapine can cause Obesity Uses disorder, Major Depressive Disorder, Autism, Cocaine
dependence
Drugs have the highest tendency to cause weight gain Extrapyramidal dysfunction (less), Gastrointestinal
SE
amongst your atypicals upset, Tremor, Hypersensitivity (rare)
QUETIAPINE [C] D2 = 5HT2A > D4 > a1 = H1 >> D1
Olanzapine, Quetiapine and Aripiprazole cause MINIMAL or
Class Atypical antipsychotic (Dibenzothiazepine) NO increases in prolactin and has a reduced risk of EPS
MOA Block of 5-HT2 receptors ≫ D2 receptors Notes
(reflected by minimal D2 antagonism)
Schizophrenia and other psychotic disorders, Bipolar Least sedating atypical antipsychotic
Uses disorder (manic episodes), Sleep promotion and No atropine-like effects
maintenance Dr. Lopez
Extrapyramidal dysfunction (less), MNEMONIC Neuroleptic Malignant Syndrome

Hyperprolactinemia (less), Postural hypotension, What are the features of neuroleptic malignant syndrome?
SE Weight gain (less), Somnolence, Fatigue, Sleep NEUROLEPTIC MALIGNANT SYNDROME
paralysis, Hypnagogic hallucinations, Cataracts, “FEVER”
priapism, QT prolongation (TDP) Fever Elevated CPK
Specific Receptor antagonism binding profile: Encephalopathy Rigidity
H1 > a1 > M1,3 > D2 > 5HT2A Vitals unstable
• Olanzapine, Quetiapine and Aripiprazole cause MINIMAL SUPPLEMENT: LIST OF ANTIPSYCHOTIC DRUGS
or NO increases in prolactin and has a reduced risk of EPS TYPICAL ATYPICAL
Notes (reflected by minimal D2 antagonism) Benperidol Amisulpride
• Quetiapine and Clozapine are amongst the atypicals that Bromperidol Aripiprazole
is LEAST LIEKLY to cause tardive dyskinesia Chlorpromazine Asenapine
• With some histamine receptor blockade Droperidol Blonanserin
• Safe in Pregnancy Flupentixol Carpipramine
Dr. Lopez
Fluphenazine Clocapramine
Fluspirilene Clotiapine
MNEMONIC Quetiapine Haloperidol Clozapine
QUETIAPINE = increase in QUIET TIME Levomepromazine Iloperidone
Drug used for sleep maintenance and promotion Loxapine Lurasidone
Molindone Mosapramine
Since one of the ways of determining response to antipsychotics Penfluridol Olanzapine
is promotion and maintenance of sleep (Imagine a schizophrenic Perazine Paliperidone
patient with florid hallucinations. Sleep is indeed a luxury), and Perphenazine Perospirone
this is where the drug quetiapine is specifically good at. Pimozide Quetiapine
Pipotiazine Remoxipride
RISPERIDONE [C] Sulpiride Risperidone
Thioridazine Sertindole
SimD PALIPERIDONE
Thiothixene Ziprasidone
Class Atypical antipsychotic (Benzisoxazole) Trifluoperazine Zotepine
MOA Block of 5-HT2 receptors ≫ D2 receptors Zuclopenthixol
Schizophrenia and other psychotic disorders, Bipolar
Uses disorder, Depression, Intractable hiccups, Tourette
syndrome LITHIUM
Extrapyramidal dysfunction (less), Weight gain (less), Clinical Use of Lithium
SE Insomnia, Hyperprolactinemia (marked), • treatment of bipolar disorder (manic-depressive)
Photosensitivity, Hyperprolactinemia o decreases manic behavior and reduces both the frequency and
Risperidone, compared to all the other atypicals, has the the magnitude of mood swings
highest propensity for causing hyperprolactinemia o protective effects against suicide and self-harm
(amenorrhea, galactorrhea) • used concurrently with antidepressants during maintenance
Notes Only antipsychotic approved for schizophrenia in the therapy
youth
o monotherapy with antidepressants can precipitate mania in
With some histamine and a-blockade
Dr. Lopez
bipolar patients
• antipsychotic agents and/or benzodiazepines are commonly
required at initiation of treatment because of slow onset of
action
LITHIUM [D] • HETEROCYCLIC ANTIDEPRESSANTS
Class Mood stabilizer o amoxapine, bupropion, maprotiline, mirtazapine
Uncertain. Suppresses inositol signaling and inhibits • MONOAMINE OXIDASE INHIBITORS (MAOIs)
MOA
glycogen synthase kinase 3 (GSK-3) o phenelzine, tranylcypromine, selegiline
Bipolar disorder, Recurrent depression,
Uses
Schizoaffective disorder
Tremor (most common), Ataxia, Aphasia, Thyroid
enlargement, Subclinical Hypothyroidism (due to
uncoupling of TSH from its G protein receptor),
SE Nephrogenic diabetes insipidus, Edema (common),
Acneiform skin eruptions, Leukocytosis, Teratogen
(Ebstein Anomaly), Bradycardia, Renal dysfunction,
Dysrhythmia
Contraindicated in sick sinus syndrome (bradycardia-
tachycardia syndrome)
Treat overdose with hemodialysis
Notes Narrow therapeutic window
Some drugs (NSAIDs, ACEi, thiazide diuretics etc.) can
increase Lithium toxicity while caffeine and
theophylline can decrease its toxicity
Lithium has the smallest molecular weight. It remains the drug of choice
for bipolar disorder. But lithium has a very narrow therapeutic index and
needless to say it has great toxicity. Think of everything that is governed
by cyclic AMP, Lithium will block it and will cause a predominance of Gi
coupling.
Lithium mnemonic lifted from USMLE:
LiTHIUM: Low Thyroid hormone, Heart (Ebstein anomaly), Insipidus
(nephrogenic diabetes insipidus, Unintentional Movement (tremor)
Dr. Calderon Jr.
SUPPLEMENT: Lithium Overdose

• threshold for toxicity is 2meq/L
• therapeutic overdoses are more common than deliberate or
accidental ingestion
o due to change in the patient's status (diminished serum
sodium, use of diuretics or fluctuating renal function)
TRICYCLIC ANTIDEPRESSANTS (TCA)
• CLINICAL MANIFESTATIONS
o neuromuscular excitability, tremors, twitching, agitation, IMIPRAMINE [D]
weakness, ataxia, leukocytosis, bradycardia, hypotension CLOMIPRAMINE [C], DESIPRAMINE [C],
• TREATMENT SimD AMITRYPTYLINE [C], NORTRYPTILINE [D], DOXEPIN,
o hemodialysis is preferred over peritoneal dialysis PROTRIPTYLINE [C], TRIMIPRAMINE [C]
NEWER AGENTS USED FOR BIPOLAR DISORDER Class Antidepressant (tricyclic antidepressant)
Carbamazepine Block norepinephrine (NE) and 5-HT transporters →
Lamotrigine potentiation of NT action at postsynaptic receptors;
MOA
Valproic Acid / Divalproex Like SNRIs plus significant blockade of ANS and
histamine receptors
Major depressive disorder not responsive to SSRI (first
ANTIDEPRESSANTS line) and SNRI, chronic pain states, Enuresis, Insomnia,
Uses
Bipolar disorder, Acute panic attacks, Phobias, ADHD,
Incontinence, OCD (Clomipramine)
Dry mouth, Constipation, urinary retention, blurred
vision and confusion – Anticholinergic effects
Orthostatic hypotension – Alpha blocking effects
SE Weight gain and Excessive sedation – Histamine
blocking
Fatigue, Confusion, , Cardiomyopathies, Arrhythmias,
SUPPLEMENT: Amine Hypothesis of Mood Tremors, Paresthesia, seizure in overdose
• brain amines, particularly NE and serotonin, are • Additive depression of the CNS with other central
neurotransmitters in pathways that function in the depressants
expression of mood • Very long half-lives
o functional decrease of activity results in depression • Drug levels are easily affected by CYP inducers and
o functional increase of activity results in mood elevation inhibitors
Other theories explaining depression
• This group is very useful for patients with
• decrease in BNDF psychomotor retardation, sleep disturbance, poor
• elevated glutamate levels are seen in depressed patients appetite and weight loss
(which explains role of ketamine, an NMDA antagonist for the • 3Cs of overdose: Coma, Cardiotoxicity, Convulsions
treatment of refractory depression) Notes • Imipramine is metabolized to desipramine while
amitriptyline is metabolized to nortriptyline
CLASSIFICATION OF ANTIDEPRESSANTS • Long-term use may lead to down-regulation of Beta
• TRICYCLIC ANTIDEPRESSANTS (TCAs) receptors → decrease in BP and depression of
o imipramine, amitriptyline cardiac conduction
• SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) – • Amitriptyline has a significant muscarinic receptor
first line blocking effect
o fluoxetine, escitalopram, paroxetine, sertraline • Lower seizure threshold
• SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS • May interfere with antihypertensive action of
(SNRIs) Clonidine
o duloxetine, venlafaxine
• SEROTONIN (5-HT2) RECEPTOR ANTAGONISTS
o nefazodone, trazodone
SUPPLEMENT: TCA Toxicity • drugs implicated include MAOIs, TCAs, dextromethorphan,
TCA Overdose meperidine, St. John's wort, and MDMA ("ecstasy")
• DOSAGE • antiseizure drugs, muscle relaxants, and blockers of 5-HT
o toxic dose: 7 mg/kg (7 tabs Imipramine 75 mg) receptors (e.g. Cyproheptadine)
o lethal dose: 15 mg/kg (14 tabs Imipramine 75 mg)
• CLINICAL PRESENTATION KEY LEARNING POINT
o agitation, delirium, neuromuscular irritability What are the features of Serotonin Syndrome?
o convulsions, and coma FAT CHD
o respiratory depression and circulatory collapse Fever Clonus
o hyperpyrexia Agitation Hyperreflexia
o cardiac conduction defects and severe arrhythmias Tremor Diaphoresis
§ ECG reveals abnormal morphology of QRS complexes,
prolonged QRS duration, abnormal size and ratio of R and SELECTIVE SEROTONIN NOREPINEPHRINE
S waves in AVR
MNEMONICS – TCA Toxicity
REUPTAKE INHIBITOR (SNRI)
What are the 3 Cs of TCA Overdose? VENLAFAXINE [C]
Coma Convulsions Cardiotoxicity DULOXETINE [C], DESVENLAFAXINE [C],
SimD
Treatment of TCA Overdose MILNACIPRAN [C]
• SUPPORTIVE MEASURES Antidepressant (serotonin-norepinephrine reuptake
Class
o fluid resuscitation for hypotension inhibitor)
o gastric decontamination with activated charcoal Inhibits neuronal reuptake of serotonin and
o control seizures with benzodiazepines MOA norepinephrine by binding to transporters for both
• ADMINISTRATION OF BICARBONATE 5HT and NE
o QRS duration >100 msec or ventricular arrhythmias Major depression, Fibromyalgia, Perimenopausal
o reverses cardiotoxicity Uses symptoms, Diabetic neuropathy, Neuropathic pain,
Chronic Pain Disorders
Hypertension (Venlafaxine) and CNS stimulation
SELECTIVE SEROTONIN REUPTAKE INHIBITOR (Insomnia, anxiety and agitation) due to
(SSRI) SE Noradrenergic effects, Hepatotoxicity (duloxetine),
FLUOXETINE [C] Withdrawal syndrome even in just one missed dose,
SimD PAROXETINE [D], CITALOPRAM [C], ESCITALOPRAM Anticholinergic symptoms
[C], SERTRALINE [C], FLUVOXAMINE [C], • Duloxetine and Desvenlafaxine is a CYP450 inhibitor
VILAZODONE • Milnacipran is more selective for NE reuptake
Class Antidepressant (selective serotonin reuptake transporter than Serotonin reuptake transporter
inhibitor) • Venlafaxine has less affinity for NE transporter than
MOA Inhibits neuronal reuptake of serotonin by inhibiting Notes desvenlafaxine and duloxetine
Serotonin Transporter (SERT) • Differ from TCA in lacking blockade of H1, M and
Uses DOC for Major Depressive Disorder, OCD, Anxiety, alpha receptors
Panic attacks, Phobias, PTSD, Eating Disorders • Increased risk for suicide in children and
(Bulimia), Premenstrual dysphoria, Alcohol adolescents
dependence, Perimenopausal vasomotor symptoms
SE Increased serotonergic activity in gut: Nausea, SEROTONIN ANTAGONIST
vomiting, diarrhea TRAZODONE [C]
Increased serotonergic tone in spinal cord: diminished
SimD NEFAZODONE [C], VORTIOXETINE
sexual function and interest
Class Antidepressant (serotonin antagonist)
Other SE related to increased serotonin: headaches,
Block 5-HT2A receptors, weak inhibitor of NE and 5HT
insomnia
transporters. Nefazodone also blocks Serotonin
Discontinuation syndrome: Paroxetine and sertraline MOA
reuptake transporters while Trazodone can also block
QT prolongation and teratogen (cardiac septal
5HT2C receptors
defects): citalopram only
Notes Major depression, Sedation, Hypnosis/Sleeping aid
• High risk of serotonin syndrome if co-administered with Uses
MAOi. Discontinue for 4 weeks of longer before initiating (Trazodone), Anxiety disorders
use of MAOi if already on SSRIs Sedation, Gastrointestinal disturbance, Orthostatic
• Fluoxetine, fluvoxamine and Paroxetine are CYP450 SE hypotension, Priapism (trazodone), Hepatotoxicity
inhibitors (nefazodone), Hyperprolactinemia
• Fluvoxamine is approved only for Obsessive-Compulsive • Trazadone is used off-label for hypnosis
behavior • Mirtazapine, Bupropion and Nefazodone, are among the
• Vilazodone can also act as a partial agonist of 5HT1A few antidepressants that is not associated with sexual
• Minimal inhibitory effect on cholinergic or adrenergic dysfunction as side effect
receptors (unlike TCAs) • May cause arrhythmias in patients with pre-existing
• DAPOXETINE is an SSRI which has been developed for cardiac disease
treatment of Premature Ejaculation taken 1-3 hours • Trazodone has modest a1 and H1 receptor blockade
prior to coitus
Notes
• Nefazodone has significant muscarinic receptor blocking
Dr. Lopez
effect
• Nefazodone is a potent CYP3A4 inhibitor
MNEMONIC: Erectile Dysfunction • Short t½ so given BID to TID
What drugs can cause erectile dysfunction? • Vortioxetine is a 5HT3 and 5HT1D antagonist and a 5HT1A
ERECTILE DYSFUNCTION agonist
Dr. Lopez
A SORE PeniS can’t Fuck Hard!
SSRIs Propranolol
Opiates Spironolactone MNEMONIC: Priapism
Risperidone Finasteride What drugs can cause PRIAPISM?
Ethanol, Estrogen Hydrochlorothiazide Tigas PeniS Qo, AyaW Bumaba!
Trazodone Alprostadil
SUPPLEMENT: Serotonin Syndrome Papaverine Warfarin
Sildenafil Bupropion
• life-threatening syndrome characterized by severe muscle Quetiapine
rigidity, myoclonus, hyperthermia, cardiovascular instability,
and marked CNS stimulatory effects, including seizures
TETRACYCLIC ANTIDEPRESSANTS / UNICYCLICS • Structurally, bupropion is similar to amphetamines so it

has stimulant features
AMOXAPINE [C] • Bupropion has a biphasic elimination
SimD MAPROTILINE [B] • Mirtazapine, Bupropion and Nefazodone, are among the
Class Antidepressant (tetracyclic antidepressant) few antidepressants that is not associated with sexual
Notes
Strong norepinephrine reuptake inhibitor and weak dysfunction as side effect
MOA serotonin reuptake inhibitor. Blocks dopamine D2 • Lowers seizure threshold
receptors. Resembles TCA in terms of effects • CYP450 inhibitor
Uses Major depression • No effect on 5HT or NE receptors or amine transporters
Dr. Lopez
Autonomic effects, Akathisia, Parkinsonism (due to
SE dopamine receptor blockade), Amenorrhea-
galactorrhea syndrome, Seizures, Cardiotoxicity MAO INHIBITORS
Lowers seizure threshold (Amoxapine) PHENELZINE [C]
Notes Lowers seizure threshold, has significant muscarinic TRANYLCYPROMINE [C], ISOCARBOXAZID [C],
SimD
receptor blocking effect SELEGILINE [C]
Class Antidepressant (monoamine oxidase inhibitor)
MIRTAZAPINE [C]
Inhibits monoamine oxidase type A and type B.
Class Antidepressant (tetracyclic antidepressant)
Increases CNS levels of NE and serotonin.
Increases amine release from nerve endings by MOA
Tranylcypromine are nonselective MAO inhibitors
MOA antagonism of presynaptic a2 adrenoceptors. Blocks
while Selegiline is a MAO-B selective inhibitor
serotonin 5HT2 receptors.
Major depression unresponsive to other drugs, Useful
Major depression unresponsive to other agents,
Uses Uses in patients with significant anxiety, phobic features
Appetite stimulation, Sedation/Sleeping aid
and hypochondriasis
Weight gain, Marked sedation, Dizziness, Blurred
SE Dizziness, Insomnia, Orthostatic hypotension, Blurred
vision, Nightmares SE vision, Arrhythmias, Diarrhea, hyperthermia, CNS
Mirtazapine, Bupropion and Nefazodone, are among the
stimulation, seizure
few antidepressants that is not associated with sexual
dysfunction as side effect • MAO inhibitors have amphetamine like features
Notes • Hypertensive crisis when taken with tyramine (indirect-
Has significant muscarinic receptor and alpha-2 blocking
effect acting sympathomimetic in cheese)
Dr. Lopez • Serotonin syndrome when taken with SSRIs
Notes • CYP450 inhibitors
BUPROPION [C]
• Long-term use may lead to down-regulation of Beta
Class Antidepressant (Unicyclic aminoketone) receptors (leading to decrease in BP)
Inhibits neuronal reuptake of dopamine and • Lower seizure threshold
MOA norepinephrine. Increases dopamine and • Selegiline may be given as skin patch
norepinephrine activity. Dr. Lopez
Major depression not responsive to other agents, Other tyramine rich food: avocado, Cheese, wine J
Uses
Smoking cessation, Alcohol dependence Remember, the releasers of norepinephrine from the presynaptic vesicles?
Weight loss, Agitation, Dizziness, Dry mouth, MNEMONIC: release the TAE: Tyramine, Amphetamine and Ephedrine
SE Dr. Calderon Jr.
Aggravation of psychosis, Seizures, Priapism
KEY LEARNING POINT Differentiate Serotonin Syndrome from NMS and Malignant Hyperthermia
NEUROLEPTIC MALIGNANT
MALIGNANT HYPERTHERMIA SEROTONIN SYNDROME
SYNDROME
Onset • Within minutes • Within hours • 1-3 days
Precipitating • Volatile anesthetics • SSRIs, MAOIs, TCAs, Meperidine,
• Antipsychotics
drug (halothane), succinylcholine MDMA, St. John’s Wort
• Massive calcium release from
Mechanism • Excess serotonin • Dopamine antagonism
SR
• Fever • Fever
• Fever
• Acidosis • Agitation
• Encephalopathy
Clinical • Rhabdomyolysis • Tremor
• Vitals unstable
features • Trismus • Clonus
• Elevated CPK
• Clonus • Hyperreflexia
• Rigidity
• Hypertension • Diaphoresis
First-line • Sedation, paralysis, intubation and
• Dantrolene • Diphenhydramine
treatment ventilation
Other • Cooling, cyproheptadine, • Cooling, Dantrolene, bromocriptine,
• Cooling
treatment chlorpromazine amantadine, diazepam
OPIOID ANALGESICS AND ANTAGONISTS 1. Close voltage gated Ca2+ channels on presynaptic nerve
terminals and reduce transmitter release
2. Open K+ channels and hyperpolarize and thus inhibit
postsynaptic neurons
Classification of Opioids
• SPECTRUM OF CLINICAL USES
o analgesics, antitussives, antidiarrheal
• STRENGTH OF ANALGESIA
o strong, moderate, weak agonists
o partial agonists exert less analgesia than full agonists
Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 • RATIO OF AGONIST TO ANTAGONIST EFFECTS
SUPPLEMENT: Opioids o agonists (receptor activators [full or partial])
• include natural opiates and semisynthetic alkaloids derived o antagonists (receptor blockers)
from the opium poppy, pharmacologically similar synthetic o mixed agonist-antagonists
surrogates, and endogenous peptides
• Mechanism of action of OPIODS: has G protein coupled
actions on neurons doing the ff:
KEY LEARNING POINTS: Half Life Opioids Opioid analgesics are the strongest ones in controlling pain. Opioid
Which opioids have the shortest and longest half-lives? receptors are abundant in the spinal neurons (ascending pathway) and
medulla (descending pathway). Morphine is the prototype opioid.
• REMIFENTANIL = shortest half-life (3-4 mins)
MNEMONIC for Morphine side effect:
• BUPRENORPHINE = longest half-life (4-8 hrs) MORPHINE = Miosis, Out of it, Respiratory depression, Pruritus,
Hypotension and Headache, In frequency, Nausea, and Emesis
Dr. Calderon Jr.
SUPPLEMENT: Opioid Receptors

Mu1 Mu2 Kappa Delta
• Analgesia (supraspinal and • Analgesia (Spinal), • Analgesia (supraspinal • Analgesia
spinal), Euphoria, Low abuse depression of and spinal), dysphoria, (supraspinal and
EFFECT potential, Miosis, ventilation, Physical sedation, addiction and spinal), depression of
Bradycardia, hypothermia, dependence, dependence, Miosis, ventilation, physical
Urinary retention Constipation (marked) Constipation dependence,
• Endorphins, Morphine, • Endorphins, Morphine,
AGONISTS • Dynorphins • Enkephalins
Synthetic opioids Synthetic opioids
• Naloxone • Naloxone • Naloxone • Naloxone
ANTAGONISTS
• Naltrexone • Naltrexone • Naltrexone • Naltrexone
KEY LEARNING POINTS MEPERIDINE [C]

Side effects of opioids with minimal or no tolerance (an Class Opioid analgesic (full agonist)
effect that does not diminish despite continued use) Strong agonist at µ and k receptors. Inhibits pain
MOA
Miosis neurotransmission. Muscarinic blocking actions.
Constipation Moderate to severe pain, Labor analgesia,
Uses
Convulsions Postoperative Shivering, Preoperative sedation
Side effects of Opioids not mediated by opioid receptors Tachycardia, Hypotension (pronounced in patients
Nausea and vomiting – stimulation of CTZ at 4th ventricle with decreased circulating volume), Seizures,
Hypotension – histamine release SE Delirium, Restlessness, Respiratory depression,
Pruritus – histamine release Increased ICP, Postural hypotension, Constipation,
Urinary retention, Pruritus, Addiction liability (less),
1/10th as potent compared to morphine
FULL AGONISTS Meperidine has the most pronounced anti-shivering
MORPHINE [C] – prototype of opioids effect (a2 antagonism)
HYDROMORPHONE [C] OXYMORPHONE [C] , HEROIN Normeperidine is the metabolite that decreases
SimD
(Synthetic derivatives of Morphine) seizure threshold. Contraindicated for patients with
Phenanthrenes Notes epilepsy.
Class
Opioid analgesic (full agonist) If given with MAOi → Hyperpyrexic coma
Strong agonist at µ receptors. Inhibits pain If given with SSRI → Serotonin syndrome
MOA neurotransmission at spinal and supraspinal sites. Pethidine is the other name of Meperidine
Variable activity at d and k receptors. MEPERIDINE DOES NOT CAUSE MIOSIS, rather it
Severe pain, Pain associated with acute myocardial causes MYDRIASIS (owing to its atropine like function)
Uses
infarction, Pulmonary edema, Adjunct in anesthesia METHADONE [C]
Miosis, Restlessness, Respiratory depression, SimD LEVOMETHADYL ACETATE, LEVORPHANOL [C]
Increased ICP, Postural hypotension, Constipation, Phenylheptylamines
SE Class
Urinary retention, Pruritus, Addiction liability, Pain Opioid analgesic (full agonist)
associated with myocardial ischemia, Bradycardia
Strong agonist at µ receptors. NMDA antagonist.
Exerts hemodynamic effects on the pulmonary MOA
Blocks monoamine reuptake transporters.
circulation
Moderate to severe pain (resistant to morphine),
Hydromorphone & Oxymorphone: Like morphine in
Uses Opioid dependence (especially for a relapsing chronic
efficacy but higher potency
heroin addict), Opioid withdrawal
Additive CNS depression with other depressants
Notes Miosis, Restlessness, Respiratory depression,
Significant first-pass effect
Increased ICP, Postural hypotension, Constipation,
Metabolized in the body to morphine-6-glucuronide
SE Urinary retention, Pruritus, Addiction liability (less)
(which has 4-6x analgesic activity as morphine) and to
Hepatic dysfunction, QT prolongation (specific to
Morphine-3-glucoronide (which has a neuroexcitatory
methadone)
properties)
Used in methadone maintenance therapy (MMT) for
opioid dependence
FENTANYL [C] Notes
Currently being investigated as a novel treatment for
SUFENTANIL (5-10x more potent than fentanyl),
leukemia
ALFENTANIL(1/5th to 1/10th as potent as fentanyl)
SimD Methadone is commonly used in patients with opioid withdrawal. It has
[C], REMIFENTANIL (same potency as fentanyl) [C],
OHMEFENTANYL a slower pharmacokinetic profile compared to Opioid. Hence, a good
thing. However, it has a long half-life, therefore it will require a greater
Phenylpiperidine
Class time to achieve a steady state. As if the patient, will think that Methadone
Opioid analgesic (full agonist) is not enough, they will try to get another form of opioid. With this action,
Strong agonist at µ receptors. Inhibits pain it will lead to additive effect and can cause further CNS depression. This
MOA neurotransmission at spinal and supraspinal sites. will lead to patient’s eventual death.
Variable activity at d and k receptors. Dr. Calderon Jr.
Severe pain, Adjunct in anesthesia, Chronic pain,

Uses PARTIAL AGONISTS
Breakthrough cancer pain
Restlessness, Respiratory depression, Increased ICP,
HYDROCODONE [C]
SE Postural hypotension, Constipation, Urinary retention, OXYCODONE [B, may be C if given in combination],
Pruritus, Addiction liability SimD
DIHYDROCODEINE
75-125 x more potent than morphine Phenanthrenes
Notes Class
May be given transdermally or via lollipop Opioid analgesic (partial agonist)
Strong agonist at µ and k receptors. Inhibits pain
neurotransmission at spinal and supraspinal sites,
MOA
binds NMDA receptors and antagonizes the effects of
glutamate
Moderate to severe pain, Cancer pain, Neuropathic ANTAGONIST
Uses pain (postherpetic neuralgia, DM neuropathy),
NALOXONE [C]
Chronic pain, opioid dependence, opioid withdrawal
NALTREXONE [C], NALMEFENE [B], ALVIMOPAN [B],
Miosis, Respiratory depression, Increased ICP, SimD
METHYLNALTREXONE [B]
Postural hypotension, Constipation, Urinary retention,
SE Class Opioid antagonist (systemic)
Pruritus, Addiction liability, Hypogonadism, Hearing
loss Competitively blocks µ, d and k receptors. Rapidly
MOA
reverses effects of opioid agonists.
There is genetic variation in the metabolism of codeine
Notes DOC for Opioid overdose (NALOXONE), Opioid and
and its derivatives Uses
alcohol dependence (NALTREXONE only)
DEXTROMETHORPHAN [C] SE Pruritus, Nausea, Vomiting
• Precipitates abstinence syndrome in patients with
SimD CODEINE [C]
opioid dependence
Class Opioid analgesic (partial agonist)
• Naltrexone reduces craving in alcohol, nicotine and
Decreases sensitivity of cough receptors. Depressing opioid dependence
MOA the medullary cough center through sigma receptor • Naltrexone & Nalmefene have longer DOA
stimulation Notes
• Naloxone and Nalmefene is IV (DOA: 12-24 hrs) while
Uses cough suppression Naltrexone is PO (DOA: 48h)
Hallucinations, Confusion, Excitation, Increased or • Alvimopan & Methylnaltrexone have poor CNS
SE decreased pupil size, Nystagmus, Seizures, Coma, penetrability → antagonize peripheral effects such as
Respiratory depression, Addiction liability constipation
Serotonin syndrome when used with SSRIs or MAOIs
Notes
Codeine is metabolized by CYP2D6 to morphine DUAL-ACTING
TRAMADOL [C]
WEAK AGONISTS SimD TAPENTADOL [C]
PROPOXYPHENE [C] Class Opioid analgesic (dual acting)
LEVOPROPOXYPHENE [C], DEXTROPROPOXYPHENE Weak agonist at µ receptor. Inhibits neuronal reuptake
SimD
[C] MOA of serotonin and norepinephrine. Inhibits pain
Phenanthrene neurotransmission.
Class
Opioid analgesic (weak agonist) Moderate pain, Chronic pain syndromes, Neuropathic
Weak agonist at µ receptors. Inhibits pain Uses pain, Fibromyalgia, Adjuncts to opioid in chronic pain
MOA
neurotransmission. syndromes
Mild to moderate pain, Restless legs syndrome, Opioid SE Seizures, Nausea, Dizziness, Pruritus, Constipation
Uses
withdrawal 5-10 x less potent compared to morphine
Miosis, Respiratory depression, Increased ICP, Lowers seizure threshold
Postural hypotension, Constipation, Urinary retention, Contraindicated in patients with a history of epilepsy
SE
Pruritus, Addiction liability, Seizures, Pulmonary Notes Serotonin syndrome when used with SSRIs
edema, Fatal arrhythmias SE profile vs other opioids: Low tendency for
Propoxyphene is chemically related to methadone but respiratory abuse and low chances for developing
with weaker analgesic activity tolerance and dependence
Withdrawn because of fatal cardiotoxicity (group 1C
Notes
antiarrhythmic activity) SUPPLEMENT: Opioid Overdose
Commonly used in suicides • triad of pupillary constriction, comatose state, and respiratory
Levopropoxyphene is used as an anti-tussive depression
• diagnosis confirmed if intravenous injection of naloxone results
MIXED AGONIST-ANTAGONIST in prompt signs of recovery
• treatment involves the use of antagonists such as naloxone and
BUPRENORPHINE [C]
other therapeutic measures, especially ventilatory support
NALBUPHINE [B], BUTORPHANOL [C], PENTAZOCINE
SimD MNEMONICS – Opioid Overdosage
[C], LEVALLORPHAN [B]
What is the triad of OPIOID OVERDOSE?
Class Opioid analgesic (mixed agonist-antagonist) P-C-R
Partial µ receptors agonist, antagonist at k & d Pupillary constriction
MOA
receptors. Inhibits pain neurotransmission. Comatose state
Moderate to severe pain, Opioid dependence, Alcohol Respiratory depression
dependence, Balanced anesthesia, opioid withdrawal
Uses You may want to see constipation and pupillary constriction in an opioid
states (buprenorphine), Postoperative shivering
overdose patient. It is a clear cut clinical entity wherein you will see a
(Butorphanol)
comatose patient with pupillary constriction (except for Meperidine).
Sedation, Dizziness, Sweating, Nausea, Anxiety, These are good clinical clues to raise suspicion of opioid overdose.
SE Hallucinations, Nightmares, Respiratory depression
Are you going to give a high level of oxygen to a patient with opioid
(less), Tolerance, Dependence liability overdose? Recall the physiology of breathing. Opioids will shut the central
Effects resistant to naloxone reversal drive for breathing which is high levels of carbon dioxide. Now giving
Nalbuphine is a strong k agonist and partial µ high levels of oxygen will shut the peripheral control wherein the main
Notes
antagonist; has a ceiling effect stimulus is low level of oxygen. It will impair the remaining drive to
Pentazocine is a k agonist and weakly µ antagonist breathe unless you will put the patient under mechanical ventilation.
Dr. Calderon Jr.
In the clinical setting, let us try to picture an opioid dependent patient
who was brought to the emergency room because of excruciating pain.
Apparently, you give Buprenorphine a partial agonist of mu receptor. As DRUGS OF ABUSE
a partial agonist it may worsen the patient’s withdrawal symptoms. DRUG ABUSE
These medications as mixed agonist will work not just in the mu receptor • use of an illicit drug or the excessive or nonmedical use of a licit
but also in the kappa receptor. Nalbuphine is an example. Somehow, it is drug
beneficial because of kappa receptor activation can lead to dysphoria.
• denotes the deliberate use of chemicals that generally are not
Definitely, the patient will not like that as a side effect. Therefore,
relatively low abuse potential than morphine.
considered drugs by the lay public but may be harmful to the
Dr. Calderon Jr. user
• primary motivation is the anticipated feeling of pleasure derived
from the CNS effects of the drug
DEPENDENCE MDMA OVERDOSE
• older term is physical or physiologic dependence • CLINICAL PRESENTATION
• state characterized by signs and symptoms, frequently the o severe hypertension, hyperthermia, delirium, psychomotor
opposite of those caused by a drug, when it is withdrawn from agitation and profound hyponatremia
chronic use or when the dose is abruptly lowered o life-threatening complications include intracranial
hemorrhage, myocardial infarction, aortic dissection, DIC,
ADDICTION rhabdomyolysis, seizures and serotonin syndrome
• older term is psychological dependence • TREATMENT
• compulsive drug-using behavior in which the person uses the o supportive care directed at control of seizures, hyperthermia,
drug for personal satisfaction, often in the face of known risks to and serotonin syndrome
health o fluid resuscitation with hypertonic saline for hyponatremia
TOLERANCE COCAINE
• decreased response to a drug, necessitating larger doses to COCAINE EFFECTS
achieve the same effect • STREET NAMES
• etiology of tolerance o “coke”, “super-speed”, “crack”
o increased disposition of the drug (metabolic tolerance) • EFFECTS
o ability to compensate for the effects of a drug (behavioral o inhibition of CNS transporters of dopamine, norepinephrine,
tolerance) and serotonin
o changes in receptor or effector systems involved in drug o marked amphetamine-like effects
actions (functional tolerance) o short-lasting euphoria, self-confidence and mental alertness
positively reinforce its continued use
ABSTINENCE SYNDROME
• also known as withdrawal syndrome COCAINE OVERDOSE
• signs and symptoms that occur on discontinuation or • CLINICAL PRESENTATION
withdrawal of a drug in a dependent person o hypertension, vasoconstriction, thrombus formation,
SUPPLEMENT: Dopamine Hypothesis of Addiction psychomotor agitation, severe hyperthermia, dyspnea, bowel
• dopamine in the mesolimbic system appears to play a ischemia, mydriasis, crack lung (hemorrhagic alveolitis)
primary role in the expression of "reward" o fatalities from arrhythmias, seizures or respiratory depression
• excessive dopaminergic stimulation may lead to pathologic • TREATMENT
reinforcement o no specific antidote is available
o behavior may become compulsive and no longer under o supportive care
control—common features of addiction o cocaine abuse during pregnancy is associated with increased
• most addictive drugs have actions that include facilitation of fetal morbidity and mortality
the effects of dopamine in the CNS
MNEMONIC COCAINE INTOXICATION
Nakakita ka ng ice-cold coke. Na-excite ka.
AMPHETAMINES AND CONGENERS Nanlaki ang mata mo.
EFFECTS OF AMPHETAMINES COCAINE = mydriasis
• REPRESENTATIVE AGENTS COCAINE WITHDRAWAL
o dextroamphetamine • CLINICAL PRESENTATION
o methamphetamine (“speed”, “ice”) o apathy, irritability, increased sleep time, disorientation
• EFFECTS o severe depression strongly reinforces compulsions
o feeling of euphoria and self-confidence that contributes to the • TREATMENT
rapid development of addiction o antidepressant drugs may be indicated
o effects of chronic high-dose abuse o infants born to mothers who abuse have possible
§ psychotic state (with delusions and paranoia) teratogenic abnormalities (cystic cortical lesions),
§ development of necrotizing arteritis, leading to cerebral increased morbidity and mortality and may be cocaine
hemorrhage and renal failure dependent
AMPHETAMINE OVERDOSE
PHENCYCLIDINE
o agitation, hypertension, tachycardia, delusions, hallucinations, • REPRESENTATIVE AGENTS
hyperthermia, seizures, death o phencyclidine (PCP; "angel dust")
• MANAGEMENT o ketamine ("special K")
o no specific antidote • EFFECTS
o control of body temperature o antagonists at the glutamate NMDA receptor
o protection against cardiac arrhythmias and seizures o no actions on dopaminergic neurons in the CNS unlike most
drugs of abuse
SUPPLEMENT: Amphetamine Withdrawal o PCP is the most dangerous hallucinogenic agent
• CLINICAL PRESENTATION o psychotic reactions, impaired judgment leading to reckless
o apathy, irritability, increased sleep time, disorientation, behavior (psychotomimetic effect)
depression
• TREATMENT PHENCYCLIDINE OVERDOSAGE
o antidepressants (amineptine, mirtazapine) are of limited • CLINICAL PRESENTATION
benefit o horizontal and vertical nystagmus, marked hypertension, and
o acidify urine to increase elimination fatal seizures
CONGENERS OF AMPHETAMINES • TREATMENT
• REPRESENTATIVE AGENTS o supportive care to control seizures and hypertension
o dimethoxymethylamphetamine (DOM) o parenteral benzodiazepines (diazepam, lorazepam) are used
o methylene ioxyamphetamine (MDA) to curb excitation and protect against seizures
o methylene dioxymethamphetamine (MDMA/ Ecstasy)
SUPPLEMENT: MISCELLANEOUS HALLUCINOGENIC AGENTS
• EFFECTS
o more selective action on the serotonin transporters in CNS • REPRESENTATIVE AGENTS
o facilitate interpersonal communication o lysergic acid diethylamide (LSD)
o act as sexual enhancers o mescaline
o causes depletion of neurons in serotonergic tracts o psilocybin
• EFFECTS SOMATROPIN [B]

o psychedelic and mind raveling effects Class Recombinant Growth hormone
o perceptual and psychological effects accompanied by Increases release of IGF-1 in the liver and cartilage.
marked somatic effects (nausea, weakness, paresthesia) MOA Stimulates skeletal muscle growth, amino acid
o Panic reactions ("bad trips") may also occur transport, protein synthesis and cell proliferation.
Growth hormone deficiency, Genetic diseases
associated with short stature (Turner, Noonan,
MARIJUANA Prader-Willi), failure to thrive due to chronic renal
Marijuana Uses
failure or SGA, AIDS wasting, improve GI function in
• psychoactive constituents in crude extracts of the plant Cannabis patients who underwent intestinal resection that led
sativa (hemp) to malabsorption syndrome
• active ingredients: tetrahydrocannabinol (THC), cannabidiol Peripheral edema, Myalgia, Arthralgia, Intracranial
(CBD), cannabinol (CBN) hypertension, pseudotumor cerebri, slipped capital
• hashish is a partially purified, more potent form SE
femoral epiphysis, progression of scoliosis,
• street names: “weed”, “pot”, “grass”, “damo”, “dope”, “Mary Jane”, hyperglycemia
“hash” Performance-enhancing drug (increases muscle mass)
• effects potentiated by concomitant use of sedative-hypnotics that is banned by athletics committees
including ethanol Notes MECASERMIN is a recombinant IGF-I agonist
EFFECTS OF MARIJUANA PEGVISOMANT is a GH receptor antagonist
• feeling of being "high," with euphoria, disinhibition, Given SC
uncontrollable laughter, changes in perception, and SUPPLEMENT:
achievement of a dream-like state
MECASERMIN [C]
• impaired mental concentration
Class Recombinant IGF-1
• vasodilation
Stimulates skeletal muscle growth, amino acid
• tachycardia MOA
transport, protein synthesis and cell proliferation
• reddened conjunctiva
Uses For children unresponsive to GH therapy
• dry mouth
SE Hypoglycemia, increased LFT, intracranial HTN
• impairment of judgment and reflexes
Remedy to hypoglycemia: give patient some snacks
SUPPLEMENT: OTHER RELATED COMPOUNDS Notes
prior to dose
Chemically related to
Amphetamine, A CNC stimulant PEGVISOMANT [C]
METHYLPHENIDATE Class GH receptor antagonist
used for ADHD. Do not use together
with antidepressants MOA Block GH receptor
A NE reuptake inhibitor; used for Uses Acromegaly
ATOMOXETINE Diarrhea, nausea, flu-like syndrome, elevated LFTs,
ADHD SE
hypersensitivity reaction
Notes Onset of action is expected within 2wks of use
ENDOCRINE PHARMACOLOGY OCTREOTIDE [B]
HYPOTHALAMIC AND PITUITARY HORMONES SimD LANREOTIDE [C]
Anterior Pituitary Hormones Class Somatostatin analog
Suppresses the release of growth hormones, glucagon,
MOA insulin, gastrin, IGF-1, serotonin and gastrointestinal
peptides
Acromegaly, Pituitary adenoma (GH-secreting),
Uses Carcinoid, Gastrinoma, Glucagonoma, Variceal
bleeding
Gastrointestinal disturbances, Gallstones,
SE
Arrhythmias/cardiac conduction abnormality
Can alter requirements for antidiabetic agents
Regular release: given BID-QID SC
Notes
If slow release: every 4wks IM
Are long-acting synthetic analogs of somatostatin
FSH, LH AND THEIR ANALOGS
• FUNCTIONS
o in women, FSH directs follicle development, whereas FSH and
LH collaborate in regulating ovarian steroidogenesis
o in men, FSH regulates spermatogenesis, whereas LH
stimulates androgen production
• CLINICAL UTILITY
o to stimulate spermatogenesis in infertile men
o to induce ovulation in women with refractory anovulation
SUPPLEMENT:
Ovulation Induction Protocol
• endogenous gonadotropin production is inhibited by
administration of a GnRH agonist or antagonist
• follicle development is driven by daily injections of a
preparation with FSH activity (menotropins, FSH, FSH
analog)
• All the anterior pituitary hormones are under the control of a
hypothalamic hormone
• final stage of oocyte maturation is induced with an injection
• All mediate their ultimate effects by regulating the production by of LH or human chorionic gonadotropin (hCG)
peripheral tissues of other hormones EXCEPT prolactin
• Four anterior pituitary hormones (TSH, LH, FSH, and ACTH) and their Complications of Ovulation Induction
hypothalamic regulators are subject to feedback regulation by the • multiple pregnancies
hormones whose production they control • ovarian hyperstimulation syndrome
• Hormones secreted by the Posterior Pituitary are: Vasopressin & • syndrome of ovarian enlargement, ascites, hypovolemia and
Oxytocin. Take note that both are potent vasoconstrictors. possibly shock
FOLLITROPIN ALFA [X] GANIRELIX [X]
MENOTROPINS (hMG) [X], UROFOLLITROPIN [X], SimD CETRORELIX [X], ABARELIX, DEGARELIX
SimD
FOLLITROPIN BETA [X] Class GnRH antagonist
Class Gonadotropin analog (FSH analog) MOA Blocks GnRH receptors. Reduces endogenous
Activates FSH receptors. Mimics effects of endogenous production of LH and FSH.
MOA
FSH. Uses Prevents premature LH surge during Controlled
Controlled ovarian hyperstimulation, Infertility due to ovarian hyperstimulation, Advanced Prostate cancer
Uses
hypogonadotropic hypogonadism in men SE Nausea, Headache, Hypersensitivity (abarelix), Hot
Headache, depression, edema, ovarian flushes, Gynecomastia, decreased libido, Decreased
hyperstimulation syndrome (ovarian enlargement, hematocrit, Osteoporosis
SE
ascites, hypovolemia, shock), multiple pregnancies in Notes Does NOT cause a tumor flare-up when used for
women, gynecomastia in men treatment of advanced prostate cancer
Follitropin alfa and beta are recombinant FSH forms Also, less likely to cause ovarian hyperstimulation
Notes while Urofollitropin is a purified preparation from syndrome
urine of postmenopausal women Degarelix is used for prostate CA while Ganirelix
prevent LH surge in controlled ovulation
CHORIOGONADOTROPIN ALFA [X] Directly inhibits the receptors and so causes antagonistic
HUMAN CHORIONIC GONADOTROPIN (hCG) [X], (decrease in hormones) effect right away. Thus, there is no
SimD
MENOTROPINS (hMG) [X], LUTROPIN ALFA flare up.
Class Gonadotropin analog (LH analog) Dr. Pereyra-Borlongan
Activates LH receptors. Mimics effects of endogenous

MOA BROMOCRIPTINE [B]
LH.
Initiation of ovulation during controlled ovarian SimD PERGOLIDE [B], CABERGOLINE [B], QUINAGOLIDE
hyperstimulation (ovulation induction), ovarian Class Dopamine agonist
Uses follicle development in women with Inhibits prolactin release from the pituitary gland.
Hypogonadotropic hypogonadism, male MOA Also slightly inhibits GH release. Dopaminergic effects
Hypogonadotropic Hypogonadism on CNS motor control and behavior
Headache, Depression, Edema; Ovarian Hyperprolactinemia, Pituitary adenoma (prolactin-
Uses
SE hyperstimulation syndrome, Multiple pregnancies in secreting), Acromegaly, Parkinson’s disease
women; Gynecomastia in men GI disturbance, Nausea, Headache, Light-headedness,
Menotropins are mixtures of FSH and LH from Orthostatic Hypotension, Fatigue, Behavioral Changes,
SE
postmenopausal women Erythromelalgia, Raynaud’s phenomenon
Notes Choriogonadotropin alfa is a recombinant hCG while (vasospasm), Pulmonary infiltrates (in high doses)
Lutropin is a recombinant LH Given PO or vaginally (for Hyperprolactinemia)
hCG given IM Slightly inhibits GH release if given in high doses
Notes CI in patients with history of psychotic illness
LEUPROLIDE [X] Erythromelalgia is a rare disorder characterized by
GONADORELIN [B], GOSERELIN [X], HISTRELIN, burning pain and warmth and redness of the extremities
SimD Dr. Pereyra-Borlongan
NAFARELIN [X], TRIPTORELIN [X]
Class GnRH analog OXYTOCIN [X]
Agonist of GnRH receptors. Increased LH and FSH SimD Demoxytocin
secretion with INTERMITTENT administration. Activates oxytocin receptors. Stimulates uterine
Reduced LH and FSH secretion with PROLONGED MOA contraction and labor. Stimulates mammary glands,
MOA lactation and milk let-down.
CONTINUOUS administration (due to downregulation
of GnRH receptors in the pituitary cells that normally Labor induction, Labor augmentation, Control of
Uses
release LH and FSH) postpartum hemorrhage
Ovarian Suppression, Controlled ovarian Fetal distress, Placental abruption, Uterine rupture,
Uses hyperstimulation, Endometriosis, Myoma uteri, SE Fluid retention (water intoxication), Hyponatremia,
Central Precocious puberty, Advanced Prostate cancer Heart failure, Seizures, Hypotension
Hot flushes, Sweats, Headache, Light-headedness, Contraindications to oxytocin include fetal distress,
SE Injection site reactions, Nausea, Osteoporosis, prematurity, abnormal presentation, CPD and
Gynecomastia, Reduced libido, Decreased hematocrit predispositions for uterine rupture
ATOSIBAN is an oxytocin receptor blocker (not yet
Symptoms of hypogonadism with continuous Notes
FDA approved since there is concern about increased
treatment rates of infant death)
Temporary exacerbation of precocious puberty or CARBETOCIN is an agonist of peripheral Oxytocin
prostate cancer, Apoplexy and Blindness during the receptors
first few weeks of therapy (remedy: co-administer
Flutamide, an androgen receptor antagonist) DESMOPRESSIN [B]
May be given Intranasally, depot formulation also Class Vasopressin/Anti-Diuretic hormone [C]
available ADH agonist. Desmopressin relatively selective for V2
Gonadorelin is a synthetic human GnRH receptors. Vasopressin V2 receptor agonist which
Leuprolide has a long agonist activity; its other name causes insertion of water channels in the collecting
MOA
is LEUPRORELIN/LEUPROLIN duct leading to more water reabsorption → decrease
the excretion of water; Act on extra-renal V2 receptors
The effect of this group of drugs will depend on the dosing
to increase Factor VIII and VWF factor
Notes that you give to the patient.
Central diabetes insipidus, Hemophilia A, von
Willebrand’s disease, Esophageal variceal bleeding,
GNRH ANALOGUES Uses
Primary nocturnal enuresis (pediatric Px), colon
PART 1 diverticula
https://qrs.ly/ygblnja
GI disturbance, Headaches, Flushing, Nausea,
SE
Hyponatremia, Seizures, Allergic reactions
May be given intranasally, PO or IV
Also contracts vascular smooth muscles via V1
GNRH ANALOGUES Notes
receptor leading to vasoconstriction (Used as
PART 2
treatment for esophageal varices or colon diverticula)
https://qrs.ly/2rblnjh
SUPPLEMENT: Diabetes Insipidus • thyroid hormones bind to intracellular receptors that control
• CLINICAL FEATURES the expression of genes responsible for many metabolic
o syndrome of polyuria, polydipsia, and hypernatremia processes
o excessive urination due to an inability of the kidney to
resorb water properly from the urine
• TYPES
o central diabetes insipidus is associated with deficient
secretion of ADH
o nephrogenic diabetes insipidus is associated with end-
organ resistance to the effects of ADH
CONIVAPTAN [C]
SimD TOLVAPTAN [C], LIXIVAPTAN
Class ADH antagonist
Antagonist at V1a, V2 receptors. Reduces renal
MOA excretion of water in conditions associated with
increased vasopressin
SIADH, Hyponatremia in hospitalized patients, offset
Uses fluid retention in acute heart failure and SIADH which
causes hyponatremia (dilutional)
SE Infusion site reactions, Hyperkalemia
Central pontine myelinolysis may occur with rapid
correction of hyponatremia
Notes Tolvaptan is more selective for V2 receptors
Lixivaptan and Tolvaptan are selectively active against the Table 38-1. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
V2 receptor
Dr. Pereyra-Borlongan Graves Disease
• autoimmune disorder where B lymphocytes produce an
THYROID AND ANTITHYROID DRUGS antibody that activates the TSH receptor (TSIs), causing
thyrotoxicosis
• these B lymphocytes are not susceptible to negative feedback
• expected thyroid profile: high T3/T4, low TSH
Key Features of Thyrotoxicosis and Hypothyroidism

THYROTOXICOSIS HYPOTHYROIDISM
• Warm, moist skin • Pale, cool, puffy skin
• Sweating, heat intolerance • Sensation of being cold
• Tachycardia, increased • Bradycardia, decreased
stroke volume, cardiac stroke volume, cardiac
output, and pulse output, and pulse
pressure pressure
• Pleural effusions,
• Dyspnea hypoventilation, and CO2
retention
• Increased appetite • Reduced appetite
• Nervousness, • Lethargy, general slowing
hyperkinesia, tremor of mental processes
• Weakness, increased deep • Stiffness, decreased deep
tendon reflexes tendon reflexes
• Infertility, decreased
• Menstrual irregularity,
libido, impotence,
decreased fertility
oligospermia
• Weight loss • Weight gain
• Exophthalmos
Prevent corneal ulcers among patients with exophthalmos!
LEVOTHYROXINE (T4) [A]

SimD LIOTHYRONINE (T3) [A], LIOTRIX [A]
Class Thyroid hormone
SUPPLEMENT: Thyroid hormones MOA Activation of nuclear receptors results in gene
Synthesis and Transport of Thyroid Hormones expression with RNA formation and protein synthesis
• TRANSPORT Uses Hypothyroidism, Myxedema coma
o iodide ion is converted to iodine by thyroid peroxidase SE Dry skin, Sweating, Tachycardia, Nervousness,
(TPO) Tremor, Weight loss, Weakness, Heat intolerance
• IODINE ORGANIFICATION Notes T4 dose must be lowered in patients with
o tyrosine residues in thyroglobulin are iodinated to form cardiovascular disease or longstanding
monoiodotyrosine (MIT) or diiodotyrosine (DIT) hypothyroidism (increased cardiosensitivity)
• COUPLING LIOTRIX is a 4:1 ratio of T4:T3
o 2 molecules of DIT combine to form T4, while 1 molecule Thyrotropin (a recombinant human TSH) is also
each of MIT and DIT combine to form T3 available
• PROTEOLYSIS Maximum effect is seen after 6-8 weeks of therapy
o T4 and T3 are released from the thyroid and transported in Liothyronine has a faster onset but shorter half-life
the blood by thyroxine-binding globulin (TBG)
MOA of T4 and T3
• T3 is about 10 times more potent than T4
• T4 is converted to T3 in target cells
SUPPLEMENT: Myxedema Coma Antithyroid drugs are the main therapy for maternal hyperthyroidism.
Both methimazole (MMI) and propylthiouracil (PTU) may be used during
pregnancy; however, PTU is preferred in the first trimester and should be
o medical emergency representing the end state of untreated replaced by MMI after this trimester. Choanal and esophageal atresia of
hypothyroidism fetus in MMI-treated and maternal hepatotoxicity in PTU-treated
o progressive weakness, stupor, hypothermia, pregnancies are of utmost concern. Maintaining free thyroxine
hypoventilation, hypoglycemia, hyponatremia, water concentration in the upper one-third of each trimester-specific reference
intoxication, shock and death interval denotes success of therapy. MMI is the mainstay of the treatment
• TREATMENT of postpartum hyperthyroidism, in particular during lactation.
§ intravenous loading dose of levothyroxine (300–400
mcg), followed by 50–100 mcg daily
SUPPLEMENT: Agranulocytosis
§ intravenous hydrocortisone is indicated if the patient has
associated adrenal or pituitary insufficiency • CLINICAL PRESENTATION
o acute severe neutropenia
Correlation to Physiology: o often heralded by sore throat or high fever
What are the physiologic effects of thyroid hormones? o increased susceptibility to infections
MNEMONIC: 4 B’s of thyroid hormone: Brain maturation, Bone growth,
Beta-adrenergic effects, and increase in Basal metabolic rate
• TREATMENT
Dr. Calderon Jr. o discontinue PTU or methimazole
PROPYLTHIOURACIL [D] o administer recombinant G-CSF to accelerate recovery
o treat with prophylactic broad-spectrum antibiotics
Class Thioamides
Inhibits thyroid peroxidase reactions. Blocks iodine GCSF: FILGRASTIN
MOA organification. Inhibits peripheral conversion of T4 GMCSF: SARGRAMOSTIM
into T3.
Uses Hyperthyroidism, Thyroid storm
RADIOACTIVE IODINE (131I) [X]
Maculopapular pruritic rash, Gastrointestinal distress,
Class Iodide
Fulminant hepatitis, Agranulocytosis, Urticaria,
Emits beta rays causing destruction of thyroid
SE Vasculitis, Lupus-like syndrome, Lymphadenopathy, MOA
parenchyma
Hypoprothrombinemia, Exfoliative dermatitis,
Uses Hyperthyroidism
Polyserositis, Arthralgia, Hypothyroidism
SE Hypothyroidism (permanent), sore throat, sialadenitis
Drug of choice for pregnant hyperthyroid patients
(does not enter placenta and breastmilk) Preferred treatment for most patients
Shorter DOA (6-8h) Permanent cure of thyrotoxicosis without surgery and
Slow onset of action (3-4 weeks for full effect) no effect on other tissues
Advantages include easy administration, effectiveness,
Propylthiouracil is rapidly absorbed, reaching peak serum low expense and absence of pain
levels after 1 hour. The bioavailability of 50–80% may be
Contraindicated in pregnant women or nursing
due to incomplete absorption or a large first-pass effect in
the liver. Given usually as 100mg TID-QID mothers
Patients should be euthyroid or on BB before RAI
Of the two, propylthiouracil is preferable during the first
Notes Onset of action is 6-12 weeks, Maximum effect seen in
trimester of pregnancy because it is more strongly protein-
bound and, therefore, crosses the placenta less readily. In 3-6 months
Notes
addition, methimazole has been, albeit rarely, associated Associated with radiation exposure: papillary thyroid CA
with congenital malformations. Administered orally in solution as sodium 131I, it is rapidly
Due to a black box warning about severe hepatitis, absorbed, concentrated by the thyroid, and incorporated
propylthiouracil should be reserved for use during the first into storage follicles
trimester of pregnancy, in thyroid storm, and in those Advantages of radioiodine include easy administration,
experiencing adverse reactions to methimazole (other than effectiveness, low expense, and absence of pain
agranulocytosis or hepatitis)
Dr. Pereyra-Borlongan Radioactive iodine should not be administered to pregnant
women or nursing mothers, since it crosses the placenta to
METHIMAZOLE [D- crosses the placenta] destroy the fetal thyroid gland and is excreted in breast milk
SimD Carbimazole [C]
Class Thioamides POTASSIUM IODIDE [D]
Inhibits thyroid peroxidase reactions. Blocks iodine LUGOL’S SOLUTION / Potassium Iodide Saturated
MOA SimD
organification. Solution (KISS)
Uses Hyperthyroidism, thyroid storm Class Iodide
Maculopapular pruritic rash, Gastrointestinal distress, Inhibit iodine organification and hormone release.
Cholestatic jaundice, Agranulocytosis, Urticaria, MOA
Reduce size and vascularity of thyroid gland.
Vasculitis, Lupus-like syndrome, Lymphadenopathy,
SE Hyperthyroidism, Thyroid storm, Preparation for
Hypoprothrombinemia, Exfoliative dermatitis,
Uses surgical thyroidectomy to reduce the size and
Polyserositis, Arthralgia, Hypothyroidism, Altered
vascularity of the thyroid gland, Radiation prophylaxis
sense of taste or smell
Iodism, Acneiform rash, Swollen salivary glands,
Drug of choice for nonpregnant hyperthyroid Px
Mucous membrane ulcerations, Conjunctivitis,
because of longer DOA (24h) SE
Rhinorrhea, Drug fever, Metallic taste, Bleeding
Prenatal exposure causes Aplasia Cutis Congenita
disorders, Anaphylactoid reactions
Slow onset of action (3-4 weeks for full effect)
Should not be used alone (escape in 2–8 weeks)
Methimazole and Carbimazole are teratogens (causes
Prevents radiation-induced thyroid damage
Aplasia Cutis Congenita)
Prenatal exposure causes fetal goiter
Given as once daily dosing
Onset is faster compared to Thioamides (2-7 days) but
THIAMAZOLE is the other name of Methimazole
effect is transient (thyroid gland escapes iodide block
Notes Because the thioamides do not inhibit the release of Notes after several weeks of treatment)
preformed thyroid hormone, their onset of activity is usually
slow, often requiring 3–4 wk for full effect. Acts through inhibition of thyroglobulin proteolysis.
Methimazole is about ten times more potent than Improvement in thyrotoxic symptoms occurs rapidly—
propylthiouracil and is the drug of choice in adults and within 2–7 days—hence the value of iodide therapy in
children thyroid storm.
Excretion is slower than with propylthiouracil; 65–70% of
a dose is recovered in the urine in 48 hours. Usually given as
30mg OD
KEY LEARNING POINTS: Wolf-Chaikoff VS Jod-Basedow o propranolol controls severe cardiovascular manifestations
Differentiate Wolf-Chaikoff effect from Jod-Basedow o hydrocortisone protects against shock and also blocks
phenomenon. peripheral conversion of T4 to T3
• Wolf-Chaikoff effect: ingestion of iodine causes
hypothyroidism MNEMONICS – Drug-Induced Hyperthyroidism
• Jod-Basedow phenomenon: ingestion of iodine causes What drugs can cause drug-induced hyperthyroidism?
hyperthyroidism CAM
Clofibrate Amiodarone Methadone
PROPRANOLOL [C]
ESMOLOL [C, D in 2nd & 3rd trim], METOPROLOL [C], Amiodarone-Induced Thyroid Disease
SimD
ATENOLOL [D] • hypothyroidism through its ability to block the peripheral
Class Beta-blocker conversion of T4 to T3
Blocks beta-receptors (control HR and other cardiac o TREATMENT: levothyroxine
abnormalities of severe thyrotoxicosis). Slows • hyperthyroidism either through an iodine-induced
MOA mechanism in persons with an underlying thyroid disease or
pacemaker activity; Inhibits peripheral conversion of
T4 into T 3 (Only Propranolol) through an inflammatory mechanism that causes leakage of
Hyperthyroidism esp Thyroid Storm, Adjunct to thyroid hormone
Uses control tachycardia, HTN and Atrial Fibrillation, Post- o TREATMENT: thioamides or corticosteroids
MI prophylaxis against sudden death OTHER ANTI-THYROID:
Bronchospasm, Cardiac depression, AV block, Anion Inhibitors:
SE
Hypotension, Bradycardia perchlorate (ClO4–), pertechnetate (TcO4–), thiocyanate (SCN–)
Esmolol may be used to treat thyrotoxicosis-related • block uptake of iodide by the gland through competitive inhibition of
arrhythmias the iodide transport mechanism
Cause clinical improvement WITHOUT altering • The major clinical use for potassium perchlorate is to block thyroidal
reuptake of I– in patients with iodide-induced hyperthyroidism (e.g.
thyroid hormone levels
amiodarone-induced hyperthyroidism). However, potassium
Onset is within hours but DOA is also short (4-6 hrs) perchlorate is rarely used clinically because it is associated with
Use Beta blockers without intrinsic sympathomimetic aplastic anemia.
Notes activity (e.g. metoprolol, propranolol, atenolol) Dr. Pereyra-Borlongan
Beta blockers cause clinical improvement of hyperthyroid

symptoms but do not typically alter thyroid hormone levels. CORTICOSTEROIDS AND ANTAGONISTS
Propranolol at doses greater than 160 mg/d may also
reduce T3 levels approximately 20% by inhibiting the
peripheral conversion of T4 to T3.
KEY LEARNING POINTS Peripheral T4 to T3 Conversion

Which drugs inhibit peripheral conversion of T4 to T3?
Propylthiouracil
Propranolol
Hydrocortisone
SUPPLEMENT: Thyroid Storm
• CLINICAL PRESENTATION Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
o sudden acute exacerbation of all of the symptoms of SUPPLEMENT: Major Groups of Corticosteroids
thyrotoxicosis, presenting as a life-threatening syndrome • GLUCOCORTICOIDS
o granulocyte count < 500 cells/mm3 o important effects on intermediary metabolism, catabolism,
o increased risk in older patients and in those receiving high- immune responses, and inflammation
dose methimazole therapy (> 40 mg/d) • MINERALOCORTICOIDS
• Treatment of Thyroid Storm o regulate sodium and potassium reabsorption in the
o PTU blocks thyroid hormone synthesis collecting tubules of the kidney
o iodides (SSKI) retards release of thyroid hormones
§ always administer PTU before iodides (SSKI)
Hydrocortisone (cortisol) is the prototype

glucocorticoid.
Betamethasone is the glucocorticoid with
the highest anti-inflammatory potency.
Fludrocortisone is the mineralocorticoid
with the highest salt-retaining potency
Outline of major pathways in adrenocortical hormone biosynthesis. The names of major adrenal secretory products are in shaded boxes. The enzymes and
cofactors for the reactions progressing down each column are shown on the left and across columns at the top of the figure. When a particular enzyme is deficient,
hormone production is blocked at points indicated by the shaded bars
• DESMOLASE – CONVERTS CHOLESTEROL TO PREGNENOLONE
• 21B hydroxylase deficiency: salt-wasting
• 11B hydroxylase: salt-wasting
• 17a hydroxylase deficiency: non-salt wasting
HYDROCORTISONE (CORTISOL) [C] Betamethasone and Dexamethasone hastens fetal lung

low-potency: DESONIDE maturation
SimD medium-potency: FLUTICASONE, MOMETASONE Prednisolone is the active metabolite of prednisone
high-potency: DESOXIMETASONE, CLOBETASOL [C] This group has a long t½, reduced salt-retaining effect
Notes
Class Glucocorticoid (short-acting, low-potency) and better penetration of lipid barriers
Activates glucocorticoid receptors, leading to altered Behavioral changes secondary to steroid use is termed
MOA gene transcription. Suppresses inflammation. “Steroid Rage”
Replaces cortisol when deficient. Dr. Pereyra-Borlongan
Acute adrenal insufficiency associated with life-

threatening shock, chronic adrenal insufficiency SUPPLEMENT: Special Considerations
Uses (Addison's disease), congenital adrenal hyperplasia, • minimize toxicities by local application, alternate-day
Insect bites, Contact dermatitis, Status asthmaticus, therapy or dose-tapering
Thyroid storm • avoid adrenal insufficiency in patients who have had long-
None common when used topically or at physiologic term therapy by giving additional "stress dose“ during
SE
replacement doses serious illness or before major surgery
• patients who are being withdrawn from long-term therapy
PREDNISONE [C if immediate release, D if delayed release] should have slow dose-tapering to allow recovery of normal
PREDNISOLONE, METHYLPREDNISOLONE [C], adrenal function
SimD MEPREDNISONE, DEXAMETHASONE [C],
FLUDROCORTISONE [C]
BETAMETHASONE [C], TRIAMCINOLONE
SimD DEOXYCORTICOSTERONE
Class Glucocorticoid
Class Mineralocorticoid
MOA Suppresses inflammation and immune response Strong agonist of mineralocorticoid receptors and
Wide variety of inflammatory, allergic, autoimmune MOA moderate activation of glucocorticoid receptors.
(collagen and rheumatic disease etc.) and neoplastic Increases Na reabsorption, K and H excretion
diseases (hematopoietic cancers), Prevention of organ Chronic adrenal insufficiency (Addison’s disease),
Uses transplant rejection, Asthma, , lung maturation in Uses Congenital adrenal hyperplasia, Adrenal replacement
preterm labor (betamethasone and dexamethasone), therapy post-adrenalectomy
chemotherapy-induced vomiting, hypercalcemia, Salt and fluid retention, Hypokalemia, Congestive
mountain sickness SE heart failure, Muscle wasting, Osteoporosis, Glucose
Adrenal suppression, Growth inhibition, Muscle intolerance, Behavioral changes
SE wasting, Osteoporosis, Salt retention, Glucose
intolerance, Behavioral changes (psychosis)
Additive hypokalemia with loop diuretics and KETOCONAZOLE [C]
thiazides Class Glucocorticoid synthesis inhibitor, Azole antifungal
Deoxycorticosterone is the precursor of aldosterone Inhibits cholesterol side-chain cleavage, cytochrome
Fludrocortisone also has significant glucocorticoid MOA P450 enzymes and other enzymes necessary for
activity synthesis of all steroids
Notes
Aldosterone is implicated in myocardial and vascular Adrenal carcinoma, Hirsutism, Breast cancer, Prostate
fibrosis and baroreceptor dysfunction Uses
cancer, Cushing’s syndrome, Fungal infections
Adrenalectomy should be done for px with adrenal tumor Hepatotoxicity, Many drug interactions, Androgenic
SE
such as pheochromocytoma effect
Potent inhibitor of CYP450 enzymes
Notes Itraconazole is an alternative to Ketoconazole
MNEMONIC: Addison VS Conn Dr. Pereyra-Borlongan
Addison’s = Addrenal insufficiency

Conn’s = adrenal exCess METYRAPONE [C]
Class Glucocorticoid synthesis inhibitor
SUPPLEMENT: Cushing’s Syndrome Selective inhibitor of steroid 11-hydroxylation,
MOA
interfering with cortisol and corticosterone synthesis
• syndrome caused by any condition that produces elevated
Diagnostic testing for adrenal function, Cushing’s
glucocorticoid levels Uses
syndrome
• causes of Cushing’s syndrome (CS)
SE Dizziness, Gastrointestinal disturbances
o iatrogenic Cushing’s syndrome due to exogenous steroid
intake is the most common cause Drug of choice for pregnant patients with Cushing’s
o adrenal CS due to cortisol-secreting adrenal adenoma Notes syndrome
Inhibitor of 11-B-hydroxylase
o pituitary CS (Cushing’s disease) due to ACTH-secreting Dr. Pereyra-Borlongan
pituitary adenoma
o ectopic CS due to paraneoplastic ACTH production (usually
SUPPLEMENT:
from lung tumors)
MIFEPRISTONE (RU486) [X]
Class Glucocorticoid antagonist
Competitive inhibitor at the GC receptor as well as
MOA
progesterone receptor
Uses Cushing Syndrome
abdominal pain and cramping, uterine cramping,
SE nausea, headache, vomiting, diarrhea, dizziness,
vaginal bleeding
also used as an approved abortifacient for medical
Notes
abortion (usually together with misoprostol)
SPIRONOLACTONE [C]
Class Aldosterone antagonist
MOA Blocks Aldosterone receptors
For hypokalemia due to other diuretics, for post-MI,
Uses
hyperaldosteronism
Hyperkalemia, anti-androgenic effect (e.g.
SE
gynecomastia)
also, with weak antagonist effect at the androgen
Notes
receptor
GONADAL HORMONES AND INHIBITORS
Benign intracranial hypertension: pseudotumor cerebri

Warn Elderly women about steroid use since it may cause osteoporosis
MNEMONICS FOR SIDE EFFECTS OF CORTICOSTEROIDS:

CUSHINGOID: Cataract, Ulcers, Striae, Hypertension, Hirsutism, Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
Immunosuppression, Infection, Necrosis of the femoral head, Glucose

elevation, Osteoporosis, Obesity, Impaired wound healing, and Diabetes MOA OF OVARIAN HORMONES
Dr. Calderon Jr.
• mechanism of action involves entry into cells, binding to
cytosolic receptors, and translocation of the receptor–hormone
CORTICOSTEROID ANTAGONISTS complex into the nucleus, where it modulates gene expression
AMINOGLUTETHIMIDE [D]
Class Glucocorticoid synthesis inhibitor SUPPLEMENT: Estrogens
Inhibits Desmolase, blocking conversion of cholesterol • major ovarian estrogen in women is estradiol
MOA to pregnenolone. Reduces synthesis of all hormonally • mixtures of conjugated estrogens from biologic sources
active steroids. (Premarin) are used for hormone replacement therapy (HRT)
Uses Breast cancer, Cushing syndrome • synthetic estrogens with high bioavailability (ethinyl
SE Skin rash, Hepatotoxicity, Hypothyroidism estradiol, mestranol) are used as hormonal contraceptives
Abused by body builders to lower circulating levels of
cortisol in the body and prevent muscle loss
Notes
Also inhibits synthesis of all hormonally active
steroids
PROGESTINS
NORGESTREL [X]
NORETHINDRONE, ETHYNODIOL, MEGESTROL,
DESOGESTREL, NORELGESTROMIN,
NORGESTIMATE, ETONOGESTREL, PROGESTERONE,
SimD
LEVONORGESTREL, DYDROGESTERONE,
ULIPRISTAL, TIBOLONE, NORETHISTERONE,
DIENOGEST
Class Progestin
Activates progesterone receptors; Changes rates of
MOA
transcription of progesterone-regulated genes
Hormone replacement therapy (given together with
Estrogen, to prevent estrogen-induced endometrial
Uses cancer), contraception, assisted reproduction (for
maintenance of pregnancy), anovulation induction
(given in high doses to suppress FSH and LH)
Hypertension, Decreased HDL, Weight gain, Reversible
SE decrease in bone mineral density, Delayed resumption
of ovulation after use
• Prevents estrogen-induced endometrial cancer
when used in combination
• Megestrol is used as an appetite stimulant
• Given PO or as vaginal cream
• Medroxyprogesterone has a better oral
bioavailability
• L-Norgestrel and Norethindrone has more
androgenic effect
• Norgestrel undergoes enterohepatic recirculation
ETHINYL ESTRADIOL [X] Notes • Effects of progesterone: induces secretory changes
in the endometrium, stabilize the endometrium,
SimD MESTRANOL [X], ESTRADIOL CYPIONATE,
affect carbohydrate metabolism and stimulate
PREMARIN, ESTRIOL
deposition of fat, high doses suppress FSH and LH
Class Estrogen
secretion
MOA Activates estrogen receptors; leads to changes in rates
• TIBOLONE is a synthetic steroid with weak
of transcription of estrogen-regulated genes
estrogenic, progestogenic and androgenic activity,
Uses Primary hypogonadism, Postmenopausal hormonal and hence is an agonist of the estrogen, progesterone
replacement therapy, Osteoporosis, Contraception, and androgen receptor. It is primarily used in
Intractable dysmenorrhea menopausal hormone therapy, postmenopausal
SE Breakthrough bleeding, Nausea, Breast tenderness, osteoporosis and endometriosis.
Migraine, Thromboembolism (DVTs), Gallbladder
disease, Hypertriglyceridemia, Hypertension, HORMONAL CONTRACEPTIVES
premature closure of the epiphysis in young females,
• contain either a combination of an estrogen and a progestin or a
Increased risk of breast and endometrial cancer
(remedy: add progesterone to the preparation) progestin alone
Notes Ethinyl • available in a variety of preparations
Estradiol has low bioavailability
o oral pills
PO/TD/IM/Intravaginal
Estradiol cypionate is IM with longer t½ o long-acting injections
Premarin is a mixture of conjugated estrogen used in o transdermal patches
HRT o vaginal rings
Ethinyl estradiol undergoes enterohepatic o intrauterine devices (IUDs)
recirculation Implants are good for 3 years J, Injectables are good for 3 months J
Effects of Estrogen: growth of genital structures and
secondary sexual characteristics, modifies serum SUPPLEMENT: Types of Oral Contraceptives
protein levels and decrease bone resorption, enhances • MONOPHASIC
coagulability of blood, increases TG and HDL levels o combination estrogen-progestin tablets that are taken in
while decreasing LDL levels, if given as continuous constant dosage throughout the menstrual cycle
infusion will inhibit FSH and LH release • BIPHASIC or TRIPHASIC
PREMARIN is from PREgnant MARe’s urINe J o combination preparations in which the progestin or
Breakthrough bleeding – bleeding in between dosages of estrogen dosage, or both, changes during the month
OCPs
o more closely mimics hormonal changes in menstrual cycle
OCPs: increase HYPERCOAGUABILITY
Dr. Pereyra-Borlongan • PROGESTIN-ONLY PREPARATIONS
Progestin-Only Pills are recommended for breastfeeding moms since
DIETHYLSTILBESTROL [X] they do not affect lactation
Class Synthetic estrogen (nonsteroidal) Dr. Pereyra-Borlongan
Activates estrogen receptors; leads to changes in rates SUPPLEMENT: Postcoital Contraceptives

MOA
of transcription of estrogen-regulated genes
• also known as emergency contraception
Atrophic vaginitis, Hormone replacement therapy,
• prevent pregnancy if administered within 72 h after
Uses Prevention of adverse pregnancy outcomes,
unprotected intercourse
Metastatic prostate cancer
• EXAMPLES: progestin (L-Norgestrel) alone, estrogen alone,
Breakthrough bleeding, nausea, breast tenderness,
combination of estrogen and progestin
migraine, thromboembolism (DVTs), gallbladder
o progestin-only preparation causes fewer side effects than
disease, hypertriglyceridemia, hypertension,
SE the estrogen-containing preparations
premature closure of the epiphysis in young females,
increased risk of breast and endometrial cancer
(remedy: add progesterone to the preparation)
Associated with Infertility, Ectopic pregnancy, Clear
Notes cell vaginal adenocarcinoma in daughters of mothers
who took DES
SELECTIVE ESTROGEN RECEPTOR MODULATORS

(SERMS)
• mixed estrogen agonists that have estrogen agonist effects in
some tissues and act as partial agonists or antagonists in other
tissues
TAMOXIFEN [D]
SimD TOREMIFENE [D]
Class Selective Estrogen Receptor Modulator
MOA Estrogen antagonist actions in breast tissue and CNS.
Estrogen agonist effects in uterus, liver and bone.
Uses Hormone-responsive breast cancer, prophylaxis of
breast CA esp. in those with high risk
SE Hot flushes, Thromboembolism (DVTs), Endometrial
hyperplasia, Endometrial cancer
MOA OF COMBINATION HORMONAL CONTRACEPTIVES
Notes Prevents osteoporosis in post-menopausal women
• inhibition of ovulation (the primary action) and decreases risk of atherosclerosis at the risk of
• effects on the cervical mucus glands, uterine tubes, and causing endometrial cancer
endometrium that decrease the likelihood of fertilization and FLUVESTRANT is a FULL ESTROGEN RECEPTOR
implantation ANTAGONIST (No agonist effect) used in hormone
receptor positive metastatic breast cancer
ESTRADIOL + NORETHINDRONE [X] Torimefene is structurally related to Tamoxifen
ETHINYL ESTRADIOL + DESOGESTREL/NORGESTREL
Given for breast cancer patients who are ER+ PR+
ETHINYL ESTRADIOL + DROSPIRENONE
SimD Dr. Pereyra-Borlongan
ETHINYL ESTRADIOL + NORGESTIMATE
ETHINYL ESTRADIOL + NORETHISTERONE RALOXIFENE [X]
Class Combined oral contraceptive Class Selective Estrogen Receptor Modulator
Combined oral contraceptive, activates estrogen and Estrogen antagonist actions in breast tissue, uterus
progesterone receptors, inhibits ovulation, effects on MOA and CNS. Estrogen agonist effects in liver and bone.
MOA cervical mucus gland, uterine tubes and endometrium Increases bone mineral density.
lead to decreased fertility, inhibit ovulation when Uses Osteoporosis, Breast cancer prevention
given before the LH surge SE Hot flushes, Thromboembolism (DVTs)
Contraception, Hypogonadism, Acne, Hirsutism, Reduces incidence of breast cancer in women who are
Uses
Dysmenorrhea, Endometriosis Notes at very high risk
Breakthrough bleeding, Nausea, Breast tenderness, No estrogenic effects on endometrial tissue
Skin pigmentation, Thromboembolism (DVTs), Breast
SE Preferred in patient with history of breast cancer in the management of
cancer (earlier onset), headache, skin pigmentation,
hot flushes.
depression, weight gain and hirsutism for older OCPs Dr. Calderon Jr.
Lifetime risk of breast cancer is NOT changed

CLOMIPHENE [X]
Does NOT protect against STDs Class Selective Estrogen Receptor Modulator
Norethindrone is a testosterone derivative while Partial agonist of estrogen receptors in pituitary.
Drospirenone is a spironolactone derivative that is MOA Reduces negative feedback by estradiol. Increases FSH
Notes antiandrogenic and LH output.
Norgestimate and Desogestrel are newer progestins Induction of ovulation for women who want to get
Combined OCPs may be used for androgen-induced Uses
pregnant
hirsutism
Hot flushes, Eye symptoms (afterimages), Headache,
Mestranol (Estrogen) may also be used in OCPs
SE Constipation, Reversible hair loss, Ovarian
enlargement, Multiple pregnancies (10%)
MEDROXYPROGESTERONE ACETATE [D]
Increased risk of low-grade ovarian cancer with long-
Class Contraceptive (progestin-only) term use
Activates progesterone receptors. Prevents May cause multiple pregnancies ; FULVESTRANT: pure
MOA conception by altering cervical mucus and creating a estrogen receptor antagonist in all tissues used in
hostile endometrium Notes breast CA resistant to tamoxifen
Uses Contraception, Hormone replacement therapy
Acts as antagonist to estrogen receptors in the pituitary →
Breakthrough bleeding, Hair loss, Dysmenorrhea,
SE inhibit negative feedback mechanism by estrogen → leads
Delayed return of fertility, Osteoporosis to pituitary stimulation causing ↑ LH and FSH
Intramuscular depot preparation (Depo-Provera) Dr. Pereyra-Borlongan
Notes
Does NOT protect against STDs
MNEMONIC: Clomiphene
LEVONORGESTREL [X] Clone Me Phlease = Clomiphene
SimD ETHINYL ESTRADIOL + LEVONORGESTREL
Class Postcoital contraceptive
Activates estrogen and/or progesterone receptors. MISCELLANEOUS ANTAGONISTS
MOA ANASTROZOLE [X]
Thickens cervical mucus. Inhibits ovulation.
Uses Emergency contraception SimD LETROZOLE, EXEMESTANE
Severe nausea, vomiting, Breast tenderness, Irregular Class Estrogen synthesis inhibitor
SE Bleeding, Headache, Dizziness (fewer SE compared to MOA Reduces estrogen synthesis by inhibiting aromatase
estrogen alone and combination contraceptives) Uses Breast cancer, Precocious puberty
Must be taken within 72 hours of unprotected sexual Hot flushes, Musculoskeletal disorders, Osteoporosis,
SE
intercourse (not effective once implantation has Joint pains
occurred) Effective against breast cancers that have become
Notes resistant to tamoxifen
Yuzpe regimen for combination emergency
contraception Exemestane is an IRREVERSIBLE inhibitor
Notes
Does NOT protect against STDs Aromatase is the enzyme which converts Testosterone to
Estrogen (Estradiol)
DANAZOL [X] ANDROGENS
Class Ovarian inhibitor (antiandrogen) SUPPLEMENT: Testosterone
Weak cytochrome P450 inhibitor and partial agonist
MOA • synthesized from progesterone and dehydroepiandrosterone
of progestin and androgen receptors
(DHEA)
Endometriosis, Fibrocystic disease, Hemophilia,
Uses • partly bound to sex hormone-binding globulin (SHBG)
Angioneurotic edema
o increased by estrogen, thyroid hormone and cirrhosis
Acne, Hirsutism, Weight gain, Menstrual disturbances,
SE o decreased by androgen, growth hormone and obesity
Hepatic dysfunction
• converted in several organs (e.g. prostate) to
Contraindicated during pregnancy and breast-feeding
Notes dihydrotestosterone (DHT), which is the active hormone in
May also act on Glucocorticoid receptors
those tissues
LEUPROLIDE [X]
GONADORELIN [B], GOSERELIN [X], HISTRELIN, CLINICAL USE OF TESTOSTERONE
SimD • replacement therapy in hypogonadism
NAFARELIN [X], TRIPTORELIN [X]
Class GnRH analog • stimulate RBC production in certain anemias
Agonist of GnRH receptors. Increased LH and FSH • promote weight gain in patients with wasting syndromes (e.g.
secretion with INTERMITTENT administration. AIDS patients)
Reduced LH and FSH secretion with PROLONGED • performance enhancement in athletes
MOA o exploited illicitly to increase muscle bulk and strength
CONTINUOUS administration (due to downregulation
of GnRH receptors in the pituitary cells that normally
release LH and FSH) TESTOSTERONE [X]
Ovarian Suppression, Controlled ovarian FLUOXYMESTERONE, METHYLTESTOSTERONE,
Uses hyperstimulation, Endometriosis, Myoma uteri, SimD TESTOSTERONE CYPIONATE, OXYMETHOLONE,
Central Precocious puberty, Advanced Prostate cancer MESTEROLONE
Hot flushes, Sweats, Headache, Light-headedness, Class Androgen
SE Injection site reactions, Nausea, Osteoporosis, Activates androgen receptors. Promotes development
Gynecomastia, Reduced libido, Decreased hematocrit MOA of male characteristics. Increases body muscle bulk
and RBC production.
Symptoms of hypogonadism with continuous Male hypogonadism, Delayed puberty, Wasting
treatment Uses
syndromes, certain types of anemias
Temporary exacerbation of precocious puberty or Virilization and menstrual irregularities in females,
prostate cancer, Apoplexy and Blindness during the SE paradoxical feminization in males, cholestatic
first few weeks of therapy (remedy: co-administer jaundice, elevated LFTs
Notes
Flutamide, an androgen receptor antagonist) Contraindicated in pregnant women and patients with
May be given Intranasally, depot formulation also prostate cancer
available Effects of androgen: secondary sexual characteristics,
Gonadorelin is a synthetic human GnRH fertility and libido, male pattern baldness, increases
Leuprolide has a long agonist activity muscle mass, increased RBC production, decreased
Notes urea nitrogen excretion, maintains normal bone
GANIRELIX [X] density
SimD CETRORELIX [X], ABARELIX, DEGARELIX Used illegally by athletes as performance enhancer
Class GnRH antagonist
Paradoxical femininization may be due to negative
Blocks GnRH receptors. Reduces endogenous
MOA feedback on physiologic testosterone levels
production of LH and FSH. Dr. Pereyra-Borlongan
Prevents premature LH surge during Controlled
Uses
ovarian hyperstimulation, Advanced Prostate cancer OXANDROLONE [X]
Nausea, Headache, Hypersensitivity (abarelix), Hot SimD NANDROLONE DECANOATE
SE flushes, Gynecomastia, decreased libido, Decreased Class Androgen (anabolic steroid)
hematocrit, Osteoporosis MOA Activates androgen receptors. Promotes development
Does NOT cause a tumor flare-up when used for of male characteristics. Increases body muscle bulk
treatment of advanced prostate cancer and RBC production. Increased ratio of anabolic-to-
Also, less likely to cause ovarian hyperstimulation androgenic activity.
Notes
syndrome Uses Illegal performance enhancement drugs in athletes
Degarelix is used for prostate CA while Ganirelix SE Virilization in females, Paradoxical feminization in
prevent LH surge in controlled ovulation males, Cholestatic jaundice, Elevated liver enzymes,
Hepatocellular carcinoma
MIFEPRISTONE (RU-486) [X] Notes This group is called “Anabolic steroids”
Glucocorticoid receptor antagonist
Class
Progesterone receptor antagonist
Pharmacologic antagonist of glucocorticoid and
MOA
progesterone receptors
Uses Medical abortion, Cushing's syndrome
Vaginal bleeding, abdominal pain, GI upset (vomiting,
SE diarrhea), uterine cramping, nausea, vomiting,
headache, dizziness, diarrhea
Combination with misoprostol results in abortion of
95% of early pregnancies
As abortifacient in early pregnancy (may be used up to
Notes 49 days after menses)
complication: failure to induce complete abortion
May cause sepsis due to unusual organisms
(Clostridium sordelli)
ANTI-ANDROGENS
** For benign and malignant prostate disease, precocious puberty,
hair loss and hirsutism **
FLUTAMIDE [D]
SimD BICALUTAMIDE, NILUTAMIDE
Class Androgen antagonist
MOA Competitive antagonist at androgen receptor
Uses Prostate cancer, Surgical castration (nilutamide)
SE Gynecomastia, Hot flushes, Impotence, Hepatoxicity
Less hepatotoxicity with bicalutamide and nilutamide
GnRH analogs (leuprolide) must be co-administered
Notes
with flutamide to prevent acute flare-up of prostate
cancer
CYPROTERONE [X]
SimD CYPROTERONE ACETATE
Class Androgen antagonist
Antagonist at androgen receptor. Marked
MOA progestational effect that suppresses the feedback Harrison’s Principles of Internal Medicine. 20th ed. 2018
enhancement of LH and FSH.
Hirsutism, Component of combined oral
Uses
contraceptives, Decreases sexual drive in men PANCREATIC HORMONES,
Hepatotoxicity, Adrenal suppression, Depression, ANTIDIABETIC DRUGS AND GLUCAGON
SE
Gynecomastia, Galactorrhea, Thromboembolism
Notes Orphan drug status
FINASTERIDE [X]
SimD DUTASTERIDE
Class Androgen synthesis inhibitor
Inhibits 5a-reductase enzyme that converts
MOA
testosterone to dihydrotestosterone
Benign prostatic hyperplasia (BPH), Male-pattern
Uses
baldness, Hirsutism
SE Impotence (rare), Gynecomastia, Depression
Controversial use in prevention of prostate cancer
Dutasteride is newer with longer t½
Notes
This group is less likely to cause impotence, infertility
and decreased libido DM Drugs Part 1
https://qrs.ly/jkboajl
MNEMONIC: Finasteride
FinAsteRIde
Five Alpha Reductase Inhibitor
Correlation to Physiology: DM Drugs Part 2
Dihydrotestosterone is the most potent form of testosterone. This is https://qrs.ly/4iboajf
essential in the development of secondary sexual characteristics in male.
Giving 5-alpha reductase aids in the management of smooth muscle
hypertrophy in the prostate.
Dr. Calderon Jr.
DM Drugs Part 3
https://qrs.ly/5dboaja
SUPPLEMENT: Diabetes Mellitus

Diabetes Mellitus
• chronic disorder of carbohydrate, fat, and protein metabolism
due to a relative or absolute deficiency in insulin secretory
response
Types of Diabetes Mellitus
• TYPE 1 DIABETES
o usually has its onset during childhood
o results from autoimmune destruction of pancreatic b cells
• TYPE 2 DIABETES
o progressive disorder characterized by increasing insulin
resistance and diminishing insulin secretory capacity
o frequently associated with obesity and is much more
common than type 1 diabetes
o usually has its onset in adulthood
Insulin
• synthesized as prohormone proinsulin
• cleavage of proinsulin and cross-linking result in formation of
insulin and a residual C-peptide
• C-peptide is used to:
o differentiate type 1 and type 2 DM
o diagnose MEN
o rule out factitious hypoglycemia
o assess insulin resistance in patients with PCOS
• neither proinsulin nor C-peptide appears to have any Activates insulin receptors → Reduces circulating
physiologic actions glucose by increasing glucose uptake. Promote
MOA
Type 1 DM: no C-peptide. Type 2: have C-peptide glucose transport and oxidation, glycogen lipid and
Dr. Pereyra-Borlongan protein synthesis and regulates gene expression
Correlation to Pathology: Diabetes Mellitus – diabetes means urine and Type 1 and Type 2 Diabetes mellitus, Diabetic
Uses
mellitus means malt or sugar. Remember, the problem with Type 1 emergencies (DKA, HHS – rapid acting), Hyperkalemia
Diabetes Mellitus is the absence of the pancreatic beta cells and in Type 2 Hypoglycemia, Insulin allergy, Immune insulin
Diabetes Mellitus is the problem is not the insulin per se but the tissue resistance, Lipodystrophy at injection site, Weight
receptor’s sensitivity to insulin. SE Gain, Increased cancer risk (linked to insulin
Dr. Calderon Jr.
resistance and hyperinsulinemia in Px with

MOA OF INSULIN
prediabetes and T2DM)
• binds to a tyrosine kinase receptor, which phosphorylates itself
• Beta-blockers may mask signs of hypoglycemia
and a variety of intracellular proteins when activated by the
hormone • All insulin preparations contain zinc
• activation of phoshphatidylinositol-3 kinase pathway and MAP • Parenteral (IV or SC)
kinase pathway • Effects of insulin: increased glycogen and protein
• translocation of glucose transporters (especially GLUT 4) to the synthesis, decreased protein catabolism, increased
cell membrane TG storage
o increase in glucose uptake • Rapid acting insulins are injected a few mins prior to
o increased glycogen synthase activity meals and they are the preferred insulin for
o increased glycogen formation continuous SC infusion devices
Insulin is also capable of inducing entry of K+ (potassium) into cells Notes • Short-acting insulins are injected more than an hour
Dr. Pereyra-Borlongan before a meal
SUPPLEMENT: Glucose Transporters • Intermediate acting insulins are often combined
with regular and rapid acting insulins
• Long acting insulins are called "peakless" insulins
The ratio of zinc and other substances to insulin influences
the rate of release and duration of action.
When mixing intermediate with rapid acting insulin, NPH
preferred over lente because lente retards the onset of
action of regular insulin
EXTENT AND DURATION OF ACTION

OF VARIOUS TYPES OF INSULIN
Harrison’s Principles of Internal Medicine. 20th ed. 2018
REPRESENTATIVE INSULIN REGIMENS

FOR THE TREATMENT OF DIABETES
Figure 397-1. Harrison’s Principles of Internal Medicine. 20th ed. 2018
Insulin Types and Activity
Harrison’s Principles of Internal Medicine. 20th ed. 201

INSULIN [B]
Rapid: LISPRO, ASPART, GLULISINE
Short: REGULAR (Humulin R)
Intermediate: NPH, LENTE (Humulin N)
SimD
Long: ULTRALENTE, GLARGINE, DETEMIR, INSULIN
DEGLUDEC
Premixed Insulin: Humulin 70 NPH/30 Regular
Class Pancreatic hormone
0.25 TO 0.50 OF AN HOUR: 15-30mins CLINICAL APPLICATION
When mixing intermediate with rapid acting insulin, NPH preferred over
A 44-year-old male presents with the complaints of polyuria
lente because lente retards the onset of action of regular insulin
Dr. Pereyra-Borlongan and polydipsia. Diagnosis of type 2 DM is made and he is started
on insulin regimen. CBG monitoring reveals:

E. Waning and Dawn Phenomenon
D. Dawn Phenomenon
C. Somogyi Effect
B: Waning of Insulin Dose
A: Normal
SUPPLEMENT: Honeymoon Period

• period in type 1 DM when exogenous insulin requirements
decrease due to an increase in the endogenous production of
insulin
• initiation of insulin therapy causes activation of residual
pancreatic beta cells
• transient phase followed by total lack of endogenous insulin
production
STRATEGIES FOR INSULIN THERAPY

• BASAL BOLUS
Harrison’s Principles of Internal Medicine. 20th ed. 2018 o most physiologic strategy because it copies the body’s
MNEMONICS: Insulin Preparations normal production of insulin as closely as possible
• LISpro = mabiLIS o long-acting insulin (BASAL) + short-acting insulin with every
• gLARGine = Go Large! meal (BOLUS)
• LANTus = LANTa na sa sobrang tagal! • SLIDING INSULIN SCALE
o fixed amounts of long-acting insulin to be given routinely
SUPPLEMENT: Hypoglycemia o amount of short-acting insulin varied depending on pre-
Hypoglycemia prandial CBG
• NEUROGLYCOPENIC SYMPTOMS
KEY LEARNING POINTS Routes of Insulin Administration
o result of central nervous system (CNS) glucose deprivation
o EXAMPLES: Why are the only routes of administration for insulin
§ behavioral changes, confusion, fatigue, seizure and loss of subcutaneous and IV?
consciousness ROUTE REASON WHY NOT USED
• NEUROGENIC (OR AUTONOMIC) SYMPTOMS Does not result in a reproducible and
o result of CNS-mediated sympathoadrenal discharge Transdermal sufficient transfer of insulin across the
o EXAMPLES: skin
§ adrenergic symptoms: palpitations, tremor, anxiety Lack of a specific peptide carrier system
Oral
§ cholinergic symptoms: sweating, hunger, paresthesia in the gut
Bioavailability was low and metabolic
KEY LEARNING POINTS - Hypoglycemia Intranasal effect lasted too short to be of clinical
Which patients are more prone to developing hypoglycemia
usefulness
with insulin use?
Overall metabolic response not
• advanced renal disease Intramuscular
comparable to SC
• elderly
Most promising; comparable to SC and IV
• children younger than 7 years Inhalation but is still presently in Phase III trials
EARLY MORNING HYPERGLYCEMIA (Exubera)
• SOMOGYI EFFECT
o when the evening dose of intermediate insulin is high, NONINSULIN ANTIDIABETIC AGENTS
hypoglycemia develops around 3:00 AM Mnemonics for your OHAs will be given during the pearls J
o as a result, counter-regulatory hormones are produced, Dr. Pereyra-Borlongan
resulting in pre-breakfast hyperglycemia
o treatment: decreasing evening dose of insulin
INSULIN SECRETAGOGUES
• WANING OF INSULIN DOSE
o when the evening dose of intermediate insulin is low, MOA OF INSULIN SECRETAGOGUES
hyperglycemia will be present both at 3:00 AM and 7:00 AM • stimulate the release of endogenous insulin by promoting
o treatment: increasing evening dose of insulin closure of potassium channels in the pancreatic B-cell
§ caution should be taken to not cause hypoglycemia while membrane
asleep • depolarizes the cell and triggers insulin release
• DAWN PHENOMENON • not effective in patients who lack functional pancreatic B cells
o insulin sensitivity becomes low between 6:00AM and 7:00 AM CHLORPROPAMIDE [C]
due to the growth hormone spike SimD TOLBUTAMIDE [C], TOLAZAMIDE [C]
o as a result, mild hyperglycemia occurs in the early morning but Class Insulin secretagogue (1st Generation Sulfonylurea)
the 3:00 AM glucose levels will be normal Increases insulin secretion from pancreatic beta cells
o waning of insulin dose and Dawn phenomenon may coexist MOA
by closing ATP-sensitive K+ channels
§ hyperglycemia will be present both at 3:00 AM and 7:00 AM, Uses Type 2 diabetes mellitus
but the 7:00 AM levels will be much higher
Hypoglycemia, Weight gain, Disulfiram reaction,
o treatment: increasing evening dose of insulin
SE Hyperemic flush after alcohol ingestion, Dilutional
§ caution should be taken to not cause hypoglycemia while
hyponatremia, Hematologic toxicity
asleep
Tolbutamide and chlorpropamide are highly protein Drug of choice for obese diabetics
bound drugs → Drugs that compete for protein binding Contraindicated in patients with renal disease,
may enhance hypoglycemic effects alcoholism, hepatic disease CHF or conditions
Requires islet cell function predisposing to tissue anoxia (Hypoxic or acidotic
Notes Lower Potency, Greater Toxicity states)
May also cause allergic reactions and rash May also cause slowing of glucose absorption from
Notes
High propensity to cause hypoglycemia especially among GIT, decreased plasma glucagon
elderly patients that’s why it is seldom used Causes a decrease in endogenous insulin production
by increasing insulin sensitivity of tissues "Insulin
Sparing Effect" therefore does not have weight gain as
GLIPIZIDE [C] a SE
GLIMEPIRIDE [C], GLYBURIDE/GLIBENCLAMIDE, Does NOT cause hypoglycemia
SimD
GLICLAZIDE
Metformin is a euglycemic agent. You may sound familiar with its trade
Class Insulin secretagogue (2nd Generation Sulfonylurea) name “Glucophage” as if the drug is eating the glucose. Metformin and
Increases insulin secretion from pancreatic beta cells its cousin Thiazolidinediones bypass the insulin receptor. I want you to
MOA by closing ATP-sensitive K+ channels → depolarization remember that both of these medications act via gene expression to
of Beta cells of the pancreas sensitize tissue receptor to insulin
Type 2 diabetes mellitus. In patients with functioning Dr. Calderon Jr.
Beta cells, reduce circulating glucose, increase SUPPLEMENT: METFORMIN COMBINATIONS:

Uses
glycogen, fat and protein formation, regulates gene • Met + Glipizide
expression • Met + Glyburide (Glucovance)
Hypoglycemia (less), Weight gain, Photosensitivity, • Met + Pioglitazone
SE Hematologic toxicity, Cholestatic jaundice • Met + Rosiglitazone (Avandamet)
(glibenclamide) • Met + Repaglinide
Contraindicated in patients with hepatic impairment • Met + Saxagliptin
and renal insufficiency • Met + Sitagliptin (Janumet)
Notes
Requires islet cell function
May come in combination with Metformin
MOA OF THIAZOLIDINEDIONES
REPAGLINIDE [C] • increase target tissue sensitivity to insulin by activating the
SimD NATEGLINIDE [C], MITIGLINIDE peroxisome proliferator-activated receptor-gamma nuclear
Class Insulin secretagogue (Meglitinide) receptor (PPAR-g receptor)
Increases insulin secretion from pancreatic beta cells • increase glucose uptake in muscle and adipose tissue
by closing ATP-sensitive K+ channels; Insulin • inhibit hepatic gluconeogenesis and have effects on lipid
Secretagogue, similar to sulfonylureas with some metabolism and the distribution of body fat
MOA • reduce both fasting and postprandial hyperglycemia.
overlap in binding sites, reduces circulating glucose,
increases glycogen, fat and protein formation and gene • reduce the risk of diabetes in high-risk patients
regulation Let’s dissect the word “ Thiazolidinediones” Thia means it has a sulfur on
Type 2 diabetes mellitus (postprandial in it. Every time you think of sulfur, think of allergies or cross-
Uses allergenicity to other sulfur-containing compounds and also lipid
hyperglycemia)
Hypoglycemia (least), Headache, Upper respiratory solubility. Azole though not an antifungal drug, I want you to think of
SE possible interaction to alcohol. Again, allergy, lipid solubility and alcohol
tract infections interaction.
Used in diabetics with sulfa allergies
Dr. Calderon Jr.
Nateglinide has the least incidence of hypoglycemia PIOGLITAZONE [C]
and may be used in CKD patients SimD ROSIGLITAZONE [C], TROGLITAZONE [B]
Requires islet cell function) Class Thiazolidinedione
Notes Very short DOA (4-8hrs only) Regulates gene expression by binding to PPAR-gamma
May come in combination with Metformin and PPAR-alpha → increases tissue sensitivity,
Has the lowest risk of developing hypoglycemia since they increases glucose uptake in muscle and adipose tissue,
have short duration of action MOA inhibits hepatic gluconeogenesis, effects on lipid
metabolism and distribution of body fat, control of
fasting and postprandial glucose; decreased risk of DM
INSULIN SENSITIZERS in high-risk patients
MOA OF BIGUANIDES Uses Type 2 diabetes mellitus, Diabetes prevention
• reduces postprandial and fasting glucose levels Fluid retention, Anemia, Weight gain, Congestive heart
failure, Bone Fractures esp in women, Cardiovascular
• activates AMP-stimulated protein kinase leading to inhibition
SE events (rosiglitazone), Hepatotoxicity (troglitazone),
hepatic and renal gluconeogenesis
Macular edema, Dyslipidemia (↑ HDL & LDL, ↓ TG),
• other effects:
increased risk of MI (Rosiglitazone)
• stimulates glucose uptake and glycolysis in peripheral tissues
• Contraindicated in pregnancy, chronic liver disease
o slows glucose absorption from the gastrointestinal tract
and congestive heart failure
o reduces plasma glucagon levels
o reduce the risk of diabetes in high-risk patients • Pioglitazone reduces mortality and macrovascular
events (myocardial infarction and stroke)
METFORMIN [B] • Rosiglitazone binds to PPAR-gamma ONLY
Class Biguanide • PPAR regulates transcription of genes encoding
Notes proteins involved in carbohydrate and lipid
Reduced hepatic and renal gluconeogenesis with
decreased endogenous glucose production, activates metabolism
MOA • May increase risk for developing Bladder Cancer
AMP-stimulated protein kinase leading to inhibition of
gluconeogenesis/endogenous glucose production Rosiglitazone and troglitazone have “Blackbox Warning”
Type 2 diabetes mellitus (first-line), Diabetes on their packaging because of the risk of CHF
Uses Increased risk by 63% for bladder CA - Pioglitazone
prevention, Polycystic ovarian syndrome Dr. Pereyra-Borlongan
GI disturbance, weight loss, lactic acidosis (especially
SE in renally and hepatically impaired patients), Vit B12
SUPPLEMENT:
malabsorption
MNEMONICS - Pioglitazone
PIOGlitazone = pampa-POGI ng INSULIN para di mo na ma-
resist
TZD COMBINATIONS: Uses Type 2 diabetes mellitus
• Pioglitazone + Glimepiride Headache, Nasopharyngitis, Upper respiratory tract
SE
• Rosiglitazone + Glimepiride infections, hypersensitivity reactions, pancreatitis
Administered orally as monotherapy or in
Notes
combination with metformin
MISCELLANEOUS AGENTS
MOA OF ALPHA-GLUCOSIDASE INHIBITORS SUPPLEMENT:
• inhibit a-glucosidase enzyme DAPAGLIFLOZIN [C]
• necessary for the conversion of complex carbohydrates to SimD EMPAGLIFLOZIN, CANAGLIFLOZIN
monosaccharides Na-glucose co-transporter 2 inhibitor (SGLT 2)
Class
• slowed absorption causes reduction of postprandial inhibitor
hyperglycemia Inhibits SGLT2 transporter → inhibits reabsorption
• lack an effect on fasting blood sugar MOA of glucose in the kidneys back to the blood →
• reduce the risk of diabetes in high-risk patients excretion of glucose out in the urine
Uses Type 2 diabetes mellitus
ACARBOSE [B] Dizziness, strong smell of urine, edema, weakness,
SE
SimD MIGLITOL [B], VOGLIBOSE nausea, vomiting, decrease in the amount of urine
Class Alpha-glucosidase inhibitor Do NOT use among renally impaired patients
Inhibits intestinal a-glucosidases → reduce conversion Increased incidence of UTI since you have higher sugar
MOA of starch and disaccharides to monosaccharides → Notes in your urine
reduce post prandial hyperglycemia Used by many to lose weight J
Uses Type 2 diabetes mellitus, Diabetes prevention Dr. Pereyra-Borlongan
Gastrointestinal disturbance (flatulence, diarrhea,

SE abdominal pain), Hypoglycemia (when taken with COLESEVELAM [B]
sulfonylureas), Increased liver enzymes Class Bile Acid Sequestrant
Relatively minor glucose-lowering benefit Binds bile acids. Lowers glucose through unknown
MOA
Treat hypoglycemia with oral glucose (dextrose) NOT mechanism
sucrose, because absorption is impaired Uses Type 2 diabetes mellitus
Notes Impaired absorption of sucrose SE constipation, dyspepsia, myalgia, asthenia
Taken immediately before a meal Remember the physiology of bile. It undergoes enterohepatic cycling. It is
Contraindicated in patients with renal and hepatic reabsorbed in the terminal ileum. BAR will cause malabsorption of fat
impairment and intestinal disorders soluble vitamins and steatorrhea.
Dr. Calderon Jr.
NOVEL ANTIDIABETIC AGENTS DRUGS FOR OBESITY

INCRETINS include Amylin & GLP-1 (Glucagon-like Peptide). Incretins are ORLISTAT [X]
substances in the body that augments glucose-stimulated insulin release Class Anti-obesity drug
by a couple of mechanisms which will be give below. Some can suppress Inhibits gastrointestinal and pancreatic lipases.
glucagon release while some would have anorectic effect. MOA
Reduces absorption of fats.

Uses Obesity, Type 2 diabetes
PRAMLINTIDE [C]
Weight loss, Flatulence, Steatorrhea, Fecal
Class Amylin analog
SE incontinence, Malabsorption of fat-soluble vitamins
Activates amylin receptors. Reduce post-meal glucose (A, D, E, K), Hepatotoxicity
excursions Suppresses glucagon release. Delays
MOA Rebound weight gain upon discontinuation
gastric emptying. Stimulates CNS to reduce appetite
Contraindicated in pregnancy, reduced hepatobiliary
(anorectic effect). Notes function and malabsorption states
Uses Type 1 and Type 2 diabetes mellitus Familiar with Xenical? J
Hypoglycemia, Gastrointestinal disturbances, nausea, Dr. Pereyra-Borlongan
SE
anorexia, headache
Administered as an injectable preparation (SC) SIBUTRAMINE [C]
Notes together with insulin to control post-prandial glucose Class Antiobesity drug
Short t1/2 of 48mins Inhibits norepinephrine and serotonin reuptake in the
MOA
CNS. Reduces appetite (anorectic effect).
EXENATIDE [C] Uses Obesity
SimD LIRAGLUTIDE [C] Dry mouth, Gastrointestinal disturbance, Tachycardia,
Class Incretin modulator (GLP-1 agonist) SE Hypertension, Cardiovascular events (myocardial
Activates GLP-1 receptors → reduction of post-meal infarction, arrhythmias), Stroke
glucose excursions. Augments glucose-stimulated Withdrawn due to increased risk of cardiovascular
MOA insulin release from pancreatic B cells. Retards gastric events and strokes
emptying. Inhibits glucagon secretion. Produces Notes Familiar with Reductil? J This has been banned since this
satiety drug is a relative of Methamphetamine J
Uses Type 2 diabetes mellitus Dr. Pereyra-Borlongan
Hypoglycemia, Acute pancreatitis, Nausea, Vomiting,

SE RIMONABANT
Headache, Anorexia, Mild Weight Loss
Administered as an injectable preparation (SC) used in Class Anti-obesity drug
combination with metformin or a sulfonylurea Selectively blocks cannabinoid-1 (CB-1) receptors.
Notes MOA
Liraglutide has possible thyroid carcinoma risk Reduces appetite (anorectic effect).
Long-acting injectables Uses Obesity, Smoking cessation, Drug addiction
SE Suicidality, Depression, Nausea
SITAGLIPTIN [B] Withdrawn because of increased risk of suicides,
Notes
SAXAGLIPTIN [B], LINAGLIPTIN [B], VILDAGLIPTIN, depression and other serious psychiatric problems
SimD
TENELIGLIPTIN
Class Incretin modulator (DPP-4 inhibitor) SUPPLEMENT:
Inhibits dipeptidyl peptidase-4 (DPP-4) that degrades An appetite suppressant which is an
PHENTERMINE
GLP-1 and other incretins → raises circulating GLP-1 amphetamine derivative. Side effects
[X]
levels. Augments glucose-stimulated insulin release will be similar with amphetamine
MOA
from pancreatic B cells. Retards gastric emptying.
Inhibits glucagon secretion. Produces satiety. Reduces
post-meal glucose excursions
MOA OF GLUCAGON
• protein hormone secreted by the A cells of the endocrine
pancreas
• increases heart rate and force of contraction
• increases hepatic glycogenolysis and gluconeogenesis
• relaxes smooth muscle
GLUCAGON [B]
Class Pancreatic Hormone
MOA Activates glucagon receptors
Severe hypoglycemia, Diagnosis of endocrine
Uses disorders, Beta-blocker overdose, Radiology of the
bowels
SE Nausea, Vomiting, Hypotension
ERGOCALCIFEROL [C]
Glucagon-secreting tumors (glucagonomas) present
SimD CHOLECALCIFEROL [C]
with decreased amino acids in blood, anemia, diarrhea,
Class Vitamin D (inactive)
Notes weight loss and necrolytic migratory erythema Regulates gene transcription via the vitamin D
Glucagon can increase heart rate and force of contraction
Increases hepatic glycogenolysis and gluconeogenesis receptor. Stimulates intestinal calcium absorption,
Dr. Pereyra-Borlongan MOA bone resorption, renal calcium and phosphate
reabsorption. Decrease PTH, promote Innate
Immunity
DRUGS THAT AFFECT BONE AND MINERAL Vitamin D deficiency (rickets, Osteomalacia, intestinal
HOMEOSTASIS osteodystrophy, CKD, chronic liver disease,
Uses
hypoparathyroidism, nephrotic syndrome)
osteoporosis, psoriasis, Renal Failure, malabsorption
SE Hypercalcemia, Hyperphosphatemia, Hypercalciuria
Commonly added to dairy products and other food
products
Notes
Given topically for psoriasis; given with calcium
supplements for osteoporosis
CALCITRIOL [C]
DOXERCALCIFEROL [B], PARICALCITOL [C],
SimD
Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 CALCIPOTRIENE [C]
Class Vitamin D (active)
HORMONAL REGULATORS Regulates gene transcription via the vitamin D
SUPPLEMENT: Parathyroid Hormone
receptor. Stimulates intestinal calcium absorption,
MOA
bone resorption, renal calcium and phosphate
Parathyroid Hormone
reabsorption. Decrease PTH
• acts on membrane G-protein-coupled receptors to increase
Secondary hyperparathyroidism in CKD,
cAMP in bone and renal tubular cells
Uses Hypocalcemia in hypoparathyroidism (calcitriol),
• inhibits calcium excretion, promotes phosphate excretion
Psoriasis (calcipotriene)
and stimulates the production of active vitamin D metabolites
SE Hypercalcemia, Hyperphosphatemia, Hypercalciuria
• promotes bone turnover by increasing the activity of both
The active form Calcitriol is preferred in patients with
osteoblasts and osteoclasts
CKD, chronic liver disease and hypoparathyroidism
o osteoclast activation is not a direct effect and instead results
Doxercalciferol is a prodrug that is converted in the
from PTH stimulation of osteoblast formation of RANK
liver to 1,25-dihydroxyvitaminD
ligand (RANKL)
Paricalcitol, Calcipotriene are analogs of calcitriol and
• at high doses, net effect of elevated PTH is increased bone Notes
are used topically for psoriasis and are being
resorption, hypercalcemia, and hyperphosphatemia
investigated for malignancies and inflammatory
• low intermittent doses of PTH produce a net increase in bone
disorders
formation
Doxercalciferol, Paricalcitol and Calcipotriene cause
• synthesis and secretion of PTH is primarily regulated by the less hypercalcemia and hypercalciuria
serum concentration of free ionized calcium
o decreased free ionized calcium stimulates PTH release
SUPPLEMENT: Calcitonin
• peptide hormone secreted by parafollicular C cells in the
TERIPARATIDE [C]
thyroid gland
Class Recombinant parathyroid hormone
• decreases serum calcium and phosphate by inhibiting bone
Acts through PTH receptors to produce a net increase
MOA resorption and inhibiting renal excretion of these minerals
in bone formation, stimulates bone turnover
• bone formation is not impaired initially, but ultimately it is
Uses Osteoporosis
reduced
Hypercalcemia, Hypercalciuria, arthralgia, rhinitis,
SE nausea, weakness, dizziness, pharyngitis, dyspepsia, CALCITONIN [C]
rash SimD SALCATONIN [C]
Must be administered in low intermittent doses to Class Thyroid hormone
Notes stimulate bone formation Acts through calcitonin receptors to inhibit bone
MOA
Used IV for osteoporosis resorption
Paget's disease of bone, Hypercalcemia, Osteoporosis,
Uses
MNEMONICS: Parathyroid Hormone Tumor marker for thyroid cancer
What are the signs and symptoms of excess PTH? SE Rhinitis, Nausea, Vomiting, Facial flushing, Tingling
• Painful bones Administered as a nasal spray
• Renal stones Used for osteoporosis but is less effective than
• Abdominal groans Notes bisphosphonates and teriparatide
• Psychiatric overtones Paget’s Disease – Bones look like Jigsaw Puzzle
MNEMONIC: Calcitonin means CALCium INside the bone

Dr. Calderon Jr.
NONHORMONAL REGULATORS CANCER CHEMOTHERAPY

ALENDRONATE [C]
ETIDRONATE [C], IBANDRONATE, PAMIDRONATE
SimD [D], RISEDRONATE [C], TILUDRONATE [C],
ZOLEDRONIC ACID [D]
Class Bisphosphonate
Suppresses the activity of osteoclasts in part via
inhibition of farnesyl Pyrophosphate synthesis. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
MOA Inhibits bone resorption and secondarily, bone

formation by acting on the basic hydroxyapatite
CANCER CHEMO PART 1
crystal structure
https://qrs.ly/vabo8z8
Paget's disease of bone, Hypercalcemia especially in
Uses
malignancies, Osteoporosis, Bone metastases
Adynamic bone, Esophagitis, Osteonecrosis of the jaw,
SE
Renal impairment, GI irritation
Take drugs with large quantities of water and avoid CANCER CHEMO PART 2
situations that permit esophageal reflux https://qrs.ly/yeboakj
Remedy for GI irritation and prevent reflux: take lots
Notes of water and keep patient in an upright position for
LOG-KILL HYPOTHESIS
30mins after intake of drug
Contraindicated in those with renal impairment, • anticancer drugs kill a fixed proportion of a tumor cell
esophageal motility disorders and peptic ulcers population, not a fixed number of tumor cells
• one rationale for drug combinations
SUPPLEMENT:
Just like your bacteria in their response to bactericidal antibiotics, highly
SEVELAMER [C] dividing cancer cells are more responsive to anticancer medications.
Class Phosphate binding resin
Correlation to Pathology:
Binds to dietary phosphate and prevents its There are multiple causation for cancer. As per Katzung and Robbins, the
MOA
absorption most important is environmental exposure. Examples include ionizing
Hyperphosphatemia in CKD, Hypoparathyroidism, radiation, viruses and oncogenes expression.
Uses
Vitamin D intoxication Recall tumor nomenclature, carcinoma (epithelial in origin) and sarcoma
SE Hypo/hypertension, Gastrointestinal disturbance (mesenchymal "think of meat" in origin).
Can significantly reduce uric acid levels Hematologic malignancy vs. solid tumors. How do they differ in terms of
Notes Contraindicated in hypophosphatemia and bowel response to chemotherapy? We use the murine model for blood
obstruction malignancies and the Gompertzian model in solid tumors. In blood
malignancies, cell number and curability is invariable and inversely
RALOXIFENE [X]
proportional. In solid tumors, they do not grow in exponential manner.
Class SERM (Selective Estrogen Receptor Modulator) Solid tumors rely on blood supply or angiogenesis. Remember in
Interacts selectively with estrogen receptors pathology, solid tumors, once they reach one third of their size, they
MOA leading to inhibition of bone resorption without already reach the peak of their growth. In clinical application,
stimulating breast or endometrial hyperplasia Gompertzian model states that when a patient with advanced cancer is
Uses Osteoporosis treated, the tumor mass is large and its growth fraction is low,
SE Increased risk of venous thromboembolism therefore the fraction of the cells killed is small.

Dr. Calderon Jr.
DENOSUMAB [X] CELL CYCLE

Class Monoclonal Antibody
Binds to RANKL and prevents it from stimulating
MOA osteoclast differentiation and function → inhibits
bone resorption
Uses Osteoporosis
SE Increased risk of infection
CINACALCET [C]
Activated calcium-sensing receptor → Inhibits PTH
MOA
secretion
Uses Hyperparathyroidism
SE Nausea
CALCIUM [A]
SimD PHOSPHATE [B], STRONTIUM [B]
Class Minerals
Multiple physiologic actions through regulation of
multiple enzymatic pathways. Sr suppresses bone
MOA Figure 54-2. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
resorption and increase bone formation, Ca and
Classification of Drugs Based on Cell Cycle
PO4 are required for bone mineralization
• CELL CYCLE NONSPECIFIC DRUGS (CCNS)
Osteoporosis, Osteomalacia, Deficiencies in Ca and
Uses o act on tumor stem cells when they are traversing the cell cycle
PO4
and when they are in the resting phase
SE Ectopic calcification
• CELL CYCLE SPECIFIC DRUGS (CCS)
Calcium Content of different Calcium supplements: o act selectively on tumor stem cells when they are traversing
Ca carbonate 40% the cell cycle, and not when they are in the G0 phase
Tricalcium phosphate 39% The concept of chemotherapy is likened to the concept of antibiotics.
Ca chloride 27% We use medications in combination to achieve to important things:
1) Synergism and
Ca acetate 25% 2) prevention of drug resistance.
Ca citrate 21% We target both cancer cells that are highly dividing (use of cell-cycle
specific) and cancer cells with low growth fraction (use of cell cycle non-
Ca lactate 13% specific drugs) at the same time.
Ca gluconate 9% Dr. Calderon Jr.
Ca gluceptate 8%
CA glubionate 6.5%
Ovarian
• Paclitaxel and Carboplatin
Carcinoma
Pancreatic
• Gemcitabine and Erlotinib
Carcinoma
• GnRH agonist (e.g. Leuprolide) or
Prostate antagonist (e.g. Abarelix) and
Carcinoma androgen receptor antagonist (e.g.
Flutamide)
• Carboplatin, Paclitaxel, and
Lung Carcinoma
Bevacizumab
Testicular • PEB regimen: Cisplatin (Platinol),
Carcinoma Etoposide, and Bleomycin
Rescue Therapy
• alleviation of toxic effects by giving rescue drugs
o Methotrexate: Leucovorin
o Cyclophosphamide: MESNA
o Doxorubicin: Dexrazoxane
o Cisplatin: Amifostine
Alkylating agents are inserted in the DNA of the cancer cells. They will
cause chain termination because the cancer cell will lack 3’OH. As a
general concept, in terms of side effect they will cause bone marrow
suppression (take a look at the following alkylating agents to appreciate
this generality. Bone marrow suppression manifested by pancytopenia
J)
Dr. Calderon Jr.
ALKYLATING AGENTS
CYCLOPHOSPHAMIDE [D]
IFOSFAMIDE [D], CHLORAMBUCIL [D],
SimD
MECHLORETHAMINE [D]
Class Alkylating agent
Forms DNA cross-links, resulting in inhibition of DNA
MOA
synthesis and function. Cell cycle non-specific.
Non-Hodgkin's lymphoma, Breast cancer, Ovarian
Uses cancer, Neuroblastoma, Chronic lymphocytic
leukemia, Wilms Tumor, Rhabdomyosarcoma
Bone marrow suppression, Hemorrhagic cystitis,
SE Hepatotoxicity, Alopecia, SIADH, Cardiac dysfunction,
SUPPLEMENT: Cancer Treatment Modalities Pulmonary toxicity
• PRIMARY INDUCTION CHEMOTHERAPY Rescue therapy is MESNA
Notes
o drug therapy is administered as the primary treatment Cystitis can be prevented with adequate hydration
• NEOADJUVANT CHEMOTHERAPY Correlation to Pathology:
o use of chemotherapy in patients with localized cancer What is the most common leukemia in adult?
before performing local therapy (surgery) What cells are you looking for?
o goal is to render the local therapy more effective Answer:
• ADJUVANT CHEMOTHERAPY Chronic Lymphocytic Leukemia;
o chemotherapy done after local treatment procedures such Smudge cells (CLL means Crushed Little Lymphocytes)
Dr. Calderon Jr.
as surgery or radiation
o reduce the risk of local and systemic recurrence and to CISPLATIN [D]
improve disease-free and overall survival SimD CARBOPLATIN [D], OXALIPLATIN [D]
EXAMPLES OF COMMONLY-USED Forms DNA cross-links, resulting in inhibition of DNA
DIAGNOSIS MOA
ANTI-CANCER DRUGS synthesis and function. Cell cycle non-specific.
Acute Testicular cancer, Ovarian cancer, Bladder cancer,
• Prednisone, Vincristine, and
Lymphocytic Lung cancer, Advanced colon cancer and pancreatic
Asparaginase or an Anthracycline Uses
Leukemia in cancer (oxaliplatin), breast cancer, H&N cancer,
plus intrathecal Methotrexate
children Gastroesophageal cancer
Acute Nausea, Vomiting, Nephrotoxicity, Neurotoxicity
Myelogenous • Cytrabine and Idrarubicin or SE
(peripheral neuritis, acoustic nerve damage)
Leukemia in Daunorubicin Rescue therapy is AMIFOSTINE
adults Notes Decrease nephrotoxicity by administering Mannitol
• Cytotoxic agents, hormonal therapy with forced hydration
with Tamoxifen or an Aromatase
Breast Carcinoma Carboplatin has a wider spectrum of coverage in solid tumors and has less
inhibitor (e.g. Anastrozole)
renal and GIT side effects and is widely used in transplant regimen.
Trastuzumab Oxaliplatin is part of your FOLFOX and FOLFIRI regimen used in the
Chronic treatment of solid tumors that are resistant to Cisplatin and Carboplatin
• Imatinib, newer tyrosine kinase
Myelogenous in the basis of mismatch repair defect.
inhibitors, interferon
Leukemia Correlation to Biochemistry:
• Fluorouracil plus Leucovorin plus Does Mismatch repair ring a bell? Mismatch repair is a defect wherein a
Colon Carcinoma newly synthesized strand is recognized, mismatch nucleotide is removed,
Oxaliplatin
and the gap is filled and resealed. Classic example is the Hereditary
• ABVD regimen: Doxorubicin Nonpolyposis Colorectal Cancer (Lynch syndrome)
Hodgkin
(Adriamycin), Bleomycin, Vincristine, MNEMONIC for Ototoxic medications: (Vocalize with feelings. Aspiriiing,
Lymphoma
Decarbazine, and Prednisone Ibuprofiing, Cisplatiing, Kanamycinng, Gentamiciing, LASiinng, pating
• CHOP regimen (Cyclophosphamide, pating pating!!!) Aspirin, Ibuprofen, Cisplatin, Kanamycin (the most
Non-Hodgkin ototoxic aminoglycoside), Gentamicin, Lasix (Furosemide, but the most
Doxorubicin, Vincristine, and
Lymphoma ototoxic loop diuretic is ethacrynic acid)
Prednisone) plus Rituximab Dr. Calderon Jr.
PROCARBAZINE [D] Recall that the only source of Folic Acid in the body is thru our diet. Recall
Class Alkylating agent also that anticancer drugs impairs normal cells also. We need Folic acid
Forms hydrogen peroxide, which generates free for biochemical processes. Example for erythrocyte maturation and DNA
synthesis. In the world of anticancer drugs, remember the rescue agents.
MOA radicals that cause DNA strand scission. Cell cycle non- Folinic acid is the rescue agent for Methotrexate. AHA!
specific.
Dr. Calderon Jr.
Hodgkin's lymphoma, Non-Hodgkin's lymphoma, 6-MERCAPTOPURINE [D]
Uses
Brain tumors SimD 6-THIOGUANINE [D], AZATHIOPRINE [D]
Bone marrow suppression, Pulmonary toxicity, Class Antimetabolite (purine)
SE Hemolysis, Neurotoxicity, Disulfiram-like reaction, Inhibits de novo purine nucleotide synthesis.
Leukemogenic, Hypersensitivity reaction MOA Activated by HGPRT. Cell cycle specific. Fludarabine
Procarbazine has the highest carcinogenic potential amongst alkylating and Cladribine inhibit ribonucleotide reductase
agent. Imagine an anticancer drug that can actually cause cancer. This Acute leukemias (AML, ALL), Chronic myelogenous
Uses
one is to remember. leukemia, Lymphomas
Dr. Calderon Jr.

Bone marrow suppression, Immunosuppression,

DACARBAZINE [C] SE
Hepatotoxicity (cholestasis, jaundice, necrosis)
6-MP metabolism inhibited by allopurinol and
Forms hydrogen peroxide, which generates free Notes
febuxostat
MOA radicals that cause DNA strand scission. Cell cycle non-
specific. A classical drug-drug interaction concept in anticancer drugs is the
inhibition of metabolism of 6-Mercaptopurine or Azathiopurine by
Hodgkin's lymphoma, Non-Hodgkin's lymphoma,
Uses addition of a xanthine oxidase inhibitor. According to Katzung, with
Melanoma, Soft Tissue Sarcoma proper dosage of xanthine oxidase inhibitor, there is a reduction in the
Alopecia, Skin Rash, Gastrointestinal distress, Bone dose of the antimetabolite need by 75%. Less expense, less side effect with
marrow suppression, Phototoxicity, Flu-like the same potency of the antimetabolite. The patient will be happy J
SE
Syndrome, CNS Toxicity (ataxia, lethargy, confusion, Dr. Calderon Jr.
neuropathy)
SUPPLEMENT: PEMETREXED [D]
BUSULFAN [D] Class Antimetabolite (purine)
Class Alkylating agent Inhibits Thymidylate Synthase, Dihydrofolate
MOA
Forms DNA cross-links, resulting in inhibition of DNA Reductase and purine nucleotide synthesis
MOA Uses Mesothelioma, non-small cell lung cancer
synthesis and function. Cell cycle non-specific.
Uses Chronic myelogenous leukemia Bone marrow suppression, skin rash, mucositis,
SE
diarrhea, fatigue, Hand-Foot Syndrome
Pulmonary fibrosis, Adrenal insufficiency, Skin
SE
pigmentation
Specific to CFU-GM line. Used as a myelosuppressive 5-FLUOROURACIL [D]
Notes Class Antimetabolite (pyrimidine)
agent prior to bone marrow transplant.
Inhibits thymidylate synthase → Inhibition of DNA
MNEMONIC Drugs causing Pulmonary Fibrosis MOA Synthesis and Function. Causes thymineless death of
“BBBAN Me” cells. Cell cycle specific.
Bleomycin Amiodarone Bladder cancer, Breast cancer, Colorectal cancer, Anal
Busulfan Nitrofurantoin cancer, Head and neck cancer, Liver cancer, Ovarian
Uses
Bromocriptine Methotrexate cancer, Skin cancer (basal cell cancer, actinic
keratoses), breast cancer
Bone marrow suppression, Gastrointestinal irritation,
Nitrosureas are special alkylating agent because they are designed for SE
brain tumors. These medications are highly lipophilic and can cross the Alopecia, mucositis, neurotoxicity
blood brain barrier. TEGAFUR is a chemotherapeutic prodrug of 5FU. It is
Notes

Dr. Calderon Jr. a component of the combination drig Tegafur-Uracil
CARMUSTINE [D]
SimD LOMUSTINE [D], BENDAMUSTINE [D] CYTARABINE [D]
Class Alkylating agent (nitrosourea) Class Antimetabolite (pyrimidine)
Forms DNA cross-links, resulting in inhibition of DNA Inhibits DNA synthesis and repair. Inhibits
MOA
synthesis and function. Cell cycle non-specific. MOA ribonucleotide reductase with reduced formation of
Uses Brain tumors, Melanoma, Skin cancer, Lymphoma, CLL dNTPs. Cell-cycle specific.
CNS toxicity (dizziness, ataxia), Nausea and vomiting, Uses Acute leukemias (AML, ALL), CML in blast crisis
SE
Bone marrow suppression, Skin flushing Gastrointestinal irritation, Bone marrow suppression,
Highly lipophilic, allowing ease of passage through SE Neurotoxicity (cerebellar dysfunction, peripheral
Notes
BBB into the CNS neuritis)
Notes Most specific for the S phase of the cell cycle
ANTIMETABOLITES CYTA CYTA pancytopenia is the side effect of Cytarabine.
Dr. Calderon Jr.
Antimetabolites mimic your purine and pyrimidines. They are inserted in
the DNA and because they are not real and purine and pyrimidines, once
inserted in the DNA of cancer cells they will cause chain termination and GEMCITABINE [D]
eventual cessation of cancer cell growth. Again, because they are inserted SimD CAPECITABINE [D]
in the DNA, as a side effect, they will cause bone marrow suppression J Class Antimetabolite (pyrimidine)
Dr. Calderon Jr.
Inhibits DNA synthesis and repair. Inhibits
MOA ribonucleotide reductase with reduced formation of
METHOTREXATE [X]
dNTPs. Cell-cycle specific.
Antimetabolite, Disease-Modifying Anti-Rheumatic
SimD Pancreatic cancer, Non-small cell lung cancer, Bladder
Drug
cancer, Non-Hodgkin's lymphoma, Breast cancer, soft
Inhibits Dihydrofolate reductase. Decreases synthesis
Uses tissue sarcoma
Class of thymidylate, amino acids, purine nucleotides. Cell
Capecitabine: HCC, Gastroesophageal cancer,
cycle specific.
colorectal cancer
Choriocarcinoma, Acute leukemias, Non-Hodgkin's
Bone marrow suppression, Neutropenia, Pulmonary
lymphoma, Primary CNS lymphoma, Breast cancer, SE
MOA toxicity, Hand-Foot Syndrome (Capecitabine)
Head and neck cancer, Bladder cancer, Rheumatoid
arthritis, Psoriasis, Ectopic pregnancy Gemcitabine is an evolution of antimetabolite because it can be used for
Bone marrow suppression, Pulmonary infiltrates and solid tumors. Think of Pancreatic cancer as the most common indication.
Uses Mnemonic, remember gems are solid! AHA!
fibrosis, Mucositis, Crystalluria, diarrhea Dr. Calderon Jr.
SE Rescue therapy is LEUCOVORIN (folinic acid)
SUPPLEMENT: HAND-FOOT SYNDROME ANTITUMOR ANTIBIOTICS
• “Palmar-Plantar erythrodysesthesia” DOXORUBICIN [D]
• a side effect of some cancer treatments DAUNORUBICIN [D], IDARUBICIN [D] , EPIRUBICIN
• redness, swelling and pain on the palms and soles, sometimes SimD
[D], MITOXANTRONE [D]
even with blistering Class Anthracycline
• may also occur elsewhere in the skin such as the knees and Intercalates between base pairs. Inhibits
elbows MOA topoisomerase II. Generates free radicals → single and
double-stranded DNA breaks. Cell cycle non-specific.
NATURAL PRODUCT ANTICANCER DRUGS Hodgkin and Non-Hodgkin lymphoma, Breast cancer,
VINCRISTINE [D] soft tissue sarcoma, Endometrial cancer, small cell and
Class Vinca alkaloid Uses non-small cell Lung cancer, Ovarian cancer, Acute
Prevents microtubule assembly. Causes cell arrest at leukemias – AML, ALL (especially Daunorubicin,
MOA Idarubicin for AML), Wilms tumor, Neuroblastoma
metaphase. Cell cycle specific.
Acute leukemias, Lymphomas, Wilms tumor, Alopecia, Nausea, Vomiting, Dilated Cardiomyopathy,
Uses SE Congestive heart failure, red urine (Doxorubicin),
Neuroblastoma, Rhabdomyosarcoma
Areflexia, Peripheral neuritis, Paralytic ileus, myelosuppression
SE Notes Rescue therapy is DEXRAZOXANE
Nausea/Vomiting, Myelosuppression, SIADH
Notes Acts primarily in M phase of cancer cell cycle MNEMONIC Doxorubicin has rubi on it. Ruby red. Think red as heart. It
will cause Cardiotoxicity AHA!
Remember, Vincristine will not likely cause bone marrow suppression Dr. Calderon Jr.
rather it will cause neuropathy. Vincristine will cause crispy nerves AHA!

BLEOMYCIN [D]
Dr. Calderon Jr.
SimD MITOMYCIN [D]

VINBLASTINE [D]
Class Vinca alkaloid Class Antitumor antibiotic
SimD VINORELBINE [D] Generates free radicals, which cause DNA strand
MOA
Prevents microtubule assembly. Causes cell arrest at breaks. Intercalates with DNA. Cell cycle specific.
MOA Hodgkin and Non-Hodgkin lymphoma, Testicular
metaphase. Cell cycle specific.
Lymphomas, Neuroblastoma, Testicular carcinoma, cancer, Head and neck cancer, Skin cancer, germ cell
Uses Uses cancer
Kaposi's sarcoma, germ cell tumor, breast cancer
Mitomycin: Superficial bladder, cancer, Gastric cancer,
Bone marrow suppression, Alopecia, Gastrointestinal
Breast cancer
SE distress, mucositis, SIADH, constipation, vascular
events Pneumonitis, Pulmonary fibrosis, Mucocutaneous
SE reactions (blisters, hyperkeratosis), Alopecia,
Notes Acts primarily in M phase of cancer cell cycle
Hypersensitivity, Fever and chills , hypotension
Notes Most specific for the G2 phase of the cell cycle
MNEMONIC: Vinca Alkaloids
vinBLASTine BLASTS the Bone marrow ACTINOMYCIN D [D]
vinblastine causes myelosuppression Class Antitumor antibiotic
Binds to double-stranded DNA. Inhibits DNA-
MOA
ETOPOSIDE [D] dependent RNA synthesis. Cell cycle non-specific.
SimD TENIPOSIDE [D] Melanoma, Wilms tumor, Rhabdomyosarcoma,
Class Podophyllotoxin Uses Choriocarcinoma, Kaposi’s sarcoma, Gestational
Inhibits DNA topoisomerase II (DNA Gyrase). Inhibits trophoblastic neoplasia
MOA Bone marrow suppression, Skin reactions,
mitochondrial electron transport. Cell cycle specific. SE
Lung cancer, Prostate cancer, Testicular cancer, Non- Gastrointestinal irritation
Uses
Hodgkin’s lymphoma, Gastric cancer Other name of actinomycin is dactinomycin. It is the oldest antitumor
SE Bone marrow suppression, GI irritation, Alopecia antibiotic.
Dr. Calderon Jr.
MISCELLANEOUS ANTICANCER AGENTS

TOPOTECAN [D] IMATINIB [D]
SimD IRINOTECAN [D] DASATINIB [D], NILOTINIB [D], CRIZOTINIB [D],
SimD
Class Camptothecin AFATINIB [D], NINTEDANIB [D], REGORAFENIB [D]
MOA Inhibits topoisomerase I. Cell cycle specific. Class Tyrosine Kinase Inhibitors
Topotecan: Advanced ovarian cancer (2nd line), Small Inhibits tyrosine kinase activity of the protein product
Uses cell lung cancer MOA of bcr-abl oncogene in CML.
Irinotecan: Metastatic colorectal cancer Inhibits c-kit tyrosine kinase in GIST.
Bone marrow suppression, Diarrhea, Nausea and Chronic Myelogenous leukemia, Gastrointestinal
SE Uses
vomiting stromal tumor (GIST)
MNEMONIC: Irinotecan! Inire! Inire! Colorectal cancer AHA!
Diarrhea, Myalgia, Fluid retention, Congestive heart
SE

Dr. Calderon Jr. failure, Drug interactions
PACLITAXEL [D] Interactions with other drugs that depend on or affect
SimD DOCETAXEL [D], CABAZITAXEL [D] the cytochrome P450 system
Notes
Class Taxane Nintedanib is also used for Idiopathic Pulmonary
Interferes with mitotic spindle. Prevents microtubule Fibrosis
MOA Disassembly into tubulin monomers. Cell cycle Maybe you are familiar with the surgeon’s brand Gleevec. This is use on
specific. GIST which has a poor prognosis
Advanced breast and ovarian cancers, lung cancer,
Dr. Calderon Jr.
Uses gastroesophageal cancer, gastric cancer, prostate TRASTUZUMAB [B]

cancer, bladder cancer, head and neck cancer SimD PERTUZUMAB [D], LAPATINIB [D]
Paclitaxel: Neutropenia, Thrombocytopenia, Class Monoclonal antibody
Peripheral neuropathy, Hypersensitivity, arrhythmias, Acts against breast cancer cells that overexpress the
MOA
SE myelosuppression HER-2/neu receptor for epidermal growth factor
Docetaxel: Neurotoxicity, Bone marrow suppression, Uses Metastatic breast cancer
fluid retention, hypersensitivity Nausea and vomiting, Chills, Fever, Headache,
SE
Remember, among the sisters, Paclitaxel will prevent microtubule
Cardiotoxicity (congestive heart failure)
disassembly. The other two Vincristine and Vinblastine prevent Just like doxorubicin, it can cause cardiomyopathy. This drug has a trade
microtubule assembly. name Herceptin. MNEMONIC: Heartceptin or if you want Trastuzumab
Dr. Calderon Jr. “tinuzuk ang puzu” AHA
Dr. Calderon Jr.
BEVACIZUMAB [C] SUPPLEMENT: Hormonal Anticancer Agents
SORAFENIB [D], SUNITINIB [D], PAZOPANIB [D], PREDNISONE [D]
SimD
LENVATINIB [D] Class Glucocorticoid
Class Monoclonal antibody Suppresses inflammation and immune response.
Inhibits binding of VEGF to VEGFR leading to MOA May trigger apoptosis and work on nondividing
inhibition of VEGF signaling. Inhibits tumor vascular cancer cells.
MOA
permeability but enhances tumor blood flow and drug Chronic lymphocytic leukemia, Hodgkin’s
Uses
delivery. lymphomas
Metastatic colorectal cancer, Breast cancer, Non-small Adrenal suppression, Growth inhibition, Muscle
Uses
cell lung cancer, Renal cancer SE wasting, Osteoporosis, Salt retention, Glucose
Hypertension, Infusion reactions, Arterial thrombosis, intolerance, Behavioral changes
SE Impaired wound healing, Gastrointestinal perforation,
Proteinuria TAMOXIFEN [D]
Lenvatinib acts a multiple kinase inhibitor against SimD TOREMIFENE [D]
Notes
VEGFR1 to 3 kinases and is used for thyroid cancer Class Selective Estrogen Receptor Modulator
MNEMONIC: BV BeVacizumab for blood vessel. It inhibits angiogenesis! Estrogen antagonist actions in breast tissue and
AHA! MOA CNS. Estrogen agonist effects in uterus, liver and

Dr. Calderon Jr. bone.
RITUXIMAB [C] Uses Hormone-sensitive breast cancer
Class Monoclonal antibody Hot flushes, Thromboembolism (DVTs),
Binds to a surface protein in NHL cells. Induces SE
Endometrial hyperplasia, Endometrial cancer
MOA complement-mediated lysis, direct cytotoxicity and Prevents osteoporosis and decreases risk of
induction of apoptosis Notes atherosclerosis at the risk of causing endometrial
Uses Non-Hodgkin lymphoma (low-grade) cancer
SE Hypersensitivity reactions, Bone marrow suppression
CETUXIMAB [C] FLUTAMIDE [D]
SimD PANITUMUMAB [C], NIMOTUZUMAB [C] SimD BICALUTAMIDE [D], NILUTAMIDE [D]
Class Monoclonal antibody Class Androgen antagonist
Binds to EGFR and inhibits downstream EGFR MOA Competitive antagonist at androgen receptor
MOA signaling, enhances response to chemotherapy and Uses Prostate cancer, Surgical castration (nilutamide)
radiotherapy Gynecomastia, Hot flushes, Impotence,
SE
Colorectal cancer, head and neck cancer (together Hepatoxicity
Uses Less hepatotoxicity with bicalutamide and
with radiotherapy), non-small cell lung cancer
Infusion reaction, skin rash, hypomagnesemia, fatigue, nilutamide
SE GnRH analogs (leuprolide) must be co-
interstitial lung disease Notes
administered with flutamide to prevent acute flare-
ERLOTINIB [D]
up of prostate cancer
SimD GEFITINIB [D] Additional androgen antagonist: ABIRATERONE
Class EGFR Inhibitor
Inhibits EGFR tyrosine kinase → inhibition of EGFR LEUPROLIDE [D]
MOA
signaling SimD GONADORELIN [B], NAFARELIN [X]
Uses Non-small cell lung cancer, pancreatic cancer Class GnRH analog
Diarrhea, hypertension, skin rash, anorexia, Increased LH and FSH secretion with intermittent
SE
interstitial lung disease MOA administration. Reduced LH and FSH secretion
with prolonged continuous administration.
INTERFERON-ALPHA [B] Controlled ovarian hyperstimulation,
Class Interferon Uses Endometriosis, Myoma uteri, Precocious puberty,
Endogenous glycoproteins with antineoplastic, Prostate cancer
MOA
immunosuppressive and antiviral actions Hot flushes, Sweats, Headache, Osteoporosis,
Hairy cell leukemia, Chronic myelogenous leukemia, SE Gynecomastia, Reduced libido, Decreased
Uses
T-cell lymphomas hematocrit, Apoplexy, Blindness
Alopecia, Myalgia, Depression, Flu-like syndrome, Must be co-administered with flutamide to prevent
SE Thyroid dysfunction, Hearing loss, Bone marrow Notes
tumor flare-up on initiation of treatment
suppression, Neurologic dysfunction
Contraindications include autoimmune disease, ANASTROZOLE [X]
Notes
history of cardiac arrhythmias and pregnancy SimD LETROZOLE [D]
Class Estrogen synthesis inhibitor
ASPARAGINASE [C] Reduces estrogen synthesis by inhibiting
Class Substrate-depleting enzyme MOA
aromatase
Hydrolyzes circulating L-asparaginase → rapid Uses Breast cancer, Precocious puberty
MOA
inhibition of protein synthesis Nausea, Diarrhea, Hot flushes, Bone and back pain,
Uses Acute lymphoblastic leukemia SE
Dyspnea, Peripheral edema
Nausea, Fever, Hypersensitivity reactions, Acute Effective against breast cancers that have become
SE Pancreatitis, Increased risk of bleeding, mental Notes
resistant to tamoxifen
depression, nephrotoxicity
OTHER ANTICANCER DRUGS
ALL-TRANS RETINOIC ACID [X] antifolate analog with activity in the
Class Vitamin A derivative PEMETREXED
S phase of the cell cycle
Allows DNA transcription and differentiation of PRALATREXATE antifolate analog
MOA immature leukemic promyelocytes into mature interferes with the process of DNA
granulocytes (differentiation therapy). FLUDARABINE, synthesis and DNA repair through
Uses Acute promyelocytic leukemia CLADRIBINE inhibition of DNA polymerase-alpha
Retinoic acid syndrome (dyspnea, fever, weight gain, and DNA polymerase-beta
SE
peripheral edema) A DNA-hypomethylating agent that
Only vitamin that can cure cancer induces differentiation and
Notes Does not directly kill cancer cells DECITABINE
apoptosis of leukemic cells; used for
Treat retinoic acid syndrome with dexamethasone myelodysplastic syndrome
An alkylating agent used a treatment “The one who began a good work among you will bring it to completion
by the day of Jesus Christ” Philippians 1:6
TEMOZOLOMIDE for brain tumors such as astrocytoma
and glioblastoma multiforme “There is only one secure foundation: a genuine, deep relationship with
A mitotic inhibitor (microtubule Jesus Christ, which you will carry through any and all turmoil. No matter
ERIBULIN inhibitor) used for metastatic breast what storms are raging all around, you’ll stand firm if you stand on His
cancer love” Charles Stanley
Decreases the production of
2 Tim 4:17
deoxyribonucleotides via inhibition
“But the Lord stood by me and strengthened me…”
of the enzyme ribonucleotide
reductase; Used for sickle-cell Matt 6:25-34
HYDROXYUREA
disease, Chronic Myelogenous “Therefore, I tell you, do not worry about your life, what you will eat or drink,
Leukemia, Cervical Cancer and or about your body, what you will wear. Isn’t there more to life than food and
more to body than clothing? Look at the bird in the sky: They do not sow, or
Polycythemia Vera; also known as
reap, or gather in barns, yet your heavenly Father feeds them. Aren’t you more
Hydoxycarbamide valuable than they are? And which of you by worrying can add even one hour to
Monoclonal antibody targeting CD30 his life? Why do you worry about clothing? Think about how the flowers of the
BRENTUXIMAB
cells; used for Hodgkin Lymphoma filed grow; they do not work or spin. Yet I tell you that not even Solomon in all
mTOR (Mammalian Target of his glory was clothed like one of these! And this is how God clothes the wild
grass, which is here today and tomorrow is tossed into the fire to heat the oven,
Rapamycin) inhibitor; used as an
EVEROLIMUS, won’t He clothe you even more, you people or little faith? So then, do not worry
immunosuppressant in organ saying “What will we eat?” or “What will we wear?” For the uncoverted pursue
SIROLIMUS
transplantation and advanced these things, and your heavenly Father knows that you need them. But above
kidney cancer all, pursue His kingdom and righteousness, and all these things will be given to
you as well. So then do not worry about tomorrow, for tomorrow will worry
Humanized anti-CD20 monoclonal
about itself. Today has enough trouble of its own.
antibody; used for Chronic
OBINUTUZUMAB
Lymphocytic Leukemia and Jeremiah 20:11
Follicular Lymphoma “But the Lord is with me to help me like an awe-inspiring warrior. Therefore
An IgG4 isotype antibody that blocks those who persecute me will fail and will not prevail over me. They will be
thoroughly disgraced because they did not succeed. Their disgrace will never be
a protective mechanism of cancer
forgotten.
cells, and allows the immune system
to destroy cancer cells. It targets the John 6:20
PEMBROLIZUMAB
programmed cell death (PD-1) “But He said to them, “It is I. Do not be afraid”
receptor of lymphocytes; For
Matt 11:28-30
metastatic melanoma and metastatic “Come to me, all you who are weary and burdened and I will give you rest. Take
non-small cell lung cancer. my yoke on you and learn from me, because I am gentle and humble in heart,
An EGFR-TK inhibitor; used for and you will find rest for your souls. For my yoke is easy to bear, and my load is
OSIMERTINIB
advanced non-small-cell lung cancer not hard to carry.
First therapeutic proteasome
BORTEZOMIB inhibitor; used for multiple myeloma Feast Declaration of Abundance: Novena to God’s Love
and mantle cell lymphoma Today, I receive all of God’s love for me.
Today, I open myself to the unbounded, limitless,
overflowing abundance of God’s universe.
Today, I open myself to God’s blessings, healing and
miracles.
Today, I open myself to God’s word so that I become more
like Jesus every day.
Today I proclaim that I’m God’s Beloved, I’m God’s Servant,
I’m God’s Powerful Champion,
And because I am blessed, I am blessing the world, In Jesus’
Name. AMEN
Keep believing God for it! Praying for all of you J

- Doc Yns Pereyra-Borlongan J <3
I know that I will never get the chance to say a valedictory speech, or get to give
an opening remark in any kind of school affair, for I was never a “stellar” student
hahaha. But let me share with you my story, that hopefully, will inspire you a bit
J
I came from a poor but hardworking family. My papa worked in Saudi as a

machine operator while my mother used to sell “isaw-isaw” when I was born. I
could say that mama had delicate pregnancies, for I was born premature and
had a prior miscarriage and two of my sisters died. One because of
hydrocephalus, and the other one due to sepsis. Because we do not have the
funds to provide for my sisters’ hospitalization, mama had to appear on national
television asking for financial aid for my sister. She was so happy when she
finally had the needed resources to pay for my sister’s operation. Unfortunately,
she died before her scheduled surgery. My mother then donated the funds to
another child who had hydrocephalus. These stories that my mother told me
were major motivators for me to become a doctor.
END OF PHARMACOLOGY Even though both my parents came from poor families themselves, they have
always believed in one important thing: that good education is the only
Edited by:
inheritance they could ever give to us. I’m sure this will sound cliché to you. But
Mark Louie C. Mann, MD I myself strongly adhere to this belief, and will surely apply this principle when
Marianne Michelle Q. de la Rosa, MD I too become a parent someday. And since my parents have always aspired for
good education for me and my siblings, they have decided to enroll us in private
catholic schools. Of course, with the great help of some our relatives abroad,
they still persevered in sending us to private schools. That’s why I have always
To all my Topnotch babies, Always Remember this: With God NOTHING
considered myself a “scholar” since elementary. Because somebody else was
IS IMPOSSIBLE (Luke 1:37) J
financing my education.
“The favors of the Lord are not exhausted, His mercies are not spent, they I could say that life was never easy when I was young. At the age of 6 I knew all
are renewed each morning, so great is His faithfulness” Lamentations kinds of household chores: cooking, ironing clothes, sweeping the floor, doing
3:22-23 the laundry etc. I even remember being able to do a perfect “sinaing”, “sinangag”
and sunny side up at the age of 6. I’m pretty sure that when it comes to equipment to buy) and have more money to give to my parents. I even
“domestication”, I belong to the 99+ percentile of people my age. And for my remember giving baon to my siblings and using my savings to pay for their
mother, that’s a great achievement. During that time, especially during summer, tuition fee. During those times, I keep thanking God that He provided for my
we had to sell balot/penoy/chicharon, biskwit and ice candy around our family. We may not be living luxuriously, but God always provided enough, and
neighborhood to help augment our parents’ income. We literally “lako” our on time. I also praise Him for keeping my family together, despite the fact that
products door-to-door. Some by coercion, some by virtue of mercy. Then, all the mama was already working as an OFW. I was a scholar of the QC SYDP
profit we will get will be used to pay our school expenses, or when times are (Scholarship Youth Development Program), so I do not need to pay any tuition
harder, to pay our Meralco bill. I can accurately remember what my notebooks fee during college. This, again, was big blessing to our family. God was very good
were, for they have the same design each and every year (for they were among to us.
the cheapest)
I still did student assistant duties, now at UPCP library (my salary was
Assignment ntbk: Lapu-Lapu (because this is ntbk number 1 and he is the very Ph25/hour which was very small hahaha. But I kept doing it, since I get to
first Filipino hero) borrow all needed books from the library since I don’t have my own book. Also,
Filipino ntbk: Apolinario Mabini (He looks very Filipino to me) we did not have any computer at home. So I would do overtime job at the lib to
AP: Andres Bonifacio (for he was the bravest for me) do some typing and printing for free yey! Or I would go on overnight at my
Science: Jose Rizal (self-explanatory) bestfriend’s house to type on her computer). Still sold food to my classmates,
MAPE: Juan Luna (because he was an artist) but of course with an upgrade! I now sell palabok, pancit and spaghetti which I
Math: the 3 martyrs (for they are more than 1) get from my friendly neighborhood cook. And sitsirya from Divisoria (hahaha).
Etc etc etc This cycle continued even until I was in med school.
I even recycle them when there are still much of the paper left. Despite these I was accepted into the Ateneo School of Medicine and Public health (ASMPH)
boring ntbk designs, I still feel blessed that I was never forced by mama to get also as a scholar. Maybe my life story was so interesting to my panel of
Jolina, Stefano Mori or Magic Temple ntbks. If you know what I mean J interviewers that I got a full scholarship. Life was still hard, for my sister is now
in college and while my brother is in High school, and both of them are studying
When I was in grade 4, my papa lost his job. That was certainly one of the in a private school. But I had so much blessings then! I got a Neo Laptop that
greatest challenge my family had ever experienced. There were many nights was gifted to me by my Tita Sarah (I used until I was in Topnotch hahaha
that we did not have electricity, we had only 1 nilagang manok (as in without imagine teaching with a laptop that would turn off when the charger was pulled
vegetables, just plain boiled chicken) for Noche Buena of 1998, our ulam was out of the socket hahaha). I always have MRT ticket load and get to go home
always adobong kangkong and dilis and we had to do extra work as students. together with my papa some days of the week (He used to work in Ortigas). I
During weekends, our whole family worked for the printing press company of would usually walk from ASMPH to Ortigas MRT station to save up on money
one of mama’s friends. At school, my sister and I would go around the campus and to lose some weight (hahaha). I would get free siomai from papa at the MRT
to get tin cans (to be sold to junk shops) and get soft drink bottles to get their station. That’s why I love going home with papa. And until now, even if he was
“deposit” (which was Php2) from the cafeteria. This is why I always bring two already gone, I would eat the same siomai when I’m at the Ortigas MRT station.
bags with me. One for my school stuff and the other for my loot. Every day I I was still doing tutorial (but now only on weekends and Friday nights since
would volunteer to become the cleaner in our class, for I will get all the tin cans Med School was more demanding) and still sold food (with the addition of
and plastics from our trash can so that I can bring them home. I didn’t have cellphone load ahahaha) so that I won’t have to ask money from my parents. I
complete books then. It was only during the third quarter of the year that I had even have my own corner at our clasroom where I leave my “honesty” store
a complete set of books. Because my teachers decided to give me a copy of the (which my batchmates would call as “Cantyña”). I also learned how to bake! I
book out of their own salary. I must say, my elementary teachers were kind to was also selling cakes and cupcakes to my schoolmates and to consultants at
me, and had always faith in me. They also collect tin cans and plastics for me. The Medical City. I also ventured into selling pasta (red sauce, white sauce,
That went on for 2yrs. I just study hard. I still manage to be at the top of our lasagna, pesto etc). I bring around 30packs of pasts to school which I sold at
class despite having to “work” and study at the same time. I knew I had to help TMC (believe me, they are always sold out), while I have a staff that sold them
my parents, the turo-turo/karinderya business they put up from papa’s at the canteen where my sister works (She was already an English teacher back
separation pay was doing ok, but the profit is not enough to meet all our needs, then). I think I also have “sales” and business skills running in my genes. I also
considering that I still have a baby brother during that time. Until finally, did market research interview sessions to earn Php2,000-3,000 per session (I
graduation came. My father found a new (and stable) job and I was admitted to will just pretend to be rich and part of the class A of the society so I can get the
a science high school (which means free tuition for me Yayyyy!). 2k fee hahaha. I always borrow clothes from my fashionable friends of course
so I can play the part well). All kinds of “raket” I think I have already done. I even
I believe that getting into a science high school was my gateway for everything, planned on applying some short course TESDA subjects to improve my skills,
and believe me, it is during high school that my teaching career started. I started hahaha which I never had the time to do.
teaching at the age of 12. Well, probably earlier since I was teaching "drama"
classes (imagining I was Judy Ann Santos) and ABCs and 1-2-3s to my neighbors. But you know, God had an even brighter and better plan for me. I reviewed for
I also did substitute teaching for a class of grade2 students when I was in grade my Pharmacy board exam with the hope that I would top the exam. It was tough,
3 when my aunt was not able to attend to her class. For the record, I came from juggling studying, tutoring and doing MBA internship at the same time. I wasn't
a family of teachers. My grandparents are teachers, my mother is a teacher, my able to attend all the classes and never had the opportunity to take any drills,
sister is a teacher and many of my aunts, uncles and cousins are teachers. That comprehensive exam or the pre-board exam. I was doing everything I can so
could probably explain it. My first tutoring stint was in June year 2000. I went that when I top the boards, the owner of the review center would hire me to be
to my Alma Mater St. Mary's College QC to pay some of my favorite teachers a a lecturer. With God's perfect will, I was 0.03 short of getting into the top10. I
visit. Little did I know that my "teaching career" will start there. My English felt devastated. I felt my dream of becoming a lecturer melt away. But I knew
teacher Ms Cecilia Asejo recommended me to one of her student's parents as a that God did this on purpose. He had the best plan for me in mind. I still felt
personal tutor in preparation for her Science High School entrance exam. I was thankful that He made me pass the boards. I sent a message to one of the owners
in my first year at Quezon City Science High School back then. I accepted the (who is also my teacher at the review center) to thank Him for teaching us and
"Job Offer" without second thoughts. I knew I needed the job. After my classes in case He needs any assistance in anything, I am just one message away.
at 4-5pm, I would assist for a while in the English Center as a student assistant.
Checking my batchmates’ quizzes, cleaning the English center or reading my Sometime in August 2010 one of the staff of the review center called me. He said
crush's English journal (hehe). After that, I would walk to Teacher's Village (just that my teacher was asking me to make the module 1 exam for the upcoming
in front of SM Annex) to go to my "tutee". My salary then was only Php50/hr, of review season. When I ended the phone call, I cried. And I cried a lot. I did not
course with free meryenda, dinner and pabaon from tita Letty and Jessica. After imagine that God would work this way. I was contacted by the review center to
around 2-3hours of tutorial, I would then head home, feeling so excited to hand make exams for them, and yes, I was still given a chance to become a lecturer. I
that Php150 to mama for her to buy us dinner the next day. While my salary as felt so thankful to God, that indeed, he answers our prayers. God is indeed
student assistant I use for my everyday expenses at school. faithful! He is the one who planted dreams and aspirations in my heart, and I am
certain that each one of them would come true, according to His perfect will.
My parents' friends learned that I was doing tutorials, so they started to hire me
as well, increasing my salary to Php150/hr. During those times, that little And so, I started teaching at Manor Review Center. At first, I was only asked to
money meant so much to me. It made me feel relieved knowing that I am helping make exams and discuss the rationale to the students. But later, one of the
my parents in earning money and not add to their financial responsibilities. My owners also asked me to teach his subject because he could not make it to the
brother and sister were also studying already, I knew my parents would get any assigned dates. I was very nervous. It was my first time to teach a class of 200+
kind of help they could have grip on. The tutorials continued, having tutorial people (except of course for NSTP hehe), and I would be teaching Microbiology
classes all days of the week. It was tough, I must admit. It took away so much for 3 days. I prayed and prepared well for the lecture, thinking that I was doing
time from me. I have less time for studying. I have less time for rest. I have less it for God and to live up to my boss' expectation. The lecture ended. I was given
time for other things I would like to pursue. I also have to sell food (Samosa, a good feedback. I was congratulated by the owners and my teaching career at
Karyoka, Siomai etc) to my classmates and teachers everyday to further Manor already started. I was given more teaching load, now teaching other
increase my income. I was the student council president. I was active in the subjects such as Organic Medicinal Chemistry, Dosage Forms, Clinical and
church choir, I would attend our weekly practices and sing my best for The Lord Hospital Pharmacy, Pharmacognosy, and the longest and probably the most
during the Holy Mass. I know that it was all God's grace that I was able to do dreaded subject of students: Pharmacology and Toxicology. I feel extremely
those things all at the same time. blessed having been trusted by my mentors to teach their subjects. And now,
God even gave me the opportunity to reach out to medical students like you
I graduated High School and went to UP for college. My clients further increased. through Topnotch J I will forever be grateful to all those people, whom God
Now, aside from Science High School entrance exam, I also taught UPCAT-ACET- used, to bring me to the state of contentment that I am in now. I am now happily
USTET entrance exam, Algebra, Geometry, Trigonometry, Calculus, Basic married, can pay for Grab rides, can drive our car, lives in a decent apartment
Sciences, Physics and Chemistry. I actually never imagined myself teaching with our loving dog Matty, and hopefully, in God’s perfect time, kids of our own
Math and hardcore science subjects, because I think I was not that good at them. J. I have already sent two of our house helpers to college (and their siblings at
But I had no choice, I needed to continue teaching. So, I prepared well for my their provinces to school) and they are now working in restaurants around the
classes. My salary got bigger, it was now Php250-350/hr. I now have more metro (both of them took HRM). I also supported one of our loyal “masahista”
money to spend for my school needs (Pharma was very expensive, so many Lab in her endeavors of working aborad. She is now in UAE working in a hotel as a
masseur. I am planning to send more students to school, and will definitely
sponsor a medical student in the future. And currently, as a medical resident in
a public hospital, God is also using me to help poor patients not only by giving
them the medical care they need, but also by providing them food, toiletries,
medicines not available in our pharmacy, even their fare back to their provinces
(as far as Visayas and Mindanao). These things, for me, are insignificant to the
amount of blessing God has bestowed upon my life. I am just paying it forward,
to people who needs it most. And as I continue living my life for the Lord, may I
continue glorifying Him with all the talents and treasures He has bestowed upon
me J HAPPY REVIEWING DEARY! J I am always praying for you, Doc! J God
bless you more! J
Doc Yns Pereyra-Borlongan J
HAPPY ARAL PO DOCTORS! J <3 - Matty, Peanut and Summer <3
Giving back
Not one to forget his humble beginnings, Romy has made conscious
efforts to “give back. Aside from his medical practice, Romy, also known as
“Dr. RA,” also dutifully served in the academe, working as a teacher,
professor, and even administrator at the De La Salle Health Sciences
Institute for 27 years.
The well-loved Dr. RA has touched the lives of many — co-workers,
students and many young Lasallian scholars. He has also helped the
children of his own staff in pursuit of a medical degree.
For years, his home and his extensive medicine library were open to
scholars. His clinic always reportedly has the longest queue of patients of
all ages at the De La Salle University Medical Center.
Dr. RA was instrumental in the construction of the DLSHSI library. “I
know how important a library is especially for poor students. Throughout
my years of studying, I survived because of the kind librarians who were
lenient when it came to my borrowing of books because they knew I didn’t
have the money to buy my own copies,” said Dr. RA.
De La Salle Health Sciences Institute now has the Romeo P. Ariniego, M.D.
Library, which houses major resources from around the world, and serves
as a converging point for students, faculty and researchers who all share
Dr. RA’s love for learning.
La Salle’s Brother Gus Boquer once shared Dr. RA’s inspiring story,
which Dr. Willie Ong wrote about in his column in The STAR.
“I believe doctors are doing God’s work. The way they help the sick and
put a smile on a poor patient never fails to amaze me. We have a doctor
here in De La Salle, Dr. Romeo P. Ariniego, who has pledged to give his life’s
earnings to De La Salle. He has already given P10 million for a new library.
And he has already donated his house and lot to De La Salle Institute, which
will take effect after he passes away. How can you not be amazed by
doctors like this?”
The poor boy from Vigan had a dream and attained it. And now his
dream is to be able to let others live their dreams, too.

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TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY MAIN DIGITAL HANDOUT BY PEREYRA-BORLONGAN RPh, MD-MBA

For inquiries visit www.topnotchboardprep.com.ph or www.facebook.com/topnotchmedicalboardprep/

PHARMACOKINETIC PRINCIPLES WATER AND LIPID SOLUBILITY OF DRUGS

FICK’S LAW OF DIFFUSION

✔PRACTICE PROBLEMS SUBCUTANEOUS ROUTE

ROUTES OF DRUG ADMINISTRATION TOPICAL ROUTE

DRUG DISTRIBUTION SPECIAL BARRIERS TO DISTRIBUTION

SUPPLEMENT: Size of the Organ DRUG METABOLISM

RECEPTOR SITES OR RECOGNITION SITES

SUPPLEMENT: Spare Receptors

VARIATIONS IN DRUG RESPONSE

EFFECTIVE DRUG CONCENTRATION

DOSAGE REGIMEN Cockcroft-Gault Equation

THERAPEUTIC WINDOW MNEMONICS: Phase I Reactions

Examples of Phase I Reactions

SUPPLEMENT: Adjustment of Dosage

FOR RENAL PATIENTS

• loss of this dependence signals a mutation BIOEQUIVALENCE

Autonomic Nervous System Skeletal muscle Vasodilation (b2 No effect

• Enteric nervous system (ENS) Secretion Increased (M3)

Trigone and Contraction (a1) Relaxation (M3)

Uterus, pregnant Relaxation (b2) Contraction (M3)-

Penis, Seminal Ejaculation (a) Erection (M)

Cholinergic Drug Effects

CHOLINOCEPTOR-ACTIVATING AND PILOCARPINE [C]

Uses Glaucoma, Sjögren syndrome, Sicca syndrome

BETHANECHOL [C] Nicotine activates ALL autonomic post ganglionic

Notes striatum system. Hence the role of your cholinergic

(Regenerates active acetylcholinesterase)

Antidote for organophosphate poisoning (first choice,

Available PO and IV forms, relatively short t½ (6hrs) ________________________________________________________________

SUPPLEMENT: OXYBUTYNIN [B] How to predict the effect of ganglion blockers?

• Atropine fever (hyperthermia)

MNEMONIC: Atropine Toxicity

• first successful agents for the treatment of hypertension but

ALPHA-2 (a2) ADRENERGIC EFFECTS

SITES OF AUTONOMIC DRUG ACTION

MISCELLANEOUS ADRENERGIC EFFECTS

Dopamine-1 (D1) Adrenergic Effects

Dopamine-2 (D2) Adrenergic Effects

SYMPATHOMIMETICS DOPAMINE [C]

SE Cardiovascular disturbance, Arrhythmias

Added to local anesthetic solutions to decrease systemic ISOPROTERENOL [C]

Asthma (adjunct to your Beta 2 agonist), Drug for

SELECTIVE BETA-1 (b1) AGONISTS

Can be caused by a preganglionic or postganglionic lesion. Tachycardia, Arrhythmias, Tachyphylaxis,

BOTH types of drugs

SUPPLEMENT: OTHER SYMPATHOMIMETICS KEY LEARNING POINTS:

SELECTIVE BETA 1 (b1) BLOCKERS

AHA OCTOBER 2017 GUIDELINES

pregnant women are as follows:

4. ADRENERGIC BLOCKERS MNEMONIC: Drug-Induced Lupus

PRAZOSIN [C] What medications may cause drug-induced lupus?

HOW DOES MINOXIDIL CAUSE EXCESSIVE FENOLDOPAM [B]

Block voltage-gated L-type calcium channels SUPPLEMENT: Malignant Hypertension

MNEMONIC: Drugs that can cause Gingival Hyperplasia

Uses Angina, Hypertension

CAPTOPRIL [C, D in 2nd & 3rd trim]

neonatal morbidity and death

KEY LEARNING POINTS Hyperkalemia