Pharmacology

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 September 2021 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
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below. Antibiotic Agents: 45
THIS HANDOUT IS NOT FOR SALE! Antibacterial agents 45
Antifungal drugs 54
INSTRUCTIONS Antiviral drugs 55
To scan QR codes on iPhone and iPad Antiprotozoal drugs 57
1. Launch the Camera app on your IOS device Anthelmintic drugs 60
2. Point it at the QR code you want to scan
3. Look for the notification banner at the top Gastrointestinal Pharmacology 61
of the screen and tap Toxicology 64
To scan QR codes on Android Management of Poisoned Patients 67
1. Install QR code reader from Play Store CNS Drugs 67
2. Launch QR code app on your device
Sedative-Hypnotic Drugs 67
4. Tap browse website Alcohols 69
Antiseizure Drug 71
This handout is only valid for the September 2021 PLE batch. General Anesthetics 74
This will be rendered obsolete for the next batch Local Anesthetics 76
since we update our handouts regularly. Skeletal Muscle Relaxants 77
Drugs Used in Parkinsonism 79
Antipsychotic Agents and Lithium 81
PHARMACOLOGY Antidepressants
Opioid Analgesics and Antagonists
84
87
By Maria Yña Eluisia T. Pereyra-Borlongan, RPh, Drugs of Abuse 88
MD-MBA Endocrine Pharmacology: 90
Contributors: Hypothalamic and Pituitary Hormones 90
Julianne Cristy B. Lopez, MD-MBA Thyroid and Anti-thyroid drugs 92
Corticosteroids and Antagonists 94
Eric E. Calderon Jr., MD
Gonadal Hormones and Inhibitors 96
Martin C. Magadia, MD
Pancreatic Hormones, Antidiabetic agents, Drugs
Tiffany Grace Uy, MD for Obesity and Glucagon
99
Drugs that affect Bone and Mineral Homeostasis 103
Approach to Topnotch Pharmacology Cancer Chemotherapy 105
• Please have the following Topnotch materials at hand:
o Topnotch Main Handout will serve as your main reference material
• Please buy the following: BASIC PRINCIPLES OF
(1) Katzung, Basic and Clinical Pharmacology 14th ed. 2018
(2) Goodman and Gilman’s The Pharmacological Basis of Therapeutics. PHARMACOLOGY
13th ed. 2018
• Pharmacology, like Biochemistry, is one of those subjects that seem very
INTRODUCTION
difficult at first, but is actually kayang-kaya. DEFINITION OF TERMS
• It’s not that hard for the following reasons: • DRUGS
o Most questions are of the recall-type o any substance that brings about a change in biologic function
o most of the answers to the questions that they ask can be found in the through its chemical actions
recommended textbook (Katzung)
o almost all questions revolve on the following themes: drug of choice,
• PHARMACODYNAMICS
mechanism of action, indications, contraindications and adverse o actions of a drug on the body
effects. o receptor interactions, dose-response phenomena, and
• Most students who self-study usually just read pharma recall or mechanisms of therapeutic and toxic action
Lippincott. The pharma lecture and handout are based purely upon • PHARMACOKINETICS
Katzung Pharmacology and Goodman & Gilman. o actions of the body on the drug
SUPPLEMENT: o concerned with
• Text in “Supplement” boxes is for additional information § Absorption
• Letter after each drug signifies its FDA Pregnancy Category. If no § Distribution
letter is found: NO FDA ASSIGNMENT YET § Metabolism
TOPIC PAGE § Excretion
Basic Principles of Pharmacology 1 § Elimination: metabolism and excretion
Pharmacokinetics 2
Pharmacodynamics 6 MNEMONIC: Pharmacokinetics vs Pharmacodynamics
Drug Evaluation and Regulation 8 pharmacoKineTics pharmacoDynaMics
Autonomic Pharmacology 9 (Katawan → Tableta) (Drugs → Man)
Cholinergic Pharmacology 10
Cholinoreceptor-Activating and Cholinesterase-
11
Inhibiting Drugs PHARMACOKINETICS vs.
Cholinoreceptor Blockers 12 PHARMACODYNAMICS
Adrenergic Pharmacology 13 https://qrs.ly/jrckbgz
Sympathomimetics 14
Adrenoreceptor Blockers 15
Treatment of Glaucoma 16
TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY MAIN DIGITAL HANDOUT BY PEREYRA-BORLONGAN RPh, MD-MBA. Page 1 of 109
This handout is only valid for the September 2021PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
PHARMACOKINETICS WATER AND LIPID SOLUBILITY OF DRUGS

• aqueous solubility is directly proportional to electrostatic charge
PHARMACOKINETIC PRINCIPLES
(ionization, polarity)
o ionized and polar drugs are more water-soluble, hence
INTRODUCTION increased clearance (less absorption)
TO PHARMACOKINETICS • lipid solubility is inversely proportional to electrostatic charge
https://qrs.ly/dhckbof (ionization, polarity)
o non-ionized and non-polar drugs are more lipid-soluble,
hence increased absorption (less clearance)
PHARMACOKINETICS: MOVEMENT OF DRUGS IN THE BODY WEAK ACIDS AND BASES
• drug molecules must travel from the site of administration to • many drugs are weak acids and weak bases which dissociate into
the site of action ionized and non-ionized forms
• pH determines the fraction of drug molecules charged (ionized)
NATURE OF DRUGS versus uncharged (non-ionized)
• SIZE AND MOLECULAR WEIGHT • predicted by Henderson-Hasselbach equation
o vary from MW 7 (lithium) to over MW 50,000 (alteplase) o relationship between pH, pKa (dissociation constant) and
§ <100 – rarely sufficiently selective in their actions concentration of charged and uncharged forms
§ majority have MW 100 to 1000
§ >1000 – poorly absorbed and poorly distributed HENDERSON-HASSELBACH EQUATION
• DRUG-RECEPTOR BONDS
o By strength: Covalent > Electrostatic > Hydrophobic
§ Electrostatic bonds: ionic bonds, hydrogen bonding, van der
Waals (permanent/induced dipoles)
o Strength of bond formed by drugs determines reversibility of
effects
§ Organophosphate bond with AChE: initially weak and
reversible-> after 24-48 hrs, forms strong covalent bones
(‘aging’), cannot be reversed by Pralidoxime
HENDERSON-HASSELBACH
WATER AND LIPID SOLUBILITY OF DRUGS EQUATION
PERMEATION is the movement of drug molecules into and within https://qrs.ly/z8ckbqo
biologic environments. It involves the ff. processes:
DISSOCIATION OF WEAK ACIDS
1. AQUEOUS DIFFUSION
• passive movement of small drugs through small water-filled
pores between the blood and extravascular space (exceptions:
brain, testes, and eye barriers that have no pores)
• affected by drug concentration and charge • protonated (HA) form is more lipid soluble and more likely to
• governed by Fick’s Law of Diffusion cross biological membranes
o Weak acid is better absorbed in acidic environment
2. LIPID DIFFUSION (Phenobarbital is better absorbed in the acidic environment of
• movement of drugs through lipid membranes between body the stomach)
compartments, and from the ECF to the ICF • unprotonated (A-) form is more water-soluble and undergoes
• most important limiting factor for permeation better clearance
• governed by Fick’s law of diffusion o Weak acid is better excreted in basic environment
• very important for the diffusion of weak acids and weak bases (Aspirin is better excreted in a basic urine)
DISSOCIATION OF WEAK BASES
3. TRANSPORT BY SPECIAL CARRIERS
• drugs that do not readily cross through membranes may be
transported across barriers by mechanisms that carry similar
endogenous substances
o ions through Na+/K+ pump • protonated (BH+) form is more water-soluble and undergoes
o neurotransmitter through reuptake transporters better clearance
o metabolites such as glucose through GLUT o Weak base is better excreted in acidic environment
o carriers for foreign molecules or xenobiotics (Amphetamine is better excreted in acidic urine)
• NOT governed by Fick’s law of diffusion and is capacity-limited • unprotonated (B) form is more lipid-soluble and more likely to
cross biological membranes
4. ENDOCYTOSIS AND PINOCYTOSIS o Weak base is better absorbed in basic environment
• endocytosis: large drugs bind to receptors, are internalized and (Allopurinol is better absorbed in the basic environment of the
released after vesicle breakdown (reverse: exocytosis) small intestines)
• small polar drugs combine with special proteins to form SUPPLEMENT: Application of HH Equation
complexes which undergo endocytosis: • excretion of a weak acid may be accelerated by alkalinizing the urine
o vitamin B12 bound to intrinsic factor with bicarbonate (HCO3-)
o iron bound to transferrin • excretion of a weak base may be accelerated by acidifying the urine
with ammonium chloride (NH4Cl) and ascorbic acid
FICK’S LAW OF DIFFUSION
• predicts the rate of movement of molecules across a barrier
Permeability Coefficient
!"#$ = ('! − '" ) × × "?@A
Thickness
• pharmacologic implications
o absorption is faster in organs with larger SA (intestinal >
stomach)
o absorption is faster in organs with thinner membranes (lung >
skin)
Titration curve for an acid of the type HA.
The heavy dot in the center of the curve indicates the pKa 5.0.
Modified Figure 2-4. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
MNEMONIC: pKa
Intramuscular Absorption is faster and more
“UP Above” complete than oral (bypasses first-pass
Unprotonated >Protonated: above pKa effect, higher bioavailability)
• Large volumes may be delivered if
drug is not too irritating (i.e. 5g of
UP Above
MgSO4)
https://qrs.ly/87ckbrz
• Anticoagulants cannot be given by
this route because they may cause
bleeding (hematomas)
✔PRACTICE PROBLEMS
IM Injections to Buttocks
1. Aspirin is a weak organic acid with a pKa of 3.5. What percentage of
Which quadrant of the buttocks is
a given dose will be in the lipid soluble form at a stomach pH of 2.5?
[JKB?GLGKAL@M] safest for IM drug administration?
BC = BDA + FGH o superolateral = safe
[O?GLGKAL@M]
[J] o superomedial = gluteus medius gait
2.5 = 3.5 + FGH o inferomedial = sciatica
[O]
[J] Bypasses the first pass effect
2.5 − 3.5 = FGH Subcutaneous
[O] Slower absorption than
[J] intramuscular route (NO blood
−1 = FGH
[O] vessels in the subcutaneous space)
#!
[J] • Large volume doses are less feasible
10 =
[O] • Anticoagulants do NOT cause
Unprotonated is 10-1 or 0.10 or 10% hematomas when administered via
Protonated is 90%
this route
Since aspirin is a weak acid, the more lipid soluble form is the Partial avoidance of the first-pass
protonated HA form. Hence, the final answer is 90%. effect
2. Atropine is a weak organic base with a pKa of 9.7. What percentage Rectal
of a given dose will be in the lipid soluble form at a pH of 7.7? (suppository) • Useful for large amounts of drugs
with unpleasant tastes and for
patients who are vomiting
ANSWER TO QUESTION 2
https://qrs.ly/ahckbsj VENOUS DRAINAGE OF THE RECTUM.
Superior Rectal Vein: IMV → PV (first-
pass)
Middle Rectal Vein: IIV → IVC
Inferior Rectal Vein: IPV → IIV → IVC
DRUG ABSORPTION Offers delivery closest to the
Inhalational respiratory tissues
ABSORPTION
• transfer of a drug from its site of administration to the Very rapid absorption with minimal
bloodstream systemic effects
• affected by 3 major factors Convenient for drugs that are gases at
1. route of administration room temperature (nitrous oxide,
2. blood flow nitric oxide) or easily volatilized
3. concentration (anesthetics)
Topical: application to skin, mucous
membranes of the eye, ear, nose,
ROUTES OF DRUG ADMINISTRATION
throat, airway, or vagina for local
SUMMARY OF ABSORPTION effect
AND ROUTES Slowest route of drug administration
OF DRUG ADMINISTRATION Absorption varies with the area of
https://qrs.ly/bbckbss application and drug formulation
Ordered by Increasing ability to retard
Topical
evaporation:
Most convenient; Most common route (more evaporation) tinctures > wet
Oral (swallowed) of drug administration dressings > lotions > gels > aerosols >
Absorption is slower powders > pastes > creams > foams >
Subject to first-pass effect (a ointments (less evaporation)
significant amount of the drug is Using dermatologic drug
metabolized in the gut wall, portal preparations for skin inflammation:
circulation and liver before it reaches the o Acute inflammation = drying
systemic circulation) agents
Direct absorption into the systemic (tinctures, wet dressings, lotions)
venous circulation, bypassing the first- o Chronic inflammation = lubricating
Buccal and pass effect agents
Sublingual (not SUPPLEMENT (creams, ointments)
swallowed) • Buccal (pouch between the gums Transdermal Application to the skin for systemic
and cheek) -> Facial vein -> Internal effect
jugular vein Absorption occurs very slowly but
• Sublingual (under the tongue) -> bypasses the first-pass effect
Lingual vein → Internal jugular vein
• IJV → brachiocephalic (innominate) vein SUPPLEMENT:
→ superior vena cava → right atrium What routes of administration undergo significant First-Pass Effect?
Intravenous Instantaneous and complete ORAL
absorption that bypasses first-pass Partially bypass? RECTAL
effect (100% bioavailability) Completely bypass? IV, IM, SC, SL, INHALATIONAL, TOPICAL,
TRANSDERMAL
Potentially more dangerous:
Inadvertent systemic introduction of
bacteria through the IV line (line
sepsis); Difficult to reverse effects
DRUG DISTRIBUTION CYTOCHROME P450 ENZYMES

• Process wherein drug reversibly leaves the bloodstream and • Involved in the Phase I metabolizing reactions
enters the target organ • Also called mixed-function oxidases
• Depends on 4 major factors: • High concentrations in the smooth endoplasmic reticulum of the liver
• Not highly selective in their substrates
• Approximately 75% are metabolized by: CYP3A4 or CYP2D6
DRUG DISTRIBUTION
https://qrs.ly/azckbt2 ENZYME INDUCTION
• results from increased synthesis of cytochrome P450 enzymes
and heme
1. SIZE OF THE ORGAN • several days are usually required to reach maximum induction
• determines concentration gradient between blood and the organ • most common strong inducers are Carbamazepine,
o Skeletal muscles are a very large organ Phenobarbital, Phenytoin, and Rifampin
§ large doses are required to actually change the MNEMONIC: CYTOCHROME P450 INDUCERS
concentration gradient
“Ethel Booba takes Phen-Phen
o Brain is a small and compact organ and Refuses Greasy Carb Shakes”
§ only a small amount of drugs is required to change Ethanol (Chronic ingestion) Griseofulvin
concentration gradient Barbiturates exc. SECOBARBITAL Carbamazepine
2. BLOOD FLOW Phenytoin St. John’s Wort/Smoking
• important determinant of the rate of drug uptake (but not the Rifampicin
OTHER ENZYME INDUCERS:
amount of drug in tissue equilibrium)
Glutethimide
• well-perfused organs will achieve high tissue concentrations Phenylbutazone
sooner than poorly perfused tissues Ritonavir (on chronic or repeated administration)
3. SOLUBILITY **SECOBARBITAL is an INHIBITOR **
• influences the concentration of the drug in the extracellular fluid
surrounding blood vessels
• Brain which is high in lipid content will dissolve high ENZYME INDUCTION
concentration of lipid soluble drugs https://qrs.ly/wlckd94
o non-ionized, non-polar drugs are more lipid-soluble
and undergo more extensive distribution
4. PROTEIN BINDING
ENZYME INHIBITION
• binding to macromolecules in blood or tissue will tend to increase
the drug’s concentration in that compartment • most significant inhibitors are Amiodarone, Cimetidine,
o acidic drugs: bound to albumin Furanocoumarins present in grapefruit juice, azole antifungals,
o basic drugs: bound to orosomucoid and a1-acid glycoprotein and the HIV protease inhibitor ritonavir
• drug metabolism may be decreased by reduction in blood flow
• bound drugs CANNOT cross membranes and exert their effect
to the metabolizing organ
• only unbound drugs CAN cross membranes and exert their effect
o EXAMPLE: Propranolol reduces hepatic blood flow
o ONLY THE FREE (UNBOUND) DRUG CAN BE ABSORBED,
DISTRIBUTED, METABOLIZED, EXCRETED AND EXERT MNEMONIC: CYTOCHROME P450 INHIBITORS
PHARMACOLOGIC EFFECT “Inhibitors Stop Cyber Kids from Eating GRApefruit QV”
o Examples: Phenytoin, Valproic acid Isoniazid Grapefruit Juice
Sulfonamides Ritonavir (on acute ingestion)
DRUG METABOLISM Cimetidine Amiodarone
Ketoconazole Quinidine
METABOLISM
Erythromycin Valproic Acid
• drugs are chemically altered in the body OTHER CYP450 INHIBITORS
• drugs may undergo 3 metabolic fates: Allopurinol Chloramphenicol
o termination of drug action (drugs are metabolized into Chlorpromazine Dicumarol
biologically inactive derivatives) Disulfiram Ethanol (acute toxicity)
o drug activation: prodrugs are metabolized in the body to Itraconazole Nortriptyline
Oral contraceptives Phenylbutazone
become active (Desmethyldiazepam – an active metabolite of
Saquinavir Secobarbital
Diazepam, Chlordiazepoxide and Flurazepam) Spironolactone Troleandromycin
o elimination without metabolism (some drugs are not modified by
the body and continue to act until they are excreted)
ENZYME INHIBITION
https://qrs.ly/alckdai
DRUG METABOLISM
https://qrs.ly/uhckd8v
Suicide Inhibitors
• bind irreversibly to metabolizing enzymes
TYPES OF METABOLIC REACTIONS o EXAMPLES: ethinyl estradiol, norethindrone, spironolactone,
PHASE 1
PHASE 2 secobarbital, allopurinol, fluroxene, PTU
BIOTRANSFORMATION/
SYNTHESIS/ CONJUGATION
FUNCTIONALIZATION
• Reactions that convert the • Reactions involve conjugation
DRUG ELIMINATION
parent drug to a more polar of subgroups to –OH, –NH2, ELIMINATION
(water-soluble) or more and –SH functions on the drug • Elimination: termination of drug action (may involve
reactive product by molecule metabolism into inactive state and/ excretion out the body)
unmasking or inserting a • makes the drug more polar Elimination = Metabolism + Excretion
polar functional group • Excretion: release of drugs/metabolites out the body (via urine,
• Hydrolysis Conjugation with: stool, bile, exhaled air)
• Oxidation • Glucuronic acid • Duration of drug action is determined by:
o Majority by cytochrome • Acetic acid o dose administered
P450 enzymes • Glutathione o rate of elimination following the last dose
• Reduction • Glycine
• Deamination • Sulfate/methyl group
Drugs may undergo Phase II metabolism before or after Phase I
DRUG EXCRETION FIRST ORDER VS.

VS ELIMINATION ZERO ORDER ELIMINATION
https://qrs.ly/82ckdan https://qrs.ly/9ickdax
Rate of elimination is MNEMONIC: Zero Order Kinetics

First-Order Elimination proportionate to the What drugs display zero order
concentration elimination kinetics?
• concentration decreases WHAT PET
exponentially over time Warfarin
Heparin
Characteristic half-life of Aspirin
elimination: concentration Tolbutamide
decreases by 50% for every half- Phenytoin ZERO-ORDER KINETICS
life Ethanol https://qrs.ly/8dckdbg
Theophylline
Most common type of
elimination
✔PRACTICE PROBLEM
Zero-Order Elimination / Rate of elimination is
ELIMINATION KINETICS
Saturable / constant regardless of
1. Which drug displays first-order elimination? Zero-order
Michaelis-Menten concentration
elimination?
Kinetics • concentration decreases linearly
over time
• Constant amount of drug being
excreted over time
Occurs when drugs have
saturated their elimination
ANSWER TO
mechanisms
ELIMINATION KINETICS
QUESTION
Figure 1-3. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 https://qrs.ly/y8ckdbn
PHARMACOKINETIC CALCULATIONS
EFFECTIVE DRUG CONCENTRATION • Most important pharmacokinetic parameter to be

• concentration of a drug at the receptor site considered in defining a rational steady state during dosage
regimen
APPARENT VOLUME OF DISTRIBUTION -$.# /0 #"121&$.1/&
!"#$%$&'# (!*) =
• volume at which drug would need to be uniformly distributed to 3"$42$ '/&'#&.%$.1/& (!5)
produce an observed blood concentration
WXYZ[\ Y] ^_Z` a[ \bc dYê STEADY STATE
V$ =
fghiXh ^_Z` jY[jc[\_h\aY[ • condition in which the average total amount of drug in the body
• can be altered by liver and kidney disease does not change over multiple dosing intervals
• rate of drug administration equals the rate of elimination
Volume of Distribution • Reached in 4-5 half-lives of the drug
Low Vd Distributed in blood
Distributed in extracellular space or body HALF-LIFE
Medium Vd
water k. lmn × VYgZXc Y] âi\_adZ\aY[
\%' =
High Vd Distributed in tissues & ogch_h[jc
• constant for drugs following first-order kinetics
CLEARANCE • disease, age, and other variables usually alter clearance of a drug
• relates the rate of elimination to the plasma concentration much more than Vd
• depends on the drug, blood flow and condition of the organs of
elimination BIOAVAILABILITY
o for a drug that is very effectively extracted by an organ, • fraction of the administered dose that reaches the systemic
clearance is flow-limited circulation
o for drugs eliminated with first-order kinetics, clearance is a • drugs administered intravenously have 100% bioavailability
constant proportion • reduced by incomplete absorption, first-pass metabolism, and
o for drugs eliminated with zero-order kinetics, elimination rate presystemic redistribution
is a constant amount • determined by computing the area under the plasma
concentration curve (AUC)
Corrected Dosage
A drug is 50% cleared by the kidney and 50% by the liver. Its
normal dosage is 200 mg/d. What is the corrected dosage in a
patient with a creatinine clearance of 20 mL/min?
CORRECTED DOSAGE
FOR RENAL PATIENTS
https://qrs.ly/rackdc6
Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
After oral administration of 500mg of Drug A, only 300mg were Cockcroft-Gault Equation
absorbed into the patient’s systemic circulation. What is its • to calculate the patient’s creatinine clearance, use the Cockcroft-
bioavailability? Gault equation
(HKI − M7#) × N#17O.$%
!""# = (× I. UV 1& 0#2$"#4)
BIOAVAILABILITY PQ × R#%S2 !%#$.1&1&#&%/!(
ANSWER TO QUESTION
https://qrs.ly/2nckdbr SUPPLEMENT:
Amount of drug in the body at any time is computed as:
p( × BFAqrA sGKs@KL?ALtGK
DOSAGE REGIMEN Steady State Concentration during the ff t½:
• plan for drug administration over a time period 1st t½ : 50%
• results in the achievement of therapeutic levels of the drug in 2nd : 75%
3rd : 87.5%
the blood without exceeding the minimum toxic concentration 4th : 93.75%
MAINTENANCE DOSE
!"#$%&$"$'& )*+& =
-.&"/"$'& × )&+#/&1 2."+3" '*$'&$%/"%#*$ PHARMACODYNAMICS
4#*"5"#."6#.#%7
• equal to the rate of elimination at steady state
• important to maintain concentration above minimum
therapeutic level:
o give large doses at long intervals
o smaller doses at more frequent intervals
LOADING DOSE RECEPTORS VS EFFECTORS

6#41%#6 3"$42$ !/&'#&.%$.1/& • Receptor: specific molecules in a biologic system with which
*/$61&7 8/4# = 9! × drugs interact to produce changes in the function of the system
;1/$<$1"$=1"1.>
• if therapeutic concentration must be achieved rapidly and the o Receptor site or recognition site: specific binding region of the
volume of distribution is large macromolecule
• if the LD is very large, dose should be given slowly to prevent • Effector: translate the drug-receptor interaction into a change
toxicity in cellular activity
o due to excessively high plasma levels during the distribution • some receptors are also effectors (Tyrosine kinase receptor in
phase insulin receptor molecule, Na/K channel in nicotinic Ach
receptor, Adenylyl cyclase)
THERAPEUTIC WINDOW
GRADED DOSE-RESPONSE RELATIONSHIP
• safe range between the minimum effective concentration and the
• Dose-response curve: graph
minimum toxic concentration of a drug
of dose (drug concentration)
o minimum effective concentration: determines the desired
versus response
trough levels of a drug given intermittently
o Plotting in log axis: yields a
o minimum toxic concentration: determines the permissible
sigmoid curve
peak plasma concentration
o efficacy (Emax) and potency
(EC50) are derived from this
curve
§ Emax: Maximal effect
achievable, with increasing
concentration of a drug
§ EC50: Concentration of the
drug, wherein half of the
maximal effect is achieved
GRADED DOSE-BINDING RELATIONSHIP

• Dose-binding curve: graph of
dose (drug concentration)
SUPPLEMENT: Adjustment of Dosage versus fraction of receptors
• renal disease or reduced cardiac output often reduces the clearance bound to drug
of drugs that depend on renal function § Bmax: Maximal number of
• impairment of hepatic clearance occurs when liver blood flow is reduced receptors bound, with
o EXAMPLES: heart failure, severe cirrhosis, other forms of liver failure increasing concentration of
a drug
ADJUSTMENT OF DOSAGE IN RENAL IMPAIRMENT § Kd = Concentration of the
!%#$.1&1&# !"#$%$&'# drug, wherein 50% of
!/%%#'.#6 8/4# = ?@ABCDA EFGA × receptors is occupied
HII 2*/21&
§ The smaller the Kd, the
• if a drug is cleared partly by the kidney and partly by other greater the affinity of a
routes, apply the equation only to the part of the dose that is drug for its receptor
eliminated by the kidney
• Spare receptors: receptors that do not bind drug, when the
drug concentration is sufficient to produce maximal effect
o they are present when Kd > EC50
o increase sensitivity to the agonist because the likelihood of
Drug-Receptor interaction increases directly proportional to
the number of receptors available
EFFICACY AND POTENCY
https://qrs.ly/u5ckdcy
GRADED DOSE-RESPONSE CURVES
https://qrs.ly/a6ckdcb
FACTORS AFFECTING DOSE RESPONSE CURVES
QUANTAL DOSE-RESPONSE RELATIONSHIP

• minimum dose required to
produce a specified response
is determined in each
member of a population
• Quantal dose-response
curve: graph of dose (drug
concentration) versus
fraction of the population
that responds at each dose
against the log of the dose Adapted from Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
administered AGONISTS
o median effective (ED50): • Constitutive activity: receptor activity in the absence of a ligand
dose at which 50% of the • Full Agonist: drug capable of fully activating the effector system
population responds when it binds to the receptor
• can be used to graph toxic/ lethal effect of the drug • Partial Agonist: drug produces less than the full effect, even
o median toxic (TD50) and median lethal (LD50) doses are derived when it has saturated the receptors
• IN THE PRESENCE OF AN AGONIST, A PARTIAL AGONIST ACTS AS AN
INHIBITOR / ANTAGONIST.
QUANTAL DOSE-RESPONSE CURVES
https://qrs.ly/brckdck
FULL vs PARTIAL
AGONISTS
https://qrs.ly/lfckdd6
ANTAGONISTS
• do not provoke a biological response upon binding to a receptor
• blocks or dampens drug response in the presence of an agonist
• classification
o pharmacologic
§ competitive (reversible)
§ non-competitive (irreversible)
o physiologic
o chemical
THERAPEUTIC INDEX
ZE)*
WO#%$5#S.1' X&6#Y =
[E)*
• A measure which relates the
dose of a drug required to
produce a desired effect to
that which produces an
undesired effect
Adapted from First Aid for the USMLE Step 1 2020. p 234
THERAPEUTIC INDEX
https://qrs.ly/fsckdcr
ANTAGONIST PART 1 ANTAGONIST PART 2

EFFICACY
https://qrs.ly/wackdde https://qrs.ly/3nckddn
• Maximal efficacy or Emax : maximal effect an agonist can
produce if the dose is taken to very high levels Pharmacologic Antagonists
o determined mainly by the nature of the receptor and its • Competitive or Reversible Antagonists: bind to receptor very
associated effector system close to the agonist receptor site, without activating the effector
o partial agonists have lower maximal efficacy than full agonists system
§ Dose-response curve: shift to the right (increased ED50)
POTENCY § effects overcome by adding more agonist
§ Examples: β-blockers (Propranolol) and β-agonists
• Potency: denotes the amount of drug needed to produce a given effect
(Isoproterenol)
o determined mainly by the affinity of the receptor for the drug
o measurement • Non-competitive or Irreversible Antagonists: acts at an
§ in graded dose-response curves, it is the EC50 or ED50 allosteric site of the receptor
(concentration/dose required to produced 50% of the § Dose-response curve: downward shift of the Emax
maximal effect) (decreased Emax)
§ in quantal dose-response curves, three potency variables are § NOT overcome by adding more agonist
measurable (ED50, TD50, LD50) § example: Norepinephrine and Phenoxybenzamine
Physiologic Antagonists TERATOGENESIS
• binds to a different receptor, producing an effect opposite to that • induction of developmental defects in the somatic tissues of the
produced by the drug it is antagonizing fetus
• Examples: Histamine and Epinephrine, Propranolol and thyroid • studied by treating pregnant female animals of at least 2 species
hormone at selected times during early pregnancy when organogenesis is
Chemical Antagonists known to take place
• interact directly with the drug being antagonized to remove it o EXAMPLES: thalidomide, isotretinoin, valproic acid, ethanol,
or to prevent it from reaching its target glucocorticoids, warfarin, lithium, and androgens
• does NOT depend on interaction with receptors
• examples: Dimercaprol for lead poisoning, Pralidoxime for COMMON TERATOGENS
organophosphate poisoning TERATOGEN EFFECT
ACE inhibitors Fetal renal damage
VARIATIONS IN DRUG RESPONSE Antiepileptic Drugs Neural tube defects
TACHYPHYLAXIS Phenytoin Fetal hydantoin syndrome
Oral hypoglycemic agents Neonatal hypoglycemia
• frequent or continuous exposure to agonists often results in
Barbiturates Neonatal dependence
short-term diminution of the receptor response.
Diethylstilbestrol (DES) Vaginal clear cell adenocarcinoma
• Many mechanisms may be responsible:
Ethanol Fetal alcohol syndrome
o Blocking access of G protein to activated receptor (ß-arrestin)
Lithium Ebstein anomaly
o Receptor molecules may be internalized by endocytosis (to Isotretinoin Craniofacial malformations
prevent exposure to extracellular molecules) lodide Congenital hypothyroidism
o Tolerance: Depletion of substrates required for downstream Misoprostol Mobius sequence
effects (EXAMPLE: depletion of thiol cofactors in nitroglycerin Penicillamine Cutis laxa
tolerance, reversible with administration of glutathione) Thalidomide Phocomelia
• e.g. Theophylline, Salbutamol. Nitrates, Dobutamine Smoking IUGR
MNEMONIC: Tachyphylaxis Tetracycline Tooth discoloration
What drugs display tachyphylaxis? Streptomycin Ototoxicity
MEDical students Love to watch CNN in HD! Methimazole Aplasia cutis congenita
Metoclopramide Nitroglycerin Sulfonamides Kernicterus
Ephedrine Nicotine Fluoroquinolones Cartilage damage
Dobutamine Hydralazine
Warfarin 1st trimester Chondrodysplasia
LSD Desmopressin
Calcitonin 2nd trimester CNS malformations
3rd trimester Bleeding diatheses
• Downregulation: Long term reduction in receptor number
due to continuous exposure to agonist
• Upregulation: Increase in receptor number, which occurs when MUTAGENESIS
receptor activation is blocked for prolonged periods • induction of changes in the genetic material of animals of any
age and therefore induction of heritable abnormalities
IDIOSYNCRATIC DRUG RESPONSE o EXAMPLES: aflatoxin, cancer chemotherapeutic drugs, and
• one that is infrequently observed in most patients other agents that bind to DNA
• EXAMPLES: Ames Test
o aplastic anemia with chloramphenicol • in vitro test for mutagenicity (using special strain of Salmonella
o cataracts with allopurinol that naturally depends on specific nutrients)
• loss of this dependence signals a mutation
Dominant Lethal Test
DRUG EVALUATION AND REGULATION • in vivo test for mutagenicity (carried out in mice)
ACUTE TOXICITY STUDIES • male animals are exposed to the test substance before mating
• required for all new drugs • abnormalities in the results of subsequent mating signal a
• involve administration of single doses of the agent up to the mutation in the male's germ cells
lethal level in at least 2 species (e.g., 1 rodent and 1 non-rodent).
CARCINOGENESIS
SUBACUTE AND CHRONIC TOXICITY STUDIES • induction of malignant characteristics in cells
• required for most agents, especially those intended for chronic • difficult and expensive to study
use • high degree of correlation between mutagenicity in the Ames
• duration: 2–4 weeks (subacute) or 6–24 months (chronic), in test and carcinogenicity in some animal tests
at least 2 species o EXAMPLES: coal tar, aflatoxin, nitrosamines, urethane, vinyl
chloride, polycyclic aromatic hydrocarbons in tobacco smoke
REPRODUCTIVE TOXICITY STUDIES
(benzo-α-pyrene)
• involves the study of the fertility effects of the candidate drug
and its teratogenic and mutagenic toxicity
• FDA uses a 5-level descriptive scale to summarize information
CLINICAL TRIAL
regarding the safety of drugs in pregnancy • requires approval by institutional committees that monitor the
ethical (informed consent, patient safety) and scientific aspects
FDA Drug Categories: and Pregnancy (study design, statistical power) of the proposed tests
PREGNANT PREGNANT
CLASS HUMAN ANIMAL EXAMPLES INVESTIGATIONAL NEW DRUG (IND)
STUDIES STUDIES • includes all the preclinical data collected up to the time of
Folic acid, Thyroid submission and the detailed proposal for clinical trials
A Safe Safe
hormones
No studies Safe Zidovudine NEW DRUG APPLICATION (NDA)
B
Safe Unsafe • constitutes the request for approval of general marketing of the
No studies Unsafe Aspirin new agent for prescription use and includes all the results of
C
No studies No studies preclinical and clinical testing
ACE inhibitors,
D Unsafe Unsafe
Anticonvulsants
Statins, OCPs, Clomiphene,
X Unsafe Unsafe Misoprostol,
High-dose Vitamin A
AUTONOMIC PHARMACOLOGY
Autonomic Nervous System
• major involuntary, unconscious,
automatic portion of the
nervous system
• concerned primarily with
visceral functions (i.e. cardiac
output, blood flow distribution,
digestion) OVERVIEW OF ANS
• major divisions: https://qrs.ly/48ckde8
o Parasympathetic ANS (PANS)
o Sympathetic ANS (SANS)
Adapted from Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
PHASE 1 TRIAL
• careful evaluation of the dose-response relationship and
pharmacokinetics among normal human volunteers (25–100
usually, only 20-50 for chemotherapeutic and other toxic drugs)
o EXCEPT in cancer and highly toxic agents (volunteer patients
with target disease)
• acute effects of the agent are studied over a broad range of
dosages
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
Figure 6-1. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
that are tolerated by sick patients Enteric nervous system (ENS)
• Primarily controlled by the ANS
PHASE 3 TRIAL
• consists of myenteric plexus (plexus of Auerbach) and
• large design involving many patients, including those submucous plexus (plexus of Meissner)
considered as “special population” (1000–5000)
• would be done by many clinicians in different SYMPATHETIC PARASYMPATHETIC
centers/hospitals/countries Thoracic
• include placebo and positive controls in a double-blind (T1-T12) and CN III, VII, IX and X
Spinal Roots
crossover design Lumbar Sacral segments of
of Origin
• explore further the spectrum of beneficial actions of the new (L1-L5) segments the spinal cord
drug, to compare it with older therapies, and to discover of the spinal cord
infrequent toxicities not seen in Phase 2 Paravertebral
chains that lie Most are located in
PHASE 4 TRIAL along the spinal the organs
Location of
column, some innervates, more
• post-marketing surveillance phase Ganglia
along the anterior distant from the
• detects toxicities that occur very infrequently aspect of the spinal cord
abdominal aorta
Preganglionic
DRUG DEVELOPMENT Short Long
fibers
https://qrs.ly/4ockdds Postganglionic
Long Short
fibers
PLASMA
BIOEQUIVALENCE MNEMONIC
(for parasympathetic nervous system)
• two related drugs are bioequivalent if they show comparable Parasympathetic NS
bioavailability and similar times to achieve peak blood Long preganglionic fibers
concentrations Acetylcholine
• used in determining safety and efficacy of generic drugs Short postganglionic fibers
Muscarinic
Acetylcholine
ORGAN SYMPATHETIC PARASYMPATHETIC
Iris radial muscle Mydriasis (ɑ1) No effect
Iris circular muscle No effect Miosis (M3)
Eye
Contraction (M3) for near vision or
Ciliary muscle Relaxes (β)
accommodation
SA node Tachycardia (β1> β2) Bradycardia (M2)
Heart
Contractility Increased (β1> β2) Decreased (atria) (M2)
Skin, splanchnic vessels Vasoconstriction (ɑ1> ɑ2) No effect
Vasodilation (β2 and less
Skeletal muscle vessels No effect
Blood importantly, M3**
vessels Endothelium of vessels in heart,
Synthetizes and releases EDRF (M3,M5)
brain and viscera
Bronchiolar smooth muscle Bronchodilation (β2) Bronchoconstriction (M3)
Smooth muscle walls Relaxation (ɑ2, β2) Contraction (M3)
Digestion
GIT Smooth muscle sphincters Contraction (ɑ1) Relaxation (M3)
Secretion Increased (M3)
ORGAN SYMPATHETIC PARASYMPATHETIC
Bladder wall (detrusor) Relaxation (β2) Contraction (M3)
Urination
Trigone and bladder sphincter Contraction (ɑ1) Relaxation (M3)
GUT Uterus, pregnant Relaxation (β2) Contraction (M3) - not sensitive
Ejaculation (ɑ) Erection (M)
Penis, Seminal vesicles
Shoot for Sympathetic Point for Parasympathetic
sweat, salivary, lacrimal,
Glands No effect Increased secretion (M)
nasopharyngeal glands
Pilomotor smooth muscle Contracts (ɑ) No effect
Increases (M)
Skin Eccrine sweat glands No effect
Sympathetic, mediated by Ach
Apocrine (stress) sweat glands Increases (ɑ) No effect
Gluconeogenesis (β2, ɑ) No effect
Liver
Glycogenolysis (β2, ɑ) No effect
Others
Fat cells Lipolysis (β3) No effect
Kidney Renin release (β1) No effect
CHOLINERGIC PHARMACOLOGY
Figure 6-2a. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
ACETYLCHOLINE CHOLINERGIC
• primary transmitter in all autonomic ganglia and at the PHARMACOLOGY
synapses between parasympathetic postganglionic neurons AND QUIZ
and their effector cells https://qrs.ly/tnckdiz
• primary transmitter at the somatic (voluntary) skeletal muscle
neuromuscular junction SUPPLEMENT:
• Butyrylcholinesterase (found in the liver) and
pseudocholinesterase (found in the plasma) are also
CHOLINERGIC cholinesterases with lower specificity for ACh
SYNAPSES This metabolizes the following drugs: Succinylcholine (the only
https://qrs.ly/3ockdew DEPOLARIZING neuromuscular blocker), Mivacurium (short acting
NON-depolarizing neuromuscular blocker)
STEP 1 – TRANSPORT AND SYNTHESIS CHOLINORECEPTORS

• Choline transferase (CHT): Na+/Choline symporter that TYPICAL RESULT OF
transports choline inside RECEPTOR NAME
LOCATION LIGAND BINDING
o Rate-limiting step Opening of Na+
o choline transport inhibited by Hemicholinium Neuronal type,
Nn and K+ channels,
• Choline acetyltransferase (ChAT): enzyme uses free acetyl CoA ganglion
depolarization
and choline to synthesize Acetylcholine Skeletal
Opening of Na+
STEP 2 – STORAGE muscle
Nm and K+ channels,
neuromuscular
• ACh is actively transported into vesicles for storage by vesicle- depolarization
junction
associated transporter (VAT) ↑ IP3 and DAG,
o inhibited by Vesamicol M1 Nerves
↑ intracellular Ca2+
STEP 3 – RELEASE Opening of K+
Myocardium,
• entry of calcium -> Calcium interaction with SNARE proteins channels,
M2 nerves, smooth
(VAMPs and SNAPs) -> triggers fusion of vesicle membrane with inhibition of cAMP
muscles
terminal membrane production
o Botulinum toxin alter synaptobrevins to prevent release of Exocrine
ACh through the enzymatic removal of 2 amino acids from one glands, vessels ↑ IP3 and DAG,
M3
or more of the fusion proteins (Smooth muscle, ↑ intracellular Ca2+
endothelium)
STEP 4 – TERMINATION inhibition of cAMP
M4 CNS
• degradation of ACh into choline and acetate by production
acetylcholinesterase (AChE) ↑ IP3 and DAG,
M5 CNS
o inhibited by INDIRECT-ACTING CHOLINOMIMETICS ↑ intracellular Ca2+
(Carbamates & Organophosphates)
MUSCARINIC TOXICITY
MEMORY AIDS • This is seen in overdosage of muscarinic agonists and certain
FOR CHOLINORECEPTORS types of mushrooms (genus: Inocybe)
https://qrs.ly/lpckdjf o CNS stimulation
o EYE: miosis, spasm of accommodation
o LUNGS: bronchoconstriction
NON-SELECTIVE CHOLINERGIC AGONIST o GIT/GUT: excessive gastrointestinal and genitourinary smooth
Drug ACETYLCHOLINE [C] muscle activity
MOA activates both nicotinic and muscarinic receptors o Increased secretory activity (sweat glands, airway,
Miotic eyedrops (constricts iris) gastrointestinal tract, lacrimal glands)
Uses o Vasodilation
during ocular surgery
PK short lived (5-30 sec) (quickly hydrolyzed by AchE) • Treatment: Atropine (Cholinergic antagonist)
DUMB BELLS * Note that the symptoms of muscarinic poisoning are essentially the same
Diarrhea (and diaphoresis) and abdominal cramps with organophosphate poisoning minus symptoms of nicotinic excess.
Urination
Miosis DIRECT ACTING CHOLINOMIMETIC (NICOTINIC)
SE Bradycardia (muscarinic) or tachycardia (nicotinic)
Emesis Nn & Nm AGONIST Nm AGONIST
Lacrimation Drugs NICOTINE [C]
SUCCINYLCHOLINE
Lethargy Varenicline [C], Lobeline
Salivation activates nicotinic
activates nicotinic
receptors (Nn and Nm)
MOA receptors (more
DIRECT ACTING CHOLINOMIMETIC (MUSCARINIC) • Nicotine: full agonist
selective for Nm)
NON-SELECTIVE M3 SELECTIVE • Varenicline: partial agonist
Drugs BETHANECHOL [C], PILOCARPINE [C], Depolarizing NMJ
CARBACHOL Cevimeline [C] Uses Smoking cessation blocker, Muscle
activates M3 receptors relaxation
• Contraction of ciliary muscle: initial muscle spasms
Activates muscarinic Generalized ganglionic
MOA helps aqueous humor and postoperative pain,
receptors (M1-M3) stimulation (hypertension,
outflow, less secretion SE prolonged action in
• Salivary glands: ↑ salivation tachycardia, nausea,
persons with abnormal
Bowel and Bladder vomiting, diarrhea)
Acute angle closure butylcholinesterase
atony (post-surgery
glaucoma, Sjögren syndrome, NICOTINIC TOXICITY
or spinal cord injury),
Sicca syndrome
congenital megacolon • largely due to the nonspecific ganglionic stimulation (affecting
Uses Sjögren Syndrome:
BBB = sympathetic, parasympathetic and neuromuscular junctions)
Xerostomia (Dry Mouth),
Bethanechol, • blockade of neuromuscular end plate depolarization
Xerophthalmia (Dry Eyes),
Bowel,
Rheumatoid Arthritis o leading to fasciculations and paralysis
Bladder Atony o CNS toxicity: stimulation (convulsions) followed by CNS
Miosis, Blurring of vision (due to depression
cyclospasm), Increased salivation, • Treatment: symptom directed (atropine for muscarinic excess,
Hypertension for Pilocarpine, diazepam & anticonvulsants for CNS stimulation, mechanical
Parasympathetic
(cyclospasm, Hypertension is an interesting ventilation if with neuromuscular blockade)
diarrhea, urination, exception to the rule for
SE promuscarinics; it may be seen INDIRECT-ACTING CHOLINOMIMETICS
vasodilation, reflex
after a brief period of
tachycardia, • bind to acetylcholinesterase (AChE) and undergo prompt
sweating) hypotension due to the
activation of sympathetic
hydrolysis
postganglionic M1 receptors in o prevents the binding and hydrolysis of endogenous
pilocarpine acetylcholine → amplify acetylcholine effects
Acetylcholinesterase inhibitors: indirect acting cholinomimetics act by
raising Ach concentrations in the synaptic cleft by inhibiting the action of
the enzyme that metabolizes Ach
INDIRECT ACTING CHOLINOMIMETICS
DRUGS FOR
ALCOHOL CARBAMATES ORGANOPHOSPHATES
ALZHEIMER’S
NEOSTIGMINE [C],
Drug RIVASTIGMINE [B],
PYRIDOSTIGMINE [C]
PHYSOSTIGMINE PARATHION, SARIN, DONEPEZIL [C]
EDROPHONIUM [C] Ambenonium,
[C] MALATHION TABUN Galantamine [B]
Demecarium,
Tacrine [C]
Echothiophate
Inhibits
Inhibits acetylcholinesterase. Amplifies
acetylcholinesterase. Inhibits acetylcholinesterase. Amplifies endogenously
MOA endogenously released ACh.
Amplifies endogenously released ACh.
Plus small direct nicotinic agonist action.
released ACh.
• Myasthenia gravis • Myasthenia gravis • Alzheimer’s disease
Reversal of
(diagnosis – Tensilon (treatment) • Rivastigmine is
Atropine
test) • Reversal of available as
poisoning Insecticide
• Differentiation of nondepolarizing Nerve transdermal patch
Uses Acute glaucoma Scabicide
cholinergic crisis and neuromuscular gases • Donepezil is combined
(physostigmine, (Malathion)
myasthenic crisis blockade with Memantine
echothiophate,
• Reversal of neuro- • Bladder and Bowel (NMDA antagonist) for
demecarium)
muscular blockade atony(Neostigmine) Alzheimer’s dementia
Dangerous
Miosis, Salivation, Nausea, Same
(Parasympathetic Rapidly
SE Vomiting, Diarrhea, Same (+) CNS effects Nausea, vomiting
effects, muscle lethal
Bradycardia (seizures)
paralysis, coma)
MYASTHENIA GRAVIS ORGANOPHOSPHATE POISONING
• An autoimmune destruction of nicotinic ACh receptors, • Accidental exposure to toxic amounts of pesticides
characterized by: • Clinical manifestation: DUMBBELLS
o fluctuating muscle
o weakness Treatment of Organophosphate Poisoning
o ocular symptoms • Atropine: addresses only MUSCARINIC symptoms
o bulbar symptoms o Notorious for causing hyperthermia in susceptible patients
o proximal muscle weakness (because Atropine suppresses thermoregulatory sweating)
• May be worsened by the ff drugs: • Pralidoxime: addresses BOTH Nicotinic and Muscarinic
o Nondepolarizing neuromuscular blockers (because the symptoms
mechanism of the disease and its MOA are similar) o Must be administered before 6-8 hours of organophosphate
o Aminoglycoside antibiotics (because these drugs interfere with bond with cholinesterase occurs (before the bond has AGED or
neuromuscular transmission) turned covalent, which is a stronger bond)
Differentiating MYASTHENIC CRISIS VS CHOLINERGIC CRISIS o has oxime group which has high affinity for phosphorus
• Myasthenic Crisis: acute worsening of symptoms due to
infection, stress or UNDERmedication SUPPLEMENT: Other Drugs for Alzheimer’s Dementia
o Edrophonium IMPROVES muscle strength NMDA receptor blocker; used for moderate
MEMANTINE [B]
to severe Dementia
• Cholinergic Crisis: excessive activation of cholinoceptors
(skeletal muscle weakness and parasympathetic signs) due to
OVERmedication
o Edrophonium WEAKENS muscle strength
ANTIDOTE TO ORGANOPHOSPHATE POISONING

Drugs ATROPINE [C] PRALIDOXIME [C]
Binds phosphorus of organophosphate. Breaks organophosphate
MOA Competitively blocks ALL muscarinic receptors bond with cholinesterase. (Regenerates active
acetylcholinesterase)
• Mydriatic, cycloplegic • Antidote for early stage cholinesterase inhibitor poisoning
• Antidote for organophosphate poisoning (1st choice) (organophosphate poisoning and nerve gas poisoning)
• Bradycardia, Hypersalivation, Decrease airway secretion during • Can relieve skeletal muscle and endplate block
Uses
general anesthesia
Co-administered with nondepolarizing NMJ blockers, to counteract the
bradycardia associated with giving an indirect acting cholinomimetic
Parasympathetic effects plus hyperthermia, flushing, delirium,
SE Muscle weakness
sedation
CHOLINERGIC ANTAGONISTS AT MUSCARINIC SITES (PARASYMPATHOLYTICS)

NON- M2 RECEPTOR M3 RECEPTOR
NON-SELECTIVE
SELECTIVE BLOCKER BLOCKERS
DICYCLOMINE OXYBUTYNIN [B]
ATROPINE [C],
[B] DARIFENACIN [C],
Drug Homatropine [C], IPRATROPIUM [B],
BENZTROPINE [C], (Dicycloverine), Solifenacin [C]
Cyclopentolate Tiotropium [B], SCOPOLAMINE [C] PIRENZEPINE
Biperiden [C], Hyoscyamine Fesoterodine [C],
[C], UMECLIDINIUM [C], (Hyoscine) Telenzepine
Trihexyphenidyl [C] [B], Tolterodine [C],
Tropicamide GLYCOPYRRONIUM [B]
Glycopyrrolate Trospium [C],
[C]
[B] Imidafenacin [C]
Competitively
Competitively Blocks
blocks all Blocks muscarinic Blocks
blocks ALL muscarinic
Competitively muscarinic receptors in muscarinic
muscarinic Competitively receptors
blocks ALL receptors. bronchial smooth receptors
MOA receptors. blocks M3 Modest M3
muscarinic Restores muscle. Prevents Significant
Antagonizes receptors selectivity,
receptors neurotransmitter vagal-stimulated M1
histamine and Reduces detrusor
balance in the bronchoconstriction selectivity
serotonin. muscle tone
basal ganglia.
OXYBUTYNIN
ATROPINE BENZTROPINE IPATROPIUM DICYCLOMINE PIRENZEPINE
Drugs SCOPOLAMINE [B]
etc. etc. etc. etc. Telenzepine
etc.
• Mydriatic,
cycloplegic
C = Cycloplegia = Parkinson’s disease
Ciliary muscle The tremors
paralysis = loss of associated with
accommodation Parkinson disease is Motion
Peptic
a result of sickness, IBS, minor
• Antidote for Urinary disease
RELATIVE EXCESS Acute Asthma, decrease acid diarrhea,
Uses organophosphate urgency (not
of cholinergic COPD secretion in GIT, decrease acid
poisoning (first incontinence available in
activity versus Nausea and secretion in GIT
choice) USA)
dopaminergic Vomiting
• Bradycardia activity in the basal-
• Hypersalivation, ganglia striatum
Decrease airway system.
secretion during
general anesthesia
Parasympathetic effects
Drowsiness,
plus hyperthermia, Blurring of vision, Dry mouth, Tachycardia,
Amnesia, Sedation,
flushing, delirium, Dry eyes, blurred vision confusion,
Blurred vision, Dry Excessive parasympatholytic
SE sedation, “Sandy eyes” Constipation, Dry etc. (Anti- urinary
eyes, Constipation, effects
(Dry eyes due to mouth, Urinary cholinergic retention,
Dry mouth,
reduced lacrimal retention effects) increased IOP
Urinary retention
secretion)
ATROPINE TOXICITY CHOLINERGIC ANTAGONISTS AT NICOTINIC SITES
• Atropine: prototype nonselective muscarinic blocker, found in (GANGLION BLOCKERS)
Atropa belladonna plant
• competitive pharmacologic antagonists at nicotinic
• Features of Atropine Toxicity:
acetylcholine receptors (NN) of both sympathetic and
o Atropine fever (hyperthermia) - due to inhibition of sweating
parasympathetic autonomic ganglia
o Atropine flush (cutaneous vasodilation)
• first successful agents for the treatment of hypertension but
o Decreased secretions
were abandoned due to severe adverse effects
o Tachycardia
o Arrhythmias (intraventricular conduction block) HEXAMETHONIUM [D],
Drug
o Constipation Trimethaphan [D], Mecamylamine [C]
o Blurred vision MOA Competitively blocks NN receptors
o CNS toxicity Uses Hypertension (obsolete), Hypertensive emergencies
• Atropine Toxicity Mnemonic: Hexamethonium: oral, IV
o HOT as a hare (hyperthermia) PK Trimethaphan: IV only, short acting
o DRY as a bone (decreased secretion) Mecamylamine: oral, enters CNS
o RED as a beet (cutaneous vasodilation) Postural Hypotension, Dry mouth, Blurred vision,
SE
o BLIND as a bat (cycloplegia) Constipation, Sexual dysfunction, Tachycardia
o MAD as a hatter (CNS toxicity)
• Treatment: Symptomatic CHOLINERGIC ANTAGONISTS AT NICOTINIC SITES
o Temperature control: use of cooling blankets
o Seizure control: Diazepam (NEUROMUSCULAR BLOCKERS)
o To reverse antimuscarinic effect: Physostigmine • used for complete skeletal muscle relaxation in surgery
• classification
o DEPOLARIZING (Succinylcholine)
MUSCARINIC ANTAGONISTS
o NONDEPOLARIZING (Tubocurarine, Pancuronium,
FOR PARKINSON DISEASE
Atracurium, Vecuronium)
https://qrs.ly/edckdk4
ADRENERGIC PHARMACOLOGY
CONTRAINDICATIONS TO MUSCARINIC BLOCKERS NOREPINEPHRINE
• cautious use in infants (since they are sensitive to the • primary transmitter at the sympathetic postganglionic
hyperthermic effects of atropine) neuron-effector cell synapses in most tissues
• acute angle-closure glaucoma (since mydriasis can block the o EXCEPTIONS:
normal drainage of aqueous humor) § eccrine sweat glands (uses ACh)
• benign prostatic hyperplasia (can precipitate further urinary § vasodilator sympathetic fibers in skeletal muscle
retention already present in this subgroup because muscarinic • it is the immediate precursor of epinephrine
antagonists will relax smooth muscle of the ureters and bladder wall)
Figure 6-2b. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
STEP 1 – SYNTHESIS STEP 4 – TERMINATION

• tyrosine is hydroxylated by tyrosine hydroxylase to DOPA • diffusion and reuptake via NET and DAT in synaptic cleft
o rate-limiting step o inhibited by Cocaine and TCAs
o inhibited by Metyrosine • metabolized by MAO and COMT into metanephrines and VMA
• DOPA is decarboxylated to dopamine o inhibited by MAOi and COMTi
• Dopamine is hydroxylated to norepinephrine
STEP 2 – STORAGE ADRENERGIC SYNAPSES
• norepinephrine and dopamine are transported into vesicles https://qrs.ly/efckdl6
o inactivated by monoamine oxidase in the cytoplasm
o Monoamine oxidase inhibitors (MAOi) increase stores of NE
and dopamine
SITES OF AUTONOMIC DRUG ACTION
• The transfer of DOPA into vesicles is BLOCKED by the drug
INHIBITORS
Reserpine STEPS
CHOLINERGIC ADRENERGIC
STEP 3 – RELEASE Synthesis Hemicholinium Metyrosine
• entry of calcium -> calcium interacts with SNARE proteins Storage Vesamicol Reserpine
(VAMPs and SNAPs) -> vesicle fuses with membrane Release Botulinum Guanethidine
o inhibited by Guanethidine Termination
Metabolism Neostigmine MAOis, COMTis
o promoted by Amphetamines and Tyramine
Reuptake None Cocaine, TCAs
* Release of NE via these agents is calcium INDEPENDENT.
ADRENOCEPTORS
• receptors that respond to catecholamines (NE, EPI and DOPA)
RECEPTOR LOCATION G 2ND MSGR MAJOR FUNCTIONS
Alpha 1 (ɑ1) Effector tissues Smooth muscle, Glands Gq ↑IP3, DAG ↑Ca2+, causes contraction, secretion
Alpha 2 (ɑ2) Nerve endings Smooth muscle Gi ¯cAMP ¯transmitter release, causes contraction
Beta 1 (β1) Cardiac muscle JG apparatus Gs ↑cAMP ↑heart rate, force ↑renin release
Relax smooth muscle ↑glycogenolysis ↑heart
Beta 2 (β2) Smooth muscle Liver, Heart Gs ↑cAMP
rate, force
Beta 3 (β3) Adipose cells Gs ↑cAMP ↑lipolysis
Dopamine 1 (D1) Smooth muscle Gs ↑cAMP Relax renal vascular smooth muscle
ADRENERGIC AGONISTS (SYMPATHOMIMETICS)

NONSELECTIVE NONSELECTIVE NONSELECTIVE: BETA NONSELECTIVE:
Drug
EPINEPHRINE [C] (Adrenaline) NOREPINEPHRINE [C] DOPAMINE [C] ISOPROTERENOL [C]
⍺1, ⍺2, β1, β3 agonist D1, ⍺1, ⍺2, β1, β3 agonist
(a > b1 >> b2 almost negligible) Dose-dependent actions:
⍺1, ⍺2, β1, β2, β3 agonist
MOA Low dose: D1 β1, β2, β3 agonist
(Β1 = β2 > Alpha) Dopamine vasoDILATES renal blood vessels Mod dose: β1
while Norepinephrine vasCONSTRICTS them Higher dose: ⍺1
• Anaphylaxis, cardiac arrest Shock esp if with renal Asthma (adjunct to your
Shock
• Severe asthma/COPD shutdown, Cardiogenic Beta 2 agonist), Drug for
First line Tx for Septic shock, Cardiogenic
• Hemostasis, Added to local Shock, Acute Heart sustained increases in HR
Uses shock
anesthetics to decrease failure (especially if (during pacemaker
Unlike epinephrine, NE has negligible beta 2
systemic absorption accompanied with insertion for
effects, so NE is not used in bronchospasm!
(increases duration of action) severe hypotension) bradydysrhythmia)
• Extreme vasospasm, tissue necrosis,
• Hypertension, arrhythmia,
excessive increase in BP, arrhythmia, MI,
stroke, MI, pulmonary
SE ischemia → decreased organ perfusion, • Cardiovascular disturbance, arrhythmia
edema, Hyperglycemia,
reflex bradycardia, metabolic acidosis
Tachycardia, Mydriasis
(due to decreased tissue blood flow)
MOA OF SYMPATHOMIMETICS • HIGH DOSE (>10 mcg/kg/min)
• direct activation of adrenoceptors o Stimulates α1 receptors
o a1: vasoconstriction, increases BP, increase pulmonary o Leads to arterial and venous vasoconstriction, increased
vascular resistance systemic vascular resistance, increased blood pressure
o b1: increased HR, conduction and contractility of heart o Reflex bradycardia may be seen at this point
o b2: bronchodilation in lungs CLINICAL APPLICATIONS OF SYMPATHOMIMETICS
o D1: vasodilation in splanchnic and renal blood vessels CLINICAL DESIRED SYMPATHOMIMETIC
• INDIRECT activation by increasing concentration of available CONDITION PARAMETER OF CHOICE
catecholamines in the synapse Acute heart
Increased cardiac
o release of stored catecholamines (amphetamine) failure b1 & D1 agonists
output
o inhibition of reuptake (cocaine) Septic chock
Hemostasis Vasoconstriction
DOPAMINE: DOSE DEPENDENT ACTIONS
Decongestion Temporary a1 agonist
• LOW DOSE (0.5 to 3 mcg/kg/min) Spinal shock maintenance of BP
o Stimulates D1 and D2 receptors Bronchospasm Bronchodilation
o Leading to vasodilation, decreased arterial blood pressure and Premature Uterine smooth b2 agonist
increased renal and splanchnic blood flow (natriuresis and labor muscle relaxation
diuresis will occur) Hypertension
Decrease BP a2 agonist
• MEDIUM DOSE (3-10 mcg/kg/min) Glaucoma
o Stimulates β1 receptors (high chronotropy and contractility)
o Results in increased cardiac output
ALPHA RECEPTOR AGONISTS
ALPHA-1 AGONISTS: ALPHA-2 AGONIST: ALPHA-2 AGONIST: ALPHA-2 AGONIST:
PHENYLEPHRINE [C], Pseudoephedrine [B],
Drug METHYLDOPA [B]
OXYMETAZOLINE [C], APRACLONIDINE [C],
CLONIDINE [C] Guanfacine [B], Guanabenz [C],
Tetrahydrozoline [C], Naphazoline[C], Brimonidine [B]
Dexmedetomidine [C], Tizanidine [C]
Xylometazoline [C], Midodrine [C]
⍺2 agonist ⍺2 agonist
⍺1 agonist
MOA ⍺2: decreases central sympathetic outflow → INHIBITION of sympathetic ⍺2: ↓ secretion of
β1: vasoconstriction, increases BP
tone and reduced blood pressure aqueous humor
Decongestant, Mydriatic, Neurogenic Hypertension, Pre-eclampsia, Gestational hypertension,
Uses hypotension, Drug-induced Cancer pain, Opioid “Conscious sedation”(Dexmedetomidine), Glaucoma
hypotension, Orthostatic hypotension, withdrawal muscle relaxant (Tizanidine)
Drug interaction with
TCA: TCAs can reduce
Oral, topical, IV the antihypertensive
PK -- --
15-60 mins effect of clonidine (due
to alpha blocking
effects of TCAs)
Sedation, Dry mouth Sedation (most common undesirable SE), Blurring of vision,
Rebound nasal congestion (Rhinitis
(common), Rebound Hemolytic Anemia ([+] Coombs test), Dry mouth,
medicamentosa), Hypertension, stroke,
SE hypertension (due to Lactation (due to ↑ prolactin secretion), hyperemia and
MI, piloerection, urinary retention, Reflex
abrupt CNS effects (mental depression, vertigo, pruritus,
bradycardia
discontinuation) nightmares, impaired mental concentration) eye discomfort
Drug ALPHA-1 AGONISTS PHENYLEPHRINE [C], etc ALPHA-2 AGONIST: CLONIDINE [C], etc
• Ocular administration causes mydriasis WITHOUT
cycloplegia; also used intranasally to produce local • Taper use prior to discontinuation to avoid rebound hypertension. If rebound
vasoconstriction as a decongestant hypertension occurs, administer Phentolamine (reversible alpha
antagonist)
• Avoid Pseudoephedrine in the 1st trimester because it
• When taken PO, there is initial increase in BP then will go down once drug
Notes may be associated with possible risk of gastroschisis
enters the CNS
• Midodrine: used for the treatment of orthostatic
• If Clonidine is given to patients with pure autonomic failure, clonidine may
hypertension INCREASE BP because the central sympatholytic effect of clonidine becomes
• High doses may cause Alpha-1 agonist overdose irrelevant whereas peripheral vasoconstriction remains intact
o DOC: Phentolamine (adrenergic blocker)
BETA RECEPTOR AGONISTS

B1 AGONIST B2 AGONIST
Drug SALBUTAMOL [C] (Albuterol),
DOBUTAMINE [B]
Terbutaline [C], Ritodrine [B], Isoxsuprine [C], Metaproterenol
β1 agonist β2 agonist
MOA
β1: increases HR and contractility β2: bronchodilator
Acute heart failure, Cardiogenic shock, Cardiac stress testing • Acute asthma attacks (DOC)
Uses
(Pharmacologic agent to induce ischemia in the myocardium.) • Tocolysis for preterm labor (terbutaline, ritodrine, Isoxsuprine)
Hypertension, Tachycardia, Arrhythmias, Premature ventricular
Tachycardia, Tremors, Nervousness, Restlessness, Arrhythmias
SE beats, Angina, Dyspnea, Tachyphylaxis, Eosinophilic
when used excessively, Loss of responsiveness (tolerance)
myocarditis, Fever, Headache, Nausea
• May precipitate arrhythmias in patient with concurrent COPD
• Dobutamine effect on alpha receptors increases at higher dose, and heart disease (!)
Notes which explains why peripheral resistance doesn’t decrease • Rapid development of tolerance
significantly with dobutamine use • Isoxsuprine may also be used as a vasodilator in Raynaud’s
phenomenon; Isoxsuprine can cause maternal pulmonary edema
SUPPLEMENT: OTHER SYMPATHOMIMETICS SUPPLEMENT: OTHER SYMPATHOMIMETICS
PHENYLPROPANOLAMINE [C] ISOXUPRINE [C]
• Act mainly by causing release of NE, but also has direct agonist activity at B2-adrenoceptor agonist that causes direct relaxation of uterine and
some adrenergic receptors. It activates A and B adrenergic receptors in the vascular smooth muscle; used in the treatment of premature labor and
respiratory mucosa → vasoconstriction and reduction in nasal secretions, as vasodilator for cerebral vascular insufficiency and Raynaud’s
tissue hyperemia, edema and nasal congestion; most commonly used as a phenomenon; may increase the HR and cause changes in BP and
nasal vasoconstrictor and an appetite suppressant ; may indirectly irritate GIT; use with caution if combined with other drugs such as
stimulate B receptors producing tachycardia and positive inotropic effect; sedatives and anesthetics
Used with CAUTION because this may precipitate Hemorrhagic Stroke,
especially among women
SELECTIVE ALPHA BLOCKERS

• Pharmacologic advantage of a1 selectivity: Reflex Tachycardia is LESS common and less severe
ALPHA-1 BLOCKER ALPHA-2 BLOCKER
Drug PRAZOSIN [C],
Doxazosin [C], Terazosin [C], Tamsulosin [B], YOHIMBINE (OBSOLETE)
Silodosin [B], Alfuzosin [B]
Blocks a2 receptors
MOA Blocks a1 receptors Note that blocking alpha-2 stops the negative feedback, ultimately
increasing catecholamine release!
Uses Benign prostatic hyperplasia, Hypertension Orthostatic hypotension, Male erectile dysfunction (obsolete)
Orthostatic hypotension (especially the first dose), but
Increased skeletal muscle activity, tremors, tachycardia,
SE little reflex tachycardia (compared to non-selective a antagonists),
hypertension, rhinorrhea, paresthesia
Increased HDL (Prazosin), Dizziness, Drowsiness, Headache
• Tamsulosin: most selective for prostatic smooth muscle
Oral tamsulosin may precipitate Intraoperative Floppy Iris Syndrome
(IFIS) in patients undergoing cataract surgery. This is characterized
Yohimbine can greatly elevate BP if administered to patients
Notes by billowing of flaccid iris, propensity for iris prolapse and progressive
intraoperative pupillary constriction
receiving NE-transport blocking drugs
• Doxazosin, Tamsulosin, Silodosin and Alfuzosin: not indicated for
use in females or for the treatment of hypertension
NON-SELECTIVE ALPHA BLOCKERS

PHENTOLAMINE [C],
Drug PHENOXYBENZAMINE [C]
Tolazoline [C]
IRREVERSIBLY blocks a (a1>a2) receptors,
MOA REVERSIBLY blocks a (a1=a2) receptors
forms a covalent bond
Pheochromocytoma (pre-surgical), Antidote to a1 agonist
Uses Pheochromocytoma (pre-surgical) overdose, Rebound Hypertension, reversal of local anesthetics in
soft tissue sites
Orthostatic hypotension, Reflex tachycardia, Orthostatic hypotension, Reflex tachycardia,
SE
Gastrointestinal irritation, myocardial ischemia Gastrointestinal irritation
Phenoxybenzamine also blocks histamine (H1), Ach and Phentolamine has minor inhibitory effects at serotonin receptors
Notes
serotonin receptors. and agonist effects at muscarinic, H1 and H2 receptors.
BETA-ADRENORECEPTOR BLOCKERS
• All beta 1 blockers are with “-olol” • All beta. Blockers name that start in P are nonselective
NON-SELECTIVE SELECTIVE
Beta-Blockers Beta-1 Blocker / CARDIOSELECTIVE BBs
ATENOLOL [D],
PROPANOLOL [C],
Drug Acebutolol [B, D in 2nd /3rd trim],
Pindolol [B], Timolol C], Nadolol [C], Levobunolol [C],
Alprenolol, Betaxolol [C], Bisoprolol [C],
Metipranolol [C], Carteolol [C], Sotalol, Labetalol [C],
Esmolol [C, D in 2nd/3rd trim],
Carvedilol [C, D in 2nd & 3rd trim]
METOPROLOL [C], NEBIVOLOL [C], Celiprolol
Blocks b1 and b2 receptors. Selectively blocks b1 receptors.
MOA
Blocks sympathetic effects on heart and BP. Reduces renin release. Blocks sympathetic effects on heart and BP.
Angina prophylaxis, Hypertension, Arrhythmias, Migraine,
Angina, Hypertension, Heart failure,
Uses Performance anxiety, Hyperthyroidism and Thyroid storm
Supraventricular tachycardia (Esmolol only)
(Propranolol), Glaucoma, Esophageal varices (Propranolol)
Bronchospasm, AV block, Heart failure, CNS sedation, Erectile Bronchospasm (less chance), AV block, Heart failure, CNS
SE dysfunction, increased VLDL and decreased HDL, Bradycardia sedation, Erectile dysfunction, increased VLDL and decreased
(Most common cardiac SE), Increased plasma potassium HDL, Increased plasma potassium
• Masks symptoms of hypoglycemia in diabetics • Beta 1 selective agents are also termed as cardio-selective
(tachycardia, tremor, anxiety), may impair hepatic glucose drugs (because 75% of beta receptors in the myocardium are
mobilization beta 1)
• Beta blockers are used for the treatment for • Beta 1 selective agents are better suited for patients with
hyperthyroidism by blocking the sympathomimetic effects of asthma or restrictive airway disease (less chance of
thyroid hormones and inhibition of peripheral conversion of bronchospasm)
thyroxine to triiodothyronine (more active form) • Also, better suited for patients with essential
• Interaction with verapamil (calcium antagonist): severe hypertension as these drugs lack inhibition of peripheral beta
hypotension, bradycardia, heart failure and cardiac 2 receptors that produce vasodilation
Notes
conduction abnormalities. • Esmolol has shortest half-life
• Carvedilol and Labetalol has combined a and b blockade
(may be used in pheochromocytoma)
• Sotalol lacks local anesthetic action and has marked class III
antiarrhythmic effects
• Propranolol: High first pass effect, highly protein bound
• Principal Contraindication to BB use: preexisting
atrioventricular heart block or cardiac failure NOT caused by
tachycardia
EFFECTS NOT RELATED TO BETA BLOCKADE GLAUCOMA DRUGS
Intrinsic Sympathomimetic Activity
• Partial agonist activity
• Effective for hypertension and angina and ideal because they’re
less likely to cause bradycardia and abnormalities in plasma
lipids
• Advantage in treating patients with asthma because these drugs
are less likely to cause bronchospasm
• Acebutolol, Pindolol, Carteolol, Labetolol, Celiprolol,
Penbutolol, Bopindolol, Oxprenolol
Local Anesthetic Activity

• Also known as “membrane-stabilizing activity” (means inhibition
of action potential propagation across the cell membrane similar
to Na channel blockers that are class I anti-arrhythmic)
• disadvantage when beta-blockers are used topically in the eye
o decreases protective reflexes
o increases the risk of corneal ulceration
• absent in Timolol and Betaxolol making them useful in Figure 6-9. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
glaucoma DRAINAGE SYSTEM OF THE EYE: FLOW OF AQUEOUS HUMOR
Ciliary body ® posterior chamber ® anterior chamber angle ®
ADRENOCEPTOR pupil ® anterior chamber ® trabecular meshwork ®
BLOCKERS canal of Schlemm ® uveoscleral veins
https://qrs.ly/77ckdze
TYPES OF GLAUCOMA
OPEN ANGLE CLOSED ANGLE
MAJOR SUBGROUPS OF BETA-BLOCKERS
• Sudden complete block of
Non-selective PROPRANOLOL, TIMOLOL
drainage system of the eye,
ACEBUTOLOL, BETAXOLOL, ESMOLOL,
Beta 1-selective causing rapid pressure
ATENOLOL, METOPROLOL • partial block of normal
buildup in the eye
Partial agonist PINDOLOL, ACEBUTOLOL drainage system of the eye,
Lacking local anesthetic • Associated with: shallow
TIMOLOL causing gradual pressure
effect anterior chamber and dilated
buildup inside the eye
Low lipid solubility ATENOLOL iris (can OCCLUDE outflow
• Sx: gradual loss of peripheral
ESMOLOL drainage pathway)
Shortest-acting vision, “halos” around lights,
ESMOL (small) lang ang half-life • Sx: severe eye pain and
gradually increasing eye pain
NADOLOL pressure, corneal cloudiness,
Longest-acting halos around lights,
NADOLOL = NAsa DOLO ang half-life
Combined u and β nausea/vomiting
NEBIVOLOL, CARVEDILOL, LABETALOL Treatment: Pharmacologic Treatment: Iridectomy
blockade
PHARMACOLOGIC TX OF GLAUCOMA IS TWO PRONGED:
• REDUCTION of aqueous humor Production
CARDIOVASCULAR DRUGS
• ENHANCEMENT of aqueous humor OUTFLOW DRUGS FOR HYPERTENSION
TREATMENT FOR GLAUCOMA

https://qrs.ly/i2ckdzf
DRUG CLASS EXAMPLES MECHANISM

Timolol,
Levobunolol,
Carteolol,
Beta
Metipranolol,
antagonists
(nonselective),
Betaxolol (b1 Decreased production
selective) of aqueous humor from
Osmotic agents Mannitol ciliary epithelium
Brimonidine,
a2 agonists
Apraclonidine
Carbonic Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
Acetazolamide,
anhydrase
Dorzolamide
inhibitors
Pilocarpine
(Non-selective
Ciliary muscle
muscarinic agonist),
contraction, opening of
Cholinomimetics Physostigmine &
trabecular meshwork → BLOOD PRESSURE HYPERTENSIVE DRUGS
Echothiopate
Increased outflow https://qrs.ly/8tckdzn https://qrs.ly/6mcke0o
(Acetylcholinesterase
inhibitor) KEY LEARNING POINTS: Target BP
Prostaglandin Latanoprost, Increased outflow via What is the blood pressure goal in hypertensive patients with
analogue Brimatoprost canal of Schlemm (JNC7) (JNC8)
Non selective a Increased outflow via • no comorbidities? < 140/90 • <150/90
Epinephrine • diabetes mellitus? < 130/80 • <140/90
agonists uveoscleral veins
• chronic kidney disease? < 130/80 • <140/90
DIURETICS
• Diuretics lower BP by decreasing volume and a direct vascular effect that is not yet fully understood
THIAZIDE DIURETICS LOOP DIURETICS
Drug HYDROCHLOROTHIAZIDE [B], FUROSEMIDE [C],
Chlorthalidone [B], Indapamide, [B] Metolazone [B] Bumetanide, [C] Torsemide, Ethacrynic acid [B]
Inhibit Na+/Cl- transporter in DCT. Inhibit Na/K/2Cl transporter in thick ascending limb of loop of Henle.
MOA Cause moderate diuresis and reduced excretion of calcium Cause powerful diuresis and increased Ca excretion.
Hypertension, Heart failure, Hypercalciuria, Renal calcium stones, Heart failure, Pulmonary edema, Hypertension, Hypercalcemia,
Uses
Nephrogenic diabetes insipidus Acute renal failure, Anion overdose
Hypokalemic metabolic “HYPER- Hypokalemic metabolic alkalosis, “OH DANG”
alkalosis, Dilutional GLUC” Hypovolemia, Potassium wasting, O-totoxicity
hyponatremia, G-lycemia Dehydration, Ototoxicity, Sulfa H-ypokalemia
Sulfa allergy, K+ wasting, L-ipidemia allergy, Hyperuricemia, D-ehydration
SE Hyperglycemia, U-ricemia Hypomagnesemia, Nephritis, A-llergy to sulfa
Hyperlipidemia, C-alcemia Hypocalcemia N-ephritis
Hyperuricemia, DIURETICS G-out
Hypercalcemia https://qrs.ly/xrcke39
• Metolazone appears in cord blood and crosses placenta and may • Ethacrynic acid is a loop diuretic that is not a sulfur-derivative,
cause hypokalemia, hyponatremia, hypoglycemia, jaundice and and therefore, can be given to Px with sulfur allergy.
thrombocytopenia.
• Less effective in edematous states compared to Loop diuretics. • Very effective in edematous and states of fluid overload.
• For diuretics remember that they can cause acid-base imbalances, • Inhibition of a different isoform of NKCC1 in the inner is thought to
both acidosis and alkalosis. be responsible for the ototoxicity that is rarely seen with high dose
• Always remember that “Where Na+ goes, water follows” and “Where IV loop diuretics
Na+ goes, HCO3- follows too” (This will be useful also for explaining • Hypercalciuria may cause nephrocalcinosis
acidosis caused by Carbonic Anhydrase inhibitors).
Notes
• Also remember that “Where K+ goes, H+ follows”
• So for diuretics that cause K+ wasting, they are expected to cause
HYPOkalemic Metabolic ALKALOSIS since H+ is also lost in the urine.
While for K+ sparing diuretics, since you retain K+, you will also retain H+,
leading to HYPERkalemic metabolic ACIDOSIS. The mechanism of
acidosis caused by Carbonic Anhydrase inhibitors is further discussed in
the diuretics chapter.
• Reabsorption of Ca caused by Thiazides greatly helps in patients with
renal Ca stones or Hypercalciuria.
SYMPATHOPLEGICS
• Drugs interfere with sympathetic control of cardiovascular function. By reducing: venous tone, heart rate, contractile force of the heart,
cardiac output and total peripheral resistance.
CENTRALLY ACTING: GANGLION POSTGANGLIONIC
ADRENERGIC BLOCKER
ALPHA-2 AGONISTS BLOCKER NEURON BLOCKER
BETA BLOCKERS:
ALPHA-1 BLOCKER: PROPRANOLOL [C],
PRAZOSIN [C], Pindolol, Timolol,
HEXAMETHONIUM
Drug RESERPINE [C], Doxazosin [C], Labetalol, Carvedilol,
[D],
CLONIDINE [C] METHYLDOPA [B] Guanethidine [C], Terazosin [C], Nadolol,
Trimethaphan [D],
Guanadrel [B] Tamsulosin [B], Levobunolol,
Mecamylamine [C]
Silodosin [B], Metipranolol,
Alfuzosin [B] Betaxolol, Bisoprolol,
Nebivolol
Reserpine:
blocks vesicular
monoamine
transporter
a2 agonist Blocks NN (VMAT) - Blocks a1 adrenergic Blocks b1 and b2
MOA
decreases central sympathetic outflow receptors Guanethidine: receptors receptors
blocks vesicular
release of NE from
the presynaptic
neuron -
Angina prophylaxis,
Hypertension,
Arrhythmias, Migraine,
Performance anxiety,
Hypertension, Hypertension Hyperthyroidism,
Benign prostatic
Cancer pain, (obsolete), Hypertension Glaucoma
Uses Pre-eclampsia hyperplasia,
Opioid Hypertensive (obsolete) Used in Chronic heart
Hypertension
withdrawal emergencies failure to control HR
but NOT acute heart
failure for it may
further depress the
heart
First dose orthostatic
hypotension,
Postural Reflex tachycardia
Sedation, Sedation, Hypotension, Dry Sedation, Severe (less chance), Dizziness, Bronchospasm, AV
Rebound Hemolytic anemia mouth, Blurred psychiatric Drowsiness, Headache, block, Heart failure,
SE
hypertension, (Positive Coombs vision, depression, Weakness, Asthenia, CNS sedation, Erectile
Dry mouth Test) Constipation, Suicidal ideation Nausea, Edema dysfunction
Sexual dysfunction Given at bedtime to
prevent orthostatic
hypotension
• Taper use • Most commonly • Since NN • Avoid in Px with • Tamsulosin: most • Masks symptoms of
before used receptors are history of selective for hypoglycemia in
discontinuing maintenance found in both depression prostatic smooth diabetics
to avoid meds for HTN sympathetic and • (Not used muscle • Carvedilol and
rebound during parasympathetic, anymore due to • Doxazosin, Labetalol: has
hypertension pregnancy; blocking both has psychiatric side Tamsulosin, Silodosin combined a and b
(Antidote: causes multiple effects) and Alfuzosin: not for blockade (may be
Notes
Phentolamine) HEMOLYTIC autonomic effects. use in females or for used in
ANEMIA as an • (Not used treatment of pheochromocytoma)
IDIOSYNCRATIC anymore due to hypertension.
REACTION serious side • Doxazosin and
effects) Terazosin: longer
duration of action
than prazosin
Modified from Figure 11-2. Katzung BG. Basic and Clinical Pharmacology 14 ed. 2018.
th
KEY LEARNING POINTS Pheochromocytoma RAAS ANTAGONISTS
What drugs are used to control blood pressure in pheochromocytoma?
Phenoxybenzamine, Phentolamine or Labetalol • Renin–angiotensin–aldosterone system (RAAS):
o composed of three major compounds: renin, angiotensin II,
and aldosterone
VASODILATORS o increases sodium reabsorption, water reabsorption, and
MNEMONIC: Drug-Induced Lupus vascular tone
What medications may cause drug-induced lupus? o increases blood volume and blood pressure
“It’s HIPP to have LUPUS!” • RAAS antagonists inhibit this effect
Hydralazine Procainamide
Isoniazid Penicillamine
MNEMONIC: Drugs that can cause Gingival Hyperplasia
“NapaCa-Pangit ng gingiVa mo”
Nifedipine Cyclosporine
Phenytoin Verapamil
SUPPLEMENT: Malignant Hypertension

• accelerated form of severe hypertension associated with rising blood
pressure and rapidly progressing end-organ damage
• MANAGEMENT
o powerful vasodilators (nitroprusside, fenoldopam, or diazoxide)
combined with diuretics (furosemide) and beta-blockers to lower
BP to 140–160/90–110
VASODILATORS
OLDER ORAL VASODILATORS CALCIUM CHANNEL BLOCKERS PARENTERAL VASODILATORS
Dihydropyridine CCB:
NIFEDIPINE [C],
Amlodipine [C],
Felodipine [C],
Non-dihydropyridine D1 RECEPTOR
Drug Nicardipine [C],
HYDRALAZINE DIAZOXIDE [C], CCB: NITROPRUSSIDE AGONIST:
Nisoldipine [C],
[B] MINOXIDIL [C] VERAPAMIL [C], [C] FENOLDOPAM
Clevidipine [C],
DILTIAZEM [C] [B]
Isradipine [C],
Levamlodipine [D],
Lacidipine [C],
Lercanidipine [C]
Block voltage-gated
Block voltage-gated
L-type calcium Causes
Alters Opens K+ channels L-type calcium
channels Relaxes venous arteriolar
intracellular in vascular smooth channels
(Vascular > Cardiac) and arteriolar vasodilation of
Ca2+ metabolism. muscle (Cardiac >
More vasoselective smooth muscle by the afferent and
MOA Relaxes arteriolar causes Vascular)
than Non-DHPRs, increasing NO → ↑ efferent
smooth muscle. hyperpolarization, More cardio-selective
greater vasodilator cGMP → smooth arterioles.
Decreases muscle relaxation than Dihydropyridine
effect than cardio- muscle relaxation Increases renal
afterload and vasodilation CCBs, hence used for
depressant effect, blood flow.
arrhythmia
hence more used for HTN
Hypertensive
Hypertension,
Angina, HTN, emergency,
Heart failure
Hypertension, Supraventricular Acute heart failure, Hypertensive
Uses (in combination Angina, Hypertension
Alopecia tachycardia, Cardiogenic shock, emergency
with ISDN),
Migraine Controlled
Pre-eclampsia
hypotension
Constipation,
Edema, Reflex Pretibial edema
Edema, Reflex tachycardia, Angina, (common), Nausea,
Tachycardia, Pericarditis, Flushing, Dizziness, Constipation,
Hypotension,
Myocardial Pulmonary Gingival Pretibial edema Hypotension,
SE Headache,
ischemia, hypertension, hyperplasia (only (common), Nausea, Hypokalemia
Cyanide Toxicity
Drug-induced Hypertrichosis, in Verapamil), Flushing, Dizziness
lupus Hirsutism, Salt and Heart failure, AV
water retention block, Sinus node
depression
• Combination • Require • Excessive cardiac • Potent vasodilators: • Very light • Short duration
treatment with concomitant use of depression may may cause reflex sensitive, with of action:
ISDN for heart diuretics and BBs occur tachycardia; may have short Duration of 10mins
failure is more to block • Never used in pro-arrhythmogenic action; given as • (Not commonly
effective than compensatory Acute Heart effect continuous used due to its
ACEIs in blacks responses Failure because it • Other infusion very short t½ )
• Used in • Minoxidil may further dihydropyridine • The most effective
Notes
hypertensive stimulates hair depress the heart CCBs cause gingival vasodilator: both an
urgencies in follicles (telogen • Diltiazem does hyperplasia too! ARTERIOLAR
pregnant phase) to NOT cause gingival (E.g. Amlodipine- vasodilator and a
patients differentiate into hyperplasia, induced gingival VENOdilator
growth follicles VERAPAMIL DOES hyperplasia)
(anagen phase)
RAAS INHIBITORS
ACE INHIBITORS ANGIOTENSION RECEPTOR BLOCKER RENIN INHIBITOR
All are Preg Cat Class D All are Preg Cat Class D
Drugs CAPTOPRIL, Enalapril, Benazepril, Fosinopril, LOSARTAN, Candesartan, Valsartan, ALISKIREN [D]
Lisinopril, Quinapril, Ramipril, Trandolapril, Irbesartan, Eprosartan, Telmisartan, “Alis ka Renin!”
Moexipril, Perindopril, Imidapril Azilsartan, Olmesartan
Blocks Angiotensin (AT1 receptors) in vascular Inhibits renin.
Inhibits ACE and formation of Angiotensin II.
MOA smooth muscle and adrenal cortex. Prevents conversion of
Decreases aldosterone secretion
Decreases aldosterone secretion. angiotensinogen to angiotensin I.
• Hypertension, Heart Failure, Diabetic • Hypertension, Heart Failure, Diabetic • Hypertension
nephropathy, Post-myocardial infarction nephropathy
Uses
Captopril has a short half-life, necessitating ARBS are as effective as ACEi but has less
2-4x a day administration cough
• Cough, Angioedema, Taste disturbance, • Hypotension, Teratogen, Hyperkalemia, • Headache, diarrhea, cough,
Hypotension, Teratogen, Hyperkalemia Hypoglycemia, Anemia, diarrhea rash, hyperkalemia, increase
• Inhibits ACE, kininase II and peptidyl dipeptidase • 1.6-6.6% of Px may experience cough as well.
in serum creatinine, renal
→ increase in endogenous vasodilators of the impairment, angioedema
• Has lower rates of cough and angioedema but
kinin family (bradykinin) may cause cough and higher rates of hypotension
angioedema
SE
• 5-20% of patients experience dry cough.
Remedy: decrease dose or shift to ARBs
• Do not give to patients with bilateral Renal
Artery stenosis since ACEi can decrease the
GFR of the stenotic kidney (due to removal of
angiotensin II-induced renal vasoconstriction)
• Use in Heart Failure: slows ventricular remodeling and increases survival in heart failure. • Contraindicated In
• Use in those with Kidney disease Pregnancy
o Delays progression of diabetic nephropathy. o Fetal harm may occur when
Decreases albumin excretion and slow progression from micro- to macroalbuminuria (renoprotective effect) given during pregnancy.
o Should not be given in patients experiencing AKI (Acute Kidney Injury) and Hyperkalemia. o Use of drugs that act on the
o Usually withheld in patients who are CKD stage 4 already because use of ACEi and ARBs may RAAS during the 2nd & 3rd
result in significant worsening of kidney function, while another study has suggested that trim reduces renal function
discontinuing these agents in patients with advanced CKD may improve renal function and increases fetal and
Notes • Contraindicated In Pregnancy neonatal morbidity and
o Use of drugs that act on the RAAS during the 2nd & 3rd trim reduces renal function and increases death.
fetal and neonatal morbidity and death
o Discontinue as soon as pregnancy is detected (fetal hypotension, neonatal skull hypoplasia,
anuria, renal failure, renal dysplasia)
• Never combine ACEi and ARBs together (Increased adverse reaction since they have the same effect
on the RAAS pathway and possible increased incidence of cancer)
Hyperkalemia from ACEi/ARBS? Aldosterone: causes an increase in sodium reabsorption and potassium
excretion at the distal tubule, ACEi and ARBs inhibit Aldosterone (hence decreased K excretion)
SUPPLEMENT: HYPERTENSION IN PREGNANCY line agent for pregnant women with chronic hypertension requiring
• NO CLEAR CONSENSUS ON THE MANAGEMENT OF MILD TO long-term drug therapy.
MODERATE HTN IN PREGNANCY. Nevertheless, drugs that have been • Oral CCBs have been shown to reduce maternal blood pressure in
listed as acceptable oral antihypertensive agents in pregnant women pregnant women, but little is known about the effects of long-term
are as follows: administration in the 1st trimester. Among the CCBs, Nifedipine has
o Methyldopa been the best studied and has been used extensively in later pregnancy.
o Labetalol • Oral HYDRALAZINE is effective as monotherapy or as add-on to
o Nifedipine methyldopa in chronic hypertension in pregnancy. In general,
• Methyldopa is a drug of first choice. It does not alter maternal cardiac hydralazine often requires combination therapy with a sympatholytic
output or blood flow to the kidneys or uterus agent (Methyldopa or BB) to help attenuate the reflex tachycardia
• The combined alpha and beta blockade of labetalol makes it a associated with hydralazine
peripheral vasodilator which has been shown to be effective in pre- • ACEi and ARBs are NOT recommended during pregnancy
eclamptic and non-proteinuric hypertension in pregnancy. However, • Diuretics are also avoided since it can reduce maternal plasma volume
because the safety record of labetalol in pregnancy in not well and can cause electrolyte disturbance
established as that of methyldopa, labetalol should be considered a 2nd
DRUGS USED IN THE TREATMENT OF ANGINA PECTORIS

ANGINA PECTORIS
• Atherosclerotic Angina
o angina of effort or classic angina
o associated with atheromatous plaques that
partially occlude 1 or more coronary arteries
o constitutes about 90% of angina cases
• Vasospastic Angina
o rest angina, variant angina, or Prinzmetal angina
o involves reversible spasm of coronaries, usually
at the site of an atherosclerotic plaque
o responsible for less than 10% of cases
o may deteriorate into unstable angina
• Unstable Angina
o unstable/crescendo angina, acute coronary
syndrome
o increased frequency and severity of attacks that
result from a combination of atherosclerotic
plaques, platelet aggregation and vasospasm
Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 o immediate precursor of a myocardial infarction
THERAPEUTIC STRATEGIES IN ANGINA NITRATE POISONING
• defect that causes anginal pain is inadequate coronary oxygen • Nitrates → meningeal blood vessel vasodilation → ↑ ICP → headache
delivery relative to the myocardial oxygen requirement • Monday Disease:
• can be corrected in 2 ways: • due to occupational exposure to nitrates
o increasing oxygen delivery (by vasodilation) • alternating development of tolerance (during the work week)
o reducing oxygen requirement (by decreasing HR) and loss of tolerance (over the weekend) every Monday
NITRATES
CYANIDE POISONING: NITRATES AS A PART OF THE ANTIDOTE
• Nitrates decrease angina by reducing cardiac work (reducing
preload) and increasing the blood flow through partially • Cyanide affects Complex IV (cytochrome oxidase) of the
occluded epicardial coronary vessels Electron Transport Chain
o Nitrates are more of a venodilator than an arteriolar • Antidote: Lilly Cyanide Kit: inhaled amyl nitrite + IV sodium
vasodilator nitrite + IV sodium thiosulfate
o Short acting nitrite to cause oxidation of Fe2+ in Hemoglobin to Fe3+ in
• Nitrates PLUS Sildenafil: a dangerous combination
methemoglobin (nitrate is used to make Methemoglobin)
o Nitrates release nitric oxide, which activates the guanylyl o Methemoglobin combines with cyanide (cyanomethemoglobin), thus
cyclase and increases the cGMP releasing cytochrome oxidase enzyme
o Sildenafil also increases cGMP (by inhibiting its degradation). o Sodium thiosulfate reacts with cyanomethemoglobin (converts to
This could lead to a very dangerous hypotension if both are nontoxic thiocyanate and methemoglobin)
used together. SUPPLEMENT: Effects of Drug Combinations
Combined
Nitrates BB or CCB Nitrates
alone alone and BB or
CCB
Reflex
Heart rate DECREASE DECREASE
increase
Arterial
Decrease DECREASE DECREASE
pressure
End-diastolic
DECREASE Increase DECREASE
pressure
Reflex No effect or
Contractility DECREASE
increase decrease
Reflex
Ejection time Increase No effect
decrease
Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 Net myocardial
DECREASE DECREASE DECREASE
O2 requirement
ANGINA DRUGS
CALCIUM CHANNEL BLOCKER
NITRATES BETA BLOCKER
All are Preg Cat Type C
Nondihydropyridine CCB: Dihydropyridine CCB:
Short acting VERAPAMIL, DILTIAZEM NIFEDIPINE PROPRANOLOL [C],
Drug Ultrashort NITROGLYCERIN, Amlodipine, Felodipine, Pindolol, Timolol,
AMYL NITRITE Isosorbide dinitrate Nicardipine, Nisoldipine, Labetalol, Carvedilol,
[C] (ISDN), Isosorbide Clevidipine, Isradipine, Nadolol, Levobunolol,
mononitrate (ISMN) Levamlodipine, Lacidipine, Metipranolol, Betaxolol,
Lercanidipine Bisoprolol, Nebivolol
• Block voltage-gated L-
• Block voltage-gated L-type type calcium channels
Releases nitric oxide (NO), increases calcium channels • (Vascular > Cardiac)
cGMP (cyclic guanosine monophosphate), • (Cardiac > Vascular)
MOA More vasoselective than Blocks b1 and b2 receptors
and relaxes smooth muscle, especially More cardio-selective than Non-DHPRs, greater
vascular Dihydropyridine CCBs, hence vasodilator effect than
used for arrhythmia cardio-depressant effect →
more used for HTN
• Angina, Acute • Angina prophylaxis,
Coronary Syndromes Hypertension,
ISMN: M for matagal Arrhythmias, Migraine,
since it has longer • Angina, HTN, Performance anxiety,
• Cyanide half-life, and M for Supraventricular Hyperthyroidism,
Uses poisoning Matibay since it does tachycardia, Migraine • Angina, Hypertension Glaucoma
(inhalational) not undergo first pass • Diltiazem is DOC for • Used in Chronic heart
effect Prinzmetal Angina failure to control HR but
NOT acute heart failure
for it may further
depress the heart
• Reflex tachycardia, Orthostatic • Constipation, Pretibial • Constipation, Pretibial • Bronchospasm, AV
hypotension, Headache, Tolerance edema (common), Nausea, edema (common), Nausea, block, Heart failure, CNS
(transdermal) Methemoglobinemia Flushing, Dizziness, Gingival Flushing, Dizziness sedation, Erectile
SE Tx for Methemoglobinemia? Low dose hyperplasia (only in dysfunction
Methylene blue Verapamil), Heart failure,
AV block, Sinus node
depression
• Part of the Lilly • Dangerous • Excessive cardiac • Potent vasodilators: may • Masks symptoms of
Cyanide Kit hypotension with depression may occur cause reflex tachycardia; hypoglycemia in
PDE inhibitors such • Never used in Acute Heart may have pro- diabetics
as Sildenafil Failure because it may arrhythmogenic effect • Carvedilol and
Notes
• First Pass effect is further depress the heart • Other dihydropyridine CCBs Labetalol: has
~90% (NTG) • Diltiazem does NOT cause cause gingival hyperplasia combined a and b
• NTG also decrease gingival hyperplasia too! (E.g. Amlodipine- blockade (may be used
platelet aggregation induced gingival hyperplasia) in pheochromocytoma)
METABOLISM MODIFIERS
• Metabolism modifiers decrease myocardial oxygen demand in general since they try make use of pathways that utilize less ATP, hence, less
amount of work for the myocardium.
Drug TRIMETAZIDINE [C] RANOLAZINE [C] IVABRADINE [D]
• Inhibit Beta oxidation of fatty acid • Reduces a late, prolonged Na+ • Inhibits If Na current in SA node →
by inhibiting 3-ketoacyl-CoA thiolase current in myocardial cells. decreases hyperpolarization-induced
which enhances glucose oxidation. Decreased intracellular Na+ inward pacemaker current → decrease HR
MOA • Prevents decrease in ATP in ischemic/ and cardiac work
→ increased Ca2+ expulsion via Na+-Ca2+
hypoxic states. exchanger →Intracellular Ca2+ Decreases HR without decreasing the BP
→decreased cardiac force and work.
Uses Angina pectoris, Tinnitus, Dizziness Angina prophylaxis Angina prophylaxis, Heart Failure
EPS, gait instability, QT prolongation, nausea, constipation, Bradycardia, Hypertension,
SE
restless leg syndrome dizziness Atrial Fibrillation
• Interacts with MAO inhibitors • CYP3A4 inhibitors increase
Notes Ranolazine concentration
• May also modify fatty acid oxidation
DRUGS USED IN HEART FAILURE CHF: Therapeutic Strategies

• direct augmentation of depressed cardiac contractility with
positive inotropic drugs
• reduction of preload or afterload with vasodilators
• removal of retained salt and water with diuretics
• reduction of afterload and salt and water retention via ACE inhibitors
• reduction of excessive sympathetic stimulation via beta-blockers
CHF Treatment:
CONGESTIVE HEART FAILURE: PATHOPHYSIOLOGY • ACUTE HEART FAILURE
• fundamental physiologic defect is decrease in cardiac output o should be treated with a loop diuretic
relative to the needs of the body o if very severe, use prompt-acting positive inotropes (beta-
o frequently associated with chronic hypertension, valvular agonists or PDE inhibitors) and vasodilators
disease, coronary artery disease, and cardiomyopathies • CHRONIC HEART FAILURE
• Clinical Manifestations: o treated with diuretics (often loop plus spironolactone) plus
o Left-sided heart failure: Orthopnea, PND, Pulmonary an ACE inhibitor and, if tolerated, a beta-blocker
Congestion o digitalis may be helpful if systolic dysfunction is prominent
o Right-sided heart failure: Hepatomegaly, Edema, Engorged
Neck Veins
POSITIVE INOTROPES
CARDIAC GLYCOSIDE BETA AGONIST PDE inhibitor
Drugs
DIGOXIN [C], Digitoxin Dobutamine Milrinone, Inamrinone
Inhibits Na+/K+ ATPase; Increases
intracellular Ca2+, increasing cardiac Increase cAMP by inhibiting its breakdown
β1 agonist
MOA contractility by PDE3 → increase in cardiac intracellular
β1: increases HR and contractility calcium.
Digitalis glycosides exert a mild inotropic
effect
Acute heart failure, Cardiogenic shock, Heart failure, pulmonary hypertension,
Uses Heart failure, Nodal arrhythmias
Cardiac stress testing intraoperative cardiac support
Hypertension, Tachycardia, Arrhythmias,
Narrow therapeutic index Premature ventricular beats, Angina,
SE Arrhythmias, Vomiting, Diarrhea, Visual Dyspnea, Tachyphylaxis (common with Arrhythmias, hypotension
changes dobutamine), Eosinophilic myocarditis,
Fever, Headache, Nausea
• Reduced clearance with quinidine,
• DOBUTAMINE and DOPAMINE are useful
amiodarone, cyclosporine, diltiazem and
in acute heart failure should not be used in chronic failure
verapamil.
Notes • Not appropriate for chronic failure because they increase morbidity and
• Arrhythmogenesis increased by
because of tolerance, lack of oral efficacy mortality
hypokalemia, hypomagnesemia and
and significant arrhythmogenic effects
hypercalcemia.
• Digoxin antibodies
o digoxin antibodies (Fab fragments; Digibind)
MOA OF DIGOXIN
https://qrs.ly/r5cke17 If digoxin antibodies are not available, Bile Acid binding resins can be
given as a substitute. Since these agents are substances 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 sterol
CARDIAC GLYCOSIDES: DIGITALIS
derivatives)
Digitalis Toxicity Dr. Pereyra-Borlongan
• increased by hypokalemia, hypomagnesemia, and hypercalcemia

MNEMONIC: Narrow Therapeutic Index
o loop diuretics and thiazides may significantly reduce serum
potassium and precipitate digitalis toxicity (causes HypoK, What drugs have narrow therapeutic index?
WALA na Cyang PaPa! VasTeD na!
HypoMg, HyperCa) Warfarin Phenobarbital
o digitalis-induced vomiting may deplete serum magnesium Aminoglycosides Phenytoin
and similarly facilitate toxicity Lithium Vancomycin
The most common ECG change seen in Digoxin toxicity is Premature Amphotericin B Theophylline
Ventricular Contractions (PVCs) Carbamazepine Digoxin
Dr. Pereyra-Borlongan
Treatment of Digitalis Toxicity

• Correction of potassium/magnesium deficiency
• Antiarrhythmic drugs
o drug of choice is LIDOCAINE
o electronic pacemaker may be required in severe cases
OTHER DRUGS FOR CHF BETA-BLOCKERS

NESIRITIDE (BNP analog, increases cGMP) may be used for acute • CARVEDILOL, LABETALOL, BISOPROLOL, NEBIVOLOL and
decompensated failure but has not been shown to reduce mortality. METOPROLOL reduce progression of chronic heart failure
Dr. Pereyra-Borlongan • beta-blockers are NOT OF VALUE in acute failure and may be
VASODILATORS detrimental if systolic dysfunction is marked
• NITROPRUSSIDE or NITROGLYCERIN for acute severe failure
with congestion ANGIOTENSIN ANTAGONISTS
• Dramatically effective in CHF due to increased afterload (e.g. • reduce aldosterone secretion, salt and water retention and
continuing hypertension in an individual who has just had an vascular resistance
infarct) • decrease ventricular remodeling (cardioprotective)
• HYDRALAZINE and ISOSORBIDE DINITRATE have been shown • reduce morbidity and mortality in chronic heart failure
to reduce mortality in African Americans • FIRST-LINE DRUGS FOR CHRONIC HEART FAILURE
• Calcium channel blockers are of NO value in CHF • ARBs have the same benefits as ACE-inhibitors
DIURETICS
• First-line therapy for both systolic and diastolic failure
• FUROSEMIDE for immediate reduction of the pulmonary
congestion and severe edema associated with acute heart failure
• SPIRONOLACTONE and EPLERENONE have significant long-
term benefits and can reduce mortality in chronic failure
NEPRILYSIN INHIBITOR: SACUBITRIL
• an antihypertensive drug used in combination
with Valsartan for Heart Failure
• It is prodrug that is activated to Sacubitrilat,
which inhibits the enzyme Neprilysin
• Neprilysin enzyme
o responsible for the degradation of atrial and
brain natriuretic peptide – two BP lowering
peptides that work mainly by reducing blood
volume
o 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.
MNEMONIC: Survival in CHF • ABNORMAL CONDUCTION

What drugs have been shown to improve survival in cases of heart failure? o conduction of an impulse that does not follow the defined path
ABA! Buhay ka pa! or reenters tissue previously excited
ACE inhibitors
Beta-blockers
TORSADES DE POINTES
Aldosterone Antagonists
• often induced by antiarrhythmics and other drugs that change
the shape of the action potential and prolong the QT interval
ANTIARRHYTHMIC DRUGS • ECG morphology: polymorphic ventricular tachycardia, often
displaying waxing and waning QRS amplitude
• associated with long QT syndrome (heritable abnormal
prolongation of the QT interval caused by mutations in the IK or
INa channel proteins)
MEMORY AID FOR
ANTI-ARRHYTHMIC DRUGS
ARRHYTHMIAS: MECHANISMS OF ARRHYTHMIAS https://qrs.ly/5dcke2f
• ABNORMAL AUTOMATICITY
o pacemaker activity that originates anywhere other than in the
sinoatrial node
SINGH-VAUGHAN WILLIAMS
CLASSIFICATION
• based loosely on the channel or receptor
affected
o CLASS 1. Sodium channel blockers
o CLASS 2. Beta-adrenoceptor blockers
o CLASS 3. Potassium channel blockers
o CLASS 4. Calcium channel blockers
CLASS 1 ANTIARRHYTHMICS • further subdivided based on their effects on AP duration

o Group 1A drugs prolong the AP duration
(SODIUM CHANNEL BLOCKERS) o Group 1B drugs shorten the AP duration
• Act on Phase 0 (zero) of cardiac action potential o Group 1C drugs have no effect on AP duration
• have local anesthetic activity • Amiodarone also has group 1 effects
• all group 1 drugs slow or block conduction in ischemic and MNEMONIC:
depolarized cells and slow or abolish abnormal pacemakers What are the drugs that can cause agranulocytosis?
• use dependent or state dependent in their action Agranulocytosis! CCCAPPIT Me!
o selectively depress tissues that are frequently depolarizing or Clozapine Phenylbutazone
relatively depolarized during rest Co-trimoxazole PTU
Colchicine Indomethacin
Aminopyrine Tocainide
Methimazole
CLASS 1 ANTIARRHYTHMICS: NA CHANNEL BLOCKERS
Class 1A Class 1B Class 1C
DISOPYRAMIDE [C], QUINIDINE [C], TOCAINIDE [C], LIDOCAINE [B], PROPAFENONE [C], FLECAINIDE [C],
Drugs
PROCAINAMIDE [C] MEXILETINE [C], PHENYTOIN [D] ENCAINIDE [B], MORICIZINE [B]
“Double Quarter Pounder” “Tomato, Lettuce, with Mayo, Please” “Chicken ay Pagkain for Enrico”
Selective use and state-dependent block
Highly selective use and state-dependent block
of INa; slowed conduction velocity and
Use- and state-dependent block of INa of INa; minimal effect in normal tissue; no
pacemaker activity
channels; some block of IK channels. effect on IK
• powerful depressants of sodium current
• slowed conduction velocity and • slows recovery of sodium channels from
• can markedly slow conduction
MOA pacemaker activity inactivation leading to prolonged ERP
velocity in atrial and ventricular cells
• prolonged AP duration and refractory • Only affect ischemic tissue: little effect on
• ECG effects
period normal cardiac cells, hence they have little
o no effect on ventricular AP
• Prolongs QRS duration and QT interval effect on the ECG
duration or the QT interval
• shortened AP duration
o increases the QRS duration
DOC for ventricular arrhythmias Refractory arrhythmias
Atrial and ventricular arrhythmias,
post-myocardial infarction, most arrhythmogenic among the class 1
Uses especially after acute myocardial
Digoxin-induced arrhythmias anti-arrhythmics (that’s why they’re only
infarction, Malaria (Quinidine)
Mexiletine: used for neuropathic pain used for refractory arrhythmias)
Arrhythmias, Hypotension
Hyperkalemia exacerbates cardiac toxicity • Increased arrhythmias (proarrhythmic
• Procainamide: Lupus-like syndrome CNS stimulation, Cardiovascular depression, effect), CNS excitation
• Disopyramide: Marked antimuscarinic effects Arrhythmias, Allergy, Agranulocytosis • Hyperkalemia exacerbates cardiac
SE
• Quinidine: Cinchonism (headache, (Tocainide) toxicity
vertigo, tinnitus), Cardiac depression, GI Hyperkalemia exacerbates cardiac toxicity • Contraindicated for post-MI
upset, Autoimmune reactions (ITP); arrhythmias.
Reduces clearance of digoxin
• Lidocaine : the least cardiotoxic among
• Crosses into breast milk conventional anti-arrhythmics; never given
• Procainamide: Short duration of action: 2- PO due to significant first pass effect
3hours only • Phenytoin: increased incidence of major
Treatment of Class 1A overdose malformations (e.g. orofacial clefts,
Notes
• Sodium Lactate to reverse drug-induced cardiac defects, fetal hydantoin
arrhythmias syndrome etc.) and cognitive defects
• Pressor sympathomimetics to reverse reported for pregnant women who use it for
drug-induced hypotension if indicated epilepsy. It is also secreted in the human
milk
CLASS 2 ANTIARRHYTHMICS CLASS 3 ANTIARRHYTHMICS

(BETA BLOCKERS) (POTASSIUM IK CHANNEL BLOCKERS)
• Act on Phase 4 • act on Phase 3
• primarily cardiac beta-adrenoceptor blockade and reduction in cAMP • hallmark is prolongation of the AP duration
o reduction of both sodium and calcium currents o caused by blockade of IK potassium channels that are
o suppression of abnormal pacemakers responsible for the repolarization of the AP
• AV node is particularly sensitive to blockers o results in an increase in ERP and reduces the ability of the
o PR interval is usually prolonged heart to respond to rapid tachycardias
• Sotalol and Amiodarone also have group 2 effects • ECG morphology: increase in QT interval
CLASS 2 ANTIARRHYTHMICS: BBs
PROPRANOLOL [C],
ESMOLOL CLASS 3 ANTIARRHYTHMICS: K CHANNEL BLOCKERS
Drugs Metoprolol [C],
[C, D in 2nd & 3rd trim]
Atenolol [D] AMIODARONE [X],
IBUTILIDE [C],
Selective block of beta-1 SOTALOL [B] Dronedarone [X],
Block of beta-receptors; Drug DOFETILIDE [C]
MOA receptors; slowed Vernakalant [X]
slowed pacemaker activity
pacemaker activity “AIDS: A-miodarone, I-butilde, D-ofetilide, S-otalol”
Acute perioperative and Strong IK block
Post-MI prophylaxis against
thyrotoxic arrhythmias, produces marked
Uses sudden death,
Supraventricular prolongation of action
Thyrotoxicosis
tachycardia (SVT) Selective IK potential and
SE Bronchospasm, Cardiac depression, AV block, Hypotension IK block and
block; refractory period.
• In CHF, reduces
beta-
prolonged Group 1 activity
progression and MOA adrenoceptor
action slows conduction
decreases incidence of block velocity; groups 2
potential & QT
potentially fatal • Used especially in interval and 4 activity
Notes
arrhythmias Thyrotoxic arrhythmias confer additional
• Sotalol is a beta-blocker anti-arrhythmic
anti-arrhythmic that has activity
Class 3 properties.
Refractory CLASS 4 ANTIARRYTHMICS: CCBs
arrhythmias, Used Drugs Non-dihydropyridine CCBs:
Ventricular off-label in many
Tx and VERAPAMIL, DILTIAZEM
arrhythmias, arrhythmias
prophylaxis of MOA block voltage-gated L-type calcium channels
Uses Atrial Dronedarone is less
atrial (cardiac > vascular)
fibrillation, toxic but less effective
fibrillation than Amiodarone. It is Uses Angina, Hypertension, Supraventricular tachycardia,
SVT
used in Afib and Atrial Migraine
flutter SE Constipation, Pretibial edema, Nausea, Flushing, Dizziness,
Dose-related Microcrystalline Gingival hyperplasia (Verapamil), Heart failure, AV block,
torsade de deposits in cornea and Sinus node depression
pointes, skin, Thyroid Notes Excessive cardiac depression may occur
Torsades de
SE Excessive beta- dysfunction (hyper- Should be avoided in Ventricular tachycardia
pointes
blockade (sinus or hypo-), Paresthesia,
bradycardia, Tremor, Pulmonary MISCELLANEOUS ANTIARRHYTHMICS
asthma) fibrosis
• MOA: Increase in diastolic IK of AV node that
• Most efficacious of all
causes marked hyperpolarization and
antiarrhythmic drugs
conduction block; reduced Ica
• Has the longest t½
• Can cause fetal harm • Use: AV nodal arrhythmias, DOC for paroxysmal
Notes (cardiac, thyroid, supraventricular tachycardia
neurodevelopmental, ADENOSINE • SE: Flushing, Hypotension, Transient chest pain,
neurological and Dyspnea
growth defects in • Has a very short t½ of 15sec
neonates) Adenosine also occurs naturally in the body as a
KEY LEARNING POINTS: Amiodarone Toxicity potent bronchoconstrictor and so this drug may also
AMIODARONE TOXICITY induce such effect
Pulmonary fibrosis Thyroid dysfunction • MOA: depresses ectopic pacemakers, including
Paresthesia Corneal deposits those caused by digitalis toxicity
Tremors Skin deposits • when treating arrhythmias, serum potassium
should be measured and normalized if abnormal
POTASSIUM
o hypokalemia is associated with an increased
AMIODARONE ION
incidence of arrhythmias, especially in patients
https://qrs.ly/v7cke2j receiving digitalis
o excessive potassium levels depress conduction
and can cause reentry arrhythmias
• MOA: poorly understood, possible increase in
CLASS 4 ANTIARRHYTHMICS Na+/K+ ATPase activity, slows the rate of SA
(CALCIUM L-TYPE CHANNEL BLOCKERS) node impulse formation in the myocardium and
• effective in arrhythmias that must traverse calcium-dependent prolongs conduction time.
cardiac tissue (e.g. the AV node) MAGNESIUM • similar depressant effects as potassium on
ION digitalis-induced arrhythmias
• cause a state- and use-dependent selective depression of Ca2+
currents • effective in some cases of TORSADES DE POINTES
• AV conduction velocity is decreased and effective refractory Sudden and large increase in Mg may cause severe
period increased respiratory paralysis
• ECG morphology Summary of the Effects of Antiarrhythmic Drugs
o PR interval is consistently increased Effect on
Dihydropyridine CCBs: not useful as antiarrhythmics because CLASS PROTOTYPE AP Effect on ECG
dihydropyridine CCBs evoke compensatory sympathetic discharge which Duration
facilitates arrhythmias rather than terminating them PROLONGS PR interval,
Dr. Pereyra-Borlongan 1A Procainamide PROLONGS
PROLONGS QRS duration
1B Lidocaine SHORTENS NO EFFECT on normal cells
1C Flecainide NO EFFECT PROLONGS QRS duration
2 Propranolol NO EFFECT PROLONGS PR interval
3 Dofetilide PROLONGS PROLONGS QT interval
4 Verapamil NO EFFECT PROLONGS PR interval
DIURETICS
SITES OF ACTION OF THE DIURETICS AND ADH DRUGS
DIURETICS
https://qrs.ly/7kcke0y
Proximal Convoluted Cortical Collecting Ducts

Tubule • last tubular site of
• carries out isosmotic sodium reabsorption
reabsorption of amino o responsible for
acids, glucose, and reabsorbing 2–5% of
numerous cations the total filtered Na+
o major site for sodium • under the influence of
chloride and sodium aldosterone, reabsorption
bicarbonate of Na+ occurs via channels
reabsorption (60-70%) o accompanied by an
• site of uric acid transport equivalent loss of K+
• site of action of or H+ ions
carbonic anhydrase • primary site of
inhibitors acidification of the urine
Thick Ascending Limb of • last site of K+ excretion
the Loop of Henle • sites of action of the
• responsible for a potassium-sparing
significant percentage of diuretics
sodium chloride
reabsorption via the
Na+/K+/2Cl– transporter Medullary Collecting Duct
• site of action of loop • reabsorption of water
diuretics occurs under the control of
• site of Calcium and antidiuretic hormone (ADH)
Magnesium reabsorption • site of action of ADH
• prostaglandins are agonists and
important in maintaining antagonists
glomerular filtration
• NSAIDs decrease the
efficacy of loop diuretics
Distal Convoluted MNEMONIC : Potassium-Sparing Diuretics
Tubule The K STAEs (stays) with K sparing diuretics!
• actively pumps sodium Spironolactone
and chloride out of the Triamterene
lumen of the nephron Amiloride
via the Na+/Cl– carrier Eplerenone
• site of action of Which drugs can cause GYNECOMASTIA?
thiazide diuretics Some Drugs Create Awesome Knockers
• responsible for Spironolactone Alcohol
approximately 5–8% of Digoxin Ketoconazole
sodium reabsorption Cimetidine
• calcium is also
MNEMONIC: Metabolic Acidosis
reabsorbed in this
segment under the ACIDazolamide causes ACIDosis
control of PTH What are the causes of HAGMA? NAGMA
Methanol Hyperalimentation
(parathyroid hormone)
Uremia Acetazolamide
DKA RTA
Paraldehyde Diarrhea
Isoniazid, Iron Ureteral diversion
Lactic Acid Pancreatic fistula
Ethanol, Ethylene glycol
Salicylates
DIURETIC DRUGS
PCT: TAL LOH: DCT: CCD:
OSMOTIC
CARBONIC ANHYDRASE LOOP DIURETICS THIAZIDE DIURETICS POTASSIUM-SPARING DIURETIC
DIURETIC
INHIBITOR
HYDROCHLOROTHIAZIDE
[B], Chlorthalidone [B],
Indapamide [B],
ACETAZOLAMIDE [C],
Drugs FUROSEMIDE [C], Metolazone [B], Aldosterone Aldosterone MANNITOL [C],
Dorzolamide [C],
Bumetanide [C], Bendroflumethiazide [C], antagonist: antagonist: GLYCERIN [C],
Brinzolamide [C],
Torsemide [C], Hydroflumethiazide [D], SPIRONOLACTONE [C], AMILORIDE [B], ISOSORBIDE [C],
Dichlorphenamide [C],
Ethacrynic acid [B] Methylclothiazide [B], EPLERENONE [B] TRIAMTERENE [C] UREA [C]
Methazolamide [C]
Polythiazide [D],
Quinethazone [C],
Trichlormethiazide [B]
Inhibits carbonic Osmotically
anhydrase. In retains water in
proximal tubule, Inhibit tubule by
Steroid inhibitors Inhibitor of
bicarbonate Na+/K+/2Cl- reducing
Inhibit Na+/Cl- of cytoplasmic ENaC epithelial
reabsorption is transporter in reabsorption in
transporter in distal aldosterone sodium
blocked and Na+ thick ascending proximal tubule,
convoluted tubule. receptor in cortical channels in
MOA excreted with HCO3. limb of loop of descending limb
Cause moderate collecting ducts. cortical collecting
In glaucoma, secretion Henle. Cause of Henle's loop,
diuresis and reduced Reduce K excretion. duct, reduces Na
of aqueous humor is powerful diuresis and collecting
excretion of calcium. Potassium-sparing reabsorption and
reduced, and in and increased Ca2+ ducts; in the
diuretic K excretion.
mountain sickness, excretion. periphery,
metabolic acidosis mannitol extracts
increases respiration water from cells
PCT: TAL LOH: DCT: CCD:
OSMOTIC
CARBONIC ANHYDRASE LOOP DIURETICS THIAZIDE DIURETICS POTASSIUM-SPARING DIURETIC
DIURETIC
INHIBITOR
Drugs Aldosterone Aldosterone
ACETAZOLAMIDE [C], FUROSEMIDE [C], HYDROCHLOROTHIAZIDE antagonist: antagonist: MANNITOL [C],
etc etc [B], etc SPIRONOLACTONE [C], AMILORIDE [B], etc
EPLERENONE [B] TRIAMTERENE [C]
Hyperaldosteronism,
Hypertension, Heart
Heart failure, failure, Hypokalemia Rhabdomyolysis,
Hypertension, Heart
Pulmonary edema, Hemolysis,
Glaucoma, Mountain failure, Hypercalciuria, Spironolactone is
Hypertension, Increased
Uses Sickness, Edema Renal calcium stones, beneficial to Hypokalemia
Hypercalcemia, intracranial
with alkalosis Nephrogenic diabetes patient with CHF. It
Acute renal failure, pressure, Acute
insipidus helps in the
Anion overdose management of
glaucoma
cardiac remodeling
.
• Drowsiness, • Hypokalemic • Hypokalemic • Hyperkalemia, • Hyperkalemia, • Transient

Paresthesia, Sulfa metabolic metabolic alkalosis, gynecomastia Acute renal volume
allergy, Renal alkalosis, Dilutional (spironolactone failure (with expansion
calcium stones, Potassium hyponatremia, only), Impotence, indomethacin), (hyponatremia,
Potassium wasting, Potassium wasting, Benign prostatic Kidney stones, pulmonary
wasting, Dehydration, Hyperglycemia, hyperplasia, Metabolic edema; followed
Hyperchloremic Ototoxicity, Sulfa Hyperlipidemia, Hyperchloremic acidosis by
metabolic allergy, Hyperuricemia, metabolic acidosis hypernatremia),
acidosis, Hepatic Hyperuricemia, Hypercalcemia, Sulfa Spironolactone acts Headache,
encephalopathy in Hypocalcemia, allergy not only on Nausea,
SE cirrhotic patients Hypomagnesemia, mineralocorticoid Vomiting,
Nephritis Careful in DM receptors but also on Dehydration
These agents cause patients: Thiazide other STEROID
acidosis since they diuretics will cause receptors such as sex
force HCO3- out of hyperpolarization of hormone receptors. This
the urine. And so, ATP dependent K explains the side
channels (pancreatic effect gynecomastia.
you lose your bases,
Such effects have
leading to acidosis beta cells) and no
NOT been reported
insulin release.
with eplerenone
because it is much
more selective than
spironolactone
• Diuresis is self- • Synergistic • Synergistic effect • Eplerenone • Should never be • used to
limiting after 2-3 ototoxicity with with loop diuretics reduces given with maintain high
days aminoglycosides • Efficacy decreased progression of DM potassium urine flow
• Efficacy by NSAIDs nephropathy and supplements
decreased by reduces mortality
Notes PGs vasodilate the
NSAIDs afferent arteriole post-MI
(which regulates and
↑ GFR). NSAIDs inhibit
PG production → ↓
GFR..
ANTIDIURETIC HORMONE AGONIST/ANTAGONIST • Terlipressin: not • Central pontine myelinosis

recommended may occur with rapid
ADH AGONIST ADH ANTAGONIST
during pregnancy as correction of hyponatremia
VASOPRESSIN [C], CONIVAPTAN [C], it causes uterine • Conivaptan (V1 & V2 inhibitor)
Drugs Desmopressin [B], Tolvaptan [C], Lixivaptan, contractions, increased has a modest risk of causing
Terlipressin [X] Demeclocycline [D], uterine pressure in hypotension due to V1
Lithium[D] Notes
early pregnancy and antagonism, Tolvaptan does not
Agonists at V1 and V2 may decrease uterine cause hypotension because it is
ADH receptors. Antagonist at V1a & V2 blood flow. It may have a selective V2 inhibitor
Activate insertion of receptors harmful effects on • Use of tolvaptan is limited to
aquaporin water pregnancy and fetus
Increases water excretion 1-2months only due to
MOA channels in collecting
(in urine) hepatotoxicity
tubule.
Vasoconstriction. *Lixivaptan is considered an OTHER CARDIOVASCULAR DRUGS
Increases water Orphan Drug
Dual endothelin receptor antagonist used in the
reabsorption BOSENTAN treatment of pulmonary artery hypertension;
Central diabetes teratogen; do NOT use in hepatically impaired patients
SIADH, Hyponatremia
insipidus, Nocturnal Stabilizes cell membranes and reduces free
*Conivaptan (parenteral),
Uses enuresis, Hemophilia, radicals, may stimulate release of dopamine
Tolvaptan (oral)
von Willebrand’s neurotransmitters in the brain, by activating the
disease central cholinergic system, may activate the central
Infusion site reactions, CITICOLINE cholinergic system (thus may be useful for Alzheimer
Hyponatremia, Hyperkalemia, Disease; it also increases ACTH. TSH, GH and LH;
Hypertension Nephrogenic diabetes insipidus, proposed for use in traumatic brain injuries, stroke,
Increases the factor Renal failure vascular dementia, Parkinson’s disease, brain aging
SE VIII activity of (lithium, demeclocycline),
An anti-histamine and CCB; promotes cerebral
patients with mild Bone and teeth abnormalities
blood flow (used to treat cerebral apoplexy, post-
hemophilia A or von (demeclocycline),
trauma cerebral symptoms and cerebral
Willebrand disease Increased liver enzymes CINNARIZINE arteriosclerosis). However, it is more commonly
(Tolvaptan)
prescribed for nausea and vomiting due to motion
sickness, chemotherapy, vertigo or Meniere’s disease
DRUGS USED FOR DYSLIPIDEMIA BILE ACID BINDING RESINS

• over 90% of bile acids are reabsorbed and returned to the liver
for reuse (enterohepatic recirculation)
• resins bind bile acids and prevent their intestinal absorption
o divert hepatic cholesterol to synthesis of new bile acids
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; little effect on HDL or TGs
CHOLESTEROL ABSORPTION BLOCKERS: EZETIMIBE
Pathogenesis of Hyperlipoproteinemia
• premature atherosclerosis is strongly associated with elevated • converted in the liver to the active glucuronide form
concentrations of lipoproteins • inhibits NPC1L1 transporter (a specific transport process in
o elevated level of low-density lipoproteins (LDL) jejunal enterocyte) that mediates gastrointestinal uptake of
o depressed level of high-density lipoproteins (HDL) cholesterol and phytosterols
o hypertriglyceridemia • prevents absorption of dietary cholesterol and cholesterol that
• hyperchylomicronemia is associated with a high incidence of is excreted in bile
acute pancreatitis o reduces cholesterol in tightly regulated hepatic pool
o compensatory increase in the synthesis of high-affinity LDL
Treatment Strategies: DIET receptors increases the removal of LDL
• cholesterol and saturated fats are the primary dietary factors
that contribute to elevated plasma lipoproteins NIACIN
• dietary measures constitute the first method of management • multiple mechanisms of actions in various tissues
o may be sufficient to reduce lipoprotein levels to a safe range o inhibits lipolysis by hormone sensitive lipase
• Alcohol raises triglyceride and VLDL levels: should be avoided o in the liver, niacin reduces VLDL synthesis
by patients with hypertriglyceridemia o in adipose tissue, niacin reduces hormone-sensitive lipase
Treatment Strategies: DRUGS activity, decreases plasma fatty acid and triglyceride levels
• drugs most effective at lowering LDL cholesterol o in capillary endothelial cells, niacin causes increased clearance
o statins, resins, ezetimibe, niacin of VLDL by lipoprotein lipase
• drugs most effective at lowering TGs, VLDL and raising HDL o niacin reduces the catabolic rate for HDL
o niacin, fibrates 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
CHOLESTEROL-LOWERING DRUGS
https://qrs.ly/xkcke42 MNEMONIC: Cutaneous Flushing
What are the drugs that cause flushing?
V-A-N-C
Vancomycin Niacin
Adenosine Calcium channel blockers
FIBRATES
• ligands for the peroxisome proliferator-activated receptor-alpha
(PPAR-a) protein
o increased synthesis by adipose tissue of lipoprotein lipase
§ enhances clearance of triglycerides
• in the liver, fibrates stimulate fatty acid oxidation
o limits supply of triglycerides and decreases VLDL synthesis
• decrease expression of apoC-III
o impedes the clearance of VLDL
o increases the expression of apoA-I and apoA-II, which in turn
increases HDL levels
• little or no effect on LDL concentrations
COMBINATION THERAPY
• all patients with hyperlipidemia are treated first with dietary
modification
• certain drug combinations provide advantages whereas others
present specific challenges
STATINS / HMG-COA REDUCTASE INHIBITORS
Antihyperlipidemic Combinations to watch out for!
• inhibition of hepatic cholesterol synthesis contributes a small
Combination Risk
amount to drug effect
Fibrate + Resin Increased risk of cholelithiasis
• greater cholesterol-lowering effect derived from the
Statin + Resin Impaired statin absorption
compensatory response of the liver
o increased number of high-affinity LDL receptors, which clear Statin + Fibrate Increased risk of myopathy, rhabdomyolysis
LDL and VLDL remnants from the blood
• direct anti-atherosclerotic effects: used in management of
coronary artery disease: for stabilization of atherosclerotic plaques
• prevent bone loss
DYSLIPIDEMIA DRUGS
STATINS
FENOFIBRATES (FIBRIC ACID
(HMG-COA REDUCTASE INHIBITOR) BILE ACID BINDING RESINS CHOLESTEROL ABSORPTION INHIBITOR VITAMINS
DERIVATIVE)
(All are Preg Cat X)
Drugs GEMFIBROZIL [C],
SIMVASTATIN, Atorvastatin,
CHOLESTYRAMINE [C], NIACIN [A, C if given in doses Bezafibrate [C]
Rosuvastatin, Fluvastatin, EZETEMIBE [C] SITOSTEROL
Colesevelam [B], Colestipol [C] exceeding RDA] FULL: Fibrates Upregulate
Pravastatin, Lovastatin, Pitavastatin
Lipoprotein Lipase
• Inhibits rate-limiting enzyme in • Binds bile acids, preventing their • Selective inhibitor of the • Cholesterol analog, takes • Decreases catabolism of • Activates PPAR-a and
cholesterol biosynthesis, HMG-CoA reabsorption and increasing NPC1L1 transporter, the place of dietary and apoA-I. Decreases VLDL increases expression of
reductase. Increased hepatic cholesterol utilization for decreasing intestinal biliary cholesterol, synthesis and secretion from lipoprotein lipase and
cholesterol uptake. Increased high- replacement → Upregulates LDL absorption of cholesterol decreasing intestinal the liver. Decreases LDL apolipoproteins (apoA-I, apoA-
affinity LDL receptors. Decreased LDL receptors → Modestly lowers LDL and other phytosterols absorption of cholesterol and cholesterol concentrations. II). Lowers triglycerides.
MOA
levels. Also causes modest reduction levels. Decreases cholesterol other phytosterols. Increases HDL cholesterol Decreases secretion of VLDL.
in triglycerides hepatic pool, increases Increases HDL.
hepatic LDL receptors →
decreases LDL and
phytosterols
Hypercholesterolemia (high LDL), Acute DOC for hypertriglyceridemia,
Hypercholesterolemia (high LDL), Hypercholesterolemia (low
coronary syndromes / Atherosclerotic Hypercholesterolemia (high Hypercholesterolemia (high hypercholesterolemia
Uses Pruritus in cholestasis, HDL,
vascular disease (primary and LDL), Phytosterolemia LDL), Phytosterolemia (low HDL, high LDL), Fat
Digitalis toxicity High LDL/ VLDL)
secondary prevention), Ischemic stroke redistribution syndrome
Flushing, Pruritus, Rashes,
Acanthosis nigricans,
Hepatotoxicity, Myopathy, Constipation, Bloating, Gritty taste, Gastrointestinal upset, Gastrointestinal irritation, Nausea, Rashes, Leukopenia,
Hepatotoxicity (increased
SE Rhabdomyolysis, Gastrointestinal Steatorrhea, Gallstones (rare), Bloating, Impotence (rare), Hepatotoxicity (mild), Hemoconcentration, Increased
with statin use), Myositis
distress, Teratogen Malabsorption (vitamin K) Coronary events Hyperuricemia, Impaired risk of cholesterol gallstones
glucose tolerance, Arrhythmias,
Amblyopia
• Increased risk of myopathy and • Increases TGs and VLDL in • Synergistic LDL-lowering • Aspirin pre-treatment • Increased risk of myopathy
rhabdomyolysis when used with patients with high TGs Treat effect with statins reduces Niacin flushing and rhabdomyolysis when
fibrates constipation with fiber • May be given as • Avoid in patients with peptic used with statins
• Given before bedtime because supplements/psyllium combination therapy with ulcer disease • Avoided in patients with
cholesterol synthesis predominantly “Ang Cholet, Colet, Colet mo! Sabi statins • Potentiates effects of hepatic or renal dysfunction
occurs at night nang you should BAR this from people • Considered a prodrug antihypertensives • May increase LDL in patients
• Simvastatin and lovastatin are with HIGH TGs! Cholestyramine, (vasodilators, ganglion with familial combined
prodrugs, all the rest are in their Colestipol and Colesevelam are Bile blockers) hyperlipoproteinemia
Note active form already Acid Resins (BAR). Don’t use in people • Decreases fibrinogen and • Higher risk of gallstone
• If given together with resins give at with HIGH TGs!” increases t-PA formation if given together
least 1hr before or 4hrs after resin • Interferes with the absorption of with resins
administration (resins decrease the some drugs and vitamins
absorption of statins) • Non-absorbable polymers that
• Has CYP450 dependent metabolism bind bile acids and similar steroids
(Drug levels adversely affected by CYP in the intestines preventing their
inhibitors) reabsorption
INHERITED LIPOPROTEINEMIAS: DRUG MANAGEMENT
TYPE CONDITION CAUSE LIPID PROFILE PRIMARY SECONDARY
TX TX
Increased chylomicrons Niacin
I Primary hyperchylomicronemia Deficiency in LPL or ApoC-II Low-fat diet
Increased triglycerides Fibrate
Increased LDL Niacin
IIA Familial hypercholesterolemia Defect in LDL receptors Statin
Normal VLDL Ezetimibe
Niacin
Increased VLDL Statin
Fibrate
Familial combined Niacin
IIB Overproduction of VLDL Increased LDL Statin
hypercholesterolemia Ezetimibe
Increased VLDL Niacin
Statin
Increased LDL Ezetimibe
Increased VLDL
Fibrate
III Familial dysbetalipoproteinemia Deficiency in ApoE remnants Statin
Niacin
Increased chylomicrons
Increased triglycerides
Fibrate
IV Familial hypertriglyceridemia Decreased clearance of VLDL Increased VLDL
Niacin
Decreased/normal LDL
Increased triglycerides
Familial combined Increased chylomicrons Fibrate
V Decreased clearance of VLDL
hypertriglyceridemia Increased VLDL Niacin
Decreased/normal LDL
DRUGS ON SMOOTH MUSCLES

HISTAMINE, SEROTONIN
AND THE ERGOT ALKALOIDS
HISTAMINE, HISTAMINE,
SEROTONIN SEROTONIN
AND ERGOT PART 1 AND ERGOT PART 2
https://qrs.ly/yccke52 https://qrs.ly/r7cke5g
AUTACOIDS HISTAMINERGIC AGENTS
• endogenous molecules with powerful pharmacologic effects that Histamine
do not fall into traditional autonomic groups • formed from the amino acid histidine, metabolized by the
• histamine and serotonin are the most important amine autacoids enzymes monoamine oxidase and diamine oxidase
SEROTONERGIC AGENTS • important pathophysiologic roles
o seasonal rhinitis (hay fever), urticaria, and angioedema
Serotonin (5 Hydroxytryptamine or 5-HT)
o control of acid secretion in the stomach
• produced from the amino acid tryptophan, metabolized by
Triple Response of Lewis (wheal, flush and flare)
monoamine oxidase
• classic demonstration of histamine effect
• physiologic roles
• mediated mainly by H1 and H2 receptors
o neurotransmitter in CNS and enteric nervous system
o local hormone that modulates gastrointestinal activity • involves a small red spot at the center of an intradermal injection
of histamine surrounded by a red edematous wheal
SEROTONIN RECEPTORS AND EFFECTS
PROTOTYPE HISTAMINE RECEPTORS AND EFFECTS
TYPE LOCATION MECHANISM EFFECTS
ANTAGONIST PROTOTYPE
TYPE LOCATION MECHANISM EFFECTS
Gi, Synaptic ANTAGONIST
5HT1D Brain -
↓cAMP inhibition Pain and
CNS Smooth itching,
excitation, muscle Gq, Diphen- broncho-
H1
smooth ↑IP3, DAG hydramine constriction,
muscle vasodilation,
Smooth
Gq, contraction/ local edema
5HT2 muscle, Ketanserin
↑IP3, DAG relaxation, Stomach,
platelets vasodilation, heart, Gastric acid
diarrhea, mast cells Gs, secretion,
broncho- H2 Cimetidine
↑cAMP cardiac
constriction
stimulation
Area
postrema
Ligand- Nerve
(CNS),
5HT3 gated ion Ondansetron Vomiting endings,
sensory and Gi, Modulation
enteric
channel H3 CNS Clobenpropit
↓cAMP of other NTs
nerves
Presynaptic
Leukocyte Gi, Leukocyte
nerve terminals Tegaserod
Gs, Intestinal H4
5HT4 in enteric (partial ↓cAMP chemotaxis
↑cAMP motility
nervous agonist)
system
H1 RECEPTOR ANTAGONISTS • Some have calcium-channel blocking activity
• Common SE: Sedation • Sedating antihistamines may enhance the sedative effects of CNS
• Should not be given to neonates because they are more susceptible depressants including alcohol, barbiturates, hypnotics, opioid
to antimuscarinic effects analgesics, anxiolytic sedatives, and antipsychotics
• Possess antimuscarinic, adrenaline-antagonising, serotonin • All are PO but can be given topical (nose and eyes)
antagonising, and local anaesthetic effects. • Negligible effect on H2 receptors
HISTAMINERGIC DRUGS
H1-RECEPTOR ANTAGONISTS H1-RECEPTOR ANTAGONISTS
H2-RECEPTOR ANTAGONISTS
(FIRST GENERATION) (SECOND GENERATION)
DIPHENHYDRAMINE [B], BROMPHENIRAMINE [C], CETIRIZINE [B], Levocetirizine [B],
Drugs CIMETIDINE [B],
Chlorpheniramine [B], CYCLIZINE [B], Meclizine [B], LORATADINE [B], Desloratadine [C],
Ranitidine [B],
Buclizine [C], Carbinoxamine [C], Dimenhydrinate [B], FEXOFENADINE [C], Terfenadine [C],
Famotidine [B],
HYDROXYZINE [C], Promethazine [C], ASTEMIZOLE [C], Azelastine [C],
Nizatidine [C]
CYPROHEPTADINE [B], Clemastine [B], Tripelennamine [B] Ebastine, Bilastine, Rupatadine [B]
Competitive pharmacologic block of
Competitive pharmacologic block of peripheral and CNS
peripheral H1 receptors. Competitive pharmacologic
MOA H1 receptors plus a- and M-receptor block.
No autonomic or anti-motion block of H2 receptors
Anti-motion sickness effect.
sickness effects.
Hay fever, Angioedema, Motion sickness, Insomnia, Dystonia,
Anti-emetic (Promethazine), for Serotonin Syndrome Peptic ulcer disease,
Uses (Cyproheptadine); Dimenhydrinate used for nausea, vomiting Hay fever, Angioedema, Urticaria Zollinger-Ellison syndrome,
and dizziness caused by motion sickness; Gastroesophageal reflux
Cyclizine used to motion sickness
CYP450 inhibitor and
None antiandrogen effects
Drowsiness, Blurred vision, Dry mouth, Urinary retention, Second generation antihistamines do like gynecomastia
SE
Anorexia, Orthostatic hypotension not cross the blood brain barrier, their (cimetidine only),
sole indication is for allergy. Decreased hepatic flow
(cimetidine)
• More likely to block autonomic receptors, also has a1
• Fatal arrhythmias from • Reduction of nocturnal acid
blocking and local anesthetic effect
interaction between secretion in gastric and
Notes azoles/erythromycin and duodenal ulcer, accelerate
If a drug contains PHEN on its name it is lipid soluble. Examples
Terfenadine/Astemizole healing and prevent
acetaminophen, phenytoin, chloramphenicol. These can cross the
blood brain barrier
• No sedation, antimuscarinic effects recurrences
ERGOT ALKALOIDS PROSTAGLANDINS AND OTHER EICOSANOIDS

Ergot Alkaloids
• complex molecules are produced by a fungus found in wet or
spoiled grain
o responsible for the epidemics of "St. Anthony's fire"
(ergotism) described during the Middle Ages
• most are partial agonists at alpha receptors and 5HT receptors
but some are potent agonist at dopamine receptors EICOSANOIDS
• Classification
o VASOSELECTIVE • important group of endogenous fatty acid derivatives that are
o UTEROSELECTIVE produced from arachidonic acid
• major families of eicosanoids include
SUPPLEMENT: DRUGS USED FOR VERTIGO o straight-chain derivatives (leukotrienes)
o cyclic derivatives (prostacyclin, prostaglandins, and
Strong antagonist of H3 receptor (leads to
increased levels of neurotransmitters histamine,
thromboxane)
acetylcholine, norepinephrine, serotonin and
GABA) and a weak agonist of H1 receptor (causes Cyclooxygenase Isoforms
BETAHISTINE
local vasodilation and increased permeability in • CYCLOOXYGENASE-1 (COX-1)
the inner ear); used for balance disorders or to o found in many tissues
alleviate vertigo symptoms associated with o important for a variety of normal physiologic processes
Meniere’s disease
• CYCLOOXYGENASE-2 (COX-2)
An anti-histamine and CCB; promotes cerebral
o found primarily in inflammatory cells
blood flow (used to treat cerebral apoplexy, post-
trauma cerebral symptoms and cerebral o major role in tissue injury (e.g. inflammation)
CINNARIZINE o synthesis of prostacyclin in the vascular endothelium and of
arteriosclerosis); more commonly prescribed for
nausea and vomiting due to motion sickness, prostaglandins important in renal function
chemotherapy, vertigo or Meniere’s disease
SUPPLEMENT: DRUGS USED FOR MIGRAINE

Selective Calcium Entry blocker with calmodulin
binding properties and H1 antagonistic activity;
FLUNARIZINE effective in the prophylaxis of migraine,
occlusive peripheral vascular disease, vertigo,
and as adjuvant for epilepsy
SEROTONERGIC DRUGS AND ERGOT ALKALOIDS
Ergot Alkaloids
5-HT1D-RECEPTOR 5-HT3-RECEPTOR 5-HT2-RECEPTOR
AGONIST ANTAGONIST ANTAGONIST 5-HT2-RECEPTOR ANTAGONIST
All are Preg Cat C All are Preg Cat B (VASOSELECTIVE) (UTEROSELECTIVE)
Drugs All are Preg Cat X
SUMATRIPTAN,
ONDANSETRON, ERGOTAMINE,
Almotriptan, Eletriptan, ERGONOVINE [C],
Granisetron, Dolasetron, Dihydroergotamine,
Frovatriptan, Naratriptan, Methylergonovine [C]
Palonosetron, Alosetron METHYLSERGIDE
Rizatriptan, Zolmitriptan
5-HT1D agonist. Pharmacologic antagonist of Partial agonist at a and 5-HT2
Partial agonist at a and 5-HT2
Causes vasoconstriction. 5-HT3 receptors in the receptors, some have potent
MOA receptors, some have potent agonist
Modulates chemoreceptor trigger zone agonist effect at Dopamine
effect at Dopamine receptors
neurotransmitter release. and enteric nervous system receptors
Chemotherapy and
DOC for acute migraine, postoperative vomiting,
Uses Migraine, Cluster headache Postpartum bleeding, Migraine
Cluster headache Irritable bowel disease
(Alosetron only)
Diarrhea, Headache, Gastrointestinal upset,
Paresthesia, Dizziness,
Malaise, Vasospasm, Gangrene, Gastrointestinal upset
Chest pain,
SE QRS and QT prolongation Uterine spasm, (Nausea, Vomiting, Diarrhea),
Coronary vasospasm,
(Dolasetron only), Retroperitoneal fibrosis Uterine spasm, Abortion
Injection site reaction
Constipation (Alosetron only) (methylsergide only)
• All are per orem only • The uterus becomes more sensitive
except for Sumatriptan to ergots during pregnancy,
which can also be given produce very powerful and long-
intranasally, transdermal lasting contraction leading to
Notes and IV (Sumatriptan has decreased bleeding
the shortest DOA of Never give before delivery of placenta
2-4hrs) • Methylergometrine/ Methylergobasin
(another name of Methylergonovine) is
a homolog of ergonovine
PROSTAGLANDIN DRUGS
PROSTAGLANDIN E2 PROSTAGLANDIN F2a ANALOG PROSTAGLANDIN I2
PROSTAGLANDIN E1 ANALOG
ANALOG (All are Preg Cat C) ANALOG
Drugs ALPROSTADIL [C] CARBOPROST, LATANOPROST,
EPOPROSTENOL [B],
MISOPROSTOL [X], “E1 (Iwan) mong DINOPROSTONE [C], Bimatoprost, Bimatoprost,
Beratoprost, Iloprost [C],
GEMEPROST [B] bukas ang Sulprostone Travoprost, Travoprost,
Treprostinil [B]
Ductus Arteriosus” Unoprostone Unoprostone
Low concentrations
Activates FP
Activates EP Activates EP contract, higher
receptors. Activates IP
receptors. Causes receptors, concentrations relax
Increases outflow receptors. Causes
increased HCO3- and causes vascular uterine and cervical Activates FP
MOA of aqueous humor, vasodilation.
mucus secretion in smooth muscle smooth muscle, receptors
reduces Reduces platelet
stomach. Uterine relaxation and soften cervix at term
intraocular aggregation
contraction vasodilation before induction
pressure
with oxytocin
Maintenance of
patent ductus
arteriosus Control of
Peptic Ulcer Disease, Pulmonary
(PDA), Erectile postpartum
Prevention of Induction of labor hypertension,
dysfunction hemorrhage, for
Uses NSAID-induced (Cervical ripening), Glaucoma Reduces platelet
Prostaglandin refractory
gastric mucosal Abortifacient aggregation in
to keep PDA postpartum bleeding,
injury, abortifacient dialysis machines
Patent, abortifacient
Indomethacin
to close
Abdominal pain,
Apnea,
Diarrhea, Uterine Alters color of the
Hypotension, Vomiting, diarrhea,
cramping, Cramping, Fetal iris, causing Hypotension,
SE Arrhythmia, transient
Miscarriage, trauma permanent eye Flushing, Headache
Priapism, bronchoconstriction
Teratogenic effect color change
Lightheadedness
(Moebius sequence)
• Misoprostol's • Given as • Approved • May cause
intended use is for injection into abortifacient in the vomiting,
NSAID-induced the cavernosa 2nd trimester diarrhea,
gastritis for erectile • Although effective transient
Notes • May also be used dysfunction in inducing labor, broncho-
together with it produces more constriction if
Mifepristone or SE than other given
Methotrexate as oxytocics systemically
safe abortifacient
PROSTAGLANDIN
AND EICOSANOIDS
https://qrs.ly/ubcke5k
Strategies of Asthma Therapy
• acute attacks of bronchospasm (relievers)
o use bronchodilators or relievers
o short-acting b2 agonists
o muscarinic antagonists
o methylxanthines
o intravenous corticosteroids
• long-term prevention and prophylaxis (controllers)
o use anti-inflammatory drugs or controllers
o corticosteroids
o long-acting b2 agonists
o mast cell stabilizers
o anti-IgE, IL5, IL5R, IL4R antibodies
o leukotriene antagonists
MECHANISM OF ACTION OF ASTHMA DRUGS

EFFECTS OF IMPORTANT EICOSANOIDS

G-
Eicosanoid Effects
Prot
LTB4 Gq Leukocyte chemotaxis
LTC4 Gq Bronchoconstriction, slow-reacting
LTD4 Gq, Gi substance of anaphylaxis
Vascular smooth muscle relaxation,
PGE1 Gs, Gq protective effects on gastric mucosa,
maintains PDA
Vascular smooth muscle relaxation,
PGE2 Gs, Gq
maintains PDA, increases uterine tone
Vascular smooth muscle relaxation
PGI2 Gs
(peripheral, pulmonary, coronary)
PGF2! Gq Increases uterine tone, decreases IOP
TXA2 Gq Platelet aggregation
OTHER DRUGS USED FOR ERECTILE

SUPPLEMENT:
DYSFUNCTION
Drugs SILDENAFIL [B], TADALAFIL [B], VARDENAFIL [B]

Class Phosphodiesterase 5 inhibitor
Inhibits PDE5 which degrades cGMP to inactive GMP →
MOA
vasodilation
Erectile dysfunction, Pulmonary Arterial Hypertension,
Uses
Raynaud’s Phenomenon
Headache, flushing, priapism, hearing loss, optic
SE
neuropathy
Do not take with Nitrates (ISDN, ISMN, NTG) because it
Notes
may lead to fatal hypotension
BRONCHODILATORS AND
OTHER DRUGS USED IN ASTHMA
NEW ASTHMA DRUGS: BIOLOGIC ANTIBODIES

• biological agents that interfere in different steps of the TH2
inflammatory cascade and are licensed in severe asthma
DRUGS USED IN ASTHMA

https://qrs.ly/mrcke63
Source: Benralizumab: A unique IL-5 inhibitor for severe asthma. Tan et al., 2016
ASTHMA Anti-IL5 and anti-IL5R (All are given SC)

• characterized by airway inflammation and episodic, reversible • Mepolizumab: anti-IL5, given SC to > 6 years old
bronchospasm • Reslizumab: anti-IL5, given IV to > 18 years old
• Major risk factor of asthma: atopy o Acts by neutralizing effects and blocking activation of
eosinophils by IL5
Pathophysiology of Asthma • Benralizumab: anti-IL5 receptor, given SC to >12 years old
• bronchoconstriction caused by release of several mediators o Targets the effector cells itself circulating and tissue eosinophils)
from IgE-sensitized mast cells Anti-IL4R
• chemotactic mediators attract inflammatory cells to the • Dupilumab: anti-IL4 receptor, given SC to >12 years old
airways, leading to chronic inflammation o binds to the α-subunit of the IL-4 receptor, with resulting
blockage of both the IL-4 and IL-13 pathways
ASTHMA DRUGS
MUSCARINIC
B2-SELECTIVE AGONIST B2-SELECTIVE AGONIST
RECEPTOR METHYLXANTHINES MAST CELL STABILIZERS
(SHORT-ACTING) (LONG-ACTING)
ANTAGONISTS
SALBUTAMOL [C] SALMETEROL,
Drugs (Albuterol), Formoterol, Clenbuterol,
IPRATROPIUM [B], THEOPHYLLINE [C], CROMOLYN,
Levalbuterol [C], Bambuterol,
Tiotropium [C], Aminophylline [C], Nedocromil,
Terbutaline [C], Arformoterol,
Umeclidinium [C], Pentoxifylline [C], LODOXAMIDE
Metaproterenol [C], Vilanterol, Indacaterol,
Glycoyrronium [B] Doxofylline [B] All are Preg Cat B
Pirbuterol [C], Procaterol [C], Olodaterol
Fenoterol [B], Bitolterol [C] All are Preg Cat C
Blocks muscarinic Prevents calcium influx
Phosphodiesterase
receptors in bronchial and stabilizes mast cells →
Activates B2-receptors in bronchial smooth muscle. inhibition &
smooth muscle. preventing degranulation
MOA Causes bronchodilation. Adenosine receptor
Prevents vagal- and release of histamine,
Potentiation of corticosteroid action. antagonist à
stimulated leukotrienes and other
bronchodilation
bronchoconstriction mediators
Acute Asthma, COPD
Glycopyrronium may
be used as a Asthma (prophylactic
Asthma prophylaxis Asthma prophylaxis,
monotherapy as against nocturnal attacks)
Acute asthma attacks (not for acute relief). Allergies (ophthalmic,
Uses maintenance for Intermittent
(drug of choice) Given together with nasopharyngeal,
COPD, also used as claudication
ICS gastrointestinal)
anti-spasmodic and (pentoxifylline only)
reduce salivation with
some anesthetics
CNS stimulation
(Insomnia, seizure,
Dry mouth, blurred
Tachycardia, Tremors, Nervousness, Restlessness, Anorexia), Cardiac Cough, Airway irritation
vision etc.
SE Arrhythmias when used excessively, Loss of stimulation Not normally used because
(Anti-cholinergic
responsiveness (tolerance, tachyphylaxis) (Arrhythmias), Tremors, may induce cough
effects)
increased BP, diuresis,
increased GI motility
• May precipitate • Increase asthma • Less toxic than B- • Antidote in overdosage • No bronchodilator
arrhythmias in patient mortality when agonists in is Beta blockers action but can prevent
with concurrent COPD used alone; patients with • Higher clearance in bronchoconstriction
and heart disease • Usual DOA: 12hrs COPD adolescents and smokers caused by antigens
• Usual DOA: 2-4hrs • Vilanterol, Indacaterol • Tiotropium and • Narrow therapeutic (both in the early and
Notes • All are given inhalational, and Olodaterol are Umeclidinium have window late BA responses)
Salbutamol, terbutaline Ultra Long-acting longer DOA than • Causes bronchodilation • May be given as
are also available PO LABAs. They have a Ipratropium and increased strength ophthalmic solution for
• Terbutaline can also be 24-hour activity for of contraction of allergic conjunctivitis
given IV (especially as once daily treatment diaphragm • May be given (Off-label)
tocolytic) for COPD and Asthma for Food allergy and IBD
CORTICOSTEROIDS LEUKOTRIENE SYNTHESIS LEUKOTRIENE Anti-IgE ANTIBODIES
INHIBITOR RECEPTOR ANTAGONIST
FLUTICASONE [C], Beclomethasone [C], ZILEUTON [C] MONTELUKAST, OMALIZUMAB [B]
Drugs
BUDESONIDE [B], Ciclesonide [C], Zafirlukast, Pranlukast
Flunisolide [C], Mometasone [C], All are Preg Cat B
Triamcinolone [C]
Inhibit synthesis of arachidonic acid by
inhibiting Phospholipase A2, reduces Blocks cysteinyl Binds IgE antibodies on
expression of COX and LT, increases Inhibitor of 5-lipoxygenase. leukotriene-1 receptor for sensitized mast cells.
responsiveness of Beta receptors in the Reduces synthesis of leukotrienes Reduces reaction to inhaled
MOA airway, bind to intracellular receptors leukotrienes. C4, D4 and E4. antigen.
and activate Glucocorticoid response Prevents airway inflammation Prevents airway Prevents activation by BA
elements in the nucleus leading to and bronchoconstriction. inflammation and triggers and subsequent release
synthesis of substances that prevent full bronchoconstriction. of inflammatory mediators
expression of inflammation and allergy
Asthma prophylaxis
(drug of choice), COPD,
Allergic rhinitis, first line treatment Asthma prophylaxis Asthma prophylaxis,
Prophylaxis of severe,
for moderate to severe BA, COPD, Exercise-, Antigen- and Exercise-, Antigen- and
Uses refractory asthma not
also used as anti-inflammatory for Aspirin-induced Aspirin-induced
responsive to all other drugs
other conditions such as bronchospasm bronchospasm
autoimmune diseases and cancer,
also for immune suppression
Flulike syndrome, Headache,
Drowsiness, Dyspepsia, Hepatitis, Fever, Angioedema,
Oropharyngeal candidiasis Gastrointestinal upset,
Elevation of liver enzymes Anaphylactic reactions,
(Advise to gargle every after use), Insomnia,
Idiopathic severe
SE Minimal systemic steroid toxicity Similar side effects with Neuropsychiatric effects,
thrombocytopenia,
(e.g. adrenal suppression), LTRA, but also associated Churg-Strauss
nasopharyngitis,
Mild growth retardation with transaminitis. So need syndrome (rare)
upper abdominal pain
to monitor liver profile
• For status asthmaticus: use IV • No bronchodilator actions • No bronchodilator • Humanized murine
prednisolone or hydrocortisone • Not recommended for acute actions monoclonal antibody, very
• Prednisolone is the active BA attack • Not recommended for expensive
Notes
metabolite of prednisone acute BA attack
• Ciclesonide has lowest systemic
steroid toxicity
DRUGS FOR COUGH

• includes mucolytics, expectorants and antitussives
MUCOLYTICS
• involves reducing disulfide bridges, to allow mucus lysis
N-ACETYLCYSTEINE [B], Carbocisteine [C],
Drugs
Ambroxol [C], Bromhexine [A], Erdosteine
decrease sputum activity ; Usually derivatives of
cysteine; reduce disulfide bridges that bind
MOA
glycoproteins to other proteins such as albumin; Also
act as antioxidants & may reduce airway inflammation
Uses Cough (available as IV, PO, IM and inhalational forms)
Chest tightness, Disagreeable odor, Drowsiness, EXPECTORANT
Fever, Hemoptysis, Increased volume of bronchial Drug GUAIFENESIN [C]
SE
secretions, Irritation of tracheal or bronchial tract, may act as an irritant to gastric vagal receptors, and
Nausea, Rhinorrhea, Stomatitis, Vomiting MOA recruit efferent parasympathetic reflexes that cause
Orally available drugs are well-tolerated; but of little glandular exocytosis of a less viscous mucus mixture
Notes
benefit in acute respiratory condition Uses Cough
• N-acetylcysteine is also used in the management of Drowsiness, Incomplete or Infrequent Bowel
acetaminophen toxicity to prevent fulminant hepatitis Movements, Inducing of a Relaxed Easy State, Stomach
SE
o NAC converts back the oxidized glutathione to the reduced form of Cramps, dizziness or headache, a rash, or. nausea,
glutathione that works as antioxidant to counteract the reactive vomiting, or stomach upset
metabolite of acetaminophen known as NAPQ1 (free radical) 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
CENTRALLY ACTING (OPIOID) CENTRALLY ACTING (NON-OPIOID) PERIPHERALLY ACTING
Drugs
DEXTROMETHORPHAN [C], Codeine [C] BUTAMIRATE CITRATE [C] LEVODROPROPIZINE [D]
Non-opioid drug with a peripheral
decreased sensitivity of the medullary/ CNS
act through receptors in the action by inhibiting the afferent
MOA cough centers to peripheral stimuli and
brainstem to inhibit cough pathways that generate the cough reflex
decreased mucosal secretion
(modulates C-fiber activity)
Uses Cough Cough Cough
Decreases secretions in the bronchioles, thickens Nausea, vomiting, heartburn, diarrhea,
Somnolence, nausea, vomiting,
SE sputum & inhibits ciliary activity, reducing fatigue, weakness, drowsiness,
diarrhea, dizziness and hypotension
clearance of thickened sputum, Constipation dizziness, headache, palpitations
• Morphine may be effective but indicated only in • Centrally acting antitussive but is • Does not cause side effects such as
intractable cough from bronchial carcinoma neither chemically or constipation or respiratory depression
Notes • Dextromethorphan has no addictive potential, pharmacologically related to which can be produced by opioid
no analgesic effect, produces less constipation opioids antitussive
and inhibition of mucociliary clearance
o bound to Ferritin, a storage protein
o children and pregnant women have increased iron requirements
ANTITUSSIVES Types of Vitamin deficient Anemias
https://qrs.ly/vqckedm • microcytic hypochromic anemia caused by iron deficiency is the
most common type of anemia
o Laboratory picture: ↓ Iron, ↓ Ferritin, ↑ TIBC
• megaloblastic anemias are caused by a deficiency of vitamin B12
SUPPLEMENT: OTHER DRUGS USED FOR COUGH or folic acid
LAGUNDI (VITEX NEGUNDO) o pernicious anemia is the most common type
• Inhibits PDE III and inhibits Ca2+ entry (acts as CCB), which partly § caused by a defect in the synthesis of intrinsic factor or by surgical
explain its bronchodilatory effect removal of that part of the stomach that secretes intrinsic factor
• Considered a potent anti-inflammatory agent and acts via inhibition
of COX2 without much interfering COX1 pathways HEMATOPOIETIC GROWTH FACTORS (IRON)
• traditionally used in hyperactive respiratory disorder, has medicinal oral: FERROUS SULFATE, Ferrous gluconate,
importance in asthma Ferrous fumarate, Ferrous carbonate
Drugs parenteral: IRON DEXTRAN, Iron sucrose,
AGENTS USED IN ANEMIAS AND Sodium ferric gluconate complex
All are Preg Cat A
HEMATOPOIETIC GROWTH FACTORS Required for the biosynthesis of heme and heme-containing
MOA
proteins, including hemoglobin and myoglobin
Iron deficiency anemia, Iron supplementation
Uses The best way to give iron is through oral preparation
added with ascorbic acid for better absorption.
Black stools (may obscure acute GI loss)
Acute overdose: necrotizing gastroenteritis, abdominal
SE pain, bloody diarrhea, shock, lethargy, dyspnea
Chronic iron overload: hemochromatosis, organ failure
(heart, liver, pancreas etc.), death
Iron content of some oral Iron preparations (% w/w)
Fe carbonate / Carbonyl Iron 100%
IRON Fe fumarate 33%
IRON Fe sulfate, dried 30%
• essential metallic component of heme Fe sulfate, hydrated 20%
• distribution of iron in the body Ferric ammonium sulfate 18%
o mostly contained in hemoglobin Fe gluconate 12%
o bound to Transferrin, a transport protein
IRON CHELATORS
IRON INTOXICATION
Acute Iron Intoxication
• usually occurs as a result of accidental ingestion of iron
supplementation tablets, commonly in children
• 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
Chronic Iron Intoxication: Hemochromatosis
• state of chronic iron overload that damages the organs that store
excess iron (heart, liver, pancreas)
• Triad: CIRRHOSIS, DIABETES MELLITUS, SKIN PIGMENTATION HEMATOPOIETIC GROWTH FACTOR (FOLATE AND VITAMIN B12)
• OCCURRENCE VITAMIN B9 VITAMIN B12
o persons with an inherited abnormality of iron absorption FOLIC ACID, Folacin
CYANOCOBALAMIN,
o persons who receive frequent transfusions for treatment of Drugs (Pteroylglutamic acid),
Hydroxocobalamin,
hemolytic disorders (e.g. thalassemia major) Folinic acid (Leucovorin),
Methylcobalamin
• TREATMENT L-methylfolate
o Phlebotomy Cofactor required for
o chronic administration of DEFEROXAMINE or DEFERASIROX essential enzymatic
Precursor of an essential
HEAVY METAL CHELATORS reactions that form
donor of methyl groups
DEFEROXAMINE [C], tetrahydrofolate,
Drugs MOA used for synthesis of
DEFERASIROX [B], DEFERIPRONE [D] convert homocysteine
amino acids, purines, and
MOA Chelates excess iron to methionine, and
deoxynucleotide.
Acute iron poisoning, Hemochromatosis not adequately metabolize
Uses treated by phlebotomy methylmalonyl-CoA
Hypotension, ARDS, Neurotoxicity, Increased Megaloblastic anemia,
Vitamin B12 deficiency,
SE susceptibility to infections Prevention of neural tube
Megaloblastic anemia
Uses defects (spina bifida),
Deferoxamine is used for acute intoxication (IV form), while (pernicious anemia,
Notes Prevention of coronary
Deferasirox and Deferiprone are for chronic (Oral) gastric resection)
artery disease
SE No significant toxicity No significant toxicity
VITAMINS (FOLATE AND B12) • Folic acid is not toxic in • Parenteral form is
FOLATE overdose but large required for
• required for normal DNA synthesis amounts can partially pernicious anemia
Pharmacokinetics compensate for Vit B12 and other
• readily absorbed by the proximal jejunum deficiency malabsorption
• only modest amounts are stored in the body • May put people with syndrome
• decrease in dietary intake within 1-6 months is followed by Notes unrecognized B12 • Hydroxocobalamin
megaloblastic anemia deficiency at risk of has a longer t½ than
Folic acid deficiency neurologic cyanocobalamin
• deficiency usually presents as megaloblastic anemia consequences of Vit B12 • Has a storage of up to
• deficiency of folic acid during pregnancy increases the risk of deficiency (which are 5yrs in the liver
neural tube defects in the fetus not compensated by
folic acid)
VITAMIN B12
• deficiency of either vitamin B12 or folic acid usually manifests as ERYTHRYOPOIESIS-STIMULATING AGENTS
megaloblastic anemia ERYTHROPOIETIN
• vitamin B12 deficiency (NOT folic acid deficiency) causes • produced in the kidney (reduced EPO synthesis in renal failure)
neurologic defects • main stimulus: Hypoxia-inducible factor 1
o Ataxic gait, impaired position and vibratory sense, spasticity • stimulates the differentiation and maturation of erythroid
• absorbed in the distal ileum in the presence of intrinsic factor progenitor cells within the bone marrow
• stored in the liver in large amounts (5-year supply) • Erythropoiesis-stimulating agents: routinely used for anemia
• 2 available forms: cyanocobalamin and hydroxocobalamin associated with renal failure
• linked to folic acid metabolism and synthesis of
deoxythymidylate (dTMP), a precursor required for DNA EPOETIN ALFA, Darbepoetin Alfa,
synthesis Drugs Methoxy Polyethylene Glycol – Epoetin Beta
Vitamin B12 Deficiency All are Preg Cat C
• administration of folic acid to patients with vitamin B12 Agonist of erythropoietin receptors expressed by red
MOA
deficiency helps refill the tetrahydrofolate pool and partially or cell progenitors
fully corrects the anemia Anemia especially associated with chronic renal
• exogenous folic acid does not correct the neurologic defects of Uses
failure, HIV infection, cancer, and prematurity, for
vitamin B12 deficiency prevention of the need for transfusion in patients
undergoing certain types of elective surgery.
• Tetrahydrofolate (THF) functions to transport single carbon SE Hypertension, Thrombosis, Pure red cell aplasia
groups, for the synthesis of DNA and other biological molecules • Hemoglobin levels should be maintained <12 g/dL
• Vitamin B12 is linked to the Folate cycle • Performance-enhancing drug in athletes
o needed for methionine synthase enzyme (involved in (prohibited use)
Notes
remethylation of homocysteine) • Darbepoetin is once a week administration, while
Methoxy Polyethylene Glycol- Epoetin Beta is 1-2x
per month administration
MYELOID GROWTH FACTORS Mechanisms of hemostasis:

MYELOID GROWTH FACTORS 1. Vasoconstriction
FILGRASTIM (G-CSF), 2. Platelet plug formation
Drugs Sargramostim (GM-CSF) [C], 3. Formation of clot via blood coagulation
Pegfilgrastim [C], Plerixafor [D], Lenograstim [C] 4. Fibrous Organization
Binds receptors on myeloid progenitors and stimulates
MOA cell maturation and proliferation. Accelerates neutrophil
recovery and reduces incidence of infection.
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
PLATELET GROWTH FACTORS

THROMBOPOIETIN
• glycoprotein made primarily in the liver that stimulates the
formation of megakaryocytes
MEGAKARYOCYTE GROWTH FACTOR

OPRELVEKIN (IL-11) [C],
Drugs Figure 37-1. Hall JE. Guyton and Hall Textbook of Medical Physiology. 13th ed. 2016
Thrombopoietin [C], Eltrombopag [C], Romiplastim [C]
1st step: Vasoconstriction:
Recombinant form of an endogenous cytokine; activates
MOA • Local autacoid factors from traumatized tissues and platelets
IL-11 receptors.
o Thromboxane A2 (TXA2): platelet activator and powerful
Secondary prevention of thrombocytopenia in patients
Uses undergoing cytotoxic chemotherapy for non-myeloid
vasoconstrictor
cancers o Endothelin: a potent endothelium derived vasoconstrictor
Fatigue, Headache, Dizziness, Anemia, Fluid • Local myogenic spasm
SE • Nervous reflexes
accumulation in the lungs, Transient atrial arrhythmias
Notes given SC OD
2nd step: Platelet plug formation (primary hemostasis)
SUPPLEMENT: OTHER DRUGS FOR HEMATOLOGIC DISORDERS • Exposed subendothelial collagen is highly thrombogenic
Small-molecule thrombopoietin (TPO)- • Platelet adhesion
receptor agonist that interacts with human o mediated by vWF (essential for binding subendothelial
TPO receptor -> initiates signaling cascades collagen to platelets) by GpIb receptor in the platelet
that induce proliferation & differentiation of surface
megakaryocytes from bone marrow • Platelet release reaction
progenitor cells
o Adenosine diphosphate (ADP): platelet aggregation
ELTROMBOPAG
Use: Indicated for treatment of o Thromboxane A2 (TXA2): platelet activator and powerful
thrombocytopenia in adults and pediatric vasoconstrictor
patients ≥6 yr with chronic immune o Serotonin: platelet aggregation and vasoconstriction
(idiopathic) thrombocytopenia (ITP) with • Platelet aggregation → platelet plug
insufficient response to corticosteroids,
immunoglobulins, or splenectomy 3rd step: Formation of clot via coagulation
• 2 coagulation pathways
DRUGS USED IN COAGULATION DISORDERS o intrinsic pathway: PTT Factor V, VIII, IX,X,XI, XII,
prothrombin, Fibrinogen
o extrinsic pathway: PT V,VII, X, prothrombin, fibrinogen
• net result of coagulation pathways: prothrombin activator
(rate limiting factor causing blood coagulation)
4th step: fibrous Organization

• Fibrin mesh stabilize your platelet plug
ANTIPLATELET DRUGS
• Arterial thrombosis is the most common cause of acute
myocardial infarction (MI), ischemic stroke, and limb gangrene
• Predominance of platelets in arterial thrombi
ANTIPLATELET DRUGS
ANTI-INFLAMMATORY, COX INH GPIIB/IIIA INHIBITOR ADP INHIBITOR PDE INHIBITOR
ASPIRIN (Acetylsalicylic acid, ASA) ABCIXIMAB [C], CLOPIDOGREL [B],
Drugs DIPYRIDAMOLE [B],
[C, D in 3rd trim], EPTIFIBATIDE [B], Ticlopidine, [B]
CILOSTAZOL [C]
Salsalate [C], Sodium salicylate TIROFIBAN [B] Prasugrel [B], Ticagrelor [C]
Nonselective, irreversible COX Inhibits phosphodiesterase III
Inhibits platelet aggregation
1&2 inhibitor. Reduces platelet Irreversibly inhibits binding of and increases cAMP in platelets
by interfering with
MOA production of thromboxane A2, a ADP to platelet receptors, and blood vessels. Inhibits
GPIIb/IIIa binding to
potent stimulator of platelet reducing platelet aggregation platelet aggregation and causes
fibrinogen and other ligands
aggregation. vasodilation.
Prevention and treatment of
arterial thrombosis (stroke, TIA, Prevention of thromboembolic
Used during PCI to
Prevention of arterial thrombosis unstable angina), complications of cardiac valve
prevent thrombosis,
(MI, TIA, CVD), Prevention of restenosis after replacement,
Adjunct to thrombolysis,
Inflammatory disorders PCI, Acute coronary syndromes Secondary prevention of
Uses Acute Coronary
(rheumatic fever, As part of the ACS regimen, a ischemic stroke (with aspirin),
Syndromes
Kawasaki disease, loading dose of 300mg Cilostazol used only in refractory
(unstable angina,
juvenile rheumatoid arthritis) Clopidogrel can reduce platelet intermittent claudication in
NSTEMI)
activity by 80% within 5hrs of patients with PAD.
administration.
Gastrointestinal toxicity,
Bleeding, Nausea, Dyspepsia,
Tinnitus, Hypersensitivity,
Hematologic Headache
Hyperventilation, HAGMA, Bleeding,
SE (neutropenia, leukopenia), (because it is a vasodilator),
Increased bleeding time, Thrombocytopenia
Thrombotic thrombocytopenic Palpitations
Nephrotoxicity (AKI and
purpura (Ticlopidine)
Interstitial Nephritis)
• Associated with Reye syndrome • Prevents vessel • GI & Hematologic SE are more • Dipyridamole, by itself, has little
in children restenosis, reinfarction common with ticlopidine or no benefit
• Do not use as NSAID for gout and death • Additive effects with aspirin • Additional MOA: inhibit uptake of
• SAMTER TRIAD: Asthma, ASA • TICAGRELOR specifically inhibits adenosine by endothelial cells
Notes
Sensitivity, Nasal Polyps ADP subtype P2Y. IN contrast to and RBC → increasing adenosine
another antiplatelet drug, it has a levels → inhibition of platelet
binding site different from ADP, aggregation; Cilostazol is
making it an allosteric antagonist contraindicated in heart failure
ASPIRIN TOXICITY HEPARIN-INDUCED THROMBOCYTOPENIA
• Toxic dose = 150 mg/kg Lethal dose = 500 mg/kg • HIT happens in 15% of patients
• Clinical presentation: HAGMA, dehydration, hyperthermia, • Pathogenesis involves opsonization of the heparin-platelet
collapse, coma complex. In immunology, large molecules are immunogenic.
o Acid Base Disorder: Respiratory alkalosis with HAGMA Large molecules like heparin are immunogenic, leading to its
§ increased respiratory drive leads to hyperventilation and own phagocytosis and a decrease number of platelet.
respiratory alkalosis • The key here is to replace heparin with a Low molecular weight
§ uncoupling of oxidative phosphorylation leads to increased heparin just like Fondaparinux or a Direct Thrombin
anaerobic metabolism via lactic acidosis and high-anion gap Inhibitor like Lepirudin.
metabolic acidosis WARFARIN
• TREATMENT
• inhibits Vitamin K epoxide reductase (which is responsible for
o no specific antidote
carboxylation reactions to activate the clotting factors II, VII, IX,
o supportive management
X, Protein C and S)
o activated charcoal / gastric lavage
o alkalinize the urine with bicarbonate
ANTICOAGULANTS
• mainly for the prevention and treatment of venous thrombosis
(pulmonary embolism, deep vein thrombosis)
HEPARIN-WARFARIN OVERLAP
• drugs which inhibit the formation of fibrin clots
• In patients requiring anticoagulation, why is an overlap between heparin
• 2 major types of anticoagulants: and warfarin usually done?
o indirect thrombin inhibitors: heparin, enoxaparin (LMWH), • Heparin rapidly inhibits the already activated factors, while
coumarin derivatives (warfarin), Warfarin inhibits the activation process of the clotting
o direct thrombin inhibitors: Lepirudin factors X, IX, VII and also inhibits Protein C and S (effect on
COMPARISON OF HEPARIN AND WARFARIN Protein C and S is faster). Protein C and S are anti-clotting.
PROPERTY HEPARINS WARFARIN o The initial inhibition of Protein C and S ultimately results in a
Large acidic temporary proclotting state.
Structure Small lipid-soluble molecule
polysaccharide
Route Parenteral Oral
• Warfarin-Skin Necrosis: due to
Site of Action Blood Liver
initial pro-clotting effect of warfarin
Onset Rapid (minutes) Slow (days)
o Blood clots block the blood vessels
Activates Impairs post-translational and cause necrosis, where an area
MOA Antithrombin modification of Factors II, VII, of skin is destroyed
III IX, and X (Vitamin K-dependent) • Heparin-Warfarin bridging is done to prevent this: You must
Monitoring PTT PT start first with Heparin to address the activated factors and
Antidote Protamine Vitamin K, FFP gradually introduce warfarin.
Mostly acute, Chronic, over weeks to
Use
over days months WARFARIN AND DRUG INTERACTIONS
Pregnancy Yes No
• cytochrome P450-inducers increase clearance and reduce the
MNEMONIC: PT/PTT anticoagulant effect of a given dose
What laboratory tests will you request to assess the extrinsic and • cytochrome P450-inhibitors reduce clearance and increase the
intrinsic coagulation pathways?
anticoagulant effect of a given dose
PiTT = PTT for intrinsic pathway
PeT = PT for extrinsic pathway
ANTICOAGULANT DRUGS
DIRECT THROMBIN ORAL DIRECT FACTOR ORAL
INDIRECT THROMBIN INHIBITORS
INHIBITORS XA INHIBITOR ANTICOAGULANT
ENOXAPARIN [B],
LEPIRUDIN [B],
Dalteparin [B],
Drug BIVALIRUDIN [B], WARFARIN [X],
Tinzaparin [B], RIVAROXABAN [C],
HEPARIN Desirudin [C], DICUMAROL,
Danaparoid, [B] APIXABAN [B]
ARGATROBAN [B], ANISINDIONE
Nadroparin [B],
DABIGATRAN [C]
FONDAPARINUX [B]
Inhibits vitamin K
Activates antithrombin Binds and potentiates epoxide reductase
III (inactivates thrombin or effect of antithrombin Binds to thrombin's Inhibit Factor Xa in (responsible for
MOA Factor IIa, Factor IXa & III on factor Xa (more active site and inhibits its the final common γ-carboxylation of the
Factor Xa by forming stable selective). Less effect enzymatic action pathway vitamin K-dependent
complexes with them) on thrombin. clotting factors: II, VII,
IX, X, Protein C & S)
Deep venous thrombosis,
Pulmonary embolism,
Myocardial infarction,
Unstable angina, Deep venous
Adjuvant to percutaneous thrombosis, Pulmonary
coronary intervention (PCI) embolism, Myocardial Chronic
and thrombolytics, Anticoagulation in patients Prevention of Venous
infarction, Unstable anticoagulation
Atrial fibrillation, with heparin-induced thromboembolism,
angina, (DVT, atrial
Uses thrombocytopenia (HIT), Prevention of stroke in
DOC for anticoagulation Adjuvant to fibrillation, valve
Percutaneous coronary patients with Atrial
during pregnancy, given percutaneous coronary replacement) EXCEPT
angioplasty (with aspirin) Fibrillation
with thrombolytics for intervention (PCI) and in pregnancy
revascularization thrombolytics,
procedures, given with Atrial fibrillation
GPIIb-IIIa inhibitors for
angioplasty and stent
placement
Bleeding,
Warfarin-induced
Bleeding, Heparin-induced skin necrosis
Bleeding, Effect- Bleeding, Dizziness,
thrombocytopenia, Bleeding, Less risk of (for patients with
SE prolonging antibodies, Diarrhea, Edema,
Osteoporosis with chronic thrombocytopenia protein C & S
Anaphylactic reactions Epistaxis
use deficiencies),
Teratogen (bone
defects, hemorrhage)
• Administered IV or SC • Does NOT require • Monitor effect with • Have rapid onset of • Monitor effects
• Monitor with aPTT aPTT monitoring aPTT action and shorter with PT
• Antidote is Protamine • Advantage over • No reversal agents half-lives than • Antidote is
Sulfate regular heparin is • Used with caution for warfarin VITAMIN K (slow)
• SULODEXIDE: A higher bioavailability patients with renal • Do not require or FFP (fast)
Heparinoid consisting of and t½ insufficiency monitoring. No • Narrow therapeutic
80% Heparin and 20% • Protamine sulfate is • Dabigatran is PO while antidotes window
dermatan sulfate only partially all the rest are parenteral • Used esp. after hip or • Active ingredient in
Notes effective in reversing • Bivalirudin also inhibits knee surgery most rat poisons
effects platelet activation • Dose adjustment • Highly protein-
• Fondaparinux is • *IDARUCIZUMAB is a needed in renally bound
given SC OD and has monoclonal antibody impaired patients
less bleeding used for reversal of
Dabigatran toxicity
(needs dose adjustment
for renally impaired
patients)
CHEMICAL ANTAGONISTS (ANTIDOTE) Bleeding, Cerebral hemorrhage, Reperfusion
SE
Drug PROTAMINE SULFATE [C] arrhythmias
Chemical antagonist of heparin. Reverses excessive • Loss of effectiveness (on 2nd use) and allergic
MOA
anticlotting activity of unfractionated heparin. reactions may be observed with streptokinase
Notes
Uses Heparin overdosage • Tx must be within 6 hrs, better if within 3hrs
Hypotension, Bradycardia, Flushing, Hypersensitivity, • Antidote is AMINOCAPROIC ACID
SE
Dyspnea
Notes Partially reverses effects of LMWHs CONTRAINDICATIONS TO THROMBOLYSIS
• history of cerebrovascular hemorrhage at any time
FIBRINOLYTIC DRUGS • non-hemorrhagic stroke or other cerebrovascular event within
• mainly for the treatment of acute myocardial infarction, the past year
ischemic stroke and massive pulmonary embolism • marked hypertension (>180/110 mmHg) at any time during the
acute presentation
THROMBOLYTIC/ FIBRINOLYTIC • suspicion of aortic dissection
STREPTOKINASE [C], ALTEPLASE [C], • active internal bleeding (excluding menses)
Drugs Anistreplase [C], Reteplase [C], Tenecteplase [C],
Urokinase [B]
Tissue plasminogen activator analog. Converts
MOA plasminogen to plasmin, which degrades the fibrin
and fibrinogen à thrombolysis
Acute myocardial infarction, Ischemic stroke,
Uses
Pulmonary embolism
PRO-CLOTTING DRUGS (PROTHROMBOTICS)

OTHER DRUGS USED FOR COAGULATION
SUPPLEMENT:
DISORDERS
• Antihemophilic factor
• Anti-inhibitor coagulant complex
• Anti-thrombin III
• Factor VIIa, VIII, IX complex
• Somatostatin: Tx of intestinal and pancreatic fistulae, excessive
secretion from endocrine tumors of the GIT, acute severe GI
hemorrhage, endoscopic retrograde cholangiopancreatography
PROTHROMBOTIC DRUGS
ANTIPLASMIN DRUG:
VITAMIN K & DERIVATIVES ADH AGONIST
Aminocaproic Acid
Drugs
VITAMIN K1 (PHYTONADIONE) [C], DESMOPRESSIN [B],
TRANEXAMIC ACID [B],
VITAMIN K2 (MENAQUINONE) Vasopressin [C], Terlipressin
Increases supply of reduced vitamin K,
Competitively inhibits plasminogen which is required for synthesis of
MOA ADH/vasopressin V2 receptor agonist
activation by inhibiting tPA functional vitamin K-dependent clotting
and anticlotting factors
Prevention and treatment of acute
Vitamin K deficiency,
bleeding episodes in patients with high
Antidote to warfarin, Hemophilia A, von Willebrand’s disease,
Uses risk of bleeding (hemophilia,
Prevention of hemorrhagic diatheses in Central diabetes insipidus
intracranial aneurysms, menstrual,
newborns
obstetric, thrombolytics, postoperative)
Thrombosis, Hypotension, Severe infusion reaction when given too Headaches, Flushing, Nausea, Hyponatremia,
SE
Myopathy, Diarrhea fast (dyspnea, chest and back pain) Seizures
Contraindicated in disseminated Increases the factor VIII activity of patients with
Notes
intravascular coagulation (DIC) mild hemophilia A or von Willebrand disease
NSAIDS, ACETAMINOPHEN, DMARDS AND ASPIRIN: DOSAGE RANGES

• low range (<300 mg/d)
DRUGS USED IN GOUT o effective in reducing platelet aggregation
o follows first-order elimination kinetics
• intermediate doses (300–2400 mg/d)
o antipyretic and analgesic effects
• high doses (2400–4000 mg/d)
o anti-inflammatory effects
o follows zero-order elimination kinetics
PARACETAMOL: OVERDOSE
Mechanism of Paracetamol Overdose
INFLAMMATION • oxidation to a cytotoxic intermediate called N-acetyl-p-
• complex response to cell injury that primarily occurs in benzoquinoneimine (NAPQI) by phase I cytochrome P450
vascularized connective tissue and often involves the immune enzymes (CYP2E1)
response • occurs if substrates for phase II conjugation reactions (acetate
• mediators of inflammation function to eliminate the cause of cell and glucuronide) are lacking
injury and clear away debris, in preparation for tissue repair • centrilobular region (zone III) is preferentially involved because
• causes pain and tissue damage it is the area of greatest concentration of CYP2E1
• antidote is N-acetylcysteine (NAC), a sulfhydryl donor
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS Stages of Paracetamol Overdose
General Classification of NSAIDs TIME
STAGE MANIFESTATIONS
• SALICYLATES PERIOD
o Aspirin 0.5 to 24 Nausea, vomiting, diaphoresis, pallor,
I
• NONSELECTIVE NSAIDs hours lethargy, malaise
o Ibuprofen, Indomethacin, Ketorolac, Piroxicam Elevated liver enzymes, oliguria,
24-72
• COX-2 SELECTIVE II azotemia, increased PT,
hours
o Celecoxib, Etoricoxib, Parecoxib hyperbilirubinemia
Jaundice, hepatic encephalopathy,
Common NSAID Toxicities 72 to 96
III bleeding diathesis, acute tubular necrosis,
• CNS: headaches, tinnitus, dizziness hours
HAGMA, coma, death
• CVS: hypertension, edema, heart failure 4 days to
• GIT: abdominal pain, dysplasia, nausea, vomiting, ulcers, IV Recovery
2 weeks
bleeding • DOSAGE
• HEMATOLOGIC: thrombocytopenia, neutropenia, aplastic o toxic dose: 150mg/kg (21 Paracetamol 500 mg tabs)
anemia o lethal dose: 15g (30 Paracetamol 500 mg tabs)
• HEPATIC: abnormal liver function tests, liver failure • TREATMENT
• PULMONARY: asthma o antidote is N-acetylcysteine
• RASHES: all types, pruritus o supportive management
• RENAL: renal insufficiency, renal failure, hyperkalemia, o gastric decontamination with activated charcoal
proteinuria
NSAIDS
ANTIPLATELET DRUG, NSAIDS (NON-SELECTIVE) NSAID (NONSELECTIVE), NSAID (NONSELECTIVE) ANALGESIC
COX2 SELECTIVE INHIBITOR
NSAID (NON-SELECTIVE) All are Preg Cat C INTRAVENOUS For PDA closure (COX-3 SELECTIVE)
IBUPROFEN, Diclofenac,
Diflunisal, Etodolac,
ASPIRIN (Acetylsalicylic acid, Fenoprofen, Flurbiprofen,
Drugs ASA), Salsalate, KETOPROFEN, Nabumetone, CELECOXIB [C], Etoricoxib [C],
KETOROLAC [C], PARACETAMOL [B]
Sodium salicylate, Naproxen, Oxaprozin, INDOMETHACIN [C] Parecoxib [X], Rofecoxib,
Dexketoprofen [B] (ACETAMINOPHEN), Phenacetin
Choline salicylate, PIROXICAM, Sulindac, Valdecoxib
Magnesium salicylate Tolmetin, MEFENAMIC ACID,
Bromfenac, Meclofenamate,
Suprofen, Aceclofenac
MOA Nonselective, IRREVERSIBLE
COX 1&2 inhibitor. Reduces NSAID (nonselective),
Nonselective reversible COX-1 Nonselective reversible COX-1 Selective COX-2 inhibitor. Selectively inhibits COX-3. Weak
platelet production of REVERSIBLE COX 1&2
and COX-2 inhibitor. Inhibits and COX-2 inhibitor. Inhibits Inhibits prostaglandin COX-1 and COX-2 inhibitor. Inhibits
thromboxane A2, a potent inhibitor. Inhibits
prostaglandin synthesis. prostaglandin synthesis. synthesis. prostaglandin synthesis.
stimulator of platelet prostaglandin synthesis.
aggregation.
Uses Post-surgical analgesic control
(moderate to severe, short-
Prevention of arterial
thrombosis (MI, TIA, CVD), Analgesia (musculoskeletal, term), mainly used for analgesia Anti-inflammatory (gout,
not for anti-inflammatory effect
Inflammatory disorders headache, dysmenorrhea), arthritis, ankylosing spondylitis), Analgesia, Antipyretic, Anti-
An effective replacement for Analgesia (mild), Antipyretic
(rheumatic fever, Kawasaki Antipyretic, Anti- Closure of patent ductus inflammatory
disease, juvenile rheumatoid inflammatory morphine in post-surgical patient arteriosus
arthritis) reducing opioid requirement by
25-50%. It has no anti-
inflammatory effect.
Gastrointestinal toxicity,
Gastrointestinal bleeding Gastrointestinal bleeding Hepatotoxicity, Renal papillary
Gastrointestinal toxicity, Pancreatitis, Nephrotoxicity,
(less than aspirin), High risk for gastrointestinal (reduced risk), Nephrotoxicity, necrosis and Interstitial nephritis
Nephrotoxicity, Tinnitus, Serious hematologic reactions
SE Nephrotoxicity (AKI and toxicity and nephrotoxicity, Myocardial infarction and (phenacetin only),
Hypersensitivity, (aplastic anemia,
Interstitial Nephritis), Allergic reactions Stroke (rofecoxib and Methemoglobinemia, Hemolytic
Hyperventilation, HAGMA thrombocytopenia), BM
Hypersensitivity reaction valdecoxib only), rash anemia
suppression
• Associated with Reye’s • Misoprostol prevents • Use generally restricted to 72 • Inhibits COX1 > COX2 • Coxibs are 10-20x COX2 > • Increased hepatotoxicity with
syndrome in children NSAID-induced gastritis hours only (due to GI and renal • Indomethacin has greater anti- COX1 alcohol use
• Prevents uric acid excretion • NSAIDs (in general) may damage) inflammatory effect compared • 50% less GI SE compared to • Preferred antipyretic in children
(don’t use in gout) cause premature closure of • Ketorolac has significant to other NSAIDs Non-selective NSAIDs (does NOT cause Reye’s
• Low doses undergo first Ductus Arteriosus analgesic effect but not anti- • Rofecoxib and Valdecoxib syndrome)
Notes order kinetics while high • Ibuprofen and inflammatory effect withdrawn from the market • Antidote is N-acetylcysteine
doses undergo zero order Indomethacin can be used to due to increased incidence of • t½ is only 2-3h
reaction close PDA thrombosis
• MELOXICAM is a
PREFERENTIAL COX2
selective inhibitor
DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS XANTHINE OXIDASE INHIBITORS

Drug ALLOPURINOL [C] FEBUXOSTAT [C]
(DMARDS)
Active metabolite Nonpurine reversible
Disease-Modifying Anti-Rheumatic Drugs (DMARDs) (alloxanthine) that that is an inhibitor of
• heterogeneous group of agents with anti-inflammatory actions irreversibly inhibits xanthine oxidase
used in several connective tissue diseases MOA
Xanthine Oxidase and (more selective than
• cause slowing or even reversal of joint damage lowers production of allopurinol). Lowers
• may take 6 weeks to 6 months for their benefits to become uric acid production of uric acid.
apparent 1st line treatment for Chronic gout, Tumor lysis
(see next page for the list of DMARDs and immune modulators) Uses chronic gout, Tumor syndrome, Allopurinol
lysis syndrome intolerance
DRUGS FOR THE TREATMENT OF GOUT Gastrointestinal upset,
GOUT Rash, Peripheral neuritis, Liver function
• may be associated with increased serum concentrations of uric Vasculitis, abnormalities, Headache,
acid SE Bone marrow Gastrointestinal upset,
• acute attacks involve joint inflammation initiated by dysfunction, rash, liver dysfunction
precipitation of uric acid crystals Aplastic anemia, (Febuxostat)
Cataracts
TREATMENT STRATEGIES FOR GOUT • Inhibits metabolism of • Withheld for 1–2 weeks
• The management of gout has 3 strategies: mercaptopurine and after an acute episode of
1. reducing inflammation during acute attacks azathioprine gouty arthritis (co-
2. accelerating renal excretion of uric acid with uricosuric drugs • Withheld for 1–2 weeks administered with
3. reducing the conversion of purines to uric acid by xanthine after an acute episode colchicine or
Notes
oxidase of gouty arthritis (co- indomethacin to avoid
administered with an acute attack)
NSAIDS IN GOUT colchicine or • Febuxostat is more
indomethacin to avoid effective than
• In addition to inhibiting prostaglandin synthase, indomethacin
an acute attack) Allopurinol
and other NSAIDs also inhibit urate crystal phagocytosis
• Indomethacin is commonly used in the initial treatment of gout
as the replacement for colchicine
• Aspirin is not used due to its renal retention of uric acid at low
doses
MICROTUBULE ASSEMBLY INHIBITOR

Drug COLCHICINE [C]
Inhibits microtubule assembly and LTB4 production
MOA leading to decreased macrophage migration and
phagocytosis
Uses Gout, Familial Mediterranean fever
Diarrhea, Nausea, Vomiting, Abdominal pain, Hepatic
necrosis, Acute renal failure, Disseminated Figure 36-7. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
SE intravascular coagulation, Seizures, Hair loss, Bone
marrow depression (aplastic anemia), Peripheral
neuritis, Myopathy
• diarrhea is the adverse effect which signals toxicity
Notes from colchicine
• Not to be given to patients with eGFR of <30
URICOSURIC AGENTS
Drugs PROBENECID [B], Sulfinpyrazone [C]
Compete with uric acid for reabsorption in the
MOA
proximal tubules. Increase uric acid excretion.
Uses Gout
Gastrointestinal irritation, Rashes, Nephrotic
SE syndrome (probenecid only), Aplastic anemia,
Sulfa Allergy
• May precipitate acute gout during early phase of
drug action (prevent by co-administering with
colchicine or indomethacin)
• Inhibit secretion of other weak acids (e.g., penicillin,
methotrexate)
• May be given together with antimicrobial agents
Notes
(particularly Penicillins) to prolong therapeutic
effect by inhibiting renal tubular excretion of
antibiotics
• A required minimum 30 ml/min GFR is important
before starting Probenecid. Other uricosuric agents
are Fenofibrate and Losartan.
DMARD DRUGS
DMARD, Cancer Chemotherapeutic Drug DMARD DMARD DMARD, Anti-malarial
Drugs TNF-A INHIBITOR:
CINCHONA ALKALOIDS: CHLOROQUINE [C],
METHOTREXATE [X] INFLIXIMAB [B], ADALIMUMAB [B], AZATHIOPRINE [D]
HYDROXYCHLOROQUINE [C]
ETANERCEPT [B], CERTOLIZUMAB [B], GOLIMUMAB [B]
Inhibits AICAR (5-Aminoimidazole-4- Suppression of T-lymphocyte responses to
Forms 6-Thioguanine, suppressing inosinic
Carboxamide Ribonucleotide) mitogens, decreased leukocyte chemotaxis,
Binds to TNF-a and prevents it from activating TNF-a acid synthesis, B-cell and T-cell function,
MOA transformylase and thymidylate synthetase, Stabilization of lysosomal enzymes,
receptor immunoglobulin production, and interleukin-2
with secondary effects on polymorphonuclear Inhibition of DNA and RNA synthesis,
secretion
chemotaxis Trapping of free radicals
Rheumatoid arthritis, SLE, JRA,
Rheumatoid arthritis, Psoriatic arthritis,
Psoriatic arthritis, Ankylosing spondylitis, Crohn’s disease, Rheumatoid arthritis, Rheumatoid arthritis, SLE,
Uses Reactive arthritis, Polymyositis, SLE,
Polymyositis, Dermatomyositis, Wegener's Other rheumatic diseases Sjögren syndrome, Malaria
Behçet disease
granulomatosis, Giant cell arteritis, Vasculitis
Bacterial infections (URTIs), Reactivation of latent
Nausea, Mucosal ulcers, Hepatotoxicity, Bone marrow suppression, Increased risk of Ocular toxicity, Dyspepsia, Nausea,
tuberculosis, Lymphoma, Demyelination, Reactivation of
SE Hypersensitivity, infections, Increased incidence of lymphoma, Vomiting, Abdominal pain, Rashes,
hepatitis B, Autoantibody formation (ANA, anti-dsDNA),
Pseudolymphomatous reaction Fever, Rash, Hepatotoxicity, Allergic reactions Nightmares
Infusion reactions, hepatoxicity, hematotoxicity, cardiotoxicity
• DMARD of first choice to treat rheumatoid • Synergistic effects with methotrexate • Cannot give Allopurinol with azathioprine • Cinchonism: Headache Tinnitus, Vertigo
arthritis • Crosses placenta (allopurinol reduces xanthine oxide catabolism
Notes
• Rescue agent is Leucovorin (folinic acid) • This group of drugs has insufficient studies proving of purine analogs à increasing 6-thioguanine
their safety among pregnant Px nucleotides à severe leukopenia)
DMARD, Cancer Chemotherapeutic Drug DMARD DMARD DMARD
Drugs SULFASALAZINE [B, D if used for a prolonged
CYCLOPHOSPHAMIDE [D] CYCLOSPORINE [C] MYCOPHENOLATE MOFETIL [D]
time or near term]
Active product (mycophenolic acid) inhibits
Forms phosphoramide mustard, which Inhibits interleukin-1 and interleukin-2 receptor inosine monophosphate dehydrogenase
Active metabolite (sulfapyridine) inhibits the
MOA cross-links DNA to prevent cell replication. production and secondarily inhibits macrophage–T-cell (important enzyme in the guanine nucleotide
release of inflammatory cytokines
Suppresses T-cell and B-cell function interaction and T-cell responsiveness synthesis) and inhibits T-cell lymphocyte
proliferation
Rheumatoid arthritis, SLE, vasculitis, Rheumatoid arthritis, SLE, Polymyositis, SLE nephritis, Vasculitis, Rheumatoid arthritis,
Uses Wegener's granulomatosis, Dermatomyositis, Wegener's granulomatosis, Wegener’s granulomatosis, Rheumatoid arthritis Inflammatory bowel disease, JRA,
Severe rheumatic diseases Juvenile rheumatoid arthritis, Tissue transplantation Least Toxic for SLE nephritis Ankylosing spondylitis
Nausea, Vomiting, Headache, Rash,
Bone marrow suppression, Hemorrhagic Gastrointestinal disturbances, Headache, Hemolytic anemia, Methemoglobinemia,
Nephrotoxicity, Hypertension, Hyperkalemia,
SE cystitis, Hepatotoxicity, Alopecia, SIADH, Hypertension, Reversible myelosuppression Neutropenia, Thrombocytopenia,
Hepatotoxicity, Gingival hyperplasia, Hirsutism
Cardiac dysfunction, Pulmonary toxicity (neutropenia) Pulmonary toxicity, Autoantibody formation
(anti-dsDNA), Reversible infertility in men
Notes • Rescue agent is MESNA
OTHER DMARDS:
GLUCOCORTICOIDS -see chapter on Endocrine Pharmacology- Reduces number of T lymphocytes, inhibits macrophage function,
GOLD COMPOUNDS: Gold compounds MOA is not well understood. Auranofin has a low PENICILLAMINE decreases IL-1, decreases rheumatoid factor, and prevents collagen
GOLD SODIUM THIOMALATE incidence of serious toxicity but the overall frequency of SE (rash, from cross-linking
(Auranofin), diarrhea) is higher with Auranofin than any other DMARD. Its TOFACITINIB Janus Kinase inhibitor (JAK); used for rheumatoid arthritis
AUROTHIOGLUCOSE utility therefore is limited by low efficacy and poor tolerability
IMMUNE MODULATORS
CO-STIMULATION MODULATOR NON-BIOLOGIC DMARD MONOCLONAL ANTIBODY MONOCLONAL ANTIBODY
Drugs
CD80 inhibitor: ABETACEPT [C] LEFLUNOMIDE [X] CD20 inhibitor: RITUXIMAB [C] TOCILIZUMAB [C]
Depletes B cells by cell-mediated and complement-
Its active metabolite inhibits Dihydroorotate
dependent cytotoxicity and stimulation of cell
Inhibits the activation of T Cells by dehydrogenase → decreased synthesis of
apoptosis by binding to CD20 antigen on the surface Binds to IL-6 → decreased T cell activation and
MOA binding to CD80 and CD86 on the ribonucleotide and arrest of stimulated cells in the G1
of B lymphocytes → reduced inflammation by inflammatory process
APC phase of cell growth. Inhibits T cell proliferation and
decreasing the presentation of antigens to T
production of autoantibodies by B cells.
lymphocytes and inhibits secretion of cytokine
For moderate to severe
Moderate to Severe Rheumatoid Arthritis
Rheumatoid Arthritis (monotherapy Moderate to Severe Rheumatoid Arthritis in patients
Uses Rheumatoid Arthritis (with Methotrexate) in patients with an inadequate
or in combination with other with an inadequate response to TNF-a.
response to TNF-a.
DMARDs)
URTI, Headache, Hypertension,
Increased risk of infection (esp. Diarrhea, Elevation of liver enzymes, Mild alopecia,
Rash, Increased risk of infection, Elevated liver enzymes,
SE URTI), Hypersensitivity reaction, Weight Gain, Increased blood pressure,
Cardiovascular events Neutropenia, Thrombocytopenia, Tuberculosis,
Infusion-related reaction Leukopenia, Thrombocytopenia
Fungal Viral and other Opportunistic infections
• Concomitant use with TNF-a • Converted to its active metabolite in the intestines • Monoclonal antibody • Screening for Tuberculosis should be done prior to
blocker is not recommended due to (A77-1726) beginning Tocilizumab
Notes
increased incidence of serious • Considered as effective as Methotrexate in
infection. Rheumatoid Arthritis
OTHER IMMUNOMODULATORS
A monoclonal antibody against IL-17; used for psoriasis and
SECUKINUMAB
ankylosing spondylitis
A monoclonal antibody against IL-2; used to prevent rejection during
BASILIXIMAB
organ transplantation
A monoclonal antibody against IL-12 and IL-23; used for Crohn’s
USTEKINUMAB
disease and psoriasis
ANTIBIOTIC AGENTS
OVERVIEW
MINIMUM INHIBITORY CONCENTRATION

• lowest concentration of antimicrobial drug capable of inhibiting
INTRODUCTION TO
growth of an organism in a defined growth medium
ANTIBACTERIAL AGENTS
https://qrs.ly/fycke6a BACTERIAL CELL WALL SYNTHESIS
INHIBITORS
PENICILLINS
MOA OF BETA-LACTAM ANTIBIOTICS
• binds to penicillin-binding proteins (PBPs) located in the
bacterial cytoplasmic membrane
• inhibits the transpeptidation reaction that cross-links the linear
peptidoglycan chain constituents of the cell wall
• activates autolytic enzymes that cause lesions in the bacterial
cell wall
• Capable of entering the blood brain barrier
PENICILLIN RESISTANCE
• enzymatic hydrolysis of beta-lactam ring by formation of beta-
lactamases (penicillinases)
o EXAMPLE: Staphylococcus aureus
o Beta-Lactamase Inhibitors (Clavulanic Acid, Sulbactam,
Tazobactam) prevent inactivation
• structural change in target PBPs
o EXAMPLES: MRSA, Pneumococci, Enterococci
• changes in the porin structures in outer cell wall impeding
Adapted from TheMediSchool.com access of Penicillins to PBPs
o EXAMPLE: Pseudomonas aeruginosa
TYPES OF ANTIBIOTIC AGENTS
• BACTERICIDAL MNEMONICS: Ampicillin/Amoxicillin
o can eradicate an infection in the absence of host defense Describe the antimicrobial coverage of extended spectrum
mechanisms Penicillins (HELPSE):
o kills bacteria Amoxicillin HELPS kill Enterococci
• BACTERIOSTATIC Haemophilus influenzae Proteus mirabilis
Escherichia coli Salmonella sp.
o inhibits microbial growth but requires host defense Listeria monocytogenes Enterococci
mechanisms to eradicate the infection
o does not kill bacteria
MNEMONIC: Antipseudomonal Penicillins
TCP: Takes Care of Pseudomonas
MNEMONIC: Bactericidal VS Bacteriostatic Antibiotics
Ticarcillin Carbenicillin Piperacillin
What antibiotics are BACTERICIDAL?
PSEUDOMONAS is actually a mnemonic AHA. What are the diseases
Very Finely Proficient At Murder!
associated with Pseudomonas? Pneumonia, Sepsis, Ecthyma
Vancomycin Aminoglycosides
gangrenosum, UTI, DM, Otitis externa, Mucopolysaccharidoses –
Fluoroquinolones Metronidazole
Cystic Fibrosis, Osteomyelitis, Nosocomial infection (HAP and VAP)
Penicillins Skin infection (in burns and hot tub folliculitis)
Dr. Calderon Jr.
What antibiotics are BACTERIOSTATIC?
We’re ECSTaTiC about bacteriostatics.
Erythromycin Trimethoprim
Clindamycin Tetracycline MEMORY AID:
Sulfamethoxazole Chloramphenicol PENICILLINS AND
CEPHALOSPORINS
https://qrs.ly/j3cke7q
PENICILLINS
NATURAL PENICILLIN ISOXAZOLYL PENICILLINS AMINO PENICILLINS ANTIPSEUDOMONAL
(Narrow spectrum) (Anti-Staphylococcal) (Extended spectrum) PENICILLINS
All are Preg Cat B All are Preg Cat B All are Preg Cat B All are Preg Cat B
Drugs
METHICILLIN, NAFCILLIN,
PENICILLIN G (IV), PIPERACILLIN, TICARCILLIN,
OXACILLIN, CLOXACILLIN, AMPICILLIN, AMOXICILLIN
PENICILLIN V (oral) CARBENICILLIN
DICLOXACILLIN
MOA Binds to penicillin-binding proteins. Inhibits transpeptidation in bacterial cell walls.
Infections due to enterococci,
DOC for syphilis, for Greater activity against G(-)
Listeria monocytogenes,
streptococcal, pneumococcal, infections. Infections due to
Uses Staphylococcal infections Escherichia coli, Proteus mirabilis,
meningococcal, G+ bacilli, Pseudomonas, Enterobacter and
Haemophilus influenzae and
spirochete infection Klebsiella
Moraxella catarrhalis (HELPSE)
Hypersensitivity,
Hypersensitivity, Complete cross-
Hypersensitivity, Hypersensitivity,
Complete cross-allergenicity allergenicity with other
Cross-allergenicity, GI upset, Complete cross-allergenicity
SE with other Penicillins, Penicillins, Gastrointestinal
Pseudomembranous colitis and with other Penicillins,
Gastrointestinal disturbances, disturbances, Interstitial
Rash (ampicillin) Gastrointestinal disturbances
seizures nephritis (methicillin),
Neutropenia (nafcillin)
• Inactivated by beta-lactamase • Resistant to inactivation • Inactivated by beta-lactamase • Inactivated by beta-lactamase
(penicillinase) by beta-lactamase (penicillinase) (penicillinase)
• Renal tubular secretion (penicillinase) • Enhanced effect when used with • Enhanced effect when used
inhibited by probenecid beta-lactamase inhibitors with beta-lactamase
Notes • Benzathine Penicillin & (clavulanic acid, sulbactam) inhibitors (clavulanic acid,
Procaine Penicillin: long- • Synergistic effect with tazobactam)
acting IM preparations aminoglycosides • Synergistic with
• Given IM but Pen V can be aminoglycosides against
given PO Pseudomonas
CEPHALOSPORINS MNEMONIC: Second Generation Cephalosporins

**Bactericidal; mostly IV; all have renal excretion Which microbes are covered by the spectrum of activity of
EXCEPT Cefoperazone and Ceftriaxone ** second generation cephalosporins?
MNEMONIC: First Generation Cephalosporins SECOND GENERATION CEPHALOSORINS
HEN PEcKS
Which microbes are covered by the spectrum of activity of first
generation cephalosporins? Haemophilus influenzae Proteus mirabilis
FIRST GENERATION CEPHALOSORINS Enterobacter aerogenes Escherichia coli
PEcK FIRST Neisseria spp. Klebsiella pneumoniae
Proteus mirabilis Serratia marcescens
Escherichia coli How do you remember second generation cephalosporins?
Klebsiella pneumoniae SECOND GENERATION CEPHALOSPORINS
In a FAMily gathering, you see your
How do you remember first generation cephalosporins? FOXy cousin wearing a FUR coat and drinking TEA.
FIRST GENERATION CEPHALOSPORINS CeFAMandole, CeFOXitin,
FADer, help me FAZ my PHarmacology boards! CeFURoxime, CefoTEtan
CeFADroxil CePHalothin CePHradine SECOND GENERATION CEPHALOSPORINS
CeFAZolin CePHapirin CePHalexin FAC! LORA the PROfessional AZhOLE is still on the FONe.
CeFAClor, LORAcarbef, CefPROzil,
CefmetAZOLE, CeFONicid
MNEMONIC: Anti-Pseudomonal Cephalosporins
ANTI-PSEUDOMONAL CEPHALOSPORINS
Ceftazidime Cefepime Cefoperazone
CEPHALOSPORINS
FIRST GENERATION SECOND GENERATION THIRD GENERATION FOURTH GENERATION
CEPHALOSPORINS CEPHALOSPORINS CEPHALOSPORINS CEPHALOSPORINS
CEFAZOLIN, CEFACLOR, CEFAMANDOLE, CEFOPERAZONE, CEFOTAXIME,
Drugs CEFADROXIL, CEFMETAZOLE, CEFONICID, CEFTAZIDIME, CEFTIZOXIME,
CEPHALEXIN, CEFUROXIME, CEFTRIAXONE, CEFIXIME, CEFEPIME, CEFTAROLINE,
CEPHALOTHIN, CEFPROZIL, CEFORANIDE, CEFPODOXIME PROXETIL, CEFPIROME
CEPHAPIRIN, CEFOXITIN, CEFOTETAN, CEFDINIR, CEFDITOREN PIVOXIL,
CEPHRADINE LORACARBEF CEFTIBUTEN, MOXALACTAM
MOA Binds to penicillin-binding proteins. Inhibits transpeptidation in bacterial cell walls.
Surgical prophylaxis,
Bone infections,
Decreased gram-positive coverage.
Infections due to
Increased gram-negative activity
gram-positive cocci Wide coverage against
Added coverage for infections (Pseudomonas, Bacteroides), against
(Staphylococci and gram-positive and gram-
Uses due to Haemophilus, Providencia, Serratia, Neisseria,
common Streptococci), negative bacteria, MRSA
Enterobacter and Neisseria Haemophilus;
E. coli and K. pneumoniae, (Ceftaroline)
DOC for gonorrhea
Skin and soft tissue
(Ceftriaxone and Cefixime)
infections,
Urinary Tract infections
Hypersensitivity, Cross-
Hypersensitivity, Cross-
allergenicity (partial with Hypersensitivity,
allergenicity (partial with Hypersensitivity, Cross-allergenicity
Penicillins, complete with Cross-allergenicity (partial
Penicillins, complete with (partial with Penicillins, complete with
SE cephalosporins), Injection site with Penicillins, complete
cephalosporins), cephalosporins), GI upset, Disulfiram
reactions, Phlebitis, GI upset, with cephalosporins), GI
Injection site reactions, reaction (Cefoperazone)
Disulfiram reaction upset
Phlebitis, GI upset
(cefamandole, cefotetan)
FIRST GENERATION SECOND GENERATION THIRD GENERATION FOURTH GENERATION
Drugs CEPHALOSPORINS CEPHALOSPORINS CEPHALOSPORINS CEPHALOSPORINS
• Increases • Increases nephrotoxicity of • Synergistic effect with aminoglycosides • Resistant to beta-lactamase.
nephrotoxicity of aminoglycosides • All have renal excretion EXCEPT Broad G(-) activity
aminoglycosides • Slight less activity against G+ Cefoperazone and Ceftriaxone • In some sources, Ceftaroline
• Minimal activity against but extended G- activity • All can penetrate the BBB EXCEPT belongs to the 5th generation
G- cocci, enterococci, • Cefuroxime has improved Cefoperazone and Cefixime of Cephalosporin
MRSA and most G- rods action against pneumococcus • Ceftriaxone and Cefotaxime are the most • More resistant to beta-
Notes and H. influenzae active Cephalosporins against Penicillin- lactamase produced by
• Cefotetan and Cefoxitin have resistant S. pneumoniae Enterobacter, Haemophilus,
good activity against B. • Ceftizoxime is commonly used Neisseria and Pneumococcus
fragilis and thus are used for against Bacteroides • Ceftaroline used for MRSA
abdominal and pelvic • Ceftriaxone has very good CNS penetration
infections • Ceftazidime has very good action on
Pseudomonas
NOVEL CEPHALOSPORINS CARBAPENEM RESISTANCE
• A novel Cephalosporin, usually combined • Production of carbapenemases (carbapenem-hydrolyzing
with Tazobactam, used for the treatment of enzymes) is the most important mechanism of carbapenem
complicated urinary tract and resistance
intraabdominal infections; very good • Other methods of resistance: Porins, efflux pumps, mutations in
CEFTOLOZANE
activity against Gram negative organisms penicillin-binding proteins
including Pseudomonas aeruginosa, most • One method of circumventing carbapenem resistance is to add
extended-spectrum-B-lactamase-producing Beta-lactamase inhibitor in combination.
organisms and some anaerobes
• Siderophore Cephalosporin: entry into BETA-LACATAMASE INHIBITORS
bacterial cells is by binding to iron, which is
• Inhibits inactivation of Penicillins by bacterial beta-lactamase
actively transported into the bacterial cells.
(penicillinase)
• Used to treat complicated urinary tract
CLAVULANIC ACID [B], SULBACTAM [B],
infections and pneumonias when no other Drugs
TAZOBACTAM [B]
options are available; Indicated for the
Inhibits inactivation of Penicillins by bacterial beta-
treatment of multi-drug-resistant Gram- MOA
CEFIDEROCOL lactamase (penicillinase)
negative bacteria including P. aeruginosa.
• Common side effects include diarrhea, Infections against beta-lactamase producing
Uses
gonococci, streptococci, E. coli and H. influenzae
infusion site reactions, constipation and
rash. May also cause serious and life- SE Hypersensitivity, Cholestatic jaundice
threatening allergic reactions, severe • Usual combinations include:
diarrhea caused by C. difficile and seizures. Amoxicillin-Clavulanate, Ampicillin-Sulbactam,
(Warning for higher mortality) Piperacillin-Tazobactam
• Most active against plasmid encoded beta
Notes
MONOBACTAM lactamases (Gonococci, Streptococci, E coli and
Drug AZTREONAM [B] H. Influenzae)
Binds to penicillin-binding proteins. Inhibits • Not good inhibitor of inducible chromosomal beta
MOA lactamases (Enterobacter, Pseudomonas, Serratia)
transpeptidation in bacterial cell walls.
Infections resistant to beta-lactamases produced by
gram-negative rods, including Klebsiella, NOVEL CARBAPENEMASE INHIBITORS
Uses Pseudomonas and Serratia Diazobicyclooctanes Share five-membered
Aztreonam is the silver bullet. It is design for gram negative (DBOs) diazabicyclooctane ring
rods. Pseudomonas is a gram-negative rod. Used to treat complicated urinary
Gastrointestinal upset, Superinfection, Vertigo, tract infections, complicated Intra-
SE AVIBACTAM
Headache, Hepatotoxicity, Skin rash abdominal Infections (cIAI)and
(Ceftazidime/
• Resistant to beta-lactamase hospital-acquired bacterial
Avibactam)
• No cross-allergenicity with Penicillins pneumonia, ventilator-associated
Notes pneumonia.
• No activity against gram-positive bacteria or
anaerobes Broadly active against a wide variety of
Gram-negative pathogens,
CARBAPENEMS RELEBACTAM including Enterobacterales, P. aeruginosa
IMIPENEM-CILASTATIN [C], ERTAPENEM [B], (Imipenem/ and the anaerobic Bacteroides spp. More
Drugs Relebactam) importantly, it has demonstrated
MEROPENEM [B], DORIPENEM [B]
Binds to penicillin-binding proteins. Inhibits excellent activity against key multidrug-
MOA resistant pathogens.
transpeptidation in bacterial cell walls.
Wide coverage against gram-positive and gram-
Uses negative bacteria. For serious infections such as Boronic acid
Derived from boronic acid
pneumonia and sepsis derivatives
Hypersensitivity, • Active against E. coli, K. pneumoniae and
SE Cross-allergenicity (partial with Penicillins), GI upset, E. cloacae complex. Used for treatment of
CNS toxicity (confusion, encephalopathy, seizures) infections (urinary tract infection,
• Reserved for serious life-threatening infections VABORBACTAM hospital-acquired
• Imipenem given with Cilastatin which acts as (Meropenem/ • pneumonia / ventilator-associated
Dihydropeptidase enzyme inhibitor Vaborbactam) pneumonia, complicated intra-
• Cilastatin inhibits renal metabolism (Hydrolysis) of abdominal infections or bloodstream
Notes imipenem by Dihydropeptidase infection) caused by carbapenem-
• Low susceptibility to B-lactamases resistant Enterobacterales (CRE).
• Active against Pseudomonas and Acinetobacter
EXCEPT Ertapenem
• Partial cross-allergenicity with Penicillins
OTHER CELL WALL INHIBITORS

GLYCOPEPTIDES PEPTIDE ANTIBIOTICS CYCLOSERINE
Drugs VANCOMYCIN [C], TEICOPLANIN [B], DALBAVANCIN [C],
BACITRACIN [C] CYCLOSERINE [C]
TELAVANCIN [C]
Inhibits cell wall synthesis by binding to the D-Ala-D-Ala terminus of Interferes with a late stage in Blocks incorporation of
MOA nascent peptidoglycan → inhibit transglycosylation → cell wall synthesis in D-Ala into the pentapeptide
prevent elongation and cross-linking of peptidoglycan chain gram-positive organisms side chain of the peptidoglycan
Serious infections caused by drug-resistant gram-positive organisms
(MRSA), sepsis, endocarditis & meningitis, Pseudomembranous colitis Infections due to gram- Drug-resistant tuberculosis
Uses
Teicoplanin and Telavancin are not absorbed in the GIT à used for positive bacteria (2nd line drug)
bacterial enterocolitis,
Red Man syndrome, Nephrotoxicity, Neurotoxicity (tremors,
SE Nephrotoxicity
Ototoxicity, Chills, Fever, Phlebitis seizures, psychosis)
• Reserved for serious life-threatening infections • Reserved for topical use • Only used as a second-
• Treat red man syndrome by slowing the rate of infusion only due to marked line agent in TB
• Use oral formulation for Pseudomembranous colitis nephrotoxicity
• Narrow spectrum
Notes
• VRSA and VRE are due to D-Ala-D-Lactate formation
• Decrease dose for renally impaired patients
• Dalbavancin has very long t½ (6-11 days) which permits once-weekly
dosing and is more active than Vancomycin
POLYMYXIN B, SUPPLEMENT: OTHER DRUGS ACTING ON CELLWALL
Drugs DAPTOMYCIN [B]
Polymyxin E Inactivates the enzyme UDP-N-
Cationic detergents. acetylglucosamine-3-enolpyruvyltransferase
Binds to cell membrane Attach to and disrupt which is important in peptidoglycan synthesis
MOA causing depolarization and bacterial cell membrane, (very early stage of bacterial cell wall synthesis)
rapid cell death bind and inactivate FOSFOMYCIN → prevents formation of N-acetylmuramic acid
endotoxin. Bactericidal. (a peptidoglycan precursor molecule); for
Gram-negative bacteria. uncomplicated UTI; safe for pregnant patients;
renal excretion; resistance emerges rapidly;
Infections caused by G (+) For salvage therapy of
synergistic with Beta lactam and quinolones
Uses bacteria including sepsis Acinetobacter,
and endocarditis Enterobacteriaceae and SUPPLEMENT: MNEMONICS – Drugs of Last Resort
Pseudomonas aeruginosa Which antibiotics are considered drugs of last resort?
Myopathy I AM your Last Shot at Victory
Eosinophilia, fever,
Monitor Creatine Imipenem Linezolid
Nephrotoxicity,
SE Phosphokinase weekly to Amikacin Streptogramins
Neurotoxicity, Rash,
check for severity of Meropenem Vancomycin
myopathy
Urticaria
• More rapidly bactericidal • Proteus and Neisseria are
than Vancomycin resistant
Notes • Inactivated by pulmonary • For Topical use only (to
surfactants so cannot be limit toxicity)
used against pneumonia • *Both are Preg Cat C
BACTERIAL PROTEIN SYNTHESIS INHIBITORS
• Gray Baby Syndrome:

MNEMONIC: Protein Synthesis Inhibitors characterized by decreased red
“AT CELLS” blood cells, cyanosis and
Aminoglycosides cardiovascular collapse
Tetracyclines • Characteristic ashen gray skin
Chloramphenicol (HNBS)*
Erythromycin (Macrolides)
Lincosamides (Clindamycin) MNEMONIC: Tetracycline
Linezolid T = TeTracyclines
Streptogramins Block aTTachment of T-RNA to acceptor site
All bacterial protein synthesis inhibitors are bacteriostatic except Teeth-racycline = tooth enamel dysplasia / discoloration
Aminoglycosides, Streptogramins, and Chloramphenicol to the
MNEMONIC: Clindamycin VS Metronidazole
following bugs: Hemophilus, Neisseria, Bacteroides and Streptococcus
pneumoniae. • CLINDAMYCIN for anaerobic infections ABOVE the diaphragm.
• METRONIDAZOLE for anaerobic infections BELOW the diaphragm.
CHLORAMPHENICOL: GRAY BABY SYNDROME SUPPLEMENT: OTHER PROTEIN SYNTHESIS INHIBITOR
• premature neonates are deficient in hepatic Inhibits translocation process during protein
glucuronosyltransferase FUSIDIC ACID or synthesis; an antibiotic isolated from the
o Glucuronidation is the way to metabolize chloramphenicol Na FUSIDATE fermentation broth of Fusidium coccineum;
(Group: Fusidane) used as topical antimicrobial against most
o Immature livers very sensitive to doses of chloramphenicol
common skin pathogens including S. aureus
PROTEIN SYNTHESIS INHIBITORS
TETRACYCLINE
MACROLIDES LINCOSAMIDE OXAZOLIDINONE STREPTOGRAMIN
All are Preg Cat D
Drugs TETRACYCLINE, DOXYCYCLINE, ERYTHROMYCIN [B], AZITHROMYCIN [B],
CLINDAMYCIN [B], LINEZOLID [C], QUINUPRISTIN-
MINOCYCLINE, TIGECYCLINE, CHLORAMPHENICOL [C] CLARITHROMYCIN [C],
LINCOMYCIN [C] TEDIZOLID [C] DALFOPRISTIN [B]
DEMECLOCYCLINE, LYMECYCLINE TELITHROMYCIN [C], ROXITHROMYCIN [B]
Binds to the 23S
Inhibits transpeptidation (catalyzed by
Binds 30S ribosomal subunit. Binds 50S subunit. ribosomal RNA of Binds 50S subunit.
MOA peptidyl transferase) at 50S subunit. Binds 50S ribosomal subunit. Bacteriostatic.
Bacteriostatic. Bacteriostatic. 50S subunit. Bactericidal.
Bacteriostatic.
Bacteriostatic.
Infections caused by
Skin and soft tissue infection, drug-resistant Infections caused
Infections caused by M. pneumoniae,
Anaerobic infections, Backup gram-positive cocci by drug-resistant
Chlamydia, Rickettsia and Vibrio, Meningitis (Streptococcus pneumoniae,
drug against gram-positive such as gram-positive cocci
Peptic ulcer disease, Lyme disease, Haemophilus influenzae, Community-acquired pneumonia, Pertussis,
Uses cocci, Endocarditis Staphylococci and such as
Malaria prophylaxis, Amebiasis, SIADH Neisseria meningitidis), Backup for Diphtheria, Chlamydial infections
prophylaxis (penicillin- Enterococcus Staphylococci and E.
(demeclocycline), Acne, Salmonella, Rickettsia and Bacteroides
allergy), PCP pneumonia, (MRSA, VRSA, VRE), faecium (MRSA,
CAP and bronchitis (Doxycycline)
Toxoplasmosis Listeria, VRSA, VRE)
Corynebacteria
Bone marrow
suppression,
GI disturbance, Teratogen Thrombocytopenia,
(tooth enamel dysplasia/ Gastrointestinal disturbance, Neutropenia,
Gastrointestinal disturbance, Gastrointestinal upset, Cholestatic hepatitis, Injection site
discoloration), Skin rash, Neutropenia, Serotonin
Aplastic anemia (idiosyncratic), Gray Hepatotoxicity, QT prolongation, reactions, severe
SE Hepatotoxicity, Nephrotoxicity, Hepatic dysfunction, syndrome (when
baby syndrome, Drug interactions, rare fulminant hepatic failure Arthralgia-
Photosensitivity, reversible Pseudomembranous colitis given together with
dose-related anemia (Telithromycin) myalgia syndrome
Vestibulotoxicity (C. difficile overgrowth) serotonergic drugs
(especially Minocycline) such as SSRIs),
Neuropathy,
Optic neuritis
• Divalent cations impair oral absorption • Inhibits hepatic drug-metabolizing • All macrolides inhibit CYP450 EXCEPT • Cross-resistance between • Resistance is due • Inhibits CYP450
(minimal for Doxycycline) enzymes causing many drug interactions Azithromycin clindamycin and macrolides to decreased enzymes, causing
• Tigecycline has the broadest spectrum • Resistance is due to the formation of • Azithromycin has highest Vd and slowest is common affinity of drug to multiple drug
and has the longest t½ (30-36hrs) acetyltransferase that inactivates drug elimination • Resistance is due to binding site interactions
• Do not drink with milk (decreased • May be used as topical agent • Telithromycin is used for macrolide-resistance methylation of binding sites
absorption with divalent cations like • Resistance is due to development of efflux and enzymatic inactivation
calcium) Chloramphenicol is a bacteriostatic pumps and production of methylase enzyme • G (-) aerobes are resistant
• High Vd, cross the placenta, antibiotic but is bactericidal to the ff: • Cross-resistance among macrolides: complete because of poor penetration
enterohepatic recycling Hemophilus influenza, Neisseria, or partial resistance with drugs acting on the through the outer
Notes • Resistance is due to development of Bacteroides and Streptococcus 50S membrane
efflux pumps for active extrusion of pneumoniae.
tetracyclines and the formation of Azithromycin has a good pharmacokinetic
ribosomal protection proteins that profile. It is neither an inhibitor or inducer of
interfere with tetracycline binding (but general substrate. Azithromycin has a
not present with Tigecycline EXCEPT in tremendous 4 day half-life and has a high
Proteus and Pseudomonas) volume of distribution. It is greater in tissue
• Tigecycline is given IV only and is macrophage than the plasma level.
unaffected by common tetracycline
resistance mechanisms
PROTEIN SYNTHESIS INH: AMINOGLYCOSIDES • bind to the 30S ribosomal subunit and interfere with protein
synthesis:
Modes of Antibacterial Action o block formation of the initiation complex
• CONCENTRATION-DEPENDENT KILLING ACTION o cause misreading of the code on the mRNA template
o as the plasma level is increased above the MIC, an o inhibit translocation
increasing proportion of bacteria are killed and at a more
rapid rate RESISTANCE TO AMINOGLYCOSIDES
o EXAMPLE: aminoglycosides
• plasmid-mediated formation of inactivating enzymes (group
• TIME-DEPENDENT KILLING ACTION
transferases)
o efficacy is directly related to time above MIC
o AMIKACIN is often resistant to many enzymes that inactivate
o efficacy independent of concentration once the MIC has
other aminoglycosides
been reached
• resistance to STREPTOMYCIN develops due to changes in the
o EXAMPLES: Penicillins, cephalosporins
ribosomal binding site
• POST-ANTIBIOTIC EFFECT
o seen in aminoglycosides & quinolones MNEMONIC: Aminoglycosides
o killing action continues when their plasma levels have AminOglycosides require O2 for transport.
declined below measurable levels They won’t work under anaerobic conditions.
o greater efficacy when administered as single large dose MNEMONICS – Aminoglycosides
o toxicity depends on a critical plasma concentration and on Mean GNATS canNOT kill anaerobes.
the time such a level is exceeded Gentamicin Nephrotoxicity
§ shorter with single large dose than multiple small doses Neomycin Ototoxicity
§ basis for once-daily aminoglycoside dosing protocols Amikacin Teratogen
Tobramycin
PHARMACOKINETICS OF AMINOGLYCOSIDES Streptomycin
• not absorbed after oral administration
o must be given IM or intravenously for systemic effect TOXICITIES OF AMINOGLYCOSIDES
• limited tissue penetration due to its water solubility • OTOTOXICITY
o do not readily cross the blood-brain barrier o MOST OTOTOXIC: kanamycin, amikacin
• glomerular filtration is the major mode of excretion o MOST VESTIBULOTOXIC: tobramycin, gentamicin
o plasma levels greatly affected by changes in renal function o cumulative ototoxicity when used with loop diuretics
• Amikacin has the narrowest therapeutic window among • NEPHROTOXICITY
aminoglycosides o acute tubular necrosis
• GROUP PREGNANCY CATEGORY: D o MOST NEPHROTOXIC: tobramycin, gentamicin
§ Toxicities of Aminoglycosides
MOA OF AMINOGLYCOSIDES • NEUROMUSCULAR BLOCKADE
• bactericidal inhibitors of protein synthesis o curare-like effect (nondepolarizing NMJ block) reversible with
• aminoglycoside transport can be enhanced by cell wall synthesis calcium and neostigmine
inhibitors (synergistic effect) • SKIN REACTIONS
• require oxygen for uptake o commonly from Neomycin and Streptomycin
o ineffective against anaerobes
AMINOGLYCOSIDES
NEOMYCIN,
Drugs GENTAMICIN, TOBRAMYCIN AMIKACIN STREPTOMYCIN
KANAMYCIN, SPECTINOMYCIN
PAROMOMYCIN
MOA Inhibit protein synthesis by binding to 30S subunit. Bactericidal.
Infections caused by
aerobic
Skin infections,
gram-negative
Bowel preparation
bacteria
Infections caused by aerobic gram- for elective surgery
(E. coli, Enterobacter, Tuberculosis, Drug-resistant
negative bacteria (E. coli, Enterobacter, (to decrease
Klebsiella, Proteus, Tularemia, Bubonic gonorrhea,
Klebsiella, Proteus, Providencia, aerobic flora),
Uses Providencia, plague, Brucellosis, Gonorrhea in
Pseudomonas, Serratia), Endocarditis Hepatic
Pseudomonas, Enterococcal penicillin-allergic
(caused by staphylococci, streptococci encephalopathy,
Serratia), endocarditis patients
and enterococci), Ocular infections Visceral
Multi Drug-
leishmaniasis
Resistant
(paromomycin)
Tuberculosis
(2 line drug)
nd
Hypersensitivity,
Nephrotoxicity
Hypersensitivity, Nephrotoxicity
(reversible),
Nephrotoxicity (reversible),
Ototoxicity
(reversible), Ototoxicity
Nephrotoxicity (reversible), Ototoxicity (irreversible), (vestibulotoxic,
SE Ototoxicity (irreversible),
Neuromuscular blockade irreversible),
(irreversible), Neuromuscular
Neuromuscular
Neuromuscular blockade,
blockade, Teratogen
blockade Anemia
(congenital deafness),
Injection site reactions
• SYNERGISTIC effect with cell wall • Synergistic effect • Synergistic effect with • Limited to topical • No cross-
synthesis (Beta Lactam and with beta-lactam beta-lactam and oral use resistance with
Vancomycin) inhibitors due to antibiotics antibiotics (Neomycin) other drugs used
enhancement of transport to the • Least resistance • Administered IM • Reverse in gonorrhea
inside of the bacterial cell but narrowest • Has widespread neuromuscular • Given IM
Notes • Gentamicin and tobramycin are the therapeutic resistance blockade with
most vestibulotoxic and nephrotoxic window • If given together with calcium
• Gentamicin and Tobramycin are the Pens can be used for gluconate and
most vestibulotoxic and nephrotoxic enterococcal neostigmine
aminoglycosides endocarditis, TB plague • Kanamycin is
and tularemia most ototoxic
SILVER
NUCLEIC ACID SYNTHESIS INHIBITORS Drug CO-TRIMOXAZOLE SULFADIAZINE [B],
Sulfonamides, trimethoprim, & fluoroquinolones
Mafenide acetate [C]
Sequential blockade of
Inhibit
Antimetabolites dihydropteroate synthase
Fluoroquinolones dihydropteroate
MOA (Sulfamethoxazole) and
synthase.
dihydrofolate reductase
Bacteriostatic.
Sulfonamides Narrow spectrum Wide spectrum (Trimethoprim). Bactericidal.
(1st generation)
Trimethoprim
Urinary tract, respiratory, ear
and sinus infections
Trimethoprim-
sulfamethoxazole
2nd generation (Haemophilus, Moraxella,
3rd generation
Uses Aeromonas), P. jiroveci Burn infections
pneumonia, Toxoplasmosis,
4th generation Nocardiosis, Cholera (backup),
Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 Typhoid fever, Shigellosis
GI upset, Acute hemolysis in G6PD deficiency,
ANTIFOLATE DRUGS Nephrotoxicity, Hypersensitivity (assume cross-
SE
hypersensitivity, SJS/TEN), Hematotoxicity, Drug
SULFONAMIDES interactions, Kernicterus
• weakly acidic compounds that have a common chemical nucleus • Displaces protein binding of • Displaces protein
resembling p-aminobenzoic acid (PABA) other drugs/bilirubin binding of other
• solubility may be decreased in acidic urine • Low solubility in acidic urine drugs/bilirubin
o combination of 3 separate sulfonamides (triple sulfa) to causing formation of stones
reduce the likelihood that any one drug will precipitate • Trimethoprim (also Pentamidine,
Notes
Classification of Sulfonamides an antiprotozoal) inhibit distal
Intermediate tubular Na reabsorption through
Short Acting Long Acting the amiloride-sensitive ENaC
Acting
Sulfacytine Sulfadiazine Sulfadoxine channel leading to urinary loss
Sulfisoxazole Sulfamethoxazole * Pyrimethamine of Na and Cl
Sulfamethizole Sulfapyridine OTHER SULFONAMIDES AND ANTIFOLATE DRUGS
* Trimethoprim SULFISOXAZOLE only for lower UTI
SULFADIAZINE-
DOC for Toxoplasmosis
TRIMETHOPRIM PYRIMETHAMINE
• structurally similar to folic acid SULFADOXINE-
2nd line agent for Malaria
• weak base that is trapped in acidic environments PYRIMETHAMINE
reaches high concentrations in prostatic and vaginal fluids used for lower UTI, may be safely given to
TRIMETHOPRIM
patients with sulfonamide allergy
co-administered with Leucovorin to limit
PYRIMETHAMINE bone marrow toxicity
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
• NEPHROTOXICITY
Figure 46-1. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 o crystalluria, hematuria
• DRUG INTERACTIONS
MOA OF ANTIFOLATES o displace protein binding affecting levels of warfarin and
• SULFONAMIDES methotrexate
o bacteriostatic inhibitors of folic acid synthesis o displace bilirubin binding sites leading to kernicterus
o competitive inhibitors of dihydropteroate synthase SUPPLEMENT: Kernicterus
o selective toxicity of sulfonamides results from the inability of • caused by increased levels of unconjugated bilirubin
mammalian cells to synthesize folic acid • due to immaturity of fetal blood brain barrier
o must use preformed folic acid that is present in the diet • histopathology
• TRIMETHOPRIM (intermediate acting) o bilirubin deposits in subcortical nuclei and basal ganglia
o selective inhibitor of bacterial dihydrofolate reductase • clinical presentation
o bacterial dihydrofolate reductase is 4–5x more sensitive to o hypo/hypertonia, lethargy, high-pitched cry, opisthotonos
inhibition by trimethoprim
• TRIMETHOPRIM PLUS SULFAMETHOXAZOLE QUINOLONES
o when the 2 drugs are used in combination, antimicrobial
MOA OF QUINOLONES
synergy results from the sequential blockade of folate
synthesis • interfere with bacterial DNA synthesis by inhibiting:
o drug combination is bactericidal o Topoisomerase II (DNA Gyrase) in gram-negative organisms
§ prevents relaxation of supercoiled DNA
RESISTANCE TO ANTIFOLATES o Topoisomerase IV in gram-positive organisms
§ interferes with the separation of replicated chromosomal
• plasmid-mediated and results from:
DNA during cell division
o decreased intracellular accumulation of the drugs
• usually bactericidal against susceptible organisms
o increased production of PABA by bacteria
• exhibit post antibiotic effect
• decrease in the sensitivity of dihydropteroate synthase to
• should not be taken with other preparations containing cations
sulfonamides
(should be taken 2 hours before or 4 hours after any product
containing cations)
• may damage growing cartilage and cause arthropathy
CLASSIFICATION AND ANTIMICROBIAL SPECTRUM • 3RD GENERATION
• 1ST GENERATION o Levofloxacin, Gemifloxacin, Moxifloxacin, Sparfloxacin,
o Nalidixic acid, Cinoxacin, Rosoxacin, Oxolinic acid Grepafloxacin, Gatifloxacin, Pazufloxacin, Tosufloxacin, Balofloxacin
o Urinary tract infections o less gram negative and more gram positive activity,
• 2ND GENERATION streptococci and enterococci
o Ciprofloxacin, Ofloxacin, Norfloxacin, Lomefloxacin, Enoxacin • 4TH GENERATION
o gram negatives, gonococci, gram positive cocci and Mycoplasma o Trovafloxacin, Alatrofloxacin, Prulifloxacin, Clinafloxacin
o broad spectrum, including anaerobes
*WITH INCREASING GENERATION, INCREASING GRAM POSITIVE
ACTIVITY (unlike cephalosporins where increasing generation leads to
increasing gram negative activity)
FLUOROQUINOLONES
SECOND GENERATION THIRD GENERATION FOURTH GENERATION
CIPROFLOXACIN, OFLOXACIN, LEVOFLOXACIN, SPARFLOXACIN, MOXIFLOXACIN, TROVAFLOXACIN [C],
Drugs NORFLOXACIN, LOMEFLOXACIN, GEMIFLOXACIN, PAZUFLOXACIN, TOSUFLOXACIN, ALATROFLOXACIN [C],
ENOXACIN BALOFLOXACIN PRULIFLOXACIN,
All are Preg Cat C All are Preg Cat C CLINAFLOXACIN
MOA Inhibits DNA replication by binding to DNA gyrase and topoisomerase IV. Bactericidal.
Urinary tract infections and GIT
infections (gram-negative rods (such as
Shigella, Salmonella, ETEC & Broad spectrum activity
Campylobacter), gonococci, gram Lung infections caused gram-positive cocci, (gram-negatives,
Uses positive cocci), Atypical pneumonia, Atypical pneumonia (Chlamydia, Mycoplasma), gram-positives),
Tuberculosis (2nd line drug), Tuberculosis (2nd line drug) Enhanced activity against
Infection of soft tissue, bones and joints; anaerobes
Intraabdominal MDR organisms (such
as Pseudomonas and Enterobacter)
Gastrointestinal distress, Gastrointestinal distress, CNS
CNS effects (dizziness, headache), Gastrointestinal distress, CNS effects (dizziness, headache), effects (dizziness, headache),
SE
insomnia, skin rash, abnormal LFTs, Tendinitis, QTc prolongation Tendinitis, QTc prolongation,
Tendonitis and Tendon rupture Hepatotoxicity (trovafloxacin)
• General SE/Note for ALL Quinolones: • Grepafloxacin withdrawn due to severe cardiotoxicity • Avoid use in young children
o Avoid use in young children and (arrhythmias), Gatifloxacin has also been withdrawn due and pregnant women
pregnant women to Diabetes mellitus • Enhance toxicity of
o Enhance toxicity of methylxanthines • Moxifloxacin has hepatic clearance → lower urinary levels, methylxanthines
(theophylline) so use in UTI is not recommended (theophylline)
o Oral absorption is impaired by • High resistance especially for C. jejuni, gonococci, G+ cocci • Widest spectrum of activity
cations like MRSA, Pseudomonas and Serratia among fluoroquinolones
• Ciprofloxacin is the most active agent • Used as alternatives to Ceftriaxone and Cefixime in • Trovafloxacin used with
against Gram Negative organisms esp. gonorrhea caution due to
Pseudomonas • Ofloxacin can be used against C. trachomatis hepatotoxicity
• General properties of quinolones: • Moxifloxacin and Gemifloxacin are the newest members of
Notes good oral bioavailability, high Vd, t½ this family and are considered to have the broadest
3-8hrs, absorption is impeded by spectrum of activity with increased activity against
antacids, elimination is via kidneys by anaerobes ang atypical agents
tubular secretion (may compete with • FQ elimination is via kidneys by tubular secretion (may
probenecid for excretion) EXCEPT for compete with probenecid for excretion) EXCEPT
MOXIFLOXACIN Moxifloxacin
• Norfloxacin does not achieve • Levofloxacin is used in CAP caused by Chlamydia,
adequate plasma levels for use in Mycoplasma and Legionella
systemic infections • Gemifloxacin, Levofloxacin, Moxifloxacin can prolong QT
• Levofloxacin has superior activity against G(+) bacteria
including S. pneumoniae ; All have relatively long t½
permitting once daily dosing
RESISTANCE TO FLUOROQUINOLONES NITROFURAN
• decreased intracellular accumulation of the drug via the Drugs NITROFURANTOIN [B, X at term]
production of efflux pumps Forms multiple reactive intermediates when acted
• changes in porin structure MOA upon by bacterial nitrofuran reductase →
• changes in the sensitivity of the target enzymes via point disrupt protein, RNA and DNA synthesis. Bactericidal.
mutations in the antibiotic binding regions Uncomplicated Urinary tract infections (EXCEPT
Uses
Proteus and Pseudomonas)
MISCELLANEOUS ANTIBACTERIALS Anorexia, Nausea, Vomiting, Skin rashes,
SE Pulmonary infiltrates, Phototoxicity, Neuropathies,
NITROIMIDAZOLE (ANTIPROTOZOAL)
Hemolysis in patients with G6PD deficiency
METRONIDAZOLE [B],
Drugs Proteus and Pseudomonas are resistant
TINIDAZOLE [C], SECNIDAZOLE [C] Notes
Contraindicated in Renal insufficiency
Reactive reduction by ferredoxin forming free
MOA radicals that disrupt electron transport chain.
TOPICAL ANTI-INFECTIVE. PSEUDOMONIC ACID
Bactericidal.
Drugs MUPIROCIN [B]
Anaerobic or mixed intra-abdominal infections,
Inhibits Staphylococcal isoleucyl tRNA synthetase.
Vaginitis (Trichomonas, Gardnerella), MOA
Uses Bactericidal.
Pseudomembranous colitis, Brain abscess,
Protozoal infections Gram positive cocci including methicillin-susceptible
Uses
and MRSA, for minor skin infections such as Impetigo
Gastrointestinal irritation, Metallic taste, Headache,
SE Dark urine, Leukopenia, Dizziness, Ataxia, Epistaxis, Stinging or burning sensation on the skin,
SE
Neuropathy, Seizures, Disulfiram reaction mild skin rash, headache
DOC for amoebiasis, giardiasis & Only used topically (available as intranasal ointment)
Notes Do not used over large infected areas such as
Pseudomembranous colitis Notes
decubitus ulcers or open surgical wounds (may lead
to resistance)
MNEMONIC: Hepatotoxicity of Anti-TB Drugs
ANTIMYCOBACTERIAL DRUGS Which anti-TB drugs are hepatotoxic?
ISO a Red PYRe!
(I saw a red fire!)
Isoniazid < Rifampin < Pyrazinamide
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
o no cross-resistance with INH
Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 o SE: severe gastrointestinal irritation and neurotoxicity
• P-AMINOSALICYLIC ACID (PAS)
o rarely used because primary resistance is common
o SE: gastrointestinal irritation, peptic ulcers, hypersensitivity
ANTIMYCOBACTERIAL AGENTS reactions, effects on kidney, liver, and thyroid function
https://qrs.ly/dycke7u • CAPREOMYCIN
o SE: ototoxicity, renal dysfunction
• CYCLOSERINE
DRUG THERAPY FOR MYCOBACTERIAL INFECTIONS o SE: peripheral neuropathy, CNS dysfunction
• chemotherapy is complicated by numerous factors • BEDAQUILINE
o Inhibits ATP synthase in mycobacteria, has in vitro activity against
o limited information about mechanisms of drug action
both replicating and nonreplicating bacilli, and has bactericidal and
o development of resistance sterilizing activity
o intracellular location of mycobacteria o Taken in combination with at least three other active medications,
o chronic nature of mycobacterial disease may be used for 24 weeks of treatment in adults with laboratory-
o patient compliance confirmed pulmonary tuberculosis if the isolate is resistant to both
• chemotherapy always involves the use of drug combinations to isoniazid and rifampin
delay the emergence of resistance and to enhance efficacy o SE: nausea, arthralgia, headache, hepatotoxicity QT prolongation
DRUGS USED IN TUBERCULOSIS

NICOTINIC ACID PYRAZINE BUTANOL
RIFAMYCINS AMINOGLYCOSIDE
DERIVATIVE DERIVATIVES DERIVATIVE
Drug RIFAMPICIN (RIFAMPIN) [C],
ISONIAZID [C] RIFABUTIN [B], RIFAPENTINE [C], PYRAZINAMIDE [C] ETHAMBUTOL [B] STREPTOMYCIN [D]
RIFAXIMIN [C]
Unknown. Converted
to active pyrazinoic Inhibits arabinosyl
acid under acidic transferases Inhibit protein
Inhibits DNA-dependent RNA conditions of involved in the synthesis by binding
Inhibits mycolic acid
MOA polymerase → inhibits RNA macrophage lysosomes. synthesis of to S12 ribosomal
synthesis. Bactericidal.
production. Bactericidal. Bacteriostatic but can arabinogalactan in subunit.
be bactericidal on mycobacterial cell Bactericidal.
actively dividing wall. Bacteriostatic.
mycobacteria.
Tuberculosis (active, latent), Atypical Tuberculosis Tuberculosis
Tuberculosis Mycobacterial Infections, Leprosy, (active), (for Drug-resistant
Uses (active, latent, Prophylaxis for meningococcal and Tuberculosis (active) atypical strains), Tularemia,
prophylaxis) staphylococcal carrier states, mycobacterial Bubonic plague,
Drug-resistant infections (MRSA, PRSP) infections Brucellosis
Hypersensitivity,
Red-orange Body Fluids, Light chain Visual disturbances
proteinuria, Nephrotoxicity
Hepatitis, Hepatotoxicity, Non- (decreased visual
(reversible),
Neurotoxicity Skin rash, Thrombocytopenia, gouty polyarthralgia, acuity, red-green
Nephritis, Hepatotoxicity, Flulike Ototoxicity
(seizures, neuritis, Asymptomatic color blindness,
(vestibulotoxic,
insomnia), Acute Syndrome, Anemia, Cholestasis hyperuricemia, retrobulbar neuritis,
SE irreversible),
hemolysis in G6PD The Rs of Rifampicin Myalgia, GIT retinal damage),
Neuromuscular
deficiency, Drug- RNA polymerase inhibitor irritation, Rash, Headache,
blockade,
induced lupus, Drug Red-orange body fluids Porphyria, Confusion,
Teratogen
interactions Rapid development of resistance Photosensitivity Hyperuricemia,
(congenital deafness),
Revs up cytochrome P450 (inducer) Peripheral neuritis
Injection site reactions
• Most important drug • Also considered a FIRST LINE • Also known as • Perform baseline • Synergistic effect
used in tuberculosis AGENT for PTB “sterilizing agent” ophthalmologic with beta-lactam
(FIRST LINE AGENT) • Potent CYP450 inducer used during the examination before antibiotics
• Prevent • Rapid development of resistance if first 2 months of starting • Administered IM
neurotoxicity by co- used alone therapy antimycobacterial
administering • Delays the emergence of resistance • Most hepatotoxic therapy
Pyridoxine to dapsone anti-TB drug • Dose adjustment if
(Vitamin B6) • RIFAXIMIN is a Rifampin derivative • Require metabolic needed in renal
• Liver metabolism by that is not absorbed in the GIT, and conversion via patients
acetylation (Filipinos so is used for the prevention of pyrazinamidases in • Always used in
Notes are fast acetylators) hepatic encephalopathy, for MTb combination with
• Potent CYP450 treatment of traveler’s diarrhea, • Decrease dose in other drugs for TB
inhibitor (off-label use: for IBS and hepatic and renal • Take with meals
• Less Active against Pseudomembranous colitis) patients
other Mycobacteria • Orange-colored metabolites • Take with meals
• Structural congener • Rifabutin is equally effective as anti-
of pyridoxine mycobacterial agent with less drug
• Best taken 1 hour interaction and it is the preferred
before or 2 hours anti-TB for AIDS patients
after meals • Best taken 1 hour before or 2 hours
after meals
DAPSONE [C], CLOFAZIMINE [C]

DRUGS USED FOR ATYPICAL MYCOBACTERIA Drugs
ACEDAPSONE [C](SULFONES) (PHENAZINE DYE)
• PROPHYLAXIS Gastrointestinal irritation, Gastrointestinal
o Clarithromycin or Azithromycin with or without Rifabutin in Fever, Skin rashes, irritation, Skin
patients with CD4 counts less than 50/L SE Methemoglobinemia, discoloration (ranging
• TREATMENT Acute hemolysis in patients from orange to red
o azithromycin or clarithromycin with ethambutol and rifabutin with G6PD deficiency brown to nearly black)
• Most active drug against
DRUGS USED IN LEPROSY M. leprae
DAPSONE [C], CLOFAZIMINE [C] • Usually in combination with
Drugs
ACEDAPSONE [C](SULFONES) (PHENAZINE DYE) rifampicin and clofazimine
Binds to guanine bases Notes
Inhibition of folic acid • Acedapsone is a repository
MOA in bacterial DNA. form of dapsone which has
synthesis. Bacteriostatic.
Bactericidal. drug action that can last for
Leprosy, PCP pneumonia Leprosy several months
Uses
(backup) (sulfone-resistance)
ANTIFUNGAL AGENTS
ANTIFUNGAL AGENTS
https://qrs.ly/ufcke85
SYSTEMIC DRUGS FOR SUPERFICIAL MYCOSES TOPICAL DRUGS FOR SUPERFICIAL MYCOSES
MICROTUBULE INHIBITORS ALLYLAMINE POLYENES AZOLES
GRISEOFULVIN [X] TERBINAFINE [B], CLOTRIMAZOLE [C],
Drug
“greasyfulvin”: it is best BUTENAFINE, MICONAZOLE, KETOCONAZOLE,
absorbed with greasy foods NAFTIFINE Drugs NYSTATIN [C],
BUTOCONAZOLE, ECONAZOLE,
Interfere with NATAMYCIN [C]
SULCONAZOLE, OXICONAZOLE,
Interferes with microtubule
ergosterol synthesis TERCONAZOLE, TIOCONAZOLE
function. Inhibits synthesis
MOA by inhibiting fungal Binds to ergosterol
and polymerization of nucleic
squalene oxidase. in fungal cell Inhibit fungal P450-dependent
acids. Fungistatic.
Fungicidal. MOA membranes, enzymes blocking ergosterol
Dermatophytosis, forming artificial synthesis. Fungistatic.
Uses Dermatophytosis
Onychomycosis pores. Fungicidal.
Headache, Mental confusion, Gastrointestinal Candidiasis Mucocutaneous candidiasis,
Gastrointestinal irritation, upset, Rash, (Oropharyngeal, Dermatophytosis, Seborrheic
Uses
SE Photosensitivity, Headache, Taste Esophageal, dermatitis, Pityriasis
Hepatotoxicity, Disulfiram disturbances, Vaginal) versicolor
reaction, Drug interactions Hepatotoxicity Nephrotoxicity None significant when
SE
• from Penicillium • Accumulates in (severe) administered topically
griseofulvum keratin • Minimal • Limited to topical use
• Accumulates in keratin • Given PO and mucocutaneous because of systemic toxicity
• Potent CYP450 Inducer topical absorption
Notes
• Contraindicated in • More effective Notes • Available as a
porphyria than griseofulvin swish and
• Absorption is increased by in onychomycosis swallow
intake of fatty meal preparation
SYSTEMIC ANTIFUNGALS
AZOLE AZOLE
Pyrimidine AZOLE
Polyene (broad spectrum, (broad spectrum, Echinocandin
antimetabolite (narrow spectrum)
Good CNS penetration) Poor CNS penetration)
Drug
FLUCONAZOLE [D], CASPOFUNGIN[C]
KETOCONAZOLE
AMPHOTERICIN B [B] FLUCYTOSINE [C] VORICONAZOLE, ITRACONAZOLE [C] ANIDULAFUNGIN,
[C]
POSACONAZOLE MICAFUNGIN
Accumulated in
fungal cells by the
action of permease
Binds to ergosterol in Inhibit fungal P450-dependent enzymes blocking ergosterol Inhibits b-glucan
and converted by
fungal cell synthesis. Fungistatic. synthase
cytosine
MOA membranes, forming decreasing fungal
deaminase to 5-
artificial pores. * Ketoconazole is rarely used due to drug interactions and narrow cell wall
FU, which inhibits
Fungicidal. spectrum synthesis
thimidylate
synthase.
Fungistatic.
Blastomycosis,
Candidiasis
Sporotrichosis,
Systemic fungal (esophageal, Disseminated
Dermatophytosis,
infections oropharyngeal, and
Cryptococcosis, Chronic Chromoblastomycosis,
(Aspergillus, vulvovaginitis), mucocutaneous
Systemic candidal mucocutaneous Alternative for
Uses Blastomyces, Candida Coccidioidomycosis, candidiasis,
infections, candidiasis, infections due to
albicans, Cryptococcal Salvage therapy
Chromoblastomycosis Dermatophytosis Aspergillus,
Cryptococcus, meningitis for invasive
Coccidioides,
Histoplasma, Mucor) (treatment and aspergillosis
Cryptococcus and
prophylaxis)
Histoplasma, Candida
Infusion reactions
Gastrointestinal Headache,
(chills, fever, muscle Gastrointestinal
disturbances Gastrointestinal
spasms,hypotension), disturbances Gastrointestinal
Myelosuppression, (vomiting, distress, Fever,
Nephrotoxicity (vomiting, disturbances (vomiting,
SE Alopecia, diarrhea), Rash, Flushing
(Renal Tubular diarrhea), diarrhea),
Hepatotoxicity Rash, (histamine
Acidosis with Rash, Rash, Hepatotoxicity
Hepatotoxicity, release), Elevated
magnesium and Hepatotoxicity
Drug interactions liver enzymes
potassium wasting)
• Control infusion • Selective toxicity • Potent CYP450 • Alternative to • Much more selective • All are given IV
reactions by slowing occurs because inhibitor (Affect Amphotericin B in for fungal cells than • Micafungin can
rate of infusion and mammalian cells Phase I the treatment of Ketoconazole but increase levels
premedication with have low levels metabolism) C. neoformans with poor entry intro of cyclosporine
antihistamines of permease and • Limited to • As effective as CNS and tacrolimus
• Additive deaminase topical use Amphotericin B in • May also be used for
nephrotoxicity with • Decrease dose in because of candidemia subcutaneous
other nephrotoxic renal patients systemic toxicity • Posaconazole has chromoblastomycosis
drugs • Has synergistic • Interferes with the BROADEST
(aminoglycosides) effect when Steroid hormone spectrum triazole
• LIPID given with synthesis (the only azole
Notes FORMULATIONS: Amphotericin B • Resistance is due with activity
Ambisome, and Triazoles. to changes in the against Rhizopus
Amphotec, Abelcet sensitivity of sp.
• Highly lipid soluble, target enzyme (mucormycosis)
poorly absorbed in • Potent CYP450
the GIT inhibitor
• High Vd except in
the CNS with a t½ of
2 weeks
• Has the WIDEST
antifungal
spectrum
ANTIVIRAL CHEMOTHERAPY AND PROPHYLAXIS
ANTIVIRAL DRUGS
https://qrs.ly/oucke89
DRUGS FOR HERPESVIRUSES

ACYCLOVIR [B], VALACYCLOVIR,
GANCICLOVIR [C], FOSCARNET [C]
Drugs PENCICLOVIR, FAMCICLOVIR, CIDOFOVIR [C]
VALGANCICLOVIR (PYROPHOSPHATE ANALOGUE)
DOCOSANOL, TRIFLURIDINE
Inhibits viral RNA polymerase, DNA
Activated by viral thymidine kinase Inhibits viral DNA Inhibits viral DNA
polymerase, and HIV reverse
MOA (TK) to forms that inhibit viral DNA polymerase, causing chain polymerase, causing
transcriptase. Binds to
polymerase termination. chain termination.
pyrophosphate binding site.
CMV retinitis,
Mucocutaneous HSV
infections,
CMV retinitis,
Infections due to Infections due to Acyclovir-resistance,
Uses Acyclovir-resistance,
HSV-1, HSV-2, VZV CMV, HSV-1, HSV-2, VZV Ganciclovir-resistance,
HSV infection in patients with AIDS
Genital warts,
Molluscum
contagiosum
Nausea, Diarrhea, Headache, Leukopenia, Nephrotoxicity, Electrolyte
Delirium, Tremor, Seizures, Thrombocytopenia, abnormalities (hypocalcemia),
SE Nephrotoxicity
Hypotension, Nephrotoxicity Mucositis, Hepatotoxicity, Genitourinary ulceration, CNS effects
(crystalluria) Seizures, Neutropenia (headache, hallucinations, seizures)
• No activity against strains of HSV • No activity against strains • Active against strains • Active against strains of HSV with
with absent Thymidine Kinase of HSV with absent of HSV with absent absent thymidine kinase activity
activity thymidine kinase activity thymidine kinase • Does not require phosphorylation
• DOCOSANOL inhibits fusion • Given as IV or intraocular activity for antiviral activity
between the HSV envelope and implant (for CMV retinitis) • Dose adjustment in • Dose adjustment in renal patients
plasma membranes • Valganciclovir is a prodrug renal patients
• VALOMACICLOVIR is an of ganciclovir with
Notes investigational agent which acts increased oral
as an inhibitor of viral DNA bioavailability
polymerase for shingles and EBV
• Dose adjustment in renal patients
• Valacyclovir is a prodrug that is
converted to Acyclovir and
reached plasma levels 3-5x (longer
t½) more than acyclovir
PROTEASE INHIBITOR
DRUGS FOR HIV INDINAVIR [C], AMPRENAVIR, ATAZANAVIR,
HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART) DARUNAVIR, INDINAVIR, LOPINAVIR, NELFINAVIR,
• initiation of treatment with 3 or more anti-retroviral drugs, if Drugs RITONAVIR, SAQUINAVIR, TIPRANAVIR,
possible, before symptoms appear FOSAMPRENAVIR, BOCEPREVIR, TELAPRIVIR
• usually 2 NRTIs plus 1 protease inhibitor Name ends in -NAVIR
• combination of different drug classes to achieve synergism and MOA Inhibit viral protein processing
combat resistance Uses HIV infection
• Hyperlipidemia, Fat redistribution, Hyperglycemia,
REVERSE TRANSCRIPTASE INHIBITORS Insulin resistance
NON-NUCLEOSIDE • Atazanavir, Fosamprenavir, Lopinavir, Nelfinavir,
NUCLEOSIDE REVERSE SE
REVERSE Saquinavir: GI distress and diarrhea
TRANSCRIPTASE • Atazanavir: Peripheral neuropathy; Amprenavir: Rash;
TRANSCRIPTASE
INHIBITORS (NRTIs) Indinavir: Hyperbilirubinemia and nephrolithiasis
INHIBITORS (NNRTIs)
ZIDOVUDINE [C], DELAVIRDINE [C],
Drugs ABACAVIR, DIDANOSINE, EFAVIRENZ, ENTRY INHIBITORS
EMTRICITABINE, ETRAVIRINE, CCR5 RECEPTOR
FUSION INHIBITOR
LAMIVUDINE, NEVIRAPINE, Drug ANATAGONIST
STAVUDINE, TENOFOVIR, RILPIVIRINE ENFUVIRTIDE MARAVIROC
ZALCITABINE Most have -VIR- in the Binds to gp41 subunit of
middle of the name viral envelope Blocks viral attachment via
Inhibit HIV reverse Inhibit HIV reverse MOA glycoprotein, preventing transmembrane
transcriptase after transcriptase. No fusion of viral and cellular chemokine receptor CCR5
MOA membranes
phosphorylation by phosphorylation
cellular enzymes required. Uses HIV infection HIV infection
HIV infection, Prevention Injection site reactions, Cough, Diarrhea, Muscle
Uses of maternal-fetal HIV HIV infection Hypersensitivity, and joint pain, Increased
SE
transmission Increased incidence of hepatic transaminases
• Lactic Acidosis with • Delavirdine, Nevirapine: bacterial pneumonia
hepatic steatosis Rash, Increased No cross-resistance with Minimal cross-resistance
Notes
• Zidovudine: Bone AST/ALT other anti-HIV drugs with other anti-HIV drugs
marrow suppression • Efavirenz:
• Abacavir: Teratogenicity INTEGRASE INHIBITOR
Hypersensitivity • Etravirine: Increased Integrase inhibitor (an enzyme essential for
SE RALTEGRAVIR
• Didanosine: Pancreatitis cholesterol, replication of HIV) leading to inhibition of
• Stavudine, Zalcitabine: Name ends in
triglycerides -GRAVIR
strand transfer; DI: avoid using rifampicin
Peripheral neuropathy NO bone marrow concomitantly (lowered blood levels)
Abacavir, Emtricitabine, suppression in NNRTs
Lamivudine and Tenofovir because these are not
are safe for pregnant incorporated in the DNA.
MNEMONIC: NNRTIs (Non-Nucleoside RT inhibitors)

“Never Ever Deliver Nucleosides”
Nevirapine Efavirenz / Etravirine Delavirdine
DRUGS FOR INFLUENZA SUPPLEMENT: MISCELLANEOUS ANTIVIRALS:

an immune response modifier effective for
UNCOATING NEURAMINIDASE IMIQUIMOD
external genital and perianal warts
INHIBITOR INHIBITOR
Drugs Licensed for the treatment of cell-mediated
AMANTADINE [C], OSELTAMIVIR [C], INOSINE immune deficiencies associated with viral
RIMANTADINE ZANAMIVIR, PERAMIVIR ACEDOBEN infections; used for genital warts, herpes virus
Inhibit early step Inhibits Neuraminidase. DIMEPRANOL infection, subacute sclerosing panencephalitis
replication and prevent Decreases release of progeny and other conditions
MOA
uncoating by binding to virus.
M2 proton channels
Influenza A and B, Shortens
Uses Influenza A only
duration of symptoms ANTIPROTOZOAL DRUGS
• GI irritation, Dizziness, • Oseltamivir:
Cerebellar dysfunction Gastrointestinal effects;
SE
(ataxia, dysarthria), • Zanamivir: Bronchospasm
Livedo reticularis in asthmatics
Amantadine is also used OSELTAMIVIR: Presently the
Notes in treating drugs of choice for influenza
Parkinsonism (including H1N1)
DRUGS FOR HBV AND HCV

LAMIVUDINE [C],
ADEFOVIR
DIPIVOXIL,
INTERFERON-a
Drugs ENTECAVIR, RIBAVIRIN [X] Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
[X]
TELBIVUDINE,
TENOFOVIR, ANTIMALARIAL DRUGS
CLEVUDINE
Inhibits
CATEGORIES
guanosine • TISSUE SCHIZONTICIDES
triphosphate o kill schizonts in the liver
Degrades viral formation. o EXAMPLE: primaquine, atovaquone
RNA via
Inhibits HBV
Prevents • BLOOD SCHIZONTICIDES
MOA activation of host capping of viral o kill these parasitic forms only in the erythrocyte
DNA polymerase
cell RNAase mRNA. o EXAMPLES: chloroquine, quinine mefloquine, atovaquone,
(ribonuclease) Blocks RNA- pyrimethamine, doxycycline, halofantrine, artemisinin
dependent • GAMETOCIDES
RNA o kills gametocides in human blood
polymerases.
o EXAMPLES: primaquine
HBV infection, Hepatitis B
• SPORONTICIDES
HCV infection, infection, HIV HCV infection,
Uses o prevent sporogony and multiplication in the mosquito
Kaposi sarcoma, infection RSV infection
Genital warts (lamivudine) o EXAMPLES: proguanil, pyrimethamine
Adefovir: Lactic
Alopecia, TREATMENT OF MALARIA
acidosis,
Myalgia, Hemolytic CLINICAL
Renal and DRUG OF CHOICE / ALTERNATIVE
Depression, anemia, SETTING
hepatic toxicity
Flu-like Conjunctival
SE Chloroquine-
syndrome, and bronchial
Entecavir: sensitive P. Chloroquine
Thyroid irritation,
Headache, falciparum
dysfunction, Teratogen
Dizziness, P. vivax and
Hearing loss Chloroquine then Primaquine
Fatigue, Nausea P. ovale
Contraindications Co-infection Early IV Uncomplicated Artemether + Lumefantrine (CoArtem) /
include between HBV administration Chloroquine- Malarone or Mefloquine or Quinine Sulfate +
autoimmune and HIV may of ribavirin resistant Clindamycin or other Artemisinin-based
disease, history increase the risk decreases P. falciparum combination regimen
of cardiac of pancreatitis mortality in Severe or Artesunate then Doxycycline or Clindamycin
arrhythmias and with lamivudine viral Complicated or CoArtem ; Quinidine gluconate /
pregnancy use hemorrhagic P. falciparum Artemether or Quinine dihydrochloride
Notes fevers
OTHER DRUGS
FOR RSV:
Pavilizumab
(monoclonal
antibody
against RSV
antigen)
ANTI-MALARIAL
CHLOROQUINE [C],
QUININE [C],
HYDROXYCHLOROQUINE, ATOVAQUONE –
Drugs QUINIDINE MEFLOQUINE [B] PRIMAQUINE
AMODIAQUINE, PROGUANIL [C]
GLUCONATE
PIPERAQUINE
Complexes with DNA Forms electron- Atovaquone disrupts
to prevent strand transferring redox mitochondrial electron
Prevents polymerization of
separation. Blocks Unknown. Blood compounds that act as transport. Blood and tissue
MOA heme into hemozoin.
DNA replication and schizonticide cellular oxidants. schizonticide.
Blood schizonticide.
transcription. Blood Tissue schizonticide. Proguanil inhibits folate
schizonticide. Gametocide. synthesis. Sporonticide.
Malaria (non-falciparum, Chemoprophylaxis
chloroquine-sensitive), (chloroquine- Malaria (radical cure
Malaria (chloroquine- Treatment and
Chemoprophylaxis resistant areas), of P. vivax, P. ovale),
resistance), chemoprophylaxis
Uses (chloroquine-sensitive Alternative to Terminal prophylaxis
Severe falciparum (chloroquine-resistant
areas), quinine in acute (vivax, ovale), PCP
malaria (quinidine) P. falciparum) – all stages
Rheumatoid arthritis, attacks of falciparum pneumonia
Amebic liver abscess malaria
GI distress, Skin rash,
GI irritation, Skin rash,
Cinchonism Headache, Dizziness,
Headaches, GI distress, Pruritus,
(headache, tinnitus, Cardiac conduction Abdominal pain, Nausea,
Peripheral neuropathies, Headaches,
vertigo), defects, Psychiatric Vomiting, Diarrhea,
SE Myocardial depression, Methemoglobinemia,
Hemolysis in G6PD disorders Headache, Rash, Increased
Retinal damage, Hemolysis in G6PD
deficiency, (psychosis), liver enzymes
Auditory impairment, deficient patients
Blackwater fever Neurologic
Psychosis, QT prolongation
symptoms, Seizures
• May precipitate porphyria • Quinine is commonly • Should be used with
used with a blood schizonticide
doxycycline or • Eradicates
Notes clindamycin to limit hypnozoites in the
toxicities liver, preventing
• DOC for malaria in malarial relapse
pregnant patients
ARTEMISININ, ARTESUNATE,
HALOFANTRINE [C],
Drugs SULFADOXINE-PYRIMETHAMINE [C] DOXYCYCLINE [D] ARTEMETHER,
LUMEFANTRINE
DIHYDROARTEMISININ
Sequential blockade of folic acid Impairs progeny of
Forms toxic free radicals in
synthesis. malarial apicoplast genes, Unknown.
MOA malarial food vacuole.
Blood schizonticide. resulting in abnormal cell Blood Schizonticide.
Blood schizonticide.
Sporonticide (pyrimethamine). division. Blood schizonticide.
Malaria (chloroquine-
Malaria (chlorine-resistant P. Chemoprophylaxis resistance), Malaria (uncomplicated
Uses
falciparum) (Multidrug-resistant) Severe falciparum malaria falciparum, quinine-resistant)
(quinidine)
GI disturbance, Abdominal pain, Diarrhea,
Teratogen (tooth enamel Vomiting, Cough, Rash,
Skin rashes, GI distress, Hemolysis, dysplasia/discoloration), Headache, Pruritus,
SE Kidney damage, Drug interactions, Hepatotoxicity, Elevated liver enzymes, Nausea, Vomiting, Diarrhea
Folic acid deficiency (pyrimethamine) Nephrotoxicity, Cardiotoxicity (prolongs PR
Photosensitivity, and QT interval),
Vestibulotoxicity Teratogen
• Competition for plasma protein • Do NOT drink with milk • Lumefantrine used in • Artemisinin-based
binding sites with other drugs (decreased absorption) combination with combination therapy is
• Pyrimethamine is a long-acting folate artemether (Co-Artem) current the first line of
antagonist • Artemether- malaria treatment
Lumefantrine(Co-Artem) recommended by the WHO
is the drug of choice for for children, adults and
uncomplicated pregnant women in 2nd or
Notes
falciparum malaria in the 3rd trimester. Due to
Philippines potential embryotoxicity of
artemisinins identified in
animal studies, artemisinins
are not considered safe for
use in 1st trimester of
pregnancy.
DRUGS FOR AMEBIASIS

DISEASE FORM DRUG(s) OF CHOICE
Asymptomatic intestinal
Luminal agent (diloxanide furoate, iodoquinol, paromomycin)
colonization
Metronidazole or Tinidazole
Amebic colitis (dysentery)
plus Luminal agent*
• Metronidazole or Tinidazole
followed by Luminal agent*
• Percutaneous or surgical drainage if:
Amebic liver abscess
o Abscess is 5 cm or greater diameter
o if they are in the left lobe
o no clinical response to medical therapy
LUMINAL AMEBICIDES TISSUE AMEBICIDES

act only in the lumen of the bowel act on organisms in the bowel wall and the liver
Drug METRONIDAZOLE [B],
DILOXANIDE EMETINE,
IODOQUINOL PAROMOMYCIN [C] TINIDAZOLE [C], NITAZOXANIDE [B]
FUROATE DEHYDROEMETINE
SECNIDAZOLE [C]
Reactive reduction
Inhibit proteins
Inhibits protein Reactive reduction by by ferredoxin
synthesis. Blocks
Unknown. Unknown. synthesis. Binds ferredoxin forming free forming free
ribosomal
OA Luminal Luminal to 16S ribosomal radicals that disrupt radicals that disrupt
movement along
amebicide. amebicide. subunit. Luminal electron transport chain. electron transport
messenger RNA.
amebicide. Tissue amebicide. chain. Tissue
Tissue amebicide.
amebicide.
Backup drug for
Severe intestinal and
severe intestinal and
Asymptomatic Mild-to-severe Asymptomatic extraintestinal amebiasis
Metronidazole- extraintestinal
cyst carriers intestinal amebiasis cyst carriers (drug of choice),
resistant amebiasis, amebiasis
of (backup), Trichomoniasis, Giardiasis,
Uses Giardiasis,
E. histolytica *Used in Intestinal Bacterial vaginosis,
Cryptosporidiosis * Reserved only for
(drug of combination with amebiasis, Anaerobic infections
(drug of choice) situations when
choice) Metronidazole Cryptosporidiosis (B. fragilis, C. difficile),
metronidazole
Peptic ulcer disease
cannot be used
Gastrointestinal
Gastrointestinal
distress, Thyroid
Gastrointestinal irritation, distress,
enlargement, Skin
Flatulence, Metallic taste, Headache, Muscle weakness,
reactions due to Headaches,
Nausea, Dark urine, Leukopenia, Gastrointestinal Cardiovascular
SE iodine toxicity, Dizziness, Rashes,
Abdominal Dizziness, Ataxia, distress dysfunction
Neurotoxicity Arthralgia
cramps Neuropathy, Seizures, (arrhythmias and
(peripheral
Disulfiram reaction congestive heart
neuropathy, visual
failure)
dysfunction)
DRUGS FOR PNEUMOCYSTOSIS AND DRUGS FOR TRYPANOSOMIASIS

TOXOPLASMOSIS Disease Stage
First-line Alternative
SULFADIAZINE- drugs drugs
PYRIMETHAMINE [C], Suramin,
Drug CO-TRIMOXAZOLE [C] Early Pentamidine
PYRIMETHAMINE + Eflornithine
West
CLINDAMYCIN Melarsoprol,
African CNS
Sequential blockade of Sequential blockade of Eflornithine Eflornithine-
involvement
dihydropteroate synthase dihydropteroate synthase Nifurtimox
MOA (sulfamethoxazole) and (sulfadiazine) and Early Suramin Pentamidine
East
dihydrofolate reductase dihydrofolate reductase CNS
African Melarsoprol -
(trimethoprim) (pyrimethamine) involvement
Prophylaxis and treatment
of pneumocystosis Prophylaxis and treatment TREATMENT OF OTHER PROTOZOA
Uses (drug of choice), of Toxoplasmosis ORGANISM DRUG OF CHOICE / ALTERNATIVE
Prophylaxis (drug of choice) Clindamycin or Quinine / Atovaquone
Babesia sp.
(T. gondii, I. belli) or Azithromycin
GI upset, Balantidium Coli Tetracycline / Metronidazole
Gastric irritation, Glossitis,
Acute hemolysis in G6PD Cryptosporidium sp. Paromomycin / Azithromycin
Neurologic symptoms
deficiency, Cyclospora cayetanensis TMP-SMX
(headache, insomnia,
Nephrotoxicity, Dientamoeba fragilis Iodoquinol/Tetracycline or Paromomycin
tremors, seizures),
Hypersensitivity (assume Metronidazole or Tinidazole /
SE Hematotoxicity Giardia lamblia
cross-hypersensitivity, Furazolidone or Albendazole
(megaloblastic anemia,
SJS/TEN), TMP-SMX / Pyrimethamine or Folinic
thrombocytopenia), Isospora belli
Hematotoxicity, Acid
Pseudomembranous colitis
Drug interactions, Microsporidia Albendazole
(clindamycin)
Kernicterus Sodium stibogluconate / Meglumine or
• Recommended at CD4 Leishmania Pentamidine or Amphotericin or
Notes
count < 200 Miltefosine or Paromomycin
TMP-SMX / Pentamidine or TMP-
Pneumocystis jirovecii Dapsone or Clindamycin + Primaquine
or Atovaquone
Pyrimethamine + Clindamycin + Folinic acid
Toxoplasma gondii or Spiramycin / Pyrimethamine +
Sulfadiazine + Folinic acid
Trichomonas vaginalis Metronidazole or Tinidazole
Trypanosoma cruzi Nifurtimox or Benznidazole
DRUGS FOR TRYPANOSOMIASIS, LEISHMANIASIS
SODIUM
STIBOGLUCONATE,
MEGLUMINE
Drug PENTAMIDINE SURAMIN EFLORNITHINE MELARSOPROL NIFURTIMOX
ANTIMONATE,
AMPHOTERICIN,
MILTEFOSINE
Organic arsenical. Unknown. Probably
Suicide inhibitor Inhibits
Unknown. Probably inhibits glycolysis or Inhibits enzyme inhibits glycolysis or
MOA of ornithine trypanothione
interferes with nucleic acid metabolism. sulfhydryl groups interferes with nucleic
decarboxylase reductase
in trypanosomes. acid metabolism.
Leishmaniasis (drug
of choice except in India)
African sleeping Chagas disease
African sleeping Alternative drugs
sickness (drug of choice),
sickness Advanced West include:
(hemolymphatic African sleeping African sleeping
(hemolymphatic African sleeping Visceral (kala-azar):
Uses stages), Prophylaxis sickness sickness
stages), sickness pentamidine, miltefosine
for pneumocystosis, (drug of choice) (backup),
Onchocerciasis (drug of choice) Cutaneous: fluconazole,
Kala-azar (visceral Mucocutaneous
(backup) metronidazole
leishmaniasis) leishmaniasis
Mucocutaneous:
amphotericin B
Respiratory Fatigue, Nausea,
Gastrointestinal Nausea, Gastrointestinal
stimulation followed Vomiting, Seizures, Shock
irritation, Vomiting, symptoms, Fever,
by depression, Fever, Rash, Headache, Diarrhea,
Reactive Abdominal pain, Headache, Myalgias,
Hypotension, Paresthesia, Neuropathies, Vomiting, Anemia,
encephalopathy Fever, Rash, Arthralgias, Rash,
SE Hypoglycemia, Renal abnormalities Thrombocytopenia,
Restlessness, Sterile abscesses,
Anemia, (proteinuria), Leukopenia,
Crosses the blood Insomnia, Cardiotoxicity
Neutropenia, Chronic diarrhea, Seizures
brain barrier Neuropathies, (T-wave changes,
Hepatitis, Hemolytic anemia,
Seizures QT prolongation)
Pancreatitis Agranulocytosis
• Does not cross the • Does not cross the • Crosses the blood • Administered • Does not cross
blood brain barrier blood brain barrier brain barrier intramuscularly the blood
Notes • Administered by • Used in combination • Considerably • Usually brain barrier
nasal spray with melarsoprol less toxic than administered
(aerosol) melarsoprol with suramin
ANTHELMINTHIC DRUGS
DRUGS ACTIVE AGAINST NEMATODES

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

Drug PRAZIQUANTEL [B] NICLOSAMIDE
Increases membrane permeability to calcium → paralysis. Causes muscle Uncouples oxidative phosphorylation or
MOA
paralysis, vacuolization and death. by activating ATPases
Drug of choice for
Alternative drug for cestode infections
trematodes (Schistosoma, Paragonimus, Clonorchis, Opisthorchis,
Uses (Taenia, Diphyllobothrium, Hymenolepsis, Dipylidium,
Fasciolopsis, Heterophyes)
Fasciolopsis, Heterophyes)
and cestodes (Taenia, Diphyllobothrium, Hymenolepsis)
Headache, Dizziness, Nausea, Malaise, drowsiness, GI upset, arthralgia,
SE Gastrointestinal distress, Headache, Rash, Fever
myalgia, pruritus, skin rash,
• Contraindicated in ocular cysticercosis (may cause irreparable eye damage) • Kills scolices and cestode segments but has no effect on ova
Notes • Used with corticosteroids in treating neurocysticercosis • Avoid ethanol consumption for 48h upon drug
• May be used as an adjunct to Albendazole in Hydatid disease administration
GASTROINTESTINAL PHARMACOLOGY
DRUGS USED IN PEPTIC ULCER DISEASE

PEPTIC ULCER DISEASE
• chronic most often solitary lesions that occur in any portion of the gastrointestinal tract exposed to the aggressive action of acid-peptic juices
• at least 98% occur either in the first portion of the duodenum or in the stomach
PEPTIC ULCER DRUGS
ANTACIDS H2-RECEPTOR ANTAGONIST PROTON PUMP INHIBITORS
Drugs MAGNESIUM-ALUMINUM OMEPRAZOLE [C], LANSOPRAZOLE [B],
CIMETIDINE [B], RANITIDINE [B],
HYDROXIDE [C], CALCIUM RABEPRAZOLE [C],
FAMOTIDINE, NIZATIDINE
CARBONATE, SODIUM BICARBONATE PANTOPRAZOLE [B], ESOMEPRAZOLE [C]
Irreversible blockade of H+/K+ ATPase in active gastric
Neutralize stomach acid by reacting Competitive pharmacologic block of
MOA parietal cells. Long-lasting reduction of meal-stimulated
with protons in the lumen of the gut H2 receptors
and nocturnal acid secretion.
Peptic ulcer disease Peptic ulcer disease (DOC), Zollinger-Ellison syndrome,
Peptic ulcer disease, Gastroesophageal reflux, Dyspepsia, SJS
MAGnesium hydroxide causes Zollinger-Ellison syndrome,
Uses diarrhea: MAGtatae ka! PPIs are given for bleeding PUD, for 3 important reasons
Gastroesophageal reflux, Dyspepsia
ALUMinum hydroxide causes 1). To maintain the stability of the clot 2). To maintain an
constipation: Ayaw LUMabas! intragastric pH of 6 and 3) to reduce mortality.
Sodium bicarbonate: belching, Gynecomastia (cimetidine only),
Diarrhea, Headache, Abdominal pain, Malabsorption
metabolic alkalosis, fluid retention Diarrhea, Headache, Fatigue, Myalgias,
(Vit B12, Ca, Fe, Zn), Infections (respiratory, enteric),
SE Calcium carbonate: hypercalcemia, Constipation, Nosocomial pneumonia,
Hypergastrinemia, Atrophic gastritis, Fractures of the
renal insufficiency, metabolic Mental status changes, Bradycardia,
hip and spine
alkalosis (milk-alkali syndrome) Hypotension, Blood dyscrasias
• Caution in giving to Px with Renal • Cimetidine is a potent inhibitor of • PPIs should be taken before meals, ideally 30mins to 1
Insufficiency CYP450 hour before breakfast
• Impairs absorption of tetracyclines, • Highly-effective in suppressing • May interfere with absorption of drugs where gastric
fluoroquinolones, itraconazole and Nocturnal acid secretion but only pH is an important determinant of their bioavailability
iron → should not be given within 2 modest effect on meal-stimulated (e.g. Ketoconazole, Ampicillin, Ferrous salts, Digoxin)
hours with these drugs secretion • Use with caution in Hepatically-impaired (Omep, Esomep,
Notes • When used regularly in large doses • Ranitidine: Adjust doses for Renally Panto) and Renally-impaired (Omep, Panto) patients
needed to significantly raise the impaired patients • PPIs are possibly associated with Clostridium difficile-
stomach pH, antacids decrease May be used for pregnant patients associated diarrhea
recurrence rate of peptic ulcers • Daily long-term use (more than 3yrs) may lead to
• Aluminum and Magnesium are malabsorption or deficiency of Vit B12
always given together to cancel out Amongst the PPI, pantoprazole has the least drug-drug
each other's adverse effect interaction.
MUCOSAL PROTECTIVE AGENTS
Drugs SUCRALFATE [B] MISOPROSTOL [X] BISMUTH SALICYLATE [C]
Binds to injured tissue and forms a Forms a protective coating on ulcerated tissue.
protective covering over ulcer beds. Activates EP receptors. Causes
Stimulates mucosal protective mechanisms, direct
Accelerates healing of peptic ulcers and increased HCO3 and mucus secretion
antimicrobial effects and sequestration of
reduces recurrence rate. in stomach. Uterine contraction.
MOA enterotoxins.
Coats the ulcer bed to protect it from the Activates PGE1 receptor which
stomach acid → healing. This drug has dual activity: mucosal protective agent
decreases acid secretion and increases
Needs frequent dosing since it will be and bactericidal effect on H. pylori from its heavy metal
mucus secretion in the stomach
washed away when you drink or eat. component (Bismuth)
Peptic ulcer disease,
Uses Peptic ulcer disease Prevention of NSAID-induced gastric Peptic ulcer disease, Dyspepsia, Infectious diarrhea
mucosal injury, Abortifacient
Abdominal pain, Diarrhea, Uterine Black stools, Darkening of tongue, Encephalopathy
SE None
cramping, Miscarriage (ataxia, headaches, confusion, seizures)
• Highly insoluble, requiring frequent dosing • Reduces stool frequency and liquidity in infectious
Notes
• Caution in chronic renal impairment diarrhea
REGIMENS RECOMMENDED FOR H. PYLORI ERADICATION DRUGS THAT PROMOTE UPPER GI MOTILITY
Drug Dose
PROKINETIC AGENTS
Triple Therapy
METOCLOPRAMIDE [B], DOMPERIDONE [C],
1. Bismuth subsalicylate plus 2 tablets qid Drugs
ERYTHROMYCIN [B]
Metronidazole plus 250 mg qid
Metoclopramide and domperidone block D2 receptors.
Tetracycline 500 mg qid
Erythromycin stimulates motilin receptors. Increases
2. Ranitidine bismuth citrate plus 400 mg bid
gastric emptying and intestinal motility.
Tetracycline plus 500 mg bid MOA
Correlation to Surgery: Erythromycin is used in bowel
Clarithromycin or 500 mg bid
preparation prior surgery because it binds to the motilin
metronidazole receptor. Diarrhea is a common side effect of macrolides.
3. Omeprazole (lansoprazole) plus 20 mg bid (30 mg bid) Antiemetic for post-operative / chemotherapy
Clarithromycin plus 250 or 500 mg bid Uses
vomiting, Diabetic Gastroparesis (drug of choice)
Metronidazole or 500 mg bid
SE Parkinsonism, Extrapyramidal effects, Hyperprolactinemia
Amoxicillin 1 gr bid
Notes Domperidone does not cross the BBB (less toxic)
Quadruple Therapy
Omeprazole (lansoprazole) 20 mg (30mg) daily
Bismuth subsalicylate 2 tablets qid LAXATIVES
Metronidazole 250 mg qid • substance that increases the probability of a bowel movement
Tetracycline 500 mg qid by several mechanisms:
o irritant or stimulant action on the bowel wall
o bulk-forming action on the stool that evokes reflex contraction
of the bowel
o softening action on hard or impacted stool
o lubricating action that eases passage of stool through the rectum
SUPPLEMENT: Melanosis Coli
• benign disorder of colonic pigmentation
• due to accumulation of brown lipofuscin pigments in macrophages
• usually result from intake of anthraquinone-containing laxatives (e.g.
Senna)
LAXATIVES
BULK-FORMING STIMULANT LAXATIVE/
STOOL SOFTENER OSMOTIC LAXATIVE
LAXATIVE CATHATRTICS
Drugs PSYLLIUM [B], LACTULOSE [B], MAGNESIUM OXIDE,
BISACODYL [B], ALOE,
METHYLCELLULOSE, DOCUSATE [C], GLYCERINE SORBITOL, MAGNESIUM CITRATE,
SENNA, CASCARA,
POLYCARBOPHIL, SUPPOSITORY, MINERAL OIL SODIUM PHOSPHATE,
CASTOR OIL
MALTODEXTRIN POLYETHYLENE GLYCOL
Indigestible, hydrophilic
Unknown. Directly
colloids that absorb
Soluble but nonabsorbable compounds stimulate enteric
water, forming a bulky, Soften stool material, permitting
MOA that result in increased stool liquidity due nervous system and
emollient gel that water and lipids to penetrate
to an obligate increase in fecal fluid colonic electrolyte and
distends the colon and
fluid secretion.
promotes peristalsis
Constipation Constipation,
Usually given to patients after MI so Hepatic encephalopathy (lactulose),
Uses Constipation Constipation
that they don’t have to do Valsalva Preparation for endoscopy
when defecating (polyethylene glycol)
• Diarrhea • Diarrhea, Aspiration (lipid pneumonitis) • Diarrhea, Flatus, Abdominal cramps, • Diarrhea,
• Malabsorption of fat-soluble • Electrolyte abnormalities Melanosis coli
SE vitamins (A, D, E, K) (hyperphosphatemia, hypocalcemia, (anthraquinone-
hypernatremia, hypokalemia, containing laxatives
hypermagnesemia) like Senna)
ANTIDIARRHEAL AGENTS ANTIEMETICS

OPIOID: DIPHENOXYLATE [C], LOPERAMIDE, 5-HT3-RECEPTOR ANTAGONIST
Drugs NON-OPIOD: KAOLIN + PECTIN, ONDANSETRON [B], GRANISETRON, DOLASETRON,
Drugs
COLLOIDAL BISMUTH, DIFENOXIN PALONOSETRON, ALOSETRON, TROPISETRON
Activates opioid receptors in enteric nervous system. Block chemoreceptor trigger zone and enteric nervous
MOA
Slows motility with negligible CNS effects. system 5-HT3 receptors.
MOA
Uses Diarrhea (nonspecific, noninfectious) 5HT3 receptors are found in the CTZ (Chemoreceptor
SE Drowsiness, Nausea, Paralytic ileus trigger zone) on the floor of the 4th ventricle of the brain
• Do not use in children less than 4 years of age Uses Vomiting (post-chemotherapy, postoperative)
Notes (increased chance of causing paralytic ileus) Headache, Dizziness, Constipation, QRS and QT
SE
• Reverse ileus by administering Bethanechol prolongation (dolasetron only)
The process of vomiting has an interplay of factors. Activating D2 receptor
in the area postrema triggers vomiting, substance P binding neurokinin MISCELLANEOUS GI DRUGS
can cause pain-induced vomiting, we may give Aprepitant in this case. An amino acid derivative of quinolinone that is
Stimulation of the cholinergic receptor in the auditory canal can cause used for mucosal protection, healing of
motion sickness, we can give an anticholinergic Scopolamine and the gastroduodenal ulcers, and treatment of
famous 5HT3 receptor antagonist in the area postrema Ondansetron for REBAMIPIDE
gastritis; Works by enhancing mucosal defense
post-operative and chemotherapy-induced vomiting. Many drugs can
scavenging free radicals and temporarily
cross the area postrema because it is devoid of the blood brain barrier.
Dr. Calderon Jr. activating genes encoding for COX-2
A prokinetic benzamide derivative unlike
DRUGS USED IN INFLAMMATORY BOWEL metoclopramide or domperidone; inhibit
ITOPRIDE dopamine and acetylcholine esterase enzyme
DISEASE and have gastrokinetic effect; for functional
IMMUNOMODULATOR: dyspepsia and gastroparesis; take before meals
MESALAMINE (5-ASA) [C], BALSALAZIDE, Changes surface tension of gas bubbles and causes
Drugs
OLSALAZINE, SULFASALAZINE, MESALAZINE SIMETHICONE collapse of foam bubbles, thus allowing easier
Unknown. Probably inhibits production of eicosanoid passage of gas and preventing gas pockets in GIT
MOA
inflammatory mediators. A gastroprokinetic agent that acts as a
Inflammatory bowel disease (mild to moderate) selective 5HT4 agonist. Its major active
Uses Used only for mild CONTROLLED cases. Flareups should metabolite, known as M1, additionally acts
be given immunosuppressants such as corticosteroids, TNF MOSAPRIDE 5HT3 antagonist, which accelerates gastric
antagonists, Cyclosporine etc. emptying throughout the whole GIT; used for
Gastrointestinal upset, Headaches, Arthralgias, Myalgias, the treatment of gastritis, GERD, functional
SE Bone marrow suppression, Malaise, Hypersensitivity dyspepsia and IBS; taken 1-2hrs before meals
reactions (severe) Increases the availability of endogenous
• TNF ANTAGONIST: opioids (enkephalins) by inhibiting
o ADALIMUMAB, CERTOLIZUMAB, INFLIXIMAB membrane-bound enkephalinase. Unlike other
opioid medications used to treat diarrhea
• CORTICOSTEROIDS:
RACECADOTRIL which reduce intestinal motility, Racecadotril
o BUDESONIDE, HYDROCORTISONE, METHYLPREDNISOLONE
has an antisecretory effect – it reduces the
secretion of water and electrolyte into the
THERAPY FOR INFLAMMATORY BOWEL DISEASE intestine; reduces both the frequency and
Disease Responsiveness duration of acute diarrhea
Therapy
severity to therapy A probiotic; has been found to produce
• Surgery BACILLUS
antimicrobial substances that are active
• Natalizumab against gram positive bacteria including
CLAUSII
• Cyclosporine Refractory Staphylococcus aureus, Enterococcus faecium
Severe and Clostridium difficile
• TNF antagonists
• Intravenous Hepatoprotectant; MOA is not yet well
understood but there are some proposals:
corticosteroids
as antioxidant, scavenger and regulator of
• TNF antagonists intracellular content of glutathione
• Oral corticosteroids as cell membrane stabilizers and permeability
Moderate • Methotrexate regulators that prevent hepatotoxic agents
• Azathioprine / 6- from entering hepatocytes as promoters of
Mercaptopurine ribosomal RNA synthesis, stimulating liver
• Budesonide (ileitis) regeneration and as inhibitor of the
SILYMARIN
• Topical corticosteroids transformation of stellate hepatocytes into
Mild (proctitis) Responsive myofibroblasts, the process responsible for the
deposition of collagen fibers leading to
• Antibiotics
cirrhosis. Anti-inflammatory and anti-
• 5-Aminosalicylates carcinogenic properties have also been
documented; is able to neutralize the
THERAPY FOR GALLSTONES hepatotoxicity of several agents, including
URSODIOL (URSODEOXYCHOLIC ACID) Amanita phalloides, ethanol, paracetamol and
Drug carbon tetrachloride in animal models
(Bile acid)
Decreases the cholesterol content of bile by reducing ROWACHOLÒ Increases biliary secretion, relieves spasms of
cholesterol secretion; appears to stabilize hepatocyte – menthol, the bile ducts, enhances metabolic liver
MOA canalicular membranes possibly through a reduction in the menthone, function and reduces biliary stasis; can also
concentration of other endogenous bile acids or through alpha and beta inhibit HMG-CoA reductase enzyme leading to
inhibition of immune-mediated hepatocyte destruction. pinene, borneol, reduced cholesterol production (maintaining
Dissolution of small cholesterol gallstones in Px with camphene, the bile above the saturation level, assisting
symptomatic gallbladder disease who refuse surgery or cineol and dissolution of gallstones and preventing
are poor surgical candidates, for prevention of gallstones olive oil precipitation of further stones)
Uses
in obese Px undergoing rapid weight loss therapy, ANORECTAL PREPARATIONS
reduces liver function abnormalities and improve liver Potent venotropic drug used in the treatment of
histology in early-stage primary biliary cirrhosis venous insufficiency; increases venous tone,
• None. Diarrhea is rare improves lymph drainage and protects
SE • Chenodeoxycholate (predecessor) has been associated DAFLONÒ
microcirculation; the flavonoids contained in Daflon
with hepatotoxicity (Diosmin +
has been demonstrated to restrain lysosome
Hesperidin)
enzymes and interfere with enzymes involved in the
THERAPY FOR KIDNEY STONE flow of arachidonic acid which causes inflammation.
It also demonstrated an antioxidant activity.
Drug POTASSIUM CITRATE Policresulen arrests bleeding by coagulating
Metabolized to bicarbonate, which alkalinizes urine & blood protein and inducing the muscle fiber of
MOA
raises urinary citrate small blood vessels to contract. The coagulating
Hypocitraturic calcium oxalate nephrolithiasis, Renal FAKTUÒ properties and acidic pH brings about the
Uses tubular acidosis with calcium stones, Uric acid lithiasis, (Policresulen antimicrobial action against E.coli, Staphylococci
Urine alkalinization + sp., Streptococci sp., Pseudomonas aeruginosa,
Abdominal discomfort, vomiting, diarrhea, loose bowel Cinchocaine) Proteus vulgaris, Candida and other bacteria.
movements, nausea. Potentially Fatal: Hyperkalemia. Thus, the wound is protected against infection;
SE Cinchocaine has local anesthetic action which
Precaution giving to those with impaired K excretion
relieved pain and itching
(e.g. severe myocardial damage or heart failure)
SOLVENTS
TOXICOLOGY Agents ALIPHATIC AROMATIC
• branch of pharmacology that encompasses the deleterious HYDROCARBONS HYDROCARBONS
effects of chemicals on biologic systems • Agents: halogenated • Agents: benzene,
solvents such as toluene, xylene
Features carbon tetrachloride,
TOXIC CHEMICALS IN THE ENVIRONMENT chloroform and
AIR POLLUTANTS trichloroethylene
Agents
CARBON MONOXIDE SULFUR DIOXIDE
• odorless, colorless gas • colorless, irritating • CNS depression • CNS depression
that competes avidly gas from (nausea, vertigo, with ataxia and
with oxygen for combustion of locomotor coma
hemoglobin fossil fuels disturbances, • long-term exposure
• affinity of CO for • forms sulfurous headache, coma) to benzene is
hemoglobin is more than acid on contact • chronic exposure associated with
200-fold greater than with mucous leads to hematotoxicity
Effects
Features that of oxygen membranes hepatotoxicity and (thrombocytopenia,
• threshold limit values of nephrotoxicity aplastic anemia,
CO: for an 8-h workday • long-term exposure to pancytopenia) and
is 25 parts per million tetrachloroethylene hematologic cancers
(ppm) or to trichloroethane (leukemia)
• in heavy traffic, the has caused peripheral
concentration of CO may neuropathy
exceed 100 ppm • removal from • removal from
• headache, confusion, • conjunctival and exposure and CNS exposure and CNS
Treatment
decreased visual acuity, bronchial irritation supportive measures supportive
cherry red skin, (bronchospasm) measures
tachycardia, syncope, • heavy exposure
coma, seizures, death may lead to HEAVY METALS AND CHELATORS
• collapse and syncope delayed pulmonary
occur when ~ 40% of edema
Effects
hemoglobin has been • chronic low-level
converted to exposure may
carboxyhemoglobin aggravate
• prolonged hypoxia can cardiopulmonary
result in irreversible disease
damage to the brain and
the myocardium
• removal of the source of • removal from
CO and 100% oxygen exposure to SO2
Treatment • Hyperbaric oxygen • relief of irritation
accelerates the and inflammation
clearance of CO Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
AIR POLLUTANTS
Agents Chelating Agent / Chelator
NITROGEN OXIDES OZONE
• a molecule with 2 or more electronegative groups that can form
• brownish irritant gas • bluish irritant gas
stable coordinate complexes with multivalent cationic metal
formed in fires and produced in air and
atoms
Features silage on farms water purification
devices and in • EXAMPLES: dimercaprol, succimer, EDTA, penicillamine,
electrical fields deferoxamine
• deep lung irritation • irritation /dryness of ANTIDOTES

and pulmonary the mucous ANTIDOTE POISON
edema membranes Acetylcysteine Acetaminophen
• irritation of the eyes, • pulmonary function Atropine Cholinesterase inhibitors
nose and throat impaired at higher Bicarbonate Quinidine, TCAs
Effects concentrations Calcium Fluoride, CCBs
• chronic exposure leads Deferoxamine Iron
to bronchitis, Digoxin antibodies
bronchiolitis, Digoxin
(Digibind)
pulmonary fibrosis and
Caffeine, Theophylline,
emphysema Esmolol
sympathomimetics
• no specific treatment • no specific treatment Ethanol Methanol, Ethylene glycol
is available is available
Flumazenil Benzodiazepines, Zolpidem
Treatment • measures to reduce • measures to reduce
Fomepizole Methanol, Ethylene glycol
inflammation and inflammation and
Glucagon Beta-adrenoceptor blockers
pulmonary edema pulmonary edema
Glucose Hypoglycemics
Hydroxocobalamin Cyanide
Naloxone Opioids analgesics
Oxygen Carbon monoxide
Physostigmine Muscarinic receptor blockers
Pralidoxime Organophosphates
Protamine sulfate Heparin
Vitamin K, FFP Warfarin
CHELATORS
EDETATE CALCIUM DEFEROXAMINE,
Drugs DIMERCAPROL SUCCIMER PENICILLAMINE
DISODIUM (EDTA) DEFERASIROX, DEFERIPRONE
Chelates arsenic and Chelates lead, Chelates copper,
Chelates lead, forming Chelates iron, forming water-
mercury, forming water- forming water- forming water-
MOA water-soluble complexes soluble complexes that are
soluble complexes soluble complexes soluble complexes
that are excreted in urine excreted in urine
excreted in urine excreted in urine. excreted in urine
Copper poisoning,
Acute arsenic poisoning, Wilson's disease,
Acute iron poisoning, Iron
Acute mercury poisoning, Lead poisoning Adjunctive therapy Chronic lead poisoning
Uses overload states (thalassemia,
Chronic lead poisoning (oral treatment) in gold, arsenic and (severe)
myelodysplastic syndrome)
(severe) lead intoxication,
Rheumatoid arthritis
Transient hypertension, Skin reactions (blushing,
Nephrotoxicity with
Tachycardia, Headache, Gastrointestinal erythema, urticaria),
proteinuria,
Nausea and vomiting, distress, Hypocalcemia, Neurotoxicity
Pancytopenia,
Paresthesia, Fever, CNS effects, Nephrotoxicity (e.g. retinal degeneration),
SE Autoimmune
Injection site reactions Skin rash, (renal tubular necrosis), Hepatotoxicity, Nephrotoxicity,
dysfunction (drug-
(pain, hematomas), Elevation of liver ECG changes Coagulopathies, Hypotension,
induced lupus,
Thrombocytopenia, enzymes ARDS, Increased susceptibility
hemolytic anemia)
Increased prothrombin time to infections
• Co-administered with • Administered at • Co-administered with
EDTA in severe chronic blood lead dimercaprol in severe
lead poisoning concentrations chronic lead poisoning
Notes greater than 45 • To prevent dangerous
mcg/dL hypocalcemia, EDTA is
given as the calcium
disodium salt
COMMON POISONING SYNDROMES

ANTIMUSCARINIC CHOLINOMIMETIC
Agents OPIOIDS SALICYLATES
POISONING (Organophosphate poisoning)
delirium, hallucinations, anxiety, agitation, seizures, coma, lethargy, sedation, confusion, lethargy, coma,
seizures, coma, tachycardia, bradycardia or tachycardia, coma, bradycardia, seizures, hyperventilation,
hypertension, hyperthermia, pinpoint pupils, salivation, hypotension, hyperthermia, dehydration,
mydriasis, decreased bowel sweating, hyperactive bowel, hypoventilation, hypokalemia, anion gap
sounds, urinary retention muscle fasciculations, paralysis pinpoint pupils, cool metabolic acidosis
use hot as a hare use DUMBBELSS mnemonic skin, decreased bowel use CHAFS mnemonic
mnemonic sounds, flaccid Coma
Clinical HOT as a hare muscles Hyperventilation
Features (hyperthermia) Acidosis/HAGMA
use PCR mnemonic
DRY as a bone Pupillary constriction Fever
(decreased secretion) Comatose state Seizures
RED as a beet Respiratory
(cutaneous vasodilation) depression
BLIND as a bat (cycloplegia)
MAD as a hatter
(CNS toxicity)
• control hyperthermia • support respiration • administer naloxone • correct acidosis and fluid
• physostigmine may be • treat with atropine and pralidoxime and electrolyte imbalance
Key
helpful, but not for tricyclic • decontaminate • alkaline diuresis /
Intervention
overdose hemodialysis to aid
elimination
Agents SEDATIVE-HYPNOTIC STIMULANTS TRICYCLIC ANTIDEPRESSANTS
disinhibition initially, later lethargy, stupor, coma agitation, anxiety, seizures antimuscarinic effects
nystagmus, decreased muscle tone, hypothermia hypertension, tachycardia, use 3Cs mnemonic
small pupils, hypotension, decreased bowel sounds arrhythmias, Coma
in severe overdose mydriasis, vertical and Convulsions
Clinical
Precaution giving to those with impaired K excretion horizontal nystagmus with PCP. Cardiotoxicity
Features
(e.g. severe myocardial damage or heart failure) skin warm and sweaty,
hyperthermia,
increased muscle tone,
possible rhabdomyolysis
• airway and respiratory support • control seizures, hypertension • control seizures
• avoid fluid overload and hyperthermia • correct acidosis and cardiotoxicity
Key
• consider flumazenil for benzodiazepine overdose with sodium bicarbonate
Intervention
• give norepinephrine for hypotension
• control hyperthermia
COMMON POISONING SYNDROMES

HEAVY METAL POISONING
LEAD ARSENIC ARSINE MERCURY IRON
Acute Inorganic Chronic Chronic
Acute Inorganic Organic
Agent Lead Poisoning Inorganic Lead Organic Lead Acute Arsenic Chronic Arsenic Inorganic
Arsine Gas Mercury Mercury Iron Poisoning
Poisoning Poisoning Poisoning Poisoning Mercury
Poisoning Poisoning
(Plumbism) Poisoning
• industrial exposures (usually via • usually due to • widely used in industrial processes • occupational • mercury-containing materials in dental laboratories • ingestion of
the inhalation of dust) tetraethyl lead or • released during burning of coal hazard formed • manufacturing of wood preservatives, insecticides ferrous sulfate
• children who have ingested large tetramethyl lead • toxicity is entirely due to the trivalent during the and batteries tablets
quantities of chips or flakes of lead- contained in form refinement and • organic mercury compounds are used as seed
Setting containing paint (PICA) antiknock processing of dressings and fungicides
gasoline certain metals • inhalation of • inhalation of • consumption of
additives used in inorganic mercury vapor fish or grains
semiconductors elemental containing
mercury methylmercury
• acute • peripheral • hallucinations, • severe • hair loss, bone • headache, • chest pain, • loosening of • Minamata • vomiting,
abdominal neuropathy headache, gastrointestinal marrow depression dyspnea, shortness of gums and disease gastrointestinal
colic (lead (wrist-drop), irritability, discomfort, and anemia, weakness, breath, nausea teeth, (cerebral bleeding,
colic) and CNS anorexia, convulsions, vomiting, rice- chronic nausea and vomiting, and vomiting, gastrointestinal palsy, lethargy, gray
changes (acute anemia, tremor, coma water stools, gastrointestinal abdominal pain kidney disturbances, deafness, cyanosis
encephalopathy) weight loss, dehydration, disturbances • massive damage, and blindness, • severe
• high mortality gastrointestinal shock • transverse bands in hemolysis gastroenteritis, neurologic mental gastrointestinal
Presentation rate symptoms • sweet, garlicky nails (Mee’s lines) (jaundice, CNS damage and retardation) necrosis,
• in children, odor in breath • skin changes hemoglobinuria) • life- behavioral pneumonitis,
growth and the stools (raindrop leading to threatening changes jaundice,
retardation, hyperpigmentation, pigment hemorrhagic (ERETHISM) seizures, coma
neurocognitive milk and roses overload and gastroenteritis • chronic excessive
deficits, complexion, renal failure followed by intake leads to
developmental hyperkeratosis) renal failure hemosiderosis or
delay hemochromatosis
• prompt • removal from • decontamination, • supportive • DIMERCAPROL • Exchange • intensive • may • uncertain • DEFEROXAMINE
chelation the source of seizure control therapy to therapy transfusion, supportive redistribute benefits from is the chelating
therapy is exposure replace water • *Arsenic is a known vigorous care mercury to the chelation agent of choice
mandatory • chelation and carcinogen hydration, • prompt CNS therapy
therapy electrolytes hemodialysis chelation with
• oral SUCCIMER • chelation • chelators are of oral SUCCIMER
in outpatients therapy with no clinical value or IM
Treatment
• EDTA ± DIMERCAPROL DIMERCAPROL
DIMERCAPROL
in severe cases
• dietary
modification
(high dietary
calcium)
MANAGEMENT OF THE POISONED PATIENT CNS DRUGS

DECONTAMINATION
SEDATIVE-HYPNOTIC DRUGS
• removal of any unabsorbed poison from the skin or
Sedative-hypnotics
gastrointestinal tract
• strategies for decontamination include:
Benzodiazepines Barbiturates Miscellaneous agents
o removal of clothing
o adsorption using activated charcoal
o gastric lavage to remove noncorrosive Short action
(triazolam)
Ultra-short action
(thiopental) Buspirone
o inducing vomiting (emesis) by administering syrup of ipecac Chloral hydrate
Intermediate action Short action
o whole bowel irrigation with a balanced polyethylene-glycol (alprazolam) (secobarbital)
Eszopiclone
Ramelteon
o cathartics decrease absorption and hasten removal of toxins Long action Long action Zaleplon
(flurazepam) (phenobarbital) Zolpidem
SUPPLEMENT: Utility of Activated Charcoal
EFFECTIVE for NOT EFFECTIVE for
• Amitriptyline • Iron • SEDATIVES (ANXIOLYTICS)
• Barbiturate • Lithium o drugs that reduce anxiety and exert a calming effect
• Carbamazepine • Potassium o degree of CNS depression should be the minimum consistent
• Digitalis • Alcohols with therapeutic efficacy
• Glycosides • Cyanide • HYPNOTICS
• Phencyclidine • Corrosive o drugs that produce drowsiness and encourage the onset and
• Propoxyphene • Acids
maintenance of a state of sleep
• Theophylline • Solvents
o involve more pronounced CNS depression than sedation
• Tricyclic antidepressants
• Valproic acid CNS Effects of Sedative-Hypnotics with increasing dose
ENHANCEMENT OF ELIMINATION
• adjust urine pH to enhance renal excretion of weak acids and bases
• hemodialysis – patient's blood is pumped through a column with a
semipermeable membrane allowing removal of many toxic
compounds
SUPPLEMENT: Utility of Hemodialysis
EFFECTIVE for NOT EFFECTIVE for
• Carbamazepine • Amphetamines
• Ethylene glycol • Antidepressants
• Lithium • Antipsychotic drugs
• Methanol • Benzodiazepines
• Metformin • Calcium channel blockers
• Phenobarbital • Digoxin
• Salicylate • Metoprolol
• Theophylline • Propranolol
• Valproic acid • Opioids
SUPPLEMENT: Herbal Medicines

COMMON SCIENTIFIC INDICATIONS
NAME NAME Figure 22-2. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
Lagundi Vitex negundo Cough, colds, fever, asthma • Barbiturates (linear slope): with increasing dose higher than
Yerba Buena
Clinopodium Pain, cough, colds, nausea, needed for hypnosis, it can cause general anesthesia and even
douglasii dizziness, pruritus depression of respiratory and vasomotor centers in the medulla,
Blumea Hypertension, kidney leading to coma and death.
Sambong
balsamifera stones
• Benzodiazepine (plateauing curve): only causes CNS depression
Tsaang gubat Carmona retusa Gastroenteritis
at proportionately greater doses (“ceiling effect”), featuring
Niyog-
niyogan
Quisqualis indica Anti-helminthic, headache comparatively better safety profile.
Akapulko Cassia alata Antifungal The GABA-A receptor: Site of Action of Sedative-Hypnotics
Ulasimang Peperonia Gout, rheumatic pains, boils,
bato pellucida abscesses
• GABA-A receptor: site of action of benzodiazepines, barbiturates
Lowers blood cholesterol and other related drugs (i.e. Zolpidem, Zaleplon, Eszopiclone)
Bawang Alium sativum
levels, antiseptic This is different from GABAB receptor, of which the agonist is the drug
Momordica Lowers blood sugar levels, Baclofen).
Ampalaya
charantia fertility regulation Dr. Pereyra-Borlongan
Guava Psidium guajava Antidiarrheal, antiseptic

• functions as a chloride ion channel, which is activated by the
BOTANICAL inhibitory neurotransmitter GABA
COMMON INTENDED USE
SUPPLEMENT
Decrease duration and intensity of cold
Echinacea
symptoms
Ephedra Treatment of respiratory ailments such as
(Ma Huang) bronchitis and asthma, and a CNS stimulant
For cholesterol lowering and
Garlic
atherosclerosis
Treatment for intermittent claudication,
Ginkgo
and cerebral insufficiency and dementia
Improvement of physical and mental
Ginseng
performance
Limitation of hepatic injury and as an
Milk thistle
antidote to Amanita mushroom poisoning
Improvement in symptoms of benign
Saw palmetto
prostatic hyperplasia
St. John’s Wort Treatment of mild to moderate depression
Improvement of ischemic heart disease and
Coenzyme Q10
for Parkinson disease
Reduction of pain associated with
Glucosamine
osteoarthritis
Melatonin Decrease jet lag symptoms and as a sleep aid Figure 22-6. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
MNEMONICS: MOA of benzo vs barbiturates CLINICAL USES OF BENZODIAZEPINES
FREnzodiazepine : FREquency PREFERRED
BarbiDURATes : DURATion CLINICAL USE
BENZODIAZEPINE
Anticonvulsant maintenance Clonazepam
MNEMONIC: Status epilepticus Lorazepam, Diazepam
BENZOS VS. BARBITURATES Skeletal muscle relaxation
Diazepam
https://qrs.ly/72cke8d (e.g. cerebral palsy)
Panic Disorders, Phobia Alprazolam, Clonazepam
Insomnia Estazolam, Flurazepam, Triazolam
Major inhibitory neurotransmitters? GABA, Glycine
Anesthesia induction Midazolam, Diazepam
Major excitatory neurotransmitters? Glutamate
Bipolar disorder Clonazepam
BENZODIAZEPINES Alcohol withdrawal Chlordiazepoxide, Diazepam
What are the 5 principle pharmacologic effects
of your benzodiazepines? BENZODIAZEPINE OVERDOSE
1. Anxiolysis • DOSAGE
2. Sedation and hypnosis o toxic dose is 1000x the therapeutic dose
3. Anticonvulsant actions • CLINICAL PRESENTATION
4. Spinal cord mediated skeletal muscle relaxation o slurred speech, ataxia, altered (decreased) mental status,
5. Anterograde amnesia respiratory depression
This effect is very specific to benzodiazepines • TREATMENT
Dr. Pereyra-Borlongan o antidote is flumazenil, a BZD receptor antagonist
o activated charcoal is useless
FLUMAZENIL
Class Antidote (benzodiazepine antagonist)
Competitive Antagonist at benzodiazepine sites on GABA-
MOA
A receptor
Uses Benzodiazepine overdose
Agitation, confusion, and precipitates benzodiazepine
SE
withdrawal for those with benzodiazepine dependence
Seizures and arrhythmias may occur when administered
Notes
in patient who took both TCAs and benzodiazepines
BENZODIAZEPINES
SHORT-ACTING INTERMEDIATE-ACTING LONG-ACTING
MIDAZOLAM [D], LORAZEPAM [D], ALPRAZOLAM [D], DIAZEPAM [D], CHLORAZEPATE,
Drugs
BROTIZOLAM, TRIAZOLAM [X], ESTAZOLAM [X], CLONAZEPAM [D], CHLORDIAZEPOXIDE [D], FLURAZEPAM, [X]
OXAZEPAM [D], ETIZOLAM LORMETAZEPAM, NITRAZEPAM, TEMAZEPAM [X] QUAZEPAM [D], FLUNITRAZEPAM
MOA Binds GABAA receptor subunits to increase frequency of chloride channel opening; membrane hyperpolarization
Acute anxiety, Panic attacks, For anxiety disorders even panic disorders For anxiety disorders, insomnia (Flurazepam),
Anesthesia induction, (Alprazolam and Clonazepam), insomnia (Estazolam), skeletal muscle relaxation (e.g. cerebral palsy -
Preoperative sedation skeletal muscle relaxation, seizure disorders Diazepam), seizure disorders, tranquilizers,
Uses
(especially Midazolam), (Clonazepam), status epilepticus (Lorazepam), status epilepticus (Diazepam),
Insomnia (Triazolam) tranquilizers, Bipolar disorder (Clonazepam), adjunct to anesthesia (Diazepam),
myoclonic and infantile spasm (Clonazepam) alcohol withdrawal (Diazepam, Chlordiazepoxide)
Anterograde amnesia, decreased psychomotor skills (especially Diazepam and Flurazepam), Unwanted daytime sedation, Respiratory
SE
depression, Tolerance, Dependence liability, rebound insomnia or anxiety, Painful on injection (diazepam)
• Rapid tissue redistribution • High dose BZD and Barbs may suppress seizure • Flunitrazepam is used as a date-rape drug
(NOT rapid elimination) but at the expense of marked sedation EXCEPT • Decreased REM sleep (hence abnormal sleep
accounts for the short duration Clonazepam and Phenobarbital patterns)
of action of this agents • Chlordiazepoxide has longest half-life (36-
Notes 200 hours) and longest spelling (many letters).
• Additive CNS depression with ethanol, antihistamines, antipsychotics, opioids and TCA
• Use lower doses in the elderly when used for insomnia
• Minor tranquilizers should be avoided in the 1st trim due to increased risk of congenital malformations.
• Maternal use shortly before delivery is associated with floppy infant syndrome. Prenatal BZD exposure slightly increases oral cleft risk.
BARBITURATES
CORRELATION: Biochemistry - Porphyria
What enzyme is deficient in acute intermittent porphyria?
MEMORY AID:
HMB Synthase
BARBITURATES
What is the most catastrophic symptom of sedative-hypnotic
https://qrs.ly/rdcke98
withdrawal?
Rebound Suicide
BARBITURATES
Ultrashort-acting Intermediate-acting Long-acting
PENTOBARBITAL [D],
Drug THIOPENTAL [C], SECOBARBITAL [D], AMOBARBITAL [D], PHENOBARBITAL [D], MEPHOBARBITAL [D],
METHOHEXITAL, THIAMYLAL BUTALBITAL [C], BUTABARBITAL [D], PRIMIDONE [D]
TALBUTAL, APROBARBITAL
Bind to GABAA receptor sites (distinct from benzodiazepines); increases duration of chloride channel opening; block glutamic acid
MOA
neurotransmission, at high doses can block NA channels
Anesthesia induction, Increased
ICP, Seizure induction for epileptic Insomnia, Seizure disorders (phenobarbital), Status
patients undergoing temporal lobe epilepticus (phenobarbital), Hyperbilirubinemias
resection (Methohexital) For insomnia and preoperative sedation (Gilbert’s syndrome)
Uses
(Secobarbital)
Thiopental used to be the induction Barbiturates, particularly phenobarbital, is
agent of choice in anesthesia before considered the DOC for seizures in infants
the discovery of propofol
Ultrashort-acting Intermediate-acting Long-acting
Drug
THIOPENTAL [C] etc PENTOBARBITAL [D] etc PHENOBARBITAL [D] etc
• Extension of CNS depressant actions, Tolerance, Dependence liability (greater than benzodiazepines)
• Contraindicated in porphyria: patients with a history of acute intermittent porphyria, variegate porphyria, hereditary porphyria
SE and symptomatic porphyria (because barbiturates promote activity of ALA synthase, thus enhancing porphyrin synthesis)
• Additive CNS depression with ethanol
• Potent inducer of CYP450 enzymes (true for all barbiturates)
Thiopental has highest lipid solubility High dose BZD and Barbs may suppress seizure but
Notes (hence rapid entry into the brain at the expenses of marked sedation EXCEPT
<1min and rapid awakening) Clonazepam and Phenobarbital
NEWER HYPNOTICS
ANXIOLYTIC: ANXIOLYTIC:
IMIDAZOPYRIDINE
Drug 5HT1A PARTIAL AGONIST MELATONIN RECEPTOR AGONIST
ZOLPIDEM [C], ZALEPLON, ESZOPICLONE BUSPIRONE REMELTEON
Bind selectively to a subgroup of GABAA Partial agonist at 5HT1A and D2 agonist Activates melatonin receptors (MT1 and
receptors, acting like benzodiazepines to enhance Buspirone for Busy People MT2 receptors) in the suprachiasmatic
MOA membrane hyperpolarization, only interact nuclei in the CNS --> decreased latency of
(Always Anxious)
with GABAA receptors with alpha-1 subunit BuSPirone like your BenzodiaZaPine sleep onset
For insomnia and sleep disorder esp. when
Insomnia, Sleep disorders, especially those
sleep onset is delayed
Uses Generalized anxiety disorder characterized by difficulty in falling asleep.
zzZZzzZZzzZZzz (sleep)
Not a controlled substance
Zolpidem, Zaleplon = Zleep disorders
Modest day-after psychomotor depression, Nonspecific chest pain, tachycardia,
Dizziness, fatigue, endocrine changes
Few amnestic effects, Tolerance, palpitations, dizziness, nervousness, tinnitus,
SE (decreased testosterone,
Dependence liability gastrointestinal distress, paresthesia,
increased prolactin)
(less than benzodiazepines) dose-dependent pupillary constriction
• Effects reversed with FLUMAZENIL • No anticonvulsant / muscle relaxant • Rapid onset of sleep with minimal
• Lack anti-convulsant, anti-anxiety and properties rebound insomnia or withdrawal
muscle relaxant effects • Minimal CNS depressant effects symptoms
• Very rapid onset of action • Minimal abuse liability • Minimal rebound insomnia or withdrawal
• May decreased REM sleep • Minimal tolerance and withdrawal symptoms
Notes
• Rebound insomnia on withdrawal from • Slow onset of action (>1week) – hence not • Minimal abuse liability
chronic use for acute anxiety • Metabolized by CYP450 (increased levels
• Has minimal effects on the sleep pattern • Metabolized by CYP3A4 in the presence of CYP1A2 or CYP2D6
and cause less daytime cognitive • Safe for pregnant patients inhibitors)
impairment as compared to BZD
“BLACKOUTS” (i.e. periods of memory loss that occurs with high levels of
ALCOHOLS alcohol intoxication) are a result of inhibition of NMDA activation (since
ethanol inhibits the ability of glutamate to open the cation associated
with NMDA receptors).
• EFFECTS ON OTHER ORGAN SYSTEMS

o slight cardiac depression, vasodilation, hypothermia, uterine
muscle relaxation
Blood Alcohol Concentration (BAC)
BAC
Effects
(mg/dL)
50-100 Sedation, subjective “high”, slower reaction times
ALCOHOLS 60-80 Impairment of driving ability (DUI)
• Methanol (wood alcohol): creates toxic formate, which causes 100-200 Impaired motor function, slurred speech, ataxia
visual disturbance, come, seizures 200-300 Emesis, stupor
• Ethylene glycol (antifreeze): creates toxic aldehydes and 300-400 Coma
oxalate, which causes kidney damage and severe acidosis >500 Respiratory depression, death
• Ethanol: multiple effects on neurotransmitters, CNS
depression; antidote in methanol and ethylene glycol poisoning CHRONIC EFFECTS OF ETHANOL
• TOLERANCE AND DEPENDENCE
o result of CNS adaptation and increased ethanol metabolism
o cross-tolerance with benzodiazepines and barbiturates
o marked psychological and physical dependence
• 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
• GASTROINTESTINAL SYSTEM
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)
2 MAJOR PATHWAYS FOR ALCOHOL METABOLISM is the most common neurologic abnormality in chronic alcoholics
• ENDOCRINE SYSTEM
ACUTE EFFECTS OF ETHANOL o gynecomastia, testicular atrophy and salt retention due to
• CNS EFFECTS altered steroid metabolism in the cirrhotic liver
o sedation, loss of inhibition, impaired judgment, slurred speech,
ataxia
• CARDIOVASCULAR SYSTEM PHARMACOLOGIC MANAGEMENT
o increased incidence of hypertension, anemia and dilated
cardiomyopathy
OF CHRONIC ALCOHOLISM
o binge drinking can cause arrhythmias NALTREXONE [C], NALOXONE [C],
o ingestion of modest quantities of ethanol (10–15 g/day) raises Drugs Nalmefene [B], Alvimopan [B], DISULFIRAM
Methylnaltrexone [B]
HDL levels and may protect against CAD
Opioid antagonist
• FETAL ALCOHOL SYNDROME
(systemic and long acting): Aldehyde
o Mental retardation (most common)
MOA Competitively blocks µ, d and k dehydrogenase
o growth deficiencies, microcephaly receptors. Rapidly reverses effects inhibition
o characteristic underdevelopment of midface region of opioid agonists.
o associated with heavy consumption of alcohol during the first Opioid and alcohol dependence
trimester of pregnancy (naltrexone only)
• NEOPLASIA
Naloxone:
o increased incidence of neoplastic diseases in GIT Uses DOC for opioid overdose Alcohol dependence
o small increase in the risk of breast cancer Naltrexone:
• IMMUNE SYSTEM DOC for opioid dependence and
o enhances inflammation in the liver and pancreas chronic alcoholism
o inhibits immune function in other tissues Pruritus, Nausea, Vomiting,
o heavy use predisposes to infectious pneumonia Hepatotoxic Nausea, headache,
SE flushing and
Don’t combine with disulfiram: hypotension
ALCOHOL INTOXICATION VS. ALCOHOL both drugs are hepatotoxic
WITHDRAWAL • Precipitate abstinence syndrome in • Drug interactions:
patients with opioid dependence decreases
WERNICKE –KORSAKOFF SYNDROME • Naltrexone reduces craving in metabolism of
• ataxia, confusion, paralysis of the extraocular muscles alcohol, nicotine and opioid Diazepam,
• seen in intoxication states dependence Phenytoin, Oral
• Associated with thiamine deficiency (Vitamin B1) • Naltrexone & Nalmefene have anticoagulants
longer DOA and isoniazid
• Rarely seen in the absence of alcoholism Notes
• Naloxone and Nalmefene is IV • Disulfiram is
• Ocular signs and ataxia improve with thiamine administration
(DOA: 12-24 hrs) while absorbed rapidly
• Left with a disabling chronic memory disordered known as (peak effect is 12
Naltrexone is PO (DOA: 48h)
Korsakoff’s psychosis (irreversible memory loss) • Alvimopan & Methylnaltrexone hours) but
MNEMONIC: Wernicke-Korsakoff Syndrome have poor CNS penetrability → eliminated slowly
Weird ACO antagonize peripheral effects (action may
Wernicke-Korsakoff Syndrome: such as constipation persist for days)
Ataxia, Confusion, Ophthalmoplegia
MNEMONICS: Disulfiram Reaction
What changes in the brain are seen in Wernicke-Korsakoff syndrome? What drugs can cause disulfiram reaction?
hemorrhagic necrosis of the mamillary bodies Clara took the Pre-Medical Test in the PM
Chlorpropamide Procarbazine
• Treatment: Cefo Perazone Metronidazole
o maintenance of vital signs Mandole
o prevention of aspiration after vomiting Tetan
o intravenous dextrose – for hypoglycemia
MNEMONIC:
o thiamine administration to protect against Wernicke-
DRUGS THAT CAUSE
Korsakoff syndrome
§ Before giving glucose in a patient with hypoglycemia, we must
DISULFIRAM REACTION
restore the dehydrogenase enzyme necessary for carbohydrate https://qrs.ly/7rcke9i
metabolism, do give thiamine to resurrect the level of dehydrogenase.
Otherwise, it will just cause more osmotic pull in the cell. OTHER ALCOHOLS
o correction of electrolyte imbalance and hydration – since METHANOL ETHYLENE GLYCOL
patients maybe dehydrated and vomiting Drugs
POISONING POISONING
• Methanol is metabolized • Ethylene glycol forms
DELIRIUM TREMENS by ADH to formaldehyde, toxic aldehyde and
• seen in chronic alcoholics when forced to reduce or discontinue alcohol which is then oxidized to oxalic acid
• a withdrawal syndrome (characteristic of motor agitation, formic acid (toxic) • Industrial exposure
Sources • Wood alcohol, windshield (by inhalation or skin
anxiety, insomnia and reduction of seizure threshold)
cleaners, “canned heat,” absorption)
commercial solvents, • Self-administration
photocopier toner (e.g. by drinking
antifreeze products)
• visual dysfunction,
gastrointestinal distress,
shortness of breath, loss
of consciousness, coma
Clinical • severe acidosis and
• accumulation of
features renal damage
formaldehyde and formic
acid causes severe acidosis,
retinal damage, and
blindness
Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 ETHANOL ETHANOL
MNEMONIC: Delirium Tremens • retards formation of • competes for
H-A-D 48 formaldehyde oxidation by alcohol
Hallucinations Delirium • acts as a preferred dehydrogenase
Autonomic instability 48-72 hours post-discontinuation substrate for alcohol FOMEPIZOLE
Tx dehydrogenase • slows or prevents
• Treatment of Delirium Tremens: • competitively inhibits the formation of oxalic
o substituting a long-acting sedative-hypnotic drug as a oxidation of methanol acid
replacement for alcohol and then gradually reducing FOMEPIZOLE
("tapering") the dose of the long-acting drug. • inhibitor of alcohol
§ DOC is long-acting benzodiazepine (e.g. diazepam, dehydrogenase
chlordiazepoxide)
ANTISEIZURE DRUG MOAs

https://qrs.ly/5gcke9r
MOA of the Antiseizure Drugs (• major MOA, ° minor MOA)

Antiseizure
Na+ Ca2+ K+ GABA Glutamate Others
Drug (AED)
NE,
Phenytoin • ° ° °
Ach
Carbamazepine • °
Valproic acid • ° ° °
Phenobarbital ° ° • °
Ethosuximide • °
Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 Benzodiazepine •
Gabapentin • °
ANTISEIZURE DRUGS Lamotrigine • ° °
Levetiracetam • • • SV2A
Topiramate • • • •
Antiseizure Drugs: Enhance GABA synaptic transmission
SUPPLEMENT: Seizures
Seizures
• finite episodes of brain dysfunction resulting from abnormal
discharge of cerebral neurons
• classification based on seizure characteristics
o simple or complex
o partial, generalized or partial with secondary generalization
Types of Seizures
• SIMPLE PARTIAL SEIZURES
o Characterized by minimal spread of abnormal discharge
§ consciousness and awareness is preserved (patient can describe
in full detail the attack) Figure 17-3. Brunton LL. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. 2018
§ convulsive jerking, paresthesia, psychic symptoms (altered • GABA (primary inhibitory neurotransmitter): when present, the
sensory perception, illusions, hallucinations, affect changes) and
GABA-A receptor opens, allowing an influx of Cl-, which in turn
autonomic dysfunction
• COMPLEX PARTIAL SEIZURES
increases membrane polarization.
o Localized discharge → becomes more widespread/ bilateral • Some Anti-seizure drugs enhance GABA transmission
o usually arise from temporal lobe o Benzos and barbiturates: act on the receptor itself
§ impaired consciousness o Gabapentin: acts presynaptically to promote GABA release
§ demonstrate automatisms (lip smacking, swallowing, scratching, o Vigabatrin and Valproate: act by reducing metabolism of GABA
walking about) o Tiagabine, act by inhibiting its reuptake (action on GAT-1)
• GENERALIZED TONIC-CLONIC SEIZURES (GRAND MAL)
o tonic phase (< 1 min): abrupt loss of consciousness, muscle rigidity Antiseizure Drugs: Enhance Na+ channel inactivation
and respiration arrest
o clonic phase (2–3 min): jerking of body muscles, with lip or tongue
biting, and fecal and urinary incontinence
• ABSENCE SEIZURES (PETIT MAL)
o begin in childhood and usually cease by age 20 yrs
§ impaired consciousness (abrupt onset, brief)
§ automatisms, loss of postural tone, or enuresis
• MYOCLONIC SEIZURES
o Sudden, brief, shock-like contractions of musculature (myoclonic
jerks)
• ATONIC SEIZURES Figure 17-2. Brunton LL. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. 2018
o Sudden loss of postural tone
• Carbamazepine, Phenytoin, Topiramate, etc: Prolong
• INFANTILE SPASMS
o Epileptic syndrome
inactivation of the Na channels, reducing ability of neurons to
o 90% of patients have their first attack before the age of 1 fire at high frequencies
• STATUS EPILEPTICUS Antiseizure Drug: Reduce current through T-type Ca2+ channel
o series of seizures (usually tonic-clonic) without recovery of
consciousness between attacks
o life-threatening emergency
MOA OF THE ANTI-SEIZURE DRUGS

• Mechanism falls under any of the 3 categories:
o Enhancement of GABAergic (INHIBITORY) Transmission
o Diminution of excitatory (usually GLUTAMATERGIC)
transmission Figure 17-4. Brunton LL. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. 2018
o Modification of ionic conductance (Na, K, Ca, etc.) and • Ethosuximide, Valproic acid (DOC for absence seizures); reduce
presynaptic transmitter release (SV2A) Ca2+ flux through Thalamic type (T-type) Ca2+ channels, reducing
pacemaker current underlying thalamic rhythm
TRADITIONAL ANTISEIZURE DRUGS
NA CHANNEL BLOCKER: GABAERGIC:
NA CHANNEL BLOCKER: HYDANTOIN NA CHANNEL BLOCKER: TRICYCLIC CA CHANNEL BLOCKERS
BRANCHED-CHAIN FATTY ACID BARBITURATE
Drug ETHOSUXIMIDE [C],
PHENYTOIN [D], FOSYPHENYTOIN, CARBAMAZEPINE [D], OXCARBAZEPINE [C], PHENOBARBITAL [D],
VALPROIC ACID [X], SODIUM VALPROATE PHENSUXIMIDE,
MEPHENYTOIN, ETHOTOIN ESLICARBAZEPINE PRIMIDONE [D]
METHSUXIMIDE
Major: Blocks voltage-gated Na+ channels
Use dependent effect of Phenytoin: It prolongs Blocks voltage-gated Na+ channels Blocks high-frequency firing of neurons Decreases Ca2+ currents
that inactivated state of Na+ channels; also Bind to GABAA receptor sites (T-type) in thalamus
Since it is structurally similar to phenytoin, its MOA is also (similar to phenytoin and carbamazepine) via
inhibits generation rapidly repetitive action (distinct from benzodiazepines);
similar (slows the rate of recovery of Na+ channels from Na channel, Blocks NMDA, Ethosuximide reduces low
MOA potentials characteristic of neurons also has actions on Na (limits
inactivation, inhibits high frequency repetitive firing of Increases GABA levels threshold T-type Ca2+
sustained repetitive firing in
Other MOA of phenytoin: also alters K+, Ca2+ neurons). It also has an effect on potentiation of voltage currents in the thalamic
neurons), Ca and glutamate
(inhibition of influx), Glutamate (decrease gated K current Broad spectrum antiseizure drug neurons.
release), GABA (enhance release)
Generalized tonic-clonic seizures,
DOC for generalized tonic-clonic seizures, DOC for bipolar disorder (acute mania),
DOC for trigeminal neuralgia, Partial seizures, Status epilepticus,
DOC for partial seizures, status epilepticus, DOC for generalized tonic-clonic seizures and
DOC for generalized tonic-clonic seizures, Insomnia, Hyperbilirubinemia
Uses arrhythmias (Group 1B Action), migraine absence seizure (especially if with GTC Absence seizures (DOC)
DOC for partial seizures, Barbiturates, particularly
Phenytoin is preferred in prolonged therapy component), partial seizures, myoclonic
Manic phase (bipolar disorder) phenobarbital, is the DOC for
for status epilepticus because it is less sedating seizures, migraine prophylaxis
infants (Katzung)
Sedation
Diplopia and ataxia (Most common – just like phenytoin), (most frequent unwanted SE),
Nystagmus (early), GI upset (Most common, in the form of Extension of CNS depressant
cognitive dysfunction, drowsiness, ataxia,
Diplopia and Ataxia (most common), nausea, vomiting, anorexia), Drowsiness actions, Tolerance, GI complaints
blood dyscrasias (i.e. aplastic anemia and agranulocytosis,
Gingival Hyperplasia (favorite to ask in the (more so if combined with other drugs), Dependence liability (MC; ex. Nausea, vomiting,
both idiosyncratic reactions),
boards), Fine Tremor (at high doses), Alopecia, (greater than benzodiazepines), anorexia),
SE Stevens-Johnson syndrome,
Hirsutism, Anemias, Peripheral neuropathy, Weight gain, Hepatotoxicity (Idiosyncratic Acute intermittent porphyria Lethargy, Headache,
erythematous rash (most common idiosyncratic
Osteoporosis, reaction esp. in infants), Behavioral changes
reaction), Do not use phenobarbital for
Teratogen (fetal hydantoin syndrome), Teratogen (neural tube defects, (euphoria)
teratogen (spina bifida and craniofacial anomalies), absence, atonic and infantile
abnormalities in Vit D metabolism spina bifida)
hyponatremia (Oxcarbazepine) spasms. It may worsen these
seizure types.
• Potent inducer of CYP450 enzymes • Potent CYP450 inducer • CYP450 INHIBITOR (unlike some of its AED • Potent inducer of CYP450
• Metabolism is NON-LINEAR (elimination • Can cause auto-induction (induce its own metabolism) relatives which are more often than not, enzymes
shift from 1st order to zero order at • Oxcarbazepine has less drug interactions INDUCERS)
moderate to high dose levels), hence serum • Also, highly protein bound (75%) • Highly protein bound (90%)
monitoring is necessary,
• Fosphenytoin is a water-soluble prodrug of
Notes phenytoin
• 90% is Highly protein bound
• Phenytoin is NOT sedating at therapeutic
doses (only at very HIGH levels)
• Phenytoin has an affinity for thyroid binding
globulin (can interfere with thyroid
function)
GABAERGIC: NA CHANNEL BLOCKER:
GABA ANALOGUE PIRACETAM MONOSACCHARIDE DERIVATIVE
BENZODIAZEPINE PHENYLTRIAZINE
Drug DIAZEPAM [D],
CLONAZEPAM [D], GABAPENTIN [C], LAMOTRIGINE [C], TOPIRAMATE [D],
LORAZEPAM [D], LEVETIRACETAM [C]
CLOBAZAM [C] PREGABALIN [C] ZONISAMIDE [C] FELBAMATE [C]
CLORAZEPATE
Blocks Ca2+ channels. Decrease
Multiple actions on synaptic function,
glutamate release. Inhibits
Selectively binds synaptic vesicular protein SV2A probably via actions on phosphorylation (Na,
Binds GABAA receptor subunits to increase neuronal discharge from seizure Blocks Na and Ca channels,
→ selectively inhibiting hypersynchronization of K, Ca, GABA, AMPA-glutamate, carbonic
MOA frequency of chloride channel opening; membrane foci. decreases glutamate, Zonisamide
epileptiform burst firing; Modifies synaptic release anhydrase)
hyperpolarization Despite its structural similarity only blocks Na channels
of glutamate and GABA. Inhibits Ca2+ channels also Felbamate also facilitate the inhibitory actions
with GABA, it’s MOA doesn’t
of GABA but its exact MOA is still unknown
directly act on GABA receptors
Generalized tonic-clonic seizures,
Absence seizures Generalized tonic-clonic seizures, Absence seizures, Partial seizures,
Partial seizures,
(second line), DOC for Partial seizures, Lennox-Gastaut syndrome, West syndrome,
Neuropathic pain (postherpetic Generalized tonic-clonic seizures, Partial seizures,
Uses Status epilepticus Myoclonic seizures, Infantile Myoclonic seizures, Migraine;
neuralgia) – first line, Migraine, Juvenile myoclonic epilepsy
spasms, Lennox-Gastaut Absence seizures, Bipolar
Fibromyalgia (Pregabalin)
syndrome disorder Felbamate is only for severe refractory seizure
states
Dizziness, ataxia, nausea, rash, Drowsiness, Dizziness, Ataxia, Psychomotor
headache, SJS / TEN slowing, Memory impairment, Paresthesia,
Anterograde amnesia, Painful on injection, (lamotrigine), severe skin Weight loss, Acute myopia, Glaucoma,
Decreased psychomotor skills, Unwanted daytime Dizziness, Sedation, Ataxia, reaction (Zonisamide) Ataxia, Asthenia, Dizziness, Sedation, Weakness, Urolithiasis (because of weak carbonic
SE
sedation, Respiratory depression, Tolerance, Nystagmus, Tremor Irritability, Hallucinations, Psychosis anhydrase effect)
Dependence liability Zonisamide may also cause Felbamate causes hepatic failure and
cognitive impairment, confusion hematotoxicity (can cause ITP, aplastic
and poor concentration anemia)
• Also have the same effect on Ca • Primarily undergoes • Drug interactions are minimal (neither an • Topiramate is a weak inhibitor of carbonic
currents like Ethosuximide glucuronidation reaction inducer/inhibitor) anhydrase
• Pregabalin is also manufactured • Lamotrigine may be used for • Antiseizure drug with the greatest number
as a combination drug with acute manic phase and as of mechanisms of action
Methylcobalamin for prophylaxis in the depressive • Topiramate can also block Na channels,
Notes neuropathic pain phase activate a hyperpolarizing K+ current and
potentiate action of GABA and block
glutamate receptor (particularly AMPA
receptor)
• Felbamate may also block glutamate
receptors
FETAL HYDANTOIN SYNDROME: TERATOGENIC EFFECT OF General Anesthesia
PHENYTOIN • A neurophysiologic state characterized by unconsciousness,
• Wide set eyes analgesia, amnesia, skeletal muscle relaxation, and loss of
• upturned nose reflexes
• mild midfacial hypoplasia / broad mandible • An ideal anesthetic should induce rapid, smooth loss of
• long upper lip with thin vermilion border consciousness, be rapidly reversible upon discontinuation and
• lower distal digital hypoplasia possess a wide margin of safety.
• Goal of anesthesiologist: smooth transition from stage 1 to stage 3
CLINICAL USES OF ANTISEIZURE DRUGS
Drugs of Stages of Anesthesia (Guedel’s signs):
Seizure Type Alternative Drugs Stage Name Events
Choice
Generalized Valproic Acid Phenobarbital, Decreased awareness of pain, sometimes
Tonic-Clonic Phenytoin Lamotrigine, 1 Analgesia with amnesia
Consciousness is impaired, not lost
Seizures Carbamazepine Topiramate
Patient is delirious or excited
Felbamate,
Carbamazepine Amnesia occurs, reflexes are enhanced,
Phenobarbital, 2 Disinhibition
and respiration is typically irregular
Partial Seizures Lamotrigine
Topiramate, Valproic Retching and incontinence may occur
Phenytoin
Acid Patient is unconscious
Lamotrigine, Surgical
3 anesthesia
No pain reflexes, regular respiration, and
Ethosuximide Levetiracetam, maintained blood pressure
Absence Seizures
Valproic Acid Zonisamide, Severe respiratory and cardiovascular
Clonazepam Medullary
4 depression
depression that requires mechanical and
Clonazepam, pharmacologic support
Myoclonic and
Levetiracetam,
Atypical Absence Valproic Acid
Topiramate,
Syndromes
Zonisamide, Felbamate
INHALATIONAL ANESTHETICS
Lorazepam Inhalational Anesthetics
Diazepam • include nitrous oxide, halothane, desflurane, enflurane,
Status Epilepticus -- isoflurane, sevoflurane, and methoxyflurane
Phenytoin
Phenobarbital • partial pressure or "tension” is a measure of concentration of
inhaled anesthetics
OTHER CLINICAL USES OF ANTISEIZURE DRUGS o standard pressure of the total inhaled mixture is atmospheric
• BIPOLAR AFFECTIVE DISORDERS: valproic acid (first-line for pressure (760 mm Hg at sea level)
mania), carbamazepine, lamotrigine o 50% nitrous oxide in the inhaled air would have a partial
• TRIGEMINAL NEURALGIA: carbamazepine (DOC), pressure of 380 mm Hg
oxcarbazepine Minimum Alveolar Anesthetic Concentration (MAC)
• NEUROPATHIC PAIN (POSTHERPETIC NEURALGIA): • best measure of potency of inhaled anesthetics
gabapentin, pregabalin • a 1.0 MAC as the partial pressure of an inhalational anesthetic in
• MIGRAINE: gabapentin, phenytoin, topiramate 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)
GENERAL ANESTHETICS • when several anesthetic agents are used simultaneously, their
MAC values are additive
Properties of Inhaled Anesthetics

Anesthetic Partition Coefficient MAC Metabolism Comments
Nitrous oxide 0.47 >100 None Incomplete anesthetic; rapid onset and recovery
Desflurane 0.42 6-7 <0.05% Low volatility; poor induction agent (pungent); rapid recovery
Sevoflurane 0.69 2.0 2-5% (fluoride) Rapid onset and recovery, unstable in soda-lime
Isoflurane 1.40 1.40 <2% Medium rate of onset and recovery
Enflurane 1.80 1.7 8% Medium rate of onset and recovery
Halothane 2.30 0.75 >40% Medium rate of onset and recovery
Methoxyflurane 12 0.16 >70% (fluoride) Very slow onset and recovery
INHALATIONAL ANESTHETICS
METHOXY-
Drugs DESFLURANE SEVOFLURANE [B] ISOFLURANE [C] ENFLURANE HALOTHANE
FLURANE
MOA Facilitate GABA-mediated inhibition; block brain NMDA and ACh-N receptors
Uses General anesthesia
Spike-and-wave
activity in EEG, Catecholamine-induced
Catecholamine- muscle twitching, arrhythmias,
Peripheral
induced breath-holding, Myocardial depression
vasodilation, Renal
arrhythmias, myocardial (direct myocardial
Bronchospasm Renal insufficiency
Peripheral depression, renal depressant effect),
SE (pulmonary irritant), insufficiency (due (due to
vasodilation, insufficiency (due Halothane Hepatitis
Peripheral vasodilation to Compound A Fluorine
Bronchodilation, to inorganic (immune mediated
formation), release)
Coronary steal fluoride ions), response characterized
bronchodilation
syndrome decreased cardiac by eosinophilia),
output, Bronchodilation
bronchodilation
METHOXY-
Drugs DESFLURANE SEVOFLURANE [B] ISOFLURANE [C] ENFLURANE HALOTHANE
FLURANE
• Desflurane is • Described as • Coronary • Has pungent • Halothane, amongst • Highest
contraindicated for sweet smelling steal odor which all inhaled potency and
patients with asthma and • Best to use syndrome, limits its use anesthetics, has the lowest MAC
hyperreactive airways sevoflurane for the highest propensity to among
• Desflurane cannot be inhalational preferential cause HEPATITIS (via inhalational
used as an agent for induction and redistribution free radical formation anesthetics
induction because of its induction of of blood from or immune mediated (very slow
Notes pungency and ability to asthmatic ischemic areas responses) onset and
cause bronchospasm patients (has the to non- • Halothane is stored in recovery)
• In terms of its PK, most ischemic amber colored
desflurane has a low bronchodilation areas, is a bottles and thymol is
blood: gas partition effect) theoretical added as a
coefficient, which possibility for preservative to
allows fast induction isoflurane use prevent oxidative
and prompt awakening decomposition
Drug NITROUS OXIDE PHYSIO CORRELATION: effect on hyperventilation on ICP
Facilitate GABA-mediated inhibition; block brain NMDA Hyperventilation to decrease PaCO2 → cerebral vasoconstriction →
MOA
and ACh-N receptors decrease in cerebral blood flow → reduction in ICP
Anesthesia for minor surgery and dental procedures,
Uses
Balanced anesthesia for major surgery CARDIOVASCULAR EFFECTS
Megaloblastic anemia on prolonged exposure, • ALL inhaled anesthetic depress normal cardiac contractility →
Euphoria (laughing gas), bronchodilation, decrease mean arterial pressure via different mechanisms
SE
Expansion of air-filled cavity to NONCOMPLIANT spaces,
o EXCEPTION: Nitrous Oxide
diffusion hypoxia
• Inhaled anesthetics have variable effect on baroreceptor reflex
• Nitrous oxide is never used as a SOLE anesthetic agents.
It is usually combined with other inhaled local • Inhaled anesthetics reduce myocardial oxygen consumption
anesthetics for a more balanced effect
• Lowest potency (highest MAC) and least cardiotoxicity RESPIRATORY EFFECTS
among inhalational anesthetics • ALL inhaled anesthetics have BRONCHODILATING properties
Notes except
• CNS effect of Nitrous oxide: only inhaled anesthetic that
INCREASES cerebral blood flow and hence INCREASE o DESFLURANE (and ISOFLURANE to a lesser extent) – can
ICP due to activation of sympathetic nervous system cause airway irritability and hence is unsuitable for induction
• Cardiac effect of Nitrous oxide: minimal circulatory o Preferred for bronchodilation is sevoflurane and halothane,
depressant (only at high doses) because it activates the SNS both sweet smelling
EFFECTS OF INHALED ANESTHETICS
MALIGNANT HYPERTHERMIA
CNS EFFECTS: variable effects depending on MAC levels
• reduction in cerebral metabolic rate is greater than vasodilation • Genetic disorder of susceptible individuals upon exposure to
→ cerebral blood flow is decreased volatile anesthetics and succinylcholine
• vasodilation is greater than reduction in cerebral metabolic rate • Signs and symptoms: muscle rigidity, hyperthermia, rapid onset
→ cerebral blood flow is increased of tachycardia, hypercapnia, hyperkalemia and metabolic
o Undesirable for patients with increased ICP (remember acidosis
Monroe-Kelly Doctrine?) ex. Brain tumor, ICH and head injury • Pathophysiology: Mutation in the ryanodine receptor (calcium
• EXCEPTION: Nitrous OXIDE release channel in the SR) of the skeletal muscle that results to
uncontrolled release of Ca2+ from the sarcoplasmic reticulum
• Caffeine-Halothane contracture test: most reliable test to
establish susceptibility
• Treatment: Dantrolene
INTRAVENOUS ANESTHETICS
“Mnemonic: The Mighty King Proposes to Oprah: Thiopental Midazolam, Ketamine, Propofol and Opioids.”
PHENCYCLIDINE
BARBITURATE BENZODIAZEPINE DERIVATIVE IMIDAZOLE
OPIOID ANALGESIC
(Ultrashort-acting) (Short-acting) (Hallucinogen drug DERIVATIVE
of abuse) PROPOFOL [B],
MIDAZOLAM [D], FOSPROPOFOL
Drug
BROTIZOLAM, FENTANYL [C], Called the “Milk of
THIOPENTAL [C],
TRIAZOLAM, MORPHINE, Amnesia”
METHOHEXITAL, KETAMINE [B] ETOMIDATE [C]
OXAZEPAM, ALFENTANIL,
THIAMYLAL
ETIZOLAM, REMIFENTANIL
LORAZEPAM
Bind to GABAA Binds GABAA
receptor sites receptor subunits
Interact with µ (mu), Potentiates GABAA
(distinct from to increase Modulates GABAA
NMDA antagonist, d (delta) and k (kappa) receptors, Blocks Na
benzodiazepines); frequency of receptors
MOA weak GABAA receptors for channels
increases chloride channel containing b3
modulation endogenous opioid * Propofol has an
duration of opening; subunits
peptides antiemetic action
chloride channel membrane
opening hyperpolarization
IV anesthetic
Anesthesia Acute anxiety, Dissociative General anesthesia
induction of choice,
induction (old), Panic attacks, anesthesia (especially in
General anesthesia,
Increased ICP, Anesthesia (analgesia, amnesia patients with Analgesia
Uses Sedation for ICU
identification of induction, and catatonia but limited cardiac or
patients and
epileptic foci Preoperative with retained respiratory
outpatient
(Methohexital only) sedation consciousness) reserve)
procedures
THIOPENTAL [C] MIDAZOLAM [D] KETAMINE [B] ETOMIDATE [C] FENTANYL [C] PROPOFOL [B],
Drugs
etc etc etc FOSPROPOFOL
Cardiovascular
Extension of CNS stimulation,
Pain on injection,
depressant Anterograde Hypertension,
Myoclonus, Bradycardia,
actions, amnesia, Increased
Postoperative vasodilation,
Tolerance, Decreased intracranial
nausea and Hypotension,
Dependence psychomotor pressure, Respiratory
vomiting, negative inotropism,
liability skills, Lacrimation and depression,
Adrenocortical pain at injection site,
(greater than Unwanted daytime salivation chest wall rigidity
SE suppression Profound apnea,
benzodiazepines), sedation, (pretreatment with (which may cause
Etomidate’s paresthesia in the
Acute intermittent Dependence anticholinergics), impaired ventilation)
propensity to perianal region
porphyria, liability, Emergence and constipation
cause (Fospropofol),
Accidental Intra- Postoperative delirium
adrenocortical Propofol Infusion
arterial injection respiratory (Post-op effects:
suppression syndrome
can lead to depression disorientation,
limits its use.
gangrene hallucination,
excitation)
• Barbiturates do • Additive CNS • Dissociative • Etomidate, • Antidote is • Contains egg
not produce depression with anesthesia seen unlike other IV NALOXONE lecithin
analgesia, can ethanol in ketamine is anesthetics, has (DOC)/NALTREXONE • Metabisulfite (an
rather cause • Antidote is characterized by minimal effects • Neuroleptanesthesia agent to prolong
hyperalgesia FLUMAZENIL thalamocortical on CV and (analgesia + amnesia) shelf life) can
• Barbiturates are • Midazolam is a dissociation respiratory happens when cause allergic
potent cerebral usual adjunct apparent in EEG functions upon Fentanyl, Droperidol reactions to
vasoconstrictors with inhalational • Ketamine induction. and Nitrous oxide are asthmatic patients
→ useful for anesthetics and produces potent HENCE, it can be given together and patients with
patients with IV opioids, has a analgesia with used as an • Faster recovery: sulfa allergies
increased ICP slow onset but little respiratory induction agent remifentanil • Propofol is ideal
• Do not mix with longer DOA depression (it is a of choice for because it has a
These drugs have fast
acidic drugs bronchodilator) unstable patients onset of action prompt recovery
(neuromuscular making it ideal for or those with (short context
blockers) → can asthmatic minimal sensitive t½) /
cause patients cardiopulmonary short duration of
Notes precipitates reserve action (8-10
• Additive CNS You can reduce • This can be minutes) due to
depression with emergence apparent in a • REMEMBER: Zero
ethanol delirium by single IV analgesic
• Potent inducer pretreatment induction dose. properties
of CYP450 with • Etomidate does • Alternative General
benzodiazepines not have
enzymes anesthetic
analgesic maintenance for
properties patients susceptible
to malignant
hyperthermia
• Fospropofol is the
water-soluble
prodrug form of
propofol but with
slower onset and
recovery
PROPOFOL INFUSION SYNDROME Local Anesthesia
• Seen in prolonged high dose infusions (>75ug/kg/min) for • Refers to a loss of sensation in a limited region of the body
longer than 24 hours accompanied by muscle paralysis and sympathetic blockade.
• Cardinal feature: metabolic (lactic) acidosis • Recovery from clinically relevant local anesthetics should be
• TRIVIA – Death of Michael Jackson spontaneous, predictable and without residual effects
o immediate COD: acute propofol intoxication
o contributory factors: drug interactions (lorazepam, MNEMONICS: Local Anesthetics
midazolam, diazepam) How will you distinguish whether local anesthetics are esters or
amides?
ESTERS have only 1 i in their names.
SUPPLEMENT: OTHER ANESTHETICS
Tetracaine, Procaine, Benzocaine
a novel sedative-analgesic agent, an AMIDES have 2 i’s in their names.
alpha-2 adrenoceptor agonist. Alpha-2 Bupivacaine, Ropivacaine, Lidocaine
receptor agonists decrease sympathetic As long as you know how to count, you can get this right!
DEXMEDETOMIDINE tone with attenuation of the MNEMONICS – Half Life of Local Anesthetics
neuroendocrine and hemodynamic Which local anesthetics have the shortest and longest half-lives?
responses to anesthesia and surgery and PROCAINE = shortest half-life (1-2 mins)
cause sedation and analgesia A PRO finishes the race fastest.
ROPIVACAINE = longest half-life (4.2 hrs)
At the end of the long ROPe.
LOCAL ANESTHETICS
MOA OF LOCAL ANESTHETICS
• block voltage-gated Na+ channels, reducing influx of Na+, • CNS EFFECTS
thereby preventing depolarization o Initial symptom of circumoral and tongue numbness and
• relationship of local anesthesia with electrolytes metallic taste
o hyperkalemia enhances local anesthetic activity o light-headedness or sedation, restlessness, nystagmus,
o hypercalcemia antagonizes local anesthetic activity generalized tonic-clonic seizures, respiratory and
Local Anesthetics as weak bases cardiovascular depression
• most are weak bases that undergo dissociation • CARDIOVASCULAR EFFECTS
o more lipid-soluble (nonionized, uncharged) form reaches o Most local anesthetics have intrinsic vasodilator quality
effective intracellular concentrations more rapidly EXCEPT cocaine, mepivacaine and ropivacaine
§ may hasten onset of block by alkalinizing solution with o use with caution in patients with preexisting cardiovascular
bicarbonate (increasing nonionized form) disease because they may develop heart block and
o once inside the axon, the ionized (charged) form of the drug is arrhythmias
the more effective blocking entity Treatment of LAST
• CANNOT inject local anesthetics into an abscess during I & D: • Treatment should be instituted during earliest sign of toxicity
o Lidocaine won’t work in an acidic environment, because • Ensure oxygenation (supplemental Oxygen) and ventilation
charged form will predominate. This will not be able to cross (control airway if necessary)
the cell membrane and exert its action • Treat seizures with benzodiazepines
LOCAL ANESTHETICS: SYSTEMIC TOXICITY (LAST) • ANTIDOTE: INTRALIPID (lipid emulsion therapy)
• adverse systemic effects following INADVERTENT
INTRAVASCULAR injection or ABSORPTION of LA from site of
administration
ESTER LOCAL ANESTHETHICS
PROCAINE, NOVOCAINE,
Drugs BENZOCAINE [C], BUTAMBEN COCAINE [X] (Drug of abuse) TETRACAINE [C]
CHOLOROPROCAINE
MOA Blockade of Na channels slows, then prevents axon potential propagation
Local anesthesia, Local anesthesia, Topical anesthesia. Local anesthesia,
Extravasation complications Used for surgeries involving the ear, Spinal anesthesia,
from venipuncture, Local anesthesia, nose, and throat procedures
Uses Epidural anesthesia,
Inadvertent intraarterial Topical anesthesia
All local anesthetics are vasodilators Topical ophthalmic
injections. Used for very
EXCEPT cocaine anesthesia
short procedures
Light-headedness, Sedation, Restlessness, Nystagmus, Seizures, Respiratory and cardiovascular depression, Skin irritation, Antibody
SE
formation,
• Shortest half-life among • Use cautiously when treating Has Intrinsic sympathomimetic activity. • Used primarily for spinal
local anesthetics sunburns or large areas of Causes vasoconstriction. So, it does NOT anesthesia (2-3hrs)
• May also be given with skin need an alpha agonist (like epinephrine) • Also available as
epinephrine • Limited for Topical use only to limit its systemic absorption Ophthalmic solution
• Benzocaine is unique in the • Long acting
• Causes mood elevation due to action
sense that it is a weak acid,
Notes on dopamine receptor
hence it exist predominantly
• Topical use only
in the non-ionized form at
physiologic pH. Special SE: Abuse liability, Severe
hypertension, Cerebral hemorrhage,
Special SE:
Cardiac arrhythmias, Myocardial
Methemoglobinemia
infarction, Stroke
(rare but serious SE)
AMIDE LOCAL ANESTHETICS
PRILOCAINE, BUPIVACAINE,
Drugs LIDOCAINE [B] ROPIVACAINE
MEPIVACAINE LEVOBUPIVACAINE
MOA Blockade of Na channels slows, then prevents axon potential propagation
Infiltration of Local anesthesia,
Local anesthesia,
Antiarrhythmic (group 1B Local anesthesia, Local anesthesia,
Uses Epidural anesthesia,
activity; used post-MI and for Dental anesthesia Epidural anesthesia
Intrathecal anesthesia
digitalis toxicity),
SE Light-headedness, Sedation, Restlessness, Nystagmus, Seizures, Respiratory and cardiovascular depression
• Routes: topical, IV, infiltration, Special SE: • Most cardiotoxic out of all the LA. • Ropivacaine is an S(-)
spinal, epidural, minor and Methemoglobinemia • Use with caution in pregnant enantiomer of bupivacaine,
major peripheral blocks (rare but serious SE) women and patients with cardiac rendering it less cardiotoxic to
• Given with epinephrine to • Administer methylene disease (may cause heart block, bupivacaine
decrease systemic absorption blue if patient arrhythmia and hypotension) • Longest half-life among local
• PROPARACAINE is another develops • Treat cardiotoxicity with anesthetics
Notes methemoglobinemia
local anesthetic commonly used in INTRALIPID/LIPOSOMAL FORMS • Treat cardiotoxicity with
ophthalmic preparations (fat emulsion used in TPN) INTRALIPID/LIPOSOMAL
Special SE: FORMS (fat emulsion used in
Transient Neurological TPN)
symptoms, Cauda equina
syndrome
SKELETAL MUSCLE RELAXANTS SKELETAL MUSCLE RELAXANTS

• neuromuscular blocking drugs are used to produce muscle
paralysis to facilitate surgery or assisted ventilation
• spasmolytic drugs are used to reduce abnormally elevated tone
caused by neurologic or muscle end plate disease
NEUROMUSCULAR BLOCKERS
TYPES OF NEUROMUSCULAR BLOCKADE
• DEPOLARIZING BLOCKADE
o neuromuscular paralysis that results from persistent
depolarization of the end plate (e.g. by succinylcholine)
• NONDEPOLARIZING OR STABILIZING BLOCKADE SUPPLEMENT: APPLICATIONS – Lethal Injection
o Competitive antagonists at the acetylcholine receptor of the What are the drugs used in lethal injection?
end plate (e.g. by tubocurarine) • Thiopental (5 g)
o Increasing doses of Ach can reverse the effect of • Pancuronium (100 mg)
nondepolarizing neuromuscular blocker (i.e. use of • Potassium chloride (100 mEq)
neostigmine or an indirect acting cholinomimetic)
INTERACTIONS OF DRUGS WITH THE ACETYLCHOLINE RECEPTOR ON THE END PLATE CHANNEL
NON-DEPOLARIZING NEUROMUSCULAR BLOCKERS

NATURAL
ISOQUINOLINE ISOQUINOLINE AMINO-STEROID
ALKALOID
Drugs
TUBOCURARINE ATRACURIUM [C], PANCURONIUM
MIVACURIUM [C] VECURONIUM [C] ROCURONIUM [C]
[C] (prototype) CISATRACURIUM [B] [C]
Long acting Short acting Intermediate-acting Intermediate-acting Intermediate-acting Long acting
Duration
(80 min) (15-21 min) (45 min) (25-40 min) (36-73 min) (85-100 min)
Competitive antagonists at skeletal muscle nicotinic acetylcholine receptors.
MOA
Pancuronium additionally has moderate block on cardiac muscarinic receptors.
Active ingredient • Skeletal muscle relaxation during intubation and general anesthesia.
of curare • Atracurium: also used for Relaxation of respiratory muscled to facilitate mechanical ventilation in the ICU
Curare – an setting
arrow poison • Pancuronium: also used for Euthanasia, Lethal injection, Strychnine poisoning
Uses
that produced
skeletal muscle Cisatracurium, vecuronium and rocuronium are NMBs considered as DOC for hemodynamically compromised
paralysis when patients (less chances for histamine release causing hypotension)
shot at animals
Respiratory
Respiratory
paralysis, Apnea, Respiratory
paralysis, Seizures, Histamine paralysis,
Prolonged apnea,
release, Apnea,
Ganglion block Respiratory paralysis, Bronchospasm Respiratory Respiratory
Tachycardia
SE (hypotension), Apnea, Histamine paralysis, Apnea paralysis, Apnea,
Cisatracurium (has atropine
Histamine release release (moderate) Hypersensitivity
have less like effects),
(moderate) with
histamine release Hypertension,
hypotension,
compared to Recurarization
Recurarization
atracurium
All effects can be reversed with NEOSTIGMINE
• Metabolized by • Both atracurium • May also reverse • SUGAMMADEX is
pseudocholinesterase and Cisatracurium effects w/ a novel reversal
(just like undergo Hoffman Sugammadex agent (chemical
succinylcholine) elimination (rapid (less) antagonist)
• Short DOA spontaneous • Undergoes specifically for
(10-20mins) breakdown) yielding elimination in bile rocuronium (but
Laudanosine can also reverse
Notes
(seizure causing) vecuronium and
• Atracurium and pancuronium to a
Cisatracurium are lesser extent
ideal for hepatic • Useful in patients
patients with renal
impairment
• Has a rapid onset
time (60-120 sec)
DEPOLARIZING NEUROMUSCULAR BLOCKERS Increased intraocular pressure,
Drug SUCCINYLCHOLINE [C] Malignant hyperthermia ((MH) – When given
Short acting together with Halothane)), Arrhythmia
Duration
Duration: 6-11 minutes, onset: 60-90 seconds Metabolized by pseudocholinesterase (just like
Notes
Agonist at ACh-N receptors causing initial twitch then mivacurium); Treatment for MH: Dantrolene
persistent depolarization. Initial depolarization
MOA causes transient contractions, followed by prolonged PHASES OF DEPOLARIZING BLOCKADE
flaccid paralysis. Depolarization is then followed by • PHASE I (DEPOLARIZATION)
repolarization that is also accompanied by paralysis o membrane depolarizes w/ initial electric discharge
Skeletal muscle relaxation during intubation and o transient fasciculations followed by flaccid paralysis
Uses general anesthesia, NMB of choice for rapid sequence
• PHASE II (DESENSITIZATION)
induction
o membrane repolarizes but receptor is desensitized to the
Post-operative muscle pain, Hyperkalemia (0.5
SE mEq/L increase), Increased intragastric pressure
effects of acetylcholine
leading to regurgitation (aspiration),
CENTRALLY ACTING SPASMOLYTIC DRUGS

ORPHENADRINE,
CHLORPHENESIN,
Drugs BACLOFEN [C] DIAZEPAM TIZANIDINE
METHOCARBAMOL,
CYCLOBENZAPRINE
GABAB agonist. Facilitates spinal Poorly understood inhibition Facilitates GABAergic transmission in
MOA a2 agonist in the spinal cord
inhibition of motor neurons of muscle stretch reflex CNS
Severe spasticity due to Chronic spasm due to cerebral palsy, Spasm due to
Acute spasm due to muscle
Uses cerebral palsy, stroke, spinal cord injury, multiple sclerosis, stroke,
injury. Inflammation
multiple sclerosis, stroke acute spasm due to muscle injury amyotrophic lateral sclerosis
Anterograde amnesia, Decreased
Sedation. Weakness.
Strong antimuscarinic psychomotor skills, Unwanted daytime Weakness, Sedation,
SE Dizziness. Confusion. Nausea,
effects sedation, Respiratory depression, Hypotension
Headache
Tolerance, Dependence liability
DIRECT-ACTING MUSCLE RELAXANT Pharmacologic strategies for Dopaminergic Therapy of

Parkinson’s Disease
• Direct-acting muscle relaxant
• MOA: Ca Channel blocker - Block RyR1
Pramipexole, Bromocriptine,
Ca2+-release channels in the sarcoplasmic ropinirole pergolide
+ +
reticulum of the skeletal muscle Dopamine
DANTROLENE receptors
• Use: Malignant Hyperthermia, Spasm due
to cerebral palsy, spinal cord injury & Salegiline,
rasagiline Tolcapone
multiple sclerosis +
• SE: Muscle weakness - -
• Antispasmodic drug which relaxes both
MAO-B COMT
skeletal and vascular smooth muscles DOPAC Dopamine 3-MT
EPERISONE
and reduces myotonia, improves circulation
and suppresses pain reflex. DOPA decarboxylase
DRUGS USED IN PARKINSONISM L-DOPA
Brain L-amino acid transporter
Blood Brain Barrier

Periphery
3-OMD L-DOPA Dopamine

COMT DOPA
decarboxylase
Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 - -
Entecapone,
PARKINSON’S DISEASE tolcapone Carbidopa Adverse
effects
• also known as paralysis agitans: neurodegenerative disease
caused by degeneration of dopaminergic neurons in the Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
substantia nigra
o Dopaminergic neurons: responsible for inhibiting excitatory DOPAMINERGIC
cholinergic output from the striatum. THERAPY
• classic triad of bradykinesia, resting tremors and dystonia OF PARKINSON’S
o progressive neurologic disease characterized by shuffling gait, DISEASE
stooped posture, resting tremor, speech impediments, https://qrs.ly/1rcke9z
movement difficulties and an eventual slowing of mental
processes and dementia LEVODOPA TREATMENT: PROBLEMS ENCOUNTERED
PARKINSON DISEASE: It’s a TRAP! Tremor, Rigidity, Akinesia, Postural Fate of Orally administered Levodopa and the effect of Carbidopa
Instability!
• The pathological hallmark of PD is the loss of the pigmented,

dopaminergic neurons of the substantia nigra pars
compacta, with the appearance of intracellular inclusions
known as Lewy bodies.
o The principal component of the Lewy bodies is aggregated α-
synuclein
• Treatment strategies:
o Restore dopaminergic activity in the basal ganglia via:
§ (1) dopamine precursors (increase level of levodopa)
§ (2) dopamine agonists
§ (3) drugs that inhibit its metabolism
o Restore balance between cholinergic and dopaminergic
neural circuitry, hence the value of your antimuscarinic
agents (4) curbing cholinergic excess
The first three will address bradykinesia and number 4 will address
dystonia and resting tremors.
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) Figure 28-4. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
• Diminishing effect on chronic therapy: As treatment with MNEMONIC Livedo Reticularis
levodopa is continued, patients eventually become less What drugs can cause livedo reticularis? A man reads FHM and GQ!
responsive to L-dopa Amantadine Gemcitabine
o Begins to diminish after 3-4 years of therapy Hydroxyurea Quinidine
Minocycline
o due to progressive destruction of nigrostriatal neurons that
occurs with disease progression
SUPPLEMENT: DRUGS FOR HUNTINGTON’S DISEASE
• ON-OFF PHENOMENA (unrelated to timing of doses)
Deplete amine transmitters especially
o alternating periods of improved mobility and akinesia, Dopamine from nerve endings by
occurring over a few hours to days during treatment reversibly inhibiting human vesicular
• WEARING-OFF PHENOMENA (related to timing of doses) TETRABENAZINE, monoamine transporter type 2 (VMAT2)
o deterioration of drug effect in between medication doses (off RESERPINE resulting in decreased uptake of
periods are characterized with marked akinesia which monoamines; reduces chorea severity;
alternate with few hours of on periods characterized by SE: hypotension, sedation, depression,
improved mobility) diarrhea
SUPPLEMENT: DRUGS FOR TOURETTE’S SYNDROME

Block central D2 receptors, reduce vocal and
motor tic frequency & severity ; SE:
HALOPERIDOL, parkinsonism and other dyskinesias,
PIMOZIDE sedation, blurred vision, dry mouth, GI
disturbance, Pimozide may cause
arrhythmia
DRUGS USED IN PARKINSONISM

DOPAMINE AGONIST: DOPAMINE AGONIST:
DOPAMINE PRECURSOR OPIOID DOPAMINE AGONIST
ERGOT NON-ERGOT
Drug BROMOCRIPTINE [B],
PRAMIPEXOLE [C],
LEVODOPA-CARBIDOPA [C] PERGOLIDE [B], APOMORPHINE [C]
ROPINIROLE [C]
CABERGOLINE [B], PIRIBEDIL
Levodopa – dopamine precursor. Partial agonist at dopamine D2 Partial agonist at dopamine D2

Agonist at dopamine D2
Carbidopa – inhibits peripheral receptors in brain, (pramipexole) and
MOA receptors. Antagonist at 5-HT
metabolism via dopa D2 agonism leads to inhibition D3 receptors (ropinirole) in
and alpha adrenoceptors.
decarboxylase. of prolactin release brain.
Rescue treatment for off-periods

Parkinson disease (addresses of Parkinson’s disease
Parkinson’s disease,
affective symptoms of PD), (temporary relief),
Uses DOC for Parkinson disease Levodopa intolerance,
Restless legs syndrome, Alcoholism, Opiate addiction,
Hyperprolactinemia
On-Off phenomenon Erectile dysfunction,
Alzheimer’s disease
GI disturbance
(anorexia, nausea and vomiting), Anorexia, Nausea, Vomiting,
Arrhythmia, Anorexia, nausea, vomiting, Dyskinesias,
Profound Hypotension,
Dyskinesia (choreoathetosis), dyskinesia, postural Postural hypotension,
Loss of consciousness,
Behavioral changes (anxiety, hypotension, behavioral Behavioral changes, Confusion,
SE QT prolongation,
agitation, confusion, delusion), changes, erythromelalgia Compulsive gambling,
Severe nausea, Dyskinesias,
On-off phenomena, (Bromocriptine), pulmonary Hypersexuality, Overeating,
Drowsiness, Sweating
Wearing-off phenomena, infiltrate (Bromocriptine) Uncontrollable tendency to fall
Postural hypotension, asleep
tachycardia
• GI disturbance is due to the • Piribedil can also act as a D3 • Contraindications: active • Use only when other
peripheral dopamine effects agonist and A2 adrenergic peptic ulcer disease, psychotic dopamine agonists and COMT
on the GI system antagonist. It is particularly illness, or recent myocardial inhibitors have failed
• PHENOTHIAZINE used for the alleviation of infarction • Premedicate with
(antipsychotics largely used as tremors. It has also been used • Behavioral changes more TRIMETHOBENZAMIDE to
antiemetics) SHOULD BE for circulatory disorders such prominent compared to prevent severe nausea
AVOIDED when taking L-dopa as intermittent claudication levodopa
because it may exacerbate PD • Decrease dose in renal
• Contraindicated in patients dysfunction
with history of psychosis • Neuroprotective
• Arrhythmia is due to the • The impulse control
Notes increased dopamine disorders arising from the
peripherally use of these drugs is
• Behavioral changes may be attributed to the activation of
treated with ATYPICAL D2/D3 receptors in the
Antipsychotics (low affinity for mesolimbic pathways of the
D2 receptors, eg clozapine, brain. Such symptoms abate
quetiapine, olanzapine, etc.) with discontinuance of use.
• Hypertensive crisis occurs
when used with monoamine
oxidase inhibitors
• Use with COMT inhibitors to
prolong duration of effect
ANTI-PARKINSONISM,
MAO TYPE B INHIBITOR COMT INHIBITOR ANTICHOLINERGIC
ANTI-INFLUENZA
Drug BENZTROPINE,
SELEGILINE [C], BIPERIDEN [C],
ENTACAPONE [C], TOLCAPONE [C] AMANTADINE [C]
RASAGILINE [C] TRIHEXYPHENIDYL,
PROCYCLIDINE
Potentiate dopaminergic
Block L-dopa metabolism by
Selective inhibitors of monoamine function by influencing the Decrease the excitatory
inhibiting catechol-O-
oxidase type B → decreased synthesis, release, or actions of cholinergic
methyltransferase in periphery
MOA degradation of dopamine. reuptake of dopamine. neurons on cells in the
(both) and CNS (tolcapone only).
Increases response to Antagonizes the effects of striatum by blocking
Net result: Prolongs response to
levodopa/carbidopa. adenosine at adenosine A2A muscarinic receptors
levodopa.
receptors
Adjunct for waning effect As adjunct for Parkinson’s
treatment to levodopa for Parkinson’s disease (wearing-off Parkinson disease, disease and Extrapyramidal
Uses
Parkinson’s disease, wearing off or phenomena), as adjunct to levodopa Influenza symptoms caused by
on-and-off phenomenon antipsychotics
Behavioral changes
Dyskinesias, GI distress, (restlessness, agitation, Drowsiness, Inattention,
Postural Hypotension, insomnia, hallucination, Confusion, Delusions,
Insomnia, Mood changes, Sleep disturbance, acute toxic psychosis), Hallucinations,
SE Dyskinesias, Gastrointestinal Orange urine, Hepatotoxicity Livedo reticularis, Atropine-like effects
distress, Hypotension (tolcapone only), GI disturbances, Urinary (urinary retention,
Neuroleptic malignant syndrome, retention, Postural constipation,
Rhabdomyolysis, Nausea, Confusion hypotension, Peripheral dry mouth)
edema
• If used with meperidine, causes • Since inhibition of dopa- • May improve • Improve tremor and
agitation, delirium and death decarboxylase upregulates other bradykinesia, rigidity rigidity, with little effect
(fatal reaction) pathways of levodopa metabolism and tremor on bradykinesia
• Serotonin syndrome occurs (COMT pathway), inhibitors of • Has anti-muscarinic • Exacerbate tardive
when used with SSRIs, TCA and COMT will improve therapeutic action dyskinesias that result
Meperidine response to levodopa treatment by from prolonged use of
• Higher doses of selective MAO-B diminishing its peripheral antipsychotic drugs
inhibitors can also inhibit MAO-A metabolism (particularly,
Notes receptor conversion to 3-OMD by COMT
pathway)
Since they are SELECTIVE MAO B
inhibitors, these drugs do not Remember, Entacapone only acts in
exhibit the “CHEESE EFFECT” (i.e. the periphery while Tolcapone acts
hypertensive crisis seen with both in the periphery and CNS.
ingestion of tyramine rich food
such as cheese whilst taking a
NON-SELECTIVE MAO inhibitor).
Remember that.
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
*Supersensitivity of the postjunctional DA receptors in the 4mo-4yr (tongue protrusion, lip None
CNS 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
ANTIPSYCHOTIC AGENTS AND LITHIUM • Hypothesis not fully satisfactory because antipsychotic drugs
are only partly effective in most patients
• Schizophrenia: involves excess activity of the dopaminergic
neuron in the mesolimbic-mesocortical pathway, causing Hard
symptoms/ Positive (HIDES): Hallucination, Illusion, Delusion,
Excitement and Suspiciousness.
• For negative signs, think of social depression (anhedonia,
avolition, anergia)
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
Schizophrenia: Dopamine Hypothesis o many antipsychotic drugs block brain dopamine receptors
• Schizophrenia is caused by a relative excess of dopamine in o dopamine agonist drugs (e.g. amphetamine, levodopa)
specific neuronal tracts in the brain exacerbate schizophrenia
CLASSIFICATION OF ANTIPSYCHOTICS
• Different classes: PHENOTHIAZINES • HETEROCYCLICS (clozapine, loxapine,
(chlorpromazine, thioridazine, fluphenazine), olanzapine, risperidone, quetiapine,
THIOXANTHENES (thiothixene) and ziprasidone, aripiprazole)
BUTYROPHENONES (haloperidol) ATYPICAL
Atypical antipsychotics address both
ANTIPSYCHOTICS
Addresses positive symptoms positive and negative effects of
(Hallucinations) of schizophrenia but not schizophrenia
TYPICAL MOA: Block 5HT2A
much effect on negative symptoms • Atypicals have a lesser propensity to
(CLASSICAL) receptors > D2
(emotional blunting, social withdrawal, lack cause EPS compared to its typical
ANTIPSYCHOTICS receptors
of motivation) counterparts, but has a higher propensity
Block more D2 • High potency typical antipsychotics (i.e. in causing metabolic derangements
receptors > 5HT2A Haloperidol, droperidol): higher chances (weight gain, endocrine problems)
receptors of causing extrapyramidal symptoms
(EPS)
• Low potency typical antipsychotics (i.e.
Thioridazine, Chlorpromazine): lower
chances of causing EPS, more likely to
cause sedation and postural
hypotension (due to alpha receptor
blockade)
TOXICITIES OF ANTIPSYCHOTICS
TYPE MECHANISM MANIFESTATIONS
Loss of accommodation, dry mouth, difficulty urinating,
Autonomic Nervous Muscarinic cholinoceptor blockade
constipation
System
⍺-adrenoceptor blockade Orthostatic hypotension, impotence, failure to ejaculate
Dopamine receptor blockade Parkinson syndrome, akathisia, dystonias
Central Nervous System Supersensitivity of dopamine receptors Tardive dyskinesia
Muscarinic blockade Toxic-confusional state
Dopamine-receptor blockade resulting in
Endocrine system Amenorrhea-galactorrhea, infertility, impotence
hyperprolactinemia
Other Possibly combined H1 and 5HT2 blockade Weight gain
TYPICAL ANTIPSYCHOTICS
(** may also be used for pruritus and as sedatives **)
PHENOTHIAZINE PIPERIDINE BUTYROPHENONE
CHLORPROMAZINE [C], Levomepromazine, THIORIDAZINE [C],
Drug Prochlorperazine [C], Promethazine, FLUPHENAZINE [C],
HALOPERIDOL [C], DROPERIDOL [C]
Thiothexene [C] (Thioxanthene), PERPHENAZINE [C],
Flupentixol (Thioxantene) TRIFLUOPERAZINE [C]
MOA Block of D2 receptors ≫ 5-HT2 receptors
Schizophrenia and other psychotic
Schizophrenia and other psychotic disorders,
Schizophrenia and other psychotic disorders, BPD (Manic phase),
Uses Manic phase of BPD, antiemetic (Promethazine
disorders Huntington's disease,
and prochlorperazine only)
Tourette's syndrome
• Postural hypotension (a) • Extrapyramidal dysfunction (D2) • Extrapyramidal dysfunction (major, D2)
• Marked sedation (H1) • Tardive dyskinesia (D2) • Tardive dyskinesia (D2)
• Extrapyramidal dysfunction (D2) • Hyperprolactinemia (D2 in • Hyperprolactinemia (D2 in
• Tardive dyskinesia (D2) tuberoinfundibular pathway), tuberoinfundibular pathway)
• Hyperprolactinemia (D2 in tuberoinfundibular Anticholinergic effects, • Neuroleptic Malignant syndrome
pathway) • Failure of ejaculation (a) Haloperidol (Haldol) is a major
• Failure of ejaculation (a) • Postural hypotension (a) tranquilizer given IM. It has the highest
SE
• Corneal and lens deposits • Retinal deposits (Thioridazine) potential for EPS and neuroleptic
• Neuroleptic malignant syndrome • Cardiotoxicity (QT prolongation – malignant syndrome.
• Contact dermatitis, (a) arrhythmias - Thioridazine)
• decreased seizure threshold
Thioridazine has the most muscarinic
blockade therefore has the least EPS
amongst the typical antipsychotics
Remember: Histamine antagonism accounts for • Thioridazine has quinidine like • Specific Receptor antagonism binding
relief of pruritus and sedating effect actions (prolongation of QT interval) profile: D2 > a1 > D4 > 5HT2A > D1 > H1
• Chlorpromazine: Prototype of all • Fluphenazine and Trifluoperazine • Weakest autonomic effects
Notes antipsychotics have very significant Parkinson-like • Least sedating among typical antipsychotics
• Levomepromazine blocks a variety of receptors effect • Some a-blockade but minimal M
including adrenergic dopamine, histamine, • Fluphenazine has less sedation receptor blockade
muscarinic and serotonin receptors compared to other anti-psychotics
ATYPICAL ANTIPSYCHOTICS
(** atypicals may be used for mania and psychotic symptoms in Alzheimer's dementia and Parkinson disease **)
DIBENZODIAZEPINE THIENOBENZODIAZEPINE DIBENZOTHIAZEPINE BENZISOXAZOLE DIHYDROINDOLONE DIHYDROCARBOSTYRIL
Drugs RISPERIDONE [C],
CLOZAPINE [B] OLANZAPINE [C] QUETIAPINE [C] ZIPRASIDONE [C] ARIPIPRAZOLE [C]
PALIPERIDONE
Partial agonist at the D2
MOA Block of 5-HT2 receptors ≫ D2 receptors
receptor
Schizophrenia and other Schizophrenia and other Schizophrenia and other Schizophrenia and other
Schizophrenia and other
Schizophrenia (DOC for refractory and psychotic disorders, psychotic disorders, psychotic disorders, psychotic disorders,
psychotic disorders, Bipolar
Uses suicidal schizophrenia) and other psychotic Bipolar disorder, Bipolar disorder (manic episodes), Bipolar disorder, Depression, Bipolar disorder,
disorder
disorders Anorexia nervosa, Sleep promotion and Intractable hiccups, Tourette Major Depressive Disorder,
(acute mania)
Depression maintenance syndrome Autism, Cocaine dependence
Extrapyramidal Extrapyramidal dysfunction
Extrapyramidal dysfunction (less),
dysfunction (less), (less), Hyperprolactinemia (less), Extrapyramidal dysfunction
Hyperprolactinemia (less),
Hyperprolactinemia (less), Postural hypotension, (less), Extrapyramidal dysfunction Extrapyramidal dysfunction
Postural hypotension, Weight gain,
Postural hypotension, Weight gain (less), Somnolence, Weight gain (less), Insomnia, (less), (less),
SE Hyperglycemia (diabetes mellitus),
Weight gain, Fatigue, Sleep paralysis, Hyperprolactinemia Postural hypotension, Gastrointestinal upset, Tremor,
Hyperlipidemia, Myocarditis,
Hyperglycemia (diabetes Hypnagogic hallucinations, (marked), Photosensitivity, QT prolongation (TDP) Hypersensitivity (rare)
Agranulocytosis, Seizures, Ileus,
mellitus), Hyperlipidemia, Cataracts, priapism, Hyperprolactinemia
Hypersalivation (sialorrhea)
Agranulocytosis QT prolongation (TDP)
• Specific Receptor antagonism binding • Specific Receptor • Specific Receptor antagonism • Risperidone, compared to all • Thioridazine and Ziprasidone • Specific Receptor antagonism
profile: antagonism binding binding profile: the other atypicals, has the has quinidine like actions binding profile:
D4 = a1 > 5HT2A > D2 = D1 profile: H1 > a1 > M1,3 > D2 > 5HT2A highest propensity for (prolongation of QT interval) D2 = 5HT2A > D4 > a1 = H1 >>
• Clozapine is the prototype of your atypicals 5HT2A > H1 > D4 > D2 > • Olanzapine, Quetiapine and causing • Ziprasidone has the greatest D1
• Relapse after discontinuation is rapid and a1 > D1 Aripiprazole cause MINIMAL or hyperprolactinemia risk for QT prolongation • Olanzapine, Quetiapine and
severe • Olanzapine, Quetiapine NO increases in prolactin and (amenorrhea, galactorrhea) (and hence don’t combine Aripiprazole cause MINIMAL
• Clozapine and Olanzapine has the and Aripiprazole cause has a reduced risk of EPS • Only antipsychotic with drugs that will have the or NO increases in prolactin
highest tendency to cause weight gain MINIMAL or NO (reflected by minimal D2 approved for same effect i.e. thioridazine, and has a reduced risk of EPS
amongst your atypicals increases in prolactin and antagonism) schizophrenia in the youth class I and 3 (reflected by minimal D2
• Only antipsychotic that reduces the risk of has a reduced risk of EPS • Quetiapine and Clozapine are • With some histamine and a- antiarrhythmics) antagonism)
suicide (reflected by minimal D2 amongst the atypicals that is blockade • No atropine-like effects • Least sedating atypical
• Reserved for treatment of schizophrenia antagonism) LEAST LIKELY to cause • Little or no tendency to antipsychotic
not amenable to other drugs • Clozapine and tardive dyskinesia cause hyperglycemia, • No atropine-like effects
Notes • With some M receptor, histamine and a- Olanzapine has the • With some histamine receptor hyperprolactinemia or
blockade highest tendency to cause blockade weight gain
• Agranulocytosis and seizures are feared weight gain amongst • Safe in Pregnancy • Increased mortality in
complications. Because of the risk of your atypicals elderly patients with
agranulocytosis, patients receiving • With some histamine and dementia-related psychosis
clozapine must have weekly blood counts M receptor-blockade • With some histamine and a-
for 6 months of treatment • Safe in Pregnancy blockade
Clozapine is not associated with EPS because it
blocks the D2C receptor (mesocortical
mesolimbic area) not the D2A (nigrostriatal
pathway). However, it is cumbersome to use this
because of the potential life-threatening
agranulocytosis which requires the patient to
have weekly CBC. Cognizant of this, other
atypical antipsychotics were born.
MNEMONICS: Olanzapine and clozapine
“O”
ANTIDEPRESSANTS
Olanzapine and clOzapine can cause Obesity
Drugs have the highest tendency to cause weight gain
amongst your atypicals
QUETIAPINE = increase in QUIET TIME

Drug used for sleep maintenance and promotion
MNEMONICS: Neuroleptic Malignant Syndrome
What are the features of neuroleptic malignant syndrome? AMINE HYPOTHESIS OF MOOD
NEUROLEPTIC MALIGNANT SYNDROME • brain amines, particularly NE and serotonin, are neurotransmitters
“FEVER”
in pathways that function in the expression of mood
Fever Elevated CPK
Encephalopathy Rigidity
o functional decrease of activity results in depression
Vitals unstable o functional increase of activity results in mood elevation
Other theories explaining depression
• decrease in BNDF
LITHIUM • elevated glutamate levels are seen in depressed patients (which
Class Mood stabilizer explains role of ketamine, an NMDA antagonist for the treatment
Uncertain. Suppresses inositol signaling and inhibits of refractory depression)
MOA
glycogen synthase kinase 3 (GSK-3)
Bipolar disorder, Recurrent depression, CLASSIFICATION OF ANTIDEPRESSANTS
Uses Schizoaffective disorder TRICYCLIC ANTIDEPRESSANTS
imipramine, amitriptyline
DOC for Bipolar disorder (TCAs)
Tremor (most common), Ataxia, Aphasia, Thyroid SELECTIVE SEROTONIN
fluoxetine, escitalopram,
enlargement, Subclinical Hypothyroidism (due to REUPTAKE INHIBITORS
paroxetine, sertraline
uncoupling of TSH from its G protein receptor), (SSRIs) – first line
SE Nephrogenic diabetes insipidus, Edema (common), SEROTONIN-
Acneiform skin eruptions, Leukocytosis, Teratogen NOREPINEPHRINE REUPTAKE duloxetine, venlafaxine
(Ebstein Anomaly), Bradycardia, Renal dysfunction, INHIBITORS (SNRIs)
Dysrhythmia SEROTONIN (5-HT2)
nefazodone, trazodone
• Contraindicated in sick sinus syndrome RECEPTOR ANTAGONISTS
(bradycardia-tachycardia syndrome) HETEROCYCLIC amoxapine, bupropion,
• Treat overdose with hemodialysis ANTIDEPRESSANTS maprotiline, mirtazapine
• Narrow therapeutic window MONOAMINE OXIDASE phenelzine,
• Lithium has great toxicity: Think of everything that is INHIBITORS (MAOIs) tranylcypromine, selegiline
governed by cyclic AMP, Lithium will block it and will
TRICYCLIC ANTIDEPRESSANTS (TCA) OVERDOSE
Notes cause a predominance of Gi coupling.
• Some drugs (NSAIDs, ACEi, thiazide diuretics etc.) can • DOSAGE
increase Lithium toxicity, while caffeine and o toxic dose: 7 mg/kg
theophylline can decrease its toxicity o lethal dose: 15 mg/kg
• Lithium mnemonic lifted from USMLE: • CLINICAL PRESENTATION
LiTHIUM: Low Thyroid hormone, Heart (Ebstein o agitation, delirium, neuromuscular irritability
anomaly), Insipidus (nephrogenic diabetes insipidus, o convulsions, and coma
Unintentional Movement (tremor)
o respiratory depression and circulatory collapse
o hyperpyrexia
CLINICAL USE OF LITHIUM o cardiac conduction defects and severe arrhythmias
• treatment of bipolar disorder (manic-depressive) § ECG reveals abnormal morphology of QRS complexes,
o decreases manic behavior and reduces both the frequency and prolonged QRS duration, abnormal size and ratio of R and S
the magnitude of mood swings waves in AVR
o protective effects against suicide and self-harm
MNEMONIC: TCA Toxicity
• used concurrently with antidepressants during maintenance
What are the 3 Cs of TCA Overdose?
therapy Coma Convulsions Cardiotoxicity
o monotherapy with antidepressants can precipitate mania in
bipolar patients
Treatment of TCA Overdose
• antipsychotic agents and/or benzodiazepines are commonly
• SUPPORTIVE MEASURES
required at initiation of treatment because of slow onset of
o fluid resuscitation for hypotension
action
o gastric decontamination with activated charcoal
o control seizures with benzodiazepines
LITHIUM OVERDOSE
• ADMINISTRATION OF BICARBONATE
• threshold for toxicity is 2meq/L o QRS duration >100 msec or ventricular arrhythmias
• therapeutic overdoses are more common than deliberate or o reverses cardiotoxicity
accidental ingestion
o due to change in the patient's status (diminished serum
sodium, use of diuretics or fluctuating renal function) SEROTONIN SYNDROME, NMS,
• CLINICAL MANIFESTATIONS AND MALIGNANT HYPERTHERMIA
o neuromuscular excitability, tremors, twitching, agitation, https://qrs.ly/backeau
weakness, ataxia, leukocytosis, bradycardia, hypotension
• TREATMENT
SEROTONIN SYNDROME
o hemodialysis is preferred over peritoneal dialysis
• life-threatening syndrome characterized by severe muscle
NEWER AGENTS USED FOR BIPOLAR DISORDER rigidity, myoclonus, hyperthermia, cardiovascular instability,
and marked CNS stimulatory effects, including seizures
• Carbamazepine
• drugs implicated include MAOIs, TCAs, dextromethorphan,
• Lamotrigine meperidine, St. John's wort, and MDMA ("ecstasy")
• Valproic Acid / Divalproex
• antiseizure drugs, muscle relaxants, and blockers of 5-HT
receptors (e.g. Cyproheptadine)
ANTIDEPRESSANTS
TRICYCLIC SELECTIVE SEROTONIN SEROTONIN-NOREPINEPHRINE SEROTONIN UNICYCLIC MONOAMINE OXIDASE
TETRACYCLIC ANTIDEPRESSANT
ANTIDEPRESSANT REUPTAKE INHIBITOR REUPTAKE INHIBITOR ANTAGONIST AMINOKETONE INHIBITOR
IMIPRAMINE [D], FLUOXETINE [C],
CLOMIPRAMINE [C], PAROXETINE [D], PHENELZINE,
Drug VENLAFAXINE, DULOXETINE,
DESIPRAMINE [C], CITALOPRAM [C], TRAZODONE [C], TRANYLCYPROMINE,
DESVENLAFAXINE, AMOXAPINE [C],
AMITRYPTYLINE [C], ESCITALOPRAM [C], NEFAZODONE [C], MIRTAZAPINE [C] BUPROPION [C] ISOCARBOXAZID,
MILNACIPRAN MAPROTILINE [B]
NORTRYPTILINE [D], SERTRALINE [C], VORTIOXETINE SELEGILINE
All are Preg Cat C
DOXEPIN, PROTRIPTYLINE FLUVOXAMINE [C], All are Preg Cat C
[C], TRIMIPRAMINE [C] VILAZODONE
Inhibits neuronal
Block 5-HT2A reuptake of Inhibits monoamine
Inhibits neuronal reuptake of Strong Increases amine
Block norepinephrine (NE) receptors, weak dopamine and oxidase type A and type
serotonin and norepinephrine norepinephrine release from nerve
and 5-HT transporters → inhibitor of NE and 5HT norepinephrine. B. Increases CNS levels
by binding to transporters for reuptake inhibitor endings by
potentiation of NT action at Inhibits neuronal reuptake of transporters. Increases dopamine of NE and serotonin.
both 5HT and NE and weak serotonin antagonism of
MOA postsynaptic receptors; serotonin by inhibiting Nefazodone also blocks and norepinephrine Tranylcypromine are
reuptake inhibitor. presynaptic a2
Like SNRIs plus significant Serotonin Transporter (SERT) Differ from TCA in lacking Serotonin reuptake activity. nonselective MAO
Blocks dopamine D2 adrenoceptors;
blockade of ANS and blockade of H1, M and alpha transporters while inhibitors while
receptors. Resembles Blocks serotonin No effect on 5HT or
histamine receptors receptors Trazodone can also Selegiline is a MAO-B
TCA in terms of effects 5HT2 receptors. NE receptors or
block 5HT2C receptors selective inhibitor
amine transporters
Major depressive disorder
not responsive to SSRI (first
DOC for Major Depressive
line) and SNRI, chronic pain Disorder, OCD, Anxiety, Major depression
states, Enuresis, Insomnia, Major depression unresponsive to other
Panic attacks, Phobias, PTSD, Major depression
Bipolar disorder, Acute Eating Disorders (Bulimia), Major depression, Fibromyalgia, Major depression, unresponsive to drugs, Useful in patients
not responsive to
panic attacks, Phobias, Premenstrual dysphoria, Perimenopausal symptoms, Sedation, other agents, with significant anxiety,
ADHD, Incontinence, other agents,
Uses Alcohol dependence, Diabetic neuropathy, Hypnosis/Sleeping aid Major depression Appetite phobic features and
Smoking cessation,
OCD (Clomipramine) Perimenopausal vasomotor Neuropathic pain, (Trazodone), stimulation, hypochondriasis
Alcohol dependence
This group is very useful for symptoms Chronic Pain Disorders Anxiety disorders Sedation/Sleeping
patients with psychomotor aid
Fluvoxamine is approved only
retardation, sleep
for Obsessive-Compulsive behavior
disturbance, poor appetite
and weight loss
• Dry mouth, Constipation, • Increased serotonergic activity • Hypertension (Venlafaxine) • Sedation, • Autonomic effects, • Weight gain, • Weight loss, • Dizziness, Insomnia,
urinary retention, blurred in gut: Nausea, vomiting, and CNS stimulation Gastrointestinal Akathisia, Marked sedation, Agitation, Orthostatic
vision and confusion – diarrhea (Insomnia, anxiety and disturbance, Parkinsonism (due Dizziness, Dizziness, Dry hypotension, Blurred
Anticholinergic effects • Increased serotonergic tone in agitation) due to Orthostatic to dopamine Blurred vision, mouth, vision, Arrhythmias,
• Orthostatic hypotension – spinal cord: diminished sexual Noradrenergic effects, hypotension, receptor blockade), Nightmares Aggravation of Diarrhea,
Alpha blocking effects function and interest Hepatotoxicity (duloxetine), Priapism Amenorrhea- psychosis, hyperthermia, CNS
• Weight gain and Excessive • Other SE related to increased Withdrawal syndrome even in (trazodone), galactorrhea Seizures, Priapism stimulation, seizure
sedation – Histamine serotonin: headaches, just one missed dose, Hepatotoxicity syndrome, Seizures,
SE blocking insomnia Anticholinergic symptoms (nefazodone), Cardiotoxicity
• Fatigue, Confusion, , • Discontinuation syndrome: Hyperprolactinemia
Cardiomyopathies, Paroxetine and sertraline
Arrhythmias, Tremors, • QT prolongation and
Paresthesia, seizure in teratogen (cardiac septal
overdose defects): citalopram only
Minimal inhibitory effect on
cholinergic or adrenergic
receptors (unlike TCAs)
MONOAMINE
TRICYCLIC SELECTIVE SEROTONIN SEROTONIN-NOREPINEPHRINE SEROTONIN TETRACYCLIC UNICYCLIC TRICYCLIC
Drugs OXIDASE
ANTIDEPRESSANT REUPTAKE INHIBITOR REUPTAKE INHIBITOR ANTAGONIST ANTIDEPRESSANT AMINOKETONE ANTIDEPRESSANT
INHIBITOR
• Additive depression of the • High risk of serotonin • Duloxetine and • Trazadone is used off- • Lowers seizure • Has significant • Structurally, • MAO inhibitors have
CNS with other central syndrome if co-administered Desvenlafaxine is a CYP450 label for hypnosis threshold muscarinic bupropion is amphetamine like features
depressants with MAOi. Discontinue for 4 inhibitor • May cause arrhythmias • Has significant receptor and similar to • Serotonin syndrome
• Lower seizure threshold weeks or longer before • Venlafaxine has less affinity in patients with pre- muscarinic receptor alpha-2 blocking amphetamines so when taken with SSRIs
• Drug levels are easily initiating use of MAOi if for NE transporter than existing cardiac disease blocking effect effect it has stimulant • CYP450 inhibitors
affected by CYP inducers already on SSRIs desvenlafaxine and duloxetine • Trazodone: modest a1 • Lowers seizure features • Long-term use may lead
and inhibitors • Fluoxetine, fluvoxamine and • Increased risk for suicide in and H1 receptor threshold • Lowers seizure to down-regulation of
• Imipramine is metabolized to Paroxetine are CYP450 children and adolescents blockade (Amoxapine) threshold Beta receptors (leading to
desipramine while inhibitors • Nefazodone has • CYP450 inhibitor decrease in BP)
amitriptyline is metabolized • Vilazodone can also act as a significant muscarinic • Lower seizure threshold
to nortriptyline partial agonist of 5HT1A receptor blocking effect • Selegiline may be given as
• Very long half-lives • DAPOXETINE is an SSRI which • Nefazodone is a potent skin patch
Notes • Long-term use may lead to has been developed for CYP3A4 inhibitor • Hypertensive crisis when
down-regulation of Beta treatment of Premature • Short t½ : given BID/TID taken with tyramine
receptors → decrease in Ejaculation taken 1-3 hours • Vortioxetine is a 5HT3 (indirect-acting sympatho-
BP and depression of prior to coitus and 5HT1D antagonist mimetic in cheese)
cardiac conduction and a 5HT1A agonist • Other tyramine rich food:
• 3Cs of overdose: Coma, Mirtazapine, Bupropion avocado, Cheese, wine
Cardiotoxicity, Convulsions and Nefazodone, are Remember, the
• Amitriptyline has a among the few Mirtazapine, Bupropion and Nefazodone, releasers of
significant muscarinic antidepressants that are among the few antidepressants that norepinephrine from
receptor blocking effect are not associated are not associated with sexual the presynaptic vesicles?
• May interfere with anti- with sexual dysfunction as side effect MNEMONIC: release the
hypertensive action of dysfunction as side TAE: Tyramine,
Clonidine effect Amphetamine, Ephedrine
KEY LEARNING POINT Differentiate Serotonin Syndrome from NMS and Malignant Hyperthermia
MALIGNANT HYPERTHERMIA SEROTONIN SYNDROME NEUROLEPTIC MALIGNANT SYNDROME
Onset • Within minutes • Within hours • 1-3 days
Precipitating drug • Volatile anesthetics (halothane), succinylcholine • SSRIs, MAOIs, TCAs, Meperidine, MDMA, St. John’s Wort • Antipsychotics
Mechanism • Massive calcium release from SR • Excess serotonin • Dopamine antagonism
• Fever • Fever
• Fever
• Acidosis • Agitation
• Encephalopathy
• Rhabdomyolysis • Tremor
Clinical features • Vitals unstable
• Trismus • Clonus
• Elevated CPK
• Clonus • Hyperreflexia
• Rigidity
• Hypertension • Diaphoresis
First-line treatment • Dantrolene • Sedation, paralysis, intubation and ventilation • Diphenhydramine
Other treatment • Cooling • Cooling, cyproheptadine, chlorpromazine • Cooling, Dantrolene, bromocriptine, amantadine, diazepam
SUPPLEMENT: Serotonin Syndrome MNEMONIC: Erectile Dysfunction MNEMONIC: Priapism
What are the features of Serotonin Syndrome? What drugs can cause erectile dysfunction? What drugs can cause PRIAPISM?
FAT CHD ERECTILE DYSFUNCTION Tigas PeniS Qo, AyaW Bumaba!
Fever Clonus A SORE PeniS can’t Fuck Hard! Trazodone Alprostadil
Agitation Hyperreflexia SSRIs Propranolol Papaverine Warfarin
Tremor Diaphoresis Opiates Spironolactone Sildenafil Bupropion
Risperidone Finasteride Quetiapine
Ethanol, Estrogen Hydrochlorothiazide
OPIOID ANALGESICS AND ANTAGONISTS OPIOID SIDE EFFECTS

• Opioid side effects with minimal or no tolerance (an effect
that does not diminish despite continued use)
o Miosis
o Constipation
o Convulsions
• Side effects of Opioids not mediated by opioid receptors
o Nausea and vomiting – stimulation of CTZ at 4th ventricle
o Hypotension – histamine release
o Pruritus – histamine release
MNEMONIC for Morphine side effect: MORPHINE = Miosis, Out of it,
Respiratory depression, Pruritus, Hypotension and Headache,
In frequency, Nausea, and Emesis
OPIOIDS Dr. Pereyra-Borlongan
• include natural opiates and semisynthetic alkaloids derived OPIOID OVERDOSE

from the opium poppy, pharmacologically similar synthetic • triad of pupillary constriction, comatose state, and
surrogates, and endogenous peptides respiratory depression
• MOA: has G protein coupled actions on neurons doing the ff: • diagnosis confirmed if intravenous injection of naloxone results
1. Close voltage gated Ca2+ channels on presynaptic nerve in prompt signs of recovery
terminals and reduce transmitter release • treatment involves the use of antagonists such as naloxone and
2. Open K+ channels and hyperpolarize and thus inhibit other therapeutic measures, especially ventilatory support
postsynaptic neurons Hypoventilation: Opioids will shut the central drive for breathing
which is high levels of carbon dioxide. Now giving high levels of
CLASSIFICATION OF OPIOIDS oxygen will shut the peripheral control wherein the main
• SPECTRUM OF CLINICAL USES stimulus is low level of oxygen. It will impair the remaining drive
o analgesics, antitussives, antidiarrheal to breathe unless you will put the patient under mechanical
• STRENGTH OF ANALGESIA ventilation.
o strong, moderate, weak agonists
o partial agonists exert less analgesia than full agonists KEY LEARNING POINTS
• RATIO OF AGONIST TO ANTAGONIST EFFECTS • By half-life: Which opioids have the shortest and longest half-lives?
o agonists (receptor activators [full or partial]) o REMIFENTANIL = shortest half-life (3-4 mins)
o antagonists (receptor blockers) o BUPRENORPHINE = longest half-life (4-8 hrs)
o mixed agonist-antagonists
OPIOID RECEPTORS
Mu1 Mu2 Kappa Delta
Analgesia (supraspinal and Analgesia (Spinal), Analgesia (supraspinal and Analgesia (supraspinal
spinal), Euphoria, Low abuse depression of ventilation, spinal), dysphoria, sedation, and spinal), depression of
Effect
potential, Miosis, Bradycardia, Physical dependence, addiction and dependence, ventilation, physical
hypothermia, Urinary retention Constipation (marked) Miosis, Constipation dependence,
Agonists • Endorphins, Morphine, Synthetic opioids • Dynorphins • Enkephalins
Antagonists • Naloxone, naltrexone
OPIOIDS
MIXED AGONIST-
PARTIAL AGONISTS WEAK AGONISTS
ANTAGONIST
BUPRENORPHINE [C],
Drug HYDROCODONE [C], PROPOXYPHENE [C], NALBUPHINE [B],
DEXTROMETORPHAN [C],
OXYCODONE [B], LEVOPROPOXYPHENE [C], BUTORPHANOL [C],
CODEINE [C]
DIHYDROCODEINE DEXTROPROPOXYPHENE [C] PENTAZOCINE [C],
LEVALLORPHAN [B]
Strong agonist at µ and k
receptors. Inhibits pain Decreases sensitivity of cough
Weak agonist at µ receptors. Partial µ receptors agonist,
neurotransmission at spinal receptors.
antagonist at k & d receptors.
MOA and supraspinal sites, binds Depressing the medullary cough
Inhibits pain Inhibits pain
NMDA receptors and center through sigma receptor
neurotransmission. neurotransmission.
antagonizes the effects of stimulation
glutamate
Mild to moderate pain, Moderate to severe pain, Opioid
Moderate to severe pain,
Restless legs syndrome, dependence,
Cancer pain, Neuropathic pain
Opioid withdrawal Alcohol dependence,
(postherpetic neuralgia, DM
Uses Cough suppression Balanced anesthesia,
neuropathy), Chronic pain, Withdrawn because of fatal
opioid withdrawal states
opioid dependence, cardiotoxicity (group 1C
(buprenorphine), Postoperative
opioid withdrawal antiarrhythmic activity)
shivering (Butorphanol)
Miosis, Respiratory
Miosis, Respiratory depression,
depression, Increased ICP, Sedation, Dizziness, Sweating,
Increased ICP, Hallucinations, Confusion,
Postural hypotension, Nausea, Anxiety, Hallucinations,
Postural hypotension, Excitation, Increased or
Constipation, Nightmares,
SE Constipation, Urinary decreased pupil size, Nystagmus,
Urinary retention, Pruritus, Respiratory depression (less),
retention, Pruritus, Seizures, Coma, Respiratory
Addiction liability, Seizures, Tolerance,
Addiction liability, depression, Addiction liability
Pulmonary edema, Dependence liability
Hypogonadism, Hearing loss
Fatal arrhythmias
• Serotonin syndrome when used • Propoxyphene is chemically • Effects resistant to naloxone
with SSRIs or MAOIs related to methadone but reversal
• Codeine is metabolized by with weaker analgesic • Nalbuphine is a strong k
Notes CYP2D6 to morphine activity agonist and partial µ
• Commonly used in suicides antagonist; has a ceiling effect
• Levopropoxyphene is used • Pentazocine is a k agonist and
as an anti-tussive weakly µ antagonist
FULL AGONIST
PHENANTHRENES PHENYLPIPERIDINE PHENYLHEPTYLAMINES
MORPHINE (opioid prototype) FENTANYL [C],
Drugs [C], Hydromorphone, SUFENTANIL, MEPERIDINE (Pethidine) [C] METHADONE [C], LEVOMETHADYL
Oxymorphone, HEROIN ALFENTANIL,
ACETATE, LEVORPHANOL
(Synthetic derivatives of REMIFENTANIL,
Morphine) OHMEFENTANYL
Strong agonist at µ receptors. Inhibits pain Strong agonist at µ and k receptors. Strong agonist at µ receptors. NMDA
MOA neurotransmission at spinal and supraspinal sites. Variable Inhibits pain neurotransmission. antagonist. Blocks monoamine
activity at d and k receptors. Muscarinic blocking actions. reuptake transporters.
Severe pain, Pain associated Moderate to severe pain (resistant to
Severe pain, Adjunct in Moderate to severe pain, Labor
with acute myocardial morphine), Opioid dependence
Uses anesthesia, Chronic pain, analgesia, Postoperative Shivering,
infarction, Pulmonary edema, (especially for a relapsing chronic
Breakthrough cancer pain Preoperative sedation
Adjunct in anesthesia heroin addict), Opioid withdrawal
Miosis, Restlessness, Tachycardia, Hypotension
Miosis, Restlessness, Respiratory
Respiratory depression, Restlessness, Respiratory (pronounced in patients with
depression, Increased ICP, Postural
Increased ICP, Postural depression, Increased ICP, decreased circulating volume),
hypotension, Constipation, Urinary
hypotension, Constipation, Postural hypotension, Seizures, Delirium, Restlessness,
SE retention, Pruritus, Addiction liability
Urinary retention, Pruritus, Constipation, Urinary Respiratory depression, Increased
(less)
Addiction liability, Pain retention, Pruritus, ICP, Postural hypotension,
Hepatic dysfunction, QT prolongation
associated with myocardial Addiction liability Constipation, Urinary retention,
(specific to methadone)
ischemia, Bradycardia Pruritus, Addiction liability (less),
• Exerts hemodynamic effects • FENTANYL:75-125 x more • 1/10th as potent compared to • Used in methadone maintenance
on the pulmonary circulation potent than morphine morphine therapy (MMT) for opioid
• Hydromorphone & • SUFENTANIL: 5-10x more • Meperidine has the most dependence
Oxymorphone: Like potent than fentanyl pronounced anti-shivering effect • Currently being investigated as a
morphine in efficacy but • REMIFENTANIL: same (a2 antagonism) novel treatment for leukemia
higher potency potency as fentanyl • Normeperidine is the metabolite Methadone is commonly used in
• Additive CNS depression • ALFENTANIL: 1/5th to that decreases seizure threshold patients with opioid withdrawal. It has
with other depressants 1/10th as potent as Contraindicated for patients with a slower pharmacokinetic profile
Notes • Significant first-pass effect fentanyl epilepsy. compared to Opioid. Hence, a good
• Metabolized in the body to • May be given • If given with MAOi → thing. However, it has a long half-life,
morphine-6-glucuronide transdermally or via Hyperpyrexic coma therefore it will require a greater time
(which has 4-6x analgesic lollipop • If given with SSRI → Serotonin to achieve a steady state.
activity as morphine) and to syndrome
Morphine-3-glucoronide • MEPERIDINE DOES NOT CAUSE
(which has a neuroexcitatory MIOSIS, rather it causes
properties) MYDRIASIS (owing to its
atropine like function)
OPIOID ANTAGONIST DUAL-ACTING
Drug NALOXONE [C], NALTREXONE [C], NALMEFENE [B],
TRAMADOL [C], TAPENTADOL [C]
ALVIMOPAN [B], METHYLNALTREXONE [B]
Competitively blocks µ, d and k receptors. Weak agonist at µ receptor. Inhibits neuronal reuptake of
MOA
Rapidly reverses effects of opioid agonists. serotonin and norepinephrine. Inhibits pain neurotransmission.
DOC for Opioid overdose (NALOXONE), Moderate pain, Chronic pain syndromes, Neuropathic pain,
Uses
Opioid and alcohol dependence (NALTREXONE only) Fibromyalgia, Adjuncts to opioid in chronic pain syndromes
SE Pruritus, Nausea, Vomiting Seizures, Nausea, Dizziness, Pruritus, Constipation
• Precipitates abstinence syndrome in patients with opioid dependence • 5-10 x less potent compared to morphine
• Naltrexone reduces craving in alcohol, nicotine and opioid dependence • Lowers seizure threshold : Contraindicated in patients with a
• Naltrexone & Nalmefene have longer DOA history of epilepsy
Notes • Naloxone and Nalmefene is IV (DOA: 12-24 hrs) while Naltrexone • Serotonin syndrome when used with SSRIs
is PO (DOA: 48h) • SE profile vs other opioids: Low tendency for respiratory abuse
• Alvimopan & Methylnaltrexone have poor CNS penetrability → and low chances for developing tolerance and dependence
antagonize peripheral effects such as constipation
DRUGS OF ABUSE • etiology of tolerance

o metabolic: increased disposition of the drug
DRUG ABUSE
o behavioral: ability to compensate for the effects of a drug
• use of an illicit drug or the excessive or nonmedical use of a licit o functional: changes in receptor or effector systems involved in
drug drug actions
• denotes the deliberate use of chemicals that generally are not
ABSTINENCE SYNDROME/ WITHDRAWAL SYNDROME
considered drugs by the lay public but may be harmful to the user
• primary motivation is the anticipated feeling of pleasure derived • signs and symptoms that occur on discontinuation or
from the CNS effects of the drug withdrawal of a drug in a dependent person
DEPENDENCE SUPPLEMENT: Dopamine Hypothesis of Addiction
• dopamine in the mesolimbic system appears to play a primary role in
• older term is physical or physiologic dependence the expression of "reward"
• state characterized by signs and symptoms, frequently the • excessive dopaminergic stimulation may lead to pathologic
opposite of those caused by a drug, when it is withdrawn from reinforcement
chronic use or when the dose is abruptly lowered o behavior may become compulsive and no longer under control—
common features of addiction
ADDICTION
• most addictive drugs have actions that include facilitation of the
• older term is psychological dependence effects of dopamine in the CNS
• compulsive drug-using behavior in which the person uses the
drug for personal satisfaction, often in the face of known risks to SUPPLEMENT: OTHER RELATED COMPOUNDS
health Chemically related to Amphetamine, A
TOLERANCE METHYLPHENIDATE CNC stimulant used for ADHD. Do not use
together with antidepressants
• decreased response to a drug, necessitating larger doses to
ATOMOXETINE A NE reuptake inhibitor; used for ADHD
achieve the same effect
DRUGS OF ABUSE
Drugs AMPHETAMINES CONGENERS OF AMPHETAMINES COCAINE PHENCYCLIDINE HALLUCINOGENS MARIJUANA
Psychoactive constituents
in crude extracts of the
plant Cannabis sativa (hemp)
Dimethoxymethylamphetamine
Active ingredients:
(DOM) Lysergic acid
tetrahydrocannabinol (THC),
Methylenedioxyamphetamine diethylamide
Representative Dextroamphetamine STREET NAMES: “coke”, “super-speed”, Phencyclidine (PCP; "angel dust") cannabidiol (CBD),
(MDA) (LSD)
Agents Methamphetamine (“speed”, “ice”) “crack” Ketamine ("special K") cannabinol (CBN)
Methylene Mescaline
dioxymethamphetamine Psilocybin Hashish is a partially
(MDMA/ Ecstasy) purified, more potent form
Street names: "weed", "pot",
"grass", "damo", "dope",
"Mary Jane", "hash"
• feeling of euphoria and self- • more selective action on the • inhibition of CNS transporters of dopamine, • antagonists at the glutamate NMDA receptor • psychedelic and • feeling of being "high,"
confidence that contributes to the serotonin transporters in CNS norepinephrine, and serotonin • no actions on dopaminergic neurons in mind raveling with euphoria,
rapid development of addiction • facilitate interpersonal • marked amphetamine-like effects the CNS unlike most drugs of abuse effects disinhibition,
• effects of chronic high-dose abuse communication • short-lasting euphoria, self-confidence and • PCP is the most dangerous • perceptual and uncontrollable laughter,
Effects
• psychotic state (w/ delusions and • act as sexual enhancers mental alertness positively reinforce its hallucinogenic agent psychological changes in perception,
paranoia) • causes depletion of neurons continued use • psychotic reactions, impaired effects and achievement of a
• development of necrotizing arteritis, in serotonergic tracts judgment leading to reckless behavior accompanied by dream-like state
→ cerebral hemorrhage, renal failure (psychotomimetic effect) marked somatic • impaired mental
AMPHETAMINE AMPHETAMINE COCAINE PHENCYCLIDINE PHENCYCLIDINE effects (nausea, concentration
MDMA OVERDOSE COCAINE OVERDOSE weakness, • vasodilation
OVERDOSE WITHDRAWAL WITHDRAWAL OVERDOSAGE WITHDRAWAL
hypertension, paresthesia) • tachycardia
severe hypertension,
vasoconstriction, • Panic reactions • reddened conjunctiva
hyperthermia, delirium,
thrombus formation, ("bad trips") • dry mouth
agitation, psychomotor agitation and apathy, irritability, horizontal and
apathy, psychomotor agitation, fever, seizures, may also occur • impairment of judgment
Clinical hypertension, profound hyponatremia increased sleep vertical
irritability, severe hyperthermia, muscle and reflexes
manifestation tachycardia, life-threatening complications time, disorientation, nystagmus,
increased sleep dyspnea, breakdown, • effects potentiated by
delusions, include intracranial severe depression marked
time, bowel ischemia, depression and concomitant use of
hallucinations, hemorrhage, mydriasis, crack lung
strongly reinforces hypertension, and
disorientation, memory loss in sedative-hypnotics
hyperthermia, myocardial infarction, (hemorrhagic alveolitis), compulsions fatal seizures
depression long-term including ethanol
seizures, death aortic dissection, DIC, fatalities from
rhabdomyolysis, seizures and arrhythmias, seizures or
serotonin syndrome respiratory depression
• no specific • antidepressants • supportive care directed at • no specific antidote • antidepressant • supportive care • supportive care
antidote (amineptine, control of seizures, is available drugs may be to control • benzodiazepines
• control of mirtazapine) hyperthermia, and serotonin • supportive care indicated seizures and and/
body are of limited syndrome • cocaine abuse • infants born to hypertension antipsychotics
temperature benefit • fluid resuscitation with during pregnancy is mothers who • parenteral
• protection • acidify urine to hypertonic saline for associated with abuse have benzodiazepines
against increase hyponatremia increased fetal possible (diazepam,
Management
cardiac elimination morbidity and teratogenic lorazepam) are
arrhythmias mortality abnormalities used to curb
and seizures (cystic cortical excitation and
lesions), increased protect against
morbidity and seizures
mortality and may
be cocaine dependent
ENDOCRINE PHARMACOLOGY
HYPOTHALAMIC AND PITUITARY HORMONES
ANTERIOR PITUITARY HORMONES
Target Organ
Anterior Pituitary Hypothalamic Target
hormone(s) or
Hormone Hormone organ
mediator(s)
Growth
Liver,
hormone-
muscle,
releasing
Growth Hormone bone, Insulin-like growth
hormone
(GH, Somatotropin) kidney, factore-1 (IGF-1)
(GHRH) (+)
and
Somatostatin
others
(-)
Thyroid- Thyrotropin-
stimulating releasing Thyroxine,
Thyroid
hormone Hormone Triiodothyronine
(TSH) (TRH) (+)
Corticotropin-
Glucocorticoids,
Adrenocorticotropin releasing Adrenal
Mineralocorticoids,
(ACTH) hormone Cortex
Androgens
(CRH) (+)
Follicle-stimulating Gonadotropin-
Estrogen,
Hormone (FSH) releasing Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
Gonads Progesterone,
Luteinizing Hormone
Testosterone
Hormone (LH) (GnRH
Prolactin (PrL) Dopamine (-) Breast -
• All the anterior pituitary hormones are under the control of a DRUGS RELATED TO OXYTOCIN
hypothalamic hormone Drugs OXYTOCIN [X], Demoxytocin
• All mediate their ultimate effects by regulating the production Activates oxytocin receptors. Stimulates uterine
by peripheral tissues of other hormones EXCEPT prolactin MOA contraction and labor. Stimulates mammary glands,
• Four anterior pituitary hormones (TSH, LH, FSH, and ACTH) and lactation and milk let-down.
their hypothalamic regulators are subject to feedback regulation Labor induction, Labor augmentation, Control of
Uses
by the hormones whose production they control postpartum hemorrhage
• Hormones secreted by the Posterior Pituitary are: Vasopressin Fetal distress, Placental abruption, Uterine rupture, Fluid
SE retention (water intoxication), Hyponatremia, Heart
& Oxytocin. Take note that both are potent vasoconstrictors.
failure, Seizures, Hypotension
• Contraindications to oxytocin include fetal distress,
ON GONADOTROPINS: OVULATION INDUCTION
prematurity, abnormal presentation, CPD and
• FUNCTIONS predispositions for uterine rupture
o in women, FSH directs follicle development, whereas FSH and Notes ATOSIBAN is an oxytocin receptor blocker (not yet FDA
LH collaborate in regulating ovarian steroidogenesis approved since there is concern about increased rates of
o in men, FSH regulates spermatogenesis, whereas LH infant death)
stimulates androgen production CARBETOCIN is an agonist of peripheral Oxytocin receptors
• CLINICAL UTILITY
DRUGS RELATED TO ADH
o to stimulate spermatogenesis in infertile men
ADH AGONIST ADH ANTAGONIST
o to induce ovulation in women with refractory anovulation
Vasopressin/Anti-Diuretic CONIVAPTAN [C],
Ovulation Induction Protocol Drugs
hormone [C], TOLVAPTAN [C],
• endogenous gonadotropin production is inhibited by DESMOPRESSIN [B] LIXIVAPTAN
administration of a GnRH agonist or antagonist Desmopressin relatively
• follicle development is driven by daily injections of a preparation selective for V2 receptors.
with FSH activity (menotropins, FSH, FSH analog) Vasopressin V2 receptor
• final stage of oocyte maturation is induced with an injection of agonist which causes
Antagonist at V1a, V2
LH or human chorionic gonadotropin (hCG) insertion of water
receptors. Reduces renal
Complications of Ovulation Induction channels in the collecting
MOA excretion of water in
• multiple pregnancies duct leading to more
conditions associated with
• ovarian hyperstimulation syndrome water reabsorption →
increased vasopressin
o syndrome of ovarian enlargement, ascites, hypovolemia and decrease the excretion of
possibly shock water; Act on extra-renal
V2 receptors to increase
Factor VIII and VWF factor
DRUGS RELATED TO PROLACTIN
Central diabetes
DOPAMINE AGONIST SIADH, Hyponatremia in
insipidus, Hemophilia A,
Drugs BROMOCRIPTINE, PERGOLIDE, CABERGOLINE, hospitalized patients,
von Willebrand’s disease,
QUINAGOLIDE *All are Preg Cat B offset fluid retention in
Uses Esophageal variceal
Inhibits prolactin release from the pituitary gland. acute heart failure and
bleeding, Primary nocturnal
MOA Also slightly inhibits GH release. Dopaminergic effects SIADH which causes
enuresis (pediatric Px),
on CNS motor control and behavior hyponatremia (dilutional)
colon diverticula
Hyperprolactinemia, Pituitary adenoma (prolactin- GI disturbance, Headaches,
Uses
secreting), Acromegaly, Parkinson’s disease Flushing, Nausea, Infusion site reactions,
SE
GI disturbance, Nausea, Headache, Light-headedness, Hyponatremia, Seizures, Hyperkalemia
Orthostatic Hypotension, Fatigue, Behavioral Allergic reactions
Changes, Erythromelalgia, Raynaud’s phenomenon • May be given intranasally, • Central pontine myelinolysis
SE PO or IV may occur with rapid
(vasospasm), Pulmonary infiltrates (in high doses)
Erythromelalgia is a rare disorder characterized by • Also contracts vascular correction of hyponatremia
burning pain and warmth and redness of the extremities smooth muscles via V1 • Tolvaptan is more
Given PO or vaginally (for Hyperprolactinemia) Notes receptor leading to selective for V2 receptors
Notes Slightly inhibits GH release if given in high doses vasoconstriction (Used as • Lixivaptan and Tolvaptan
CI in patients with history of psychotic illness treatment for esophageal are selectively active
varices or colon against the V2 receptor
diverticula)
SUPPLEMENT: Diabetes Insipidus
• CLINICAL FEATURES • TYPES
o syndrome of polyuria, polydipsia, and hypernatremia o central diabetes insipidus is associated with deficient secretion of ADH
o excessive urination due to an inability of the kidney to resorb water o nephrogenic diabetes insipidus is associated with end-organ
properly from the urine resistance to the effects of ADH
GROWTH HORMONE
GH AGONIST GH ANTAGONIST
RECOMBINANT GH RECEPTOR
Drug RECOMBINANT GROWTH HORMONE SOMATOSTATIN ANALOG
IGF-1 ANTAGONIST
SOMATROPIN [B] MECASERMIN [C] PEGVISOMANT [C] OCTREOTIDE [B], LANREOTIDE [C]
Stimulates skeletal
Increases release of IGF-1 in the liver and muscle growth, Suppresses the release of growth
cartilage. Stimulates skeletal muscle amino acid hormones, glucagon, insulin, gastrin,
MOA Block GH receptor
growth, amino acid transport, protein transport, protein IGF-1, serotonin and gastrointestinal
synthesis and cell proliferation. synthesis and cell peptides
proliferation
Growth hormone deficiency, Genetic
diseases associated with short stature
Acromegaly,
(Turner, Noonan, Prader-Willi), failure to For children
Pituitary adenoma (GH-secreting),
Uses thrive due to chronic renal failure or SGA, unresponsive to GH Acromegaly
Carcinoid, Gastrinoma, Glucagonoma,
AIDS wasting, improve GI function in therapy
Variceal bleeding
patients who underwent intestinal resection
that led to malabsorption syndrome
• Peripheral edema, Myalgia, Arthralgia, • Hypoglycemia, • Diarrhea, nausea, flu- • Gastrointestinal disturbances,
Intracranial hypertension, pseudotumor increased LFT, like syndrome, elevated Gallstones, Arrhythmias/cardiac
SE
cerebri, slipped capital femoral epiphysis, intracranial HTN LFTs, hypersensitivity conduction abnormality
progression of scoliosis, hyperglycemia reaction
• Performance-enhancing drug (increases • Remedy to • Onset of action is • Can alter requirements for
muscle mass) that is banned by athletics hypoglycemia: give expected within 2wks of antidiabetic agents
committees patient some use • Regular release: given BID-QID SC
Notes
• Given SC snacks prior to • If slow release: every 4wks IM
dose • Are long-acting synthetic analogs of
somatostatin
GONADOTROPINS
FSH ANALOG LH ANALOG GnRH AGONIST GnRH ANTAGONIST
CHORIOGONADOTROPI
FOLLITROPIN ALFA, N ALFA [X], HUMAN
MENOTROPINS (hMG), CHORIONIC LEUPROLIDE, GONADORELIN, GOSERELIN, GANIRELIX, CETRORELIX,
Drugs
UROFOLLITROPIN, GONADOTROPIN (hCG), HISTRELIN, NAFARELIN, TRIPTORELIN ABARELIX, DEGARELIX
FOLLITROPIN BETA MENOTROPINS (hMG),
LUTROPIN ALFA
All are Preg Cat X
Agonist of GnRH receptors. Increased LH and
FSH secretion with INTERMITTENT
Activates FSH
Activates LH receptors. administration. Reduced LH and FSH secretion Blocks GnRH receptors.
receptors. Mimics
MOA Mimics effects of with PROLONGED CONTINUOUS Reduces endogenous
effects of endogenous
endogenous LH. administration (due to downregulation of production of LH and FSH.
FSH.
GnRH receptors in the pituitary cells that
normally release LH and FSH)
Initiation of ovulation
during controlled ovarian
hyperstimulation
Controlled ovarian Ovarian Suppression,
(ovulation induction), Prevents premature LH surge
hyperstimulation, Controlled ovarian hyperstimulation,
ovarian follicle development during Controlled ovarian
Uses Infertility due to Endometriosis, Myoma uteri,
in women with hyperstimulation,
hypogonadotropic Central Precocious puberty,
Hypogonadotropic Advanced Prostate cancer
hypogonadism in men Advanced Prostate cancer
hypogonadism, male
Hypogonadotropic
Hypogonadism
Headache, depression,
edema, ovarian Headache, Depression,
Nausea, Headache,
hyperstimulation Edema;
Hot flushes, Sweats, Headache, Hypersensitivity (Abarelix),
syndrome (ovarian Ovarian hyperstimulation
Light-headedness, Injection site reactions, Hot flushes, Gynecomastia,
SE enlargement, ascites, syndrome,
Nausea, Osteoporosis, Gynecomastia, decreased libido,
hypovolemia, shock), Multiple pregnancies in
Reduced libido, Decreased hematocrit Decreased hematocrit,
multiple pregnancies women;
Osteoporosis
in women, Gynecomastia in men
gynecomastia in men
• Follitropin alfa and • Menotropins are • Symptoms of hypogonadism with continuous • Does NOT cause a tumor flare-
beta are mixtures of FSH and LH treatment up when used for treatment of
recombinant FSH from postmenopausal • Temporary exacerbation of precocious advanced prostate cancer
forms while women puberty or prostate cancer, Apoplexy and • Less likely to cause ovarian
Urofollitropin is a • Choriogonadotropin Blindness during the first few weeks of hyperstimulation syndrome
purified preparation alfa is a recombinant therapy (remedy: co-administer Flutamide, an • Degarelix is used for prostate
Notes from urine of hCG while Lutropin is a androgen receptor antagonist) CA while Ganirelix prevent LH
postmenopausal recombinant LH • May be given Intranasally, depot formulation surge in controlled ovulation
women also available Directly inhibits the receptors
• Gonadorelin is a synthetic human GnRH and so causes antagonistic
• Leuprolide has a long agonist activity; its other (decrease in hormones) effect
name is leuprorelin/leuprorelin right away. Thus, there is no
flare-up
The effect of GnRH agonists will depend on the dosing that you give • TRANSPORT
to the patient. o iodide ion is converted to iodine by thyroid peroxidase (TPO)
• IODINE ORGANIFICATION
o tyrosine residues in thyroglobulin are iodinated to form
monoiodotyrosine (MIT) or diiodotyrosine (DIT)
• COUPLING
o 2 molecules of DIT combine to form T4, while 1 molecule each
GNRH ANALOGUES 1 GNRH ANALOGUES 2 of MIT and DIT combine to form T3
https://qrs.ly/s7ckebh https://qrs.ly/9uckebx • PROTEOLYSIS
Dr. Pereyra-Borlongan o T4 and T3 are released from the thyroid and transported in the
blood by thyroxine-binding globulin (TBG)
THYROID AND ANTITHYROID DRUGS
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 pressure output, and pulse pressure
Pleural effusions,
Dyspnea hypoventilation,
Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 and CO2 retention
Increased appetite Reduced appetite
Synthesis and Transport of Thyroid Hormones Nervousness, hyperkinesia, Lethargy, general slowing of
tremor mental processes
Weakness, increased deep Stiffness, decreased deep
Thyroid tendon reflexes tendon reflexes
gland Menstrual irregularity, Infertility, decreased libido,
Transport Peroxidase Organification
Thyroglobulin decreased fertility impotence, oligospermia
I— I— I° MIT-DIT-T3-T4
Weight loss Weight gain
Iodides
- - Exophthalmos
- Proteolysis
Iodides,
thioamides
DRUGS FOR HYPERTHYROIDISM
SCN —, ClO4 —
Graves Disease
• autoimmune disorder where B lymphocytes produce an
Peripheral
T4, T3 antibody that activates the TSH receptor (TSIs), causing
Blood
Tissues thyrotoxicosis
T4, T3 Radiocontrast media, • these B lymphocytes are not susceptible to negative feedback
- β-blockers,
corticosteroids,
• expected thyroid profile: high T3/T4, low TSH
amiodarone
T3
Adapted from Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
DRUGS FOR HYPERTHYROIDISM

THIOAMIDE IODIDE IODINE BETA BLOCKER
POTASSIUM IODIDE [D], PROPRANOLOL [C],
Drug METHIMAZOLE [D], RADIOACTIVE IODINE LUGOL’S SOLUTION / ESMOLOL [C],
PROPYLTHIOURACIL [D]
Carbimazole (131I) [X] Potassium Iodide METOPROLOL [C],
Saturated Solution (KISS) ATENOLOL [D]
Emits beta rays
causing destruction of Blocks beta-receptors
thyroid parenchyma (control HR and other
Inhibits thyroid Inhibit iodine
Administered orally cardiac abnormalities of
peroxidase reactions. Inhibits thyroid organification and
in solution as sodium severe thyrotoxicosis).
Blocks iodine peroxidase reactions. hormone release.
MOA 131I, it is rapidly Slows pacemaker
organification. Blocks iodine Reduce size and
absorbed, activity;
Inhibits peripheral organification. vascularity of thyroid
concentrated by the Inhibits peripheral
conversion of T4 into T3. thyroid, and
gland.
conversion of T4 into T 3
incorporated into (Only Propranolol)
storage follicles
Hyperthyroidism, Hyperthyroidism esp
Thyroid storm, Thyroid Storm, Adjunct
Preparation for surgical to control tachycardia,
Hyperthyroidism, Hyperthyroidism, Hyperthyroidism
Uses thyroidectomy to reduce HTN and Atrial
Thyroid storm Thyroid storm
the size and vascularity Fibrillation,
of the thyroid gland, Post-MI prophylaxis
Radiation prophylaxis against sudden death
Maculopapular pruritic
Maculopapular pruritic
rash,
rash,
Gastrointestinal distress, Iodism, Acneiform rash,
Gastrointestinal distress, Hypothyroidism
Cholestatic jaundice, Swollen salivary glands,
Fulminant hepatitis, (permanent),
Agranulocytosis, Mucous membrane
Agranulocytosis, sore throat, Bronchospasm,
Urticaria, Vasculitis, ulcerations,
Urticaria, Vasculitis, sialadenitis Cardiac depression,
SE Lupus-like syndrome, Conjunctivitis,
Lupus-like syndrome, AV block, Hypotension,
Lymphadenopathy, Rhinorrhea, Drug fever,
Lymphadenopathy, Associated with Bradycardia
Hypoprothrombinemia, Metallic taste, Bleeding
Hypoprothrombinemia, radiation exposure:
Exfoliative dermatitis, disorders,
Exfoliative dermatitis, papillary thyroid CA
Polyserositis, Arthralgia, Anaphylactoid reactions
Polyserositis, Arthralgia,
Hypothyroidism, Altered
Hypothyroidism
sense of taste or smell
Drugs PROPYLTHIOURACIL METHIMAZOLE [D], etc IODINE (131I) POTASSIUM IODIDE [D], PROPRANOLOL [C], etc
• Drug of choice for • Drug of choice for • Preferred treatment • Should not be used • Esmolol may be used to
pregnant nonpregnant for most patients alone (escape in 2–8 treat thyrotoxicosis-
hyperthyroid Px hyperthyroid Px • Permanent cure of weeks) related arrhythmias
preferable during the because of longer DOA thyrotoxicosis • Prevents radiation- • Onset is within hours
first trimester of (24h) and increased without surgery induced thyroid but DOA is also short (4-
pregnancy because it is potency and no effect on damage 6 hrs)
more strongly protein- • Methimazole and other tissues • Prenatal exposure • Use Beta blockers
bound and, therefore, Carbimazole are • Advantages include causes fetal goiter without intrinsic
crosses the placenta less teratogens (causes easy administration, • Onset is faster compared sympathomimetic
readily Aplasia Cutis effectiveness, low to Thioamides (2-7 activity (e.g.
• Shorter DOA (6-8h) Congenita) in the 1st expense and days) but effect is metoprolol,
trimester absence of pain transient (thyroid propranolol, atenolol)
• Faster onset of action:
Reaches effect within • Given as once daily • Contraindicated in gland escapes iodide • Beta blockers cause
hrs dosing pregnant women block after several clinical improvement of
• THIAMAZOLE is the or nursing mothers weeks of treatment) hyperthyroid
Due to a black box other name of • Acts through inhibition symptoms but do not
Notes since it crosses the
warning about severe Methimazole of thyroglobulin typically alter thyroid
hepatitis, placenta to destroy
• Slow onset of action (3- the fetal thyroid proteolysis. hormone levels.
propylthiouracil should
4 weeks for full effect) gland and is excreted • Propranolol at doses
be reserved for use Improvement in
during the first Because the thioamides in breast milk greater than 160 mg/d
thyrotoxic symptoms may also reduce T3
trimester of pregnancy, do not inhibit the release
• Patients should be occurs rapidly—within
in thyroid storm, and in of preformed thyroid levels approximately
euthyroid or on BB 2–7 days—hence the
those experiencing hormone, their onset of 20% by inhibiting the
before RAI value of iodide therapy
adverse reactions to activity is usually slow, in thyroid storm.
peripheral conversion
• Onset of action is 6-
methimazole (other often requiring 3–4 wk of T4 to T3.
12 weeks, Maximum
than agranulocytosis or for full effect.
hepatitis) effect seen in 3-6
months
PTU is preferred in the first trimester and should be replaced by Methimazole (MMI) after this trimester.
Choanal and esophageal atresia of fetus in MMI-treated and maternal hepatotoxicity in PTU-treated pregnancies are of utmost concern.
Maintaining free thyroxine concentration in the upper one-third of each trimester-specific reference interval denotes success of therapy.
MMI is the mainstay of the treatment of postpartum hyperthyroidism, in particular during lactation.
SUPPLEMENT: Agranulocytosis OTHER ANTI-THYROID
AGRANULOCYTOSIS Anion Inhibitors: perchlorate (ClO4–), pertechnetate (TcO4–),
o acute severe neutropenia: granulocyte count < 500 cells/mm3 thiocyanate (SCN–)
o often heralded by sore throat or high fever • block uptake of iodide by the gland through competitive inhibition of
o increased susceptibility to infections the iodide transport mechanism
o increased risk in older patients and in those receiving high-dose • The major clinical use for potassium perchlorate is to block thyroidal
methimazole therapy (> 40 mg/d) reuptake of I– in patients with iodide-induced hyperthyroidism (e.g.
• CLINICAL PRESENTATION amiodarone-induced hyperthyroidism). However, potassium
o acute severe neutropenia perchlorate is rarely used clinically because it is associated with
o often heralded by sore throat or high fever aplastic anemia
o increased susceptibility to infections
• TREATMENT DRUGS FOR HYPOTHYROIDISM
o discontinue PTU or methimazole Myxedema Coma
o administer recombinant G-CSF to accelerate recovery
o treat with prophylactic broad-spectrum antibiotics
• CLINICAL PRESENTATION
GCSF: FILGRASTIN o medical emergency representing the end state of untreated
GMCSF: SARGRAMOSTIM hypothyroidism
Dr. Pereyra-Borlongan o progressive weakness, stupor, hypothermia, hypoventilation,
hypoglycemia, hyponatremia, water intoxication, shock and death
THYROID STORM • TREATMENT
• CLINICAL PRESENTATION § intravenous loading dose of levothyroxine (300–400 mcg),
o sudden acute exacerbation of all of the symptoms of followed by 50–100 mcg daily
thyrotoxicosis, presenting as a life-threatening syndrome § intravenous hydrocortisone is indicated if the patient has
• Treatment of Thyroid Storm associated adrenal or pituitary insufficiency
o PTU blocks thyroid hormone synthesis
o iodides (SSKI) retards release of thyroid hormones DRUGS FOR HYPOTHYROIDISM
§ always administer PTU before iodides (SSKI) THYROID HORMONE
Drugs LEVOTHYROXINE (T4) [A],
o propranolol controls severe cardiovascular manifestations
LIOTHYRONINE (T3) [A], LIOTRIX [A]
o hydrocortisone protects against shock and also blocks
Activation of nuclear receptors results in gene
peripheral conversion of T4 to T3 MOA
expression with RNA formation and protein synthesis
WOLF-CHAIKOFF VS JOD-BASEDOW Uses Hypothyroidism, Myxedema coma
• Wolf-Chaikoff effect: ingestion of iodine causes hypothyroidism SE
Dry skin, Sweating, Tachycardia, Nervousness, Tremor,
• Jod-Basedow phenomenon: ingestion of iodine causes Weight loss, Weakness, Heat intolerance
hyperthyroidism • T4 dose must be lowered in patients with
KEY LEARNING POINTS cardiovascular disease or longstanding
Which drugs inhibit peripheral What drugs can cause drug- hypothyroidism (increased cardiosensitivity)
conversion of T4 to T3? induced hyperthyroidism? • LIOTRIX is a 4:1 ratio of T4:T3
Notes
Propylthiouracil CAM • Thyrotropin (a recombinant human TSH) is also
Propranolol Clofibrate, Amiodarone, available
Hydrocortisone Methadone Maximum effect is seen after 6-8 weeks of therapy
Liothyronine has a faster onset but shorter half-life
AMIODARONE-INDUCED THYROID DISEASE
• hypothyroidism through its ability to block the peripheral SUPPLEMENT: Thyroid hormones
conversion of T4 to T3 MOA of T4 and T3
o TREATMENT: levothyroxine • T4 is converted to T3 in target cells
• hyperthyroidism either through an iodine-induced mechanism in • T3 is about 10 times more potent than T4
persons with an underlying thyroid disease or through an • thyroid hormones bind to intracellular receptors that control the
inflammatory mechanism that causes leakage of thyroid hormone expression of genes responsible for many metabolic processes
o TREATMENT: thioamides or corticosteroids MNEMONIC: 4 B’s of thyroid hormone: Brain maturation, Bone
growth, Beta-adrenergic effects, and increase in Basal metabolic rate
CORTICOSTEROIDS AND ANTAGONISTS
GLUCOCORTICOID ACTIVITY
https://qrs.ly/8qckec0
MAJOR GROUP OF CORTICOSTEROIDS

• GLUCOCORTICOIDS
o important effects on intermediary metabolism, catabolism,
immune responses, and inflammation
Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 • MINERALOCORTICOIDS
o regulate sodium and potassium reabsorption in the collecting
tubules of the kidney
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
Dr. Pereyra-
Borlongan
SOME COMMONLY USED NATURAL AND SYNTHETIC CORTICOSTEROIDS FOR GENERAL USE:
Equivalent
Activity1 Forms Available
Agent Oral Dose (mg)
Anti-inflammatory Topical Salt-Retaining
Short- to medium-acting glucocorticoids
Hydrocortisone
1 1 1 20 Oral, injectable, topical
(cortisol)
Cortisone 0.8 0 0.8 25 Oral
Prednisone 4 0 0.3 5 Oral
Prednisolone 5 4 0.3 5 Oral, injectable
Methylprednisolone 5 5 0.25 4 Oral, injectable
Meprednisone2 5 - 0 4 Oral, injectable
Intermediate-acting glucocorticoids
Triamcinolone 5 53 0 4 Oral, injectable, topical
Paramethasone2 10 - 0 2 Oral, injectable
Fluprednisolone2 15 7 0 1.5 Oral
Long-acting glucocorticoids
Betamethasone 25-40 10 0 0.6 Oral, injectable, topical
Dexamethasone 30 10 0 0.75 Oral, injectable, topical
Mineralocorticoids
Fludrocortisone 10 0 250 2 Oral
Desoxycorticosterone
0 0 20 - Injectable, pellets
acetate2
1 Potency relative to hydrocortisone, 2 Outside United States, 3 Triamcinolone acetonide: Up to 100. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
GLUCOCORTICOID RELATED DRUGS
GLUCOCORTICOID
GLUCOCORTICOIDS GLUCOCORTICOID SYNTHESIS INHIBITOR
ANTAGONIST
INTERMEDIATE TO LONG 11-B-
SHORT-ACTING, DESMOLASE CYP450
ACTING, HYDROXYLASE
LOW-POTENCY INHIBITOR INHIBITOR
MEDIUM to HIGH POTENCY INHIBITOR
low-potency:
HYDROCORTISONE
Drug PREDNISONE [C],
[C](CORTISOL),
PREDNISOLONE,
DESONIDE
METHYLPREDNISOLONE MIFEPRISTONE
medium-potency: AMINO- KETOCONAZOLE METYRAPONE
[C], MEPREDNISONE, (RU486) [X]
FLUTICASONE, GLUTETHIMIDE [D] [C] [C]
DEXAMETHASONE [C],
MOMETASONE
BETAMETHASONE [C],
high-potency:
TRIAMCINOLONE
DESOXIMETASONE,
CLOBETASOL [C]
Inhibits
Inhibits Desmolase, cholesterol side- Selective
Activates glucocorticoid
blocking chain cleavage, inhibitor of
receptors, leading to Competitive
conversion of cytochrome steroid 11-
altered gene inhibitor at the GC
Suppresses inflammation cholesterol to P450 enzymes hydroxylation,
MOA transcription. receptor as well as
and immune response pregnenolone. and other interfering with
Suppresses progesterone
Reduces synthesis enzymes cortisol and
inflammation. Replaces receptor
of all hormonally necessary for corticosterone
cortisol when deficient.
active steroids. synthesis of all synthesis
steroids
Wide variety of
inflammatory, allergic,
Acute adrenal autoimmune (collagen
insufficiency associated and rheumatic disease Adrenal
with life-threatening etc.) and neoplastic carcinoma,
Diagnostic
shock, chronic adrenal diseases (hematopoietic Hirsutism,
testing for
insufficiency cancers), Prevention of Breast cancer,
Breast cancer, adrenal
Uses (Addison's disease), organ transplant Prostate cancer, Cushing Syndrome
Cushing syndrome function,
congenital adrenal rejection, Asthma, lung Cushing’s
Cushing’s
hyperplasia, Insect bites, maturation in preterm syndrome,
syndrome
Contact dermatitis, labor (betamethasone and Fungal
Status asthmaticus, dexamethasone), infections
Thyroid storm chemotherapy-induced
vomiting, hypercalcemia,
mountain sickness
Adrenal suppression,
Growth inhibition,
Muscle wasting,
Osteoporosis (especially Abdominal pain
among elderly women), Hepatotoxicity, and cramping,
None common when
Salt retention, Skin rash, Many drug Dizziness, uterine cramping,
used topically or at
SE Glucose intolerance, Hepatotoxicity, interactions, Gastrointestinal nausea, headache,
physiologic replacement
Behavioral changes Hypothyroidism Androgenic disturbances vomiting, diarrhea,
doses
(psychosis) effect dizziness,
vaginal bleeding
Behavioral changes
secondary to steroid use
is termed “Steroid Rage”
• Hydrocortisone • Betamethasone and • Abused by body • Potent • Drug of choice • also used as an
(cortisol) is the Dexamethasone builders to lower inhibitor of for pregnant approved
prototype hastens fetal lung circulating levels CYP450 patients with abortifacient for
glucocorticoid. maturation of cortisol in the enzymes Cushing’s medical abortion
• Betamethasone is the • Prednisolone is the body and prevent • Itraconazole is syndrome (usually together
glucocorticoid with the active metabolite of muscle loss an alternative with
highest anti- prednisone • Also inhibits to misoprostol)
inflammatory potency. • This group has a long t½, synthesis of all Ketoconazole
• Fludrocortisone is the reduced salt-retaining hormonally active
mineralocorticoid with effect and better steroids
Notes the highest salt- penetration of lipid
retaining potency barriers
Special considerations in corticosteroid use
• Minimize toxicities by local application, alternate-day
therapy or dose-tapering
• Avoid adrenal insufficiency in patients who have had
long-term therapy by giving additional "stress
dose“ during serious illness or before major surgery
• Patients who are being withdrawn from long-term
therapy should have slow dose-tapering to allow
recovery of normal adrenal function
CUSHING’S SYNDROME o pituitary CS (Cushing’s disease) due to ACTH-secreting
• syndrome caused by any condition that produces elevated pituitary adenoma
glucocorticoid levels o ectopic CS due to paraneoplastic ACTH production (usually
• causes of Cushing’s syndrome (CS) from lung tumors)
o iatrogenic Cushing’s syndrome due to exogenous steroid MNEMONICS FOR SIDE EFFECTS OF CORTICOSTEROIDS:
CUSHINGOID: Cataract, Ulcers, Striae, Hypertension, Hirsutism,
intake is the most common cause
Immunosuppression, Infection, Necrosis of the femoral head, Glucose
o adrenal CS due to cortisol-secreting adrenal adenoma elevation, Osteoporosis, Obesity, Impaired wound healing, and Diabetes
MINERALOCORTICOID RELATED DRUGS
MINERALOCORTICOID MINERALOCOTICOID
AGONIST ANTAGONIST
Drug
FLUDROCORTISONE [C],
SPIRONOLACTONE
DEOXYCORTICOSTERONE
Strong agonist of
mineralocorticoid receptors and
moderate activation of Blocks Aldosterone
MOA
glucocorticoid receptors. receptors
Increases Na reabsorption,
K and H excretion
Chronic adrenal insufficiency
(Addison’s disease), Congenital
adrenal hyperplasia, Adrenal For Heart failure,
replacement therapy post- For hypokalemia due
Uses adrenalectomy to other diuretics,
for post-MI,
Adrenalectomy should be done hyperaldosteronism
for px with adrenal tumor such
as pheochromocytoma
Salt and fluid retention,
Hypokalemia, Congestive heart Hyperkalemia, anti-
SE failure, Muscle wasting, androgenic effect
Osteoporosis, Glucose (e.g. gynecomastia)
intolerance, Behavioral changes
• Additive hypokalemia with • Also, with weak
loop diuretics and thiazides antagonist effect at
• Deoxycorticosterone is the the androgen
precursor of aldosterone receptor
Notes • Fludrocortisone also has
significant glucocorticoid activity
• Aldosterone is implicated in
myocardial and vascular fibrosis
and baroreceptor dysfunction
GONADAL HORMONES AND INHIBITORS
ESTROGENS AND PROGESTINS

ESTROGENS
• major ovarian estrogen in women is estradiol
• MOA: involves entry into cells, binding to cytosolic receptors,
and translocation of the receptor-hormone complex into the
nucleus, where it modulates gene expression
• mixtures of conjugated estrogens from biologic sources
(Premarin) are used for hormone replacement therapy (HRT)
• synthetic estrogens with high bioavailability (ethinyl estradiol,
mestranol) are used as hormonal contraceptives
SYNTHETIC ESTROGEN
ESTROGEN
(NONSTEROIDAL)
ETHINYL ESTRADIOL [X],
MESTRANOL [X],
Drugs ESTRADIOL CYPIONATE, DIETHYLSTILBESTROL
PREMARIN, ESTRIOL (DES) [X]
“PREMARIN is from
PREgnant MARe’s urine”
Activates estrogen receptors; leads to changes in rates
MOA
of transcription of estrogen-regulated genes
Primary hypogonadism, Atrophic vaginitis,
Postmenopausal hormonal Hormone replacement
replacement therapy, therapy, Prevention of
Uses
Osteoporosis, adverse pregnancy
Contraception, outcomes, Metastatic
Intractable dysmenorrhea prostate cancer
ETHINYL ESTRADIOL [X], DIETHYLSTILBESTROL MOA of Combination Hormonal Contraceptives
Drugs
etc (DES) [X] • inhibition of ovulation (the primary action)
Breakthrough bleeding, Nausea, Breast tenderness, • effects on the cervical mucus glands, uterine tubes, and
Migraine, Thromboembolism (DVTs), endometrium that decrease the likelihood of fertilization and
Gallbladder disease, Hypertriglyceridemia, implantation
SE Hypertension, premature closure of the epiphysis in
young females, Types of Oral Contraceptives
Increased risk of breast and endometrial cancer
• MONOPHASIC
(remedy: add progesterone to the preparation)
o combination estrogen-progestin tablets that are taken in
• Ethinyl Estradiol has low • Associated with
constant dosage throughout the menstrual cycle
bioavailability Infertility, Ectopic
PO/TD/IM/Intravaginal pregnancy, Clear cell • BIPHASIC or TRIPHASIC
• Estradiol cypionate is IM vaginal o combination preparations in which the progestin or estrogen
with longer t½ adenocarcinoma in dosage, or both, changes during the month
• Premarin is a mixture of daughters of mothers o more closely mimics hormonal changes in menstrual cycle
conjugated estrogen used who took DES • PROGESTIN-ONLY PREPARATIONS
in HRT o recommended for breastfeeding moms since they do not affect
• Effects of Estrogen: growth lactation
of genital structures and
Notes secondary sexual Postcoital Contraceptives/ Emergency Contraception
characteristics, modifies • prevent pregnancy if administered within 72 h after
serum protein levels and unprotected intercourse
decrease bone resorption, • progestin (L-Norgestrel) alone, estrogen alone, combination of
enhances coagulability of estrogen and progestin
blood, increases TG and o progestin-only preparation causes fewer side effects than the
HDL levels while
estrogen-containing preparations
decreasing LDL levels, if
given as continuous
infusion will inhibit FSH Oral Contraceptives: Contraindications and Disease Risk
and LH release Contraindications
Absolute
PROGESTINS
• Women age >35 years who smoke > 15 cigarettes per day
NORGESTREL [X],
NORETHINDRONE, ETHYNODIOL, MEGESTROL, • Known ischemic heart disease or multiple risk factors for
DESOGESTREL, NORELGESTROMIN, NORGESTIMATE, cardiovascular disease (older age, smoking, diabetes, and
Drugs ETONOGESTREL, PROGESTERONE, LEVONORGESTREL, hypertension)
DYDROGESTERONE, ULIPRISTAL, TIBOLONE, • Previous thromboembolic event, stroke or known
NORETHISTERONE, DIENOGEST thrombogenic mutations
Activates progesterone receptors; Changes rates of • Complicated valvular heart disease
MOA
transcription of progesterone-regulated genes • Complicated solid organ transplantation
Hormone replacement therapy (given together with • Hypertension (systolic >160 mmHg or diastolic >100 mmHg)
Estrogen, to prevent estrogen-induced endometrial • Systemic lupus erythematous (positive or unknown
Uses cancer), contraception, assisted reproduction (for antiphospholipid antibodies
maintenance of pregnancy), anovulation induction • Cirrhosis, hepatic adenoma or hepatoma
(given in high doses to suppress FSH and LH)
• Pregnancy and early postpartum (<21 days)
Hypertension, Decreased HDL, Weight gain,
• undiagnosed abnormal uterine bleeding
SE Reversible decrease in bone mineral density, Delayed
Relative
resumption of ovulation after use
• Hypertension (adequately controlled or systolic 140-159 or
• Prevents estrogen-induced endometrial cancer
diastolic 90-99)
when used in combination
• Women receiving anticonvulsant drug therapy
• Megestrol is used as an appetite stimulant
• Women following bariatric surgery (malabsorptive
• Medroxyprogesterone has a better oral
procedure)
bioavailability
Disease Risks
• L-Norgestrel and Norethindrone has more
Increased
androgenic effect
• Effects of progesterone: induces secretory changes • Coronary heart disease- increased in smokers >35; no
Notes in the endometrium, stabilize the endometrium, relation to progestin type
affect carbohydrate metabolism and stimulate • Hypertension-relative risk 1.8 (current users) and 1.2
deposition of fat, high doses suppress FSH and LH (previous users)
secretion • Venous thrombosis relative risk ~4; may be higher with
third-generation progestin, drospirenone, and patch;
TIBOLONE is a synthetic steroid with weak estrogenic,
compounded by obesity (tenfold increased risk compared
progestogenic and androgenic activity, and hence is an
agonist of the estrogen, progesterone and androgen
with nonobese, no OCP); markedly increased with factor V
receptor. It is primarily used in menopausal hormone Leiden or prothrombin gene mutations
therapy, postmenopausal osteoporosis and endometriosis. • Stroke—slight increase; unclear relation to migraine
headache
HORMONAL CONTRACEPTIVES • Cerebral vein thrombosis-relative risk ~13-15; synergistic
• contain either a combination of an estrogen and a progestin or a with prothrombin gene mutation
progestin alone • Cervical cancer—relative risk 2—4
• available in a variety of preparations • Breast cancer—may increase risk, particularly in carriers of
o oral pills BRCA1 and possibly BRCA2
o long-acting injections (good for 3 months) Decreased
o implants (good for 3 years) Ovarian cancer—50% reduction in risk
o transdermal patches Endometrial cancer—40% reduction in risk
o vaginal rings
o intrauterine devices (IUDs) 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
CONTRACEPTIVES *Do not protect against STIs
PROGESTIN-ONLY
COMBINED ORAL CONTRACEPTIVE POSTCOITAL CONTRACEPTIVE
CONTRACEPTIVE
ESTRADIOL + NORETHINDRONE [X]
Drugs ETHINYL ESTRADIOL + DESOGESTREL/NORGESTREL
MEDROXY-PROGESTERONE LEVONORGESTREL,
ETHINYL ESTRADIOL + DROSPIRENONE
ACETATE [D] ETHINYL ESTRADIOL + LEVONORGESTREL
ETHINYL ESTRADIOL + NORGESTIMATE
ETHINYL ESTRADIOL + NORETHISTERONE
Combined oral contraceptive, activates estrogen and Activates progesterone
progesterone receptors, inhibits ovulation, effects on receptors. Prevents Activates estrogen and/or progesterone
MOA cervical mucus gland, uterine tubes and endometrium lead conception by altering receptors. Thickens cervical mucus. Inhibits
to decreased fertility, inhibit ovulation when given before cervical mucus and creating ovulation.
the LH surge a hostile endometrium
Contraception, Hypogonadism, Acne, Hirsutism, Contraception, Hormone
Uses Emergency contraception
Dysmenorrhea, Endometriosis replacement therapy
Breakthrough bleeding, Nausea, Breast tenderness, Skin
pigmentation, Thromboembolism (DVTs), Breast cancer Breakthrough bleeding, Severe nausea, vomiting, Breast tenderness,
(earlier onset), headache, skin pigmentation, depression, Hair loss, Dysmenorrhea, Irregular Bleeding, Headache, Dizziness
SE weight gain and hirsutism for older OCPs Delayed return of fertility, (fewer SE compared to estrogen alone and
OCPs: increase HYPERCOAGUABILITY Osteoporosis combination contraceptives)
Breakthrough bleeding – bleeding in between dosages of OCPs
• Lifetime risk of breast cancer is NOT changed • Intramuscular depot • Must be taken within 72 hours of
Notes • Combined OCPs may be used for androgen-induced preparation unprotected sexual intercourse (not
hirsutism (Depo-Provera) effective once implantation has occurred)
SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS)
Drug TAMOXIFEN [D], TOREMIFENE [D] RALOXIFENE [X] CLOMIPHENE [X]
Estrogen antagonist actions in
Estrogen antagonist actions in breast tissue and breast tissue, uterus and CNS. Partial agonist of estrogen receptors in
MOA CNS. Estrogen agonist effects in uterus, liver and Estrogen agonist effects in pituitary. Reduces negative feedback by
bone. liver and bone. Increases bone estradiol. Increases FSH and LH output.
mineral density.
Induction of ovulation for women who want to
Osteoporosis, Breast cancer
Hormone-responsive breast cancer, prophylaxis of get pregnant
prevention
breast CA esp. in those with high risk Acts as antagonist to estrogen receptors in the
Uses Preferred in patient with pituitary → inhibit negative feedback
Given for breast cancer patients who are ER+ PR+ history of breast cancer in the mechanism by estrogen → leads to pituitary
management of hot flushes. stimulation causing ↑ LH and FSH
Hot flushes, Eye symptoms (afterimages),
Hot flushes, Thromboembolism (DVTs), Hot flushes,
SE Headache, Constipation, Reversible hair loss,
Endometrial hyperplasia, Endometrial cancer Thromboembolism (DVTs)
Ovarian enlargement, Multiple pregnancies (10%)
• Prevents osteoporosis in post-menopausal women • Reduces incidence of breast • Increased risk of low-grade ovarian cancer
and decreases risk of atherosclerosis at the risk of cancer in women who are at with long-term use
causing endometrial cancer very high risk
Notes • No estrogenic effects on
FLUVESTRANT is a FULL ESTROGEN RECEPTOR
ANTAGONIST (No agonist effect) for hormone receptor endometrial tissue
positive metastatic breast cancer resistance to Tamoxifen
MISCELLANEOUS ESTROGEN ANTAGONISTS
OVARIAN GLUCOCORTICOID AND
AROMATASE
INHIBITOR GnRH AGONISTS GNRH ANTAGONISTS PROGESTERONE
INHIBITOR
(ANTIANDROGEN) RECEPTOR ANTAGONIST
Drugs LEUPROLIDE, GONADORELIN [B],
ANASTROZOLE [X],
GOSERELIN, HISTRELIN, NAFARELIN, GANIRELIX [X], CETRORELIX,
LETROZOLE, DANAZOL [X] MIFEPRISTONE (RU-486) [X]
TRIPTORELIN ABARELIX, DEGARELIX
EXEMESTANE
All are Preg Cat X except Gonadorelin
Reduces estrogen Agonist of GnRH receptors.
synthesis by Increased LH and FSH secretion
inhibiting Weak cytochrome with INTERMITTENT
aromatase Blocks GnRH receptors.
P450 inhibitor and administration. Reduced LH and Pharmacologic antagonist
Reduces endogenous
MOA Aromatase is partial agonist of FSH secretion with PROLONGED of glucocorticoid and
production of LH and
the enzyme progestin and CONTINUOUS administration progesterone receptors
FSH.
which converts androgen receptors (due to downregulation of GnRH
Testosterone to receptors in the pituitary cells that
Estrogen(Estradiol) normally release LH and FSH)
Endometriosis, Ovarian Suppression, Controlled
Prevents premature LH
Breast cancer, Fibrocystic disease, ovarian hyperstimulation,
surge during Controlled Medical abortion,
Uses Precocious Hemophilia, Endometriosis, Myoma uteri,
ovarian hyperstimulation, Cushing's syndrome
puberty Angioneurotic Central Precocious puberty,
Advanced Prostate cancer
edema Advanced Prostate cancer
Hot flushes, Acne, Hirsutism, Hot flushes, Sweats, Headache, Nausea, Headache, Vaginal bleeding,
Musculoskeletal Weight gain, Light-headedness, Injection site Hypersensitivity (Abarelix), abdominal pain, GI upset
SE disorders, Menstrual reactions, Nausea, Osteoporosis, Hot flushes, Gynecomastia, (vomiting, diarrhea),
Osteoporosis, disturbances, Gynecomastia, Reduced libido, decreased libido, uterine cramping, nausea,
Joint pains Hepatic dysfunction Decreased hematocrit hematocrit, Osteoporosis headache, dizziness
• Effective against • Contraindicated • Symptoms of hypogonadism • Does NOT cause a tumor • Combination with
breast cancers during pregnancy with continuous treatment flare-up when used for misoprostol results in
that have become and breast- • Temporary exacerbation of treatment of advanced abortion of 95% of early
resistant to feeding precocious puberty or prostate prostate cancer pregnancies
Notes tamoxifen • May also act on cancer, Apoplexy and Blindness • Degarelix is used for • Complication: failure to
Exemestane is an Glucocorticoid during the first few weeks of prostate CA while induce complete abortion
IRREVERSIBLE receptors therapy (remedy: co-administer Ganirelix prevent LH àsepsis d/t unusual
inhibitor Flutamide, an androgen receptor surge in controlled organisms
antagonist) ovulation (Clostridium sordelli)
ANDROGENS CLINICAL USE OF TESTOSTERONE

TESTOSTERONE • replacement therapy in hypogonadism
• stimulate RBC production in certain anemias
• synthesized from progesterone and dehydroepiandrosterone
(DHEA) • promote weight gain in patients with wasting syndromes (e.g.
AIDS patients)
• partly bound to sex hormone-binding globulin (SHBG)
o increased by estrogen, thyroid hormone and cirrhosis • performance enhancement in athletes
o decreased by androgen, growth hormone and obesity o exploited illicitly to increase muscle bulk and strength
o converted in several organs (e.g. prostate) to • Effects of androgen: secondary sexual characteristics, fertility
dihydrotestosterone (DHT), which is the active hormone in and libido, male pattern baldness, increases muscle mass,
those tissues increased RBC production, decreased urea nitrogen excretion,
maintains normal bone density
ANDROGENS ANABOLIC STEROIDS

Drugs TESTOSTERONE [X], FLUOXYMESTERONE, METHYLTESTOSTERONE,
OXANDROLONE [X], NANDROLONE DECANOATE
TESTOSTERONE CYPIONATE, OXYMETHOLONE, MESTEROLONE
MOA Activates androgen receptors. Promotes development of male characteristics. Increases body muscle bulk and RBC production.
Male hypogonadism, Delayed puberty, Wasting syndromes, certain
Uses Illegal performance enhancement drugs in athletes
types of anemias
Virilization and menstrual irregularities in females,
paradoxical feminization in males, cholestatic jaundice, elevated LFTs Virilization in females, Paradoxical feminization in males,
SE Cholestatic jaundice, Elevated liver enzymes,
Paradoxical femininization may be due to negative feedback on Hepatocellular carcinoma
physiologic testosterone levels
• Contraindicated in pregnant women and patients with prostate cancer • Increased ratio of anabolic-to-androgenic activity.
Notes
• Used illegally by athletes as performance enhancer
ANTI-ANDROGENS
** For benign and malignant prostate disease, precocious puberty,
hair loss and hirsutism **
ANDROGEN SYNTHESIS INHIBITOR
ANDROGEN RECEPTOR ANTAGONIST
(5-ALPHA -REDUCTASE INHIBITOR)
Drug FINASTERIDE [X], DUTASTERIDE
FLUTAMIDE [D], CYPROTERONE [X],
BICALUTAMIDE, NILUTAMIDE CYPROTERONE ACETATE FinAsteRIde
Five Alpha Reductase Inhibitor
Antagonist at androgen Inhibits 5a-reductase enzyme that converts
receptor. Marked testosterone to dihydrotestosterone
MOA Competitive antagonist at androgen receptor progestational effect that Dihydrotestosterone is the most potent form of
suppresses the feedback testosterone, essential in the development of male
enhancement of LH and FSH. secondary sexual characteristics.
Benign prostatic hyperplasia (BPH), Male-pattern
Hirsutism, Component of baldness, Hirsutism
Prostate cancer, Surgical castration
Uses combined oral contraceptives,
(Nilutamide) Giving 5-alpha reductase aids in the management
Decreases sexual drive in men
of smooth muscle hypertrophy in the prostate.
Hepatotoxicity, Adrenal
Gynecomastia, Hot flushes, Impotence, suppression, Depression,
SE Impotence (rare), Gynecomastia, Depression
Hepatoxicity Gynecomastia, Galactorrhea,
Thromboembolism
• Less hepatotoxicity with bicalutamide and • Orphan drug status • Controversial use in prevention of prostate
nilutamide cancer
Notes • GnRH analogs (leuprolide) must be co- • Dutasteride is newer with longer t½
administered with flutamide to prevent acute
flare-up of prostate cancer
PANCREATIC HORMONES,
ANTIDIABETIC DRUGS AND GLUCAGON
DIABETES MELLITUS
• chronic disorder of carbohydrate, fat, and protein metabolism
due to a relative or absolute deficiency in insulin secretory • TYPE 2 DIABETES
response o progressive disorder characterized by increasing insulin
resistance and diminishing insulin secretory capacity
Types of Diabetes Mellitus
o frequently associated with obesity and is much more common
• TYPE 1 DIABETES
than type 1 diabetes
o usually has its onset during childhood
o usually has its onset in adulthood
o results from autoimmune destruction of pancreatic b cells Type 1 DM: no C-peptide. Type 2: have C-peptide
INSULIN Duration of Action of Different Types of 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
physiologic actions
MOA of Insulin
• binds to a tyrosine kinase receptor, which phosphorylates itself Figure 41-1. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
and a variety of intracellular proteins when activated by the
hormone STRATEGIES FOR INSULIN THERAPY
• activation of phoshphatidylinositol-3 kinase pathway and MAP • BASAL BOLUS
kinase pathway o most physiologic strategy because it copies the body’s
• translocation of glucose transporters (especially GLUT 4) to normal production of insulin as closely as possible
the cell membrane o long-acting insulin (BASAL) + short-acting insulin with every
o increase in glucose uptake meal (BOLUS)
o increased glycogen synthase activity • SLIDING INSULIN SCALE
o increased glycogen formation o fixed amounts of long-acting insulin to be given routinely
o amount of short-acting insulin varied depending on pre-
Insulin is also capable of inducing entry of K+ (potassium) into cells
prandial CBG
INSULIN [B]
• Rapid: LISPRO, ASPART, GLULISINE Routes of Insulin Administration: subcutaneous and IV
OTHER ROUTES REASON WHY NOT USED?
• Short: REGULAR (Humulin R)
Does not result in a reproducible and sufficient
• Intermediate: NPH, LENTE (Humulin N) Transdermal
Drug transfer of insulin across the skin
• Long: ULTRALENTE, GLARGINE, DETEMIR, Oral Lack of a specific peptide carrier system in the gut
INSULIN DEGLUDEC Bioavailability was low and metabolic effect lasted
• Premixed Insulin: Humulin 70 NPH/30 Regular Intranasal
too short to be of clinical usefulness
Activates insulin receptors → Reduces circulating glucose Intramuscular Overall metabolic response not comparable to SC
by increasing glucose uptake; Promote glucose transport Most promising; comparable to SC and IV but is
MOA Inhalation
and oxidation, glycogen lipid and protein synthesis and still presently in Phase III trials (Exubera)
regulates gene expression
Type 1 and Type 2 Diabetes mellitus, Diabetic ON INSULIN: HONEYMOON PERIOD
Uses
emergencies (DKA, HHS – rapid acting), Hyperkalemia
• period in type 1 DM when exogenous insulin requirements
Hypoglycemia, Insulin allergy, Immune insulin resistance,
decrease due to an increase in the endogenous production of
Lipodystrophy at injection site, Weight Gain, Increased
SE
cancer risk (linked to insulin resistance and
insulin
hyperinsulinemia in Px with prediabetes and T2DM) • initiation of insulin therapy causes activation of residual
• Beta-blockers may mask signs of hypoglycemia pancreatic beta cells
• All insulin preparations contain zinc • transient phase followed by total lack of endogenous insulin
• Parenteral (IV or SC) production
• Effects of insulin: increased glycogen and protein
synthesis, decreased protein catabolism, increased TG INSULIN AND HYPOGLYCEMIA
storage Hypoglycemia
• Rapid acting insulins are injected a few mins prior to • NEUROGLYCOPENIC SYMPTOMS
meals and they are the preferred insulin for continuous o result of central nervous system (CNS) glucose deprivation
Notes
SC infusion devices o EXAMPLES:
• Short-acting insulins are injected more than an hour § behavioral changes, confusion, fatigue, seizure and loss of
before a meal consciousness
• Intermediate acting insulins are often combined with • NEUROGENIC (OR AUTONOMIC) SYMPTOMS
regular and rapid acting insulins o result of CNS-mediated sympathoadrenal discharge
• Long acting insulins are called "peakless" insulins o EXAMPLES:
• *The ratio of zinc and other substances to insulin § adrenergic symptoms: palpitations, tremor, anxiety
influences the rate of release and duration of action § cholinergic symptoms: sweating, hunger, paresthesia
• At Risk for Insulin-related Hypoglycemia: Advanced renal
Insulin Types and Activity disease, elderly, children <7 y/o
Peak Duration
Rapid Acting 0.25 to 0.5 3 to 4
Lispro, Aspart, Glulisine NONINSULIN ANTIDIABETIC AGENTS
Short Acting 0.5 to 3 5 to 7
Regular
Intermediate Acting 8 to 12 18 to 24
NPH, Lente
Long Acting 8 to 16 18 to 28
Ultralente
Ultra-Long Acting No peak >24
Glargine, Detemir, Lantus
• 0.25 TO 0.50 OF AN HOUR: 15-30mins
• When mixing intermediate with rapid acting insulin, NPH preferred
over Lente because Lente retards the onset of action of regular insulin
Figure 41-3. Katzung and Trevor’s Pharmacology Examination and Board Review. 11 ed. 2015
th
NON-INSULIN
ANTI-DIABETIC AGENTS
https://qrs.ly/47ckedb
INSULIN SECRETAGOGUES
MOA OF INSULIN SECRETAGOGUES
• stimulate the release of endogenous insulin by promoting closure of
potassium channels in the pancreatic B-cell membrane
• depolarizes the cell and triggers insulin release
• not effective in patients who lack functional pancreatic B cells
SECRETAGOGUES
1st Generation Sulfonylurea 2nd Generation Sulfonylurea Meglitinides
MEGLITINIDE,
Drugs CHLORPROPAMIDE, TOLBUTAMIDE,
GLIPIZIDE [C], GLIMEPIRIDE [C], REPAGLINIDE [C],
TOLAZAMIDE
GLYBURIDE/GLIBENCLAMIDE, GLICLAZIDE NATEGLINIDE [C],
All are Preg Cat C
MITIGLINIDE
MOA Increases insulin secretion from pancreatic beta cells by closing ATP-sensitive K+ channels
Type 2 diabetes mellitus
In patients with functioning Beta cells, reduce Type 2 diabetes mellitus
Uses Type 2 diabetes mellitus
circulating glucose, increase glycogen, fat and protein (postprandial hyperglycemia)
formation, regulates gene expression
Hypoglycemia (least),
Hypoglycemia, Weight gain,
Headache, Upper respiratory
Disulfiram reaction, Hyperemic flush
Hypoglycemia (less), Weight gain, Photosensitivity, tract infections
after alcohol ingestion,
SE Hematologic toxicity, Cholestatic jaundice Has the lowest risk of
Dilutional hyponatremia,
(glibenclamide) developing hypoglycemia
Hematologic toxicity,
since they have short duration
Hypersensitivity reaction, rash of action
• Tolbutamide and chlorpropamide are • Contraindicated in patients with hepatic • Used in diabetics with sulfa
highly protein bound drugs → Drugs impairment and renal insufficiency allergies
that compete for protein binding may • Requires islet cell function • Nateglinide has the least
enhance hypoglycemic effects • May come in combination with Metformin incidence of hypoglycemia
• Requires islet cell function and may be used in CKD
Notes
• Lower Potency, Greater Toxicity patients
High propensity to cause hypoglycemia • Requires islet cell function
especially among elderly patients that’s • Very short DOA (4-8hrs only)
why it is seldom used • May come in combination
with Metformin
INSULIN SENSITIZERS MOA OF THIAZOLIDINEDIONES
MOA OF BIGUANIDES • increase target tissue sensitivity to insulin by activating the
• reduces postprandial and fasting glucose levels peroxisome proliferator-activated receptor-gamma nuclear
• activates AMP-stimulated protein kinase leading to inhibition receptor (PPAR-g receptor)
hepatic and renal gluconeogenesis • increase glucose uptake in muscle and adipose tissue
• other effects: • inhibit hepatic gluconeogenesis and have effects on lipid
o stimulates glucose uptake and glycolysis in peripheral tissues metabolism and the distribution of body fat
o slows glucose absorption from the gastrointestinal tract • reduce both fasting and postprandial hyperglycemia.
o reduces plasma glucagon levels • reduce the risk of diabetes in high-risk patients
o reduce the risk of diabetes in high-risk patients
SENSITIZERS
Biguanide Thiazolidinedione
Drugs
PIOGLITAZONE [C],
METFORMIN [B]
ROSIGLITAZONE [C], TROGLITAZONE [B]
Activates AMP-stimulated protein kinase leading to Regulates gene expression by binding to PPAR-gamma
inhibition of hepatic and renal gluconeogenesis and PPAR-alpha → increases tissue sensitivity, increases
MOA Metformin and its cousin Thiazolidinediones bypass the glucose uptake in muscle and adipose tissue, inhibits hepatic
insulin receptor. Both of these medications act via gene gluconeogenesis, effects on lipid metabolism and distribution
expression to sensitize tissue receptor to insulin of body fat, control of fasting and postprandial glucose
Type 2 diabetes mellitus (first line), Diabetes
Uses prevention, Polycystic ovarian syndrome Type 2 diabetes mellitus, Diabetes prevention
Drug of choice for obese diabetics
Fluid retention, Anemia, Weight gain,
Congestive heart failure, Bone Fractures especially in
GI disturbance, weight loss, lactic acidosis
women, Cardiovascular events (rosiglitazone),
SE (especially in renally and hepatically impaired patients),
Hepatotoxicity (troglitazone), Macular edema,
Vit B12 malabsorption
Dyslipidemia (↑ HDL & LDL, ↓ TG), increased risk of MI
(Rosiglitazone)
• Contraindicated in patients with renal disease, • Contraindicated in pregnancy, chronic liver disease and
alcoholism, hepatic disease CHF or conditions congestive heart failure
predisposing to tissue anoxia (Hypoxic or acidotic • Pioglitazone reduces mortality and macrovascular events
states) (myocardial infarction and stroke)
• May also cause slowing of glucose absorption from GIT • Rosiglitazone binds to PPAR-gamma ONLY
Notes and decreased plasma glucagon • PPAR regulates transcription of genes encoding proteins
• Causes a decrease in endogenous insulin production by involved in carbohydrate and lipid metabolism
increasing insulin sensitivity of tissues "Insulin • May increase risk for developing Bladder Cancer
Sparing Effect" therefore does not have weight gain as • Increased risk by 63% for bladder CA – Pioglitazone
a SE Rosiglitazone and troglitazone have “Blackbox Warning” on
• Does NOT cause hypoglycemia their packaging because of the risk of CHF
OTHER NON-INSULIN ANTIDIABETIC DRUGS
ALPHA-GLUCOSIDASE INCRETIN MODULATOR
AMYLIN ANALOG SGLT2 INHIBITOR
INHIBITOR GLP-1 Agonist DPP-4 Inhibitor
EXENATIDE [C], SITAGLIPTIN [B],
DAPAGLIFLOZIN,
Drugs ACARBOSE [B], LIRAGLUTIDE [C], SAXAGLIPTIN [B],
EMPAGLIFLOZIN,
MIGLITOL [B], PRAMLINTIDE [C] LIXISENATIDE, LINAGLIPTIN [B],
CANAGLIFLOZIN
VOGLIBOSE SEMAGLUTIDE, VILDAGLIPTIN,
DULAGLUTIDE TENELIGLIPTIN
Inhibits dipeptidyl
Activates amylin peptidase-4 (DPP-4) that NA-GLUCOSE CO-
receptors. Reduce Activates GLP-1 degrades GLP-1 and other TRANSPORTER 2
Inhibits intestinal a- post-meal glucose receptors → reduction of incretins (SGLT 2) INHIBITOR
glucosidases → reduce excursions post-meal glucose → raises circulating GLP-1 Inhibits SGLT2
conversion of starch and Suppresses excursions. levels. transporter
MOA disaccharides to glucagon release. → inhibits reabsorption
monosaccharides → Delays gastric Reduces post-meal of glucose in the kidneys
reduce post prandial emptying. glucose excursions. back to the blood →
hyperglycemia Stimulates CNS to excretion of glucose out
Augments glucose-stimulated insulin release from
reduce appetite in the urine
pancreatic B cells. Retards gastric emptying. Inhibits
(anorectic effect).
glucagon secretion. Produces satiety
Type 2 diabetes mellitus, Type 1 and Type 2 Type 2 diabetes
Uses Type 2 diabetes mellitus Type 2 diabetes mellitus
Diabetes prevention diabetes mellitus mellitus
Gastrointestinal
Dizziness,
disturbance (flatulence, Hypoglycemia, Hypoglycemia, Headache, Nasopharyngitis,
strong smell of urine,
diarrhea, abdominal Gastrointestinal Acute pancreatitis, Upper respiratory tract
edema, weakness,
SE pain), Hypoglycemia disturbances, Nausea, Vomiting, infections,
nausea, vomiting,
(when taken with nausea, anorexia, Headache, Anorexia, hypersensitivity reactions,
decrease in the amount
sulfonylureas), Increased headache Mild Weight Loss pancreatitis
of urine
liver enzymes
• Relatively minor • Administered as • Administered as an • Administered orally as • Do NOT use among
glucose-lowering an injectable injectable monotherapy or in renally impaired
benefit preparation (SC) preparation combination with metformin patients
• Treat hypoglycemia together with (SC - Long-acting Incretins are substances in the • Increased incidence
with oral glucose insulin to control injectables ) body that augments of UTI since you have
(dextrose) NOT post-prandial • Used in glucose-stimulated insulin higher sugar in your
sucrose, because glucose combination with release. Some can suppress urine
Notes
absorption is impaired • Short t1/2 of metformin or a glucagon release while some • Used by many to lose
• Taken immediately 48mins sulfonylurea would have anorectic effect weight
before a meal • Liraglutide has
• Contraindicated in possible thyroid
patients with renal and carcinoma risk
hepatic impairment and
intestinal disorders
SUPPLEMENT: ORLISTAT
Drug SIBUTRAMINE [C] RIMONABANT
BILE ACID SEQUESTRANT (Xenical)
Drug COLESEVELAM [B] • Rebound • Withdrawn due to • Withdrawn
Binds bile acids. Lowers glucose through unknown weight gain increased risk of because of
MOA
mechanism upon cardiovascular increased
Uses Type 2 diabetes mellitus discontinuation events and strokes risk of
constipation, dyspepsia, myalgia, asthenia • Contraindicated suicides,
Familiar with
SE Lack of bile acids will cause malabsorption of fat- Note in pregnancy, depression
Reductil? This has
soluble vitamins and steatorrhea. reduced and other
been banned since
hepatobiliary this drug is a serious
function and relative of psychiatric
DRUGS FOR OBESITY problems
malabsorption Methamphetamine
ORLISTAT states
Drug SIBUTRAMINE [C] RIMONABANT
(Xenical)
Selectively SUPPLEMENT:
blocks An appetite suppressant which is an
Inhibits Inhibits PHENTERMINE
cannabinoid- amphetamine derivative. Side effects will be
gastrointestinal norepinephrine and [X]
1 (CB-1) similar with amphetamine
and pancreatic serotonin reuptake
MOA receptors.
lipases. Reduces in the CNS. Reduces
Reduces GLUCAGON
absorption of appetite (anorectic
appetite
fats. effect). GLUCAGON
(anorectic
effect). Class Pancreatic Hormone (secreted by A cells of pancreas)
Obesity, MOA Activates glucagon receptors
Smoking Severe hypoglycemia, Diagnosis of endocrine
Obesity, Type 2
Uses Obesity cessation, disorders, Beta-blocker overdose, Radiology of the
diabetes
Drug
Uses bowels
addiction Glucagon can increase heart rate and force of contraction
Dry mouth, Increases hepatic glycogenolysis and gluconeogenesis
Weight loss, Relaxes smooth muscle
Gastrointestinal
Flatulence,
disturbance, SE Nausea, Vomiting, Hypotension
Steatorrhea, Fecal
Tachycardia, Glucagon-secreting tumors (glucagonomas) present
incontinence, Suicidality,
Hypertension, Notes with decreased amino acids in blood, anemia, diarrhea,
SE Malabsorption of Depression,
Cardiovascular weight loss and necrolytic migratory erythema
fat-soluble Nausea
events (myocardial
vitamins (A, D, E,
infarction,
K),
arrhythmias),
Hepatotoxicity
Stroke
DRUGS THAT AFFECT BONE AND MINERAL HOMEOSTASIS
DRUGS AFFECTING
BONE AND MINERAL
HOMEOSTASIS
https://qrs.ly/28ckec4
Figure 42-2. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
HORMONAL REGULATORS PARATHYROID HORMONE

Active Vitamin D • acts on membrane G-protein-coupled receptors to increase
Organ PTH cAMP in bone and renal tubular cells
Metabolites
Indirectly increases • inhibits calcium excretion, promotes phosphate excretion and
calcium and phosphate stimulates the production of active vitamin D metabolites
Increased calcium and
Intestine absorption by • promotes bone turnover by increasing the activity of both
phosphate absorption
increasing Vitamin D osteoblasts and osteoclasts
metabolites o osteoclast activation is not a direct effect and instead results
Increased resorption of from PTH stimulation of osteoblast formation of RANK ligand
Decreased calcium
calcium and phosphate (RANKL)
excretion,
Kidney but usually net increase in • at high doses, net effect of elevated PTH is increased bone
increased phosphate
urinary calcium due to resorption, hypercalcemia, and hyperphosphatemia
excretion
effects in GI tract and bone • low intermittent doses of PTH produce a net increase in bone
Direct effect is increased formation
Calcium and phosphate calcium and phosphate
• Stimulus: decreased free ionized calcium stimulates PTH release
resorption increased by resorption;
continuous high indirect effect is MNEMONICS: Parathyroid Hormone
Bone concentrations. Low promoting What are the signs and symptoms of excess PTH?
intermittent doses mineralization by Painful bones
increase bone increasing the Renal stones
formation availability of calcium Abdominal groans
and phosphate Psychiatric overtones
Serum calcium CALCITONIN
Net effect Serum calcium and
increased,
on serum phosphate both • peptide hormone secreted by parafollicular C cells in the thyroid gland
serum phosphate
levels increased • decreases serum calcium and phosphate by inhibiting bone
decreased
resorption and inhibiting renal excretion of these minerals
• bone formation is not impaired initially, but ultimately it is reduced
RECOMBINANT
PARATHYROID VITAMIN D CALCITONIN
HORMONE
Drug
VITAMIN D (INACTIVE) VITAMIN D (ACTIVE)
CALCITONIN,
TERIPARATIDE [C] ERGOCALCIFEROL [C], CALCITRIOL [C], DOXERCALCIFEROL [B],
SALCATONIN
CHOLECALCIFEROL [C] PARICALCITOL [C], CALCIPOTRIENE [C]
Acts through calcitonin
Acts through PTH receptors to inhibit bone
receptors to produce a Regulates gene transcription via the vitamin D receptor. Stimulates intestinal resorption
MOA net increase in bone calcium absorption, bone resorption, renal calcium and phosphate reabsorption.
formation, stimulates Decrease PTH, promote Innate Immunity MNEMONIC: Calcitonin
bone turnover means CALCium INside
the bone
Paget's disease of bone,
Vitamin D deficiency (rickets, Osteomalacia, intestinal osteodystrophy, CKD,
Hypercalcemia,
Uses Osteoporosis chronic liver disease, hypoparathyroidism, nephrotic syndrome) osteoporosis,
Osteoporosis, Tumor
psoriasis, Renal Failure, malabsorption
marker for thyroid cancer
VITAMIN D (INACTIVE)
VITAMIN D (ACTIVE) CALCITONIN,
Drug TERIPARATIDE [C] ERGOCALCIFEROL [C],
CALCITRIOL [C], etc SALCATONIN
CHOLECALCIFEROL [C]
Hypercalcemia,
Hypercalciuria,
Rhinitis, Nausea,
arthralgia, rhinitis,
SE Hypercalcemia, Hyperphosphatemia, Hypercalciuria Vomiting, Facial flushing,
nausea, weakness,
Tingling
dizziness, pharyngitis,
dyspepsia, rash
• Must be • Commonly added to dairy • The active form Calcitriol is preferred in • Administered as a nasal
administered in low products and other food patients with CKD, chronic liver disease spray
intermittent doses products and hypoparathyroidism • Used for osteoporosis
to stimulate bone • Given topically for psoriasis; • Doxercalciferol is a prodrug that is but is less effective than
formation given with calcium supplements converted in the liver to 1,25- bisphosphonates and
• Used IV for for osteoporosis dihydroxyvitaminD teriparatide
Notes osteoporosis • Paricalcitol, Calcipotriene are analogs of
calcitriol and are used topically for
psoriasis and are being investigated for
malignancies and inflammatory disorders
• Doxercalciferol, Paricalcitol and
Calcipotriene cause less hypercalcemia
and hypercalciuria
NONHORMONAL REGULATORS
ANTI-RANKL
PHOSPHATE
BISPHOSPHONATES SERM MONOCLONAL CALCIUM [A]
BINDING RESIN
ANTIBODY
ALENDRONATE [C],
ETIDRONATE [C],
Drug
IBANDRONATE,
SEVELAMER RALOXIFENE DENOSUMAB CINACALCET CALCIUM, PHOSPHATE,
PAMIDRONATE [D],
[C] [X] [X] [C] STRONTIUM
RISEDRONATE [C],
TILUDRONATE [C],
ZOLEDRONIC ACID [D]
Interacts
Suppresses the activity
selectively with
of osteoclasts in part via Multiple physiologic actions
estrogen Binds to RANKL
inhibition of Farnesyl Activated through regulation of multiple
receptors and prevents it
Pyrophosphate Binds to dietary calcium- enzymatic pathways.
leading to from stimulating
synthesis. phosphate and sensing Strontium suppresses bone
MOA inhibition of osteoclast
Inhibits bone resorption prevents its receptor → resorption and increase bone
bone resorption differentiation and
and secondarily, bone absorption Inhibits PTH formation, Ca and PO4 are
w/o stimulating function → inhibits
formation by acting on secretion required for bone
breast or bone resorption
the basic hydroxyapatite mineralization
endometrial
crystal structure
hyperplasia
Paget's disease of bone,
Hypercalcemia HyperPTH in
especially in CKD, HypoPTH, Osteoporosis, Osteomalacia,
Uses Osteoporosis Osteoporosis HyperPTH
malignancies, Vitamin D Deficiencies in Ca and PO4
Osteoporosis, Bone intoxication
metastases
Adynamic bone,
Esophagitis, Hypotension,
Increased risk Increased risk of
SE Osteonecrosis of the hypertension, Nausea Ectopic calcification
of VTE infection
jaw, Renal impairment, GI disturbance
GI irritation
• Take drugs with large • Can Calcium Content of different
quantities of water significantly Calcium supplements:
and avoid situations reduce uric Ca carbonate 40%
that permit esophageal acid levels Tricalcium
39%
reflux • Contraindicated phosphate
• Remedy for GI irritation in hypoPO4 Ca chloride 27%
and prevent reflux: take and bowel Ca acetate 25%
lots of water and keep obstruction Ca citrate 21%
Notes
patient in an upright Ca lactate 13%
position for 30mins Ca gluconate 9%
after intake of drug Ca gluceptate 8%
• Contraindicated in those CA glubionate 6.5%
with renal impairment,
esophageal motility
disorders and peptic
ulcers
HyperPTH – hyperphosphatemia, HypoPTH – hypophosphatemia, HypoPO4 – hypophosphatemia
CANCER CHEMOTHERAPY
LOG-KILL HYPOTHESIS Classification of Drugs: Based on Cell Cycle
• anticancer drugs kill a fixed proportion of a tumor cell • CELL CYCLE NONSPECIFIC DRUGS (CCNS)
population, not a fixed number of tumor cells o act on tumor stem cells when they are traversing the cell cycle
• Drug combinations are done to achieve: 1) Synergism and 2) and when they are in the resting phase
prevention of drug resistance. • CELL CYCLE SPECIFIC DRUGS (CCS)
• We target both cancer cells that are highly dividing (use of cell- o act selectively on tumor stem cells when they are traversing
cycle specific) and cancer cells with low growth fraction (use of cell the cell cycle, and not when they are in the G0 phase
cycle non-specific drugs) at the same time.
ANTICANCER DRUGS: ACTING ON THE CELL CYCLE CANCER TREATMENT MODALITIES
• PRIMARY INDUCTION CHEMOTHERAPY
o drug therapy is administered as the primary treatment
• NEOADJUVANT CHEMOTHERAPY
o use of chemotherapy in patients with localized cancer before
performing local therapy (surgery)
o goal is to render the local therapy more effective
• ADJUVANT CHEMOTHERAPY
o chemotherapy done after local treatment procedures such as
surgery or radiation
o reduce the risk of local and systemic recurrence and to
improve disease-free and overall survival
CHEMOTHERAPY AND TOXICITIES
Face is puffy
from decadron C for Cispla4n/Carbopla4n:
Nephrotoxic, acous4c nerve damage
V for Vincris4ne:
D Peripheral neuropathy
D for Doxorubicin: cardiotoxic
B for Bleomycin: pulmonary fibrosis
CHEMOTOX MAN
https://qrs.ly/1eckef3
C for Cispla4n/Carbopla4n:
Nephrotoxic, acous4c nerve damage
CY for Cyclophosphamide:
56 56
hemorrhagic cys44s
M for MTX, 5 for 5-FU, 6 for 6-MP:

myelosuppression
M M V for Vincris4ne:
Peripheral neuropathy
Adapted from med-source.blogspot.com
MNEMONIC Drugs causing Pulmonary Fibrosis RESCUE THERAPY

“BBBAN Me” • alleviation of toxic effects by giving rescue drugs
Bleomycin Amiodarone o Methotrexate: Leucovorin
Busulfan Nitrofurantoin
o Cyclophosphamide: MESNA
Bromocriptine Methotrexate
o Doxorubicin: Dexrazoxane
o Cisplatin: Amifostine
SUPPLEMENT: HAND-FOOT SYNDROME
• “Palmar-Plantar erythrodysesthesia”
• a side effect of some cancer treatments
• redness, swelling and pain on the palms and soles, sometimes even
with blistering
• may also occur elsewhere in the skin such as the knees and elbows
ALKYLATING AGENTS
CYCLOPHOSPHAMIDE, IFOSFAMIDE, CISPLATIN, CARBOPLATIN, CARMUSTINE, LOMUSTINE,
CHLORAMBUCIL, OXALIPLATIN BENDAMUSTINE
Drug PROCARBAZINE [D] DACARBAZINE [C] BUSULFAN [D]
MECHLORETHAMINE (NITROSOUREAS)
All are Preg Cat D All are Preg Cat D All are Preg Cat D
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 (pancytopenia)
MOA
Forms DNA cross-links, resulting in inhibition of DNA synthesis and function. Forms hydrogen peroxide, which generates free radicals that cause Forms DNA cross-links, resulting in inhibition of DNA synthesis and
Cell cycle non-specific. DNA strand scission. Cell cycle non-specific. function. Cell cycle non-specific.
Testicular cancer, Ovarian cancer,
Bladder cancer, Lung cancer,
Non-Hodgkin's lymphoma, Advanced colon cancer and Brain tumors, Melanoma,
Breast cancer, Ovarian cancer, pancreatic cancer (oxaliplatin), Skin cancer, Lymphoma, CLL
Neuroblastoma, breast cancer, H&N cancer,
Gastroesophageal cancer Hodgkin's lymphoma, Hodgkin's lymphoma, Nitrosoureas are special
Chronic lymphocytic leukemia,
Uses Non-Hodgkin's lymphoma, Non-Hodgkin's lymphoma, Chronic myelogenous leukemia alkylating agent because they are
Wilms Tumor, Rhabdomyosarcoma
Oxaliplatin is part of your Brain tumors Melanoma, Soft Tissue Sarcoma designed for brain tumors. These
FOLFOX and FOLFIRI regimen medications are highly lipophilic
CLL is most common leukemia in adults, and can cross the blood brain
used in the treatment of solid
with Smudge cells barrier.
tumors that are resistant to
Cisplatin and Carboplatin in the
basis of mismatch repair defect
Bone marrow suppression, Alopecia, Skin Rash,
Bone marrow suppression, Pulmonary toxicity, Hemolysis, Gastrointestinal distress, CNS toxicity (dizziness, ataxia),
Nausea, Vomiting, Nephrotoxicity, Pulmonary fibrosis,
Hemorrhagic cystitis, Hepatotoxicity, Neurotoxicity, Bone marrow suppression, Nausea and vomiting,
SE Neurotoxicity (peripheral Adrenal insufficiency,
Alopecia, SIADH, Cardiac dysfunction, Disulfiram-like reaction, Phototoxicity, Flu-like Syndrome, Bone marrow suppression,
neuritis, acoustic nerve damage) Skin pigmentation
Pulmonary toxicity Leukemogenic, CNS Toxicity (ataxia, lethargy, Skin flushing
Hypersensitivity reaction confusion, neuropathy)
• Rescue therapy is MESNA • Rescue therapy is AMIFOSTINE • Forms hydrogen peroxide, • Forms hydrogen peroxide, • Specific to CFU-GM line. Used as • Highly lipophilic, allowing ease
• Cystitis can be prevented with • Decrease nephrotoxicity by which generates free radicals which generates free radicals a myelosuppressive agent prior of passage through BBB into the
adequate hydration administering Mannitol with that cause DNA strand scission. that cause DNA strand scission. to bone marrow transplant. CNS
forced hydration Cell cycle non-specific. Cell cycle non-specific.
Notes • Carboplatin has a wider • Procarbazine has the highest
spectrum of coverage in solid carcinogenic potential amongst
tumors and has less renal and alkylating agent.
GIT side effects and is widely
used in transplant regimen..
ANTIMETABOLITES
ANTIMETABOLITE, DMARD PURINE PYRIMIDINE
6-MERCAPTOPURINE, 6- GEMCITABINE,
Drug
METHOTREXATE [X] THIOGUANINE, AZATHIOPRINE PEMETREXED [D] 5-FLUOROURACIL [D] CYTARABINE [D] CAPECITABINE
All are Preg Cat D All are Preg Cat D
Antimetabolites mimic your purine and pyrimidines. They are inserted in the DNA and because they are not real purine and pyrimidines, once inserted in the DNA of cancer cells they will cause chain termination and
eventual cessation of cancer cell growth. Because they are inserted in the DNA, as a side effect, they will cause bone marrow suppression.
Inhibits de novo purine nucleotide
Inhibits Dihydrofolate reductase. Inhibits thymidylate synthase →
MOA synthesis. Activated by HGPRT. Inhibits Thymidylate Synthase,
Decreases synthesis of thymidylate, Inhibition of DNA Synthesis and Inhibits DNA synthesis and repair. Inhibits ribonucleotide reductase
Cell cycle specific. Fludarabine Dihydrofolate Reductase and
amino acids, purine nucleotides. Cell Function. Causes thymineless with reduced formation of dNTPs. Cell-cycle specific.
and Cladribine inhibit purine nucleotide synthesis
cycle specific. death of cells. Cell cycle specific.
ribonucleotide reductase
Drug METHOTREXATE [X] 6-MERCAPTOPURINE, etc PEMETREXED [D] 5-FLUOROURACIL [D] CYTARABINE [D] GEMCITABINE, CAPECITABINE
Pancreatic cancer,
Choriocarcinoma, Acute leukemias, Bladder cancer, Breast cancer, Non-small cell lung cancer,
Non-Hodgkin's lymphoma, Primary CNS Colorectal cancer, Anal cancer, Bladder cancer,
Acute leukemias (AML, ALL),
lymphoma, Breast cancer, Head and Mesothelioma, Head and neck cancer, Acute leukemias (AML, ALL), Non-Hodgkin's lymphoma,
Use Chronic myelogenous leukemia,
neck cancer, Bladder cancer, non-small cell lung cancer Liver cancer, Ovarian cancer, CML in blast crisis Breast cancer, soft tissue sarcoma
Lymphomas
Rheumatoid arthritis, Psoriasis, Ectopic Skin cancer (basal cell cancer, Capecitabine: HCC,
pregnancy actinic keratoses) Gastroesophageal cancer,
colorectal cancer
Bone marrow suppression, Gastrointestinal irritation, Bone marrow suppression,
Bone marrow suppression, Pulmonary Bone marrow suppression, Bone marrow suppression,
Immunosuppression, Bone marrow suppression, Neutropenia, Pulmonary toxicity,
SE infiltrates and fibrosis, Mucositis, skin rash, mucositis, diarrhea, Gastrointestinal irritation,
Hepatotoxicity (cholestasis, Neurotoxicity (cerebellar Hand-Foot Syndrome
Crystalluria, diarrhea fatigue, Hand-Foot Syndrome Alopecia, mucositis, neurotoxicity
jaundice, necrosis) dysfunction, peripheral neuritis) (Capecitabine)
Rescue therapy is LEUCOVORIN 6-MP metabolism inhibited by TEGAFUR is a chemotherapeutic Most specific for the S phase of
(folinic acid) allopurinol and febuxostat prodrug of 5FU. It is a component the cell cycle
Notes
We need Folic acid for erythrocyte of the combination drug Tegafur-
maturation and DNA synthesis Uracil
NATURAL PRODUCT ANTICANCER DRUGS *All are Preg Cat D
VINCA ALKALOID PODOPHYLLOTOXIN CAMPTOTHECIN TAXANE
Drugs
VINCRISTINE VINBLASTINE, VINORELBINE ETOPOSIDE, TENIPOSIDE TOPOTECAN, IRINOTECAN PACLITAXEL, DOCETAXEL, CABAZITAXEL
Prevents microtubule assembly. Causes cell arrest at metaphase. Inhibits DNA topoisomerase II Interferes with mitotic spindle.
Inhibits topoisomerase I.
MOA Cell cycle specific. (DNA Gyrase). Inhibits mitochondrial Prevents microtubule disassembly into tubulin monomers.
Cell cycle specific.
Acts primarily in M phase of cancer cell cycle electron transport. Cell cycle specific. Cell cycle specific.
Acute leukemias, Lymphomas, Lymphomas, Neuroblastoma, Lung cancer, Prostate cancer, Topotecan: Advanced ovarian cancer (2nd Advanced breast and ovarian cancers, lung cancer,
Uses Wilms tumor, Neuroblastoma, Testicular carcinoma, Kaposi's sarcoma, Testicular cancer, Non-Hodgkin’s line), Small cell lung cancer gastroesophageal cancer, gastric cancer, prostate cancer,
Rhabdomyosarcoma germ cell tumor, breast cancer lymphoma, Gastric cancer Irinotecan: Metastatic colorectal cancer bladder cancer, head and neck cancer
• Areflexia, Peripheral neuritis, • Bone marrow suppression, • Bone marrow suppression, GI • Bone marrow suppression, Diarrhea, • Paclitaxel: Neutropenia, Thrombocytopenia, Peripheral
Paralytic ileus, Alopecia, Gastrointestinal distress, irritation, Alopecia Nausea and vomiting neuropathy, Hypersensitivity, arrhythmias,
Nausea/Vomiting, mucositis, SIADH, constipation, myelosuppression
SE Myelosuppression, SIADH vascular events • Docetaxel: Neurotoxicity, Bone marrow suppression, fluid
Vincristine will not likely cause vinBLASTine BLASTS the Bone marrow retention, hypersensitivity
bone marrow suppression rather vinblastine causes myelosuppression
it will cause neuropathy
ANTITUMOR ANTIBIOTICS *All are Preg Cat D
Drug DOXORUBICIN, DAUNORUBICIN, IDARUBICIN, EPIRUBICIN, MITOXANTRONE BLEOMYCIN, MITOMYCIN ACTINOMYCIN D (Dactinomycin)
Class Anthracycline Antitumor antibiotic Antitumor antibiotic
Generates free radicals, which cause DNA strand breaks.
Intercalates between base pairs. Inhibits topoisomerase II. Binds to double-stranded DNA.
Intercalates with DNA.
MOA Generates free radicals → single and double-stranded DNA breaks. Inhibits DNA-dependent RNA synthesis.
Cell cycle specific.
Cell cycle non-specific. Cell cycle non-specific.
Most specific for the G2 phase of the cell cycle
Hodgkin and Non-Hodgkin lymphoma, Breast cancer, soft tissue sarcoma, Endometrial Hodgkin and Non-Hodgkin lymphoma, Testicular cancer, Melanoma, Wilms tumor, Rhabdomyosarcoma,
Uses cancer, small cell and non-small cell Lung cancer, Ovarian cancer, Acute leukemias – Head and neck cancer, Skin cancer, germ cell cancer Choriocarcinoma, Kaposi’s sarcoma,
AML, ALL (especially Daunorubicin, Idarubicin for AML), Wilms tumor, Neuroblastoma Mitomycin: Superficial bladder, cancer, Gastric cancer, Breast cancer Gestational trophoblastic neoplasia
Pneumonitis, Pulmonary fibrosis,
Alopecia, Nausea, Vomiting, Dilated Cardiomyopathy, Congestive heart failure, Bone marrow suppression, Skin reactions,
SE Mucocutaneous reactions (blisters, hyperkeratosis), Alopecia,
red urine (Doxorubicin), myelosuppression Gastrointestinal irritation
Hypersensitivity, Fever and chills, hypotension
Notes • Rescue therapy is DEXRAZOXANE
MISCELLANEOUS ANTICANCER DRUGS
IMATINIB, DASATINIB, TRASTUZUMAB [B], BEVACIZUMAB [C],
NILOTINIB, CRIZOTINIB, PERTUZUMAB [D], SORAFENIB, SUNITINIB, CETUXIMAB, ERLOTINIB,
AFATINIB, NINTEDANIB, LAPATINIB [D] ALL-TRANS
PAZOPANIB, LENVATINIB PANITUMUMAB, GEFITINIB INTERFERON- ASPARAGINASE
Drug REGORAFENIB RITUXIMAB [C] RETINOIC ACID
NIMOTUZUMAB ALPHA [B] [C]
[X]
Brand: Gleevec Brand: Herceptin All are Preg Cat D except All are Preg Cat C All are Preg Cat D
All are Preg Cat D Bevacizumab
Substrate- Vitamin A
Class Tyrosine Kinase Inhibitors Monoclonal antibody EGFR TK Inhibitor Interferon
depleting enzyme derivative
Inhibits binding of VEGF to Binds to a surface Allows DNA
VEGFR leading to inhibition protein in NHL transcription and
of VEGF signaling. Inhibits Binds to EGFR and
Acts against breast cells. Induces Endogenous differentiation of
Inhibits tyrosine kinase activity tumor vascular inhibits Hydrolyzes
cancer cells that complement- Inhibits EGFR glycoproteins with immature
of the protein product of BCR- permeability but enhances downstream EGFR circulating L-
overexpress the HER- mediated lysis, tyrosine kinase → antineoplastic, leukemic
MOA ABL oncogene in CML. tumor blood flow and drug signaling, enhances asparaginase →
2/neu receptor for direct cytotoxicity inhibition of EGFR immunosuppressive promyelocytes
Inhibits c-kit tyrosine kinase in delivery. response to rapid inhibition of
epidermal growth and induction of signaling and antiviral into mature
GIST. chemotherapy and protein synthesis
factor BV: BeVacizumab for blood apoptosis actions granulocytes
radiotherapy
vessel. It inhibits (differentiation
angiogenesis! CD20 inhibitor therapy).
Colorectal cancer,
Hairy cell leukemia,
Metastatic colorectal head and neck
Chronic Myelogenous leukemia, Non-Hodgkin Non-small cell Chronic Acute Acute
Metastatic breast cancer, Breast cancer, Non- cancer (together
Uses Gastrointestinal stromal tumor lymphoma (low- lung cancer, myelogenous lymphoblastic promyelocytic
cancer small cell lung cancer, Renal with radiotherapy),
(GIST) grade) pancreatic cancer leukemia, T-cell leukemia leukemia
cancer non-small cell lung
lymphomas
cancer
Alopecia, Myalgia,
Nausea, Fever,
Depression, Flu-like
Nausea and vomiting, Hypertension, Infusion Hypersensitivity
Infusion reaction, Diarrhea, syndrome, Thyroid Retinoic acid
Chills, Fever, reactions, Arterial Hypersensitivity reactions, Acute
Diarrhea, Myalgia, Fluid skin rash, hypertension, skin dysfunction, syndrome
Headache, thrombosis, Impaired reactions, Bone Pancreatitis,
SE retention, Congestive heart hypomagnesemia, rash, anorexia, Hearing loss, Bone (dyspnea, fever,
Cardiotoxicity wound healing, marrow Increased risk of
failure, Drug interactions fatigue, interstitial interstitial lung marrow weight gain,
(congestive heart Gastrointestinal suppression bleeding, mental
lung disease disease suppression, peripheral edema)
failure) perforation, Proteinuria depression,
Neurologic
nephrotoxicity
dysfunction
• Interactions with other drugs • Lenvatinib acts a multiple • Contraindications • Only vitamin that
that depend on or affect the kinase inhibitor against include can cure cancer
cytochrome P450 system VEGFR1 to 3 kinases and autoimmune • Treat retinoic
Notes • Nintedanib is also used for is used for thyroid cancer disease, history of acid syndrome
Idiopathic Pulmonary Fibrosis cardiac with
arrhythmias and dexamethasone
pregnancy
MISCELLANEOUS ANTICANCER DRUGS
ERLOTINIB, GEFITINIB INTERFERON-ALPHA [B] ASPARAGINASE [C] ALL-TRANS RETINOIC ACID [X]
Drug
*All are Preg Cat D
Class EGFR TK Inhibitor Interferon Substrate-depleting enzyme Vitamin A derivative
Allows DNA transcription and differentiation of
Inhibits EGFR tyrosine kinase → inhibition Endogenous glycoproteins with antineoplastic, Hydrolyzes circulating L-asparaginase →
MOA immature leukemic promyelocytes into mature granulocytes
of EGFR signaling immunosuppressive and antiviral actions rapid inhibition of protein synthesis
(differentiation therapy).
Non-small cell lung cancer, Hairy cell leukemia, Chronic myelogenous leukemia,
Uses Acute lymphoblastic leukemia Acute promyelocytic leukemia
pancreatic cancer T-cell lymphomas
Alopecia, Myalgia, Depression, Flu-like syndrome, Nausea, Fever, Hypersensitivity reactions,
Diarrhea, hypertension, skin rash, Retinoic acid syndrome
SE Thyroid dysfunction, Hearing loss, Bone marrow Acute Pancreatitis, Increased risk of bleeding,
anorexia, interstitial lung disease (dyspnea, fever, weight gain, peripheral edema)
suppression, Neurologic dysfunction mental depression, nephrotoxicity
Contraindications include autoimmune disease, history Only vitamin that can cure cancer
Notes
of cardiac arrhythmias and pregnancy Treat retinoic acid syndrome with dexamethasone
HORMONAL ANTICANCER DRUGS

TAMOXIFEN, TOREMIFENE FLUTAMIDE, BICALUTAMIDE,
LEUPROLIDE [D], GONADORELIN [B],
Drug PREDNISONE [D] NILUTAMIDE ANASTROZOLE [X] ,LETROZOLE [D]
NAFARELIN [X]
All are Preg Cat D All are Preg Cat D
Selective Estrogen Receptor
Class Glucocorticoid Androgen antagonist GnRH analog Estrogen synthesis inhibitor
Modulator
Suppresses inflammation and immune Estrogen antagonist actions in breast Increased LH and FSH secretion with intermittent
Competitive antagonist at androgen Reduces estrogen synthesis by inhibiting
MOA response. May trigger apoptosis and tissue and CNS. Estrogen agonist administration. Reduced LH and FSH secretion
receptor aromatase
work on nondividing cancer cells. effects in uterus, liver and bone. with prolonged continuous administration.
Controlled ovarian hyperstimulation,
Chronic lymphocytic leukemia, Prostate cancer,
Uses Hormone-sensitive breast cancer Endometriosis, Myoma uteri, Precocious puberty, Breast cancer, Precocious puberty
Hodgkin’s lymphomas Surgical castration (nilutamide)
Prostate cancer
Adrenal suppression, Growth inhibition,
Hot flushes, Thromboembolism Hot flushes, Sweats, Headache, Osteoporosis,
Muscle wasting, Osteoporosis, Salt Gynecomastia, Hot flushes, Nausea, Diarrhea, Hot flushes, Bone and
SE (DVTs), Endometrial hyperplasia, Gynecomastia, Reduced libido, Decreased
retention, Glucose intolerance, Impotence, Hepatoxicity back pain, Dyspnea, Peripheral edema
Endometrial cancer hematocrit, Apoplexy, Blindness
Behavioral changes
• Prevents osteoporosis and decreases • Less hepatotoxicity with • Must be co-administered with flutamide to • Effective against breast cancers that
risk of atherosclerosis at the risk of bicalutamide and nilutamide prevent tumor flare-up on initiation of treatment have become resistant to tamoxifen
causing endometrial cancer • GnRH analogs (leuprolide) must be
Notes
co-administered with flutamide to
prevent acute flare-up of prostate
cancer
END OF PHARMACOLOGY – PHASE 0
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APPENDIX 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
To all my Topnotch babies, Always Remember this: With God NOTHING catholic schools. Of course, with the great help of some our relatives abroad,
IS IMPOSSIBLE (Luke 1:37) J they still persevered in sending us to private schools. That’s why I have always
considered myself a “scholar” since elementary. Because somebody else was
“The favors of the Lord are not exhausted, His mercies are not spent, they financing my education.
are renewed each morning, so great is His faithfulness” Lamentations
I could say that life was never easy when I was young. At the age of 6 I knew all
3:22-23
kinds of household chores: cooking, ironing clothes, sweeping the floor, doing
the laundry etc. I even remember being able to do a perfect “sinaing”, “sinangag”
“The one who began a good work among you will bring it to completion and sunny side up at the age of 6. I’m pretty sure that when it comes to
by the day of Jesus Christ” Philippians 1:6 “domestication”, I belong to the 99+ percentile of people my age. And for my
mother, that’s a great achievement. During that time, especially during summer,
“There is only one secure foundation: a genuine, deep relationship with we had to sell balot/penoy/chicharon, biskwit and ice candy around our
Jesus Christ, which you will carry through any and all turmoil. No matter neighborhood to help augment our parents’ income. We literally “lako” our
what storms are raging all around, you’ll stand firm if you stand on His products door-to-door. Some by coercion, some by virtue of mercy. Then, all the
love” Charles Stanley profit we will get will be used to pay our school expenses, or when times are
harder, to pay our Meralco bill. I can accurately remember what my notebooks
2 Tim 4:17 were, for they have the same design each and every year (for they were among
“But the Lord stood by me and strengthened me…” the cheapest)
Matt 6:25-34 Assignment ntbk: Lapu-Lapu (because this is ntbk number 1 and he is the very
“Therefore, I tell you, do not worry about your life, what you will eat or drink, first Filipino hero)
or about your body, what you will wear. Isn’t there more to life than food and Filipino ntbk: Apolinario Mabini (He looks very Filipino to me)
more to body than clothing? Look at the bird in the sky: They do not sow, or AP: Andres Bonifacio (for he was the bravest for me)
reap, or gather in barns, yet your heavenly Father feeds them. Aren’t you more Science: Jose Rizal (self-explanatory)
valuable than they are? And which of you by worrying can add even one hour to MAPE: Juan Luna (because he was an artist)
his life? Why do you worry about clothing? Think about how the flowers of the Math: the 3 martyrs (for they are more than 1)
filed grow; they do not work or spin. Yet I tell you that not even Solomon in all Etc etc etc
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, I even recycle them when there are still much of the paper left. Despite these
won’t He clothe you even more, you people or little faith? So then, do not worry boring ntbk designs, I still feel blessed that I was never forced by mama to get
saying “What will we eat?” or “What will we wear?” For the uncoverted pursue Jolina, Stefano Mori or Magic Temple ntbks. If you know what I mean J
these things, and your heavenly Father knows that you need them. But above
all, pursue His kingdom and righteousness, and all these things will be given to When I was in grade 4, my papa lost his job. That was certainly one of the
you as well. So then do not worry about tomorrow, for tomorrow will worry greatest challenge my family had ever experienced. There were many nights
about itself. Today has enough trouble of its own. that we did not have electricity, we had only 1 nilagang manok (as in without
vegetables, just plain boiled chicken) for Noche Buena of 1998, our ulam was
Jeremiah 20:11 always adobong kangkong and dilis and we had to do extra work as students.
“But the Lord is with me to help me like an awe-inspiring warrior. Therefore During weekends, our whole family worked for the printing press company of
those who persecute me will fail and will not prevail over me. They will be one of mama’s friends. At school, my sister and I would go around the campus
thoroughly disgraced because they did not succeed. Their disgrace will never be to get tin cans (to be sold to junk shops) and get soft drink bottles to get their
forgotten. “deposit” (which was Php2) from the cafeteria. This is why I always bring two
bags with me. One for my school stuff and the other for my loot. Every day I
John 6:20 would volunteer to become the cleaner in our class, for I will get all the tin cans
“But He said to them, “It is I. Do not be afraid” and plastics from our trash can so that I can bring them home. I didn’t have
complete books then. It was only during the third quarter of the year that I had
Matt 11:28-30 a complete set of books. Because my teachers decided to give me a copy of the
“Come to me, all you who are weary and burdened and I will give you rest. Take book out of their own salary. I must say, my elementary teachers were kind to
my yoke on you and learn from me, because I am gentle and humble in heart, me, and had always faith in me. They also collect tin cans and plastics for me.
and you will find rest for your souls. For my yoke is easy to bear, and my load is That went on for 2yrs. I just study hard. I still manage to be at the top of our
not hard to carry. class despite having to “work” and study at the same time. I knew I had to help
my parents, the turo-turo/karinderya business they put up from papa’s
Feast Declaration of Abundance: Novena to God’s Love separation pay was doing ok, but the profit is not enough to meet all our needs,
considering that I still have a baby brother during that time. Until finally,
Today, I receive all of God’s love for me. graduation came. My father found a new (and stable) job and I was admitted to
Today, I open myself to the unbounded, limitless, a science high school (which means free tuition for me Yayyyy!).
overflowing abundance of God’s universe.
Today, I open myself to God’s blessings, healing and I believe that getting into a science high school was my gateway for everything,
miracles. and believe me, it is during high school that my teaching career started. I started
teaching at the age of 12. Well, probably earlier since I was teaching "drama"
Today, I open myself to God’s word so that I become more classes (imagining I was Judy Ann Santos) and ABCs and 1-2-3s to my neighbors.
like Jesus every day. I also did substitute teaching for a class of grade2 students when I was in grade
Today I proclaim that I’m God’s Beloved, I’m God’s Servant, 3 when my aunt was not able to attend to her class. For the record, I came from
I’m God’s Powerful Champion, a family of teachers. My grandparents are teachers, my mother is a teacher, my
And because I am blessed, I am blessing the world, In Jesus’ sister is a teacher and many of my aunts, uncles and cousins are teachers. That
could probably explain it. My first tutoring stint was in June year 2000. I went
Name. AMEN to my Alma Mater St. Mary's College QC to pay some of my favorite teachers a
visit. Little did I know that my "teaching career" will start there. My English
Keep believing God for it! Praying for all of you J teacher Ms Cecilia Asejo recommended me to one of her student's parents as a
- Doc Yns Pereyra-Borlongan J <3 personal tutor in preparation for her Science High School entrance exam. I was
in my first year at Quezon City Science High School back then. I accepted the
"Job Offer" without second thoughts. I knew I needed the job. After my classes
I know that I will never get the chance to say a valedictory speech, or get to give at 4-5pm, I would assist for a while in the English Center as a student assistant.
an opening remark in any kind of school affair, for I was never a “stellar” student Checking my batchmates’ quizzes, cleaning the English center or reading my
hahaha. But let me share with you my story, that hopefully, will inspire you a bit crush's English journal (hehe). After that, I would walk to Teacher's Village (just
J in front of SM Annex) to go to my "tutee". My salary then was only Php50/hr, of
course with free meryenda, dinner and pabaon from tita Letty and Jessica. After
I came from a poor but hardworking family. My papa worked in Saudi as a around 2-3hours of tutorial, I would then head home, feeling so excited to hand
machine operator while my mother used to sell “isaw-isaw” when I was born. I that Php150 to mama for her to buy us dinner the next day. While my salary as
could say that mama had delicate pregnancies, for I was born premature and student assistant I use for my everyday expenses at school.
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 My parents' friends learned that I was doing tutorials, so they started to hire me
funds to provide for my sisters’ hospitalization, mama had to appear on national as well, increasing my salary to Php150/hr. During those times, that little
television asking for financial aid for my sister. She was so happy when she money meant so much to me. It made me feel relieved knowing that I am helping
finally had the needed resources to pay for my sister’s operation. Unfortunately, my parents in earning money and not add to their financial responsibilities. My
she died before her scheduled surgery. My mother then donated the funds to brother and sister were also studying already, I knew my parents would get any
another child who had hydrocephalus. These stories that my mother told me kind of help they could have grip on. The tutorials continued, having tutorial
were major motivators for me to become a doctor. classes all days of the week. It was tough, I must admit. It took away so much
time from me. I have less time for studying. I have less time for rest. I have less
Even though both my parents came from poor families themselves, they have time for other things I would like to pursue. I also have to sell food (Samosa,
always believed in one important thing: that good education is the only Karyoka, Siomai etc) to my classmates and teachers everyday to further
inheritance they could ever give to us. I’m sure this will sound cliché to you. But increase my income. I was the student council president. I was active in the
I myself strongly adhere to this belief, and will surely apply this principle when church choir, I would attend our weekly practices and sing my best for The Lord
TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY MAIN DIGITAL HANDOUT BY PEREYRA-BORLONGAN RPh, MD-MBA. Appendix Page 1
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
equipment to buy) and have more money to give to my parents. I even masseur. I am planning to send more students to school, and will definitely
remember giving baon to my siblings and using my savings to pay for their sponsor a medical student in the future. And currently, as a medical resident in
tuition fee. During those times, I keep thanking God that He provided for my a public hospital, God is also using me to help poor patients not only by giving
family. We may not be living luxuriously, but God always provided enough, and them the medical care they need, but also by providing them food, toiletries,
on time. I also praise Him for keeping my family together, despite the fact that medicines not available in our pharmacy, even their fare back to their provinces
mama was already working as an OFW. I was a scholar of the QC SYDP (as far as Visayas and Mindanao). These things, for me, are insignificant to the
(Scholarship Youth Development Program), so I do not need to pay any tuition amount of blessing God has bestowed upon my life. I am just paying it forward,
fee during college. This, again, was big blessing to our family. God was very good to people who needs it most. And as I continue living my life for the Lord, may I
to us. 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
I still did student assistant duties, now at UPCP library (my salary was bless you more! J
Ph25/hour which was very small hahaha. But I kept doing it, since I get to
borrow all needed books from the library since I don’t have my own book. Also, Doc Yns Pereyra-Borlongan J
we did not have any computer at home. So I would do overtime job at the lib to
do some typing and printing for free yey! Or I would go on overnight at my
bestfriend’s house to type on her computer). Still sold food to my classmates,
but of course with an upgrade! I now sell palabok, pancit and spaghetti which I
get from my friendly neighborhood cook. And sitsirya from Divisoria (hahaha).
This cycle continued even until I was in med school.
I was accepted into the Ateneo School of Medicine and Public health (ASMPH)
also as a scholar. Maybe my life story was so interesting to my panel of
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
in a private school. But I had so much blessings then! I got a Neo Laptop that
was gifted to me by my Tita Sarah (I used until I was in Topnotch hahaha
imagine teaching with a laptop that would turn off when the charger was pulled
out of the socket hahaha). I always have MRT ticket load and get to go home
together with my papa some days of the week (He used to work in Ortigas). I
would usually walk from ASMPH to Ortigas MRT station to save up on money
and to lose some weight (hahaha). I would get free siomai from papa at the MRT
station. That’s why I love going home with papa. And until now, even if he was
already gone, I would eat the same siomai when I’m at the Ortigas MRT station.
I was still doing tutorial (but now only on weekends and Friday nights since
HAPPY ARAL PO DOCTORS! J <3 - Matty, Peanut and Summer <3
Med School was more demanding) and still sold food (with the addition of
cellphone load ahahaha) so that I won’t have to ask money from my parents. I
even have my own corner at our clasroom where I leave my “honesty” store
(which my batchmates would call as “Cantyña”). I also learned how to bake! I
was also selling cakes and cupcakes to my schoolmates and to consultants at Giving back
The Medical City. I also ventured into selling pasta (red sauce, white sauce, Not one to forget his humble beginnings, Romy has made conscious
lasagna, pesto etc). I bring around 30packs of pasts to school which I sold at efforts to “give back. Aside from his medical practice, Romy, also known as
TMC (believe me, they are always sold out), while I have a staff that sold them “Dr. RA,” also dutifully served in the academe, working as a teacher,
at the canteen where my sister works (She was already an English teacher back professor, and even administrator at the De La Salle Health Sciences
then). I think I also have “sales” and business skills running in my genes. I also Institute for 27 years.
did market research interview sessions to earn Php2,000-3,000 per session (I
The well-loved Dr. RA has touched the lives of many — co-workers,
will just pretend to be rich and part of the class A of the society so I can get the
students and many young Lasallian scholars. He has also helped the
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
children of his own staff in pursuit of a medical degree.
planned on applying some short course TESDA subjects to improve my skills, For years, his home and his extensive medicine library were open to
hahaha which I never had the time to do. scholars. His clinic always reportedly has the longest queue of patients of
all ages at the De La Salle University Medical Center.
But you know, God had an even brighter and better plan for me. I reviewed for Dr. RA was instrumental in the construction of the DLSHSI library. “I
my Pharmacy board exam with the hope that I would top the exam. It was tough, know how important a library is especially for poor students. Throughout
juggling studying, tutoring and doing MBA internship at the same time. I wasn't my years of studying, I survived because of the kind librarians who were
able to attend all the classes and never had the opportunity to take any drills, lenient when it came to my borrowing of books because they knew I didn’t
comprehensive exam or the pre-board exam. I was doing everything I can so have the money to buy my own copies,” said Dr. RA.
that when I top the boards, the owner of the review center would hire me to be De La Salle Health Sciences Institute now has the Romeo P. Ariniego, M.D.
a lecturer. With God's perfect will, I was 0.03 short of getting into the top10. I Library, which houses major resources from around the world, and serves
felt devastated. I felt my dream of becoming a lecturer melt away. But I knew as a converging point for students, faculty and researchers who all share
that God did this on purpose. He had the best plan for me in mind. I still felt Dr. RA’s love for learning.
thankful that He made me pass the boards. I sent a message to one of the owners
La Salle’s Brother Gus Boquer once shared Dr. RA’s inspiring story,
(who is also my teacher at the review center) to thank Him for teaching us and
which Dr. Willie Ong wrote about in his column in The STAR.
in case He needs any assistance in anything, I am just one message away.
“I believe doctors are doing God’s work. The way they help the sick and
Sometime in August 2010 one of the staff of the review center called me. He said put a smile on a poor patient never fails to amaze me. We have a doctor
that my teacher was asking me to make the module 1 exam for the upcoming here in De La Salle, Dr. Romeo P. Ariniego, who has pledged to give his life’s
review season. When I ended the phone call, I cried. And I cried a lot. I did not earnings to De La Salle. He has already given P10 million for a new library.
imagine that God would work this way. I was contacted by the review center to And he has already donated his house and lot to De La Salle Institute, which
make exams for them, and yes, I was still given a chance to become a lecturer. I will take effect after he passes away. How can you not be amazed by
felt so thankful to God, that indeed, he answers our prayers. God is indeed doctors like this?”
faithful! He is the one who planted dreams and aspirations in my heart, and I am The poor boy from Vigan had a dream and attained it. And now his
certain that each one of them would come true, according to His perfect will. dream is to be able to let others live their dreams, too.
And so, I started teaching at Manor Review Center. At first, I was only asked to
make exams and discuss the rationale to the students. But later, one of the
owners also asked me to teach his subject because he could not make it to the
assigned dates. I was very nervous. It was my first time to teach a class of 200+
people (except of course for NSTP hehe), and I would be teaching Microbiology
for 3 days. I prayed and prepared well for the lecture, thinking that I was doing
it for God and to live up to my boss' expectation. The lecture ended. I was given
a good feedback. I was congratulated by the owners and my teaching career at
Manor already started. I was given more teaching load, now teaching other
subjects such as Organic Medicinal Chemistry, Dosage Forms, Clinical and
Hospital Pharmacy, Pharmacognosy, and the longest and probably the most
TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY MAIN DIGITAL HANDOUT BY PEREYRA-BORLONGAN RPh, MD-MBA. Appendix Page 2
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INSTRUCTIONS
For those who have printed the initial handout: • On atropine, Page 12
Please use this handout as a guide to correct the initial handout. Drugs ATROPINE [C]
Page guides are available to assist you in doing so. MOA Competitively blocks ALL muscarinic receptors
• Mydriatic, cycloplegic
• Antidote for organophosphate poisoning (1st choice)
PHARMACOLOGY – PHASE 0 • Bradycardia, Hypersalivation, Decrease airway
Uses secretion during general anesthesia
CORRECTIONS Co-administered with nondepolarizing NMJ blockers, to
By Yns Pereyra-Borlongan, MD counteract the bradycardia associated with giving an
indirect acting cholinomimetic
Sympathetic effects plus hyperthermia, flushing,
• On steady state, Page 5 SE
delirium, sedation
STEADY STATE
• condition in which the average total amount of drug in the body NON-SELECTIVE
does not change over multiple dosing intervals Drug ATROPINE [C], Homatropine [C], Cyclopentolate [C],
• rate of drug administration equals the rate of elimination Tropicamide [C]
• Reached in 3-4 half-lives of the drug Competitively blocks ALL muscarinic
MOA
receptors
• On pilocarpine, Page 11 and Page 17 • Mydriatic, cycloplegic
NON-SELECTIVE M3 SELECTIVE C = Cycloplegia = Ciliary muscle paralysis = loss of
accommodation
PILOCARPINE [C], • Antidote for organophosphate poisoning (first
Drugs BETHANECHOL [C], Cevimeline [C] Uses
choice)
CARBACHOL Pilocarpine can agonize M1-M3, but
• Bradycardia
does more so extensively at M3.
Dr. Pereyra-Borlongan • Hypersalivation, Decrease airway secretion during
general anesthesia
DRUG CLASS EXAMPLES MECHANISM Sympathetic effects plus hyperthermia,
Timolol, SE flushing, delirium, sedation, “Sandy eyes” (Dry eyes
Levobunolol, due to reduced lacrimal secretion)
Carteolol,
Beta • On midodrine, Page 15
Metipranolol,
antagonists
(nonselective), Drug ALPHA-1 AGONISTS PHENYLEPHRINE [C], etc
Decreased
Betaxolol (b1 • Ocular administration causes mydriasis WITHOUT
production of
selective) cycloplegia; also used intranasally to produce local
aqueous humor from
Osmotic agents Mannitol vasoconstriction as a decongestant
ciliary epithelium
Brimonidine, • Avoid Pseudoephedrine in the 1st trimester because it
a2 agonists
Apraclonidine Notes may be associated with possible risk of gastroschisis
Carbonic • Midodrine: used for the treatment of orthostatic
Acetazolamide,
anhydrase hypotension
Dorzolamide
inhibitors • High doses may cause Alpha-1 agonist overdose
Pilocarpine o DOC: Phentolamine (adrenergic blocker)
(Selective Ciliary muscle
muscarinic agonist), contraction, opening
• Table headers for page 86
Cholinomimetics Physostigmine & of trabecular
Echothiopate meshwork →
(Acetylcholinesterase Increased outflow
inhibitor)
Increased outflow
Prostaglandin Latanoprost,
via
analogue Brimatoprost
canal of Schlemm
Non selective a Increased outflow
Epinephrine
agonists via uveoscleral veins
END OF PHARMACOLOGY – PHASE 0 CORRECTIONS
TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY PHASE 0 CORRECTION HANDOUT BY DR. YNS PEREYRA-BORLONGAN Page 1 of 1
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TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY PHASE 2 HANDOUT BY DR CALDERON JR. and DR. LOPEZ
Important Legal Information

The handouts, videos and other review materials, provided by Topnotch Medical Board Which of the following statements is most correct
Preparation Incorporated are duly protected by RA 8293 otherwise known as the regarding beta blocking agents?
Intellectual Property Code of the Philippines, and shall only be for the sole use of the person: A. Esmolol’s pharmacokinetics are compatible
a) whose name appear on the handout or review material, b) person subscribed to Topnotch
Medical Board Preparation Incorporated Program or c) is the recipient of this electronic with chronic topical use
communication. No part of the handout, video or other review material may be reproduced, B. Metoprolol blocks β2 receptors selectively
shared, sold and distributed through any printed form, audio or video recording, electronic 4.
medium or machine-readable form, in whole or in part without the written consent of C. Nadolol lacks β2-blocking action
Topnotch Medical Board Preparation Incorporated. Any violation and or infringement, D. Pindolol is a β antagonist with high
whether intended or otherwise shall be subject to legal action and prosecution to the full membrane-stabilizing (local anesthetic)
extent guaranteed by law.
activity
E. Timolol lacks the local anesthetic effects
DISCLOSURE A 25-year-old hypertensive female wishes to
responsibility of the person, whose name appears therein, that the handouts/review become pregnant. Her physician informs her that
materials are not photocopied or in any way reproduced, shared or lent to any person or she will have to switch to another antihypertensive
disposed in any manner. Any handout/review material found in the possession of another
drug. Which of the following drugs is absolutely
8293. Topnotch review materials are updated every six (6) months based on the current contraindicated in pregnancy?
trends and feedback. Please buy all recommended review books and other materials listed 5.
A. Atenolol
below.
THIS HANDOUT IS NOT FOR SALE! B. Captopril
C. Methyldopa
D. Prazosin
REMINDERS E. Propranolol
For Phase 2:
1. Finish the Phase 0 handout and Phase 1 video before proceeding to the
A 73-year-old man with an inadequate response to
Phase 2 handout and video. other drugs is to receive digoxin for heart failure.
2. Phase 2 handouts are based on commonly used review books and Which of the following is the best documented
previous question feedback from students. mechanism of beneficial action of cardiac
2. Answer the Pre-Test (Guide Questions) first prior to watching the video glycosides?
lectures. A. A decrease in calcium uptake by the
3. The guided content of the video lectures are in the 2nd part of the Phase 6.
sarcoplasmic reticulum
2 handouts and are meant to complement the video lecture. B. An increase in ATP synthesis
C. A modification of the actin molecule
This handout is only valid for the September 2021 PLE batch. D. An increase in systolic cytoplasmic calcium
This will be rendered obsolete for the next batch levels
since we update our handouts regularly. E. A block of cardiac β adrenoceptors
Chronic heart failure is commonly treated with a
combination of drugs that both improve symptoms
PHARMACOLOGY – PHASE 2 and provide long-term benefits. Three drugs or drug
groups that have been shown in clinical trials to
By Eric Eusebio Calderon Jr., MD provide benefits in patients with chronic heart
Julianne Lopez, MD-MBA, DPBA failure are
7. A. ACE inhibitors, carvedilol, and spironolactone
Which statement about the distribution of drugs to B. Alpha1-selective antagonists, digoxin, and
specific tissues is most correct? hydrochlorothiazide
A. Distribution to an organ is independent of C. Digoxin, β-agonists, and nitroglycerin
blood flow D. Dobutamine, propranolol, and furosemide
B. Distribution is independent of the solubility of E. Verapamil, isosorbide dinitrate, and
the drug in that tissue furosemide
1. C. Distribution depends on the unbound drug A 60-year-old woman has been admitted to the
concentration gradient between blood and the coronary care unit with a left ventricular
tissue myocardial infarction. She develops acute severe
D. Distribution is increased for drugs that are heart failure with marked pulmonary edema with
strongly bound to plasma proteins rales but no evidence of peripheral edema or weight
E. Distribution has no effect on the half-life of the gain. Which one of the following drugs would be
8.
drug most useful?
Drug metabolism in humans usually results in a A. Digoxin
product that is B. Furosemide
A. Less lipid soluble than the original drug C. Minoxidil
B. More likely to distribute intracellularly D. Propranolol
2. E. Spironolactone
C. More likely to be reabsorbed in the kidney
tubules Which one of the following drugs binds bile acids in
D. More lipid soluble than the original drug the intestine, thus preventing their return to the
E. Less water soluble than the original liver via the enterohepatic circulation?
A 30-year-old man is admitted to the emergency A. Niacin
9.
department after taking a suicidal overdose of B. Fenofibrate
reserpine. His blood pressure is 50/0 mm Hg and C. Simvastatin
heart rate is 40 bpm. Which of the following would D. Cholestyramine
be the most effective cardiovascular stimulant? E. Ezetimibe
3. The patient started on gemfibrozil. What is the
A. Amphetamine
B. Clonidine major mechanism of action of this drug?
C. Cocaine A. ↑ excretion of bile acid salts
D. Norepinephrine 10. B. ↑expression of high-affinity LDL receptors
E. Tyramine C. ↑ secretion of VLDL by the liver
D. ↑ triglyceride hydrolysis by lipoprotein lipase
E. ↓ uptake of dietary cholesterol
TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY PHASE 2 HANDOUT BY DR CALDERON JR. and DR. LOPEZ Page 1 of 13
An elderly man is brought to the emergency
After being counseled about lifestyle and dietary department 30 min after the onset of right-sided
changes, the patient was started on atorvastatin. weakness and aphasia (difficulty speaking).
During his treatment with atorvastatin, it is Imaging studies ruled out cerebral hemorrhage as
important to routinely monitor serum the cause of his acute symptoms of stroke. Over the
concentrations of which of the following? next 2 days, the patient’s symptoms resolved
11.
A. Blood Urea Nitrogen completely. To prevent a recurrence of this disease,
17.
B. Alanine and Aspartate Aminotransferase the patient is most likely to be treated indefinitely
C. Platelets with which of the following?
D. RBC A. Aminocaproic acid
E. Uric acid B. Aspirin
A patient with an incurable cancer is suffering from C. Enoxaparin
pain that is gradually increasing in intensity and D. Lepirudin
levorphanol (a strong μ-receptor agonist) is E. Warfarin
prescribed. With chronic use of the drug, tolerance Which of the following is the most appropriate drug
is not likely to develop to constipation or to for immediate treatment of this acute attack of gout?
12.
A. Euphoria A. Allopurinol
B. Nausea and vomiting 18. B. Indomethacin
C. Pupillary constriction C. Methotrexate
D. Sedation D. Morphine
E. Urinary retention E. Probenecid
A 25 year old medical student has episodes of Co-administered to a patient being treated with
excessive sleepiness and with times of hyperactivity azathioprine, which drug will result in severe
for the past 4 weeks. He was encountering such hematotoxicity?
difficulties on his medical school life adjusting to A. Allopurinol
19.
some environmental changes from his typical used B. Cholestyramine
to collegiate life. He manifests excessive talking, C. Digoxin
oriented too much to sexual activities, and D. Lithium
13. uncontrolled impulsivity in buying stuffs. Which of E. Theophylline
the following drugs is the most appropriate initial A sexually active woman presents with left lower
pharmacologic treatment for his anxiety? quadrant abdominal pain and a purulent vaginal
A. Carbamazepine discharge that, on Gram stain, revealed gram-
B. Haloperidol negative rods. What drug combination will have an
C. Lamotrigine adequate empiric coverage of the organisms
D. Lithium 20. involved?
E. Sertraline A. Azithromycin
14-16. A homeless middle-aged male patient presents in B. Ceftriaxone + Doxycycline
the emergency department in a state of intoxication. You C. Metronidazole
note that he is behaviorally disinhibited and rowdy. He D. Norfloxacin + Ampicillin
tells you that he has recently consumed about a pint of a E. Trimethoprim + Sulfamethoxazole
red-colored liquid that his friends were using to “get high.” A 25 year-old lady is taking metronidazole for a
He complains that his vision is blurred and that it is “like vaginal infection. Which of the following will you
being in a snowstorm.” His breath smells a bit like advice her while she is on treatment?
formaldehyde. He is acidotic. 21. A. Do not drink wine while you are on treatment.
Which of the following is the most likely cause of the B. You may take it with phenobarbital.
intoxicated state of the patient? C. Avoid taking cimetidine.
A. Ethanol D. Do not worry, the drug has no side effects.
14. B. Ethylene glycol 22-23. A patient with AIDS has a CD4 count of 45/ul. He is
C. Isopropanol being maintained on a 3-drug regimen of indinavir,
D. Hexane didanosine and zidovudine.
E. Methanol For prophylaxis against opportunistic infections, he is also
After assessing and stabilizing the patient’s airway, receiving ganciclovir, fluconazole, rifabutin and
respiration, and circulatory status, fomepizole was trimethoprim-sulfamethoxazole.
administered intravenously. Which of the following The drug most likely to suppress herpetic infections
most accurately describes the therapeutic purpose and provide prophylaxis against CMV retinitis in
of the fomepizole administration? this patient is
A. Accelerate the rate of elimination of the toxic A. Fluconazole
15. 22.
liquid consumed B. Ganciclovir
B. To combat acidosis C. Indinavir
C. To inhibit the metabolic production of the D. Rifabutin
toxic metabolite E. Trimethoprim-sulfamethoxazole
D. To prevent alcohol withdrawal seizure The dose of indinavir may need to be increased
E. To sedate the patient above normal this is because
The regular ingestion of moderate or heavy amount A. Fluconazole slows gastric emptying
of alcohol predisposes to hepatic damage after B. Ganciclovir increases the renal clearance of
overdose of acetaminophen because of chronic indinavir
23.
ethanol ingestion C. Indinavir has to be taken with meals
A. Blocks acetaminophen metabolism D. Rifabutin increases liver drug-metabolizing
16.
B. Causes thiamine deficiency enzymes
C. Displaces acetaminophen from plasma E. Sulfamethoxazole displaces indinavir from
proteins plasma proteins
D. Induces liver metabolizing enzymes
E. Inhibits renal clearance of acetaminophen
A young girl was brought to you for vulvar and Which of the following is a correct application of the
perianal itching most pronounced at night. You drug mentioned?
suspect that she has a worm infestation. A scotch A. Ergonovine – Alzheimer’s disease
tape test which revealed D-shaped eggs. 33. B. Cetirizine – Hay fever
24. A. Praziquantel C. Alosetron – obstetric hemorrhage
B. Pyrantel Pamoate D. Ondansetron - Migraine
C. Iodoquinol E. Ranitidine – Parkinson’s disease
D. Metronidazole Which of the following receptors, when
E. Ivermectin antagonized, is responsible for addressing BOTH
What chemotherapeutic drug is strongly associated positive and negative symptoms of schizophrenia?
with hemorrhagic cystitis? 34. A. D2
A. Cyclophosphamide B. H1
25. B. Doxorubicin C. Alpha 1
C. Fluorouracil D. 5HT2a
D. Methotrexate Which of the following antipsychotic drugs has a
E. Tamoxifen high affinity for 5-HT2 receptors, does not cause
Baby C, a 5 year old boy was brought to the pediatric EPS, and is reported to increase risk of significant
ER after ingesting 100 ml of diphenhydramine prolonged QT prolongation?
syrup. Diphenhydramine is a weak base with a pKa A. Chlorpromazine
35.
of 8.8. Which of the following statements about this B. Ziprasidone
case of overdose is correct? C. Clozapine
A. Accelerate urinary excretion by giving an D. Olanzapine
26.
acidifying agent E. Risperidone
B. Do stat hemodialysis. F. Haloperidol
C. Accelerate urinary excretion by giving an This particular antiglaucoma drug acts by ciliary
alkalinizing agent muscle contraction which will lead to opening up
D. More of the drug would be ionized at a blood the trabecular meshwork which will lead to
pH (7) than at stomach pH (2) increased outflow, relieving eye pressure
36.
Which of the following drugs that is known to be A. Pilocarpine
useful for the treatment of hypercalcemia in Paget’s B. Physostigmine
disease has the side effect of causing jaw necrosis at C. Echothiopate
higher doses? D. ALL OF THE ABOVE
27.
A. Magnesium Brimatoprost is an anti-glaucoma medication that
B. Teriparatide works by the following mechanism of action:
C. Raloxifene A. Increases aqueous humor outflow via the
D. Pamidronate canal of Schlemm
A 56 year old man with oat cell carcinoma of the lung B. Increases aqueous humor outflow via
37.
is admitted to the hospital after having grand mal uveoscleral veins
seizures. Laboratory studies reveal the following C. Increases aqueous humor outflow via ciliary
information: muscle contraction
Na: 110 mEq/L D. Decreases aqueous humor production from
serum Osmolarity: 225 mOsm/L ciliary epithelium
28. Urine Osmolarity: 650 mOsm/L. Which statement about the drug SOTALOL is
INCORRECT?
What treatment is appropriate for this patient? A. It is a GROUP 2 anti-arrhythmic
A. Mecasermin 38. B. It is a GROUP 3 anti-arrhythmic
B. Conivaptan C. It is a K channel blocker
C. Octreotide D. It is a Beta blocker
D. Desmopressin E. None of the statements are incorrect
Which of the following drugs is best given for What is the drug of choice for the management of
premenopausal POST Modified radical mastectomy atropine toxicity?
women? A. Pralidoxime
39.
A. Anastrozole B. Echothiophate
29.
B. Raloxifene C. Glucagon
C. Danazol D. Physostigmine
D. Tamoxifen Which of the following drug/s is/are used for the
E. Clomiphene closure of ductus arteriosus in preterm infants?
Which of the following drugs is used for the A. Indomethacin
40.
treatment of acromegaly? B. Ibuprofen
A. Pegvisomant C. Naproxen
30.
B. Somatropin D. ALL of the above
C. Mecasermin Which of the following symptoms can be addressed
D. Conivaptan by pralidoxime but not by atropine in a case of
What is the ovulation induction method of choice for organophosphate poisoning?
women with PCOS? 41. A. Miosis
A. Danazol B. Bronchoconstriction
31.
B. Goserelin C. Diarrhea
C. Ganirelix D. Respiratory paralysis
D. Clomiphene
Pair the correct opioid receptor and action for the
drug LOPERAMIDE
A. Mu receptor - antagonist
B. Μu receptor - agonist
32.
C. Delta receptor – antagonist
D. Delta receptor – agonist
E. Kappa receptor – antagonist
F. Kappa receptor - agonist
Which of the following best describes the RATIONALE
mechanism of action of benzodiazepines?
A. Stimulate release of GABA from nerve endings
in the brain Which statement about the distribution of drugs to
B. Inhibit GABA transaminase to increase brain specific tissues is most correct?
42. levels of GABA A. Distribution to an organ is independent of
C. Activate GABA-B receptors in the spinal cord blood flow
D. Increase frequency of opening of chloride ion B. Distribution is independent of the solubility of
channels that are coupled to GABA-A receptors the drug in that tissue
E. Block glutamate receptors in the neuronal 1. C. Distribution depends on the unbound drug
pathways in the brain concentration gradient between blood and
the tissue
Which calcium channel blocker is useful for
D. Distribution is increased for drugs that are
preventing cerebral vasospasm in patients with
strongly bound to plasma proteins
subarachnoid hemorrhage?
E. Distribution has no effect on the half-life of the
A. Amlodipine
43. drug
B. Nifedipine
C. Diltiazem
D. Verapamil
E. Nimodipine
Which of the following symptoms is an expected side
effect of your antidiabetic drug dipeptidyl peptidase
4 (DPP-4) inhibitors?
44. A. Nasopharyngitis
B. Diarrhea
C. Nausea
D. Lactic acidosis
Which of the following antidiabetic drug is the
LEAST likely to cause hypoglycemia?
A. Insulin
45.
B. Metformin
C. Glyburide
D. Repaglinide
What is the mechanism of action of dicycloverine, an
antispasmodic medication used for the treatment of
irritable bowel syndrome? • Plasma volume (3 liters)
46. A. Chloride channel activator • Blood volume (5 liters)
B. 5HT3 antagonist • Extracellular fluid (12-14 liters)
C. Muscarinic antagonist • Total Body Water (40-42 liters)
D. D2 antagonist
Which gastrointestinal agent is used for the DISTRIBUTION
treatment of peptic ulcer disease by creating a • systemic circulationàORGAN and TISSUE
viscous sticky polymer over ulcers to accelerate • Plenty of drugs bind to plasma protein (albumin) with a balance
healing? between bound and free molecule
47.
A. Hyoscyamine • DRUG + PROTEIN (active, free)àCOMPLEX (inactive, bound)
B. Erythromycin • COMPETITION BETWEEN DRUGS FOR PROTEIN BINDING
C. Misoprostol • E.g. Sulfonamides and bilirubin in neonatesà
D. Sucralfate Hyperbilirubinemiaà Kernicterus
Which of the following anti TB drugs cause • Warfarin and sulfonamides-àdisplacement of Warfarin-à
peripheral neuropathy? increase free Warfarin
A. Pyrazinamide
48.
B. Isoniazid UNIQUE BARRIERS TO DISTRIBUTION
C. Ethambutol
• Placental Barrier
D. Rifampicin
o Most low molecular weight medicines cross the placenta
If ketamine is used as a sole anesthetic to manage o E.g. lithium + , PTU vs. Methimazole, ethanol +, Heparin vs.
suturing of a 2 cm arm laceration of a 7 year old Warfarin
child, its actions will include o CRITERIA FOR SAFER DRUGS IN PREGNANCY: water
A. Respiratory depression soluble, large molecule and highly protein-bound
49.
B. Bradycardia
• Blood Brain Barrier
C. Hypotension
o Permeable only to lipid soluble or low molecular weight drugs
D. Analgesia
o Example: Lithium +, ethanol +, Levodopa and Dopamine
E. Bronchoconstriction
What is the mechanism of action of the drug Drug metabolism in humans usually results in a
tamsulosin, used for the treatment of hypertension product that is
and benign prostatic hyperplasia? A. Less lipid soluble than the original drug
50. A. Alpha 1 agonist B. More likely to distribute intracellularly
2.
B. Alpha 1 antagonist C. More likely to be reabsorbed in the kidney
C. Alpha 2 agonist tubules
D. Alpha 2 antagonist D. More lipid soluble than the original drug
E. Less water soluble than the original
BIOTRANSFORMATION
• less lipid- soluble
• more water-soluble and more readily excreted
BIOTRANSFORMATION: PHASE I METABOLISM (REDUCTION,
OXIDATION AND HYDROLYSIS)
• Microsomal metabolism
• CYP450
o Localized in SER and have absolute requirement for
molecular oxygen and NADPH
BIOTRANSFORMATION: PHASE I METABOLISM (REDUCTION, BETABLOCKERS
OXIDATION AND HYDROLYSIS) ß-Blocker Subgroup,
1. Hydrolysis Examples
Features
o Example: local anesthetics Propranolol and timolol are typical;
o Clinical Correlation: Patient with deficient Nonselective
block both ß1 and ß2
Pseuodocholinesterases will have an increase level of Atenolol, acebutolol, and metoprolol
Succinylcholine-à prolonged MUSCLE RELAXATION ß1-selective are typical; possibly less hazardous
2. Monoamine oxidases in asthmatic patients
o Amine NEUROTRANSMITTERS Acebutolol and pindolol are typical;
o Endogenous: Dopamine, NE and 5HT Partial agonist possibly less hazardous in asthmatic
o Exogenous: Tyramine patients
3. Alcohol metabolism (Non-microsomal) Lacking local Timolol is the prototype; important
o AlcoholàAldehyde-àAcetate anesthetic effect for use in glaucoma
Atenolol is the prototype; may
BIOTRANSFORMATION: PHASE II METABOLISM Low lipid solubility
reduce CNS toxicity
(METHYLATION, GLUCURONIDATION, ACETYLATION,
Esmolol (an ester) is the shortest
SULFATION) Very short and long
acting and used only IV; nadolol is
1. Glucuronidation acting
the longest acting
o Key enzyme: TRANSFERASES
Combined ß and a
o Examples: Morphine and Chloramphenicol Carvedilol, labetalol
blockade
o Clinical correlation: Source: Katzung Basic and Clinical Pharmacology 14th edition
§ Gray baby syndrome.
§ 2. deficiency of enzymes--> GILBERT syndrome and Blood
Drug Cardioselective ISA Sedation
CRIGLER-NAJAR lipid
2. Acetylation Acebutolol + ++ ---- ----
o There is genotypic variation: fast and slow Atenolol + --- ↑↑
o Drug-induced SLE by slow acetylators Metoprolol + + ↑↑
3. GLUTATHIONEàdepletion in acetaminophen toxicity Pindolol ++ + ---
o Clinical correlation: Propranolol +++ ↑↑
§ Major Metabolism: Hepatic glucoronosyl transferase Timolol ++ ↑↑
§ Minor Pathway: reactive metabolite (NAPQ1)
A 25-year-old hypertensive female wishes to
A 30-year-old man is admitted to the emergency become pregnant. Her physician informs her that
department after taking a suicidal overdose of she will have to switch to another antihypertensive
reserpine. His blood pressure is 50/0 mm Hg and drug. Which of the following drugs is absolutely
heart rate is 40 bpm. Which of the following would contraindicated in pregnancy?
5.
be the most effective cardiovascular stimulant? A. Atenolol
3.
A. Amphetamine B. Captopril
B. Clonidine C. Methyldopa
C. Cocaine D. Prazosin
D. Norepinephrine E. Propranolol
E. Tyramine HYPERTENSIVE MANAGEMENT IN PREGNANCY
ADRENERGIC PHARMACOLOGY 1. Methyldopa (alpha 2 agonist)
o ↓ in sympathetic outflow ↓ TPR but also ↓in heart rate
o Indication Moderate to Severe HPN
o Side-effect (+) Coombs test, edema and CNS depression
o Drug Interactions ↓ alpha 2 agonist anti HPN if combined with
TCA
2. Hydralazine
o ↓ TPR via arteriolar dilation
o Indication Moderate to Severe HPN
o SE: SLE-like, slow acetylators, edema and reflex tachycardia
3. Labetalol (both for Chronic Pre-existing HPN and Pre-
eclampsia)
A 73-year-old man with an inadequate response to

other drugs is to receive digoxin for heart failure.
Which of the following is the best documented
mechanism of beneficial action of cardiac
glycosides?
A. A decrease in calcium uptake by the
6.
sarcoplasmic reticulum
B. An increase in ATP synthesis
C. A modification of the actin molecule
D. An increase in systolic cytoplasmic calcium
levels
E. A block of cardiac β adrenoceptors
Which of the following statements is most correct

regarding beta blocking agents?
A. Esmolol’s pharmacokinetics are compatible
with chronic topical use
4. B. Metoprolol blocks β2 receptors selectively
C. Nadolol lacks β2-blocking action
D. Pindolol is a β antagonist with high membrane-
stabilizing (local anesthetic) activity
E. Timolol lacks the local anesthetic effects
Chronic heart failure is commonly treated with a
combination of drugs that both improve symptoms
and provide long-term benefits. Three drugs or drug
groups that have been shown in clinical trials to
provide benefits in patients with chronic heart
failure are
A. ACE inhibitors, carvedilol, and
7.
spironolactone
B. Alpha1-selective antagonists, digoxin, and
hydrochlorothiazide
C. Digoxin, β-agonists, and nitroglycerin
D. Dobutamine, propranolol, and furosemide
E. Verapamil, isosorbide dinitrate, and
furosemide
THERAPEUTIC STRATEGY FOR HEART FAILURE Source: USMLE
• ↓ preload: diuretics, ACE inhibitors, ARBs and venodilators • Indications: Acute Pulmonary Edema, Heart failure, HPN, Edema,
• ↓ afterload: ACE inhibitors, ARBs and arteriolar dilators Hypercalcemic states
• ↑ contractility of the heart: digoxin, beta agonists and PDE III • Side effects: Hypokalemia, Hyponatremia, Hypomagnesemia,
inhibitors Hyperuricemia, Ototoxicity, sulfonamide hypersensitivity
• ↓ cardiac remodeling: ACE inhibitors, ARBS, spironolactone ,
beta blockers A 60-year-old woman has been admitted to the
coronary care unit with a left ventricular
DIGOXIN myocardial infarction. She develops acute severe
• Direct effect: heart failure with marked pulmonary edema with
o inhibition of Na-K ATPaseà↑ intracellular Na+àdecreases rales but no evidence of peripheral edema or weight
Na/Ca2+ exchangerà gain. Which one of the following drugs would be
8.
↑ calcium release from SRà↑actin-myosin most useful?
interactionà↑contractile force A. Digoxin
B. Furosemide
• Indirect effect: inhibition of neuronal Na-K ATPase à ↑vagal
C. Minoxidil
actiivity
D. Propranolol
• Indications: CHF, SVT except WPW
E. Spironolactone
• Pharmacokinetics: long ½ life, needs renal adjustment and
Which one of the following drugs binds bile acids in
tissue protein binding displace by other drugs (Verapamil,
the intestine, thus preventing their return to the
Quinidine)
liver via the enterohepatic circulation?
• Side Effects: (Early) Nausea, Anorexia and ECG changes
A. Niacin
• Side Effects: (Late) visual disturbance (halos), disorientation in 9.
B. Fenofibrate
toxic dose and arrythmia C. Simvastatin
• Management of toxicity: Fab antibodies, supportive for D. Cholestyramine
electrolytes and anti arrhythmic (Class IB) E. Ezetimibe
• Drug-drug interaction: Diuretics ↓ K+ ↓ Mg2+, ↑Ca2+, Quinidine CHOLESTYRAMINE
and Verapamil
• is an anion-exchange resin that binds negatively charged bile
INOTROPES
acids and bile salts in the small intestine
• The resin/ bile acid complex is excreted in the feces, thus
preventing the bile acids from returning to the liver by the
enterohepatic circulation
Source: USMLE
CLINICAL CORRELATION: INTERNAL MEDICINE

• Diastolic dysfunction (CHF with preserved ejection fraction) is
best treated with β blockers and diuretics.
• Beta Blockers for Ejection Fraction of <40%
• Aldosterone antagonist is beneficial for Ejection Fraction <35%
FUROSEMIDE
• MOA: inhibition of NA-K-2Cl symport in TALà ↓ K+ in TALà ↓
back diffusion of K+ à ↓ + potential à ↓ Mg2+ and Ca2+
àdiuresis
Source: Katzung Basic and Clinical Pharmacology 14TH edition
OPIOID ANALGESICS
• these are the endogenous endorphin (μ), dynorphin (κ )and
enkephalins (δ)
• Prototype: Morphine
• Signaling mechanism: Gi coupling
• Are the most powerful drugs for the relief of pain
• Attenuate both emotional and sensory aspects of pain
• Indications: Analgesia, sedation and euphoria
MORPHINE
• is a strong (μ) agonist for analgesia (↑ pain tolerance and
↓perception and reaction to pain) and adjunct to anesthesia
• Side effect: Respiratory depression
• Minimal cardiovascular effect (except histamine release)
• Smooth muscles (relaxation of longitudinal muscles and
constriction of circular muscles) GIT, GUT, Biliary tree and
HEPATIC LIPOPROTEIN SYNTHESIS pupils
• Nausea and vomiting
• Pharmacokinetics: Glucuronidation--> active Morphine-6
glucuronide
DIFFERENT OPIOIDS
Classification Drug Features
Antimuscarinic (No
Miosis)
Meperidine Tachycardia, no spasm of
(Demerol) GI/GU
Metabolized via CYP450-
Full agonist àNormeperidine
Use in maintenance of
Methadone
opioid
Cough suppressant,
Codeine analgesia and used with
NSAIDS combination
Can cause precipitation of
Partial withdrawal (μ antagonist
Buprenorphine
agonist precipitation of
The patient started on gemfibrozil. What is the
withdrawal)
major mechanism of action of this drug?
κ agonist spinal analgesia
A. ↑ excretion of bile acid salts Mixed
Nalbuphine, dysphoria
B. ↑expression of high-affinity LDL receptors agonist and
10. Pentazocine μ antagonist precipitation
C. ↑ secretion of VLDL by the liver antagonist
of withdrawal
D. ↑ triglyceride hydrolysis by lipoprotein
lipase
E. ↓ uptake of dietary cholesterol OPIOID ANTAGONIST
Classification Drug Features
After being counseled about lifestyle and dietary Opioid Given IV for reversal of
changes, the patient was started on atorvastatin. Naloxone respiratory depression
antagonist
During his treatment with atorvastatin, it is
Given oral to reduce
important to routinely monitor serum
Opioid craving for alcohol and
concentrations of which of the following? Naltrexone
11. antagonist used in opiate
A. Blood Urea Nitrogen
B. Alanine and Aspartate Aminotransferase addiction
C. Platelets Opioid Treatment for opioid-
Methylnaltrexone induced constipation
D. RBC antagonist
E. Uric acid Used to address
Alpha 2
Clonidine withdrawal in chronic
A patient with an incurable cancer is suffering from agonist
opioid intake
pain that is gradually increasing in intensity and
levorphanol (a strong μ-receptor agonist) is IMPORTANT TO REMEMBER ABOUT OPIOIDS
prescribed. With chronic use of the drug, tolerance • Classic Triad of acute toxicity: pinpoint pupils, respiratory
is not likely to develop to constipation or to
12. depression and coma
A. Euphoria
• ABUSE POTENTIAL
B. Nausea and vomiting
o Pharmacodynamic tolerance except MIOSIS and
C. Pupillary constriction
CONSTIPATION
D. Sedation
o Physical and psychological dependence
E. Urinary retention
• Withdrawal symptoms
o Yawning
o Lacrimation, rhinorrhea, salivation, sweating, anxiety
o CNS-originating pain
A 25 year old medical student has episodes of

excessive sleepiness and with times of hyperactivity
for the past 4 weeks. He was encountering such
difficulties on his medical school life adjusting to
some environmental changes from his typical used
to collegiate life. He manifests excessive talking,
oriented too much to sexual activities, and
13. uncontrolled impulsivity in buying stuffs. Which of
the following drugs is the most appropriate initial
pharmacologic treatment for his anxiety?
A. Carbamazepine
B. Haloperidol
C. Lamotrigine
D. Lithium
E. Sertraline
LITHIUM
• A drug of choice for Bipolar disorder
• MOA: Prevents recycling of inositol monophosphatase
• (↓ PIP2) by blocking inositol - ↓IP3,DAG, Calcium (Gq)
• ↓ cAMP
• Side effects:
o Narrow Therapeutic Index, life-threatening seizure
o Hypothyroidism with goiter
o Nephrogenic Diabetes insipidus (Give Amiloride)
o Teratogenic: Ebstein anomaly
14-16. A homeless middle-aged male patient presents in

the emergency department in a state of intoxication. You
note that he is behaviorally disinhibited and rowdy. He
tells you that he has recently consumed about a pint of a
red-colored liquid that his friends were using to “get high.”
He complains that his vision is blurred and that it is “like
being in a snowstorm.” His breath smells a bit like
Source: Katzung Basic and Clinical Pharmacology 14TH edition
formaldehyde. He is acidotic.
Which of the following is the most likely cause of the An elderly man is brought to the emergency
intoxicated state of the patient? department 30 min after the onset of right-sided
A. Ethanol weakness and aphasia (difficulty speaking).
14. B. Ethylene glycol Imaging studies ruled out cerebral hemorrhage as
C. Isopropanol the cause of his acute symptoms of stroke. Over the
D. Hexane next 2 days, the patient’s symptoms resolved
E. Methanol completely. To prevent a recurrence of this disease,
After assessing and stabilizing the patient’s airway, 17.
the patient is most likely to be treated indefinitely
respiration, and circulatory status, fomepizole was with which of the following?
administered intravenously. Which of the following A. Aminocaproic acid
most accurately describes the therapeutic purpose B. Aspirin
of the fomepizole administration? C. Enoxaparin
A. Accelerate the rate of elimination of the toxic D. Lepirudin
15.
liquid consumed E. Warfarin
B. To combat acidosis ASPIRIN
C. To inhibit the metabolic production of the
toxic metabolite Similar
SALSALATE, SODIUM SALICYLATE
D. To prevent alcohol withdrawal seizure Drugs
E. To sedate the patient Drug Class Antiplatelet drug, NSAID (salicylate)
The regular ingestion of moderate or heavy amount Nonselective, irreversible COX inhibitor.
of alcohol predisposes to hepatic damage after MOA Reduces platelet production of thromboxane
overdose of acetaminophen because of chronic A2, a potent stimulator of platelet aggregation.
ethanol ingestion Prevention of arterial thrombosis (MI, TIA,
A. Blocks acetaminophen metabolism Clinical CVD), Inflammatory disorders (rheumatic fever,
16. Use Kawasaki disease, juvenile rheumatoid
B. Causes thiamine deficiency
C. Displaces acetaminophen from plasma arthritis)
proteins Gastrointestinal toxicity, Nephrotoxicity,
D. Induces liver metabolizing enzymes Toxicities Tinnitus, Hypersensitivity, Hyperventilation,
E. Inhibits renal clearance of acetaminophen HAGMA
Uncoupler of oxidative phosphorylation
Notes Associated with Reye syndrome in children
Prevents uric acid excretion (don’t use in gout)
CLINICAL CORRELATION: BIOCHEMISTRY

• UNCOUPLING of the oxidative phosphorylation of the
Electron Transport Chain-->increase Respirationàdecrease
PCO2àRESPIRATORY ALKALOSIS
• Renal compensation: Increase bicarbonate elimination
CLINICAL CORRELATION: INTERNAL MEDICINE • Inhibits metabolism of mercaptopurine
• LowàModerate dose: decrease tubular SECRETION of uric acid and azathioprine
• High Dose: decrease tubular REABSORPTION of uric acid • Withheld for 1–2 wk after an acute episode of
Notes
gouty arthritis (co-administered with
CLINICAL CORRELATION: SURGERY AND HISTOLOGY colchicine or indomethacin to avoid an acute
attack)
A sexually active woman presents with left lower
Is it okay to stop aspirin quadrant abdominal pain and a purulent vaginal
few days prior surgery? discharge that, on Gram stain, revealed gram-
Explain the mechanism negative rods. What drug combination will have an
adequate empiric coverage of the organisms
20. involved?
A. Azithromycin
B. Ceftriaxone + Doxycycline
Which of the following is the most appropriate drug C. Metronidazole
for immediate treatment of this acute attack of gout? D. Norfloxacin + Ampicillin
A. Allopurinol E. Trimethoprim + Sulfamethoxazole
18. B. Indomethacin PELVIC INFLAMMATORY DISEASE
C. Methotrexate
D. Morphine
E. Probenecid
GOUTY ARTHRITIS
Source: USMLE
A 25 year-old lady is taking metronidazole for a

vaginal infection. Which of the following will you
advice her while she is on treatment?
A. Do not drink wine while you are on
21.
treatment.
B. You may take it with phenobarbital.
Source: USMLE Step 1 by Tao Le
C. Avoid taking cimetidine.
D. Do not worry, the drug has no side effects.
22-23. A patient with AIDS has a CD4 count of 45/ul. He is

being maintained on a 3-drug regimen of indinavir,
didanosine and zidovudine.
For prophylaxis against opportunistic infections, he is also
receiving ganciclovir, fluconazole, rifabutin and
trimethoprim-sulfamethoxazole.
The drug most likely to suppress herpetic infections
and provide prophylaxis against CMV retinitis in
this patient is
A. Fluconazole
Source: Katzung Basic and Clinical Pharmacology 14th ed 22.
B. Ganciclovir
TREATMENT STRATEGIES FOR GOUT C. Indinavir
1. reducing inflammation during acute attacks D. Rifabutin
2. accelerating renal excretion of uric acid with uricosuric drugs E. Trimethoprim-sulfamethoxazole
3. reducing the conversion of purines to uric acid by xanthine The dose of indinavir may need to be increased
oxidase above normal this is because
A. Fluconazole slows gastric emptying
Co-administered to a patient being treated with B. Ganciclovir increases the renal clearance of
azathioprine, which drug will result in severe indinavir
23.
hematotoxicity? C. Indinavir has to be taken with meals
A. Allopurinol D. Rifabutin increases liver drug-metabolizing
19. enzymes
B. Cholestyramine
C. Digoxin E. Sulfamethoxazole displaces indinavir from
D. Lithium plasma proteins
E. Theophylline CD4 ETIOLOGY CLINICAL SYNDROME
ALLOPURINOL M. tuberculosis Disseminated tuberculosis
Drug Class Antigout drug (xanthine oxidase inhibitor) HSV HSV esophagitis
< 500
Active metabolite (alloxanthine) irreversibly C. albicans Esophageal candidiasis
MOA inhibits xanthine oxidase and lowers HHV-8 Kaposi’s sarcoma
production of uric acid P. jiroveci PCP pneumonia
Clinical T. gondii Cerebral toxoplasmosis
Chronic gout, Tumor lysis syndrome
Use < 200 C. neoformans Meningoencephalitis
Gastrointestinal upset, Rash, Peripheral C. immitis Coccidioidomycosis
Toxicities neuritis, Vasculitis, Bone marrow dysfunction, C. parvum Chronic diarrhea
Aplastic anemia, Cataracts
CD4 ETIOLOGY CLINICAL SYNDROME
M. avium Invasive pulmonary disease
< 50 H. capsulatum Histoplasmosis
CMV CMV retinitis
A young girl was brought to you for vulvar and Which of the following drugs that is known to be
perianal itching most pronounced at night. You useful for the treatment of hypercalcemia in Paget’s
suspect that she has a worm infestation. A scotch disease has the side effect of causing jaw necrosis at
tape test which revealed D-shaped eggs. higher doses?
27.
A. Praziquantel A. Magnesium
B. Pyrantel Pamoate B. Teriparatide
C. Iodoquinol C. Raloxifene
D. Metronidazole D. Pamidronate
E. Ivermectin
A 56 year old man with oat cell carcinoma of the lung
24. is admitted to the hospital after having grand mal
seizures. Laboratory studies reveal the following
information:
Na: 110 mEq/L
serum Osmolarity: 225 mOsm/L
28. Urine Osmolarity: 650 mOsm/L.
What treatment is appropriate for this patient?

A. Mecasermin
B. Conivaptan
C. Octreotide
What chemotherapeutic drug is strongly associated D. Desmopressin
with hemorrhagic cystitis?
A. Cyclophosphamide Which of the following drugs is best given for
25. B. Doxurubicin premenopausal POST Modified radical mastectomy
C. Fluouracil women?
D. Methotrexate A. Anastrozole
29.
E. Tamoxifen B. Raloxifene
RESCUE AGENTS FOR ANTICANCER DRUGS C. Danazol
MEDICATION RESCUE AGENT D. Tamoxifen
E. Clomiphene
METHOTREXATE LEUCOVERIN
CYCLOPHOSPHOMIDE MESNA
DOXORUBICIN DEXRAZOXANE
CISPLATIN AMIFOSTINE
CHEMOTOX MAN
ß Clomiphene: anEestrogen
ß Danazol: cytochrome p450

inhibitor
Source: USMLE
Baby C, a 5 year old boy was brought to the pediatric

ER after ingesting 100 ml of diphenhydramine ß Anastrozole: aromatase
syrup. Diphenhydramine is a weak base with a pKa inhibitor
of 8.8. Which of the following statements about this
case of overdose is correct? ß SERMS: TAMOXIFEN,
A. Accelerate urinary excretion by giving an RALOXIFENE
26.
acidifying agent
B. Do stat hemodialysis.
C. Accelerate urinary excretion by giving an
alkalinizing agent
D. More of the drug would be ionized at a blood Which of the following drugs is used for the
pH (7) than at stomach pH (2) treatment of acromegaly?
A. Pegvisomant
30.
B. Somatropin
C. Mecasermin
D. Conivaptan
What is the ovulation induction method of choice for

women with PCOS?
A. Danazol
31.
B. Goserelin
C. Ganirelix
D. Clomiphene
Pair the correct opioid receptor and action for the Summary
drug LOPERAMIDE First Generation Second Generation
A. Mu receptor - antagonist Antipsychotics Antipsychotics
B. Μu receptor - agonist Mechanism • D2 antagonism • 5-HT2A/D2
32.
C. Delta receptor – antagonist of action antagonism
D. Delta receptor – agonist • Rapid D2 dissociation
E. Kappa receptor – antagonist • 5-HT11A agonism
F. Kappa receptor - agonist Other Antagonism of M1, H1, Antagonism of M1, H1, 5-
effects and ɑ1 receptors, HT2C, ɑ1 receptors,
Which of the following is a correct application of the among others among others
drug mentioned?
A. Ergonovine – Alzheimer’s disease Which of the following antipsychotic drugs has a
33. B. Cetirizine – Hay fever high affinity for 5-HT2 receptors, does not cause
C. Alosetron – obstetric hemorrhage EPS, and is reported to increase risk of significant
D. Ondansetron - Migraine prolonged QT prolongation?
E. Ranitidine – Parkinson’s disease A. Chlorpromazine
35.
B. Ziprasidone
Which of the following receptors, when C. Clozapine
antagonized, is responsible for addressing BOTH D. Olanzapine
positive and negative symptoms of schizophrenia? E. Risperidone
34. A. D2 F. Haloperidol
B. H1
C. Alpha 1 This particular antiglaucoma drug acts by ciliary
D. 5HT2a muscle contraction which will lead to opening up
DOPAMINE PATHWAYS RELEVANT TO SCHIZOPHRENIA the trabecular meshwork which will lead to
SYMPTOMS increased outflow, relieving eye pressure
36.
A. Pilocarpine
B. Physostigmine
C. Echothiopate
D. ALL OF THE ABOVE
Brimatoprost is an anti-glaucoma medication that

works by the following mechanism of action:
A. Increases aqueous humor outflow via the
canal of Schlemm
B. Increases aqueous humor outflow via
FIRST GENERATION ANTIPSYCHOTICS (FGA) 37.
uveoscleral veins
C. Increases aqueous humor outflow via ciliary
muscle contraction
D. Decreases aqueous humor production from
• They lower neurotransmission in the ciliary epithelium
4 dopamine pathways DRUG CLASS EXAMPLES MECHANISM
• They can also block H1, M1, and ɑ1 Timolol,
receptors. Levobunolol,
Carteolol,
Beta
Metipranolol,
antagonists
(nonselective),
Decreased
Betaxolol (b1
production of
selective)
SECOND GENERATION ANTIPSYCHOTICS (SGA) aqueous humor from
Osmotic agents Mannitol
ciliary epithelium
• are 5HT2A antagonists Brimonidine,
a2 agonists
Apraclonidine
Carbonic
Acetazolamide,
anhydrase
Dorzolamide
inhibitors
Pilocarpine
(Selective Ciliary muscle
muscarinic agonist), contraction, opening
Cholinomimetics Physostigmine & of trabecular
Echothiopate meshwork →
(Acetylcholinesterase Increased outflow
SGAS DISSOCIATE RAPIDLY FROM D2 RECEPTORS inhibitor)
FGA Clozapine and other SGAs Increased outflow
Prostaglandin Latanoprost,
Bind to D2 receptors: Tight Binding to D2 receptors: Loose via
analogue Brimatoprost
canal of Schlemm
HIGH D2 OCCUPANCY, HIGH EPS RISK Non selective a Increased outflow
Epinephrine
agonists via uveoscleral veins
Which statement about the drug SOTALOL is
INCORRECT?
A. It is a GROUP 2 anti-arrhythmic
38. B. It is a GROUP 3 anti-arrhythmic
C. It is a K channel blocker
D. It is a Beta blocker
E. None of the statements are incorrect
What is the drug of choice for the management of
atropine toxicity?
A. Pralidoxime
39.
B. Echothiophate
C. Glucagon
D. Physostigmine
Which of the following drug/s is/are used for the
closure of ductus arteriosus in preterm infants?
A. Indomethacin
40.
B. Ibuprofen
C. Naproxen
D. All of the above
Which calcium channel blocker is useful for

preventing cerebral vasospasm in patients with
subarachnoid hemorrhage?
A. Amlodipine
43.
B. Nifedipine
C. Diltiazem
D. Verapamil
E. Nimodipine
Which of the following symptoms is an expected side

effect of your antidiabetic drug dipeptidyl peptidase
4 (DPP-4) inhibitors?
44. A. Nasopharyngitis
B. Diarrhea
C. Nausea
D. Lactic acidosis
Which of the following symptoms can be addressed

by pralidoxime but not by atropine in a case of
organophosphate poisoning?
41. A. Miosis
B. Bronchoconstriction
C. Diarrhea
D. Respiratory paralysis
“The authors concluded that metformin induced lifespan

extension via inhibiting mTORC1 and activating AMPK
through the “lysosomal” pathway. It was noted that the
metformin-treated worms looked healthier (fewer age pigments)
and had an attenuated age-related decline in fitness (locomotion
body bends)
Which of the following antidiabetic drug is the
LEAST likely to cause hypoglycemia?
Which of the following best describes the A. Insulin
45.
mechanism of action of benzodiazepines? B. Metformin
A. Stimulate release of GABA from nerve endings C. Glyburide
in the brain D. Repaglinide
B. Inhibit GABA transaminase to increase brain
levels of GABA What is the mechanism of action of dicycloverine, an
42. antispasmodic medication used for the treatment of
C. Activate GABA-B receptors in the spinal cord
D. Increase frequency of opening of chloride irritable bowel syndrome?
ion channels that are coupled to GABA-A 46. A. Chloride channel activator
receptors B. 5HT3 antagonist
E. Block glutamate receptors in the neuronal C. Muscarinic antagonist
pathways in the brain D. D2 antagonist
Which gastrointestinal agent is used for the Which of the following anti TB drugs cause
treatment of peptic ulcer disease by creating a peripheral neuropathy?
viscous sticky polymer over ulcers to accelerate A. Pyrazinamide
48.
healing? B. Isoniazid
47.
A. Hyoscyamine C. Ethambutol
B. Erythromycin D. Rifampicin
C. Misoprostol
D. Sucralfate
If ketamine is used as a sole anesthetic to manage

suturing of a 2 cm arm laceration of a 7 year old
child, its actions will include
A. Respiratory depression
49.
B. Bradycardia
C. Hypotension
D. Analgesia
E. Bronchoconstriction
What is the mechanism of action of the drug

tamsulosin, used for the treatment of hypertension
and benign prostatic hyperplasia?
50. A. Alpha 1 agonist
B. Alpha 1 antagonist
C. Alpha 2 agonist
D. Alpha 2 antagonist
END OF PHARMACOLOGY PHASE 2
TOPNOTCH MEDICAL BOARD PREP PHARMA PHASE 3 DIGITAL HANDOUT BY DR. PEREYRA-BORLONGAN
A 55 y/o woman with CHF is to be
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REMINDERS
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at least the Phase 1 videos prior to watching the Phase 3 videos
2. The guided content of the video lectures are seen within the handout.
Answers to questions / blanks will be seen in the Phase 3 video.
Dose at which 50% of the

INSTRUCTIONS MEDIAN EFFECTIVE
individuals exhibit the specified
For those who have printed the initial handout: DOSE
quantal effect
Please use this handout as a guide to correct the initial handout.
Page guides are available to assist you in doing so.
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MEDIAN TOXIC DOSE
manifest a particular toxic effect
This handout is only valid for the September 2021 PLE batch.
This will be rendered obsolete for the next batch
since we update our handouts regularly.
PHARMACOLOGY – PHASE 3
by Maria Yña Eluisia T. Pereyra-Borlongan, RPh, MD
PART 1
GENERAL PHARMACOLOGY
Refers to the amount of a drug that
BIOAVAILABILITY Transfer of drug from site of
reaches the systemic circulation ABSORPTION
administration to bloodstream
Used to determine the safety and

BIOEQUIVALENCE Refers the apparent volume into VOLUME OF
efficacy of generic drugs
which the drug can distribute DISTRIBUTION
Measures the dose or concentration

required to bring about 50% of the POTENCY Elimination of drug at a constant ZERO ORDER
drug’s maximal effect rate KINETICS
TOPNOTCH MEDICAL BOARD PREP PHARMA PHASE 3 DIGITAL HANDOUT BY DR. PEREYRA-BORLONGAN Page 1 of 20
Elimination at a rate that is

FIRST ORDER
proportional to the serum
KINETICS
concentration of the drug
Addition of a polar moiety (sulfate, PHASE II

acetate or glucuronate) METABOLISM
Use of CYP 450 system oxidation,

reduction, hydrolysis or PHASE I METABOLISM
deamination
Refers to the dosage range between

the minimum effective therapeutic
THERAPEUTIC
concentration or dose and
WINDOW
minimum toxic concentration or
dose
COMPETITIVE /
Substance that shifts the graded
REVERSIBLE
dose-response curve to the right
ANTAGONIST
Substance that does not produce the

same maximum effect and is PARTIAL AGONIST
exhibited by a decrease in the Emax
Describes the rate at which a
specific drug is cleared from the CLEARANCE NON-COMPETITIVE /
system Substance that depress the graded-
IRREVERSIBLE
dose response curve
Refers to the amount of time ANTAGONIST
required for the amount of the drug
in the body to decrease to half of its HALF LIFE An antagonist that interacts directly
CHEMICAL
value after the administration of the with the agonist and not at all or
ANTAGONIST
drug has been stopped only incidentally with the receptor?
Defined as the single amount of drug

that is needed to achieve a desired LOADING DOSE The action of the drug on the body PHARMACODYNAMICS
plasma concentration quickly
Amount of drug that must be given

over time in order to maintain MAINTENANCE DOSE The action of the body on the drug PHARMACOKINETICS
desired plasma concentration
Used as a measure of drugs safety THERAPEUTIC INDEX Permeation that is governed by AQUEOUS DIFFUSION
Fick’s Law LIPID DIFFUSION
𝑻𝑫𝟓𝟎
Formula for therapeutic index Permeation that is saturable and
𝑬𝑫𝟓𝟎 CARRIER TRANSPORT
inhibitable
Adverse effect that is infrequently

IDIOSYNCRATIC
observed in most patients
Responsiveness decreases as a
consequence of continued drug TOLERANCE
administration
Responsiveness diminishes rapidly

TACHYPHYLAXIS
after drug administration
AUTONOMIC DRUGS
Induction of developmental defects
in the fetus
TERATOGENESIS ADRENERGIC AGENTS
PREFERRED
RECEPTOR LOCATION ACTION
SUBSTRATE
Smooth
Induction of malignant Alpha 1 Vasoconstriction Epi > NE
CARCINOGENESIS muscles
characteristics in cells
Nerve Inhibits release of
Alpha 2 Epi > NE
terminals neurotransmitters
Induction of changes in the Increase rate and Isoproterenol
genetic material of animals of any MUTAGENESIS Beta 1 Heart
contractility > Epi > NE
age Respi
smooth Broncho / Isoproterenol
Beta 2
muscles; vasodilation > Epi > NE
ROUTE OF DRUG ADMINISTRATION uterus
Splanchnic Vasodilation of
100% bioavailability INTRAVENOUS D1 and renal renal blood Dopamine
vessels vessels
Nerve
First pass effect ORAL Regulates
D2 terminals Dopamine
neurotransmitters
of CNS
Partial avoidance of the first pass
RECTAL, SUBLINGUAL
effect
CHOLINERGIC AGENTS
PREFERRED
Application to skin for local effect TOPICAL RECEPTOR LOCATION ACTION
SUBSTRATE
M1 CNS Stimulation Ach
Application to skin for systemic M2 Heart Decrease HR Ach
TRANSDERMAL
effect Smooth Gut peristalsis
Muscle GI Bladder contraction
M3 Ach
GU Pulmo Bronchoconstriction
PHASES OF DRUG STUDIES Eye Pupil constriction
Small number of volunteers PHASE I
MAJOR
RECEPTOR LOCATION MECHANISM
FUNCTIONS
Post-marketing surveillance PHASE IV ↑IP3-DAG
M1 Nerve endings Gq-coupled
cascade
↓cAMP,
Heart, some
“Does it work in patients?” PHASE II M2 Gi-coupled activates K+
nerve endings
channels
Randomized, double-blind, Effector cells:
PHASE III smooth ↑IP3-DAG
controlled trials M3 Gq-coupled
muscle, glands, cascade
A drug for a rare disease ORPHAN DRUG endothelium
Depolarizes,
Case of overdose with a weak base evokes
NN ANS ganglia Ion channel
(ex. Diphenhydramine, atropine). ACIDIFYING AGENT action
What agent will you use (Ammonium chloride) potential
to hasten urinary excretion? Depolarizes,
Neuromuscular evokes
Case of overdose with a weak acid NM Ion channel
ALKALINIZING AGENT end plate action
(ex. aspirin). What agent will you potential
(Sodium Bicarbonate)
use to hasten urinary excretion?
pH = pKa + log U/P CHOLINERGIC DRUGS
2.5 = 3.5 + log U/P
2.5 – 3.5 = log U/P BETHANECHOL
Drug X is a weak organic acid with a Bowel and bladder atony
-1 = log U/P (direct acting muscarinic
pKa of 3.5. What percentage of a agonist; M2-M3)
10-1 = U/P
given dose will be in the lipid
soluble form at a stomach pH of 2.5?
unprotonated is 10-1 Sjögren syndrome (Xerostomia, PILOCARPINE
or 0.10 or 10% Xerophthalmia and rheumatoid (direct acting muscarinic
protonated is 90% arthritis) agonist; M1-M2-M3)
EDROPHONIUM
PREGNANT PREGNANT Diagnosis of myasthenia gravis, Indirect acting
CLASS HUMAN ANIMAL EXAMPLES differentiation of myasthenic cholinomimetic
STUDIES STUDIES and cholinergic crisis MOA: Hydrolysis of
Folic acid, Thyroid cholinesterase
A Safe Safe
hormones
No studies Safe Zidovudine Treatment of myasthenia gravis PYRIDOSTIGMINE
B
Safe Unsafe
No studies Unsafe Aspirin
C
No studies No studies Reversal of non-depolarizing
NEOSTIGMINE
ACE inhibitors, neuromuscular block
D Unsafe Unsafe
Anticonvulsants
Statins, OCPs,
Clomiphene,
X Unsafe Unsafe Treatment of glaucoma PHYSOSTIGMINE
Misoprostol, High-
dose Vitamin A
METHACHOLINE
Diagnosis of bronchial hyper- Direct acting
reactivity cholinomimetic
M3 Agonist
DONEPEZIL,
Treatment of Alzheimer’s disease RIVASTIGMINE
Acetylcholinesterase
inhibitor (reversible) IPRATROPIUM
Why is Ipratropium the preferred
less likely to cause
bronchodilator in patients with
tachycardia and cardiac
comorbid COPD and heart disease? arrhythmias
What is Sjögren Syndrome? What are the signs of atropine toxicity?
What is myasthenia gravis?
ADRENERGIC AGENTS
DOC for Anaphylactic shock,
Adjunct to local anesthesia, EPINEPHRINE
What are the signs and symptoms of organophosphate Cardiac arrest, Croup
poisoning?
Acute CHF, Cardiac stress testing DOBUTAMINE
Acute CHF, Shock (cardiogenic,

DOPAMINE
septic)
• LOW DOSE (1-5 mcg/kg/min)

o vasodilation in the splanchnic and renal vascular beds via D1
receptors increased renal blood flow and urine output
• MEDIUM DOSE (5-15 mcg/kg/min)
o increased renal blood flow, heart rate, cardiac contractility,
and cardiac output via β receptors
• HIGH DOSE (>15 mcg/kg/min)
CHOLINERGIC ANTAGONISTS o vasoconstriction and increased blood pressure via α receptors
Induction of mydriasis and

TROPICAMIDE
cycloplegia Alpha > Beta receptor affinity NOREPINEPHRINE
Sinus bradycardia ATROPINE Nasal congestion, Mydriasis

PHENYLEPHRINE
WITHOUT cycloplegia
Parkinson disease BIPERIDEN SE: Rebound hypertension on

CLONIDINE
discontinuation
Chronic obstructive pulmonary IPRATROPIUM SE: Hemolytic anemia (positive

disease (COPD) (M3 antagonist) METHYLDOPA
Coombs test)
Motion sickness, Sea sickness SCOPOLAMINE

Bronchial asthma, COPD SALBUTAMOL
Gastrointestinal spasms HYOSCYAMINE, HNBB

Tocolysis for preterm labor TERBUTALINE
Treatment for Organophosphate ATROPINE +

Poisoning / Nerve gas poisoning PRALIDOXIME
ADRENERGIC ANTAGONIST CARDIOVASCULAR DRUGS

ANTI-HYPERTENSIVE DRUGS
Preoperative treatment of PHENOXYBENZAMINE
(irreversible non selective Hypertension with comorbid
pheochromocytoma, Irreversible alpha blocker) CHF/DM SE: cough, angioedema,
CAPTOPRIL
contraindicated in bilateral RAS,
Treatment of rebound teratogenic
PHENTOLAMINE
hypertension, antidote for 𝛼1
(reversible) ACE-inhibitor intolerance LOSARTAN
agonist overdose
Benign prostatic hyperplasia, Hypertension with comorbid BPH PRAZOSIN

SE: First dose orthostatic PRAZOSIN
hypotension Pre-eclampsia (maintenance
Angina prophylaxis, medication) SE: hemolytic anemia METHYLDOPA
Hyperthyroidism, Masks (positive Coombs test)
hypoglycemia in diabetics; PROPRANOLOL
SE: Bronchospasm, Erectile Pre-eclampsia (acute BP lowering),
dysfunction SE: reflex tachycardia, drug- HYDRALAZINE
induced lupus
Intrinsic sympathomimetic activity PINDOLOL
Hypertensive emergency,
MINOXIDIL
SE: hypertrichosis
Beta-1 selectivity ATENOLOL
Hypertensive emergency,
NITROPRUSSIDE
SE: cyanide poisoning
Treatment of glaucoma TIMOLOL
Treatment of cyanide poisoning AMYL NITRITE
Combined alpha- and beta-blockade LABETALOL COMPLEX IV

Which portion of the electron (CYTOCHROME
transport chain is affected by OXIDASE)
KEY LEARNING POINTS: Beta-Blockers cyanide? of the Electron Transport
Chain
What are the major subgroups of beta-blockers?
INHALED AMYL
Non-selective Propranolol, Timolol
NITRITE +
Acebutolol, Betaxolol, Esmolol, What is the antidote for cyanide
Beta 1-selective IV SODIUM NITRITE +
Atenolol, Metoprolol poisoning?
IV SODIUM
Partial agonist Pindolol, Acebutolol
THIOSULFATE
Lacking local
Timolol
anesthetic effect
Low lipid ANTI-ANGINAL DRUGS
Atenolol
solubility
Shortest-acting Esmolol Relief of acute anginal attacks,
NTG, ISDN
Longest-acting Nadolol SE: headache, tolerance
Combined 𝝰 and β
Nebivolol, Carvedilol, Labetalol Angina maintenance,
blockade
Vascular > Cardiac effect,
NIFEDIPINE
SE: flushing, edema, gingival
What drugs are used to control PHENOXYBENZAMINE, hyperplasia
blood pressure in PHENTOLAMINE OR Angina maintenance,
pheochromocytoma? LABETALOL Cardiac > Vascular, Vasospastic
angina, Raynaud’s phenomenon, DILTIAZEM
does NOT cause gingival
hyperplasia
Supraventricular tachycardia,
Cardiac > Vascular effect, VERAPAMIL
SE: gingival hyperplasia
Why do patients taking nitrates

Due to meningeal
usually experience throbbing
vessel vasodilation
headaches?
Why is calcium-dependent CCBS BLOCK L-TYPE

neurotransmission or hormone CALCIUM CHANNELS
other functions use N-, P-,
release not affected by CCBs? and R-types
What drugs can cause gingival hyperplasia?
DRUGS FOR HEART FAILURE What are the drugs that can cause agranulocytosis?
Positive inotrope for heart failure,

SE: arrhythmias (PVC, AVB), DIGOXIN
yellow visual halos
Treatment of pulmonary edema in

CHF, First Line for Acute Heart FUROSEMIDE
Failure
First-line drug for chronic CHF,

ACE-I, ARBs
Cardioprotective, Renoprotective
ACE-I/ARBS, BETA-
Improves survival
BLOCKERS,
(decreases mortality) in CHF
SPIRONOLACTONE
Decreases hospitalizations in CHF DIGOXIN
Improves survival in CHF patients

HYDRALAZINE + ISDN
of African-American descent
Dihydropyridine CCBs
evoke compensatory
sympathetic
Why are dihydropyridine calcium
discharge which
channel blockers not useful as
facilitates
antiarrhythmics?
arrhythmias rather
than terminating
them
ANTIARRHYTHMIC DRUGS
Treatment of all types of Summary of the Effects of Antiarrhythmic Drugs
arrhythmias, WPW syndrome, PROCAINAMIDE Effect on AP
CLASS PROTOTYPE Effect on ECG
SE: drug-induced lupus Duration
PROLONGS PR
For atrial and ventricular interval,
1A Procainamide PROLONGS
arrhythmia, SE: Cinchonism QUINIDINE PROLONGS QRS
(headache, tinnitus, vertigo) duration
NO EFFECT on
1B Lidocaine SHORTENS
normal cells
Post-MI arrhythmias, Digitalis PROLONGS QRS
LIDOCAINE 1C Flecainide NO EFFECT
arrhythmias, SE: seizures duration
PROLONGS PR
2 Propranolol NO EFFECT
interval
Contraindicated post-MI, PROLONGS QT
FLECAINIDE 3 Dofetilide PROLONGS
Refractory arrhythmias interval
PROLONGS PR
4 Verapamil NO EFFECT
interval
Perioperative and thyrotoxic
ESMOLOL
arrhythmias, SVT
DIURETICS
Beta blocker, Group 3 activity, Acts on PCT, Treatment of glaucoma
SE: dose-dependent torsades de SOTALOL and mountain sickness, SE: NAGMA, ACETAZOLAMIDE
pointes hepatic encephalopathy
Most efficacious antiarrhythmic,

For Refractory Arrhythmia,
AMIODARONE
SE: skin deposits, pulmonary
fibrosis, hyper/hypothyroidism
Outpatient management of SVT,

VERAPAMIL
SE: gingival hyperplasia
• Class IA: prolongs AP

duration
What are the effects of Class I
• Class IB: shortens AP
antiarrhythmics on action potential
duration
duration?
• Class IC: no effect on
AP duration
Acts on TAL, Treatment of Which drugs can cause gynecomastia?
pulmonary edema, Most efficacious
diuretics, SE: Ototoxicity, FUROSEMIDE
Hypokalemia, Hypocalcemia,
Sulfur allergy except?
Acts on DCT (NaCl Transporter)
SE: Hyperglycemia,
HCTZ
Hyperlipidemia, Hyperuricemia,
Hypercalcemia, Sulfur allergy
Acts on CCD, SE: Gynecomastia,

SPIRONOLACTONE
Hyperkalemia
ANTI-CHOLESTEROL DRUGS
Acts on PCT, DCT and CCD,
HMG-CoA reductase inhibitor,
Treatment of rhabdomyolysis and
MANNITOL Lowers LDL, SE: hepatotoxicity, SIMVASTATIN
increased ICP, contraindicated in
rhabdomyolysis, myopathy
heart failure
Bile acid binding resin, Lowers LDL,

CHOLESTYRAMINE
SE: constipation, steatorrhea
What are the causes of
• HAGMA?
• NAGMA? Cholesterol absorption blocker,
Lowers LDL; SE: Hepatotoxicity esp EZETIMIBE
with Statin use
Reduces all building blocks for
hyperlipidemia, Increases HDL,
NIACIN
Lowers LDL and TG, SE: flushing,
hyperglycemia, hyperuricemia
PPAR-𝛼 activator, upregulates
GEMFIBROZIL,
lipoprotein lipase, Lowers TG,
FENOFIBRATE
SE: gallstones, additive myopathy
Why are statins used in the For stabilization of

management of coronary artery atherosclerotic
disease? plaques
• Vancomycin;
• Adenosine;
What are the drugs that cause
flushing? • Niacin;
• Calcium channel
blockers
What are the adverse effects associated with loop diuretics?
HISTAMINERGICS / SEROTONERGICS
Treatment of hypersensitivity
(food allergy, rhinitis, hay fever,
DIPHENHYDRAMINE
angioedema), SE: sedation,
antimuscarinic effect
Adjunct for motion sickness, vertigo MECLIZINE
Treatment of hypersensitivity, non- CETIRIZINE,

sedating LORATADINE
Treatment of peptic ulcers,

CIMETIDINE
SE: gynecomastia
Drug of choice for migraine and

SUMATRIPTAN
cluster headache
Treatment for postop and post-

ONDANSETRON
chemo vomiting
Adjunct for migraine and cluster

ERGOTAMINE
headache
Treatment of postpartum bleeding ERGONOVINE
SE: retroperitoneal fibrosis METHYLSERGIDE
PROSTAGLANDIN DERIVATIVES
Treatment of megaloblastic anemia,
DRUG ANALOGUE CLINICAL USE CYANOCOBALAMIN
Vitamin B12 deficiency
Alprostadil PGE1 Erectile dysfunction
Misoprostol PGE1 NSAID-induced gastritis
Latanoprost PGF2⍺ Chronic glaucoma Treatment of megaloblastic anemia,
Abortifacient, Prevention of neural tube defects FOLIC ACID
Dinoprost PGE2 (spina bifida)
induction of labor
Abortifacient,
Carboprost PGF2⍺
postpartum hemorrhage
Epoprostenol PGI2 Pulmonary hypertension Anemia in chronic kidney disease ERYTHROPOIETIN
Treatment of neutropenia and

FILGRASTIM
agranulocytosis
Treatment of chemotherapy-
OPRELVEKIN
induced thrombocytopenia
ANTI-ASTHMA DRUGS ANTICOAGULANTS

Acute treatment of DVT, PE and
SABA:
Drug of choice for acute asthma AMI, SE: bleeding,
SALBUTAMOL / HEPARIN
attacks thrombocytopenia, monitor with
ALBUTEROL
PTT
Low molecular weight heparin,
Adjunct for asthma maintenance LABA: SALMETEROL less risk of thrombocytopenia, ENOXAPARIN
does not need monitoring
Prophylaxis for nocturnal asthma, Treatment of heparin-induced

SE: seizures, THEOPHYLLINE LEPIRUDIN
thrombocytopenia
antidote: Propranolol
Bronchodilator of choice in COPD Antidote to heparin-induced

IPRATROPIUM PROTAMINE SULFATE
and in patients with heart disease bleeding
Chronic anticoagulation,
Stabilizes mast cells,
CROMOLYN SE: bleeding, skin necrosis, WARFARIN
No bronchodilator effect
many drug interactions
Drug of choice for asthma
maintenance FLUTICASONE,
SE: oral candidiasis, growth BUDESONIDE
stunting
Lipoxygenase inhibitor,
ZILEUTON
SE: increased AST/ALT
Blocks receptor of slow-reacting

substances of anaphylaxis MONTELEUKAST
(Leukotrienes C4, D4, E4)
Antidote to Warfarin
FFP
(immediate reversal)
Anti-IgE antibody OMALIZUMAB
Antidote to Warfarin
VITAMIN K
(reversal over time)
HEMATOLOGIC AGENTS
HEMATOPOIETIC GROWTH FACTORS PiTT
PTT FOR INTRINSIC
Treatment of iron deficiency What laboratory tests will you PATHWAY
FERROUS SULFATE request to assess the extrinsic and
anemia
intrinsic coagulation pathways? PeT
PT FOR EXTRINSIC
Iron content of some oral Iron preparations (% w/w) PATHWAY
Fe carbonate / Carbonyl Iron 100% • Warfarin’s effect
Fe fumarate 33% requires elimination
of preformed
Fe sulfate, dried 30% In patients requiring
clotting factors
Fe sulfate, hydrated 20% anticoagulation, why is an overlap
(8 - 60h)
Ferric ammonium sulfate 18% between heparin and warfarin
• To bypass the initial
Fe gluconate 12% usually done?
prothrombotic
effect of Warfarin
(skin necrosis)
THROMBOLYTIC AGENTS Compete with uric acid for

reabsorption in the proximal PROBENECID
Thrombolysis in AMI, ischemic CVD tubules
ALTEPLASE
and PE, SE: bleeding
Active metabolite (Alloxanthine)
irreversibly inhibits Xanthine
ALLOPURINOL
Bacteria-derived thrombolytic, Oxidase enzyme and lowers
decreased effect on subsequent STREPTOKINASE production of uric acid
uses due to antibody formation
Antidote to thrombolytic overdose AMINOCAPROIC ACID

Nonpurine, reversible inhibitor of
Xanthine Oxidase, Allopurinol FEBUXOSTAT
intolerance
ANTIPLATELET DRUGS
Irreversible COX inhibitor, Instant
prevention of arterial thrombosis,
SE: tinnitus, hypersensitivity, Reye
ASPIRIN PART 2
syndrome PENICILLINS
ADP inhibitor, Additive effects with Narrow spectrum Penicillins PENICILLIN G,
CLOPIDOGREL
Aspirin SE: hypersensitivity, GI upset PENICILLIN V
Glycoprotein IIb-IIIa inhibitor ABCIXIMAB
Phosphodiesterase inhibitor,
DIPYRIDAMOLE
Cardiac stress testing
SAMTER TRIAD
What is the triad of aspirin • Asthma
hypersensitivity? • Aspirin sensitivity
• Nasal polyps Penicillinase-resistant penicillins,
used primarily for staph infections
METHICILLIN
SE: interstitial nephritis,
ANTI-INFLAMMATORY AGENTS neutropenia
Extended-spectrum penicillinase
Irreversibly inhibits
ASPIRIN susceptible, AMPICILLIN
Cyclooxygenase 1 and 2
SE: pseudomembranous colitis
Reversible inhibitor of Antipseudomonal penicillins,

IBUPROFEN SE: hypertension, hypervolemia, PIPERACILLIN
Cyclooxygenase 1 and 2
bleeding
Irreversibly inhibits
CELECOXIB
Cyclooxygenase 2
Weak and reversible inhibition of

COX, antipyretic of choice in PARACETAMOL
pediatric population
DMARD of choice for Rheumatoid

METHOTREXATE CEPHALOSPORINS
arthritis
1st generation cephalosporin,
High bone penetration,
CEFAZOLIN
Surgical prophylaxis,
TNF-𝛼 Blocker INFLIXIMAB Greatest gram positive coverage
2nd generation cephalosporin,
Added gram negative coverage, CEFAMANDOLE
Forms 6-Thioguanine and cannot be SE: Disulfiram reaction
AZATHIOPRINE
given with Allopurinol 3rd generation cephalosporin,
Pseudomonas coverage, CEFOPERAZONE
SE: Disulfiram reaction
SE: Ocular toxicity & Ototoxicity CHLOROQUINE Most efficacious cephalosporin for
CEFTAZIDIME
Pseudomonas aeruginosa
4th generation cephalosporin, Broad
spectrum activity (gram positive CEFEPIME
Primarily used for IBD SULFASALAZINE and gram negative)
Which cephalosporin has the best
CEFTRIAXONE
penetrance to the BBB?
PROTEIN SYNTHESIS INHIBITORS
Binds to 50S subunit,

SE: aplastic anemia, gray baby CHLORAMPHENICOL
syndrome
Binds to 30S subunit,

SE: tooth enamel discoloration, TETRACYCLINE
Photosensitivity
OTHER CELL WALL SYNTHESIS INHIBITORS

Silver bullet against gram negative
bacteria, No gram positive activity,
AZTREONAM
WITH ANTI-PSEUDOMONAL
COVERAGE
CLAVULANIC ACID,
AVIBACTAM,
Beta-lactamase inhibitors
SULBACTAM,
TAZOBACTAM (CAST)
Binds to 50S subunit, DOC for
Treatment of MRSA, penicillin-allergic patients, ERYTHROMYCIN
VANCOMYCIN
SE: red man syndrome SE: diarrhea, cholestatic jaundice
Drug of last resort, Broad spectrum Binds to 50S subunit,

of activity (gram positive, gram Highest volume of distribution, AZITHROMYCIN
negative, anaerobes), IMIPINEM-CILASTIN Single dose administration
SE: CNS toxicity (confusion,
encephalopathy & seizures) Binds to 50S subunit,
IMIPENEM; anaerobic coverage, CLINDAMYCIN
AMIKACIN; SE: pseudomembranous colitis
Which antibiotics are considered MEROPENEM;
drugs of last resort? LINEZOLID;
STREPTOGRAMINS; Binds to 50S subunit, LINEZOLID,
VANCOMYCIN Vancomycin-resistance STREPTOGRAMIN
FLUOROQUINOLONES
2nd generation quinolone,
Treatment of urinary tract
CIPROFLOXACIN
infections and GIT infections,
SE: tendinitis
3rd generation quinolone,

AMINOGLYCOSIDES Treatment of pulmonary infections
LEVOFLOXACIN
Bactericidal, Binds to 30S subunit,
Treatment of endocarditis, GENTAMICIN 3rd generation quinolone, Broad
SE: nephrotoxicity, ototoxicity spectrum of activity, Anaerobic
MOXIFLOXACIN
coverage, Treatment of ocular
infections
Treatment of ocular infections TOBRAMYCIN
GATIFLOXACIN
SE: diabetes mellitus
Tuberculosis STREPTOMYCIN
GREPAFLOXACIN
SE: Cardiotoxicity
Treatment of drug-resistant
SPECTINOMYCIN
gonorrhea
4th generation quinolone,
TROVAFLOXACIN
SE: hepatotoxicity
Widest spectrum of activity,
Pseudomonas coverage, narrow AMIKACIN
therapeutic window
Treatment of hepatic
NEOMYCIN
encephalopathy
OTHER ANTIMICROBIALS
Anaerobic and antiprotozoal
coverage, 1st line treatment of
pseudomembranous colitis, METRONIDAZOLE
SE: Disulfiram reaction, metallic
taste, neurotoxicity
Treatment of urinary tract

NITROFURANTOIN
infections, SE: pulmonary fibrosis
SULFONAMIDES
ANTI-MYCOBACTERIAL AGENTS
Bactericidal, Inhibits mycolic acid
synthesis, SE: hepatotoxicity,
Vitamin B6 deficiency (peripheral
ISONIAZID
neuropathy, sideroblastic anemia)
drug-induced lupus,
Potent CYP450 inhibitor
Bactericidal, Inhibits DNA-
dependent RNA polymerase,
SE: red orange urine, RIFAMPICIN
Hepatotoxicity (minor),
CYP450 Inducer
Blocks Dihydropteroate Synthase SULFAMETHOXAZOLE Static, Inhibits arabinoglactan
synthesis, SE: visual dysfunction
ETHAMBUTOL
(retrobulbar neuritis, color
Blocks dihydrofolate reductase TRIMETHOPRIM blindness)
Static but Cidal on actively dividing
Sequential blockade in folate MTB, SE: hyperuricemia, PYRAZINAMIDE
synthesis, Urinary tract infections, hepatotoxicity (most)
SE: hypersensitivity (SJS, TEN), TMP-SMX
kernicterus, hemolysis in patients
with G6PD Cidal, Binds to 30S, IM
STREPTOMYCIN
SE: nephrotoxicity, ototoxicity
Treatment of burn infections SULFADIAZINE
DRUGS FOR LEPROSY

Most active drug against M. leprae,
Inhibits folate synthesis,
DAPSONE
SE: methomoglobinemia,
hemolysis in G6PDH deficiency
Inhibits DNA-dependent RNA
polymerase, SE: red-orange urine,
RIFAMPICIN
Delays onset of dapsone
resistance
Phenazine dye, Binds to guanine
bases, SE: red-orange skin CLOFAZIMINE
discoloration
ANTIFUNGALS
Most efficacious antifungal drug,
Forms artificial pores,
AMPHOTERICIN B
SE: Nephrotoxicity (RTA, Infusion
related)
Topical treatment of
dermatophytosis and candidiasis,
KETOCONAZOLE
SE: gynecomastia, CYP450
inhibitor
DOC for treatment and secondary
prophylaxis against Cryptococcal FLUCONAZOLE
meningitis
Interferes with fungal microtubules,

GRISEOFULVIN
SE: potent CYP450 inducer
Treatment of candidiasis
(oropharyngeal, esophageal,
NYSTATIN
vaginal), Swish and swallow
or suppository preparations
ANTIVIRAL DRUGS
Treatment of HSV and VZV,
SE: crystalluria,
ACYCLOVIR
Requires activation by viral
thymidine kinase
Treatment of CMV,
Requires activation by viral GANCICLOVIR
thymidine kinase
Treatment of HSV, VZV and CMV,

FOSCARNET,
Does NOT require viral
CIDOFOVIR
thymidine kinase activation
Prevents viral uncoating,
Influenza A coverage, SE:
AMANTADINE
cerebellar dysfunction, livedo
reticularis
Neuraminidase inhibitor, DOC for
OSELTAMIVIR
influenza
Treatment of Hepatitis B infection LAMIVUDINE
Treatment of Hepatitis C and RSV

RIBAVIRIN
infection
ANTIRETROVIRAL DRUGS
Nucleoside reverse transcriptase
inhibitor (NRTI), Requires
phosphorylation, Primary drug for ZIDOVUDINE
HIV, Prevents vertical transmission
of HIV, SE: lactic acidosis
Non-nucleoside reverse
transcriptase inhibitor (NNRTI), No
DELAVIRDINE
phosphorylation required,
SE: hepatotoxicity
Protease inhibitor,
SE: fat redistribution syndrome,
RITONAVIR
hyperlipidemia, insulin
resistance
DOC for Enterobius PYRANTEL PAMOATE
DOC for Trichinosis THIABENDAZOLE
DOC for trematodes and cestodes

PRAZIQUANTEL
EXCEPT echinococcosis
ANTI-MALARIAL Back-up drug to Praziquantel NICLOSAMIDE

Primary drug for malaria, Prevents
heme polymerization into
CHLOROQUINE
hemozoin, SE: retinal damage,
hearing loss CENTRAL NERVOUS SYSTEM
Chloroquine-resistance, Severe SEDATIVE HYPNOTICS
malaria, DOC for pregnant patients Acute anxiety attacks,
QUININE
with malaria, SE: hypoglycemia, Anesthesia induction, MIDAZOLAM
Blackwater fever, cinchonism Preoperative sedation
Eradication of hypnozoites of Seizure disorders
PRIMAQUINE (status epilepticus), DIAZEPAM
P. vivax and ovale
Alcohol withdrawal, Tranquilizer
Chemoprophylaxis MEFLOQUINE, Antidote to benzodiazepine
FLUMAZENIL
(chloroquine-resistant areas) MALARONE overdose
Chemoprophylaxis Anesthesia induction,

DOXYCYCLINE THIOPENTAL
(multi-drug resistant areas) Lethal injection, Truth serum
Seizure disorders in children,

ARTEMETHER / SE: precipitates porphyria, PHENOBARBITAL
DOC for malaria in the Philippines potent inducer of CYP450
LUMEFANTRINE
(P. falciparum)
(Co-Artem)
ANTIPROTOZOAL
Asymptomatic cyst carriers of DILOXANIDE
E. histolytica DUROATE
CHLORDIAZEPOXIDE
Amebic dysentery, Trichomoniasis, Which benzodiazepine has the longest half-life
Bacterial vaginosis, METRONIDAZOLE (36-200 hours)
longest half-life? longest spelling
SE: Disulfiram reaction
(many letters)
Cryptosporidium parvum infection NITAZOXANIDE
Pneumocystis jirovecii pneumonia TMP-SMX
PYRIMETHAMINE-
Toxoplasmosis
SULFADIAZINE
MELARSOPROL ±
African sleeping sickness (T. brucei)
SURAMIN
Chagas disease (T. cruzi) NIFURTIMOX
SODIUM
Leishmaniasis
STIBOGLUCONATE
ANTIHELMINTHIC DRUGS
Inhibits helminthic microtubules,
MEBENDAZOLE
Ovicidal
Inhibits helminthic microtubules,

Ovicidal and Larvicidal, DOC for ALBENDAZOLE
hydatid disease (echinococcosis)
DOC for Filaria and Loa loa, DIETHYL-

SE: filarial fever CARBAMAZINE
DOC for Strongyloides and

IVERMECTIN
Onchocerca, SE: Mazzotti reaction
ANTI-SEIZURE DRUGS Lowest MAC (highest potency),

Potent CYP450 inducer, slowest induction and recovery; METHOXYFLURANE
SE: gingival hyperplasia, SE: renal insufficiency
PHENYTOIN
hirsutism, fetal hydantoin
syndrome Dissociative anesthesia, NMDA
Potent CYP450 inducer, receptor blocker; KETAMINE
DOC for partial seizures and SE: Emergence delirium
CARBAMAZEPINE
trigeminal neuralgia,
SE: blood dyscrasias Anesthesia for patients with limited
Potent CYP450 inhibitor, cardiopulmonary reserve; ETOMIDATE
DOC for GTC and myoclonic SE: adrenal suppression
VALPROIC ACID
seizures,
SE: teratogen (spina bifida) Prolonged sedation, “milk of
PROPOFOL
Potent CYP450 inducer, amnesia”; SE; hypotension
DOC for seizures in children and PHENOBARBITAL
pregnant women, SE: porphyria
LOCAL ANESTHETICS
How will you distinguish whether local anesthetics are esters
DOC for absence seizures or amides?
ETHOSUXIMIDE
SE: behavioral changes
DOC for status epilepticus

DIAZEPAM
SE: anterograde amnesia
Treatment of neuropathic pain; Which local anesthetics have the shortest and longest half-
GABAPENTIN lives?
SE: nystagmus, tremor
Antiseizure for pregnant women;

LAMOTRIGINE
SE: Stevens-Johnson syndrome
CLINICAL USES OF ANTISEIZURE DRUGS

Seizure
Drugs of Choice Alternative Drugs
SKELETAL MUSCLE RELAXANTS
Type
Prototype nondepolarizing
Generalized neuromuscular blocker, TUBOCURARINE
• Valproic Acid • Phenobarbital,
Tonic- SE: orthostatic hypotension
• Phenytoin • Lamotrigine,
Clonic
Seizures • Carbamazepine • Topiramate Undergoes Hoffman elimination,
• Felbamate, SE: bronchospasm, Most frequently
• Carbamazepine ATRACURIUM
Partial Phenobarbital, used nondepolarizing
• Lamotrigine neuromuscular blocker
Seizures Topiramate,
• Phenytoin
Valproic acid
Lethal injection, Strychnine poisoning;
• Lamotrigine, PANCURONIUM
SE: hypertension
Absence • Ethosuximide Levetiracetam,
Seizures • Valproic Acid • Zonisamide, Reversal agent for nondepolarizing
Clonazepam
neuromuscular blockade SE: miosis, NEOSTIGMINE
Myoclonic • Clonazepam, salivation, diarrhea
and Levetiracetam,
Atypical • Valproic Acid Topiramate, Depolarizing neuromuscular blocker,
Absence Zonisamide, SE: malignant hyperthermia,
SUCCINYLCHOLINE
Syndromes Felbamate Affected by pseudocholinesterase
• Lorazepam activity
Status • Diazepam
-- ANTI-PARKINSONISM
Epilepticus • Phenytoin
• Phenobarbital LEVODOPA +
Drug of choice for Parkinson’s disease
CARBIDOPA
GENERAL ANESTHETICS
Treatment of hyperprolactinemia,
Highest MAC (lowest potency), SE: erythromelalgia, pulmonary BROMOCRIPTINE
NITROUS OXIDE fibrosis
SE: euphoria
Facilitate GABA-mediated Adjunctive drug for wearing-off

ENTACAPONE
inhibition, block NMDA and Ach-N DESFLURANE phenomena SE: red orange urine
receptor; SE: Pulmonary irritant
Facilitate GABA-mediated Anti-parkinsonism drug with antiviral
inhibition, block NMDA and Ach-N properties, SE: livedo reticularis, AMANTADINE
recePtor; SE: Postoperative HALOTHANE cerebellar ataxia
hepatitis, Malignant
hyperthermia Improves tremor and rigidity but has
BENZTROPINE,
no effect of bradykinesia,
BIPERIDEN
SE: atropine-like effects
What are the primary signs of Parkinson Disease?
ANTI-DEPRESSANTS
Tricyclic antidepressant, Treatment of
ANTI-PSYCHOTIC DRUGS enuresis, SE: atropine-like effects, IMIPRAMINE
cardiotoxicity
Prototype typical antipsychotic,
SE: corneal/lens deposits, failure of CHLORPROMAZINE Selective serotonin reuptake inhibitor
ejaculation (SSRI), First line drug for major
FLUOXETINE
depressive disorder, SE: erectile
Treatment of floridly psychotic dysfunction, serotonin syndrome
patients, SE: Major EPS (neuroleptic HALOPERIDOL
malignant syndrome) Serotonin-Norepinephrine reuptake
VENLAFAXINE
inhibitor (SNRI), SE: hypertension
DOC for suicidal and refractory
CLOZAPINE
schizophrenics, SE: agranulocytosis
Serotonin antagonist, SE: priapism TRAZODONE
2nd gen (5HT >>> D2),
SE: marked weight gain, OLANZAPINE
Tetracyclic antidepressant, Smoking
hyperglycemia
cessation, SE: weight loss, priapism, BUPROPION
seizures
2nd gen (5HT >>> D2), SE: priapism,
QUETIAPINE
hypnagogic hallucinations Monoamine oxidase inhibitor,
SE: hypertensive crisis when taken PHENELZINE
with tyramine, serotonin syndrome
DOC for schizophrenia in the youth,
RISPERIDONE What are the features of tricyclic antidepressant overdose?
SE: marked hyperprolactinemia
For mania and SIADH,

SE: nephrogenic diabetes insipidus, LITHIUM
teratogen (Ebstein’s anomaly)
What are the features of neuroleptic malignant syndrome?
NEUROLEPTIC MALIGNANT
MALIGNANT HYPERTHERMIA SEROTONIN SYNDROME
SYNDROME
Onset • Within minutes • Within hours • 1-3 days
Precipitating • Volatile anesthetics (halothane), • SSRIs, MAOIs, TCAs, Meperidine,
• Antipsychotics
drug succinylcholine MDMA, St. John’s Wort
Mechanism • Massive calcium release from SR • Excess serotonin • Dopamine antagonism
• Fever • Fever
• Fever
• Acidosis • Agitation
• Encephalopathy
• Rhabdomyolysis • Tremor
Clinical features • Vitals unstable
• Trismus • Clonus
• Elevated CPK
• Clonus • Hyperreflexia
• Rigidity
• Hypertension • Diaphoresis
First-line • Sedation, paralysis, intubation and
• Dantrolene • Diphenhydramine
treatment ventilation
• Cooling, cyproheptadine, • Cooling, Dantrolene, bromocriptine,
Other treatment • Cooling
chlorpromazine amantadine, diazepam
OPIOIDS
Replacement therapy for opioid
METHADONE
Prototype opioid (full agonist), dependence
SE: Miosis, Respiratory depression, MORPHINE
Constipation
DEXTRO-
Cough suppression METHORPHAN,
Severe pain, Breakthrough cancer
CODEINE
pain, Available in lollipop form or FENTANYL
transdermal patch
Balanced anesthesia, Frequently
NALBUPHINE
abused by healthcare professionals
Opioid of choice for acute pancreatitis,
MEPERIDINE
Does NOT cause miosis, SE: seizures
Which antithyroid drug inhibit peripheral conversion to T4 to
T3?
Antidote to opioid overdose NALOXONE
Treatment of opioid dependence NALTREXONE
Which opioids have the shortest and longest half-lives? What drugs can cause drug-induced hyperthyroidism?
CORTICOSTEROIDS
Acute adrenal insufficiency, status

HYDROCORTISONE
asthmaticus, thyroid storm
Prototype oral glucocorticoid,

SE: adrenal suppression, Cushing PREDNISONE
syndrome
ENDOCRINE AND METABOLIC DRUGS
HYPOTHALAMIC-PITUITARY DRUGS
Hastens fetal lung maturation BETAMETHASONE
Treatment of genetic short stature,
SOMATROPIN
failure to thrive
Mineralocorticoid replacement for
Treatment of acromegaly, variceal chronic adrenal insufficiency (Addison FLUDROCORTISONE
OCTREOTIDE disease)
bleeding
Treatment of hyperprolactinemia,
BROMOCRIPTINE FEMALE GONADAL HORMONES
prolactinoma
Most frequently used synthetic
Labor induction / augmentation, estrogen in OCPs, SE: hypertension,
ETHINYL
Control of postpartum hemorrhage, OXYTOCIN DVT/PE, endometrial CA,
ESTRADIOL
SE: fluid retention contraindicated in women
(age > 35) who are heavy smokers
Treatment of central diabetes
DESMOPRESSIN
insipidus SE: clear cell vaginal adenoCA in DIETHYL-
daughter STILBESTROL
THYROID DRUGS
Prevents estrogen-induced
NORGESTREL
Treatment of hypothyroidism, endometrial CA
LEVOTHYROXINE
myxedema coma
DMPA
Inhibits thyroid peroxidase, Blocks Depot
OCP of choice in lactating women
peripheral conversion to T4 to T3, DOC medroxyprogesterone
PTU
in pregnant hyperthyroid patients acetate
SE: agranulocytosis
Hormone-responsive breast CA,
Inhibits thyroid peroxidase, TAMOXIFEN
SE: endometrial CA
SE: agranulocytosis, teratogen METHIMAZOLE
(aplasia cutis)
Ovulation induction,
Preferred treatment for CLOMIPHENE
SE: multiple pregnancies
hyperthyroidism, RAI
SE: permanent hypothyroidism
Treatment of endometriosis DANAZOL

Reduces size and vascularity of thyroid
SSKI
gland
Symptomatic treatment of Medical abortion MIFEPRISTONE

hyperthyroidism, decreases PROPANOLOL
peripheral conversion of T4 to T3
Differentiate Wolf-Chaikoff effect from Jod-Basedow
phenomenon.
MALE GONADAL HORMONES What are the signs and symptoms of excess PTH?
Treatment of male hypogonadism,

SE: virilization, paradoxical TESTOSTERONE
feminization
Anabolic steroids, Illegal performance

OXANDROLONE
enhancers
Treatment of prostate cancer, Co-

FLUTAMIDE +
administered to prevent acute flare-
LEUPROLIDE
ups of tumor GI DRUGS
ALUMINUM
5𝛼 reductase inhibitor, Treatment of Neutralizes stomach acids,
HYDROXIDE /
benign prostatic hyperplasia and male FINASTERIDE SE: diarrhea-constipation (cancels
MAGNESIUM
pattern baldness each other)
HYDROXIDE
Greatly suppresses nocturnal acid
ANTI-DIABETIC AGENTS secretion, H2 blocker, CIMETIDINE
SE: gynecomastia
Most efficacious antidiabetic drug,
Activates tyrosine kinase, INSULIN Irreversible blockade of H+/ K+
SE: hypoglycemia, lipodystrophy ATPase, DOC for peptic ulcer disease OMEPRAZOLE
and Zollinger-Ellison syndrome
1st generation SU, SE: hypoglycemia,
CHLORPROPAMIDE
weight gain, Disulfiram reaction Prokinetic agent, Antiemetic,
METOCLOPRAMIDE
DOC for diabetic gastroparesis
2nd generation SU, SE: less
GLIPIZIDE
hypoglycemia/wt gain Osmotic laxative, Treatment of hepatic
LACTULOSE
encephalopathy
Newer insulin secretagogue,
REPAGLINIDE
NO hypoglycemia
Stimulant laxative, SE: melanosis coli SENNA
First line antidiabetic drug, Decreases
gluconeogenesis, SE: lactic acidosis, METFORMIN Opioid antispasmodic, DOC for
weight loss (DOC for obese diabetics) noninfectious diarrhea, LOPERAMIDE
SE: paralytic ileus (in children)
Acts on PPAR-𝛾, Insulin sensitizer,
PIOGLITAZONE
SE: CHF
𝛼-glucosidase inhibitor, SE: flatulence ACARBOSE
• insulin has
Why is there paradoxical
prolonged half life
improvement of diabetes in patients
due to decreased
with end-stage renal disease?
clearance
DRUGS FOR BONE METABOLISM
Inactive vitamin D, Treatment of

ERGOCALCIFEROL
rickets and osteomalacia
Active vitamin D, Treatment of

CALCITRIOL
secondary hyperparathyroidism
ANTINEOPLASTIC DRUGS
Treatment of Paget’s disease of bone, ALKYLATING AGENTS
hypercalcemia, Tumor marker for CALCITONIN
Treatment of lymphomas,
medullary thyroid CA CYCLO-
SE: hemorrhagic cystitis,
PHOSPHAMIDE
Rescue agent: Mesna
Suppresses osteoclast activity,
Treatment of Paget’s disease of bone ALENDRONATE
For Lymphoma (MOPP)
and osteoporosis, SE: esophagitis MECHLOR-
SE: marked vesicant actions
ETHAMINE
(skin blistering)
Phosphate-binding resin SEVELAMER
Treatment of colon cancer,
CISPLATIN,
SE: ototoxicity, nephrotoxicity,
CARBOPLATIN
Rescue agent: Amifostine
For Lymphoma
SE: Disulfiram reaction, PROCARBAZINE
Leukemogenesis
For Testicular cancer, Most specific for

G2 phase, SE: Pulmonary fibrosis, BLEOMYCIN
Bone marrow-sparing
Treatment of brain tumors,

CARMUSTINE
SE: CNS toxicity
MISCELLANEOUS ANTI-NEOPLASTICS
ANTIMETABOLITES Tyrosine kinase inhibitor, Treatment
Treatment of lymphomas and GTN, of CML, SE: fluid retention, multiple IMATINIB
SE: myelosuppression, pulmonary drug interactions
METHOTREXATE
fibrosis, Rescue agent: Leucovorin
(folinic acid) Treatment of metastatic breast and
Treatment of acute leukemias, gastric cancer, active against cells TRASTUZUMAB
SE: myelosuppression, 6- expressing HER-2/NEU
hepatotoxicity, Metabolism MERCAPTOPURINE
inhibited by allopurinol Inhibits VEGF, Treatment of metastatic
BEVACIZUMAB
Treatment of colorectal and skin cancers
cancer, Causes thymine-less death of 5-FLUOROURACIL
cells SE: myelosuppression Differentiation therapy, Treatment of ALL-TRANS
acute promyelocytic leukemia, RETINOIC ACID
Treatment of CML in blast crisis, Only vitamin that can cure cancer (ATRA)
Most specific for the S phase of the cell CYTARABINE
cycle
Inhibits ribonucleotide reductase,

GEMCITABINE
Treatment of pancreatic cancer
PLANT DERIVATIVES
Prevents microtubule assembly, VINCRISTINE,

SE: peripheral neuropathy VINBLASTINE
Podophyllotoxin, Inhibits DNA

topoisomerase II, Treatment of lung
ETOPOSIDE
cancer, Non-Hodgkin’s lymphoma and
GTN TOXICOLOGY
Camptothecin, Inhibits DNA Acute arsenic poisoning, Acute
topoisomerase I, Treatment of small TOPOTECAN mercury poisoning, Chronic severe DIMERCAPROL
cell lung cancer lead poisoning, SE: hypertension
Pica, ingestion of flakes of paint,
Prevents microtubule disassembly, abdominal colic, acute
PACLITAXEL LEAD
Advanced breast and ovarian cancers encephalopathy, wrist drop, mental
retardation
Chronic lead poisoning
ANTITUMOR ANTIBIOTICS (oral treatment), mild to moderate SUCCIMER
Intercalating agent, SE: dilated cases, SE: GI disturbance
cardiomyopathy, Rescue agent: DOXORUBICIN
Dexrazoxane Chronic severe lead poisoning, acute
symptomatic cases EDTA
SE: hypocalcemia, renal toxicity
Treatment of melanoma, Wilms tumor
ACTINOMYCIN D
and GTN Rice-water stools, garlicky breath,
Mee’s lines, raindrop pigmentation, ARSENIC
milk and roses complexion
Minamata disease (cerebral palsy,

deafness, blindness, mental ORGANIC MERCURY
retardation)
Side effect of amiloride • Hyperkalemia
Severe GI necrosis, hemosiderosis, • Pregnancy
IRON
restrictive cardiomyopathy • Sinus nodal
Contraindications to the use
tachycardia
of amiodarone
• Concommitant digoxin
Acute iron poisoning, intake
DEFEROXAMINE
Hemochromatosis Drug that can loosen phlegm
and make respiratory mucus • Bromhexine
thinner
Hepatotoxicity, Kayser-Fleischer Responsible for tingling
COPPER
rings, sunflower cataracts sensation of hands among the • Isoniazid
TB medications
• High doses of
Copper poisoning, Wilson's disease, physostigmine
PENICILLAMINE Possible etiologies of
SE: drug-induced lupus • Nicotine poisoning
cholinergic crisis
• Exposure to nerve
agent
• Steroids
END OF PHARMACOLOGY PHASE 3 Management of Crohn’s
• Surgery
disease
• Immunomodulators
• Carboprost
Drugs that can be used for
• Carbetocin
BUZZWORDS patients with uterine atony
• Ergometrine
Inhibits the degradation of
QUESTION ANSWER sympathetic amines thereby
• Tolcapone
• Promotes satiety via increasing sympathetic
hypothalamic receptor activity
• Slows down gastric Responsible for not
Effects of Pramlintide • Varicella IgG
emptying time developing chicken pox with
antibodies
• Inhibits inappropriate prior chicken pox vaccine
secretion of glucagon Drug that blocks mast cell
Medication given after • Thyroxine for degranulation preventing
• Ketotifen
pituitary adenoma resection hypothyroidism release of histamine in
• Niacin asthma exacerbation
Combination drugs with Drug most used for rate
• Ezetimibe
statin with added benefits control with atrial fibrillation • Digoxin
• Colestipol
Drug that acts as a in rapid ventricular response
somatostatin analog for • Octreotide Atypical anti-psychotic drug
acromegaly associated with reduced • Clozapine
Empiric treatment for septic extrapyramidal symptoms
• Vancomycin Indication for the use of
arthritis • Unstable angina
Anti-fungal drug with good diltiazem
• Fluconazole Contraindications of using • Fever
CSF penetration
• Triglycerides diphenoxylate in patients • Infectious diarrhea
Administration of fenofibrate with diarrhea • Bloody stool
• Cholesterol
reduces the following Avoid giving with
• LDL
Drug to address nasal dextromethorphan to avoid • Hydrazine
• Phenylephrine serotonin syndrome
congestion and rhinorrhea
Drug that decreases
• Amoxapine
absorption of cholesterol • Ezetimibe
Medications associated with • Bromocriptine
from the GIT
development of dyskinesia • Haloperidol
Drugs that achieve relaxation • Ipratropium bromide
• Levodopa
of smooth muscle in • Terbutaline
• Hypersensitivity
Adverse effects associated bronchial asthma • Theophylline
• Neurotoxicity
with aminoglycoside Antibiotics for purulent
• Ototoxicity • Clocaxillin
discharge from a stab wound
• Decreasing levels of Most common complication
MOA of allopurinol for
uric acid by inhibiting • Constipation
treatment of gout of sucralfate for gastric ulcer
xanthin oxidase
• TNF alpha inhibitors,
Blocks muscarinic receptors
Methotrexate,
for treatment of nausea and • Hyoscine
DMARDs Rituximab
vomiting
• No effect on disease
Should be corrected before
• Vitamin D deficiency remission
starting denosumab therapy
• Trichloroacetic acid
Inhibits the reabsorption of Treatment of infections with
• Dapagliflozin • Podophyllin
glucose in the kidney human papilloma virus
• Imiquimod
Improves urine flow in
patients with bladder • Betanechol • Nephrotoxicity
neuropathy Adverse effects associated • Ototoxicity
• Decrease LDL with Streptomycin • Neuromuscular
Expected effects from niacin blockade
• Decrease triglyceride
for dyslipidemia Given along with leuprolide
• Decrease cholesterol
in the treatment of prostate
Notorious side effect of • Finasteride
• Erectile dysfunction cancer to counteract
finasteride
testosterone production
• Vancomycin
Drug of choice for whipworm,
Effective treatment for MRSA • Ceftaroline • Albendazole
pinworm, and tapeworm
• Linezolid
Drug of choice for flukes or Symptom associated with side
• Praziquantel • Urinary retention
trematodes effect of ipratropium bromide
Anticholinergic crisis • Atropine poisoning Risk of hypoglycemia with
Drug that suppresses this drug is low when used as • Pioglitazone
• Dextromethorphan a monotherapy
coughing reflex
A broad spectrum anti- • Fexofenadine
• Mebendezole Third generation
helminthic agent • Bilastine
antihistamines
Drug that can prevent • Levocetirizine
bleeding from esophageal • Beta blockers • Corneal micro deposits
varices • Thyroid function
Findings associated with
Drug associated with abnormalities
• Ketamine long-term use of amiodarone
dissociative anesthesia • Light sensitive blue gray
Serotonin norepinephrine discoloration of the skin
reuptake inhibitor drug used Treatment for giardiasis • Metronidazole
• Duloxetine
for neuropathic pain and Effective drug for treatment
fibromyalgia • Ceftriaxone
of soft chancre/chancroid
Contraindication for Drugs for infections
• Hemorrhagic stroke • Azithromycin
thrombolytic agent alteplase complicated by presence of
Drug of choice for shigella • Quinolones – first line • Ciprofloxacin
atypical organisms
infection • Azithromycin Drugs that increase the risk • Gemfibrozil
First line drug of choice for of myopathy when added to • Fenofibrate
• Amoxicillin
Streptococcus pharyngitis simvastatin for dyslipidemia • Clofibrate
• Narrow therapeutic • Aggressive evaluation
Characteristics of window and treatment
theophylline • Metabolized by • Associated with
CYP450 Management principles for
occurrence of
Increases plasma • Cholestyramine complicated UTI
antibiotic resistance
concentration of • Probenecid • Address the cause of
methotrexate • Omeprazole the complication
• Varicella zoster Increase motility and resting
• Metoclopramide
Acyclovir treatment • CMV infection tone of GIT for gastroparesis
• HSV infection Antibiotic that has activity
Drug that can induce against Treponema, • Doxycycline
• Sevoflurane Chlamydia, and Neisseria
malignant hyperthermia
• Inhibits Drug of choice for patients
MOA of bupropion as an anti- • Ampicillin (category B)
norepinephrine 18-weeks AOG with UTI
depressant
dopamine reuptake • Competitive non-
Cardiac effect associated with
• Duloxetine selective inhibition of
Treatment of generalized Theophylline
• Escitalopram phosphodiesterase
anxiety disorder
• Clonazepam Dopamine receptor agonist • Cabergoline
Antibiotic of choice for Prokinetic agent that acts as
• Metronidazole • Mosapride
Trichomoniasis selective 5HT4 agonist
Common side effect of beta • Bronchospasm Quinoline associated with
• Nalidixic acid
blockers in patients with • Difficulty of breathing bacterial resistance
bronchial asthma • Wheezing • Sedation
Effects of morphine at mu
Treatment of uncomplicated • Cotrimoxazole • Respiratory depression
opioid receptor
UTI that can be shortened to • Norfloxacin • Analgesia
three days • Trimethoprim MOA of spironolactone for
• Being an androgen
Drug that is destroyed by the increased facial hair with
receptor antagonist
acidic environment in the • Sucralfate male pattern distribution
stomach • Nosocomial pneumonia
MOA of anticonvulsant action • Inhibition of voltage • MRSA infections
Linezolid activity
of gabapentin gated calcium channels • Intraabdominal infection
Drug of choice for by Enterococcus
• Metronidazole Contraindicated in patients with • Calcium channel
trichomonads
• Immunosuppressants bleeding esophageal varices blockers
Modalities used in the • Acetylcholinesterase Drug that is started when
management of myasthenia inhibitors morphine withdrawal • Buprenorphine
gravis • Intravenous symptoms have occurred
immunoglobulins Side effects of spironolactone • Hyperkalemia
Drug that inhibits purine Inhibitor of DPP4 • Sitagliptin
• Azathioprine
synthesis • Hypocalcemia
Nephrotoxic drug that should Side effects of prednisone • Hyperglycemia
• Netilmicin
be avoided in CKD patients • Hypertension
Inhibits glycoprotein IIb/IIIa • Prevents the secretion
receptors found on the • Abciximab of H+ in the tubule
surface of platelets • Inhibits carbonic
Antagonizes the effect of Actions of acetazolamide
• Eplerenone anhydrase
endogenous aldosterone • Promotes Na+ and K+
Treatment for Pseudomonas • Cefoperazone excretion
• Doxycycline Appropriate agent for • Reteplase
• Intramuscular cerebral ischemic attack • Thrombolytic therapy
Suitable treatment for
benzathine penicillin Increased toxicity of digoxin • Destroying enteric
uncomplicated syphilis
• Intramuscular when antibiotic is given bacteria that naturally
ceftriaxone concomitantly inactivate digoxin

Pharmacology

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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/

PHARMACOKINETICS WATER AND LIPID SOLUBILITY OF DRUGS

DRUG DISTRIBUTION CYTOCHROME P450 ENZYMES

DRUG EXCRETION FIRST ORDER VS.

Rate of elimination is MNEMONIC: Zero Order Kinetics

EFFECTIVE DRUG CONCENTRATION • Most important pharmacokinetic parameter to be

LOADING DOSE RECEPTORS VS EFFECTORS

GRADED DOSE-BINDING RELATIONSHIP

QUANTAL DOSE-RESPONSE RELATIONSHIP

ANTAGONIST PART 1 ANTAGONIST PART 2

STEP 1 – TRANSPORT AND SYNTHESIS CHOLINORECEPTORS

ANTIDOTE TO ORGANOPHOSPHATE POISONING

CHOLINERGIC ANTAGONISTS AT MUSCARINIC SITES (PARASYMPATHOLYTICS)

STEP 1 – SYNTHESIS STEP 4 – TERMINATION

ADRENERGIC AGONISTS (SYMPATHOMIMETICS)

BETA RECEPTOR AGONISTS

SELECTIVE ALPHA BLOCKERS

NON-SELECTIVE ALPHA BLOCKERS

Local Anesthetic Activity

TREATMENT FOR GLAUCOMA

DRUG CLASS EXAMPLES MECHANISM

SUPPLEMENT: Malignant Hypertension

DRUGS USED IN THE TREATMENT OF ANGINA PECTORIS

DRUGS USED IN HEART FAILURE CHF: Therapeutic Strategies

• increased by hypokalemia, hypomagnesemia, and hypercalcemia

Treatment of Digitalis Toxicity

OTHER DRUGS FOR CHF BETA-BLOCKERS

MNEMONIC: Survival in CHF • ABNORMAL CONDUCTION

CLASS 1 ANTIARRHYTHMICS • further subdivided based on their effects on AP duration

CLASS 2 ANTIARRHYTHMICS CLASS 3 ANTIARRHYTHMICS

Proximal Convoluted Cortical Collecting Ducts

• Drowsiness, • Hypokalemic • Hypokalemic • Hyperkalemia, • Hyperkalemia, • Transient

ANTIDIURETIC HORMONE AGONIST/ANTAGONIST • Terlipressin: not • Central pontine myelinosis

DRUGS USED FOR DYSLIPIDEMIA BILE ACID BINDING RESINS

DRUGS ON SMOOTH MUSCLES

ERGOT ALKALOIDS PROSTAGLANDINS AND OTHER EICOSANOIDS

SUPPLEMENT: DRUGS USED FOR MIGRAINE

MECHANISM OF ACTION OF ASTHMA DRUGS

EFFECTS OF IMPORTANT EICOSANOIDS

OTHER DRUGS USED FOR ERECTILE

Drugs SILDENAFIL [B], TADALAFIL [B], VARDENAFIL [B]

NEW ASTHMA DRUGS: BIOLOGIC ANTIBODIES

DRUGS USED IN ASTHMA

ASTHMA Anti-IL5 and anti-IL5R (All are given SC)

DRUGS FOR COUGH

MYELOID GROWTH FACTORS Mechanisms of hemostasis:

PLATELET GROWTH FACTORS

MEGAKARYOCYTE GROWTH FACTOR

4th step: fibrous Organization

PRO-CLOTTING DRUGS (PROTHROMBOTICS)

NSAIDS, ACETAMINOPHEN, DMARDS AND ASPIRIN: DOSAGE RANGES

DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS XANTHINE OXIDASE INHIBITORS

MICROTUBULE ASSEMBLY INHIBITOR

MINIMUM INHIBITORY CONCENTRATION

CEPHALOSPORINS MNEMONIC: Second Generation Cephalosporins

OTHER CELL WALL INHIBITORS

BACTERIAL PROTEIN SYNTHESIS INHIBITORS

• Gray Baby Syndrome:

DRUGS USED IN TUBERCULOSIS