Medical Program

Pharmacology PHAR 681

The primary objective of the Pharmacology course is to provide the student with a solid basis for understanding the pharmacology of therapeutic agents, and thus with a foundation for future clinical decision making with respect to pharmacological therapies.

The course begins with a basic principles module exploring the fundamental principles of pharmacokinetics and pharmacodynamics. This is followed by systematic discussion of the major drug used in specific clinical situations. Topics covered include the pharmacology of the autonomic and central nervous systems, cardiovascular, respiratory, gastrointestinal, renal, endocrine, and autacoid pharmacology, and chemotherapy. Particular emphasis is placed on the mechanisms of action, therapeutic, and adverse effects and clinical indications of drugs used in medical practice.

The lecture sequence has been coordinated with the Pathophysiology course and the schedules have been subdivided into different subject blocks to facilitate learning across disciplines.

Each lecture has well-defined learning objectives intended to help students organize their study and prepare for examinations.

For advanced discussion of selected topics, the class is divided into small groups, and short clinical cases are presented and discussed by students under the guidance of a group facilitator.

 

Learning Objectives

 

BASIC PRINCIPLES (Lectures 1-8)

DRUG RECEPTORS & PHARMACODYNAMICS

By the end of this session, the student should be able to:

  • Define the following terms: pharmacology, pharmacodynamics, pharmacokinetics, pharmacotherapy and toxicology.
  • Define selectivity and specificity.
  • Define receptor and list the different classes of receptors with which drugs interact.
  • Describe graded and quantal dose-response curves for a drug. Define KD, Emax, EC50, ED50, TD50 and LD50.
  • Define efficacy and potency.
  • Define agonist, antagonist, full agonist, partial agonist, and inverse agonist.
  • Describe the different mechanisms of receptor and nonreceptor antagonism.
  • Describe desensitization, tachyphylaxis, tolerance and resistance. Explain the mechanisms that underlie such phenomena.
  • Explain therapeutic index and therapeutic window.

 

MOLECULAR MECHANISMS OF DRUG ACTION

By the end of this session, the student should be able to:

  • Describe the different types of molecular interactions by which pharmacologic agents exert their effects.

 

PHARMACOKINETICS

By the end of this session the student should be able to:

  • Describe the factors that govern the absorption and distribution of drugs and their routes and mechanisms of elimination.
  • Describe the main routes of drug administration.
  • Explain the effect of pH on drug absorption.
  • Explain ion trapping.
  • Define bioavailability and bioequivalence.
  • Describe the various factors that affect drug distribution.
  • List the major mechanisms responsible for drug metabolism.
  • Describe how metabolism affects drug structure and function.
  • Explain the first-pass effect.
  • List Phase I and Phase II reactions of drug metabolism.
  • List the main organs involved in drug metabolism.
  • Describe the main features and properties of the cytochrome P450 enzyme family.
  • Explain how drugs are chemically altered by cytochrome P450 enzymes.
  • Explain the clinical relevance of enzyme induction and enzyme inhibition.
  • List the main drugs that can act as inhibitors and inducers of cytochrome P450 isoenzymes.
  • Outline the main molecular mechanisms of cytochrome P450 induction.
  • Explain the clinical relevance of the induction of drug transporters.
  • List examples of toxic metabolism (eg acetaminophen).
  • List the main factors that can affect drug metabolism  (genetic, diet & environmental, age, diseases, drug-drug interactions).

 

CLINICAL PHARMACOKINETICS

By the end of this session the student should be able to:

  • Define clearance, volume of distribution, extraction ratio, bioavailability,  half-life, loading dose and maintenance dose.
  • Calculate the volume of distribution given a loading dose and the plasma drug concentration at time zero.
  • Explain the difference between first-order and zero-order kinetics of drug elimination.
  • List examples of drugs that follow zero-order kinetics.
  • Describe the concept of steady-state with regard to plasma drug concentrations.
  • Explain the importance of different pharmacokinetic parameters for the duration of drug action.
  • Calculate the drug plasma levels reached after a given number of half-lives during drug administration.
  • Calculate the drug plasma levels reached after a given number of half-lives when drug administration is discontinued.
  • Use pharmacokinetic concepts and principles to design a rational dosage regimen.
  • Calculate a loading dose to achieve a target plasma drug level given the drug’s volume of distribution.
  • Given a drug’s elimination clearance, calculate the maintenance dose needed to achieve or maintain an average steady-state drug level using either a continuous infusion or a fixed-dose, fixed-time interval regimen.
  • Given the half-life of a drug, calculate the accumulation factor.

 

ADVERSE EFFECTS OF DRUGS

By the end of this session the student should be able to:

  • Describe and explain the general mechanisms of drug toxicity, including the differences between on-target and off-target effects.
  • Describe how the production of toxic metabolites can contributes to adverse effects.
  • Describe the differences between type A and type B adverse drug reactions.
  • Discuss the different kinds of drug-drug interactions (pharmacokinetic, pharmacodynamic and drug-herb interactions) in the context of drug toxicity.
  • Describe the pathology of drug toxicity and explain the differences between the temporal aspects of toxicity, cellular toxicity and organ and tissue toxicity.
  • Discuss the use of drugs in pregnancy with respect to the FDA pregnancy categories.

 

PHARMACOLOGY OF THE AUTONOMIC NERVOUS SYSTEM (Lectures 10-14)

INTRODUCTION TO THE PHARMACOLOGY OF THE ANS

By the end of this session the student should be able to:

  • Compare and contrast the anatomy of the sympathetic and parasympathetic divisions of the autonomic nervous system (ANS).
  • Describe the main functions of the SNS and the PNS.
  • Classify autonomic nerves based on the primary neurotransmitters released from their terminals.
  • Describe the synthesis, storage, release and inactivation of acetylcholine.
  • Describe the synthesis, storage, release and inactivation of norepinephrine.
  • Describe the location and function of cholinergic and adrenergic receptor subtypes and the signaling mechanisms associated with them.
  • Describe presynaptic regulation of acetylcholine and norepinephrine release.
  • Describe how the central nervous system controls the activity of the ANS.
  • Explain what tone is, and apply knowledge of predominant tone to the regulation of dually-innervated organs.
  • Describe the baroreceptor reflex. Explain how an infusion of norepinephrine triggers a baroreceptor reflex leading to bradycardia.
  • Explain the effects of adrenergic and cholinergic drugs on the different tissues of the eye.

 

CHOLINERGIC AGONISTS AND ANTAGONISTS

By the end of this session, the student should be able to:

  • List the different classes of cholinergic and anticholinergic drugs.
  • Describe the muscarinic and nicotinic actions of acetylcholine.
  • Discuss the actions of acetylcholine on the cardiovascular system.
  • Describe the actions, uses and adverse effects of muscarinic agonists.
  • Describe the actions, uses and adverse effects of nicotinic receptor agonists.
  • Describe the mechanism of action, uses and adverse effects of the indirect-acting cholinergic agonists (anticholinesterases).
  • Compare and contrast the effects of direct-acting and indirect-acting cholinergic agonists on the cardiovascular system.
  • Explain why anticholinesterases are reversible or irreversible, and indicate which anticholinesterases are in each category.
  • Describe the mechanism by which pralidoxime reactivates phosphorylated acetylcholinesterase.
  • Describe the mechanism of action, actions, uses and contraindications of muscarinic receptor antagonists and discuss the different pharmacokinetic properties of the tertiary amines and the quaternary ammonium compounds.
  • Describe the mechanism of action of the ganglion blockers and predict their effects by applying knowledge of the predominant tone of a dually-innervated organ.
  • Describe the mechanism of action, uses and main adverse effects of the nondepolarizing and the depolarizing neuromuscular blockers.
  • Describe the mechanism of action of the drugs that act presynaptically on cholinergic neurons: inhibitors of acetylcholine synthesis, storage and release.

 

ADRENERGIC AGONISTS AND ANTAGONISTS

By the end of this session, the student should be able to:

  • Describe the pharmacological effects, uses and adverse effects of the endogenous catecholamines.
  • Contrast the cardiovascular effects of a low dose and a high dose of epinephrine.
  • Explain the baroreceptor reflex.
  • Describe the pharmacological effects, uses and adverse effects of  agonists.
  • Compare, contrast & explain the cardiovascular effects of epinephrine, norepinephrine and isoproterenol.
  • Describe the pharmacological effects, uses and adverse effects of 1 and 2 agonists.
  • Describe the pharmacological effects, uses and adverse effects of the indirect-acting and mixed-action adrenergic agonists.
  • Describe the pharmacological effects, uses and adverse effects of  and adrenergic antagonists.
  • Explain epinephrine reversal.
  • Describe the pharmacological effects, uses and adverse effects of drugs that act presynaptically on the adrenergic neuron (inhibitors of norepinephrine synthesis, storage or release, metabolism and reuptake).

 

CHEMOTHERAPY OF MICROBIAL DISEASES (Lectures 15-21)

PRINCIPLES OF ANTIMICROBIAL THERAPY

By the end of this session the student should be able to:

  • Define the terms: antibiotic, empiric antimicrobial therapy, selective toxicity, bacteriostatic and bactericidal.
  • Define MIC and MBC.
  • Describe the post-antibiotic effect (PAE)
  • Define chemotherapeutic spectrum.
  • Describe the basic principles of combination therapy with antimicrobial drugs.
  • Describe the terms synergism and antagonism and describe mechanisms of synergistic and antagonistic action.
  • Define bacterial resistance and describe the mechanisms involved in acquiring bacterial resistance.
  • Describe the basic principles of antimicrobial chemoprophylaxis.
  • Discuss potential adverse effects of antimicrobial drugs.
  • Discuss the classification of antimicrobial drugs based upon the mechanism of action and explain the modes of action of various antimicrobial drugs.

 

INHIBITORS OF CELL WALL SYNTHESIS

By the end of this session the student should be able to:

  • List the different classes of antimicrobial drugs that act by inhibiting cell wall synthesis (-lactam compounds, vancomycin, bacitracin).
  • Describe the structural relationship of the penicillin molecule with antimicrobial activity.
  • Explain the mechanism of action of β-lactam antibiotics.
  • Classify penicillins according to their spectrum of antimicrobial activity (natural, antistaphylococcal, extended spectrum, antipseudomonal penicillins).
  • Describe the pharmacologic properties and uses of the penicillins in each class.
  • Explain the rationale for combining β-lactamase inhibitors with penicillins.
  • Explain the rationale of combining penicillins and aminoglycosides.
  • Describe the pharmacokinetic properties of penicillins.
  • Describe the repository penicillins.
  • Describe the adverse effects and contraindications of penicillins.
  • Discuss the stability of penicillins to acid or -lactamase.
  • Explain the mechanism of action of cephalosporins.
  • Describe the four generations of cephalosporins with specific examples and the differences in their antimicrobial spectrum, pharmacokinetic properties.
  • Describe the uses and adverse effects of cephalosporins.
  • Describe the spectrum, uses and adverse effects of carbapenems and monobactams.
  • Explain the rationale for combining imipenem with cilastatin.
  • Discuss the mechanism of action, uses and adverse effects of vancomycin and bacitracin.
  • Explain the terms cross-hypersensitivity.

 

PROTEIN SYNTHESIS INHIBITORS

By the end of this session the student should be able to:

  • Discuss the mechanism of action of each class of protein synthesis inhibitors (Tetracyclines, Macrolides, Aminoglycosides, Spectinomycin, Clindamycin, Chloramphenicol, Streptogramins, & Oxazolidinones).
  • Explain the mechanism of acquired drug resistance.
  • Explain the rational basis for combination therapy with an aminoglycoside and a penicillin, cephalosporin, or vancomycin.
  • Describe the pharmacokinetic properties of each class of protein synthesis inhibitors.
  • Define concentration-dependent killing and time-dependent killing.
  • Discuss the postantibiotic effect of aminoglycosides.
  • Explain the importance of peak and trough levels of aminoglycosides.
  • Discuss the need for aminoglycoside dose adjustment in patients with compromised renal function.
  • Discuss the adverse effects of each class of protein synthesis inhibitors.
  • Describe drug interactions of macrolides due to inhibition of cytochrome P450 enzymes.
  • Describe the primary therapeutic indications of each class of protein synthesis inhibitors.

 

FOLATE ANTAGONISTS

By the end of this session the student should be able to:

  • Explain the mechanism of action of sulfonamides and trimethoprim.
  • Describe the pharmacokinetic properties, mechanism of acquired resistance, clinical uses, adverse effects and contraindications of sulfonamides and trimethoprim.
  • Discuss the antimicrobial synergy due to sequential blockade with co-trimoxazole.

 

QUINOLONES AND FLUOROQUINOLONES

By the end of this session the student should be able to:

  • Describe the mechanism of action of fluoroquinolones.
  • Classify fluoroquinolones in groups according to their antimicrobial spectrum.
  • Describe the pharmacokinetics properties of fluoroquinolones
  • Describe the adverse effects and contraindications of fluoroquinolones.

 

ANTIMYCOBACTERIALS

DRUGS FOR TUBERCULOSIS

By the end of this session the student should be able to:

  • List the first-line agents and the alternative second-line agents used for the chemotherapy of tuberculosis.
  • Describe the mechanisms of action, pharmacokinetic properties and adverse effects of the drugs used for the chemotherapy of tuberculosis.
  • Explain the drug interactions of rifampin with anticoagulants and other drugs, such as oral contraceptives.
  • Discuss the pharmacokinetic advantages of rifabutin over rifampin.
  • Describe the mechanism of resistance to the drugs used for the chemotherapy of tuberculosis.
  • Describe the recommended regimens used for chemotherapy of tuberculosis.
  • Describe the regimen recommended for chemoprophylaxis of tuberculosis.
  • Describe the drugs active against atypical mycobacteria.

 

DRUGS FOR LEPROSY

By the end of this session the student should be able to:

  • Describe the drugs used in the treatment of leprosy (Hansen's disease), their mechanism of action and adverse effects.
  • Describe the drugs used for reversing the lepra reactions and the erythema nodosum leprosum reaction.
  • Explain the WHO regimen for treatment of leprosy.

 

CARDIOVASCULAR PHARMACOLOGY (Lectures 22-28)

DIURETICS

By the end of this session the student should be able to:

  • Describe the normal regulation of fluid and electrolytes by the kidneys.
  • Describe the location and function of major ion transporters and channels on renal epithelial membranes.
  • Explain how sodium transport influences the reabsorption of other ions and water in the kidney.
  • Explain how abnormal renal function can cause hypertension or edema.
  • Describe the mechanism of action of the different classes  of diuretics.
  • Describe the changes that occur with electrolyte transport, water reabsorption and hemodynamics when specific diuretics inhibit kidney function.
  • Explain how thiazides and loop diuretics can cause metabolic alkalosis.
  • Explain how diuretic therapy can lead to hyponatremia.
  • Describe the metabolic imbalances with diuretic therapy on glucose, urate, lipids, calcium, magnesium and potassium. Explain the underlying mechanisms involved.
  • Describe the clinical consequences of interactions between diuretics and drugs such as cardiac glycosides, oral hypoglycemics, NSAIDs and angiotensin inhibitors.
  • Describe why reduced renal perfusion can limit the use of thiazide diuretics.
  • Describe the therapeutic uses of diuretics.

ANTIHYPERTENSIVE DRUGS

By the end of this session the student should be able to:

  • Describe the short-term and long-term regulation of blood pressure.
  • Discuss the etiology of hypertension.
  • Discuss the mechanism of action of each class of antihypertensive drugs.
  • Describe the adverse effects of antihypertensive drugs.
  • Describe the use of antihypertensive drugs in hypertensive emergencies and in pregnancy (e.g. eclampsia).
  • Discuss subgroups with special antihypertensive drug considerations (e.g. African-Americans, diabetics, renal failure patients).
  • Discuss the guidelines of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

 

DRUGS USED IN HEART FAILURE

By the end of this session the student should be able to:

  • Describe the action potential in different types of cardiac cells (sinus node, AV node, atrium, His bundle, Purkinje cell, ventricle cell).
  • Discuss the relationship between cellular cardiac electrical activity and the ECG.
  • Explain the mechanisms that control myocardial contractility and the autonomic control of the heart.
  • Describe the pathophysiology of heart failure and the compensatory physiological responses.
  • Describe the New York Heart Association Classification of Heart Failure.
  • Describe the therapy goals in heart failure.
  • Describe the mechanism of action, pharmacokinetic properties, adverse effects and clinical indications of drugs used in heart failure.
  • Compare and contrast the management of acute and chronic heart failure.

 

ANTIARRHYTHMIC DRUGS

By the end of this session the student should be able to:

  • Describe the electrophysiology of normal cardiac rhythm
  • Define arrhythmias and describe the mechanisms of cardiac arrhythmias
  • List antiarrhythmic drugs and classify them according to the Vaughn-Williams classification into classes I, II, III and IV, including other miscellaneous agents.
  • Explain the molecular mechanism of action of each drug in each drug class.
  • Describe the actions of antiarrhythmic drugs and their effect on the phases of the cardiac action potential.
  • Describe the routes of administration, biotransformation and excretion of antiarrhythmic drugs.
  • Describe the pharmacokinetics properties of antiarrhythmic drugs.
  • Describe the adverse effects of antiarrhythmic drugs.
  • Describe the significance of electrolyte and acid-base imbalance in arrhythmia generation and their influence on antiarrhythmic drug action.

 

ANTIANGINAL DRUGS

By the end of this session, the student should be able to:

  • Describe the different types of angina.
  • Describe the pathophysiology of angina.
  • Describe the mechanism of action and pharmacokinetic properties of drugs used in the management of angina.
  • Describe the organ system effects and adverse effects of antianginal drugs.
  • Describe the use of antianginal drugs in classic (effort-related), vasospastic and unstable angina pectoris.

 

AUTACOIDS AND AUTACOID ANTAGONISTS (Lecture 29)

By the end of this session the student should be able to:

  • Describe the synthesis, storage, release, mechanism of action, effects, clinical uses & toxicity of histamine.
  • Describe the major classes of histamine receptors and discuss their tissue distribution, signalling mechanism and function.
  • Describe the different classes of histamine antagonists, their actions, uses, adverse effects & drug interactions.
  • Compare and contrast the adverse effects of the first and second generation H1 receptor antagonists.
  • Describe the synthesis, storage, release, mechanism of action & effects of serotonin.
  • Describe the major types of serotonin receptors.
  • Describe the actions, uses & adverse effects of serotonin agonists and antagonists.
  • Describe the synthesis, mechanism of action, uses & adverse effects of eicosanoids.
  • Describe the mechanism of action, uses and adverse effects of the leukotriene modifiers (leukotriene-receptor antagonists and inhibitors of leukotriene synthesis).
  • Briefly discuss the major properties of corticosteroids and NSAIDs

 

RESPIRATORY PHARMACOLOGY(Lecture 30)

By the end of this session the student should be able to:

  • Outline the pathophysiology of asthma.
  • Describe the role of various mediators (histamine, acetylcholine, proteases, leukotrienes C4, D4; prostaglandins; cytokines) in asthma.
  • Explain the molecular mechanism of action of drugs used in asthma.
  • Differentiate the effects on the lung of the quick relief drugs and the drugs used for long term control.
  • Describe the routes of administration of each drug.
  • Describe the principal adverse effects of the drugs of each class.
  • Describe the clinically important drug interactions of the drugs of each class
  • Describe the principal contraindications of the drugs of each class.
  • Discuss the beneficial aspects of aerosol formulations versus oral formulations.
  • Discuss the use of combinations of agents in the chronic management of asthma.
  • Describe the management of acute asthma.
  • Describe the main features of COPD.
  • Discuss the drugs used for the treatment of COPD.
  • Discuss the 2007 guidelines for management of asthma from the National Heart, Lung and Blood Institute.
  • Discuss the 2008 guidelines for management of COPD from the Global Initiative for Obstructive Lung Disease (GOLD).

 

GASTROINTESTINAL DRUGS (Lectures 32 & 33)

By the end of this session, the student should be able to:

  • Describe the mechanism of action, effects, and adverse effects drugs used to treat peptic ulcer disease and gastroesophageal reflux disease.
  • Describe the mechanism of action, effects and adverse effects of prokinetic agents.
  • List the main classes of laxative agents and discuss their mechanisms of action, their adverse effects, indications and contraindications.
  • Discuss the main classes of antidiarrheal drugs, their mechanisms of action, adverse effects, indications and contraindications.
  • Describe the main drugs used to treat irritable bowel syndrome.
  • Describe the main antiemetic drugs, their mechanisms of action, adverse effects, indications and contraindications.
  • Describe the main drugs used to treat inflammatory bowel disease.
  • List the pancreatic enzyme supplements and their indications.

  

ORAL, PARENTERAL AND IMPLANTED CONTRACEPTIVES (Lecture 34)

By the end of this session, the student should be able to:

  • List the different contraceptive methods available and compare their effectiveness.
  • Discuss combination and progestin-only contraceptives.
  • Explain what is meant by monophasic, biphasic or triphasic combination contraceptives.
  • Describe the mechanism of action, adverse effects and contraindications of contraceptives.
  • Describe the organ system effects of contraceptives.
  • Discuss the beneficial effects of contraceptives.
  • Describe the adverse effects, contraindications and cautions of contraceptives.
  • Describe advantages and disadvantages of various contraceptives, including both oral and non-oral formulations.
  • Describe important drug interactions with hormonal contraceptives.
  • Describe the agents used for postcoital contraception.

 

DRUGS ACTING ON THE UTERUS:
OXYTOCICS AND TOCOLYTICS (Lecture 35)

By the end of this session the student should be able to:

  • Explain the molecular mechanism of action of each drug in each drug class.
  • Describe the receptors targeted by the oxytocics and the sensitivity of the uterus to the various oxytocics during the three trimesters of pregnancy.
  • State the usual route(s) of administration, onset and duration of action of the various oxytocic agents.
  • State the usual route(s) of administration as well as onset and duration of action of the various tocolytic agents.
  • Describe the potential adverse effects of the oxytocic agents in the mother (uterine, extrauterine) and in the infant.
  • Describe the clinical use of the individual oxytocics.
  • Identify the potential benefits and risks of administering tocolytic agents to the mother and baby.

 

DRUGS USED IN DISORDERS OF COAGULATION (Lecture 36)

By the end of this session the student should be able to:

  • Explain hemostasis and its regulation.
  • Define venous and arterial thrombosis.
  • Describe the role of Vitamin K for the synthesis of coagulation factors and Proteins C and S.
  • Describe the molecular mechanism of action, indications, adverse effects & contraindications of platelet aggregation inhibitors, anticoagulants and thrombolytic drugs.
  • Describe the tests used to monitor warfarin and heparin therapy.
  • Explain the management of heparin and warfarin overdosing.
  • List the drug interactions that potentiate or attenuate the anticoagulant effect of warfarin.
  • Describe the mechanism of action, indications and adverse effects of aminocaproic acid.
  • Describe the uses of plasma fractions.

 

AGENTS USED IN ANEMIAS (Lecture 37)

By the end of this session, the student should be able to:

  • Define anemia.
  • Describe the causes of different anemias.
  • Explain the type of anemia expected as a result of deficiencies of iron, erythropoietin, vitamin B12 and folic acid.
  • Discuss the pharmacologic agents used in anemias.
  • Describe the basic pharmacology and pharmacokinetic properties of iron.
  • Describe the uses and toxicity of iron and the preparations available.
  • Describe the pharmacokinetics and pharmacodynamics of vitamin B12. Discuss the two biochemical reactions that require vitamin B12 as a cofactor. Explain the “methylfolate trap”.
  • Describe the uses of vitamin B12. Discuss pernicious anemia. Explain why folic acid alone is contraindicated in the treatment of pernicious anemia.
  • Describe the pharmacokinetics and pharmacodynamics of folic acid.
  • Describe the uses of folic acid.
  • Describe the pharmacokinetics, pharmacodynamics, uses and adverse effects of the hematopoietic growth factors (erythropoietin, darbepoetin, myeloid growth factors, and megakaryocyte growth factors).
  • Discuss the use of the myeloid growth factors in cancer chemotherapy-induced neutropenia.
  • Discuss the pharmacologic agents used to treat sickle cell disease.

 

ANTIHYPERLIPIDEMICS (Lecture 38)

By the end of this session the student should be able to:

  • Describe the types of hyperlipidemias (I, II, III, IV & V) and the alterations in serum lipids found in each type.
  • Describe the relationship between serum lipid levels and cardiovascular risk.
  • Describe the etiology of hyperlipidemias (primary vs secondary)
  • Describe the mechanism of action, adverse effects and indications of the various antihyperlipidemic agents.
  • Describe the pleiotropic effects of statins.

 

NSAID (Lecture 39)

By the end of this session the student should be able to:

  • Outline the main functions of COX-1 and COX-2.
  • Describe the mechanism of action, indications, adverse effects and contraindications of the NSAIDs.
  • Discuss the clinical relevance of the COX-2-selective NSAIDs.
  • Describe the organ effects of aspirin and the NSAIDs.
  • Describe the effects of aspirin on respiration, metabolism, acid-base and electrolyte balance.
  • Discuss the differences in relative risk of gastrointestinal adverse effects associated with NSAIDs.
  • Describe the mechanism of action, indications, adverse effects and contraindications of acetaminophen.
  • Describe the principles of treatment of acetaminophen toxicity.

 

DMARDS (Lecture 40)

By the end of this session the student should be able to:

  • Outline the pathophysiology of rheumatoid arthritis.
  • Outline the use of the NSAIDS and DMARDS in rheumatoid arthritis.
  • Describe the mechanisms of action of the different DMARDs.
  • Recognize the time required before the onset of action of the DMARDs.
  • Describe the main adverse effects, indications and contraindications of the DMARDs.
  • Describe the main combination regimens for the management of rheumatoid arthritis.
  • Discuss potential drug interactions between drugs used in combination regimens.

 

DRUGS USED IN GOUT (Lecture 41)

By the end of this session the student should be able to:

  • Outline the pathophysiology of acute gouty arthritis and chronic tophaceous gout.
  • Outline the biochemistry of purine metabolism and its relevance to the pathophysiology of gout.
  • Differentiate between drugs used to treat acute and chronic gout.
  • Describe the mechanism of action, pharmacologic effects, adverse effects and contraindications of the drugs used to treat gout..
  • Explain why colchicine or an NSAID must be administered when starting allopurinol therapy.

 

OPIOID ANALGESICS (Lecture 42)

By the end of this session the student should be able to:

  • Explain the molecular mechanism of action of opioid analgesics.
  • List the different types of opioid receptors and their signalling mechanisms.
  • Describe the physiological effects of each receptor type.
  • Discuss the mechanisms of spinal, supraspinal and peripheral analgesia.
  • Discuss the classification of opioids in strong agonists, partial agonists, mixed agonists-antagonists and antagonists.
  • Describe the receptor type activity of major opioids.
  • Describe the organ system effects of morphine and other major opioids.
  • Describe the pharmacokinetic properties of opioids.
  • List the uses, adverse effects, contraindications and drug interactions of opioid analgesics.
  • Explain how agonist-antagonists and partial agonists differ in their utility and adverse effect profile when compared to strong agonists.
  • Discuss the main properties of the following specific agents: morphine, heroin, meperidine, fentanyl, methadone, codeine, oxycodone, propoxyphene, tramadol, diphenoxylate, loperamide, pentazocine, nalbuphine, buprenorphine, naloxone, naltrexone and dextrometorphan.

 

PAIN MANAGEMENT (Lecture 43)

By the end of this session the student should be able to:

  • Identify characteristics of the different types of pain: nociceptive, inflammatory, neuropathic, and functional.
  • Describe the clinical presentation of pain.
  • Select an appropriate method of pain assessment.
  • Recommend an appropriate choice of analgesic regimen for a patient, based on type and severity of pain, and other patient-specific parameters.
  • Describe the WHO analgesic ladder for pain management.
  • List the analgesic agents used to treat mild to moderate pain, moderate pain and severe pain.  Describe their mechanism of action and adverse effects.
  • List the adjuvant drugs used to manage the adverse effects of analgesic drugs and to augment analgesia.
  • List the drugs used in the treatment of neuropathic pain. List the drugs used in the treatment of diabetic neuropathy, postherpetic neuralgia and trigeminal neuralgia

 

PHARMACOGENOMICS (Lecture 44)

By the end of this session the student should be able to:

  • Define pharmacogenomics.
  • Describe how pharmacokinetic and pharmacodynamic genetic variations can influence drug responses.
  • Describe the effects of genetic variations of butyrylcholinesterase, N-acetyltransferase 2, CYP2D6, thiopurine S-methyltransferase, 5-Lipoxygenase, the CYP isoforms involved in the metabolism of warfarin & the molecular target of warfarin (vitamin K epoxide reductase), and EGFR.

 

ANTIFUNGAL DRUGS (Lecture 45)

By the end of this session the student should be able to:

  • Classify antifungal drugs by their mechanism of action and their clinical use.
  • Describe the mechanism of action of each class of antifungal drugs.
  • Describe the pharmacokinetic properties of the various antifungal drugs.
  • Describe the important adverse effects of the various antifungal drugs.
  • Discuss the potential drug interactions of griseofulvin and ketoconazole.
  • Describe the major therapeutic indications of antifungal drugs.

 

ANTIVIRAL DRUGS (Lecture 46)

By the end of this session the student should be able to:

  • Classify antiviral drugs based upon their site of action.
  • Discuss the mechanism of action and adverse effects of agents used to treat HSV, VZV and CMV infections.
  • Discuss the mechanism of action and adverse effects of anti-hepatitis agents.
  • Discuss the mechanism of action and adverse effects of anti-influenza agents.
  • Describe mechanisms of resistance.
  • Discuss potential drug interactions.

 

ANTIRETROVIRAL DRUGS (Lecture 47)

By the end of this session the student should be able to:

  • Classify anti-HIV drugs based upon their site of inhibition in the viral replication cycle.
  • Discuss the mechanism of action and adverse effects of the different classes of anti-HIV drugs: nucleoside reverse transcriptase inhibitors, nucleotide reverse transcriptase inhibitors,  nonnucleoside reverse transcriptase inhibitors, protease inhibitors, reverse transcriptase inhibitors  and entry inhibitors.
  • Explain the use of combination of different classes of anti-HIV drugs.
  • Describe the various drug combinations used for the treatment of HIV infections.
  • Discuss clinically significant drug interactions pertaining to antiretroviral combinations.
  • Discuss the use of antiretroviral drugs in pregnancy.

 

ANTIMALARIAL DRUGS (Lecture 48)

By the end of this session the student should be able to:

  • Outline the life cycle of the four Plasmodium species that cause malaria.
  • Describe the various locations in the life cycle of malarial parasites where the antimalarial drugs are effective.
  • Describe the mechanisms of action and pharmacokinetic properties of the antimalarial drugs.
  • Describe the adverse effects of the antimalarial drugs.
  • List the drugs of choice for treatment of uncomplicated and severe malaria.
  • List the drugs of choice for treatment of uncomplicated and severe malaria in pregnant women.
  • Describe the regimen for prophylaxis for chloroquine-sensitive and chloroquine-resistant areas.
  • Describe the regimen for prophylaxis for chloroquine-sensitive and chloroquine-resistant areas for pregnant women.
  • Discuss the WHO 2006 Guidelines for Treatment of Malaria.
  • Discuss the current CDC guidelines for treatment of malaria.

 

ANTIPARASITIC DRUGS (Lecture 49)

By the end of this session the student should be able to:

  • List the drugs of choice and alternative drugs available for treatment of diseases due to various helminths.
  • Describe the mechanism of action, spectrum, indications, adverse effects & contraindications of the drugs used in the chemotherapy of commonly encountered helminthic infections.
  • Describe the mechanism of action and adverse effects of drugs used for the treatment of amebiasis.
  • Describe the drugs of choice for the treatment of asymptomatic, mild to moderate and severe intestinal disease, and hepatic abscess due to E. histolytica.
  • Describe the opportunistic infections that commonly occur in AIDS patients and the drugs used for their prophylaxis and treatment.
  • Describe the drugs used for the treatment of giardiasis, trypanosomiasis and leishmaniasis.

 

ANTICANCER DRUGS (Lectures 50- 52)

By the end of this session the student should be able to:

  • Explain the role of chemotherapy in the management of patients with cancer.
  • Explain the concept of “cell kill” in cancer patients.
  • Classifiy anticancer drugs based on their cell cycle specificity.
  • Describe the principles and advantages of combination chemotherapy.
  • Explain the mechanisms of resistance to anticancer drugs.
  • Describe the mechanism of action and the common toxicities for each class of anticancer drugs.
  • List the major therapeutic indications of various anticancer drugs.

 

IMMUNOPHARMACOLOGY (Lecture 53)

By the end of this session the student should be able to:

  • Outline the main aspects of the immune response.
  • Define the general principles of immunosuppression.
  • Describe the mechanism of action, clinical uses and toxicities of immunosuppressant drugs.
  • Describe the mechanism of action, clinical uses and toxicities of immunostimulants.
  • Describe the different types of allergic reactions to drugs.
  • Discuss methods of desensitization to drugs.

 

DEVELOPMENT AND REGULATION OF DRUGS (Lecture 54)

By the end of this session students should be able to:

  • Describe the drug discovery process.
  • Describe drug screening and toxicity testing.
  • Describe clinical drug evaluation and regulatory approval.
  • Describe the major legislation pertaining to drugs in the US.
  • Describe the several phases involved in the investigation of a new drug and discuss the characteristics of each of the phases.
  • Describe the drug approval process.
  • Describe drug labelling. Explain the purpose of black box warnings.
  • Explain “off-label” drug use.
  • Define orphan drugs.
  • Describe the five schedules of controlled substances.

 

ENDOCRINE PHARMACOLOGY (Lectures 56-62)

HYPOTHALAMIC AND PITUITARY HORMONES (Lecture 56)

By the end of this session the student should be able to:

  • List the anterior pituitary and hypothalamic hormones.
  • Describe the link between hypothalamic, pituitary and target gland hormones.
  • Describe the receptors for anterior pituitary and hypothalamic hormones and the signalling mechanisms associated with them.
  • Describe the mechanism of action, uses, adverse effects and contraindications of growth hormone and growth hormone antagonists.
  • Describe the mechanism of action, uses, adverse effects and contraindications of the gonadotropins.
  • Describe the mechanism of action,  uses, adverse effects and contraindications of gonadotropin-releasing hormone, its analogs and its antagonists.
  • Describe the mechanism of action of prolactin. Describe the symptoms associated with abnormal prolactin release. Describe the mechanism of action, effects, uses, toxicity and contraindictions of dopamine agonists.
  • Describe the mechanism of action, effects and uses of thyroid-stimuling hormone and of thyrotropin-releasing hormone.
  • Describe the mechanism of action, effects, uses, toxicity and contraindictions of the posterior pituitary hormones and their antagonists.

 

THYROID AND ANTITHYROID DRUGS (Lecture 57)

By the end of this session the student should be able to:

  • Outline the regulation and the key steps in thyroid hormone synthesis, secretion and peripheral metabolism .
  • Describe the chemical structure of thyroxine, triiodothyronine and reverse triiodothyronine
  • Describe the pharmacokinetic properties of thyroid hormones.
  • Explain the mechanism of action of thyroid hormones.
  • Describe the physiological effects of thyroid hormones.
  • Describe the major manifestations of thyrotoxicosis and hypothyroidism.
  • Describe the preparations of thyroid hormones currently available.
  • Describe the mechanism of action, primary effects and adverse effects of antithyroid drugs.
  • Explain the rationale for the use of propranolol in the treatment of hyperthyroidism.
  • Describe the therapeutic uses of thyroid and antithyroid drugs.

 

ADRENOCORTICOSTEROIDS & ADRENOCORTICAL ANTAGONISTS (Lecture 58)

By the end of this session the student should be able to:

  • Explain the physiologic regulation of the hypothalamic-pituitary-adrenal axis.
  • Describe the major steps in the biosynthesis of steroids.
  • List the natural and synthetic adrenocortical steroids.
  • Describe the mechanism of action of corticosteroids.
  • Describe the actions of corticosteroids on intermediary metabolism, growth and development, electrolyte homeostasis, immune and inflammatory responses.
  • Describe the pharmacodynamic properties of natural and synthetic corticosteroids. Compare and contrast the glucocorticoid versus the mineralocorticoid activity of the natural and synthetic corticosteroids.
  • Describe the regulation of aldosterone synthesis and release by angiotensin II.
  • List the main natural and synthetic mineralocorticoids.
  • List the adrenocortical antagonists and discuss their mechanism of action, uses, and adverse effects.
  • Describe the diagnostic and therapeutic uses of corticosteroids.
  • Describe the adverse effects, drug interactions and contraindications of corticosteroids.
  • Explain the rationale for slow withdrawal following chronic therapy with glucocorticoids.

 

GONADAL HORMONES & INHIBITORS (Lecture 59)

By the end of this session the student should be able to:

  • Describe the gametogenic and steroidogenic functions of the ovary and their regulation by gonadotropins.
  • List the main properties of natural and synthetic estrogens.
  • Describe the mechanism of action of estrogens.
  • Describe the pharmacokinetic properties of estrogens.
  • Describe the main effects of estrogens on: cardiovascular function, metabolism, electrolyte and water balance, blood coagulation, reproductive function, plasma proteins and blood lipids.
  • Describe the main uses, adverse effects and contraindications of estrogens.
  • List the main estrogen preparations available.
  • Describe the estrogen antagonists, the Selective Estrogen Receptor Modulators (SERM) and the inhibitors of estrogen synthesis. Discuss their pharmacologic effects and uses.
  • List the main natural and synthetic progestins.
  • Describe the pharmacokinetic properties of progestins.
  • Describe the mechanism of action and main effects of progestins.
  • Describe the main uses, adverse effects and contraindications of progestins.
  • Describe the mechanism of action, effects, uses and adverse effects of antiprogestins.
  • List the sources of androgens and describe the regulation of their secretion.
  • Describe the metabolism of testosterone to active and inactive metabolites.
  • Discuss the importance of dihydrotesterone formation and binding to androgen receptors in the prostate gland and other organs.
  • Describe the effects of androgens on growth and development.
  • Describe the mechanism of action, uses, adverse effects and contraindications of androgens.
  • Describe the androgen preparations available.
  • Describe the mechanism of action, effects, uses, adverse effects and contraindications of the androgen recepor antagonists, the inhibitors of androgen synthesis and the inhibitors of 5α-reductase).

 

ANTIDIABETIC DRUGS (Lectures 60 & 61)

By the end of this session the student should be able to:

  • Describe the effects of insulin and glucagon on metabolism.
  • Describe the pathophysiology of diabetes mellitus type 1 and type 2.
  • Describe the mechanism of action, effects, uses, adverse effects & drug interactions of the agents used in the pharmacotherapy of type 1 and type 2 diabetes.
  • Describe the mechanism of action, effects, uses & adverse effects of glucagon.
  • Explain the goals of therapy for type 2 diabetes.
  • Discuss the 2008 guidelines from the American Diabetes Association & the European Association for the Study of Diabetes

 

AGENTS THAT AFFECT BONE MINERAL HOMEOSTASIS (Lecture 62)

By the end of this session the student should be able to:

  • Describe the physiological actions of the hormonal regulators of calcium and phosphate homeostasis (PTH, vitamin D, FGF23, calcitonin, glucocorticoids and estrogens).
  • Describe the pharmacologic agents used in disorders of bone mineral homeostasis. Explain the molecular mechanism of action, effects, adverse effects and uses of drugs used in disorders of bone mineral homeostasis.
  • Describe the available preparations of calcitonin, vitamin D and calcium supplements.

 

CNS PHARMACOLOGY (Lectures 63-73)

INTRODUCTION TO CNS PHARMACOLOGY (Lecture 63)

By the end of this session the student should be able to:

  • List the major neurotransmitters in the brain and the receptors on which they act.
  • Compare and contrast G protein coupled receptors and ligand-gated ion channels and describe the major effector systems coupled to various G-proteins.
  • Differentiate between excitatory and inhibitory neurotransmitters.
  • Identify the presynaptic and postsynaptic sites where drugs can act to affect synaptic transmission.
  • Differentiate between hierarchical and nonspecific neuronal systems of the CNS.

 

ANTIDEPRESSANTS (Lecture 63)

By the end of this session the student should be able to:

  • Describe the monoamine hypothesis of depression. Describe its strenghts and weaknesses.
  • List the major classes of antidepressant drugs and their primary cellular targets: MAOIs, TCAs, SSRIs, SNRIs,  SARIs, NDRIs,
  • Describe the mechanism of action, actions, pharmacokinetic properties, uses, adverse effects, contraindications and drug interactions of the major classes of antidepressant drugs.
  • Discuss the drugs used for bipolar disorder.  Describe the mechanism of action and adverse effects of lithium.
  • Discuss the use of alternatives to lithium (eg valproate, carbamazepine, lamotrigine, atypical antipsychotics).

ANTIPSYCHOTICS (Lecture 64)

By the end of this session the student should be able to:

  • Describe schizophrenia and discuss the theories regarding its neurochemical basis.
  • List the major antipsychotic agents.
  • Describe the mechanism of action of antipsychotic drugs
  • Contrast the major properties of the conventional antipsychotics with those of the atypical antipsychotics.
  • Contrast the adverse effects of conventional antipsychotics with those of the atypical antipsychotics.
  • Describe neuroleptic malignant syndrome and its management and treatment.
  • Compare the effectiveness of classical and atypical antipsychotics in the treatment of both positive and negative signs of schizophrenia.
  • List the main uses of antipsychotic drugs.

 

SEDATIVE-HYPNOTICS (Lecture 65)

By the end of this session the student should be able to:

  • Define sedation and hypnosis.
  • Describe the structure and function of the GABAA receptor.
  • Describe the effects of various sedative/hypnotic drugs on GABAergic transmission and their differences in their binding sites on the GABAA receptor.
  • Describe the actions of agonists, antagonists and inverse agonists at the GABAA receptor.
  • Explain the uses of flumazenil.
  • Describe the pharmacokinetics properties of benzodiazepines.
  • Compare and contrast the effects of barbiturates, benzodiazepines, and non-benzodiazepine benzodiazepine-receptor agonists on induction and maintenance of sleep  and their adverse effects.
  • Explain why drugs acting at benzodiazepine receptors have replaced barbiturates as the sedative-hypnotics of choice.
  • List the therapeutic uses of benzodiazepines, barbiturates and non-benzodiazepine benzodiazepine-receptor agonists.
  • Describe the mechanism of action, actions, uses and adverse effects of buspirone, ramelteon , chloral hydrate and other drugs used as sedative-hypnotics or anxyolytics..

 

DRUGS FOR ANXIETY (Lecture 66)

By the end of this session the student should be able to:

  • Describe the features of the main anxiety disorders.
  • List the drugs used for generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive compulsive disorder, post-traumatic stress disorder and performance anxiety; describe their mechanism of action, primary effects and adverse effects.
  • Outline the goals of therapy for each type of anxiety disorder.
  • Explain why antidepressants have replaced benzodiazepines as the drugs of choice for most anxiety disorders.

 

ANTIEPILEPTIC DRUGS (Lecture 67)

By the end of this session the student should be able to:

  • List the major types of seizures.
  • List the major classes of antiepileptic drugs and the seizures against which they are effective.
  • Describe the mechanism of action, indications, adverse effects & contraindications of antiepileptic drugs.
  • Discuss the risks of antiepileptic drugs during pregnancy.
  • List the antiepileptic drugs that induce P450 enzymes.
  • Discuss other therapeutic uses of antiepileptic drugs.
  • Describe the main non-pharmacological antiepileptic therapies.

 

TREATMENT OF PARKINSON’S DISEASE (Lecture 68)

By the end of this session the student should be able to:

  • Discuss current hypotheses about the etiology and pathophysiology of Parkinson's disease.
  • Describe the molecular mechanism of action, adverse effects, drug interactions and contraindications of the drugs used in Parkinson’s disease.
  • Describe the rationale for the use of the different classes of drugs used in Parkinson's disease.

 

GENERAL ANESTHETICS (Lectures 69 & 70)

By the end of this session the student should be able to:

  • Define the terms “general anesthesia” and “balanced anesthesia.”
  • Describe the objectives of general anesthesia, the characteristics of an ideal anesthetic, and the stages of general anesthesia.
  • List the drugs commonly used in combination with inhalation anesthetics in balanced anesthesia.
  • Describe the mechanisms of action, adverse effects, drug interactions and contraindications of general anesthetics.
  • Define MAC and explain how MAC is used in anesthesiology.
  • Describe how physical properties of inhaled anesthetics influence potency and onset.

LOCAL ANESTHETICS (Lecture 71)

By the end of this session the student should be able to:

  • Discuss the mechanism of action, adverse effects, pharmacokinetic properties, uses, drug interactions and contraindications of local anesthetics.
  • List the significant differences between amide and ester-type local anesthetics.
  • List the common adverse effects of local anesthetics and indicate appropriate treatments should they occur.
  • Describe the common routes of administration of local anesthetics.
  • Describe methods used to restrict local anesthetics to a desired site of action and indicate how these methods reduce adverse effects.

 

SKELETAL MUSCLE RELAXANTS (Lecture 72)

By the end of this session the student should be able to:

  • Describe the mechanism of action, pharmacokinetic properties, actions, uses, adverse effects and drug interactions of nondepolarizing and depolarizing neuromuscular blockers.
  • Describe the mechanism of action, uses and adverse effects of spasmolytic drugs.

 

>DRUGS OF ABUSE (Lecture 73)

By the end of this session students should be able to:

  • Define drug abuse, addiction, physical dependence and tolerance.
  • Describe properties, toxic effects, abuse potential and uses (if any) of CNS depressants, psychostimulants, nicotine, opioids, marijuana, psychedelic agents, inhalants and anabolic steroids.
  • Discuss approaches to treat withdrawal syndromes and addiction.

 

TOXICOLOGY (Lectures 74 & 75)

By the end of this session the student should be able to:

  • Describe the toxic effects caused by common drugs, occupational & environmental toxic chemicals, and heavy metals, their clinical presentation, and treatment.

 

BOTANICALS & NUTRITIONAL SUPPLEMENTS (Lecture 76)

By the end of this session the student should be able to:

  • Differentiate between dietary supplements and drugs.
  • List the most widely used botanical products and describe their purported medical uses, and mechanisms of action.
  • Describe adverse effects of herbal products.
  • Describe serious drug interactions that can occur between herbal products and prescription medicines (e.g. St John’s Wort and HIV protease inhibitors).
  • Recognize that in many cases the medical value of these substances has not been demonstrated in controlled clinical trials.
  • Appreciate that these substances are marketed without governmental review of efficacy and safety.
  • List herbal products to be avoided in pregnancy.
  • Understand that there is little or no regulation of herbal products, so that products may not contain the quantity of active compound listed on the bottle.

 

END OF LIFE CARE (Lecture 77)

By the end of this session the student should be able to:

  • Describe the most common symptoms that accompany terminal illness.
  • Discuss the interventions employed to treat symptoms such as pain, dyspnea, nausea and vomiting, constipation, pressure ulcers, confusion, depression and stress at the end of life.