CVS Module Topic 1.

Drugs used in Chronic Ischemic Heart Disease (L)

Specific learning outcome From this lecture, students should be able to Knowledge
list other drugs and drug classes used in the treatment of chronic ischaemic heart disease: a. organic nitrates (*glyceryl trinitrate, isorsorbide dinitrate) b. beta adrenoceptor antagonists (*propranolol) c. calcium channel blockers (*diltiazem, verapamil) d. antiplatelet agents ( to be discussed in lecture on acute coronary syndrome) e. selective sinus node inhibitor /funny channel inhibitor (*ivabradine) f. metabolic agent (*trimetazidine) Beta-adrenoceptor antagonists and calcium channel blokers also discussed in lectures on antihypertensive drugs, antiarrhythmic drugs and drugs used in the treatment of CCF. 2. discuss the mechanisms of actions and pharmacological effects with respect to the following: a. mechanism of action at the cellular level b. hemodynamic actions of antianginal drugs, including their coronary (and how this may cause coronary steal syndrome and peripheral vasodilator actions. c. effects of each antianginal drug or drug class on the determinants of myocardial oxygen consumption (heart rate, myocardial wall tension, etc.) and/or oxygen supply (coronary blood flow). d. the cardiac actions of antianginal drugs (electrophysiologic, coronary vasodilator, inotropic actions). e. actions of antianginal drugs on the peripheral circulation (arterial, venous) and their effects on ventricular preload and afterload. discuss the pharmacokinetics of antiangnal drugs: a. routes of administration, biotransformation b. significance of a "first-pass effect" for orally administered nitrates and the rationale underlying sublingual, intranasal and patch administration of nitrates. c. the time-course of antianginal activity (onset and duration of action). d. problem of dose intervals and tolerance development with nitrates. discuss the therapeutic indications of antianginal drugs: a. use of antianginal drugs in classic (effort-related) angina pectoris and vasospastic angina pectoris. b. use of antianginal drugs as prophylaxis discuss the adverse effects, drug interactions and contraindications of antianginal drugs

3.

4.

5.

Skills
Nil

Attitude
Nil

Content synopsis
1. Basic pathophysiology of myocardial ischemia. 2. Differences of atherosclerotic coronary artery disease and coronary artery spasm (Prinzmetal's) in the production of myocardial ischemia and angina pectoris. 3. Drugs used for treatment of an chronic ischemic heart disease. 4. The mechanisms of actions, pharmacokinetics, therapeutic uses, adverse effects and interactions of these drugs.

Topic 2. Drugs Used in the treatment of Acute Coronary Syndrome (L)

Specific learning outcome From this lecture, students should be able to Knowledge
1. 2. list the clinical entities referred to Acute Coronary Syndrome- ACS (acute ayocardial ischemia - STEMI & NSTEMI), & Unstable Angina) list the pharmacological agents used in treatment of ACS: a. Adenosine diphosphate receptor antagonists (*clopidogrel, **ticlopidine) b. Phosphodiesterase inhibitors (*dipyridamole) c. Glycoprotein iib/iiia receptor antagonists (*abciximab, others: eptifibatide, tirofiban) d. Anticoagulants: Heparins (*heparin, enoxaparin), warfarin e. Thrombin inhibitors (*lepirudin) f. Thrombolytic agents (*alteplase, anistreplase, streptokinase, urokinase)

For Anticoagulants, please refer to CVS module Year 1)

3. 4. 5.
6. 7. 8. 9.

describe the mechanism of action, pharmacological effects, clinically relevant pharmacokinetic features, therapeutic uses and adverse effects of these agents. Describe the use of thrombolytic agents as first-line in the therapy of ACS (and stroke) and as adjuncts in the nonpharmacological management of coronary artery disease (e.g. surgical stent implantation). Explain the differences in the mechanisms of action of the antiplatelets. List other therapeutic indications for long-term use of antiplatelet agents (e.g. aspirin, and clopidogrel) in patients with claudication associated with chronic occlusive peripheral arterial disease and stroke. Discuss the use of morphine in the pain of MI, the long-term use of acetylsalicylic acid (antiplatelet activity) as prophylaxis and the use of adrenergic blocking agents for cardiac protection. Pharmacokinetics: Discuss the route and time of administration of thrombolytic agents. Therapeutic indications: Use of thrombolytic in the acute management of myocardial infarction, discuss the use of antiplatelet drugs, anticoagulant drugs, nitroglycerin, adrenergic blocking agents and angiotensin converting

enzyme inhibitors as adjunctive agents in the management of myocardial infarctions.

Skills
Nil

Attitude
Nil

Content synopsis
1. Drug list: 2. Basic pathophysiology of ACS 3. Mechanism of action and pharmacological effects of thrombolytics and antiplatelets. 4. Adverse effects of thrombolytics and antiplatelets. 5. Pharmacotherapy of ACS with thrombolytics, antiplatelets and other drugs as adjunctive agents in the management of myocardial infarctions. 4. Other clinical uses of antiplatelets.

Topic 3. Lipid lowering drugs (L)

Specific learning objectives From this lecture, students should be able to: Knowledge
1. 2. 3. define hyperlipidemia and explain the rationale to treat hyperlipidemia. list the drug classes and their prototypes used as lipid-lowering drugs: HMG CoA reductase inhibitor: *simvastatin, lovastatin, atorvastatin, rosuvastatin and pravastatin Bile acid sequestrant: *cholestyramine and colestipol Nicotinic acid: *Niacin Fibrates: *Gemfibrozil Cholesterol Absorption Inhibitor: *Ezetimibe describe the mechanism of action of each drug class and their effects on different types of serum lipids. describe the essential pharmacokinetic features of drug classes used for hyperlipidemia. discuss the adverse effects with special reference to the muscle and liver toxicities. discuss clinically important drug interactions and contraindications.

4. 5. 6. 7.

Skills
Nil

Attitude
Nil

Content synopsis
1. Classes of lipoproteins and their transport in both the exogenous and endogenous pathways. Classification of lipid-lowering drugs. Pharmacokinetics, mechanism of action and effects of the lipidloweringdrugs. Therapeutic uses, adverse effects, contraindications and drug interactions of lipid-loweringdrugs. Non-pharmacological treatment of hyperlipidemia.

2.
3. 4. 5.

Topic 4. Drug Treatment in Arrhythmias (L)

Specific learning outcome From this lecture, students should be able to Knowledge 1.
describe briefly the types and pathophysiologic mechanisms of cardiac arrhythmias (abnormal automaticity, abnormal impulse conduction). 2. describe the phases of myocardial action potential and how they are related with ECG. 3. describe the types of ion channels involved in to the different phases of myocardial action potential. 4. classify antiarrhythmic drugs according to the Vaughn-Williams classification into classes I, II, III, IV and other miscellaneous agents. 5. describe the IA (*quinidine), IB (*lidocaine) and IC (*flecainide, propafenone) subclasses of sodium channel blockers with regards to a. their effects on depolarization and repolarization. b. pharmacokinetics. c. main adverse effects. 6. describe the class II antiarrhythmic drugs (*propranolol), mechanism of their antiarrythmic action, pharmacokinetics, main adverse effects. 7. describe the class III antiarrhythmic drugs (*ibutilide, amiodarone), mechanism of their antiarrhythmic action, pharmacokinetics, main adverse effects. 8. describe the class IV antiarrhythmic drugs (*verapamil), mechanism of their antiarrhythmic action, pharmacokinetics, main adverse effects. 9. describe the miscellaneous antiarrhythmic drugs (digoxin, magnesium sulphate, potassium), mechanism of their antiarrhythmic action, pharmacokinetics, main adverse effects. 10. describe the use of antiarrhythmic drugs in supraventricular arrhythmias and ventricular arrhythmias. 11. describe the pro-arrhythmic effect of antiarrhythmic drugs, list the drugdrug interactions among antiarrhythmic drugs.

Skills
Nil

Attitude
Nil

Content synopsis 1. Pathophysiology of cardiac arrhythmias. 2. Classes of anti-arrhythmic drugs.

a.

Class 1: Sodium channel blocking drugs b. Class 2: adrenoceptor blocking drugs. c. Class 3: Potassium channel blockers. d. Class 4: Calcium channel blocking drugs e. Miscellaneous antiarrhythmic drugs. Mechanisms of actions, clinically relevant pharmacokinetics of antiarrhythmic drugs, major therapeutic use and adverse effects. 3. Use of antiarrhythmic drugs in supraventricular arrhythmias and ventricular arrhythmias 4. Pro-arrhythmic effect and drug-drug interactions.

SGS Questions Topic 1: Drugs Used In Chronic Ischemic Heart Disease

What is the definition of angina pectoris? Identify the three types of angina Which type accounts for most angina cases? What is the treatment strategy for angina? What does myocardial oxygen demand depend on? Name four major classes of drugs used to treat angina. Why is aspirin useful in treating angina? Nitrates How do nitrates relieve angina? What is the principal physiological effect of low doses of nitroglycerin? What happens at higher doses of nitrates? Give TWO examples of nitrates and their routes of administration. What is the pharmacokinetics of nitroglycerin? What are the therapeutic uses of nitroglycerin? Does tolerance develop to nitrates? What are the problems with nitrates due to vasodilation? When are nitrates contraindicated? Name another important use for nitrates other than angina. Calcium Channel Blockers Give three examples of this drug class What is the mechanism of action? What are the therapeutic uses? What are the special traits of verapamil? What is the site of action for nifedipine? What are the special traits of diltiazem? How can Ca2+ channel blockers be administered? List the possible toxic effects of the calcium channel blockers.

 Blockers What is the role of blockers in angina? What are the contraindications to the use of these drugs? How do you decide which blocker to use? Can anti-anginal drugs be used in combination?

Topic 2: Drugs Used In Acute Coronary Syndrome

The following table shows Drugs used in acute coronary syndrome and where the pharmacology has been taught. Drug class Nitrates Beta-blockers Where its covered Dugs used in chronic ischaemic heart disease (Year 2) Antihypertensives (Year 1) Dugs used in chronic ischaemic heart disease (Year 2) Antihypertensives (Year 1) Dugs used in chronic ischaemic heart disease (Year 2) Antiarrythymic (Year 2) Anticoagulants (Year 1) Drugs used in acute coronary syndrome (Year 2) Drugs used in acute coronary syndrome (Year 2) Opioids (CNS module, Year 2)

Calcium channel blockers

Anticoagulants Antiplatelets Fibrinolytics Morphine Questions: 1. Regarding fibrinolytics: a. Give three examples of fibrinolytics. b. What is the function of the fibrinolytic system? c. What is the role of plasmin in the fibrinolytic system? d. Do fibrinolytics distinguish between beneficial homestatic plugs and unwanted thrombi?

e. What are the contraindications to fibrinolytic therapy? f. How are all fibrinolytics administered? 2. Regarding streptokinase: a. Where does streptokinase come from? b. When do you use it? c. How does streptokinase work? d. What are the toxicities of streptokinase? 3. Regarding urokinase: a. How does urokinase work? b. What are its therapeutic uses? c. What is the main adverse effect? 4. Regarding Tissue Plasminogen Activator , Alteplase: a. Classify tissue plasminogen activator (TPA). b. What is the major advantage of TPA over other thrombolytics? c. What are the indications for this agent? d. State its adverse effects. e. How do you reverse the actions of streptokinase, urokinase, and TPA?

4. What is the role of antiplatelet drugs in clot formation? 5. Regarding aspirin: a. What is aspirins mechanism of action? b. What is aspirins role in patients with ischaemic heart disease? c. State aspirins adverse effects. 6. regarding ticlopidine a. Describe the mechanism of action. b. What are its uses? c. What are the adverse effects of this drug? 7. Regarding clopidogrel: a. What is it?

8. Regarding glycoprotein iib and iiia inhibitors: a. State the prototype drug b. How do glycoprotein iib and iiia inhibitors work? c. How are they administered? d. What are they use for? e. How long do their effects last? f. What are their toxicities? 9. Regarding dipyridamole: a. What is dispyridamoles mechanism of action? 10. Classify fibrinolytics with examples 11. Fill in the blanks: Directly acting fibrinolytics include _______________________ & _________while indirectly acting fibrinolytics include _________ 12. What is the mechanism of action of streptokinase 13. Enumerate adverse effects of streptokinase 14. Bleeding due to streptokinase can be controlled with _______________ 15. Differentiate between streptokinase & alteplase (t-PA) 16. What are the advantages of fibrin specific fibrinolytics? 17. List the indications for fibrinolytics 18. List the contraindications of fibrinolytics 19. List the therapeutic uses of antiplatelets 20. Classify anti-platelets according to their mechanism of action 21. Why a small dose of aspirin is the NSAID of choice as antiplatelet in coronary & cerebrovascular diseases?

22. What is the mechanism of action of ticlopidine? Why it is less preferred to aspirin? 23. What are the advantages of clopidogrel over ticlopidine? 24. What is the main indication of GP IIb/IIIa blockers?

Topic 3: Lipid Lowering Drugs

1. Classify lipid lowering drugs according their mechanism of action. 2. Characterize the hypolipidemic drugs according their action to the different types of lipoproteins. 3. A 63-year-old woman presented with myalgia and muscle weakness in both lower extremities, and this had begun 5 days prior to admission. She had been taking simvastatin (40 mg/day) for over 6 years due to dyslipidemia, and she had never experienced relevant symptoms. The patient also had an elevated triglyceride level and had been started on gemfibrozil, 600 mg twice daily, one month before. The serum creatine kinase level was 45,990 IU/L (8 months prior, it was 407 IU/L), the myoglobin level was 229 ng/mL (normal serum myoglobin levels range from 30 to 90 ng/ml). The aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were elevated to 1,487 IU/L and 820 IU/L, respectively, but the other liver function tests were within normal limits and the hepatitis viral markers were nonspecific. The urine color was darkbrownish, and the urinanalysis result was three + for blood by dipstick analysis, but the microscopic examinations for red blood cells (RBCs) and white blood cells (WBCs) were within normal limits. State the complication developed in this patient. That could provoke this complication?

Topic 4: Drug Treatment in Arrhythmias

1. Classify the antiarrhythmics according their mechanism of action
(Vaughan Williams classification). Define pro-arrhythmic (arrhythmogenic) effect.

2. List and explain the inappropriate combinations of antiarrhythmic

drugs.

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