PHARMACOLOGY OF THE
CARDIOVASCULAR SYSTEM - Objectives
Dr. C. Ferguson Dr. P. J. Gatti Dr. O. T. Randall Dr. R. E. Taylor Dr. C. Curry Dr. O. D. Polk
PHARMACOLOGY OF THE CARDIOVASCULAR SYSTEM
PRIMARY DRUGS - All capital letters
SECONDARY DRUGS - Small letters
+Indicates that drug listed in the 200 most commonly prescribed drugs in 1989 (National Prescription Audit). All of the first 100 and most of the second 100 of the top 200 drugs prescribed are included in this document.)
Dr. Clifford L. Ferguson
 | DIURETICS AND DRUGS AFFECTING RENAL FUNCTION AND ELECTROLYTE METABOLISM INCLUDING WATER, SALT AND IONS |
1. Review of Renal Physiology/Biochemistry
2. Diuretics
a) Drugs to be considered: ACETAZOLAMIDE, AMILORIDE, ETHACRYNIC ACID, FUROSEMIDE, bumetanide, HYDROCHLOROTHIAZIDE, CHLORTHALIDONE, mannitol, POTASSIUM CHLORIDE, SPIRONOLACTONE, TRIAMETERENE
b) Principles and Knowledge Objectives
| Describe and understand the important role of the organic acid secretory system for the actions of some diuretics and for various interactions of diuretics with other types of drugs. |
| Describe the sites in the nephron where diuretics and other agents act: i.e., glomerulus, proximal tobule, loop of Henle (thin limb; medullary and cortical thick ascending limb), distal tubules and collecting ducts. |
| Explain the mechanism of action of each class of diuretics or other agents. |
| Compare the effects of prototypical diuretics or agents on excretion of various electrolytes and compare effects on cardiovascular system as to antihypertensive effects. |
| Describe the therapeutic uses of these agents, e.g., edema causing dysfunction resulting from decreased cardiac, liver and renal function, and use in treatment of poisoning. State appropriate agents to be used in each condition. |
| Relate absorption, distribution and excretion to particular therapeutic uses; e.g., the use of osmotic diuretics or vasodilators such as dopamine to increase urine flow in cases of impending renal failure. |
| Describe the interactions of diuretics with other drugs such as cardiac glycosides, oral anticoagulants, oral hypoglycemics, uricosuric drugs, aminoglycoside antibiotics and non-steroidal anti-inflammatory drugs. |
| State the adverse effects of diuretics related to and unrelated to water and electrolyte excretion. |
| Relate effects of diuretics that would contraindicate their use in certain conditions, e.g., use of osmotic diuretics in pulmonary edema. |
| Describe and understand the mechanisms whereby furosemide and thiazides are useful in the management of various calcium metabolism disorders. |
3. Agents Affecting that Renal Conservation of Water
| Drugs to be considered: benzothiadiazides, desmopressin acetate (DDAVP), dopamine, demeclocycline |
Principles and knowledge objectives to be considered:
| Describe the site and mechanism of agents used to treat diabetes insipidus. |
| Describe the adverse effects of hydrochlorothiazide and arginine vasopressin related to and unrelated to renal function. |
| Be familiar with other agents such as chlorpropamide and clofibrate that act in antidiuretic hormone sensitive diabetes insipidus. |
| Know that demeclocycline is used in water intoxication due to inappropriate secretion of antidiuretic hormone. |
| Be aware that lithium compounds cause a syndrome like diabetes insipidus. |
Minimum list of drugs affecting renal function to be considered:
ACETAZOLAMIDE
+AMILORIDE
benzothiadiazides
+bumetanide
+CHLORTHALIDONE
demeclocycline
desmopressin acetate (DDAVP)
dopamine
ETHACRYNIC ACID
+FUROSEMIDE
+HYDROCHLOROTHIAZIDE
INDAPAMIDE
mannitol
+POTASSIUM CHLORIDE (e.g. Slow-K)
SPIRONOLACTONE
+TRIAMTERENE
PRIMARY DRUGS - All capital letters
SECONDARY DRUGS - Small letters
+Indicates that drug is listed in the 200 most commonly prescribed drugs in 1989 (National Prescription Audit). All of the first 100 and most of the second 100 of the top 200 drugs prescribed are included in this document.
Dr. Philip J. Gatti/Dr. O.T. Randall
| Anti-Hypertensive and Related Drugs |
a) Drugs to be considered:
ANTENOLOL HYDRALAZINE NITROPRUSSIDE
ANGIOTENSIN (I & II) HYDROCHLOROTHIAZIDE phentolamine
betaxolol INDAPAMIDE pindolol
CAPTOPRIL LABETOLOL PRAZOSIN
chlorthalidone lisinopril PROPRANOLOL
CLONIDINE metazolone reserpine
DIAZOXIDE methyldopa spironolactone
DILTIAZEM metoprolol triamterene
ENALAPRIL minoxidil trimethaphan
guanabenz nadolol verapamil
guanadrel NIFEDIPINE terazosin
guanethidine NITROGLYCERIN (I.V.) timolol
b) Principles and knowledge objectives
 | Mechanism of action |
| Actions on organ systems |
3) Pharmacokinetics
| Describe the routes of administration, biotransformation and excretion of antihypertensive drugs. |
| Describe the time-course of their antihypertensive activity (onset and duration of action) for each class of agents. |
4) Therapeutic indications
| Describe the use of antihypertensive drugs in mild, moderate and severe essential hypertension. |
| Describe the use of antihypertensive drugs in hypertensive emergencies. |
5) Adverse effects, drugs interactions and contraindications
| Describe the cardiac and extracardiac side-effects of antihypertensive drugs. |
Dr. Robert E. Taylor
C. Inotropic Agents
| Introduction to inotropics -consider the acute inotropic effects of catecholamines - i.e. epinephrine and norepinephrine. |
| Drugs to be considered: DIGOXIN, DIGITOXIN, dopamine, amrinone, non-selective phosphodiesterase inhibitors (e.g. THEOPHYLLINE), selective phosphodiesterase inhibitors (e.g. milrinone) |
| Principles and knowledge objectives. |
1) Mechanism of action
| -Explain the ionic basis for the mechanism of action of the cardiac glycosides - Na+-K+ ATPase inhibition; Na/Ca exchanger |
| -Describe the electrophysiologic effects of cardiac glycosides on artial and ventricular muscle and specialized conducting tissue (SA node, AV node and Purkinje Fibers) |
| Describe the effects of cardiac glycosides on myocardial contractility. |
| -Explain the significance of direct and indirect (autonomic) actions of the cardiac glycosides. |
2) Actions on organ systems
| -Describe the hemodynamic actions of cardiac glycosides in the failing heart. |
| -Describe the extracardiac actions of cardiac glycosides. |
Pharmacokinetics
| Describe the routes of administration, the extent of oral absorption and bioavailability, the routes of elimination and extent of biotransformation of the cardiac glycosides. Relate these to physiocochemical properties of cardiac glycosides. |
| Contrast pharmacolkinetics in young and old patients. |
| Describe the time-course of the cardia actions of digitalis glycosides (onset and duration of action). |
| Explain the concept of digitalization (loading dose) and maintenance therapy. Review the "plateau principle" with regard to maintenance therapy without a loading dose. |
4) Therapeutic indications
| Describe the use of digitalis glycosides in congestive heart failure |
| Other treatment regimens used in CHF - use of vasodilators, diuretics, afterload reduction |
| Describe the use of digitalis glycosides in atrial tachyarrhythmias. |
5) Adverse effects, drug interactions and contraindications
| Describe the cardiac (delayed after depolarizations and arrhythmias) and extracardiac manifestations of digitalis toxicity |
| Describe the significance of changes in serum electrolyte levels (potassium, sodium, calcium, magnesium) with regard to digitalis toxicity, the concomitant use of diuretics in patients with congestive heart failure; age, hypothyroidism and renal disease. |
| Describe the interactions of digitalis glycosides and quinidine, verapamil, and other relevant drugs. |
6) Other
| Understand the role of reduction in afterload and preload in the actions of positive inotropic agents |
| Explain the role of dopamine and dobutamine in the treatment of acute and chronic heart failure. |
| How do the phosphodiesterase inhibitors (e.g. milrinone increase the force of myocardial contraction? |
| Newer concepts in inotropic drugs (e.g. calcium sensitizers). |
| Vasodilars (e.g. ACE inhibitors, nitroglycerin, nitroprusside, hydralazine, etc). |
Dr. Philip J. Gatti
D. Anti-Arrhythmic Pharmacology
| Review of Cardiovascular Physiology |
Review of properties of the heart including contractility, automaticity, excitability, refractory period, and conduction; excitation contraction coupling and electrical activity of the heart including the action potential and electrocardiogram.
| Cardiac Drugs |
A. Anti-Arrhythmic Agents
Drugs to be considered: Quinidine, procainamide, lidocaine, tocainide, mexiletine, encainide flecainide, propranolol, sotalol, amiodarone, bretylium, verapamil, diltiazem.
| Principles and knowledge objectives.
|
| -Classify antiarrhythmic drugs as to class I, IA, IB, IC, II, III, IV |
2) Pharmacokinetics
| Describe the routes of administration, biotransformation and excretion of selected antiarrhythmic drugs. |
3) Therapeutic indications
| Describe the use of antiarrhythmic drugs in supraventricular arrhythmias (atrial flutter, atrial fibillation, paroxysmal supraventricular tachycardia, junctional arrhythmias). |
| Describe the use of antiarrhythmic drugs in ventricular arrhythmias (ventricular premature beats, ventricular tachycardia, ventricular fibrillation). |
4) Adverse effects, drug interactions and contraindications
| Describe the cardiac and extracardiac manifestations of toxicity from antiarrhythmic drugs. |
| Describe the possible contraindications of antiarrhythmic drugs in the presence of heart
block or congestive heart failure, and precautions and contraindications in other
conditions. |
Dr. Clifford Ferguson
E. Anti-Anginal Drugs
Drugs to be considered:
DILTIAZEM NIFEDIPINE
dipyridamole NITROGLYCERIN
isosorbide dinitrate PROPRANOLOL
nadolol timolol
b) Principles and knowledge objective
1) Mechanisms of action
| Describe the basic pathophysiology of myocardial ischemia. |
| Explain the significance of atherosclerotic coronary artery disease and coronary artery disease and coronary artery spasm (Prinzmetal's) in the production of myocardial ischemia and angina pectoris. |
| Describe the hemodynamic actions of antianginal drugs, including their coronary and peripheral vasodialator actions. |
| Describe the effects of each antianginal drug or drug class on the determinants of myocardial oxygen consumption (heart rate, myuocardial wall tension, etc.) |
2) Actions on organ systems
| Describe the cardiac actions of anti-anginal drugs (electrophysiologic, coronary vasodilator, inotropic actions). |
| Describe the actions of anti-anginal drugs on the peripheral circulation (arterial, venous) and their effects on ventricular preload and afterload. |
3) Pharmacokinetics
| -Describe the routes of administration, biotransformation and excretion of anti-anginal drugs. |
| -Describe the significance of a "first-pass effect" for orally administered anti-anginal drugs. |
| -Describe the time-course of anti-anginal activity (onset and duration of action). |
| -Describe the problem of dose intervals and tolerance development with the nitrates. |
4) Therapeutic indications
| Describe the use of anti-anginal drugs in classic (effort-related) angina pectoris and vasospastic angina pectoris. |
| Describe the use of "myocardial preservation" and discuss the use of anti-anginal drugs in the context of acute myocardial infarction. |
5) Adverse effects, drug interactions and contraindications
| -Describe the cardiac and extra-cardiac side-effects of anti-anginal drugs. |
| -Describe the beneficial and adverse interactins between anti-anginal drugs and between
anti-anginal drugs and others
Dr. Octavius Polk |
F. Pharmacology of Shock
Learning Objectives
| Definition and pathophysiology of shock; what are the critical sites in the circulation and abnormalities in tissue oxygenation affected by shock syndromes. | ||||||||||||||||||
| Describe the determinants of blood pressure and cardiac output. | ||||||||||||||||||
| Shock syndromes: types and causes | ||||||||||||||||||
| Define the quantitative clinical parameters of shock
| ||||||||||||||||||
| Clinical approach to the patient in shock
| ||||||||||||||||||
| Laboratory
| ||||||||||||||||||
| Treatment of shock
|
Drugs to be considered:
Epinephrine
Norepinephrine
Dopamine
Dobutamine
Isoproterenol
Amrinone
milrinone
Sodium bicarbonate
Dr. Robert E. Taylor
G. Drugs Acting on the Blood and Blood Forming Organs
| -Review erythropeietin and normal control of erythropoiesis. |
| -Describe the proposed mechanisms for the control of intestinal absorption of iron, vitamin B-12 (B12) and folic acid (FA). |
| -Describe the sources, transport, metabolism, storage, and excretion of iron, B-12 and FA. |
| -State the factors which influence the bioavailability of iron, B-12 and FA. |
| -Know how to calculate a parenteral dosage of iron. |
| -Describe the phases of acute and chronic toxicity in iron poisoning and its treatment. |
| -Describe the biochemical systems which are impaired in B-12 and FA deficiency and the role of cyanocobalamin and folic acid in correcting the metabolic defect in DNA thymine and methionine synthesis. |
| -Describe the metabolic reasons why folic acid will correct the erythropoietic lesion but not the neurologic lesion in Addisonian pernicious anemia. |
| -Describe the problems associated with using iron, B-12 and FA in mixtures of shot-gun preparations. |
| -Review GM-CSF and its physiological effects on hematopoiesis. |
| -Describe the pharmacologic management of chronic iron overload disease (e.g., chronic blood transfusion, iron malabsorption disease, etc.). |
Drugs to consider:
IRON (FERROUS SULFATE, iron dextran)
DEFEROXAMINE
ERYTHROPOIETIN
FOLIC ACID
GM-CSF
G-CSF
Dr. Robert E. Taylor
H. Anticoagulant, Antithrombotic and Thrombolytic Drugs
1. Knowledge objectives:
| State the appropriate routes of administration of heparin and the oral anticoagulants. |
| Describe the extent of binding of oral anticoagulants to plasma protein. |
| Explain the pharmacokinetics and pharmacodynamic variability of oral anticoagulants between patients. |
| Describe the relationship between the chemical structure of the oral anticoagulants and vitamin K and its importance in determining the mechanism of action of the oral anticoagulants. (Post ribosomal gamma carboxylation of Factor II, VII, IX, X in the hepatocyte. |
| State the sites of action of heparin in the coagulation process. |
| Describe the relationship between mechanism of action and speed of onset of action and t-1/2 of heparin and the oral anticoagulants. |
| State the interaction of heparin with protamine sulfate. |
| Consider the problems associated with thrombolytic therapy, e.g., streptokinase inn primary post MI. |
| Consider adjuncts to thrombolytic therapy, e.g., antithrombin, antiplatelet. |
| Describe the use of desmopressin in factor VIII deficiency and Von Willebrands disease. |
| Describe the side effects of heparin and warfarin. |
| State the antidotes of heparin and warfarin toxicity. |
| State the contraindications to anticoagulant therapy. |
| Describe the mechanism of action, indication, and complications of thrombolytic therapy. |
| Explain the difference between available thrombolytic agents. |
| Describe the laboratory monitoring of heparin, warfarin and thrombolytic agents. |
2. Drugs to consider:
ACETYLSALICYLIC ACID sulfinpyrazone
HEPARIN VITAMIN K
PROTAMINE SULFATE WARFARIN SODIUM (Coumadin)
STREPTOKINASE DESMOPRESSIN ACETATE (DDAVP)
LOW MOLECULAR WEIGHT HEPARIN
(Epsilon amino caproic acid) Urokinase
Tranxenic Acid APSAC (acylated plasminogen streptokinase
(Epsilon amino caproic acid) complex)
APSAC
tissue-type plasminogen activator (tPA)
H. Minimum list of drugs affecting blood:
+ACETYLSALICYLIC ACID
DEFEROXAMINE
DESMOPRESSIN ACETATE (DDAVP)
ERYTHROPROTEIN
IRON (FERROUS SULFATE, iron dextran)
FOLIC ACID
HEPARIN
PROTAMINE SULFATE
STREPTOKINASE
sulfinpyrazone
tissue-type plasminogen activator (tPA)
urokinase
VITAMIN B-12
VITAMIN K
+WARFARIN SODIUM
Thrombolytic and Hemorrheologic Agents in Myocardial Infarction and Vascular Disease
See Drugs Acting on the Blood and Blood Forming Organs for Thrombolytics, Anticoagulants and Antithrombotic Drugs. Describe the use of thrombolytic agents as first-line therapy of acute post-myocardial infarction. Consider the proper use of morphine in the pain of MI, the long-term use of acetylsalicylic acid (antiplatelet activity) as prophylaxis and PENTOXIFLYLLINE for use in patients with claudication associated with chronic occlusive peripheral arterial disease. Clinical responses are thought to result from improved flexibility of erythrocytes and reduced blood viscosity.
