|
Pdf Version of this
file
Subcommittee:
|
NAME
|
SCHOOL
EMAIL
|
|
David Taylor (Chair)
|
East Carolina University taylorda@mail.ecu.edu
|
|
Don Allen
|
University of South Carolina
|
|
Steve Baker
|
University of Florida
|
|
Henry R. Besch
|
Indiana University
|
|
Ted Brody
|
Michigan State University
|
|
R.W. (Willie) Caldwell
|
Medical College of Georgia
|
|
Vincent Chiappinelli
|
George Washington University
|
|
Garrett Gross
|
Medical College of Wisconsin
|
|
Joseph Hume
|
University of Nevada at Reno
|
|
Rocky Kass
|
Columbia University
|
|
Philip Marcus
|
New York College of Osteopathic Medicine
|
|
Jim Potter
|
University of Miami
|
1. Review
of Cardiovascular Physiology (2)
Review the properties of
the heart including contractility (e.g. excitation-contraction coupling)
and electrical activity (e.g. the action potential, automaticity,
excitability, refractory period, conduction and the relationship to the
electrocardiogram). Review
the concepts of inotropism, chronotropism, dromotropism and lusitropism
as they pertain to mechanism of action of commonly used drugs.
Review neuroendocrine
properties of the heart (both response and output).
Discuss mechanisms of
growth, hypertrophy and signal transduction.
Review the intrinsic and
extrinsic regulation of the cardiovascular system.
Describe cardiac and vascular smooth
muscle cellular pathobiology including mechanisms of apoptosis and responses
to hypoxia, reperfusion, ischemia and mechanical and oxidative stress.
2. Drugs Used for Cardiac and
Cardiovascular Therapy
A. Anti-Arrhythmic
Agents (3)
1) Drugs
and Drug Classes to Consider:
ADENOSINE
AMIODARONE
Atropine
β-ADRENOCEPTOR ANTAGONISTS (e.g.
METOPROLOL, SOTALOL) Bretylium
CALCIUM CHANNEL BLOCKERS (e.g. DILTIAZEM, VERAPAMIL)
Digoxin
Disopyramide
Dofetilide
Flecainide
Ibutilide
LIDOCAINE
Mexiletine
PROCAINAMIDE
Propafenone
QUINIDINE
2) Principles and knowledge objectives:
a) Introduction
to Cardiac Electrophysiology
Describe
the ionic basis of the cardiac action potential.
Discuss
the role of specific ions and conductances in the production and
propogation of the cardiac action potential.
Review
the electrophysiological differences between normal atrial and normal
ventricular cardiac muscle cells and between specialized and normal
cardiac cells.
Describe
how cardiac electrical activity is altered in the production of cardiac
arrhythmias.
Discuss
the relationship between cellular cardiac electrical activity and the
electrocardiogram.
b) Pharmacological
Agents: Mechanism of action
Describe the pathophysiologic
mechanisms of cardiac arrhythmias (abnormal automaticity, triggered
rhythms, reentrant rhythms and abnormal impulse conduction).
Classify
antiarrhythmic drugs according to the Vaughn-Williams classification into
classes I, II, III and IV including other miscellaneous agents, though
recognizing the limitations of this classification system.
Describe the
slow (calcium-dependent) and fast (sodium-dependent) responses, their
relevance to sinoatrial, atrial, AV-nodal and ventricular tissues, and
their alteration by antiarrhythmic drugs.
Describe the electrophysiologic
actions of antiarrhythmic drugs in normal and abnormal myocardial and
conduction tissue, and their effect on the phases of the cardiac action
potential.
Describe the
indirect autonomic actions of these drugs.
Describe
the effect of age on fast and slow channels and on the agents affecting
these channels.
Discuss
the pharmacogenomics of long QT syndrome and the relationship of genetics
to drug selection.
Know
the two forms of this disorder (i.e. drug-induced [or acquired LQT] and
congenital) and which ion channels are responsible for each.
Know
the classes of drugs that can produce acquired LQTS and that the
therapeutic management of congenital
LQTS depends on the genotype, despite a uniform phenotype.
c)
Pharmacological
Agents: Actions on organ
systems
Describe
the relevant extracardiac actions of antiarrhythmic drugs with special
reference to amiodarone.
d) Pharmacological
Agents: Pharmacokinetics
Describe
the routes of administration, biotransformation and excretion of selected
antiarrhythmic drugs.
Describe
the pharmacokinetics and time-course of the cardiac actions of
antiarrhythmic drugs (onset and duration of action).
Discuss the impact of reduced cardiac
output due to myocardial infarction and cardiomyopathy on drug half-life
and pharmacodynamics.
Describe
the influence of age on pharmacokinetic parameters, i.e., liver
metabolism (lidocaine, procainamide, and propranolol) and elimination
through kidney (digoxin and sotalol).
e) Pharmacological
Agents: Therapeutic
indications
Describe
the use of antiarrhythmic drugs in supraventricular arrhythmias (atrial
flutter, atrial fibrillation, paroxysmal atrial tachycardia, junctional
arrhythmias).
Describe the use of antiarrhythmic drugs
in ventricular arrhythmias (ventricular premature beats, ventricular
tachycardia, ventricular fibrillation).
Discuss
the utility of antiarrhythmic drugs in combination with electrical
cardioversion or implantable converters-defibrillators.
f) Pharmacological
Agents: Adverse effects,
drug interactions and contraindications
Describe
the cardiac and extracardiac manifestations of toxicity from
antiarrhythmic drugs.
Describe
the beneficial and adverse interactions among antiarrhythmic drugs and between
antiarrhythmic drugs and cardiac glycosides.
Describe
the significance of electrolyte and acid-base imbalance in arrhythmia
generation and their influence on antiarrhythmic drug action.
Describe
the possible contraindications of antiarrhythmic drugs in the presence of
heart block or congestive heart failure, and the precautions and
contraindications in other conditions.
B. Management
of Acute and Chronic Heart Failure (2)
1) Drugs
and Drug Classes to Consider
ANGIOTENSIN
CONVERTING ENZYME INHIBITORS (e.g. ENALAPRIL)
ANGIOTENSIN
RECEPTOR ANTAGONISTS
(e.g. LOSARTAN)
Inamrinone
ADRENOCEPTOR ANTAGONISTS (e.g.
CARVEDILOL; METOPROLOL)
ADRENOCEPTOR
AGONISTS (e.g.
DOBUTAMINE; DOPAMINE)
DIGOXIN
DIURETICS (e.g. Furosemide; SPIRONOLACTONE)
PHOSPHODIESTERASE
INHIBITORS (e.g.
INAMRINONE; MILRINONE)
NESIRITIDE
VASODILATORS (e.g. HYDRALAZINE,
NITROPRUSSIDE)
2) Principles
and knowledge objectives
a) Introduction
to cardiac inotropism
Describe
the acute inotropic, dromotropic, and chronotropic effects of
catecholamines (e.g. epinephrine, norepinephrine, dopamine,
isoproterenol). Discuss the
lusitropic actions of the catecholamines as they relate to normal and
abnormal cardiac function.
Compare and contrast the management of
acute and chronic heart failure.
Describe
the basic pathophysiology of heart failure and the cardiac and
extracardiac compensatory mechanisms that are activated.
b)
Pharmacological
Agents: Mechanism of action
Describe
the effects of digoxin on myocardial contractility.
Explain
the ionic basis for the mechanism of action of digoxin and the cardiac
glycosides as a classs of agents:
discuss the roles of Na+, K+-ATPase inhibition and the Na+/Ca2+ exchanger.
Describe
the electrophysiologic effects of digoxin on atrial and ventricular
muscle and specialized conducting tissue.
Explain
the significance of direct and indirect (autonomic) actions of digoxin.
Describe
the positive inotropic effects of the β-adrenoceptor-agonists and
phosphodiesterase inhibitors.
Explain
the effects of adrenoceptor antagonists and ACE-inhibitors on cardiac
function and ventricular remodeling in the setting of heart failure.
c) Pharmacological
Agents: Actions on organ
systems
Describe
the hemodynamic actions of digoxin in the failing heart.
Describe
the extracardiac actions of digoxin.
Explain
the effects of vasodilators on preload and afterload.
Describe
the extracardiac actions of the adrenoceptor agonists, adrenoceptor
antagonists, phosphodiesterase inhibitors and ACE-inhibitors.
d) Pharmacological
Agents: Pharmacokinetics
Describe
the routes of administration, the extent of oral absorption and
bioavailability, the routes of elimination and extent of
biotransformation of digoxin and
other drugs used in heart failure.
Relate
these to physicochemical properties of digoxin.
Contrast
the pharmacokinetics of digoxin in young and old patients.
Describe
the time-course of the cardiac actions of cardiac glycosides (onset and
duration of action) with special reference to pharmacokinetic differences
between digoxin and digitoxin (used for descriptive purposes).
Explain the concept of digitalization
(loading dose) and maintenance therapy.
Review
the "plateau principle" with regard to maintenance therapy without
a loading dose.
e) Pharmacological
Agents: Therapeutic
indications
Describe
the use of digoxin in congestive heart failure and in atrial arrhythmias.
Describe
the role of adrenoceptor agonists, adrenoceptor antagonists,
vasodilators, diuretics and ACE-inhibitors in the treatment of acute and
chronic heart failure.
f) Pharmacological
Agents: Adverse effects,
drug interactions and contraindications
Describe
the cardiac (delayed depolarizations and arrhythmias) and extracardiac
manifestations of digoxin toxicity (digoxin levels > 2.5 ng/ml).
Describe
the significance of changes in serum electrolyte levels (potassium,
sodium, calcium, magnesium) with regard to digoxin toxicity.
Discuss
the potential adverse effects with concomitant use of diuretics (both
potassium-sparing and potassium depleting) in the elderly or in patients
with congestive heart failure, hypothyroidism and renal disease.
Describe
the interactions of digoxin and quinidine, verapamil, and other relevant
drugs.
Describe
the cardiac and extracardiac side effects and limitations of the
antagonist agents, vasodilators, phosphodiesterase inhibitors, and
ACE-inhibitors.
C. Antihypertensive
and Related Drugs (4)
1) Drugs
and Drug Classes to Consider
a-ADRENOCEPTOR ANTAGONISTS (e.g. PRAZOSIN; DOXAZOSIN)
ACE INHIBITORS (e.g. ENALAPRIL;
BENAZEPRIL CAPTOPRIL; FOSINOPRIL; LISINOPRIL; QUINAPRIL)
ANGIOTENSIN
RECEPTOR ANTAGONISTS
(e.g. LOSARTAN; VALSARTAN; CANDASARTAN)
b-ADRENOCEPTOR
ANTAGONISTS (e.g.
ATENOLOL; PROPRANOLOL; TIMOLOL; NADOLOL; LABETOLOL)
CALCIUM CHANNEL BLOCKERS (e.g.
AMLODIPINE; FELODIPINE; NICARDIPINE; NIFEDIPINE)
CENTRALLY ACTING ANTIHYPERTENSIVE
AGENTS (e.g. CLONIDINE)
DIURETICS (e.g.
HYDROCHLOROTHIAZIDE; INDAPAMIDE) VASODILATORS (e.g. NITROPRUSSIDE;
HYDRALAZINE)
D-1 Dopamine agonists (Fenoldopam mesylate) used in hypertensive emergencies
Endothelin Receptor
antagonists (Bosentan)
2) Principles
and knowledge objectives
a) Introduction
to the Vascular System and its Regulation
Review
the determinants of systemic arterial blood pressure including the role
of the autonomic nervous system, the regulation of fluid volume and the
renin-angiotensin system.
Describe
the role of the central nervous system in the regulation of blood
pressure.
Discuss
the role of vascular endothelium and locally released regulators of
vascular tone in the maintenance of blood pressure.
List
the types of hypertension and the relative prevalence of each.
Describe
the current views for the etiology of essential
hypertension.
b) Pharmacological
Agents: Mechanism of action
Discuss
the mechanism of action of each of the several classes of agents used to
manage hypertension according the site of action within the pathogenesis
of hypertension.
Describe
the mechanism by which each antihypertensive drug or drug class exerts
its therapeutic function.
c) Pharmacological Agents: Actions on organ systems
Review the
end organ effects of hypertension and the beneficial effects achieved by
therapeutic management of the
disease.
Describe
the actions of antihypertensive drugs on the heart, renal blood flow and
renal function.
Describe
the relevant actions of antihypertensive drugs in other organ systems
(CNS, other).
d) Pharmacological Agents: Pharmacokinetics
Describe
the use of antihypertensive drugs in mild, moderate and severe essential
hypertension.
Describe
the time-course of their antihypertensive activity (onset and duration of
action) for each class of agents.
e) Pharmacological Agents: Therapeutic indications
Discuss
the role of non-pharmacological treatment modalities in the management of hypertension.
Describe the
use of antihypertensive drugs in mild, moderate and severe essential
hypertension.
Describe the use
of antihypertensive drugs in hypertensive emergencies and in pregnancy
(e.g. eclampsia).
Describe
the use of antihypertensive drugs in pheochromocytoma.
Discuss
subgroups with special antihypertensive drug considerations (e.g.
African-Americans, diabetics, isolated systolic hypertension esp. in
elderly patients, renal failure patients).
f) Pharmacological
Agents: Adverse effects, drug interactions and contraindications
Describe the cardiac and extracardiac
side effects of antihypertensive drugs.
Describe the
beneficial and adverse interactions between antihypertensive drugs and
between antihypertensive drugs and other therapeutic agents.
D. AntiAnginal
Drugs (1)
1) Drugs and Drug Classes to consider:
ANTIPLATELET
AGENTS (e.g. Clopidogrel)
ADRENOCEPTOR
ANTAGONISTS (e.g. PROPRANOLOL)
CALCIUM CHANNEL BLOCKERS (e.g. NIFEDIPINE)
VASODILATORS
2) Principles
and knowledge objectives
a) Introduction
to Coronary Blood Flow and its Regulation
Describe
the normal regulation of coronary blood flow and the relationship to the
events of the cardiac cycle.
Describe
the normal determinants of cardiac oxygen consumption and supply.
Describe
the basic pathophysiology of myocardial ischemia.
Explain
the significance of atherosclerotic coronary artery disease and coronary
artery spasm (Prinzmetal's) in the production of myocardial ischemia and
angina pectoris.
b) Pharmacological
Agents: Mechanisms of action
Describe
the hemodynamic actions of antianginal drugs, including their coronary
and peripheral vasodilator actions.
Describe
the 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).
Describe
the effects of the antianginal drugs at the cellular level.
c) Pharmacological
Agents: Actions on organ systems
Describe
the cardiac actions of antianginal drugs (electrophysiologic, coronary
vasodilator, inotropic actions).
Describe
the actions of antianginal drugs on the peripheral circulation (arterial,
venous) and their effects on ventricular preload and afterload.
d) Pharmacological
Agents: Pharmacokinetics
Describe the
routes of administration, biotransformation and excretion of antianginal
drugs.
Describe the
significance of a "first-pass effect" for orally administered
antianginal drugs and the rationale underlying sublingual, intranasal and
patch administration of nitrates.
Describe
the time-course of antianginal activity (onset and duration of action).
Describe
the problem of dose intervals and tolerance development with the
nitrates.
e) Pharmacological
Agents: Therapeutic indications
Describe the
use of antianginal drugs in classic (effort-related) angina pectoris and
vasospastic angina pectoris.
Describe
the concept of "myocardial preservation" and discuss the use of
antianginal drugs in the context of acute myocardial infarction with
particular emphasis on adrenoceptor antagonists.
f) Pharmacological
Agents: Adverse effects, drug interactions and contraindications
Describe the cardiac and extra-cardiac
side effects of antianginal drugs.
Describe the
beneficial and adverse interactions between antianginal drugs and between
antianginal drugs and other cardiovascular drugs.
E. Drugs
for hyperlipidemias (1)
1) Drugs
and Drug Classes to consider:
CHOLESTYRAMINE
Colestipol
FIBRIC ACID DERIVATIVES (e.g.
GEMFIBROZIL, FENOFIBRATE)
HMG CoA REDUCTASE INHIBITORS (e.g.
ATORVASTATIN, LOVASTATIN, PRAVASTATIN)
Nicotinic acid
Ezetimibe
2) Principles
and Knowledge Objectives
a) Lipid Interactions with the
Cardiovascular System
Discuss cholesterol
synthesis, transport, export, excretion, and receptor mediated cellular
uptake.
Review
“normal” values for lipid levels.
Discuss the
relevant hypotheses regarding the etiology of hyperlipidemias (e.g.
intrinsic versus extrinsic elevations in plasma lipids).
Describe the
basic pathophysiology of atherosclerotic vascular disease and its
relationship to the hyperlipidemias (“cholesterol” or “infectious agent”.
Describe the
types of hyperlipidemias (I, II, III, IV, and V) and the alterations in serum
lipids in each type (triglycerides, cholesterol, LDL, HDL, LDL,
lipoproteins).
Discuss the
lipid profile characteristic of insulin-resistant diabetics.
Discuss
genetic conditions leading to hyperlipidemia.
Describe
the concept of “plaque stability”.
b) Pharmacological
Agents: Mechanism of action
Describe
the actions of each drug class on serum lipids, and compare and contrast
the mechanism of each of these actions.
Characterize
these agents according to their action to reduce lipid synthesis or
enhance removal.
Identify
the role of antioxidants in the management of hyperlipidemia.
c) Pharmacological
Agents: Actions on organ
systems
Describe
the relevant actions of these drugs, other than on lipid metabolism (e.g.
pleitrophic effects).
Discuss
drug-induced alterations in plasma lipids (e.g. protease
inhibitor-induced hyperlipidemia; estrogen-induced hypolipidemia).
Discuss
the role of the HMG CoA reductase inhibitors in preventing acute coronary
events and stroke and as adjuncts in the management of dementia and other
pathological disorders.
d) Pharmacological
Agents: Pharmacokinetics
Describe
the absorption, distribution, metabolism and excretion (ADME) of drugs
used for hyperlipidemias.
Compare
and contrast the pharmacokinetics of nicotinic acid and fibric acids.
e) Pharmacological
Agents: Therapeutic
indications
Describe
the non-pharmacological management of hyperlipidemia (i.e. life style modifications
and natural remedies that may benefit patients).
Describe
the use of these agents in familial and acquired hyperlipidemias, and
their efficacy in atherosclerotic vascular disease.
Discuss
important multicenter clinical trial data documenting efficacy in
multiple patient groups.
Discuss
new National Cholesterol Education Program (NCEP) guidelines for lowering
LDL.
Discuss
the apparent lack of a threshold effect (lower is always better, even in
the normal range of LDL).
f) Pharmacological
Agents: Adverse effects,
drug interactions and contraindications
Describe
the cardiovascular and other systemic side effects of these drugs with
special reference to the muscle and liver toxicities.
Describe the beneficial and adverse interactions
between these drugs, and their interactions with digoxin, oral
anticoagulants, and other relevant drugs.
F. Thrombolytic and Hemorrheologic Agents in the Management of Myocardial
Infarction / Acute Coronary Syndrome and Chronic Treatment of Cardiovascular
Diseases (1)
1) Drugs
and Drug Classes to Consider
ADENOSINE DIPHOSPHATE RECEPTOR
ANTAGONISTS (e.g. CLOPIDOGREL, TICLOPIDINE)
DIPYRIDAMOLE
GLYCOPROTEIN
IIb/IIIA RECEPTOR ANTAGONISTS (e.g. ABCIXIMAB, eptifibatide, tirofiban)
HEPARINS (e.g. ENOXAPARIN; HEPARIN)
WARFARIN
THROMBIN INHIBITORS (e.g.
bivalirudin, lepirudin, argatroban, ximelagatran)
THROMBOLYTIC
AGENTS (e.g. ALTEPLASE, anistreplase, reteplase, STREPTOKINASE,
tenecteplase, UROKINASE)
2) Principles
and Knowledge Objectives
a) Introduction
to Coagulation and Thrombus Formation
See
Section I Drugs Acting on the Blood and Blood-forming Organs for
Thrombolytics, Anticoagulants and Antithrombotic Drugs.
Describe
the physiology of hemostasis and the steps that are targets for drug use
and drug development.
Describe
the role of platelet aggregation in hemostasis.
Discuss
the role and contribution of the intrinsic and extrinsic pathways in
formation of fibrin.
Discuss
the pathophysiology of thrombus formation in arteries and veins.
b) Pharmacological Agents: Mechanism of action
Describe
the use of thrombolytic agents as first-line in the therapy of acute
post-myocardial infarction and stroke. Discuss the role of acute
catheter-mediated intervention as an alternative or complementary
strategy.
Consider
the spectrum of agents available for cardioprotection and plaque
stabilization in the setting of acute coronary syndrome.
c) Pharmacological
Agents: Action on Organ Systems
Discuss the
long-term use of antiplatelet agents (e.g. ASPIRIN, PENTOXIPHYLLINE and
clopidogrel) in patients with claudication associated with chronic
occlusive peripheral arterial disease and stroke.
Describe
the use of thrombolytic agents as first-line agents in the acute therapy
of post-myocardial infarction and as adjuncts in the nonpharmacological
management of coronary artery disease (e.g. surgical stent implantation).
Consider
the proper 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.
d) Pharmacological Agents: Pharmacokinetics
Discuss
the appropriate use of parenteral versus oral anticoagulants.
Discuss
the route and time of administration of thrombolytic agents.
e) Pharmacological
Agents: Therapeutic Indications
Describe
the use of thrombolytic and anticoagulant agents in th | 
