ANTI-ANGINAL AGENTS

Dr. D.R. Kapusta

Objectives:

  1. Describe the pathophysiological features associated with angina.
  1. Describe the differences between angina pectoris and variant (Prinzmetal’s) angina.
  1. List three classes of drugs used in the therapeutic management of angina and provide specific examples of each.
  1. State whether each class of anti-anginal agents is effective for the management of angina pectoris, variant (Prinzmetal’s) angina, or both.
  1. Describe the mechanisms of action of nitroglycerin in the management of angina pectoris and variant angina.
  1. List the limitations of nitroglycerin as an anti-anginal agent.
  1. List the routes of administration of nitroglycerin and features regarding its oral bioavalability.
  1. List the adverse effects caused by nitroglycerin therapy.
  1. Describe the use of beta-blockers in the therapeutic management of angina.
  1. Describe why beta-blockers are contraindicated for use in patients with variant (Prinzmetal’s) angina.
  1. List the adverse effects caused by beta-blocker therapy.
  1. Describe the use of calcium channel blockers (antagonists) in the therapeutic management of angina.
  1. Name drugs that belong to each of the three classes of calcium channel blockers.
  1. State the mechanisms of action by which calcium channel blockers are effective in the management of angina.
  1. Describe the relative potency of the three classes of calcium channel blockers on vascular smooth muscle tone, AV conduction and cardiac contractility.
  1. Describe the limitations of calcium channel blockers therapy in regards to drug interactions, and use in patients with A-V conduction defects.
  1. List the adverse effects caused by calcium channel blocker therapy.
  1. Describe other therapeutic uses for calcium channel blockers.
  1. Ischemic heart failure
  2. Pathophysiology of Angina
  3. Clinical Syndromes of Myocardial Ischemia
  4. Stable Syndromes

a)Chronic stable angina

  1. Unstable Syndromes

a)Sudden death

b)Acute myocardial infarction

c)Unstable angina

  1. Other Syndromes

a)Silent ischemia

b)Variant (Prinzmetal’s) angina

  1. Anti-anginal Drugs
  2. Organic nitrates
  3. Drugs

a)Nitroglycerin

b)Isosorbide dinitrate

c)Amyl nitrite

  1. Mechanism of action - relaxation of vascular smooth muscle via increasing cGMP
  2. Differential action of nitrovasodilators on vascular smooth muscle
  1. Limitations

a)Development of tolerance

b)Hepatic metabolism

c)Stimulation of sympathetic activity and the renin angiotensin system

  1. Adverse effects
  1. Beta-blockers
  2. Drugs

a)propranolol (and others)

(1)Mechanism of action

  1. Limitations

a)Contraindicated in vasospastic (Prinzmetal's variant) angina

  1. Adverse effects
  1. Calcium channel blockers (CCB’s)
  2. Categories of CCB’s

a)Benzothiazepine

(1)Drugs

(2)Diltiazem

b)Dihydropyridine

(1)Nifedipine

(2)Nicardipine

(3)Nimodipine

(4)Felodipine

(5)Amlodipine

(6)Isradipine

c)Diphenylalkylamine

(1)Verapamil

d)Others

(1)Bepridil (also has action to block fast sodium channels)

  1. Mechanism of action - inhibit calcium entry through voltage-gated L-type calcium channels

Relative Potency of Cardiovascular Effects of Calcium Antagonists

Drug / Coronary Vasodilation / Suppresion of SA Node Automaticity / Suppression of AV Node Conductance / Suppression of Contraction
Verapamil / ++ / +++ / +++ / ++
Nifedipine / +++ / + / + / +
Nicardipine / +++ / + / + / +
Diltiazem / ++ / +++ / ++ / +
  1. Limitations

a)Significant hepatic first-pass metabolism

b)Verapamil and diltiazem are contraindicated in patients with A-V conduction defects

c)Verapamil increases serum digoxin levels and can cause digoxin toxicity

  1. Adverse effects

a)Constipation, headache, flushing, dizziness, ankle edema, reflex tachycardia

b)Nifedipine - fluid retention and peripheral edema

  1. Potential beneficial effects

a)CCB's may improve renal hemodynamics and glomerular filtration rate in hypertensive patients with compromised renal function

  1. Therapeutic (labeled) uses

a)Angina

(1)Vasospastic (Prinzmetal's variant)

(2)Chronic stable (classic effort-associated)

(3)Unstable

b)Essential hypertension

c)Supraventricular arrhythmias

  1. Unlabeled Uses

a)Migraine headache

b)Raynaud's syndrome

c)Cardiomyopathy

d)Congestive heart failure

  1. Combination drug therapy for angina

a)Nitrovasodilators and beta-blockers

b)Nitrovasodilators and inhibitors of platelet aggregation

c)Nitrovasodilators and calcium channel blockers

d)Nitrovasodilators and hypolipidemic therapy