Chapter 49 Drugs For Angina Pectoris

CHAPTER 49

DRUGS

FOR

ANGINA PECTORIS

angina pectoris – sudden pain beneath the sternum, often radiating to the left shoulder and arm - precipitated when the oxygen supply to the heart is insufficient to meet oxygen demand - secondary to atherosclerosis of the coronary arteries Drug Therapy Goals:

prevention of myocardial infarction (MI) and death - drugs used are cholesterol-lowering drugs - antiplatelet drugs prevention of myocardial ischemia and anginal pain

I. A.

ANGINA PECTORIS:

PATHOPHYSIOLOGY

AND

TREATMENT STRATEGY

FORMS OF ANGINA PECTORIS 1. Chronic Stable Angina (Exertional Angina or Angina of Effort) - triggered most often by an increase in physical activity - emotional excitement, large meals, and cold exposure may also precipitate an attack - occurs in response to strain - underlying cause is coronary artery disease (CAD), characterized by deposition of fatty plaque on the arterial wall - if artery is only partially occluded by plaque, blood flow will be reduced and angina pectoris will result - if complete vessel blockage occurs, blood flow will stop and MI (heart attack) will occur - goal of antianginal therapy is to reduce the intensity and frequency of anginal attacks - tactics = increase cardiac oxygen supply, which there is little we can do about or decrease oxygen demand with drugs that decrease heart rate, contractility afterload, and preload - can be treated with organic nitrates, beta blockers, and calcium channels blockers - all three relieve the pain of stable angina primarily by decreasing cardiac oxygen demand - drugs only provide symptomatic relief, they do not affect the underlying pathology (CAD) - to reduce MI, all patients should receive an antiplatelet drug (aspirin)

- patients should attempt to avoid factors that lead to chest pain, such as overexertion, heavy meals, emotional stress, and exposure to cold - should be encouraged to quit smoking and to establish a regular program of aerobic exercise - overweight patients should be given a restricted calorie diet 2.

Variant Angina (Prinzmetals’ Angina, Vasospastic Angina) - caused by coronary artery spasm, which restricts blood flow to the myocardium - secondary to insufficient oxygenation of the heart - pain is produced at any time, even during rest and sleep - goal of therapy is to reduce the incidence and severity of attacks - treated primarily by reducing oxygen demand, variant angina is treated by increasing cardiac oxygen supply - increased with vasodilators, which prevent or relieve coronary artery spasm - calcium channel blockers and organic nitrates - treatment is symptomatic only, drugs do not alter the underlying pathology 3.

Unstable Angina - medical emergency - results from severe CAD complicated by vasospasm, platelet aggregation, and transient coronary thrombi or emboli - patients may present with either symptoms of angina at rest, new onset exertional angina or intensification of existing angina - treatment strategy is to maintain oxygen supply and decrease oxygen demand - goal is to reduce pain and prevent progression of MI or death - all patients should be hospitalized - acute management consists of anti-ischemic therapy combined with antiplatelet and anticoagulation therapy Anti-ischemic Therapy: * nitroglycerin – sublingually (tablet or spray) followed by IV therapy * beta blocker – if contraindicated, substitute with nondihydropryridine calcium channel blocker (verapamil or diltiazem) * supplemental oxygen * IV morphine sulfate * angiotensin-converting enzyme inhibitor

Antiplatelet Therapy: * aspirin * clopidogrel (plavix) * abciximab (reopro) * eptifibatide (intefrilin) or tirofiban (aggrastat) Anticoagulant Therapy: * subcutaneous low-molecular weight heparin

II.

ORGANIC NITRATES - relieve angina by causing vasodilation

A.

NITROGLYCERIN - effective, fast acting, and inexpensive - remains the drug of choice for relieving acute anginal attacks - applications of specific preparations are based on their time course: • rapid onset are employed to terminate an ongoing anginal attack – applications are administered as soon as pain begins • rapid acting preparations can also be used for acute prophylaxis of angina – preparations are taken just prior to anticipated exertion • long acting preparations are used to provide sustained protection against anginal attacks

Specific Preparations: Sublingual Tablets (beneath the tongue) & Translingual Spray (oral mucosa) - absorbed directly through the oral mucosa and into the bloodstream - bypasses the liver, temporarily avoiding metabolism - effects begin rapidly (1 – 3 minutes) and persist up to 1 hour - ideal for termination of ongoing anginal attack and short term prophylaxis when exertion is anticipated - if 1 tablet is insufficient, 1 or 2 additional tablets should be taken at 5 minute intervals - patient should be instructed to place the tablet under the tongue and leave it there while it dissolves – ineffective if swallowed - shelf life can be prolonged by storing tablets in a tightly closed, dark container - patients should be instructed to write the date of opening on the container and to discard unused tablets 6 months later

Sustained-Release Oral Tablets and Capsules – intended for long-term prophylaxis only - cannot act rapidly enough to terminate an ongoing anginal attack - can cause tolerance - should be taken only once or twice daily - should be swallowed whole, no crushing or chewing Transdermal Delivery Systems – patches look like bandaids and contain a reservoir from which nitroglycerin is slowly released - effects being within 30 – 60 minutes and persist as long as the patch remains in place (up to 14 hrs) - application site should be rotated to avoid local irritation - tolerance develops if there is no “patch free” interval of 10 – 12 hours - cannot be used to abort an ongoing attack Topical Ointment – used for sustained protection against anginal attacks - applied to the skin of the chest, back, abdomen, or anterior thigh - effects begin within 20 – 60 minutes and may persist up to 12 hrs - uninterrupted use can cause tolerance Intravenous Infusion – employed only rarely to treat angina pectoris - limited to patients who have failed to respond to other medications - additional uses include treatment of heart failure associated with MI, treatment of perioperative hypertension, and production of controlled hypotension for surgery - administration should be performed using a glass IV bottle and the administration set provided by the manufacturer

III.

BETA BLOCKERS

- propranolol, metoprolol - important for sable angina, but are not effective against vasospastic angina - exercise tolerance is increased and the frequency and intensity of anginal attacks are lowered - reduce anginal pain primarily by decreasing cardiac oxygen demand by blocking beta1 receptors in the heart, decreasing the heart rate and contractility - cause modest reduction in arterial pressure - increase oxygen supply by slowing the heart rate, increasing the time in diastole, increasing the time during which blood flows through myocardial vessels - additional benefit of blunting reflex tachycardia Adverse Effects: conduction, reduction of

can cause bradycardia, decreased atrioventricular (AV) contractility, insomnia, depression, bizarre dreams and

sexual dysfunction can promote bronchoconstriction can mask signs of hypoglycemia

IV.

CALCIUM CHANNEL BLOCKERS - verapamil, diltiazem, and nifedipine - all can block calcium channels in VSM, primarily in arterioles - result is arteriolar dilation and reduction of peripheral resistance

(afterload) - can relax coronary vasospasm - used to treat both • stable angina by promoting relaxation of peripheral arterioles, resultant decreasing afterload reduces cardiac oxygen demand • variant angina by promoting relaxation of coronary artery spasm, increasing cardiac oxygen supply - verapamil and diltiazem can produce modest additional reduction in oxygen demand by suppressing heart rate and contractility - major adverse effects are cardiovascular = dilation of peripheral arterioles lowers blood pressure, inducing reflex tachycardia