THE PHARMACOLOGICAL MANAGEMENT OF MYOCARDIAL-ISCHEMIA

Nitroglycerin therapy, whether given as a sublingual rapid-acting agent, an intermediate-acting mononitrate, or as a long-acting preparation, is effective in the treatment of acute anginal pain. Stimulation of endothelium-derived growth factor production, vasodilatation, and antiplatelet effects account for nitroglycerin's mechanisms of action, once patient tolerance, the ''time-zero'' effect, and the ''rebound'' phenomenon are overcome. Newer coronary vasodilators, such as the nicotinamide nitrate nicorandil and the syndomine derivatives molsidomine and persidomine have the potential to overcome nitrate tolerance. Angiotensin-converting enzyme inhibitors are now used to alter infarct expansion and ventricular remodeling, reduce symptomatic and asymptomatic ventricular dysfunction, and lower morbidity and mortality in postischemic congestive heart failure. Beta-blockers with peripheral and coronary vasodilating actions are potentially useful in reducing infarct size. Bepridil is a long-acting calcium-channel blocker with antiarrhythmic and antianginal effects that decrease oxygen consumption. Redistribution of coronary blood flow from nonischemic to ischemic areas is thought to occur with methylxanthines, by inhibition of adenosine receptors. Magnesium, an agent with multiple effects, remains underused for the treatment of acute myocardial infarction. Finally, adjunctive therapy with antiplatelet agents such as aspirin, ticlopidine, and specific monoclonal antibodies is used both for primary prevention and in the setting of acute ischemia.