CARVEDILOL - A NOVEL CARDIOVASCULAR DRUG WITH MULTIPLE ACTIONS

Carvedilol (Fig. 1) is a novel multiple action drug that has recently been introduced to the market for the treatment of mild to moderate hypertension (7,8,24-26). In extensive clinical trials conducted worldwide, comparisons to all major classes of antihypertensive agents, including captopril, nifedipine, and atenolol, have demonstrated that once-daily therapy with carvedilol is both highly efficacious and possesses a favorable side effect profile. Clinical trials are currently in progress to establish the utility of carvedilol in angina and congestive heart failure. Carvedilol is both a competitive beta-adrenoceptor antagonist (76,93,94) and an arterial vasodilator (73). At higher concentrations, carvedilol is also a calcium channel antagonist (73,75,93,94). The vasodilatory actions result primarily from alpha-1-adrenoceptor blockade (73,75,76), although in certain vascular beds, calcium channel blockade may also contribute to vasodilation (96,124). In addition to these actions on the heart and vasculature, carvedilol has also been shown to possess significant antioxidant and antiproliferative actions. These multiple actions are responsible for the antihypertensive efficacy of the drug in animals (93,94,105,106) and in humans (7,8,24-26), and may also work in conjunction to provide effective therapy in angina and congestive heart failure. The antihypertensive response produced by carvedilol is associated with a decrease in peripheral vascular resistance with either no change or only a moderate reduction in heart rate. The reduction in peripheral vascular resistance produced by carvedilol is indicative of arterial vasodilation (7,8,108), and the lack of reflex tachycardia is a direct consequence of the beta-adrenoceptor blocking property of the drug (7). Carvedilol has been shown in animal models to protect all the major organ systems that comprise the cardiovascular system, specifically the kidney, heart, vasculature, and brain.