John E. Francis

Chapter 7. Cardiovascular Agents

Publisher Summary This chapter discusses potentially important non-diuretic hypotensive, antiarrythmic and antianginal agents. The oldest known hypotensives is sodium nitroprusside. It is indicated for rapid reduction of blood pressure in hypertensive crisis and is given only as an intravenous infusion because its effect is evanescent. Clinically it was also used to produce controlled hypotension during anaesthesia and renal angiography and to manage patients with acute myocardial infarction and chronic heart failure. Recent clinical studies supported the utility of minoxidil in combination with a β-blocker and a diuretic in severe hypertension. This combination was helpful in improving renal function in some patients with nephrosclerosis. Addition of propranolol to minoxidil appears necessary not only to reduce tachycardia and plasma renin activity but also to reduce the incidence of myocardial anoxia. Other antihypertensivas that is under investigation is MJ-10459-2 shows potent antihypertensive effects in several animal models, probably by a mechanism of attenuated sympathetic function because of peripheral nore-pinephrine depletion. Verapamil, an antiarrhythmic agent, normalizes sinus rhythm at 10 mg. i.v. in a number of patients with supraventricular tachycardia. Its mode of action that results from the ability to block calcium transport across the myocardial cell membrane sets it apart from other well-known antiarrhythmic agents.

Chapter 7. Antihypertensive Agents

Publisher Summary This chapter discusses the development and clinical studies of antihypertensive agents. Clonidine is effective at low doses without postural hypotension or lasting sedative side effects in two long term studies. A comparison with reserpine illustrated clonidines lack of depressive reactions and the combination with chlorthalidone were even more effective than clonidine alone. The danger of hypertensive rebound and other side effects on sudden withdrawal from clonidine was noted. Minoxidil is a useful hypotensive agent in uremic patients with severe hypertension or those with malignant or accelerated hypertension refractory to conventional drugs. Compared to hydralazine, the drug was more potent, longer acting, and showed no signs of tolerance development. It causes a marked increase in serum renin activity, cardiac hyperactivity and sodium retention but co-administration of a β-blocker and a diuretic counteracts this side effect. The clinical trials of propranolol continue to illustrate its utility as a hypertensive with activity improved by addition of a vasodilator such as hydralazine in severe hypertension or with hydrochlorthiazide in mild to moderate hypertension. The antihypertensive effect of prostaglandin A, in man is thought mainly due to its effect on renal circulation where it causes vasodilatation and excretion of water and sodium.