Hydralazine receptor antagonists

Vasodilators. Hydralazine causes direct relaxation of arteriolar smooth muscle. An important consequence of this vasodilation, however, is reflex tachycardia (T CO). It may also cause sodium retention (T plasma volume). The resulting increase in CO tends to offset effects of the vasodilator. Therefore, these drugs are most effective when administered along with sympathetic agents such as P-adrenergic receptor antagonists, which prevent unwanted compensatory responses by the heart. 

Aluminum salts, cholestyramine, and colestipol may decrease absorption of /3 blockers. Pheny-toin, rifampin, and phenobarbital, as well as smoking, induce hepatic biotransformation enzymes and may decrease plasma concentrations of /3 receptor antagonists that are metabolized extensively (e.g., propranolol). Cimetidine and hydralazine may increase bioavailability of propranolol and metoprolol by affecting hepatic blood flow, fi Receptor antagonists can impair the clearance o/lidocaine. 

The cardiac consequences of baroreceptor-mediated activation of the sympathetic nervous system with minoxidil are similar to those with hydralazine there is an increase in heart rate, myocardial contractility, and myocardial consumption. Thus, myocardial ischemia can be induced by minoxidil in patients with coronary artery disease. The cardiac sympathetic responses are attenuated by concurrent administration of a /3 adrenergic blocker. The adrenergically-induced increase in renin secretion also can be ameliorated by a /3 receptor antagonist or an ACE inhibitor, with enhancement of blood pressure control. 

NSAiDs ACE inhibitors + NSAIDs Alpha blockers + NSAiDs Angiotensin II receptor antagonists + Aspirin or NSAiDs Beta blockers + Aspirin or NSAiDs Calcium-channel blockers + Aspirin or NSAiDs Guanethidine + NSAiDs Hydralazine + NSAiDs Thiazide and related diuretics + NSAiDs... 

Pinacidil is three- and tenfold more potent than hydralazine and minoxidil, respectively. It does not interact with alpha, beta, cholinergic, or histaminergic receptors, and also does not produce vasodilation via an indirect effect that is mediated by adenosine, prostaglandin, or endothelial-derived relaxant factor. Its vasodilating activity does not resemble that brought about by the conventional calcium-channel antagonists. Thus, pinacidil-induced vascular relaxation is a direct effect mediated by a novel mechanism. 

The rationale for the use of oral vasodilator drugs in the pharmacotherapy of CHF derived from the experience with the parenteral agents phentolamine and nitroprusside in patients with severe heart failure and elevated systemic vascular resistance. Although a number of vasodilators may improve symptoms in heart failure, only the hydralazine-isosorbide dinitrate combination and antagonists of the renin-angiotensin system (ACE inhibitors and ATj receptor blockers) have been shown to improve survival in prospective randomized trials. Table 33-1 summarizes some properties of vasodilators used to treat heart failure. 

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