Clinical applications of slow channel blocking compounds

Abstract

The slow-channel blockers constitute a structurally diverse group of drugs with varying mechanisms of action, propensities for site of greatest cardiovascular activity, and clinical efficacy. They share however the property of blocking the slow inward channel in heart muscle and of inhibiting calcium fluxes in smooth muscle. Their in vivo and in vitro actions must be distinguished. The overall actions represent a balance of direct and autonomically-mediated reflex actions interacting with the compounds' varying degrees of intrinsic non-competitive sympathetic antagonism. A knowledge of the pharmacodynamic differences between these drugs allows the physician to select the most appropriate agent for a given clinical situation. The central role of calcium in the cellular processes in the heart and the vascular system forms the basis for the utility of this class of drugs in a wide variety of cardiovascular disorders. Current intensive experimental and clinical investigations are likely to further define the roles of nifedipine, verapamil and diltiazem and their congeners in cardiovascular therapeutics. The prospect of development of newer compounds with greater selectivity of action is real. As pointed out by Braunwald (1982 a,b), with further clarification of the mechanisms of actions of these compounds and elucidation of the role of calcium fluxes throughout the body, more specific and potent agents may be developed. The apparent efficacy of the nifedipine congener nimodipine, in the treatment of cerebral vasospasm associated with subarachnoid hemorrhage (Allen et al., 1983) may simply be the first of a large number of 'specific' or targeted slow channel blockers. The development of such compounds may offer further therapeutic possibilities in the control of a variety of cardiocirculatory diseases.