An Overview of Slow Channel Blocking Drugs: Pharmacological Basis for Therapeutic Applications

Abstract

The use of voltage clamps in cardiac muscle has permitted the separation of two inward depolarizing membrane currents. The first is the fast sodium current, with rapid kinetics of activation and inactivation, which is blocked by local anesthetics. The second is the slow current carried largely by calcium ions, having slow kinetics with a long time constant of inactivation. Agents which selectively block this current are called Ca antagonists. Such agents are heterogeneous structurally; they also block calcium currents in smooth muscle and therefore produce coronary as well as peripheral vasodilatation. The most significant agents are verapamil, gallopamil, nifedipine, diltiazem and tiapamil. They have a varying spectrum of pharmacological effects with respect to changes they produce on heart rate, afterload, preload, contractility, coronary flow and on the AV node. A similar spectrum of therapeutic effects is apparent in different clinical disorders, in particular vasospastic angina, stable and unstable angina, cardiac arrhythmias, hypertension, hypertrophic cardiomyopathy and possibly other disorders. Indeed, the full range of clinical disorders which may respond to calcium antagonists is still not fully delineated and may well be at least as extensive as that for β-adrenoceptor blocking drugs. The advent of calcium antagonists in the last decade represents one of the most significant advances in cardiovascular therapeutics.

Hypertrophic Cardiomyopathy, a Modern View of the Etiology and Treatment of This Pathology

“…Ишемия миокарда является одним из важных патофизиологических механизмов прогрессирования ГКМП. Основным препаратом, доказавшим свою эффективность в ее лечении, является верапамил [8,16].…”

Interaction between Ca2+ channel blockers and isoproterenol on L‐type Ca2+ current in canine ventricular cardiomyocytes

“…The positive chronotropic, dromotropic, bathmotropic and inotropic actions of adrenergic activation are associated with a marked increase in L-type Ca 2+ current in the surface membrane of cardiomyocytes (Van der Heyden et al 2005). In contrast, Ca 2+ channel-blocking drugs, called Ca 2+ antagonists, decrease the amplitude of this current providing thus effective treatment of several cardiovascular disorders such as cardiac arrhythmias, ischaemic heart disease and hypertension (Singh 1982, Clusin 2003. In spite of the tremendous mass of data obtained on the cardiac effects of beta-adrenergic activation/isoproterenol and Ca 2+ channel blockers alone, little is known about the interactions of these agents when they are applied simultaneously.…”