Classification of calcium antagonists

Abstract

Drugs of several chemical families have been identified as calcium antagonists. This article examines some pharmacologic properties of these drugs to clarify their terminology and their classification and to provide a rationale for their clinical use. Studies with nifedipine show quantitatively that the therapeutic effect in angina is related to the interaction of this drug with membrane calcium channels in human coronary arteries. This gives support to a classification based on studies at the molecular, tissue and organ levels. Among calcium antagonists, calcium entry blockers are defined as agents able to block calcium inward fluxes evoked by various stimuli. They may be subdivided in 2 groups. Group I is the group of selective calcium entry blockers. Group IA consists of those agents selective for slow calcium channels in myocardium (slow channel blockers); the leading agents are verapamil, nifedipine and diltiazem. Group IB contains agents without action on slow calcium channels in myocardium but with selective action on arteries; the leading agents are cinnarizine and flunarizine. Group II is the group of nonselective calcium entry blockers. Group IIA contains agents acting at similar concentration on calcium and on fast sodium channels. Group IIB consists of agents interacting with calcium channels while having another primary site of action. Other agents modulate calcium movements by an action on sodium-calcium exchange and by an action within the cell. Their identification requires the use of cell biology. The actual clinical uses of these drugs are consistent with this pharmacologic classification.