Calcium-channel antagonists: mechanisms of action, vascular selectivities, and clinical relevance

The calcium-channel antagonists represent three separate structural categories of drugs. They share a common action--the blockade of calcium-ion flow through one specific type of calcium channel. The chemical heterogeneity of these agents is reflected in their pharmacologic and therapeutic diversity. The calcium-channel antagonists enjoy significant use in cardiovascular medicine for the treatment of hypertension, angina, and some cardiac arrhythmias. However, the 1,4-dihydropyridines, the most potent antihypertensive calcium-channel blockers, lack antiarrhythmic properties. The selectivity of action of calcium-channel antagonists rests upon a number of factors, including pathways of calcium mobilization, types of channel activated, state-dependent interactions, and the pathological state of the tissue. An understanding of these factors is important to the rational application of these drugs and to the development of newer agents with different specificities.