Chapter 23. Calcium Antagonists

Abstract

Calcium antagonists can be classified into two groups: calcium entry blockers and intracellular calcium antagonists. In most tissues, calcium is highly compartmentalized with ionic activities across cellular and intracellular membranes often differing by a factor of 1000 or more. The source of calcium for necessary and specific physiological functions cited above is either the extracellular compartments, that is, the basement membrane, the ground substance, or the extracellular fluids or the intracellular calcium storage pools, that is, mitochondria, endoplasmic reticulum, nucleus, inner aspect of the plasma membrane, and possibly secretory vesicles. The extracellular calcium, the intracellular calcium, or both (depending upon the tissue and the stimulus) are involved in initiating the physiological or pharmacological response. Although the inhibition of the slow inward calcium currently is a property common to all calcium entry blockers, most of these agents possess other major pharmacological properties that most assuredly contribute to their mechanisms of action. Thus, local anesthetics block the rapid inward sodium channel. Intracellular calcium antagonists interfere with the physiological functions of calcium by inhibiting the action or mobilization of intracellular calcium, or by enhancing the sequestration of this cation by intracellular organelles or its efflux from the cell. As therapeutic agents, calcium antagonists hold considerable promise particularly for the management of cardiovascular pathologies.