Calcium Channel Blockers

Calcium Channel Blockers

1. Definition & historical overview

• Calcium channel blockers (CCBs) — also termed Ca²⁺ entry blockers or Ca²⁺ channel antagonists — are drugs that inhibit the influx of extracellular Ca²⁺ through voltage-gated L-type ("slow") Ca²⁺ channels in vascular smooth muscle and cardiac myocytes, producing vasodilatation and negative cardiac actions (G&G 14e Ch.31, p.613; KDT 8e Ch.40, pp.591–2).
• The two principal pharmacodynamic actions of all CCBs are (i) relaxation of smooth muscle, especially vascular (arteriolar), and (ii) negative chronotropic, inotropic and dromotropic actions on the heart — but the ratio of these effects differs by chemical class, which is the single most important organising concept of the topic (KDT 8e Ch.40, p.592; G&G 14e Ch.31, p.613).
• Historical anchor: Fleckenstein and colleagues (1960s) introduced the concept that drugs can alter cardiac and smooth-muscle contraction by blocking Ca²⁺ entry into myocytes (Fleckenstein 1967–69). Verapamil (developed in Germany, 1962) was the first clinically available CCB — a coronary vasodilator (a congener of papaverine) found by Haas & Hartfelder (1962) to have additional negative inotropic and chronotropic effects not seen with nitrates; Fleckenstein (1967) attributed this to inhibition of excitation–contraction coupling via reduced Ca²⁺ movement (G&G 14e Ch.31, p.613; KDT 8e Ch.40, p.591).
• CCBs as a class were "a major contribution of the 1970s" to antianginal therapy and are now first-line in hypertension and angina, and (non-DHPs only) in supraventricular arrhythmias (KDT 8e Ch.40, p.585).
• Note on physiology vs disease: hypertension is largely the result of increased peripheral vascular resistance; because vascular smooth-muscle contraction depends on free cytosolic Ca²⁺, blocking transmembrane Ca²⁺ entry lowers BP by arteriolar relaxation — the rationale for CCBs in HTN (G&G 14e Ch.32, pp.633–4).