Cardiac Muscle

CCBs decrease the force of myocardial contraction by blocking the inward flow of calcium ions through the slow channels of the cell membrane during phase 2 (plateau phase) of the action potential. The diminished entry of calcium ions into the cells thereby fails to trigger the release of large amounts of calcium from the sarcoplasmic reticulum within the cell. This free calcium is needed for excitation-contraction coupling, an event that activates contraction by allowing cross-bridges to form between the actin and myosin filaments of muscle. The number of actin and myosin cross-bridges formed within the sarcomere determines the force of the heart’s contraction. Decreasing the amount of calcium ions released from the sarcoplasmic reticulum causes fewer actin and myosin cross-bridges to be formed, thus decreasing the force of contraction and resulting in a negative inotropic effect. This decreases cardiac output.

Cardiac Conduction System (SA and AV Nodes)

In these tissues, CCBs decrease automaticity in the SA node and decrease conduction in the AV node. Automaticity means that a cell depolarizes spontaneously and initiates an action potential without an external stimulus. Automaticity is a normal characteristic of SA nodal cells. Depolarization (Phase 0) of the action potential is normally generated by the inward calcium ion current through slow channels. Thus, agents that can block the inward calcium ion current across the cell membrane of SA nodal tissue decrease the rate of depolarization and depress automaticity. The result is a variable decrease in heart rate (a negative chronotropic effect) (Figure 21-1). Similarly, an agent that decreases calcium ion influx across the cell membrane of the AV node slows AV nodal conduction (negative chronotropic effect) and prolongs AV refractory time. When AV conduction is prolonged, fewer atrial impulses reach the ventricles, thus slowing the rate of ventricular contractions.

Vascular Smooth Muscle

The smooth muscle of the coronary and peripheral vessels has a significant influence on afterload and the hemodynamics of circulation. The decreased force of smooth muscle contraction results in coronary artery dilation, which lowers coronary resistance and improves blood flow through collateral vessels, as well as oxygen delivery to ischemic areas of the heart. CCBs dilate the main coronary arteries and arterioles in both normal and ischemic regions. Therefore, drugs with these actions are helpful in the treatment of angina pectoris.

CCBs reduce arterial pressure at rest and at given levels of exercise by dilating peripheral arterioles and reducing the total peripheral resistance (afterload) against which the heart works, resulting in reduced blood pressure. This unloading of the heart reduces myocardial energy consumption and oxygen requirements and probably accounts for the effectiveness of CCBs in chronic stable angina and causes a decrease in blood pressure.

CCBs are potent inhibitors of coronary artery spasm. This property increases myocardial oxygen delivery in patients with coronary artery spasm and is responsible for the effectiveness of CCBs in vasospastic angina.