Pharmacology: The therapeutic benefits achieved with diltiazem are related to its ability to inhibit the influx of calcium ions during membrane depolarization of cardiac and vascular smooth muscle.
Mechanism of Action: Diltiazem acts in the following ways: Angina Due to Coronary Artery Spasm: Diltiazem has been shown to be a potent dilator of coronary arteries both epicardial and subendocardial. Spontaneous and ergonovine-induced coronary artery spasms are inhibited by diltiazem.
Exertional Angina: Diltiazem has been shown to produce increase in exercise tolerance, probably due to its ability to reduce myocardial oxygen demand. This is accomplished via reductions in heart rate and systemic blood pressure at submaximal and maximal exercise workloads. In animal models, diltiazem interferes with the slow inward (depolarizing) current in excitable tissue. It causes excitation-contraction uncoupling in various myocardial tissues without changes in the configuration of the action potential. Diltiazem produces relaxation of coronary vascular smooth muscle and dilation of both large and small coronary arteries. The resultant increases in coronary blood flow (epicardial and subendocardial) occur in ischemic and non-ischemic models, and are accompanied by dose-dependent decreases in blood pressure and decreases in peripheral resistance.