Diltiazem is a calcium ion influx inhibitor (calcium entry blocker or calcium ion antagonist).
The therapeutic effect of this group of drugs is believed to be related to their specific cellular action of selectively inhibiting transmembrane influx of calcium ions into cardiac muscle and vascular smooth muscle. The contractile processes of these tissues are dependent upon the movement of extracellular calcium into the cells through specific ion channels. Diltiazem blocks transmembrane influx of calcium through the slow channel without affecting to any significant degree the transmembrane influx of sodium through the fast channel. This results in a reduction of free calcium ions available within cells of the above tissues. Diltiazem does not alter total serum calcium.
Angina: The precise mechanism by which diltiazem relieves angina has not been fully determined, but it is believed to be brought about largely by its vasodilator action.
In angina due to coronary spasm, diltiazem increases myocardial oxygen delivery by dilating both large and small coronary arteries and by inhibiting coronary spasm at drug levels which cause little negative inotropic effect. The resultant increases in coronary blood flow are accompanied by dose-dependent decreases in systemic blood pressure and decreases in peripheral resistance.
In angina of effort it appears that the action of diltiazem is related to the reduction of myocardial oxygen demand. This is probably caused by a decrease in blood pressure brought about by the reduction of peripheral resistance and of heart rate.
Hypertension: The antihypertensive effect of diltiazem is believed to be brought about largely by its vasodilatory action on peripheral blood vessels with resultant decrease in peripheral vascular resistance.
Hemodynamic and Electrophysiologic Effects: Diltiazem produces antihypertensive effects both in the supine and standing positions. Resting heart rate is usually slightly reduced. During dynamic exercise, increases in diastolic pressure are inhibited while maximum achievable systolic pressure is usually unaffected. Heart rate at maximum exercise is reduced.
Studies to date, primarily in patients with normal ventricular function, have shown that cardiac output, ejection fraction, and left ventricular end-diastolic pressure have not been affected.
Chronic therapy with diltiazem produces no change, or a decrease, in circulating plasma catecholamines. However, no increased activity of the renin-angiotensin-aldosterone axis has been observed. Diltiazem inhibits the renal and peripheral effects of angiotensin II.
In man i.v. diltiazem in doses of 20 mg prolongs AH conduction time and AV node functional and effective refractory periods by approximately 20%. Chronic oral administration of diltiazem in doses up to 540 mg/day has resulted in small increases in PR interval. Second-degree and third-degree AV block have been observed. In patients with sick sinus syndrome, diltiazem significantly prolongs sinus cycle length (up to 50% in some cases). |
