The Haemodynamic Effects of Nifedipine, Verapamil and Diltiazem in Patients with Coronary Artery Disease

Abstract

Of the 3 most widely used calcium antagonists--nifedipine, verapamil and diltiazem--nifedipine is the most potent arterial vasodilator. Increases in cardiac output and coronary blood flow following nifedipine administration result in part from the afterload reduction. Reflex adrenergic stimulation produces an increase in heart rate and masks a direct inhibitory effect on myocardial contractility. The negative inotropic action of nifedipine is observed during intracoronary administration or may be made apparent by concurrent beta-blocker therapy. While verapamil is also a potent vasodilator, negative inotropic and dromotropic properties are more apparent in therapeutically used dosages. Reflex sympathetic activation is also triggered by verapamil, with an offsetting of the negative inotropic effects such that little change in cardiac output results. A decrease in myocardial oxygen consumption, with or without a decrease in coronary sinus blood flow, has regularly been observed following verapamil administration. Reduced oxygen demand appears to be a major mechanism of its antianginal effect. The heart rate X systolic pressure product is decreased both by the fall in arterial pressure and, particularly after oral administration, by a decrease in heart rate. Diltiazem produces similar haemodynamic and electrophysiological effects to those of verapamil but has less potency in inducing arterial dilatation and more of a tendency to slow the heart rate. Diltiazem does not appear to cause significant increases in coronary blood flow or bring about improvement in ejectional and isovolumic indices of myocardial contraction - evidence of its intrinsic negative inotropic effect.

INCREASED VASCULAR SELECTIVITY AND PROLONGED PHARMACOLOGICAL EFFICACY OF THE L‐TYPE Ca2+ CHANNEL ANTAGONIST LERCANIDIPINE IN HUMAN CARDIOVASCULAR TISSUE

“…[1][2][3][4] The so-called 'first-generation' calcium channel blockers, like nifedipine, are characterized by a poor vascular selectivity that leads to inotropic impairment, especially in situations of an already decreased cardiac function, or in situations where a combination with a beta-blocker is desirable for the treatment of the patient. [5][6][7][8] Furthermore, the fast onset and short duration of the pharmacological effects of the first-generation calcium channel blockers results in a compensatory activation of the sympathetic nervous system, 9 which may unfavourably influence the outcome of the patients.…”

Lipid emulsion alleviates the vasodilation and mean blood pressure decrease induced by a toxic dose of verapamil in isolated rat aortae and an in vivo rat model

“…19 In addition, the reported potency of the vasodilation induced by calcium channel blockers in an isolated vessel is in the following decreasing order: nifedipine, verapamil, and diltiazem. 20 The calcium channel blocker-induced inhibition of the contraction evoked by phenylephrine, which leads to vasodilation, is more potent with nifedipine than with verapamil. 21 Supporting these previous reports, the potency of the calcium channel blockers in the current study in producing vasodilation in isolated endothelium-denuded rat aortae was in the following decreasing order: nifedipine, verapamil, diltiazem, and bepridil (Table 1).…”

Nifedipine toxicity is exacerbated by acetyl l‐carnitine but alleviated by low‐dose ketamine in zebrafish in vivo

“…In vivo studies show that vasodilation induced by nifedipine is relatively greater than that produced by other CCBs (Beaughard, Michelin, Tisne‐Versailles, & Lamar, ). Relative potency of the vasodilation produced by CCBs in isolated vessels has been shown to be highest in nifedipine followed by verapamil and diltiazem (Soward, Vanhaleweyk, & Serruys, ). The major difference between these three CCBs is that both verapamil and diltiazem induce bradycardia and hypotension, whereas nifedipine induces not only hypotension but also reflex sinus tachycardia (Proano, Chiang, & Wang, ).…”