Soward A L, Vanhaleweyk G L, Serruys P W
Drugs. 1986 Jul;32(1):66-101. doi: 10.2165/00003495-198632010-00004.
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.
在三种最常用的钙拮抗剂——硝苯地平、维拉帕米和地尔硫䓬中，硝苯地平是最有效的动脉血管扩张剂。服用硝苯地平后心输出量和冠状动脉血流量的增加部分是由于后负荷降低所致。反射性肾上腺素能刺激会使心率加快，掩盖了其对心肌收缩力的直接抑制作用。硝苯地平的负性肌力作用在冠状动脉内给药时可观察到，或者通过同时使用β受体阻滞剂治疗可使其显现出来。虽然维拉帕米也是一种有效的血管扩张剂，但其负性肌力和负性变传导性特性在治疗剂量下更为明显。维拉帕米也会引发反射性交感神经激活，抵消负性肌力作用，从而使心输出量变化不大。服用维拉帕米后，无论冠状动脉窦血流量是否减少，心肌耗氧量都会有规律地降低。氧需求降低似乎是其抗心绞痛作用的主要机制。心率×收缩压乘积的降低既源于动脉压下降，尤其是口服给药后，也源于心率降低。地尔硫䓬产生的血流动力学和电生理效应与维拉帕米相似，但在诱导动脉扩张方面效力较弱，且更倾向于使心率减慢。地尔硫䓬似乎不会导致冠状动脉血流量显著增加，也不会改善心肌收缩的射血和等容指数——这证明了其内在的负性肌力作用。
