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Mechanisms by which inhibitors of Ca2+ influx lower the blood pressure:
Effects on peripheral resistance
Verapamil, diltiazem and the dihydropyridine inhibitors of Ca2+ influx all cause dilatation of arteries and arterioles,
thereby lowering peripheral resistance. This is the main mechanism by which these agents lower the blood pressure.
The relative selectivity of the dihydropyridines for smooth muscle as opposed to cardiac muscle helps to explain why,
in the treatment of hypertension, the dihydropyridines are preferred to diltiazem or verapamil.
| Drug | Effect on cardiac output |
|---|---|
| Dihydropyridines | No reduction. May, instead, be increased |
| Diltiazem | Unchanged |
| Verapamil | Some reduction |
For more detail of drug effects on cardiac output click the appropriate link:
The fall in peripheral resistance evoked by dihydropyridine inhibitors of Ca2+ influx lowers mean arterial blood pressure. This triggers change in baroreceptor activity such that reflex tachycardia ensues (this is less likely with sustained release formulations of the dihydropyridines). Since the dihydropyridines have relatively little direct cardio-inhibitory effect, they do not directly oppose the reflex tachycardia. The tachycardia together with the fall in peripheral resistance dictate that cardiac output does not fall and may even increase slightly.
The fall in peripheral resistance evoked by diltiazem lowers mean arterial blood pressure. This triggers change in baroreceptor activity such that reflex tachycardia might tend to ensue. However diltiazem has significant, direct inhibitory effects on the sinoatrial node and cardiac conducting tissue that tend to provoke bradycardia. These two opposing effects balance each other so that little or no change in heart rate occurs. Cardiac output therefore remains unchanged.
The fall in peripheral resistance evoked by verapamil lowers mean arterial blood pressure. This triggers change in baroreceptor activity such that reflex tachycardia might tend to ensue. However verapamil has strong, direct inhibitory effects on the sinoatrial node and cardiac conducting tissue that provoke bradycardia. The direct effect of verapamil more than compensates for its reflex effect so that bradycardia occurs. The bradycardia together with some reduction in the force of cardiac contraction dictate that cardiac output falls.
