Verapamil (Isoptin, Covera), in addition to its use as an antiarrhythmic agent, has been employed extensively in the management of variant (Prinzmetal’s) angina and effort-induced angina pectoris. It selectively inhibits the voltage-gated calcium channel that is vital for action potential genesis in slow-response myocytes, such as those found in the sinoatrial and A-V nodes.
Spontaneous phase 4 depolarization, a characteristic of normal sinoatrial nodal cells, relies on progressive in-hibition of an outward potassium current and an in-crease in a slow inward current that is carried by NA+ and Ca++ ions. Verapamil decreases the rate of rise and slope of the slow diastolic depolarization, the maximal diastolic potential, and the membrane potential at the peak of depolarization in the sinoatrial node.
Verapamil fails to exert any significant electrophysi-ological effects on atrial muscle.
Verapamil impairs conduction through the A-V node and prolongs the A-V nodal refractory period at plasma concentrations that show no effect on the His-Purkinje system.
The most important electrocardiographic change produced by verapamil is prolongation of the PR inter-val, a response consistent with the known effects of the drug on A-V nodal transmission. Verapamil has no ef-fect on intraatrial and intraventricular conduction. The predominant electrophysiological effect is on A-V con-duction proximal to the His bundle.
Usual IV doses of verapamil are not associated with marked alterations in arterial blood pressure, periph-eral vascular resistance, heart rate, left ventricular end-diastolic pressure, or contractility.
The pharmacokinetic characteristics of verapamil:
Oral bioavailability : 20–35%
Onset of action : 1–2 hours
Peak response : 1–2 hours
Duration of action : 8–10 hours
Plasma half-life : 2.8–7.4 hours
Primary route of metabolism : Hepatic; active metabolite
Primary route of excretion : Renal (30% unchanged)
Therapeutic serum concentration : 0.125–0.4 μg /mL
Verapamil is useful for slowing the ventricular response to atrial tachyarrhythmias, such as atrial flutter and fib-rillation. Verapamil is also effective in arrhythmias sup-ported by enhanced automaticity, such as ectopic atrial tachycardia and idiopathic left ventricular tachycardia.
Orally administered verapamil is well tolerated by most patients. Most complaints are of constipation and gas-tric discomfort. Other complaints include vertigo, headache, nervousness, and pruritus.
Verapamil must be used with extreme caution or not at all in patients who are receiving β-adrenoceptor block-ing agents. Normally, the negative chronotropic effect of verapamil will in part be overcome by an increase in re-flex sympathetic tone. The latter is be prevented by si-multaneous administration of a β-adrenoceptor block-ing agent, which exaggerates the depressant effects of verapamil on heart rate, A-V node conduction, and myocardial contractility. The use of verapamil in chil-dren less than 1 year of age is controversial.