CLASS IV
Verapamil
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.
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