Drug Interactions between methoxyflurane and mibefradil

MONITOR: Calcium channel blockers may potentiate the cardiac depressant and hypotensive effects of volatile (halogenated) anesthetics, and vice versa, due to their similar pharmacologic action on the cardiovasculature. Serious consequences of this interaction may include cardiovascular collapse, ventricular impairment, and/or conduction disturbances, particularly in patients with underlying cardiac complications. The interaction may be more likely with verapamil and diltiazem due to their dromotropic and chronotropic effects. In one case report, administration of enflurane in a patient treated with atenolol and diltiazem resulted in worsening of preexisting atrioventricular and sinus node dysfunction. In another case, severe sinus bradycardia progressed to asystole when enflurane was administered in a patient treated with diltiazem. Atrioventricular block has also been reported with enflurane and verapamil. In animal studies, anesthesia with halothane, enflurane, or isoflurane has been reported to increase plasma concentrations of verapamil due to decreased total clearance.

MANAGEMENT: Discontinuation of calcium channel blockers prior to surgery is generally not recommended because of the rebound effect in patients with coronary heart disease or arterial hypertension. However, extreme care must be taken when administering halogenated anesthetics to patients under treatment with calcium channel blockers. Hemodynamic and electrocardiographic monitoring are recommended during the operation and postoperatively, and the dosage of one or both drugs adjusted as necessary.