CARDIAC ACTIONS OF ANTIHISTAMINES

Two of the nonsedating antihistaminic drugs, terfenadine and astemizol e, have recently been recognized in rare cases to induce the syndrome of torsades de pointes, i.e. QT interval prolongation and life-threate ning ventricular tachycardia. Each was found to prolong cardiac repola rization when its metabolic elimination was impaired, such as by liver disease or drugs that inhibit the 3A family of cytochrome P450. In vi tro studies indicate that this action is due to blockade of one or mor e of the cardiac potassium channels that determine the duration of the action potential. Prescription guidelines are now available to reduce the risk of developing arrhythmias with these two drugs. Two agents r ecently marketed in the United States, loratidine and cetirizine, appe ar to lack the ability to prolong repolarization and induce torsades d e pointes. Evaluation of the potential cardiac actions of investigatio nal antihistamines is essential and may be of value for some of the ol der conventional agents.