CLASS-III ANTIARRHYTHMICS IN OVERDOSE - PRESENTING FEATURES AND MANAGEMENT PRINCIPLES

Class III (Vaughan-Williams classification) antiarrhythmic drugs prolo ng the cardiac action potential without affecting depolarisation. The 3 class III drugs currently in general use are amiodarone, sotalol and bretylium. The presenting features of acute toxicity are different fo r each agent and are, therefore, discussed separately. Several new cla ss III antiarrhythmic agents are under development, including dofetili de and d-sotalol, but specific data on overdoses of these potent class III drugs are not yet available. Amiodarone toxicity following acute overdose is rare because poor bioavailability and a large volume of di stribution limit the peak serum concentration. Toxicity is low even if high serum concentrations are reached. The major risks from acute ove rdose are hypotension (intravenous administration only) and arrhythmia if other factors, such as hypokalaemia or additional antiarrhythmic a gents are present. Management is chiefly directed at reducing absorpti on with activated charcoal or cholestyramine, and monitoring for arrhy thmia. Sotalol is a beta-blocker with additional class III activity. O ral bioavailability is high, and overdosed patients can present with b radycardia, hypotension and major haemodynamic collapse. The combinati on of bradycardia and prolongation of the QT interval is associated wi th malignant arrhythmias such as torsade de pointes. Management princi ples include observation and correction of bradycardia with endocardia l pacing, intravenous adrenergic drugs and glucagon. The risk of arrhy thmia can be substantially reduced by intravenous potassium and magnes ium supplements. d-Sotalol is a potent class III drug devoid of beta-b locking activity and may be expected to share the proarrhythmic affect s of the racemic mixture in overdose, without pronounced hypotension a nd bradycardia. Intravenous bretylium in overdose causes an initial hy pertensive effect, followed by profound hypotension from systemic vaso dilation. Management is directed at controlling hypotension with volum e expansion and norepinephrine (noradrenaline).