title: Class III antiarrhythmics in overdose. Presenting features and management principles.
abstract: Class III (Vaughan-Williams classification) antiarrhythmic drugs prolong 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 for each agent and are, therefore, discussed separately. Several new class III antiarrhythmic agents are under development, including dofetilide 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 distribution limit the peak serum concentration. Toxicity is low even if high serum concentrations are reached. The major risks from acute overdose are hypotension (intravenous administration only) and arrhythmia if other factors, such as hypokalaemia or additional antiarrhythmic agents are present. Management is chiefly directed at reducing absorption with activated charcoal or cholestyramine, and monitoring for arrhythmia. Sotalol is a beta-blocker with additional class III activity. Oral bioavailability is high, and overdosed patients can present with bradycardia, hypotension and major haemodynamic collapse. The combination of bradycardia and prolongation of the QT interval is associated with malignant arrhythmias such as torsade de pointes. Management principles include observation and correction of bradycardia with endocardial pacing, intravenous adrenergic drugs and glucagon. The risk of arrhythmia can be substantially reduced by intravenous potassium and magnesium supplements. d-Sotalol is a potent class III drug devoid of beta-blocking activity and may be expected to share the proarrhythmic affects of the racemic mixture in overdose, without pronounced hypotension and bradycardia. Intravenous bretylium in overdose causes an initial hypertensive effect, followed by profound hypotension from systemic vasodilation. Management is directed at controlling hypotension with volume expansion and norepinephrine (noradrenaline).
authors.affiliation: Department of Cardiological Sciences, St George's Hospital Medical School, London, England.
authors.forename: E W
authors.initials: EW
authors.lastname: Leatham
authors.forename: D W
authors.initials: DW
authors.lastname: Holt
authors.forename: W J
authors.initials: WJ
authors.lastname: McKenna
mesh_terms: D000638:Amiodarone / Q000493:pharmacokinetics / Q000494:pharmacology / Q000506:poisoning; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000506:poisoning*; D001682:Biological Availability; D001949:Bretylium Compounds / Q000493:pharmacokinetics / Q000494:pharmacology / Q000506:poisoning; D062787:Drug Overdose; D006801:Humans; D013015:Sotalol / Q000493:pharmacokinetics / Q000494:pharmacology / Q000506:poisoning
chemical_list: D000889:Anti-Arrhythmia Agents; D001949:Bretylium Compounds; D013015:Sotalol; D000638:Amiodarone; C045166:bretylium