Propafenone Poisoning—A Case Report with Plasma Propafenone Concentrations

Abstract

Propafenone is an anti-arrhythmic drug used in the management of supraventricular and ventricular arrhythmias. It is metabolised through cytochrome P450 2D6 pathways; the major metabolites possess antiarrhythmic activity. The cytochrome P450 CYP2D6 is coded by more than 70 alleles resulting in great genetic polymorphism of CYP2D6 isoenzymes, and up to 7% of Caucasian population are poor metabolisers. This case report describes a patient with severe overdose of propafenone who presented with coma, seizures and cardiotoxicity. The patient was managed with intravenous glucagon, hypertonic sodium bicarbonate, hypertonic saline and inotropic support. The propafenone and its 5-hydroxypropafenone (5-OHP) metabolite were measured by high-performance liquid chromatography with ultraviolet detection (no assay was available at the time to measure N-despropyl propafenone concentrations). Toxicological screen showed propafenone concentrations at a maximum of 1.26 mg/L at 9-10 h post-presentation, falling to 0.25 mg/L at 27-28 h postpresentation. No propafenone metabolite 5-OHP was detected in any sample analysed. No antidepressant or analgesic drugs were detected in toxicological screen. Propafenone overdose has been reported to be associated with features of severe cardiovascular and CNS toxicity. Aggressive treatment, meticulous monitoring and supportive care was associated with a good outcome in this case.

Predicting adverse side effects of drugs

“…CYP2D6 encodes a subunit of the cytochrome P450 superfamily of enzymes. The gene is specifically expressed in the right ventricle and its genetic polymorphism is known to be associated with cardiotoxicity, including a patient's poor anti-arrhythmic activity, severe cardiovascular, or dilated cardiomyopathy [ 30 , 31 ].…”

Malign Arrhytmia Development Due To Propafenone Over Dose: A Case Report

“…It is reasonable to suspect that HCO 3 would benefit patients with propafenone toxicity, but the literature in this setting is limited. Ovaska et al [11] reported a patient that was was managed with intravenous glucagon, sodium bicarbonate, hypertonic saline and this treatment was associated with a good outcome. Recently D'Orazio [12] reported that sodium bicarbonate bolus and infusion shortened the QRS length to 90 ms. To avoid persistent hypotension and ECG abnormalities, 1 mEq/kg sodium bicarbonate administration in every 4-6 hours is recommended.…”

Comparative Study of Drug Interactions in Benzodiazepine Associated Deaths

“…3). Propafenone is a class 1C (sodium channel blockers) antiarrhythmic drug used for the treatment of ventricular arrhythmias [42]. Propafenone undergoes extensive metabolism via the CYP2D6 and CYP3A4.…”

“…Intoxication with propafenone is rare, a limited number of cases of lethal self-poisoning being reported in the literature [43]. Overdose may induce arrhythmia and conduction disturbance, complex, tachycardia, right bundle branch blocks, congestive heart failure and hypotension, seizures [42]. Interactions of propafenone with diazepam are not documented.…”