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  • Title: Propafenone. A reappraisal of its pharmacology, pharmacokinetics and therapeutic use in cardiac arrhythmias.
    Author: Bryson HM, Palmer KJ, Langtry HD, Fitton A.
    Journal: Drugs; 1993 Jan; 45(1):85-130. PubMed ID: 7680987.
    Abstract:
    Propafenone is an orally active sodium channel blocking agent with beta-adrenoceptor antagonist and weak calcium antagonist activity. The pharmacokinetic profile of propafenone is complex, characterised as typically nonlinear, saturable, stereoselective and dependent on both dose and debrisoquin metaboliser phenotype; individualised dosage titration is required. Both placebo- and drug-controlled studies have confirmed the efficacy of propafenone in the treatment of premature ventricular complexes, ventricular couplets and nonsustained ventricular tachycardia; in a large meta-analysis, propafenone together with amiodarone, flecainide and encainide were significantly more effective in the control of ventricular ectopy than other antiarrhythmic agents. However, the use of propafenone in these indications, like that of other antiarrhythmic agents, is likely to be limited to patients with a favourable risk-to-benefit ratio. Propafenone has also demonstrated efficacy in the treatment of malignant ventricular arrhythmias (ventricular fibrillation and sustained ventricular tachycardia); preliminary mortality data obtained with propafenone have been encouraging in this patient group. In addition, propafenone has a favourable noncardiac tolerability profile and beta-adrenoceptor antagonist activity, which may offer advantages in some specific patient groups. The area of research concerning propafenone which has shown the greatest expansion over the past 5 years is in the treatment of supraventricular arrhythmias. Propafenone has marked efficacy in patients with Wolff-Parkinson-White syndrome and has been recommended as a first-line prophylactic agent in those with rapid anterograde conduction. Propafenone is also effective in the conversion of atrial fibrillation to sinus rhythm, although comparative studies are required to determine advantages over more established agents. Propafenone use has been successfully extended to children with limited data demonstrating consistent efficacy in the control of junctional ectopic tachycardia. As with all antiarrhythmic agents, propafenone has the potential to induce arrhythmias. Comparative studies are required to assess in more detail the cardiac tolerability profile of propafenone against other class Ic agents. In conclusion, propafenone offers a broad spectrum of activity in the treatment of cardiac arrhythmias, although its use in patients with potentially malignant arrhythmias will remain limited for the present. Due to its unique pharmacodynamic profile, propafenone deserves consideration as an individual agent.
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