Propafenone: An Effective Agent for the Management of Supraventricular Arrhythmias

Abstract

Propafenone is a sodium channel blocking antiarrhythmic drug. It also has beta-adrenergic, potassium channel, and weak calcium channel blocking activity. The drug is metabolized in the liver with rates dependent on the debrisoquin phenotype. The saturable metabolism results in nonlinear pharmacokinetics. The metabolites retain sodium channel blocking activity but little beta-adrenergic blocking activity. Both controlled and noncontrolled studies have documented its efficacy in a variety of supraventricular arrhythmias. Intravenous propafenone is effective in converting atrial fibrillation to normal sinus rhythm. Chronic oral administration decreases the frequency of recurrence of atrial fibrillation and paroxysmal supraventricular tachycardia. The drug is particularly effective in the Wolff-Parkinson-White syndrome. The drug may produce SA block in patients with underlying sinus node dysfunction. Propafenone has comparatively few noncardiac side effects. It is a useful primary drug or an alternative to more commonly used drugs used for the treatment of supraventricular arrhythmias.

Atrial-Selective Sodium Channel Block Strategy to Suppress Atrial Fibrillation: Ranolazine versus Propafenone

“…Within a therapeutic range of concentrations, in addition to I Na , propafenone produces relatively mild inhibition of I Kr , I to , I Ca , and ␤-adrenoreceptors (Grant, 1996). We demonstrate an effect of propafenone to potently depress I Na -mediated parameters in both atrial and ventricular preparations at moderate to slow pacing rates.…”

“…This difference reflects the various exposure durations that are required to achieve a steady state in electrophysiological actions of the agents (Delgado et al, 1985;Antzelevitch et al, 2004). The concentrations of the drugs used were within the therapeutic relevant ranges of ranolazine and propafenone achieved when the drugs are prescribed at their recommended doses (Grant, 1996;Antzelevitch et al, 2011). To compare the antiarrhythmic potential of propafenone and ranolazine, we used an acetylcholine (ACh; 0.5-1.0 M)-dependent AF model in coronary-perfused right atria, where persistent AF is inducible in 100% of preparations (by a single premature beat or rapid pacing) (Burashnikov and Antzelevitch, 2003;Burashnikov et al, 2007).…”

“…4). Atrial-selective prolongation of APD 90 by ranolazine and propafenone is likely caused by their effect to block I Kr (Grant, 1996;Antzelevitch et al, 2004). Indeed, specific I Kr block with N- [4-[1-[2-(6-methylpyridin-2-yl) ethyl]piperidine-4-carbonyl]phenyl] (E-4031) produces atrialpredominant prolongation of APD 90 and ERP in canine preparations at a CL of 500 ms (Burashnikov et al, 2008).…”

Propafenone and Its Metabolites Preferentially Inhibit IKrin Rabbit Ventricular Myocytes

“…Propafenone is effective in the medical therapy of a variety of supraventricular as well as ventricular tachyarrhythmias in children (Paul and Janousek, 1994) and adults (Grant, 1996). Although categorized as a sodium channel-blocking agent in the Vaughan Williams antiarrhythmic drug classification scheme, propafenone potently inhibits a number of repolarizing potassium currents in cardiac myocytes isolated from humans (Gross and Castle, 1998;Seki et al, 1999) as well as from animals (Duan et al, 1993;Slawsky and Castle, 1994;Delpón et al, 1995;Christé et al, 1999;Cahill et al, 2001).…”

Clinical Comparison of Ibutilide and Propafenone for Converting Atrial Flutter

“…Propafenone is a class Ic antiarrhythmic drug that has weak β-adrenergic antagonist properties [8]. Duan et al [9] found that propafenone blocked the transient outward, delayed rectifier and inward rectifier potassium currents in rabbit atrial myocytes.…”