Propafenone Ibutilide

Conversion of AF to NSR can also be accomplished with a subset of antiarrhythmic drugs (including 2-7) that act directly on cardiac muscle cells (myocytes) and antagonize either the sodium channel-mediated propagation currents (procainamide 2, flecainide 3, propafenone 4), or the inwardly rectifying (7 ) potassium channel currents (ibutilide 5, dofetilide 6). Some of the antiarrhythmics have actions at both potassium and sodium channels (i.e., dronedarone 7 and its close structural progenitor... 

The most common mechanism of dysrhythmias at the molecular level is by inhibition of the potassium channels known as IK, which are encoded by the human ether-a-go-go-related gene (HERG). The antidysrhythmic drugs that affect these channels include almokalant, amiodar-one, azimilide, bretylium, dofetilide, ibutilide, sematilide, D-sotalol, and tedisamil (all drugs with Class III actions) and bepridil, disopyramide, prenylamine, procainamide, propafenone, quinidine, and terodiline (all drugs with Qass I actions). Other drugs that affect these channels but are not used to treat cardiac dysrhythmias include astemizole and terfenadine (antihistamines), cisapride, erythromycin, haloperidol, sertindole, and thioridazine. 

Some evidence suggests that patients taking ibutilide have a less marked increase in QT interval, without a change in efficacy, when they are also given propafenone or flecainide. 

The increase in QTc interval after intravenous ibutilide 2 mg was less in patients treated with propafenone (5 patients) or flecainide (1 patient) than in 85 other patients who had taken ibutilide alone (34 versus 65 milliseconds). The effect appeared to be dose-related, with higher propafenone doses causing the largest attenuation in the ibutilide-induced QT prolongation. The efficacy of ibutilide was unaltered. In a further study, 71 patients with atrial fibrillation or atrial flutter receiving either propafenone 300 to 900 mg daily or flecainide 100 to 300 mg daily underwent cardioversion with a single intravenous dose of ibutilide 1 mg over 10 minutes, followed if necessary by a further dose after an interval of 10 minutes. Torsade de pointes occurred in one patient with profound sinus node suppression after cardioversion, but the mean ibutilide-induced QTc interval was attenuated (20 + 54 milliseconds compared to reported range of 47 to 90 milliseconds) without a decrease in efficacy. However, the authors note that the risk of sustained torsade de pointes in this study appears to be similar to that seen in other studies of ibutilide. ... 

Ibutilide, a class in antiarrhythmic, is known to increase the QT interval, so increasing the risk of torsade de pointes arrhythmia. Class Ic antiarrhythmics such as propafenone and flecainide generally shorten the QT interval. It is possible that class Ic antiarrhythmics may usefully attenuate the risk of torsade de pointes with ibutilide, and ibutilide may be... 

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