Disease relevance of propafenone

• We randomly assigned patients who had had at least one episode of atrial fibrillation within the previous six months to amiodarone or to sotalol or propafenone, given in an open-label fashion [1].
• The close time relationship between the administration of the drug and the acute onset of the liver damage, the histological findings, and the reappearance of biochemical signs of liver dysfunction upon rechallenge with the same medication strongly suggest that propafenone was involved in the pathogenesis of this syndrome [2].
• The recurrence rate of arrhythmia during treatment with propafenone was estimated to be approximately one fifth of the recurrence rate during treatment with placebo [3].
• Propafenone prolonged refractoriness and slowed conduction of the atrium, the atrioventricular node, and accessory atrioventricular bypass tracts, and these effects provided antiarrhythmic action to halt tachycardia [4].
• Termination of supraventricular tachycardia occurred in 15 of the 20 patients receiving propafenone but 0 of the 11 patients receiving placebo (p less than 0.01) [4].

Psychiatry related information on propafenone

• Probable propafenone-induced transient global amnesia [5].
• His symptoms of amnesia resolved approximately 6-7 hours after discontinuing the propafenone therapy [5].
• In conclusion, in patients with NSNF propafenone 1. does not affect sinus node automatism and 2. prolongs significantly DSACT, which, however, remains within the upper normal limit [6].

High impact information on propafenone

• Adverse events requiring the discontinuation of drug therapy occurred in 18 percent of the patients receiving amiodarone, as compared with 11 percent of those treated with sotalol or propafenone (P=0.06) [1].
• Nine subjects (with the extensive-metabolizer phenotype) metabolized most of the propafenone to 5-hydroxy propafenone, and five (with the poor-metabolizer phenotype) did not produce this metabolite [7].
• In this study, we tested the hypothesis that genetically determined variations in the biotransformation of propafenone to its 5-hydroxy metabolite account for variations in the drug's beta-blocking action [7].
• Propafenone also had a higher affinity for beta 2 receptors in vitro than either of its major metabolites [7].
• Subgroup analysis showed that among patients without heart disease, 78% of those receiving propafenone and 56% of those receiving placebo converted to sinus rhythm within 8 hours (P = 0.02) [8].

Chemical compound and disease context of propafenone

• Class I antiarrhythmic drugs such as quinidine or propafenone maintain sinus rhythm in approximately 50% of patients at 1 year and have risks for proarrhythmia and noncardiac toxicity [9].
• All recordings were used to discern ventricular tachycardia (VT) or ventricular fibrillation (VF) induced by repetitive extrastimulation (S2-S5) or 10-second burst stimulation at 25 to 200 Hz at baseline and after addition of procainamide (20 micromol/L) or propafenone (1 micromol/L) to the perfusate [10].
• CONCLUSIONS: Ibutilide, with a unique increase in atrial refractoriness, was more effective in conversion of atrial flutter than were propafenone and amiodarone [11].
• The relationship between debrisoquine metabolic phenotype and the pharmacokinetics and pharmacodynamics of propafenone was studied in 28 patients with chronic ventricular arrhythmias (22 extensive metabolizers [EMs] and six poor metabolizers [PMs] of debrisoquine) [12].
• Atrial flutter was terminated by each test drug in all dogs except for flecainide and propafenone in one dog each [13].

Biological context of propafenone

• We determined the efficacy, pharmacokinetics, and plasma concentration-response relationships of propafenone, a promising new antiarrhythmic drug [14].
• Clinical pharmacology of propafenone [14].
• Propafenone had no effect on blood pressure, heart rate, PA interval, AV node refractoriness or rate of reentrant tachycardia [15].
• The only side effect of propafenone noted was a decrease in systolic blood pressure of 9 +/- 9 mm Hg [16].
• In patients with myocardial impairment, echocardiographic assessment of left ventricular function indicated a decrease in ejection fraction during propafenone therapy (32 versus 24%, p less than 0.05), while no change was observed in patients with normal left ventricular function [17].

Anatomical context of propafenone

• We conclude that propafenone is metabolized via the same cytochrome P-450 responsible for debrisoquine's 4-hydroxylation, and that its pharmacokinetics and concentration-response relationships and the incidence of central nervous system side effects are different in patients of different debrisoquine metabolic phenotype [12].
• The effects of propafenone on the delayed rectifier K+ current were studied in guinea pig ventricular myocytes by using the patch-clamp technique [18].
• Propafenone did not change the mean arterial blood pressure but slightly increased right atrial, pulmonary artery and capillary wedge pressures resulting in mild depression of the cardiac index (2.6 +/- 0.8 liters/min per m2 before and 2.3 +/- 0.7 liters/min per m2 after; p less than 0.001) [19].
• The effects of the antiarrhythmic drug propafenone at Kv2.1 channels were studied with wild-type and mutated channels expressed in Xenopus laevis oocytes [20].
• We have chosen the antiarrhythmic propafenone, for which in vivo data indicated an interaction between (S)- and (R)-propafenone, as a model substance to study the mechanism underlying that interaction in human liver microsomes [21].

Associations of propafenone with other chemical compounds

• Inhibition of debrisoquine 4-hydroxylation by propafenone was demonstrated both in vivo and in a human liver microsomal system in vitro [12].
• After loading and dose titration phases were completed, the maintenance doses of drugs were 450 to 900 mg/day for propafenone and 160 to 960 mg/day for sotalol [22].
• In contrast, propafenone did not alter the kinetics of mexiletine enantiomers in subjects in the poor metabolizer group except for a slight decrease in the formation of hydroxymethylmexiletine [23].
• In addition, potentiation of disturbing central nervous system adverse effects may occur during combination therapy of propafenone and lidocaine [24].
• Kinetics and resting and exercise-induced hemodynamic and ECG effects of nicainoprol, a new antiarrhythmic structurally resembling propafenone or propranolol, were investigated in eight healthy male subjects receiving a 1-hour infusion (100 mg) and oral dose (200 mg) in a randomized-crossover fashion [25].

Gene context of propafenone

• CONCLUSION: Propafenone is a potent CYP2D6 inhibitor that may cause an increase in plasma concentrations of coadministered CYP2D6 substrates [23].
• Our data indicate that N-dealkylation of propafenone is mediated via CYP3A4 and CYP1A2 [26].
• Structural requirements for activity of propafenone-type modulators in P-glycoprotein-mediated multidrug resistance [27].
• An indirect conclusion from these in vivo data might be that propafenone is not a substrate of the UGT1A1 isoform [28].
• Two months after discontinuing propafenone, serum aminotransaminase and ALK concentrations had normalized and GGT had decreased and remained only slightly elevated [29].

Analytical, diagnostic and therapeutic context of propafenone

• Intravenous propafenone for termination of reentrant supraventricular tachycardia. A placebo-controlled, randomized, double-blind, crossover study [4].
• Differences in electrophysiological variables were assessed at baseline and during propafenone perfusion [30].
• After successful cardioversion, all patients received propafenone therapy and were followed up for 48 h [31].
• If 20 minutes after the initiation of this infusion there was no conversion to sinus rhythm, the patient received a second intravenous infusion over 10 minutes (either propafenone or placebo, whichever was not given first) [16].
• Concomitant use of propafenone in patients with implantable cardioverter-defibrillators with recurrent ventricular or atrial tachyarrhythmias should not interfere with proper device function [32].

References