Disease relevance of Enkaid

• Suppression of ventricular arrhythmias by encainide [1].
• There was an excess of deaths due to arrhythmia and deaths due to shock after acute recurrent myocardial infarction in patients treated with encainide or flecainide [2].
• In the Cardiac Arrhythmia Suppression Trial, designed to test the hypothesis that suppression of ventricular ectopy after a myocardial infarction reduces the incidence of sudden death, patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo [2].
• Nine of eleven patients receiving encainide and 23 of 28 patients receiving flecainide who had repeat programmed ventricular stimulation while receiving drug therapy still had inducible, poorly tolerated ventricular tachycardia [3].
• Encainide is well tolerated and prevents recurrence of reentrant tachycardia in patients with Wolff-Parkinson-White syndrome very effectively [4].

High impact information on Enkaid

• Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial [2].
• Stroke volume index decreased with procainamide (-5 +/- 1 ml/m2, p less than 0.001), tocainide (-7 +/- 1 ml/m2, p less than 0.001), and encainide (-8 +/- 1 ml/m2, p less than 0.001), but the decline was significantly greater with encainide than with procainamide (p less than 0.05) [5].
• In a randomized, crossover study, the hemodynamic responses to single oral doses of procainamide (750 mg), tocainide (600 mg), and encainide (50 mg) given to 21 patients with severe chronic heart failure were compared [5].
• Moreover, it was only with the adoption of the dose-titration strategy that we were able to safely demonstrate that plasma MODE concentrations higher than those routinely observed during encainide therapy were required to substantially alter cardiac electrophysiology [6].
• Antiarrhythmic activity, electrocardiographic effects and pharmacokinetics of the encainide metabolites O-desmethyl encainide and 3-methoxy-O-desmethyl encainide in man [7].

Chemical compound and disease context of Enkaid

• Comparative study of encainide and quinidine in the treatment of ventricular arrhythmias [8].
• Comparative study of encainide and disopyramide in chronic ventricular arrhythmias: a double-blind placebo-controlled crossover study [9].
• Treatment of atrioventricular node reentrant tachycardia with encainide: reversal of drug effect with isoproterenol [10].
• In two patients, episodes of tachycardia were markedly reduced with the administration of encainide in combination with sotalol (one patient) and amiodarone (one patient) [11].
• 4 In Langendorff-perfused guinea-pig hearts, only lorcainide provided complete protection against ouabain-induced ventricular fibrillation, while 6 of 6, 3 of 6 and 2 of 6 hearts fibrillated in the presence of encainide, lignocaine and ORG 6001 respectively, but with infusion durations significantly higher than control [12].

Biological context of Enkaid

• We determined the pharmacokinetics, efficacy and therapeutic plasma concentration of encainide, a new antiarrhythmic drug that affects His-Purkinje conduction but not ventricular refractoriness [13].
• Encainide did not reduce exercise capacity or left ventricular ejection fraction at rest or during supine exercise [14].
• The effects of encainide on ventricular arrhythmia and left ventricular function were studied in 21 patients with chronic, high-grade ventricular arrhythmia using a prospective, 3-month, placebo-controlled, single-blind trial design [14].
• Clinical pharmacology and antiarrhythmic efficacy of encainide in patients with chronic ventricular arrhythmias [13].
• Pharmacogenetics and encainide [15].

Anatomical context of Enkaid

• Electrophysiologic and clinical effects of oral encainide in paroxysmal atrioventricular node reentrant tachycardia [16].
• Mild central nervous system side effects developed in two patients, but both could continue taking oral encainide [11].
• Genetically determined stereoselective excretion of encainide in humans and electrophysiologic effects of its enantiomers in canine cardiac Purkinje fibers [17].
• METHODS: Membrane currents were studied using the single suction pipette voltage clamp technique in freshly dissociated cat ventricular myocytes bathed in HEPES buffered physiological saline at 32 degrees C. RESULTS: Flecainide and encainide decreased IK with IC50 values of 2.1 microM and 6 microM, respectively [18].
• 1. Standard microelectrode methods have been used to record action potentials from guinea-pig ventricular myocardium and dog Purkinje fibres, and to study the effects of the two major metabolites of encainide, O-desmethyl encainide (ODE) and 3-methoxy-O-desmethyl encainide (MODE) [19].

Associations of Enkaid with other chemical compounds

• The use of encainide and flecainide was discontinued because of excess mortality [2].
• Ten patients suffering from chronic premature ventricular complexes (greater than 60/h) were treated orally in a double-blind crossover study with encainide (50 mg three times a day) and disopyramide (200 mg three times a day), with five 7 day study periods: survey, placebo, encainide or disopyramide, washout placebo and disopyramide or encainide [9].
• Diltiazem inhibited the first-pass metabolism of encainide, resulting in increased bioavailability [20].
• This information, combined with a full understanding of the drugs' clinical pharmacology now makes it possible to predict the clinical outcome for drugs such as encainide, flecainide, mexiletine, propafenone and combinations of these drugs with quinidine [21].
• The disposition kinetics of the new antiarrhythmic agent encainide are a function of the genetic polymorphism which also controls debrisoquin 4-hydroxylation [22].

Gene context of Enkaid

• Encainide suppresses atrial fibrillation resulting from topical application of aconitine in the anesthetized dog and ventricular fibrillation induced by chloroform asphyxiation in the mouse [23].
• However, despite the fact that the changes in atrioventricular (PR) and intraventricular (QRS) conduction times produced by encainide were different in extensive and poor metabolizer subjects and correlated with CYP2D6 activity, the electrocardiographic response was never 100% specific and sensitive for the identification of either phenotype [24].
• To assess whether decreased sodium channel activity contributes to sudden death in vivo, the response to encainide (20 mg/kg) was assessed: 6 of 10 young CN mice died because of asystole, whereas 0 of 10 wild-type mice died (P < 0.01) [25].
• Angina pectoris with encainide in dilated cardiomyopathy [26].
• Furthermore, the Cardiac Arrhythmia Pilot Study compared moricizine in postinfarction patients with encainide and flecainide [27].

Analytical, diagnostic and therapeutic context of Enkaid

• Drug therapy. Encainide [28].
• INTERVENTIONS: Invasive hemodynamic measurements were done (using a balloon-tipped thermodilution catheter) before and for 3 hours after a single oral dose of 50 mg of encainide [29].
• Differences between the electrophysiologic actions of the antiarrhythmic agent encainide have been reported after short-term intravenous and oral administration [30].
• Treatment of frequent ventricular arrhythmia with encainide: assessment using serial ambulatory electrocardiograms, intracardiac electrophysiologic studies, treadmill exercise tests, and radionuclide cineangiographic studies [14].
• Using programmed electrical stimulation of the heart, long-term electrocardiographic monitoring and exercise testing, the effect of intravenous and oral encainide for termination and prevention of incessant supraventricular tachycardia was assessed in 11 patients (aged 25 to 58 years) [11].

References