The Experts below are selected from a list of 87 Experts worldwide ranked by ideXlab platform

Melvin M. Scheinman - One of the best experts on this subject based on the ideXlab platform.

Paul C Gillette - One of the best experts on this subject based on the ideXlab platform.

  • developmental electrophysiology of Encainide and its major metabolites on the purkinje fiber action potential
    Neonatology, 1994
    Co-Authors: Christopher L Case, Kenneth W Hewett, Paul C Gillette
    Abstract:

    Objective. With clinical data suggesting that neonates may be more prone to developing electrophysiologic side effects from Encainide, this study investigates the in vitro developmental electrophysiologic effects of Encainide and its major metabolites on the action potential parameters of the canine cardiac Purkinje fiber. Methods. With standard microelectrode techniques, the in vitro tonic and rate-related effects of Encainide, and its major metabolites (3-methoxy-4-hydroxy Encainide, MODE, and O-dimethyl Encainide, ODE) were investigated using mature and immature canine cardiac Purkinje fibers. Results. The significant developmental differences in the effects of these compounds on the canine Purkinje fiber illustrated in this study are: (1) 1 × 10––6M Encainide depresses Vmax in neonatal Purkinje fibers, yet not in the adult. (2) 1 × 10––6M MODE lengthens APD90 in the neonate, yet it has no substantial effect in the adult. (3) 1 × 10––6M ODE shortens APD90 in the adult, yet it has no appreciable effect on the neonate. (4) Rate-related effects of Encainide and ODE are more pronounced in adult Purkinje fibers. Conclusion. In contrast to other in vitro studies on class I anti-arrhythmic agents, neonatal canine Purkinje fibers seem to be more sensitive than the adult to the tonic depolarization depressant effect of Encainide. This in vitro sensitivity parallels clinical experience with the drug in neonatal patients. Although Encainide is no longer available for clinical use, these findings highlight the fact that the immature conduction system may show markedly different sensitivities to different class I agents despite the fact that these agents share similar qualitative pharmacologic properties.

  • proarrhythmia cardiac arrest and death in young patients receiving Encainide and flecainide
    Journal of the American College of Cardiology, 1991
    Co-Authors: Frank A Fish, Paul C Gillette, Woodrow D Benson
    Abstract:

    Abstract The potential for proarrhythmic responses to the class IC sodium channel-blocking drugs Encainide and flecainide has not been well described in young patients. Therefore, data were retrospectively collected from 36 institutions regarding 579 young patients who were administered Encainide or flecainide for treatment of supraventricular tachycardias (Encainide 86 patients, flecainide 369 patients) or ventricular arrhythmias (Encainide 21 patients, flecainide 103 patients) to assess the frequency of proarrhythmia, cardiac arrest and death during therapy (adverse events). The two drugs were similar in regard to efficacy (flecainide 71.4%, Encainide 59.8%) and rate of proarrhythmic responses (flecainide 7.4%; Encainide 7.5%). However, patients receiving Encainide more frequently experienced cardiac arrest (Encainide 7.5% vs. flecainide 2.3%, p Detailed data were provided for 44 patients experiencing one or more adverse events. Patient age, previous drug trials, concomitant therapy and days of inpatient monitoring were similar for patients receiving Encainide or flecainide. However, echocardiographic left ventricular shortening before treatment was lower among pationts receiving Encainide (0.23 ± 0.09) than among those receiving flecainide (0.34 ± 0.06, p Fifteen patients with an ostensibly normal heart and normal ventricular function experienced proarrhythmia during treatment for supraventricular tachycardia, but only 3 of the 15 had a cardiac arrest or died. The relatively high incidence of adverse events should be considered when contemplating treatment with Encainide or flecainide, particularly among patients with underlying heart disease.

Peter E Pool - One of the best experts on this subject based on the ideXlab platform.

  • efficacy of Encainide in supraventricular arrhythmias
    Cardiovascular Drugs and Therapy, 1990
    Co-Authors: Peter E Pool
    Abstract:

    This review summarizes the data from all the studies conducted in the United States and Europe that have evaluated the efficacy of Encainide in patients with a variety of supraventricular arrhythmias. Using clinical criteria of efficacy, Encainide was found to be effective or partially effective in 77% of patients evaluated by electrophysiologic means. Similar levels of efficacy were observed in patients with AV as well as AV nodal reentry arrhythmias. Patients with other forms of supraventricular arrhythmias in smaller series also experienced comparable degrees of efficacy. Encainide was discontinued because of intolerance by 8% of the patients in these studies: 6% because of side effects and 2% because of proarrhythmia.

John K Gibson - One of the best experts on this subject based on the ideXlab platform.

  • effects of ibutilide on spontaneous and induced ventricular arrhythmias in 24 hour canine myocardial infarction a comparative study with sotalol and Encainide
    Journal of Cardiovascular Pharmacology, 1992
    Co-Authors: Lewis V Buchanan, Glenn Kabell, Uta M Turcotte, Marshall N Brunden, John K Gibson
    Abstract:

    : The electrophysiologic and antiarrhythmic effects of ibutilide, sotalol, and Encainide were compared in dogs 24 h after myocardial infarction. Ibutilide (0.03 to 0.3 mg/kg i.v.) prevented the induction of ventricular arrhythmias in 100% of the dogs that had demonstrated inducible ventricular arrhythmias prior to treatment. This antiarrhythmic action was associated with significant increases in ventricular refractoriness and monophasic action potential duration. Sotalol (1.0 to 10.0 mg/kg i.v.) increased the ventricular refractory period and monophasic action potential duration and prevented the induction of ventricular arrhythmias in 75% of the dogs that demonstrated inducible ventricular tachyarrhythmias at baseline. Although 10 mg/kg of sotalol was required to prevent the initiation of ventricular tachycardia, this dose produced marked cardiovascular depression and hypotension in 50% of the dogs tested. Neither ibutilide nor sotalol significantly decreased the incidence of spontaneous ventricular arrhythmias. The class IC agent Encainide (0.3 to 3.0 mg/kg i.v.) was successful in preventing the induction of ventricular arrhythmias in only 20% of the dogs tested. However, in contrast to ibutilide and sotalol, Encainide significantly reduced spontaneous arrhythmias. Atrial and ventricular refractoriness were significantly increased only after the highest dose of Encainide tested (3.0 mg/kg). Over the dose ranges studied, the relative efficacy for prevention of pacing-induced ventricular arrhythmias was ibutilide greater than sotalol much greater than Encainide. For suppression of spontaneous ventricular arrhythmias, the relative efficacy was Encainide much greater than ibutilide = sotalol.(ABSTRACT TRUNCATED AT 250 WORDS)

Dan M Roden - One of the best experts on this subject based on the ideXlab platform.

  • genetically determined stereoselective excretion of Encainide in humans and electrophysiologic effects of its enantiomers in canine cardiac purkinje fibers
    Clinical Pharmacology & Therapeutics, 1991
    Co-Authors: Jacques Turgeon, Christian Funckbrentano, Holly T Gray, Harris N Pavlou, Chandra Prakash, Ian A Blair, Dan M Roden
    Abstract:

    Encainide metabolism is mediated by the polymorphically distributed cytochrome P450IID6, which displays stereoselectivity for some substrates. In this study we found that urinary recovery during steady-state Encainide in three poor metabolizers was high (49% to 80%), consisted mainly of unchanged Encainide, was nonstereoselective (± ratio, 0.985 to 1.049), and was unchanged by quinidine, a potent inhibitor of P450IID6. In contrast, in seven extensive metabolizers the ± urinary ratios were 1.20 ± 0.06 for Encainide and 0.81 ± 0.06 (both p < 0.01) for the cytochrome P450IID6 products O-desmethylEncainide plus 3-methoxy-O-desmethylEncainide; with quinidine the total percentage recovery rose from 4% ± 4% to 37% ± 9% because of increased recovery of unchanged Encainide and became nonstereoselective (± ratio, 0.84 ± 0.08 [Encainide alone] versus 0.97 ± 0.05 [Encainide plus quinidine]). In vitro, Encainide enantiomers depressed the maximum rate of metabolism with similar frequency and concentration dependence. We conclude that (-)-Encainide undergoes preferential metabolism by cytochrome P450IID6; however, this genetically determined stereoselective disposition is unlikely to play a major role in mediating the clinical actions of Encainide. Clinical Pharmacology and Therapeutics (1991) 49, 488–496; doi:10.1038/clpt.1991.59

  • genetically determined steady state interaction between Encainide and quinidine in patients with arrhythmias
    Journal of Pharmacology and Experimental Therapeutics, 1990
    Co-Authors: Jacques Turgeon, Christian Funckbrentano, Harris N Pavlou, Wilson Wong, Dan M Roden
    Abstract:

    A genetically determined pharmacokinetic and pharmacodynamic interaction between quinidine and single doses of Encainide in healthy volunteers has previously been described. In subjects with the extensive metabolizer phenotype, quinidine blunted Encainide-induced QRS prolongation (a marker of sodium channel block) because it impaired Encainide biotransformation to the potent active metabolites O-desmethyl Encainide (ODE) and 3-methoxy-O-desmethyl Encainide. Therefore, the purpose of this study was to test the hypothesis that quinidine would inhibit sodium channel block (and by inference arrhythmia suppression) during Encainide therapy in patients with the extensive metabolizer phenotype. Surprisingly, however, in eight extensive metabolizer patients, the extent of QRS prolongation during chronic Encainide therapy was unaltered by quinidine (139 +/- 21 vs. 139 +/- 22 msec) whereas arrhythmia suppression was enhanced (64 +/- 22 to 77 +/- 19%; P = .05). Plasma concentration data demonstrated that although Encainide metabolism to ODE was partially impaired by quinidine, subsequent 3-methoxy-O-desmethyl Encainide formation from ODE was virtually completely inhibited; thus steady-state plasma ODE remained unchanged whereas plasma Encainide increased 10-fold (21 +/- 30 to 240 +/- 118 ng/ml; P less than .05). In contrast, no changes in disposition or in pharmacodynamics were observed in two poor metabolizers. It is concluded that the effect of this drug interaction in patients is determined by differential sensitivities to inhibition by quinidine of Encainide O-demethylation and subsequent ODE 3-methoxylation. Evaluation of potential drug interactions should include assessment of possible genetic factors as well as of steady-state effects.