Comparison of the effects of placebo and encainide on programmed electrical stimulation and ventricular arrhythmia frequency

Duff, Henry J.; Roden, Dan M.; Dawson, Albert K.; Oates, John A.; Smith, Raymond A.; Woosley, Raymond L.

doi:10.1016/0002-9149(82)90181-3

Cited by 22 publications

(2 citation statements)

References 20 publications

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“…The occurrence of proarrhythmia during encainide therapy may also correlate with ODE at toxic plasma concentrations. 28,[30][31][32] Not only is there greater potential for rapid accumulation of ODE and MODE in renal failure patients, but washout of these metabolities after withdrawal from chronic oral therapy is prolonged, allowing for sustained antiarrhythmic and potentially arrhythmogenic effects. Animal studies suggest that high plasma ODE concentrations (300-600 ng/ml) correlate with decreased spontaneous ventricular fibrillation thresholds and increased energy requirements for defibrillation.…”

Section: Discussionmentioning

confidence: 99%

Encainide dosing in patients with severe renal dysfunction: Report of a case and literature review

Fronc

Porter

Nydegger

et al. 1992

Clinical Cardiology

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Summary: Dosage of encainide for patients with lethal ventricular arrhythmias is based on pharmacodynamic effects and efficacy of arrhythmia suppression, coupled with metabolizer phenotype and extent of renal and hepatic dysfunction. Decreased clearance in patients with renal dysfunction necessitates a reduction in dosage to avoid toxic and dose-related proarrhythmic effects. This case represents a patient with severe renal dysfunction and sustained ventricular tachycardia who achieved electrophysiologically guided suppression of induced ventricular tachycardia at a steady-state encainide dose of only 25 mg daily, significantly lower than package insert or compendial recommendations for initial dosage in patients with renal insufficiency. Documented "therapeutic" metabolite concentrations correlated to electrophysiologic response. Literature review illustrates the complexity of encainide dosage in such individuals and underscores the need for therapeutic drug monitoring to individualize dosage.

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Section: Discussionmentioning

confidence: 99%

Encainide dosing in patients with severe renal dysfunction: Report of a case and literature review

Fronc

Porter

Nydegger

et al. 1992

Clinical Cardiology

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“…Duff et al [53] examined encainide therapy in 8 patients for treatment of recurrent ventricular arrhythmias refractory to empiric therapy with at least two antiarrhythmic agents, one of which was procainamide or quinidine. Encainide was found to be effective in suppressing ventricular arrhythmias, as assessed by ambulatory monitoring during 6 months of outpatient therapy.…”

Section: Ventricular Tachycardia/fibrillationmentioning

confidence: 99%

Encainide

Antonaccio

Gomoll

Byrne

1989

Cardiovasc Drug Ther

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Encainide is a class IC antiarrhythmic agent having little or no effect on action-potential duration or maximum diastolic potential but decreasing the maximum rate of phase O depolarization as well as increasing atrial and ventricular effective refractory periods. In intact animals or humans, encainide increases the AH, PR, QRS, and H-V intervals while not affecting the sinus node cycle length or JT interval. QT interval increases only by the concomitant increase in the QRS interval. Encainide is metabolized to O-demethyl encainide (ODE) and 3-methoxy-ODE (MODE), both of which are also antiarrhythmics with similar pharmacology to encainide. Encainide and its metabolites have little negative inotropic activity and ancillary pharmacology. Consequently, encainide has little or no effect on hemodynamic variables in patients with either normal or compromised cardiac function. The drug is well tolerated, with side effects being mainly those associated with its local anesthetic activity such as blurred vision and dizziness. Encainide is particularly effective in patients with excessive premature ventricular complexes (PVCs) and less so in patients with sustained ventricular tachycardia (VT). Like all antiarrhythmics, encainide may aggravate or precipitate new arrhythmias (proarrhythmia). The overall incidence of proarrhythmia is about 10%, with less occurring in patients with PVCs and more in those with sustained VT; also, the incidence of proarrhythmia is higher in patients with underlying heart disease. Encainide is also effective for the treatment of supra-ventricular arrhythmias, including atrial fibrillation, PSVT (both PAF as well as reentry of the nodal or W-P-W type), and ectopic atrial tachycardia. Its dosage and role in antiarrhythmic therapy are discussed.

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Increased incidence of side effects after encainide: A newly developed antiarrhythmic drug

Schwarz

Hust

et al. 1984

Clinical Cardiology

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Summary:In a clinical trial the efficacy of encainide, a newly developed class I antiarrhythmic agent, was compared with the well-known mexiletine. Nine patients with different underlying cardiac disease and chronic complex ventricular ectopies (documented by 24-h Holter monitoring, confirmed during the initial placebo period) entered the study. The dosage of encainide was increased from 25 to 75 mg three times daily and the antiarrhythmic effect monitored by repeated 24-h Holter registration and in some patients by treadmill exercise testing. During the clinical followup we noted a high incidence of so-called "minor side effects" (headache, dizziness, blurred vision, tremor, and nausea), which caused us to terminate the study. In all instances adverse effects emerged before ectopic activity was suppressed satisfactorily prohibiting further increment of dosage. These results indicate that encainide cannot be regarded as an antiarrhythmic drug of first choice in routine clinical application.

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Comparison of the effects of placebo and encainide on programmed electrical stimulation and ventricular arrhythmia frequency

Cited by 22 publications

References 20 publications

Encainide dosing in patients with severe renal dysfunction: Report of a case and literature review

Encainide dosing in patients with severe renal dysfunction: Report of a case and literature review

Encainide

Increased incidence of side effects after encainide: A newly developed antiarrhythmic drug

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