Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Encainide is a class IC antiarrhythmic agent that has been under clinical investigation for the last decade. Laboratory and clinical studies have demonstrated it to be a potent suppressor of ventricular extrasystoles. It is effective in approximately one-half of patients with malignant ventricular arrhythmias. The preliminary experience in patients with supraventricular arrhythmias indicates that the drug is particularly effective in arrhythmias associated with an accessory pathway. Side effects most commonly include blurred vision, nausea, heart block, and proarrhythmic effects. The hemodynamic effect of oral encainide are insignificant in patients with well-preserved left ventricular function. Despite minimal myocardial depression in patients with left ventricular dysfunction, there is the potential for worsening of heart failure. Encainide has a short half-life of 3 hours, but has 2 active metabolites with longer half-lives. No clinically significant drug interaction has been demonstrated with encainide therapy.
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PMID:Encainide: its electrophysiologic and antiarrhythmic effects, pharmacokinetics, and safety. 312 82

The safety issues relevant to treatment with encainide in patients with supraventricular arrhythmia were reviewed based on 349 patients enrolled in clinical trials in the United States and Europe. Although 20% of patients had a history of congestive heart failure, cardiomegaly, or cardiomyopathy at entry, there was no case of new or worsened heart failure. There were 5 cases (1.4%) of proarrhythmia in adults, reflecting a worsening of the arrhythmia being treated or of a coexisting ventricular arrhythmia. The profile of drug-related adverse effects was comparable to that previously reported, causing discontinuance in 6% of patients. The effects most often seen were dizziness, visual disturbance, headache, nausea and vertigo. Only 1 patient had clinically significant abnormal laboratory values, possibly reflecting hepatocellular injury in conjunction with viral hepatitis. Most responders received a daily dose of 75 to 200 mg/day, generally given in 3 divided doses. Encainide has a very favorable safety profile for use in the treatment of supraventricular arrhythmias.
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PMID:Safety considerations and dosing guidelines for encainide in supraventricular arrhythmias. 314 70

This article reviews clinical pharmacokinetic data on 8 new antiarrhythmic agents. Some of these drugs have been studied extensively while others are relatively new, with incomplete data due to limited evaluation. Amiodarone is a class III antiarrhythmic drug which is effective in treating many atrial and ventricular arrhythmias that are refractory to other drugs. Amiodarone accumulates extensively in tissues and its disposition characteristics are best described by models with 3 and 4 compartments. Its apparent volume of distribution is very large (1300 to 11,000L) and its elimination half-life very long (53 days). A delay of up to 28 days from of treatment to onset of antiarrhythmic effect may be observed, and the antiarrhythmic effect may persist for weeks to months following cessation of therapy. Clinically significant drug interactions have been observed with amiodarone and warfarin, digoxin, quinidine and procainamide. Encainide is a class Ic antiarrhythmic drug. Although it has a short elimination half-life (1 to 3h), 2 major metabolites with antiarrhythmic effects accumulate in the plasma of patients during long term therapy. Plasma concentrations of O-demethyl encainide appear to correlate with the antiarrhythmic effect. Flecainide, another class Ic antiarrhythmic agent, has an elimination half-life of 14 hours which makes it suitable for twice daily dosing. Flecainide elimination is prolonged in patients with low output heart failure. Significant drug interactions with digoxin and cimetidine have been reported. Lorcainide is also a class Ic antiarrhythmic drug, the bioavailability of which is nonlinear. Clearance of the drug is reduced during long term therapy. A major active metabolite, norlorcainide, accumulates in the plasma of patients during long term therapy and its concentration exceeds that of lorcainide by a factor of 2. The elimination half-lives of lorcainide (9h) and norlorcainide (28h) allow for once or twice daily dosing. Mexiletine, a class Ib antiarrhythmic drug, is structurally similar to lignocaine (lidocaine). A sustained release formulation provides effective plasma concentrations when administered twice daily. The apparent volume of distribution of mexiletine is 5.0 to 6.6 L/kg, and the elimination half-life varies from 6 to 12 hours in normal subjects and from 11 to 17 hours in cardiac patients. Mexilitine is extensively metabolised but the metabolites are not pharmacologically active. Renal elimination of mexiletine is pH dependent. Drugs which induce hepatic metabolism significantly alter the pharmacokinetics of mexiletine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetics of the newer antiarrhythmic agents. 643 21