To gain insight into possible mechanisms of and predisposing factors for torsades de pointes during terfenadine therapy, spontaneous reports in the US Food Drug Administration's Spontaneous Reporting System database were examined. Based on characteristics cases, vitro cardiac electrophysiologic studies conducted to test hypothesis that terfenadine, not its major metabolite, has actions similar those quinidine is responsible this form toxicity.Spontaneous from general medical community.As...

Acute caffeine in subjects who do not normally ingest methylxanthines leads to increases blood pressure, heart rate, plasma epinephrine, norepinephrine, renin activity, and urinary catecholamines. Using a double-blind design, the effects of chronic administration on these same variables were assessed. Near complete tolerance, terms both humoral hemodynamic variables, developed over first 1-4 d caffeine. No long-term catecholamines, or catecholamines could be demonstrated. Discontinuation...

To investigate the relation between acetvlator phenotype and development of procainamide-induced lupus, we determined rate antinuclear antibodies in 20 patients known acetylator receiving chronic procainamide therapy. The duration therapy required to induce 50 per cent slow (11) rapid (nine) acetylators was 2.9 7.3 months respectively. median total dose that produced ant;bodies 1.5 g kilogram 6.1 After one year had developed 18 patients. Retrospective studies whom lupus revealed for...

Terfenadine is a nonsedating H1-antagonist that when overdosed, used with hepatic compromise, or given ketoconazole results in accumulation of parent terfenadine, prolongation the QT interval, and torsades de pointes susceptible patients. Nine subjects were recommended dose terfenadine (60 mg every 12 hours) for 7 days before initiation oral erythromycin (500 8 hours). All increased metabolite concentrations after addition 1 week. The maximum concentration by mean 107% area under...

Sex hormones are known to exert direct and indirect effects on cardiovascular function, but their cardiac repolarization have not been elucidated. The phase of the action potential or QT interval ECG is regulated largely by potassium channels such as delayed rectifier currents HK2 IsK.The ovariectomy (OVX) estradiol (E2) dihydrotestosterone (DHT) treatment were evaluated HK2, HERG, IsK mRNA levels, duration, quinidine-induced changes in isolated rabbit hearts. 0.7-kilobase downregulated...

The relationship between debrisoquine metabolic phenotype and the pharmacokinetics pharmacodynamics of propafenone was studied in 28 patients with chronic ventricular arrhythmias (22 extensive metabolizers [EMs] six poor [PMs] debrisoquine). EMs were characterized by a shorter elimination half-life (5.5 +/- 2.1 vs 17.2 8.0, p less than .001), lower average plasma concentration (Cp) (1.1 0.6 2.5 0.5 ng/ml/mg daily dosage, higher oral clearance (1115 1238 264 48 ml/min, .001). active...

We have evaluated the ability of various opioid agonists, including methadone, l-α-acetylmethadol (LAAM), fentanyl, meperidine, codeine, morphine, and buprenorphine, to block cardiac human <i>ether-a-go-go</i>-related gene (HERG) K⁺current (I_HERG) in cells stably transfected with HERG potassium channel gene. Our results show that LAAM, buprenorphine were effective inhibitors I_HERG, IC₅₀ values 1 10 μM range. The other drugs tested far less potent...

Numerous medications prolong the rate-corrected QT (QTc) interval and induce arrhythmias by blocking ionic current through cardiac potassium channels composed of subunits expressed human ether-a-go-go-related gene (HERG). Recent reports suggest that high doses methadone cause torsades de pointes. To date, no controlled study has described an association between QTc prolongation. The only commercial formulation parenteral available in United States contains preservative chlorobutanol....

We sought to determine the response rate and safety of intravenous amiodarone in patients with ventricular tachyarrhythmias refractory standard therapies. Numerous small retrospective reports suggest a amiodarone, yet no controlled prospective trials exist. Two hundred seventy-three recurrent hypotensive lidocaine, procainamide bretylium were randomized receive one three doses amiodarone: 525, 1,050 or 2,100 mg/24 h (mean [±SE] dose 743.7 ± 418.7, 1,175.2 483.7, 1,921.2 688.8 mg,...

Recent case series have associated the synthetic opioid, methadone, with QT prolongation and torsades de pointes (TdP) ventricular arrhythmia.To review analyze adverse events (QT TdP) reported to Food Drug Administration (FDA) determine patient characteristics, dosages of outcomes methadone-treated patients.The study design was a retrieval retrospective analysis reports methadone voluntarily FDA MedWatch program from 1969 October 2002. Reports were accessed via QSCAN (DrugLogic, Reston, VA),...

Background:We sought to determine the extent of potentially inappropriate outpatient prescribing for elderly patients, as defined by Beers revised list drugs be avoided in populations. Methods:We conducted a retrospective cohort study using prescription claims database large, national pharmaceutical benefit manager.The included 765423 subjects 65 years or older, who were covered manager and filed 1 more drug during 1999.Main outcome measures proportion filled concern prescriptions 2...

Women are known to have a longer electrocardiographic Q-T than men, which may contribute their being at greater risk of developing drug-induced polymorphic ventricular arrhythmias. However, little is about the underlying mechanisms. In present study, we evaluated potential gender differences in interval isolated perfused rabbit hearts using Langendorff technique and density outward potassium currents single myocytes whole-cell patch-clamp technique. We found that female demonstrated...

Context.—Erythromycin is a widely used antibiotic that infrequently causes QT-prolongation and torsades de pointes cardiac arrhythmias. For antiarrhythmic drugs, women are at higher risk for these arrhythmias, but few other classes of drugs have been studied.Objectives.—To determine whether female sex factor arrhythmias associated with erythromycin, if this can be correlated in vitro measurements the QT-response to erythromycin male rabbit hearts.Design.—Food Drug Administration (FDA)...

Objectives To establish whether the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine are affected by concomitant administration grapefruit juice to determine any effect is dependent on timing in relation dose terfenadine. Methods Twelve healthy volunteers were studied a prospective randomized trial. The primary end points QT prolongation surface electrocardiogram pharmacokinetic parameters: area under concentration-time curve (AUC), maximum concentration, time...

We studied the antiarrhythmic effect of a range oral doses encainide in 11 patients with stable high-frequency ventricular arrhythmias. Total suppression arrhythmia was documented 10 at wide and plasma concentrations, subsequently verified placebo-controlled crossover study. Drug elimination rapid (the half-life 1.9 to 3.8 hours), but margin between efficacy side effects sufficiently for therapy every six 12 hours be feasible all patients, continuing outpatient treatment months. Marked...