QT Interval Prolongation as a Biomarker for Torsades de Pointes and Sudden Death in Drug Development

نویسنده

  • Gregory D. Sides
چکیده

Prolongation of the QT interval on the surface 12-lead electrocardiogram is widely accepted as a biomarker for the potential of a drug to produce torsades de pointes and/or sudden death. Detection of drug-induced prolongation of the QT interval in animals and man is frequently confounded by extrinsic and intrinsic factors that limit the ability to detect a true drug effect. In particular drugs that increase heart rate show an apparent increase in QT interval that confounds assessment of a true drug effect on cardiac ventricular repolarization. The basis for the use of the QT interval as a biomarker will be examined.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Dose-Dependent Effects of Methadone on QT interval in Patients under Methadone Maintenance Treatment

Background: The role of methadone in QTc prolongation, Torsades de Pointes (TdP) arrhythmia and sudden cardiac death has been debated. Because of widespread use of methadone in methadone maintenance treatment (MMT) centers, we aimed to study dose-related effects of methadone on QTc prolongation. Methods: In a comparative observational study, 90 patients who were under MMT were evaluated. Patien...

متن کامل

Ziprasidone and hypokalemia: a case of 2 predisposing factors for QTc prolongation without development of torsades de pointes.

Sir: Although concerns about sudden cardiac arrhythmia death associated with the use of an antipsychotic drug actually predate the description of torsades de pointes, it is this fatal arrhythmia and its electrocardiographic (ECG) predictor (corrected QT [QTc] interval prolongation) that have become of increasing concern related to the use of antipsychotic medications during recent years. The fi...

متن کامل

ADVERSE DRUG REACTION QT prolongation due to roxithromycin

Roxithromycin and other macrolide antimicrobials are widely used for a broad variety of infections such as upper respiratory tract infection and community acquired pneumonia. Prolongation of the QT interval, torsade de pointes polymorphic ventricular tachycardia, and sudden death are well described but little known adverse reactions common to all macrolides. We report the case of a 72 year old ...

متن کامل

Key clinical considerations for demonstrating the utility of preclinical models to predict clinical drug-induced torsades de pointes.

While the QT/QTc interval is currently the best available clinical surrogate for the development of drug-induced torsades de pointes, it is overall an imperfect biomarker. In addition to low specificity for predicting arrhythmias, other issues relevant to using QT as a biomarker include (1) an apparent dissociation, for some drugs (for example, amiodarone, sodium pentobarbital, ranolazine) betw...

متن کامل

Mechanisms, Risk Factors, and Management of Acquired Long QT Syndrome: A Comprehensive Review

Long QT syndrome is characterized by prolongation of the corrected QT (QTc) interval on the surface electrocardiogram and is associated with precipitation of torsade de pointes (TdP), a polymorphic ventricular tachycardia that may cause sudden death. Acquired long QT syndrome describes pathologic excessive prolongation of the QT interval, upon exposure to an environmental stressor, with reversi...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 18  شماره 

صفحات  -

تاریخ انتشار 2002