Editorials

Risk of torsades de pointes with non-cardiac drugs

BMJ 2000; 320 doi: http://dx.doi.org/10.1136/bmj.320.7243.1158 (Published 29 April 2000) Cite this as: BMJ 2000;320:1158

Doctors need to be aware that many drugs can cause QT prolongation

  1. Yee Guan Yap, British Heart Foundation research fellow,
  2. John Camm, professor of cardiology and head (jcamm@sghms.ac.uk)
  1. Department of Cardiological Sciences, St George's Hospital Medical School, London SW17 0RE

    Many antiarrhythmic drugs are known to prolong ventricular repolarisation and provoke torsades de pointes. Recently, an increasing number of non-cardiac drugs have also been reported to have the same effects. These drugs share the same ability to block the rapid component of the delayed rectifier potassium channel (IKr), resulting in inhomogeneous lengthening of action potential, T wave abnormality, and QT interval prolongation. Depolarisation current at the tail of a prolonged action potential induces early after depolarisations, which in the setting of inhomogeneous ventricular recovery provokes torsades de pointes. Many doctors are unaware of the proarrhythmic risk associated with some non-cardiac drugs. With few exceptions, most papers published in scientific journals are anecdotal case reports. Notifications to regulatory authorities, the World Health Organisation, and pharmaceutical companies thus constitute much of the evidence base.

    Two non-sedating antihistamines, terfenadine and astemizole, attracted regulatory attention in the early 1990s and have since been restricted to prescription only in the United Kingdom because of their unexpected association with QT prolongation, torsades de pointes, and sudden death.12 The adverse effects of terfenadine appeared to depend on concentration, occurring at supraclinical doses or at normal doses in patients also …

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