Pro-Arrhythmic Effects of Noncardiac Medications: Lessons From Macrolide Antibiotics.

S udden death resulting from medications prescribed with good intentions is an everpresent threat first recognized nearly a century ago (1,2). As early as 1923, when quinidine was first used as antiarrhythmic therapy, a disturbing phenomenon was noted: some patients treated with quinidine suffered from sudden collapses, sometimes ending in unexpected deaths (2). These events were first attributed to “embolism” (2) or “nervous-system depression” (1). It was only in 1964, when Selzer and Wray (3) first documented polymorphic ventricular tachyarrhythmias (VTA) as the cause for quinidine syncope. The phenomenon of “drug-induced arrhythmia” became even more puzzling when medications with no cardiac indications, understandably assumed to be free of cardiac effects, were also reported to provoke arrhythmia (4). The first medication was the antipsychotic thioridazine. In 1966, Schoonmaker et al. (4) described a patient with schizophrenia who had normal QT at baseline but developed QT prolongation during thioridazine therapy. This thioridazine-induced QT prolongation “resembled quinidine effect” and was therefore considered benign, so when the patient developed polymorphic VTA, he was treated with no other but quinidine (he eventually survived thanks to cardiac pacing) (4). This twisted course of events emphasizes the lack of