Cardiovascular safety of second-generation antihistamines

Reports of serious cardiac arrhythmia associated with some second-generatio n antihistamines have prompted concern for their prescription. This article reviews the nature of the adverse events reported and concludes that the b lockade of potassium channels, particularly the subtype responsible for the rapid component of the delayed rectifier current (I-Kr) is largely respons ible for such adverse cardiac events. Consequently, antihistamines with lit tle or no interaction with these channels are expected to have the greatest safety margin. The main cardiac arrhythmia of concern is that of torsades de pointes, a potentially fatal phenomenon characterized by prolonged ventr icular depolarization that manifests as a prolonged QT interval and polymor phic ventricular tachycardia, with twisting of the QRS complexes. Based on preclinical and clinical evidence, it appears that loratadine, cetirizine, and fexofenadine are safe from cardiac arrhythmia via the I-Kr channel, whe reas astemizole and terfenadine have a propensity to cause ventricular tach yarrhythmias.