Blockade of cardiac potassium and other channels by antihistamines

The use of terfenadine and astemizole, two long-acting nonsedating histamin e H-1 receptor antagonists, has been associated with prolongation of the QT interval, development of ventricular arrhythmias, particularly torsade de pointes, and sudden cardiac death. Both drugs block the rapidly activating component of the delayed rectifier channel, I-Kr. At much higher concentrat ions, they also block several other cardiac channels (Na+, Ca2+, K+). Since many other antihistamines can also block one or other of the cardiac ion c urrents (e.g. loratadine blocks the human cardiac K+ channel, hKv 1.5, with the same potency as terfenadine), these results are also reviewed and thei r clinical relevance discussed. Because of the proarrhythmic risk, some antihistamines should be taken only at the recommended doses and avoided in patients with liver disease or in those taking medications that inhibit oxidative cytochrome P-450 enzymes. T hese drugs should also be avoided in those with the congenital long QT synd rome or with secondary forms of delayed repolarisation (hypokalaemia, brady cardia, drug-induced QT prolongation). Identification of predisposing facto rs could enable physicians to anticipate, and thereby avoid, this potential ly lethal complication of antihistamine therapy.