Blockade of cardiac potassium and other channels by antihistamines

• Published in: Drug safety Vol. 21; no. Supplement 1; pp. 11 - 18
• Main Authors: DELPON, E, VALENZUELA, C, TAMARGO, J
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Auckland Adis international 1999
• Subjects: Animals; Biological and medical sciences; Drug toxicity and drugs side effects treatment; Heart - drug effects; Histamine Antagonists - pharmacology; Humans; Ion Channels - antagonists & inhibitors; Medical sciences; Myocardium - metabolism; Pharmacology. Drug treatments; Potassium Channel Blockers; Toxicity: cardiovascular system; Human; Wave burst; Arrhythmia; Pathogenesis; Toxicity; Cardiovascular disease; Ionic channel; Ionic current; Antihistaminic; Excitability disorder; Heart disease; Antagonist; H1 Histamine receptor; Potassium
• ISSN: 0114-5916
• DOI: 10.2165/00002018-199921001-00003

The use of terfenadine and astemizole, two long-acting nonsedating histamine H1 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 concentrations, they also block several other cardiac channels (Na+, Ca2+, K+). Since many other antihistamines can also block one or other of the cardiac ion currents (e.g. loratadine blocks the human cardiac K+ channel, hKv1.5, with the same potency as terfenadine), these results are also reviewed and their 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. These drugs should also be avoided in those with the congenital long QT syndrome or with secondary forms of delayed repolarisation (hypokalaemia, bradycardia, drug-induced QT prolongation). Identification of predisposing factors could enable physicians to anticipate, and thereby avoid, this potentially lethal complication of antihistamine therapy.