Cardiotoxicity of new antihistamines and cisapride.

Abstract

Although the new second-generation nonsedative antihistamines terfenadine and astemizole were launched as highly selective and specific H(1)-receptor antagonists, they were later found to cause prolongation of the QT-interval and severe cardiac arrhythmias. The prolongation of the QT-interval is caused by the blockade of one or more of the cardiac potassium channels, among which the delayed rectifier I(Kr), encoded by the HERG-gene, appears to be the most significant. The potency of the prokinetic drug cisapride to block I(Kr) appears to be similar to that of terfenadine (IC(50) about 50 nmol/l). These drugs cause problems when overdosed, used in combination with inhibitors of their CYP3A4-mediated metabolism, or when given to individuals with altered drug kinetics (the aged) or patients with existing cardiac disease (congenitally long QT). Moreover, interactions with other QT-interval prolonging drugs require special attention. Active hydrophilic metabolites of the second-generation antihistaminic compounds (ebastine-carebastine, loratadine-desloratadine, terfenadine-fexofenadine, astemizole-norastemizole) are new compounds with probably reduced risk for drug interactions and cardiac toxicity.

• Authors: Ilari Paakkari
• Journal: Toxicology letters (Toxicol Lett) Vol. 127 Issue 1-3 Pg. 279-84 (Feb 28 2002) ISSN: 0378-4274 [Print] Netherlands
• PMID: 12052668 (Publication Type: Journal Article, Review)

Chemical References

• Benzimidazoles
• Butyrophenones
• Histamine H1 Antagonists
• Piperidines
• Serotonin Receptor Agonists
• Triprolidine
• carebastine
• Loratadine
• Terfenadine
• Astemizole
• acrivastine
• ebastine
• Cisapride
• tecastemizole
• Cetirizine

Topics

• Arrhythmias, Cardiac (chemically induced)
• Astemizole (adverse effects)
• Benzimidazoles (adverse effects)
• Butyrophenones (adverse effects)
• Cetirizine (adverse effects)
• Cisapride (adverse effects)
• Heart Diseases (chemically induced, physiopathology)
• Histamine H1 Antagonists (adverse effects)
• Humans
• Loratadine (adverse effects)
• Piperidines (adverse effects)
• Serotonin Receptor Agonists (adverse effects)
• Terfenadine (adverse effects)
• Triprolidine (adverse effects, analogs & derivatives)