General Medical Information

Second-generation and Third-generation Antihistamines

Richard L. Mabry

The first nonsedating antihistamines (terfenadine, astemizole) are relatively lipid insoluble and cross the blood-brain barrier poorly. These preparations are essentially free of undesirable anticholinergic effects. However, because they can cause cardiac arrhythmia when administered in conjunction with drugs using the P-450 metabolic pathway, both have been withdrawn from distribution in the United States. Other new antihistamines include relatively nonsedating preparations (loratadine, cetirizine), a safer, nonsedating acid metabolite of terfenadine (fexofenadine), and topical forms (levocabastine, azelastine). A congener of loratadine is in the investigational stage. Because of unique drug interactions and properties, the prescribing literature must be consulted before any new antihistamine is used.