Pharmacology of antihistamines.

Abstract

Unlike the classic antihistamines, the new H1-receptor antagonists do not block cholinergic or central H1 receptors and thus do not produce the side effects, such as sedation, impaired psychomotor performance, and excessive mucosal drying, that are commonly associated with the older agents. Important pharmacokinetic and pharmacodynamic differences that exist among this class of antihistamines translate into varying pharmacologic effectiveness. Terfenadine, loratadine, and cetirizine are all rapidly absorbed in healthy and allergic volunteers (peak plasma levels, 2 to 5 hours); astemizole, however, has an initial distribution phase of 2 to 3 days. Further, astemizole has the longest time to relief of symptoms in this class; histamine wheal inhibition is not apparent until the second day of 10 mg dosing and does not peak for 9 to 12 days. In comparison, terfenadine's antihistaminic action peaks at 3 to 4 hours, loratadine's at 4 to 6 hours, and cetirizine's at 4 to 10 hours. However, whereas the recommended dose of loratadine (10 mg) confers 50% wheal inhibition, 60 mg terfenadine produces an 85% to 90% inhibition. In addition, loratadine and cetrizine have apparent dose-related sedative effects.