Pharmacology of antihistamines

Abstract

H1-antihistamines, the mainstay of treatment for urticaria, were developed from anticholinergic drugs more than 70 years ago. They act as inverse agonists rather than antagonists of histamine H1-receptors which are members of the G-protein family. The older first generation H1-antihistamines penetrate readily into the brain to cause sedation, drowsiness, fatigue and impaired concentration and memory causing detrimental effects on learning and examination performance in children and on impairment of the ability of adults to work and drive. Their use should be discouraged. The newer second-generation H1-antihistamines are safer, cause less sedation and are more efficacious. Three drugs widely used for symptomatic relief in urticaria, desloratadine, levocetirizine and fexofenadine are highlighted in this review. Of these levocetirizine and fexofenadine are the most potent in humans in vivo. However, levocetirizine may cause somnolence in susceptible individuals, whereas fexofenadine has a relatively short duration of action and may be required to be given twice daily for all round daily protection. Although desloratadine is less potent, it has the advantages of rarely causing somnolence and having a long duration of action.

Keywords: Cetirizine; H1-antihistamines; desloratadine; fexofenadine; hydroxyzine; levocetirizine; loratadine.

Figure 1

(a) Diagram of a histamine H₁-receptor in a membrane showing seven transmembrane domains. Histamine stimulates the receptor following its penetration into the central core of the receptor. (b) A surface view of an activated receptor with histamine linking domains III and V. (c) A surface view of an inactive receptor with cetirizine linking domains IV and VI

Figure 2

Diagrammatic representation of the pharmacokinetics and pharmacodynamics of levocetirizine for a single oral dose of levocetirizine[3132]