Pharmacology of Antihistamines

摘要

This article reviews the molecular biology of the interaction of histamine with its H₁-receptor and describes the concept that H₁-antihistamines are not receptor antagonists but are inverse agonists i.e. they produce the opposite effect on the receptor to histamine. It then discourages the use of first-generation H₁-antihistamines in clinical practice today for two main reasons. First, they are less effective than second generation H₁-antihistamines. Second, they have unwanted side effects, particularly central nervous system and anti-cholinergic effects, and have the potential for causing severe toxic reactions which are not shared by second-generation H₁-antihistamines. There are many efficacious and safe second-generation H₁-antihistamines on the market for the treatment of allergic disease. Of the three drugs highlighted in this review, levocetirizine and fexofenadine are the most efficacious in humans in vivo . However, levocetirizine may cause somnolence in susceptible individuals while fexofenadine has a relatively short duration of action requiring twice daily administration for full all round daily protection. While desloratadine is less efficacious, it has the advantages of rarely causing somnolence and having a long duration of action. Lastly, all H₁-antihistamines have anti-inflammatory effects but it requires regular daily dosing rather than dosing 'on-demand' for this effect to be clinically demonstrable.