Clinical comparison of histamine H1-receptor antagonist drugs

Nearly 40 million Americans have symptoms of upper respiratory allergies, making antihistamines among the most frequently used pharmacologic agents. Although there are mediators of allergic symptoms in addition to histamine, therapy for allergic rhinitis and urticaria has focused upon the use of antihistamines. The classic histamine H1-receptor antagonists, however, are not selective for the H1 site and produce a variety of dopaminergic, serotonergic, and cholinergic responses leading to considerable adverse effects in the central nervous system consequent to both their pharmacologic nonselectivity and their ability to penetrate the blood-brain barrier readily. The second-generation antihistamines were a major advance in the therapy of allergic rhinitis, because they do not penetrate the blood-brain barrier as rapidly and are also designed for greater specificity at H1-receptor. Given their greater selectivity for the H1-receptor, they cause fewer undesirable central nervous system actions, whereas their efficacy is similar to that of the classic antihistamines used in the treatment of allergic rhinitis. Selecting among these antihistamines for the treatment of allergic rhinitis has focused on their pharmacokinetics and adverse effect profiles. The potential cardiotoxic effects of some antihistamines when their metabolism is inhibited requires caution in prescribing these agents. The antiallergic and antiasthmatic effects of several newer antihistamines are being explored. For the clinician, making the therapeutic decision among H1-receptor antagonists requires a comprehensive knowledge of their diverse effects.