Du Buske L M
Immunology Research Institute of New England, Fitchburg, MA 01420, USA.
J Allergy Clin Immunol. 1996 Dec;98(6 Pt 3):S307-18. doi: 10.1016/s0091-6749(96)80116-3.
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.
近4000万美国人有上呼吸道过敏症状，这使得抗组胺药成为最常用的药物之一。尽管除组胺外还有其他过敏症状介质，但变应性鼻炎和荨麻疹的治疗主要集中在使用抗组胺药上。然而，经典的组胺H1受体拮抗剂对H1位点不具有选择性，会产生多种多巴胺能、5-羟色胺能和胆碱能反应，由于其药理非选择性和易于穿透血脑屏障的能力，会在中枢神经系统产生相当多的不良反应。第二代抗组胺药是变应性鼻炎治疗的一大进步，因为它们穿透血脑屏障的速度较慢，而且设计成对H1受体具有更高的特异性。鉴于它们对H1受体具有更高的选择性，它们引起的中枢神经系统不良反应较少，而其疗效与用于治疗变应性鼻炎的经典抗组胺药相似。在这些抗组胺药中选择用于治疗变应性鼻炎，重点在于它们的药代动力学和不良反应情况。某些抗组胺药在代谢受抑制时可能产生心脏毒性作用，因此在开这些药物时需要谨慎。几种新型抗组胺药的抗过敏和抗哮喘作用正在研究中。对于临床医生来说，在H1受体拮抗剂之间做出治疗决策需要全面了解它们的多种作用。
