Spector S L
Department of Medicine, UCLA School of Medicine, USA.
Drugs. 1997 Sep;54(3):369-84. doi: 10.2165/00003495-199754030-00002.
Leukotrienes constitute a class of inflammatory mediators synthesised from arachidonic acid, a product of cell membrane metabolism. Synthesis occurs in the 5-lipoxygenase enzyme pathway, which produces several species of leukotrienes, each with characteristic biological activities. With regard to asthma, the leukotrienes are particularly important because of their ability to directly and potently mediate bronchoconstriction; in addition, they specifically stimulate the secretion of mucus into the airways and the extravasation of fluids and proteins into the airway tissues, both of which contribute to airway obstruction. A number of antileukotriene agents have been developed with the goal of modulating the inflammatory process in various disease states. These agents fall into 2 general classes: leukotriene receptor antagonists and leukotriene synthesis inhibitors. Results of antileukotriene agents in preclinical and clinical trials indicate that antileukotriene agents attenuate the response to challenges with inhaled leukotrienes, cold air, exercise, aspirin and allergen; in addition, they have shown efficacy in clinical asthma and have not been associated with serious adverse effects. Although results to date indicate that these medications are well tolerated and effective in the treatment of asthma, the recent approval by the FDA of 2 antileukotriene agents will give physicians further insight into how patients with asthma respond to them.
白三烯是一类由花生四烯酸合成的炎症介质，花生四烯酸是细胞膜代谢的产物。其合成发生在5-脂氧合酶途径，该途径产生多种白三烯，每种白三烯都有独特的生物学活性。对于哮喘而言，白三烯尤为重要，因为它们能够直接且强烈地介导支气管收缩；此外，它们还能特异性地刺激气道黏液分泌以及液体和蛋白质渗出到气道组织中，这两者都会导致气道阻塞。为了调节各种疾病状态下的炎症过程，人们研发了多种抗白三烯药物。这些药物主要分为两大类：白三烯受体拮抗剂和白三烯合成抑制剂。抗白三烯药物在临床前和临床试验中的结果表明，此类药物可减轻对吸入白三烯、冷空气、运动、阿司匹林和过敏原激发试验的反应；此外，它们在临床哮喘治疗中已显示出疗效，且未发现严重不良反应。尽管迄今为止的结果表明这些药物耐受性良好且对哮喘治疗有效，但美国食品药品监督管理局（FDA）近期批准的两种抗白三烯药物将使医生进一步了解哮喘患者对此类药物的反应情况。
