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用于治疗炎症性肠病的药物的风险效益评估。

Risk-benefit assessment of drugs used in the treatment of inflammatory bowel disease.

作者信息

Hanauer S B, Stathopoulos G

机构信息

Department of Medicine, University of Chicago Medical Center, Illinois.

出版信息

Drug Saf. 1991 May-Jun;6(3):192-219. doi: 10.2165/00002018-199106030-00005.

Abstract

Although the aetiology of inflammatory bowel disease remains elusive, many agents are available for the control of symptoms and inflammation. Knowledge of drug pharmacology, indications and side effects is essential to ensure the best possible clinical care while minimising toxicity and inappropriate use. Sulfasalazine consists of sulfapyridine linked to mesalazine (5-aminosalicylic acid) via an azobond. Its use is indicated in the treatment of mild to moderately active ulcerative colitis and in the prevention of relapse in patients with quiescent disease. Patients with mild to moderate colonic or ileocolonic Crohn's disease also benefit from this drug, as do a proportion of patients with isolated small bowel disease. Sulfasalazine has not been uniformly effective in preventing relapse in Crohn's disease, although many clinicians continue its use in patients who respond initially. A high incidence of side effects which limit therapy include intolerance, hypersensitivity reactions and impairment of male infertility. The newer aminosalicylates offer targeted delivery of mesalazine to the bowel, with fewer side effects. Topical mesalazine has proved extremely effective in patients with distal ulcerative colitis; oral forms are effective in the treatment of mild to moderately active ulcerative colitis and in relapse. Both types appear to be effective in the treatment of Crohn's disease, and possibly in preventing relapse. There is no current clinical advantage of one mesalazine preparation over another, nor is there an indication for their use in sulfasalazine-treated patients who have satisfactory response without adverse effects. Corticosteroids are indicated for more severe disease activity where the aminosalicylates have limited efficacy-specifically to induce remission in patients with severe or refractory ulcerative colitis or Crohn's disease. They should not be used to maintain disease remission or in the prevention of postoperative recurrence. Topical corticosteroids allow their local use in distal colitis with minimal systemic side effects. Long term use is limited by side effects, many of which are dose related, although alternate-day therapy may lessen the incidence. Immunosuppressive agents are beneficial for the treatment of refractory inflammatory bowel disease unresponsive to other medications, and may also facilitate the withdrawal of steroids in refractory patients. Mercaptopurine has an added benefit in the treatment of Crohn's disease fistulae; the role of cyclosporin in bowel disease has not been established and its use cannot currently be recommended. The potential toxicity of immunosuppressive agents warrants careful consideration of their use by both physician and patient. Metronidazole is indicated for the treatment of mild to moderate Crohn's disease, including perineal disease. Common side effects include peripheral neuropathy and nausea.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

尽管炎症性肠病的病因仍不明确,但有许多药物可用于控制症状和炎症。了解药物药理学、适应证及副作用对于确保提供最佳临床护理、同时将毒性和不当用药降至最低至关重要。柳氮磺胺吡啶由通过偶氮键与美沙拉嗪(5-氨基水杨酸)相连的磺胺吡啶组成。其用于治疗轻至中度活动性溃疡性结肠炎以及预防病情缓解患者的复发。轻至中度结肠或回结肠克罗恩病患者也可从该药中获益,部分孤立性小肠疾病患者亦是如此。尽管许多临床医生仍继续让最初有反应的克罗恩病患者使用柳氮磺胺吡啶,但它在预防克罗恩病复发方面并非一直有效。限制治疗的副作用发生率较高,包括不耐受、过敏反应以及男性不育受损。新型氨基水杨酸制剂可将美沙拉嗪靶向递送至肠道,副作用较少。局部用美沙拉嗪已被证明对远端溃疡性结肠炎患者极为有效;口服剂型对轻至中度活动性溃疡性结肠炎的治疗及复发有效。两种类型似乎对克罗恩病的治疗均有效,可能也有助于预防复发。目前一种美沙拉嗪制剂相对于另一种并无临床优势,对于在柳氮磺胺吡啶治疗下反应良好且无不良反应的患者,也没有使用它们的指征。对于氨基水杨酸制剂疗效有限的更严重疾病活动,即用于诱导重度或难治性溃疡性结肠炎或克罗恩病患者的缓解,需使用皮质类固醇。它们不应被用于维持疾病缓解或预防术后复发。局部用皮质类固醇可在远端结肠炎局部使用,全身副作用最小。长期使用受副作用限制,其中许多与剂量相关,尽管隔日疗法可能会降低发生率。免疫抑制剂对治疗对其他药物无反应的难治性炎症性肠病有益,也可能有助于难治性患者停用类固醇。巯嘌呤在治疗克罗恩病瘘管方面有额外益处;环孢素在肠道疾病中的作用尚未确立,目前不推荐使用。免疫抑制剂的潜在毒性值得医生和患者在使用时仔细考虑。甲硝唑用于治疗轻至中度克罗恩病,包括会阴疾病。常见副作用包括周围神经病变和恶心。(摘要截取自400字)

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