Dajani E Z, Agrawal N M
G.D. Searle & Co., Northwestern University, Chicago, Ill.
Dig Dis. 1995 Jan;13 Suppl 1:48-61. doi: 10.1159/000171526.
One of the most serious side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) is upper gastrointestinal mucosal damage that may result in erosions, ulcerations and other serious complications. NSAIDs reduce endogenous prostaglandins, and this reduction is relevant to their pharmacology and toxicity. The stomach and to some extent the duodenum are the major organs involved in the mucosal toxicity of NSAIDs. With the availability of the synthetic prostaglandin misoprostol, it has become possible to prevent NSAID-induced gastroduodenal ulcers without compromising the beneficial antirheumatic and analgesic effects of NSAID therapy. In fact, misoprostol is the only drug with established long-term efficacy in preventing NSAID-induced gastroduodenal ulcers in rheumatic patients. The purpose of this communication is to critically review the efficacy of gastric antisecretory drugs, mucosal protective drugs and misoprostol when used for the prevention of NSAID-induced ulcers, considering only data from well-controlled, randomized, double-blind clinical studies. The histamine H2-receptor antagonist ranitidine has been shown to be effective in preventing NSAID-induced duodenal ulcers, but has no efficacy in preventing NSAID-induced gastric ulcers. In a direct comparative trial with ranitidine, misoprostol (200 micrograms qid) was significantly more effective than ranitidine (150 mg bid) in preventing gastric ulcers in chronic NSAID users. The inactivity of ranitidine in preventing gastric ulcers indicates that the pathogenesis of NSAID-induced gastric ulcers is not related to gastric acid. Limited but conflicting data exist with omeprazole. The mucosal-coating drug sucralfate has not been found effective in preventing NSAID ulcers. In fact, in a direct comparative trial, misoprostol (200 micrograms qid) was significantly more effective than sucralfate (1 g qid) in preventing gastric ulcers in patients receiving chronic NSAID therapy. No meaningful data exist with organic bismuth salts, a group of drugs which has mucosal coating and protective properties. From this brief overview, we conclude: (1) mucosal-coating compounds have no therapeutic role in preventing NSAID-induced ulceration; (2) gastric antisecretory drugs are not effective in preventing NSAID-induced gastric ulcers, and (3) misoprostol is the only antiulcer drug proven to be effective for preventing NSAID-induced gastric and duodenal ulcers in patients receiving chronic NSAID. Misoprostol represents a major therapeutic advance for the management of NSAID-induced mucosal injury.
非甾体抗炎药（NSAIDs）最严重的副作用之一是上消化道黏膜损伤，这可能导致糜烂、溃疡及其他严重并发症。NSAIDs会减少内源性前列腺素，这种减少与其药理作用和毒性相关。胃以及在一定程度上十二指肠是参与NSAIDs黏膜毒性作用的主要器官。随着合成前列腺素米索前列醇的出现，在不影响NSAIDs治疗有益的抗风湿和止痛效果的情况下，预防NSAIDs引起的胃十二指肠溃疡成为可能。事实上，米索前列醇是唯一在预防风湿性疾病患者NSAIDs引起的胃十二指肠溃疡方面具有确定长期疗效的药物。本通讯的目的是严格审查抑酸药物、黏膜保护药物和米索前列醇在用于预防NSAIDs引起的溃疡时的疗效，仅考虑来自严格对照、随机、双盲临床研究的数据。组胺H2受体拮抗剂雷尼替丁已被证明在预防NSAIDs引起的十二指肠溃疡方面有效，但在预防NSAIDs引起的胃溃疡方面无效。在与雷尼替丁的直接对比试验中，米索前列醇（200微克，每日4次）在预防慢性NSAIDs使用者的胃溃疡方面比雷尼替丁（150毫克，每日2次）显著更有效。雷尼替丁在预防胃溃疡方面无效表明NSAIDs引起的胃溃疡的发病机制与胃酸无关。关于奥美拉唑的数据有限且存在矛盾。黏膜保护药物硫糖铝未被发现对预防NSAIDs溃疡有效。事实上，在一项直接对比试验中，米索前列醇（200微克，每日4次）在预防接受慢性NSAIDs治疗患者的胃溃疡方面比硫糖铝（1克，每日4次）显著更有效。对于具有黏膜保护特性的有机铋盐类药物，没有有意义的数据。从这个简要概述中，我们得出结论：（1）黏膜保护化合物在预防NSAIDs引起的溃疡方面没有治疗作用；（2）抑酸药物在预防NSAIDs引起的胃溃疡方面无效；（3）米索前列醇是唯一被证明对预防接受慢性NSAIDs治疗患者的NSAIDs引起的胃和十二指肠溃疡有效的抗溃疡药物。米索前列醇代表了NSAIDs引起的黏膜损伤治疗方面的一项重大进展。
