Yeomans N D
Department of Medicine, University of Melbourne, Australia.
Ital J Gastroenterol Hepatol. 1999;31 Suppl 1:S89-92.
The treatment of a peptic ulcer occurring in a patient who is taking non-steroidal anti-inflammatory drugs depends on whether or not the patient can readily stop taking the non-steroidal anti-inflammatory drug. If they can, healing is generally rapid, and can be achieved with any effective ulcer-healing agent. When the non-steroidal anti-inflammatory drug cannot be easily stopped, ulcer healing is slower and the treatment of choice is to heal the ulcer with a proton pump inhibitor. The risk of ulceration in patients taking non-steroidal anti-inflammatory drugs can be reduced by two main strategies: the choice of non-steroidal anti-inflammatory drug and its dosage on the one hand, and the use of prophylactic co-therapy on the other. The two are not of course mutually exclusive. It is now clear that not all non-steroidal anti-inflammatory drugs are equally damaging. Several studies have shown that the shorter half life drugs (at least in their recommended dosages) are generally less ulcerogenic. There is clear dose-dependence, so the drugs should be used at the lowest effective dose, and non-steroidal anti-inflammatory drugs should not be given in combination without careful weighing of risks and benefits. Giving either omeprazole or misoprostol concurrently with a non-steroidal anti-inflammatory drug substantially reduces the risk of ulceration. Full dosage histamine H2-receptor antagonists give good protection against non-steroidal anti-inflammatory drug-associated duodenal ulcers, but two large trials with ranitidine showed no protection against gastric ulcer. One study of double dosage famotidine did show a reduction in gastric ulcer incidence as well. Recently, two large randomized trials have compared omeprazole 20 mg daily head-to-head with ranitidine and misoprostol. Overall, the proton pump inhibitor was more effective than the other two for ulcer prevention, although it is interesting that erosions seemed to be prevented better by the prostaglandin. The biggest challenge for clinical judgement is when to use prophylactic co-therapy. Patients for whom this should be especially considered are those who have had a prior ulcer, the elderly, those needing higher non-steroidal anti-inflammatory drug dosage or co-therapy with vascular-protective aspirin, and those whose other medical conditions make them less likely to survive a gastrointestinal haemorrhage or perforation.
正在服用非甾体抗炎药的患者发生消化性溃疡时,治疗方法取决于患者能否轻易停用非甾体抗炎药。如果可以,溃疡通常愈合迅速,使用任何有效的溃疡愈合剂均可实现愈合。当难以停用非甾体抗炎药时,溃疡愈合较慢,治疗的首选方法是使用质子泵抑制剂来愈合溃疡。服用非甾体抗炎药的患者发生溃疡的风险可通过两种主要策略降低:一方面是选择非甾体抗炎药及其剂量,另一方面是使用预防性联合治疗。当然,这两者并非相互排斥。现在很清楚,并非所有非甾体抗炎药的损害程度都相同。多项研究表明,半衰期较短的药物(至少在其推荐剂量下)通常致溃疡作用较小。存在明确的剂量依赖性,因此药物应使用最低有效剂量,并且在未仔细权衡风险和益处之前,不应联合使用非甾体抗炎药。同时给予奥美拉唑或米索前列醇与非甾体抗炎药可大幅降低溃疡风险。全剂量组胺H2受体拮抗剂对非甾体抗炎药相关的十二指肠溃疡有良好的保护作用,但两项使用雷尼替丁的大型试验表明对胃溃疡无保护作用。一项关于双倍剂量法莫替丁的研究确实也显示胃溃疡发病率有所降低。最近,两项大型随机试验将每日20毫克奥美拉唑与雷尼替丁和米索前列醇进行了直接比较。总体而言,质子泵抑制剂在预防溃疡方面比其他两种药物更有效,不过有趣的是,前列腺素似乎在预防糜烂方面效果更好。临床判断面临的最大挑战是何时使用预防性联合治疗。特别应考虑进行预防性联合治疗的患者包括有过溃疡病史者、老年人、需要更高剂量非甾体抗炎药或与血管保护剂阿司匹林联合治疗者,以及其他疾病状况使其更难以承受胃肠道出血或穿孔的患者。