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胃和十二指肠溃疡的新型治疗方法:最新进展

Novel therapeutic approaches to gastric and duodenal ulcers: an update.

作者信息

Dajani E Z, Klamut M J

机构信息

International Drug Development Consultants Corporation, 1549 RFD, Long Grove, IL 60047-9532, USA.

出版信息

Expert Opin Investig Drugs. 2000 Jul;9(7):1537-44. doi: 10.1517/13543784.9.7.1537.

Abstract

Over the last 25 years, a remarkable revolution in the pathophysiology and treatment of gastric and duodenal ulcers has occurred. Effective therapies were developed not only to heal ulcers, but also to cure most patients. The two principal causes for gastric and duodenal ulcers are either infection with Helicobacter pylori or the use of non-steroidal anti-inflammatory drugs (NSAIDs). With H. pylori eradication, gastric and duodenal ulcers are rapidly becoming historical diseases. This communication reviews the salient pharmacology of the novel anti-ulcer drugs currently in development, with particular emphasis on the treatment of gastric and duodenal ulcers. Intense research is currently focused on the development of proton pump inhibitors primarily for the treatment and prevention of gastroesophageal reflux disease. The older proton pump inhibitors, omeprazole and lansoprazole, are effective in healing gastric and duodenal ulcers. Furthermore, both drugs are effective in eradicating H. pylori when given with various antibiotics. Pantoprazole, rabeprazole and esomeprazole are new proton pump inhibitors, which appear to have comparable therapeutic profiles with omeprazole and lansoprazole. Rebamipide is a new mucosal protective drug, which is effective in healing gastric ulcers. Polaprezinc and nocloprost are also mucosal protective drugs, which are in clinical development. However, none of these three cytoprotective drugs have been evaluated for their efficacy in eradicating H. pylori when given in combination with antibiotics. Likewise, no published literature exists on the use of these drugs for preventing NSAID-induced ulcers. With the rapid eradication of H. pylori currently happening in the developed world, the therapeutic challenge is now directed toward preventing NSAID-associated ulcer. Significant reduction of NSAID-induced ulcers is achieved by using continuous prophylactic anti-ulcer therapy (misoprostol or omeprazole) or by using NSAIDs possessing selective COX-2 inhibitory activity. However, outcome clinical studies are needed to compare the adjuvant anti-ulcer therapies given with COX-1 inhibitors versus the selective COX-2 inhibitors given alone.

摘要

在过去25年里,胃,胃和十二指肠溃疡的病理生理学及治疗发生了显著变革。不仅研发出了有效的溃疡愈合疗法,还能治愈大多数患者。胃和十二指肠溃疡的两个主要病因是感染幽门螺杆菌或使用非甾体抗炎药(NSAIDs)。随着幽门螺杆菌的根除,胃和十二指肠溃疡正迅速成为历史疾病。本文综述了目前正在研发的新型抗溃疡药物的主要药理学,尤其着重于胃和十二指肠溃疡的治疗。目前大量研究集中在主要用于治疗和预防胃食管反流病的质子泵抑制剂的开发上。较老的质子泵抑制剂奥美拉唑和兰索拉唑在愈合胃和十二指肠溃疡方面有效。此外,这两种药物与各种抗生素联用时在根除幽门螺杆菌方面也有效。泮托拉唑、雷贝拉唑和埃索美拉唑是新型质子泵抑制剂,其治疗效果似乎与奥美拉唑和兰索拉唑相当。瑞巴派特是一种新型黏膜保护药物,对愈合胃溃疡有效。聚普瑞锌和诺氯前列素也是正在临床开发中的黏膜保护药物。然而,这三种细胞保护药物在与抗生素联用时根除幽门螺杆菌的疗效均未得到评估。同样,也没有关于这些药物用于预防NSAID诱导的溃疡的已发表文献。随着发达国家目前幽门螺杆菌的迅速根除,治疗挑战现在转向预防NSAID相关溃疡。通过持续预防性抗溃疡治疗(米索前列醇或奥美拉唑)或使用具有选择性COX-2抑制活性的NSAIDs可显著减少NSAID诱导的溃疡。然而,需要进行临床结局研究来比较与COX-1抑制剂联用的辅助抗溃疡疗法与单独使用选择性COX-2抑制剂的效果。

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