Bannwarth B, Berenbaum F
Service de rhumatologie, groupe hospitalier Pellegrin, université Victor Segalen, Bordeaux.
Rev Med Interne. 1999 Aug;20 Suppl 3:341s-345s. doi: 10.1016/s0248-8663(99)80506-2.
The use of non steroidal anti-inflammatory drugs as analgesic or anti-inflammatory agents is primarily limited by their toxicity to the gastrointestinal tract. Two strategies have been developed recently in order to improve the safety of these drugs. The first approach is the linking of a nitric oxide-releasing moiety to the available compounds. The rationale is that nitric oxide may prevent non steroidal anti-inflammatory drugs-induced ulcerations by preventing mucosal ischemia. The second approach is based on the discovery of two isoforms (COX-1 and COX-2) of the cyclo-oxygenase enzyme. It was hypothesized that the constitutively expressed COX-1 isoenzyme leads to the synthesis of prostaglandins with homeostatic functions whereas COX-2 is merely responsible for the production of prostaglandins mediating pain, fever and inflammation. Accordingly, selective COX-2 inhibitors have been developed. Clinical trials indicate that these compounds are roughly as effective as the available non steroidal anti-inflammatory agents without causing acute gastrointestinal damage. There is some evidence that both COX-1 and COX-2 isoforms are involved in the production of prostaglandins associated with inflammation and homeostatic functions. Finally, the true benefit/risk ratio of these new non steroidal anti-inflammatory drugs remains to be assessed.
非甾体抗炎药作为镇痛药或抗炎药的使用主要受其对胃肠道毒性的限制。最近已开发出两种策略以提高这些药物的安全性。第一种方法是将释放一氧化氮的部分与现有化合物相连。其基本原理是一氧化氮可通过防止黏膜缺血来预防非甾体抗炎药引起的溃疡。第二种方法基于环氧化酶的两种同工型（COX-1和COX-2）的发现。据推测，组成性表达的COX-1同工酶导致具有稳态功能的前列腺素的合成，而COX-2仅负责介导疼痛、发热和炎症的前列腺素的产生。因此，已开发出选择性COX-2抑制剂。临床试验表明，这些化合物的疗效大致与现有的非甾体抗炎药相同，且不会引起急性胃肠道损伤。有证据表明，COX-1和COX-2同工型均参与与炎症和稳态功能相关的前列腺素的产生。最后，这些新型非甾体抗炎药的真正效益/风险比仍有待评估。
