[New nonsteroidal anti-inflammatory agents: nitric oxide donors and selective cyclooxygenase-2 inhibitors].
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.
Bannwarth
B
B
Service de rhumatologie, groupe hospitalier Pellegrin, université Victor Segalen, Bordeaux.
Berenbaum
F
F
D000700:Analgesics / Q000009:adverse effects / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004064:Digestive System / Q000187:drug effects; D005334:Fever / Q000188:drug therapy / Q000503:physiopathology; D005753:Gastric Mucosa / Q000098:blood supply; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D007511:Ischemia / Q000517:prevention & control; D007527:Isoenzymes / Q000145:classification; D020030:Nitric Oxide Donors / Q000009:adverse effects / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D011448:Prostaglandin Antagonists / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000009:adverse effects / Q000145:classification; D011453:Prostaglandins / Q000096:biosynthesis; D018570:Risk Assessment; D012449:Safety; D013276:Stomach Ulcer / Q000517:prevention & control
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D020030:Nitric Oxide Donors; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011451:Prostaglandin-Endoperoxide Synthases