Clinical experience with cyclooxygenase-2 inhibitors.
Rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic conditions requiring long-term therapy for pain relief. Currently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) provide symptomatic efficacy, but are frequently associated with gastrointestinal (GI) toxicities such as dyspepsia and ulcerations. In a small but significant number of cases, complications including perforations and massive bleeding develop and these may be fatal. A desirable therapeutic strategy would maintain efficacy while minimizing gastric intolerance. Two potential approaches have been suggested: (i) administration of NSAIDs in combination with gastroprotective compounds; or (ii) administration of potentially safer anti-inflammatory compounds which act via selective inhibition of cyclooxygenase-2 (COX-2). The selective COX-2 inhibitors rofecoxib and celecoxib consistently demonstrate efficacy comparable to conventional NSAIDs in patients with RA and OA, but have a significantly reduced propensity to cause GI toxicity. In many cases, the gastric effects of therapeutically active doses of COX-2 inhibitors are indistinguishable from placebo. The safety benefits of COX-2 inhibitors given alone appear similar to combined therapy with conventional NSAIDs and gastroprotective agents. Findings warrant the consideration of COX-2 inhibitors as first-line therapy in patients requiring long-term pain relief.
Lanas
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Gastroenterology Department, University Hospital Clinic, E-50009 Zaragoza, Spain.
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D010003:Osteoarthritis / Q000150:complications / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D011451:Prostaglandin-Endoperoxide Synthases; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases