[Selective inhibitors of cyclooxygenase-2 (COX-2), celecoxib and parecoxib: a systematic review].

Abstract

Cyclooxygenase (COX) enzymes mediate prostaglandin generation. COX-1 is expressed in all cells, producing prostaglandins that maintain cellular homeostasis, and COX-2 is an inducible enzyme that generates inflammatory prostaglandins at sites of inflammation and healing. Nonsteroidal antiinflammatory drugs (NSAIDs) that nonselectively inhibit COX-1 and COX-2 continue to be an important option for the management of pain. However, despite the potential advantages of NSAIDs, including their opioid-sparing effect and reduced opioid-related side effects, improved analgesia, and attenuation of the inflammatory pain response, several side effects limit their use. NSAIDs predispose to ulcer formation and upper gastrointestinal bleeding, impaired coagulation, cardiovascular effects and renal dysfunction. Selective cyclooxygenase-2 (COX-2) inhibitors were designed based on the hypothesis that selective inhibition of the COX-2 isoform should reduce pain and inflammation without compromising the integrity of the gastric mucosa. Celecoxib and parecoxib are two COX-2 inhibitors (coxibs) that are approved for the relief of acute postoperative pain and symptoms of chronic inflammatory conditions such as osteoarthritis and rheumatoid arthritis. They have similar pharmacological properties but a slightly improved gastrointestinal safety profile compared with traditional NSAIDs. Celecoxib is an orally administered coxib. Agents such as celecoxib, which are highly COX-2 specific and have shown excellent efficacy in relieving inflammation and associated pain, unfortunately exhibit only modest aqueous solubility, thus restricting dosing options. Parecoxib is the sulfonamide-based prodrug of valdecoxib and is the only parenterally administered coxib available to date. There is no evidence demonstrating any greater degree of pain relief between these two coxibs. However, parenteral preparations may be especially useful in the immediate postoperative period, when patients are unable to take oral medication or are experiencing nausea and vomiting.