Cyclooxygenase inhibitors, NSAID - Coxibs, NSAID with specific anti- COX-2 activity
NSAID inhibiting selectively COX-2, called coxibs, have antiinflammatory, antalgic and antipyretic properties aproximatively similar to that of the nonselective NSAID but induce less digestive disorders (gastric pains, ulcers).
They may not elicit asthma attack in asthmatic patients contrary to nonselective NSAID and aspirin by diverting the metabolism of arachidonic acid towards leukotrienes, probably by lack of PGE2 which normally inhibits the 5-lipooxygenase.
Coxibs, rofecoxib and celecoxib in particular, were launched on the market for treatment of the pain of osteoarthritis and rheumatoid arthritis, where they aimed at supplanting the conventional NSAID. Parecoxib, presented in injectable solution, is indicated in the treatment of postoperative acute pain.
Coxibs, in particular rofecoxib, have severe cardiovascular adverse effects such as myocardial infarction. This adverse effect led MSD laboratory to withdraw rofecoxib , Vioxx * from the market. The explanation of this toxicity could be inhibition of biosynthesis of prostaglandin PGI2 in the endothelium (where COX-2 and not COX-1 is responsible for PGI2synthesis), without inhibition of the biosynthesis of thromboxane A2 in platelets which induces a prothrombotic status. The conventional NSAID inhibit both biosynhesis of PGI2 (anti-aggregating effect, vasodilator) and of TXA2 (aggregating and vasoconstrictive effects).
Since COX-2 is involved in ovulation, implantation and perhaps embryogenesis, COX-2 NSAID are disadvised in pregnant woman in the first months of pregnancy and during last months to avoid abnormally prolonging the pregnancy.
Many other therapeutic uses were considered for coxibs but their cardiovascular adverse effects do not encourage their use on a large scale.
Parecoxib used in postoperative conditions does not increase the risk of bleedings as the nonselective NSAID but it could increase the risk of thromboses.
Celecoxib |
CELEBREX * Capsules |
Valdecoxib |
BEXTRA* Tablets |
Parecoxib is a prodrug, which is administered by injectable route. In the body it is quickly converted into the active product, valdecoxib.
Diagram of parecoxib biotrasformations
Compared chemical structures of rofecoxib, celecoxib and valdecoxib: one can see that celecoxib and valdecoxib are sulphonamides, - SO2 NH2.
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