4.Valdecoxib Valdecoxib,a diaryl-substituted isoxazole,is a new highly selective COX-2 inhibitor. The analgesic dose for valdecoxib is 20 mg twice daily.Gastrointestinal and other toxicities are similar to those of the other coxibs.Valdecoxib has no effect on platelet aggregation or bleeding time.Serious reactions have been reported in sulfonamide-sensitive individuals.Valdecoxib was withdrawn from the market in the USA in early 2005 in response to FDA concerns about cardiovascular risks and Stevens-Johnson syndrome,but the drug is still available in other countries. NONSELECTIVE COX INHIBITORS 1.Diclofenac Diclofenac is a phenylacetic acid derivative that is relatively nonselective as a COX inhibitor. Adverse effects occur in approximately 20%of patients and include gastrointestinal distress,occult gastrointestinal bleeding,and gastric ulceration,though ulceration may occur less frequently than with some other NSAIDs.A preparation combining diclofenac and misoprostol decreases upper gastrointestinal ulceration but may result in diarrhea.Another combination of diclofenac and omeprazole was also effective with respect to the prevention of recurrent bleeding,but renal adverse effects were common in high-risk patients.Diclofenac at a dosage of 150 mg/d appears to impair renal blood flow and glomerular filtration rate.Elevation of serum aminotransferases may occur more commonly with this drug than with other NSAIDs. A 0.1%ophthalmic preparation is recommended for prevention of postoperative ophthalmic inflammation and can be used after intraocular lens implantation and strabismus surgery.A topical gel containing 3%diclofenac is effective for solar keratoses.Diclofenac in rectal suppository form can be considered a drug of choice for preemptive analgesia and postoperative nausea.In Europe,diclofenac is also available as an oral mouthwash and for intramuscular administration. 2.Diflunisal Although diflunisal is derived from salicylic acid,it is not metabolized to salicylic acid or salicylate.It undergoes an enterohepatic cycle with reabsorption of its glucuronide metabolite followed by cleavage of the glucuronide to again release the active moiety.Diflunisal is subject to capacity-limited metabolism,with serum half-lives at various dosages approximating that of salicylates.In rheumatoid arthritis the recommended dose is 500-1000 mg daily in two divided doses.It is claimed to be4. Valdecoxib Valdecoxib, a diaryl-substituted isoxazole, is a new highly selective COX-2 inhibitor. The analgesic dose for valdecoxib is 20 mg twice daily. Gastrointestinal and other toxicities are similar to those of the other coxibs. Valdecoxib has no effect on platelet aggregation or bleeding time. Serious reactions have been reported in sulfonamide-sensitive individuals. Valdecoxib was withdrawn from the market in the USA in early 2005 in response to FDA concerns about cardiovascular risks and Stevens-Johnson syndrome, but the drug is still available in other countries. NONSELECTIVE COX INHIBITORS 1. Diclofenac Diclofenac is a phenylacetic acid derivative that is relatively nonselective as a COX inhibitor. Adverse effects occur in approximately 20% of patients and include gastrointestinal distress, occult gastrointestinal bleeding, and gastric ulceration, though ulceration may occur less frequently than with some other NSAIDs. A preparation combining diclofenac and misoprostol decreases upper gastrointestinal ulceration but may result in diarrhea. Another combination of diclofenac and omeprazole was also effective with respect to the prevention of recurrent bleeding, but renal adverse effects were common in high-risk patients. Diclofenac at a dosage of 150 mg/d appears to impair renal blood flow and glomerular filtration rate. Elevation of serum aminotransferases may occur more commonly with this drug than with other NSAIDs. A 0.1% ophthalmic preparation is recommended for prevention of postoperative ophthalmic inflammation and can be used after intraocular lens implantation and strabismus surgery. A topical gel containing 3% diclofenac is effective for solar keratoses. Diclofenac in rectal suppository form can be considered a drug of choice for preemptive analgesia and postoperative nausea. In Europe, diclofenac is also available as an oral mouthwash and for intramuscular administration. 2. Diflunisal Although diflunisal is derived from salicylic acid, it is not metabolized to salicylic acid or salicylate. It undergoes an enterohepatic cycle with reabsorption of its glucuronide metabolite followed by cleavage of the glucuronide to again release the active moiety. Diflunisal is subject to capacity-limited metabolism, with serum half-lives at various dosages approximating that of salicylates. In rheumatoid arthritis the recommended dose is 500-1000 mg daily in two divided doses. It is claimed to be