Celecoxib selective toxicity

Selective COX-2 inhibitors are ideal agents to combine with chemoradiotherapy for several reasons. First, they have been shown to enhance the effect of various chemotherapeutic agents and radiation on cancer cells. Second, selective COX-2 inhibitors are relatively safe. They do not have severe gastrointestinal toxicity, which is common in many nonselective NSAIDs. For example, celecoxib, a selective COX-2 inhibitor which is currently being used for patients with arthritis, is 375-fold more selective for COX-2 compared to COX-1 (94), and in large randomized, multicenter, placebo-controlled, double-blind trials conducted in patients with rheumatoid arthritis, celecoxib proved to be less toxic than nonselective inhibitors of COX-1 and COX-2, and no more toxic than a placebo (95). Third, high-dose celecoxib (600 mg bid) has no effect on serum thromboxane or platelet function (96). This is obviously important in patients receiving... 

Celecoxib (Celebrex) and rofecoxib (Vioxx) are highly selective COX-2 inhibitors. Because of this, they produce less erosion of the GI mucosa and cause less inhibition of platelet aggregation than do the nonselective COX inhibitors. Short-term (6 months-to a year) clinical trials have shown that celecoxib and rofecoxib produce less GI toxicity than nonselective NSAIDs. However, serious GI bleeding and ulceration have occurred in patients taking these drugs, and long-term prospective studies of their safety have yet to be completed. Like the nonselective NSAIDs, the selective COX-2 inhibitors can produce renal side effects such as hypertension and edema. 

Selective inhibition of COX-2 has the objective of preserving anti-inflammatory activity whilst avoiding gastric mucosal toxicity. Rofecoxib, celecoxib and meloxicam vary in their selectivity for COX-2. The incidence of peptic ulcers and their complications with rofecoxib is similar to that seen when proton pump inhibitors are co-administered with nonselective NSAIDs. The adverse effect profile of these drugs remains fully to be evaluated. 

In conclusion, clinical trials have shown that COX-2-selective NSAIDs seem to be less toxic to the gastrointestinal mucosa than traditional ones. However, life-threatening ulcer complications have been reported in patients taking both celecoxib (81,96,97) and rofe-coxib (79). The FDA and other regulatory authorities require that drug information sheets for celecoxib and rofecoxib carry gastrointestinal ulcer warnings similar to those for older NSAIDs. 

Celecoxib 1.34 (1.19-1.52) Naproxen 1.35 (0.97-1.88) Ibuprofen 1.51 (0.95-2.41) Acetaminophen 1.29 (1.17-1.42) Naproxen is associated with the highest risk of AMI/GI events in those not taking aspirin. Celecoxib and acetaminophen AMI/GI risk is similar and less than the other NSAIDs (selective and non-selective). Celecoxib and naproxen are the least toxic in comparison to the other NSAIDs in those using aspirin. 

Celecoxib is a COX-2-selective inhibitor. Its advantage over nonselective NSAIDs may be reduced gastrointestinal toxicity. Celecoxib is being used in patients who need NSAIDs but who... 

NSAIDs can be classified on the basis of their COX inhibitory and selective properties. Most NSAIDs inhibit both COX-1 and COX-2 to some extent. Most are mainly COX-1 inhibitory, e.g., aspirin, ibuprofen, diclofenac, naproxen, while some are COX-2 inhibitory, e.g., celecoxib, rofecoxib, and lumiracoxib. Vane et al. established the relative inhibitory potencies of NSAID COX-1 and COX-2 inhibitors. NSAIDs with the highest gastrointestinal toxicity have the highest COX-1 selectivity. 

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