Conclusions and References - Part 7: Cyclooxygenase-2-Selective Inhibitors: Translating Pharmacology into Clinical Utility

The magnitude of NSAID use, the high incidence of gastropathy in NSAID users, and the significant morbidity and mortality of NSAID-associated GI outcomes underscore the need for less toxic NSAIDs. In a single decade since the discovery of COX-2, a deeper appreciation of the complexity of prostaglandin metabolism has emerged, leading to new therapeutic avenues capable of overcoming the limitations of classical NSAID toxicity. Despite the challenges of defining COX selectivity, the paradigm that COX-1-sparing drugs are safer has successfully guided the development of promising new anti-inflammatory agents. Patient variability, pharmacodynamics, and preexisting risk factors influence COX-2-specificity, which is why it has been imperative to show COX specificity in large clinical trials with adequate numbers of patients and events. Clinical trials convincingly show that agents specifically inhibiting COX-2 are equivalent in efficacy to nonselective NSAIDs and have a lower incidence of GI toxicity. Although clinical specificity of COX-2 inhibitors has been shown, there is still much not known about COX-1 and COX-2 across the spectrum of health and disease. Intimate knowledge of the pharmacology of COX- 2 inhibitors in health and disease will likely open the door to new clinical applications for these drugs.

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