It is well recognized that nonsteroidal antiinflammatory drugs (
NSAIDs) induce gastrointestinal (GI) ulcerations, perforation and
bleeding, which clearly limit their therapeutic value. The recent introduction of
NSAIDs with selective
cyclooxygenase-2 (COX-2) inhibitory effect is a major pharmacologic milestone in
therapeutics. Selective
COX-2 inhibitors exhibit considerable dissociation between their antiinflammatory/
analgesic action and their GI toxicity. However, from a therapeutic consideration, there are still several unresolved and confusing issues with these drugs such as: the pharmacologic classification of the COX-2 selectivity; therapeutic value as antirheumatic/
analgesic drugs; potential toxicity in patients at risk for the development of
ulcer-related complications or patients with
inflammatory bowel disease and potential renal toxicity. Although existing clinical efficacy studies with
celecoxib and
rofecoxib, two selective
COX-2 inhibitors, were associated with considerably lower ulcerogenic rates when compared with nonselective
NSAIDs, there are no long term outcome studies with these drugs similar to the MUCOSA trial performed with
misoprostol. Furthermore, the selectivity of
COX-2 inhibitors appears to be specific to the stomach and duodenum but not the kidney. While awaiting additional long term studies with selective
COX-2 inhibitors, we recommend instituting prophylactic
therapy with
misoprostol in patients at risk for the development of
ulcer related complications. In conclusion, we believe that the introduction of selective
COX-2 inhibitors will revolutionize the treatment of
pain and
inflammation. However, additional basic and clinical studies are required to address the pharmacologic and therapeutic uncertainties for this class of drugs.