Nonsteroidal anti-inflammatory drugs: practical and theoretical considerations in their selection

Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed frequently for patients with painful musculoskeletal conditions: Each year, physicians write approximately 60 million NSAID prescriptions. Because of the magnitude of patient exposure, gastrointestinal and other side effects of NSAIDs are a significant clinical concern. The mechanism of action of NSAIDs is inhibition of cyclooxygenase with secondary inhibition of proinflammatory prostaglandins. This mechanism also accounts for gastrointestinal toxic side effects of NSAIDs. Two forms of cyclooxygenase, cox-1 and cox-2, appear to be differentially inhibited by NSAIDs. Because cox-1 is responsible for maintaining normal physiologic function in gastric mucosa and other tissue, "ideal" NSAIDs would suppress only cox-2. The design of future NSAIDs-related peptic ulceration is characterized by its location in the gastric antrum, asymptomatic nature, and ability to develop through both topical and systemic effects of NSAIDs. Major risk factors for patients with rheumatoid arthritis include age >60 years, magnitude of disability, concomitant use of corticosteroids, larger doses/longer duration of NSAID treatment, and a history of peptic ulcer disease. A prophylactic strategy includes the identification of high-risk patients and, if NSAIDs must be used, the addition of misoprostol.