Section Review: Pulmonary-Allergy, Dermatological, Gastrointestinal & Arthritis: Development of NSAIDs with reduced gastrointestinal and renal toxicity

Abstract

While nonsteroidal anti-inflammatory drugs remain among the most widely used medications, their use continues to be associated with significant toxicity, particularly in the gastrointestinal tract and kidney. As more is learned about the pathogenesis of these adverse effects, several strategies have been taken to develop NSAIDs that are less toxic. Many such strategies have failed to have significant impact on the frequency and/or severity of NSAID-related adverse effects. However, recently, two new approaches have been taken which show great promise. Selective inhibitors of the inducible isoform of prostaglandin synthase are reported to spare the gastrointestinal tract. As we know little about the possible physiological role of this isoform of prostaglandin synthase, there are some concerns about the true potential for these compounds. A second approach is the linking of standard NSAIDs to a nitric oxide-releasing moiety. Studies in experimental models are extremely encouraging, demonstrating that these compounds retain the desired effects of the NSAID, but do not produce injury in the gastrointestinal tract or kidney.