Management of gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs during the therapy of rheumatic diseases. The rheumatologist's perspective.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used therapeutic agents for many important rheumatic diseases. A large body of evidence indicates that the anti-inflammatory effects as well as the toxic side effects of NSAIDs can be attributed to their ability to inhibit prostaglandin synthesis. The most frequent side effect leading to discontinuation of NSAID therapy is upper gastrointestinal toxicity. This is a major problem for rheumatologists and their patients since alternatives to NSAIDs are not readily available. The mechanism of upper gastrointestinal toxicity associated with NSAIDs can be attributed to their common ability to inhibit gastric PGE2 synthesis, which suggests that gastrointestinal side effects often may not be avoided by substituting another NSAID, a prediction borne out by many patients with rheumatic diseases. However, there is some evidence that some patients may differ in their susceptibility to gastrointestinal and other toxic effects, though this concept has not been rigorously studied in clinical trials. Thus, although changing the specific NSAID may prevent gastrointestinal toxicity in some patients, many are intolerant to all NSAIDs. Patients who benefit from a specific NSAID, but in whom gastrointestinal toxicity develops, have limited options. Another NSAID may be substituted but at the risk of losing therapeutic efficacy and/or of continuing toxicity. Alternatively, the side effects may be controlled while continuing therapy with the NSAID by one of several measures, including the use of antacids or a histamine (H2)-receptor antagonist, such as cimetidine. The use of enteric-coated salicylates or nonacetylated salicylates may also provide satisfactory alternatives. However, patients who have experienced major gastrointestinal toxicity, such as massive bleeding or active peptic ulcers, should usually avoid NSAID therapy.