Current medicinal approaches to the treatment of rheumatoid arthritis.

Aspirin, nonacetylated salicylates, and numerous other nonsteroidal antiinflammatory drugs (NSAIDs) are used in rheumatoid arthritis (RA) patients to decrease joint inflammation and improve function. The choice of medication and its optimum dosage must be individualized because of marked intersubject variations in drug metabolism, excretion, antiinflammatory and analgesic efficacy, and susceptibility to adverse effects. Equivalent doses of aspirin and of nonacetylated salicylates are equally antiinflammatory in RA, although the nonacetylated salicylate is a poor inhibitor of prostaglandin synthesis. Chronopharmacology studies suggest that many patients may have better efficacy and fewer side effects with evening doses than with morning doses of certain NSAIDs; however, the optimum time must be individualized by trial and error because some patients do better with other regimens. The gastric, renal, and platelet adverse effects of NSAIDs are related to their inhibition of prostaglandin synthesis, and tend to be related to dose and intensity of therapy. Various strategies can minimize the impact of these side effects, such as coadministration of gastric protectants or the use of short half-life NSAIDs to decrease the duration of preoperative NSAID withdrawal needed to ensure adequate platelet coagulation during surgery. An intramuscular analgesic NSAID is now available and is reported to be equivalent to morphine sulfate in some painful postsurgical conditions. Although associated with many problems, chronic corticosteroid therapy is, or has been, a major therapeutic component for many RA patients who consequently are unable to respond adequately to the stresses of general anesthesia and surgery because of complete or partial adrenal insufficiency. These patients must be given appropriate supplemental corticosteroid therapy perioperatively.