The NSAIDs decrease the sensitivity of vessels to bradykinin and histamine, affect lymphokine production from T lymphocytes, and reverse the vasodilation of inflammation. To varying degrees, all newer NSAIDs are analgesic, anti-inflammatory, and antipyretic, and all (except the COX-2–selective agents and the nonacetylated salicylates) inhibit platelet aggregation. NSAIDs are all gastric irritants and can be associated with GI ulcers and bleeds as well, although as a group the newer agents tend to cause less GI irritation than aspirin. Nephrotoxicity, reported for all NSAIDs, is due, in part, to interference with the autoregulation of renal blood flow, which is modulated by prostaglandins. Hepatotoxicity also can occur with any NSAID.
Although these drugs effectively inhibit inflammation, there is no evidence that—in contrast to drugs such as methotrexate, biologics, and other DMARDs—they alter the course of any arthritic disorder.
Several NSAIDs (including aspirin) reduce the incidence of colon cancer when taken chronically. Several large epidemiologic studies have shown a 50% reduction in relative risk for this neoplasm when the drugs are taken for 5 years or longer. The mechanism for this protective effect is unclear.
Although not all NSAIDs are approved by the FDA for the whole range of rheumatic diseases, most are probably effective in RA, seronegative spondyloarthropathies (SpA, eg, PsA and arthritis associated with inflammatory bowel disease), OA, localized musculoskeletal syndromes (eg, sprains and strains, low back pain), and gout (except tolmetin, which appears to be ineffective in gout).
TABLE 36–1 Properties of aspirin and some other nonsteroidal anti-inflammatory drugs.
1Major anti-inflammatory metabolite of aspirin. 2Salicylate is usually given in the form of aspirin. 3Total urinary excretion including metabolites. 4Nabumetone is a prodrug; the half-life and urinary excretion are for its active metabolite. 5A single daily dose is sufficient because of the long half-life.
Adverse effects are generally quite similar for all of the NSAIDs: 1.
Central nervous system: Headaches, tinnitus, dizziness, and rarely, aseptic meningitis.
2.
Cardiovascular: Fluid retention, hypertension, edema, and rarely, myocardial infarction and congestive heart failure (CHF).
3.
Gastrointestinal: Abdominal pain, dyspepsia, nausea, vomiting, and rarely, ulcers or bleeding.
4.
Hematologic: Rare thrombocytopenia, neutropenia, or even aplastic anemia.
5.
Hepatic: Abnormal liver function test results and rare liver failure.
6.
Pulmonary: Asthma.
7.
Skin: Rashes, all types, pruritus.
8.
Renal: Renal insufficiency, renal failure, hyperkalemia, and proteinuria.
Aspirin’s long use and availability without prescription diminishes its glamour compared with that of the newer NSAIDs. Aspirin is now rarely used as an anti-inflammatory medication and will be reviewed only in terms of its antiplatelet effects (ie, doses of 81–325 mg once daily).
1.