Aspirin: Mechanism of action, major toxicities, and use in rheumatic diseases
- Steven B Abramson, MD
Steven B Abramson, MD
- Professor of Medicine and Pathology
- New York University School of Medicine
- Section Editor
- Daniel E Furst, MD
Daniel E Furst, MD
- Section Editor — Treatment Issues in Rheumatology
- Professor of Rheumatology, University of Washington, Seattle
- Professor of Rheumatology, Washington University of Florence, Florence, Italy
- Professor of Rheumatology, University of California in Los Angeles (Emeritus)
- Director of Research, Pacific
Aspirin, an acetylated salicylate (acetylsalicylic acid), is classified among the nonsteroidal antiinflammatory drugs (NSAIDs). These agents reduce the signs and symptoms of inflammation and exhibit a broad range of pharmacologic activities, including analgesic, antipyretic, and antiplatelet properties. Aspirin was first introduced by the drug and dye firm Bayer in 1899. Aspirin and the other NSAIDs do not generally change the course of the disease process in those conditions where they are used for symptomatic relief.
The mechanism of action, efficacy, and toxicity of aspirin in rheumatic and other inflammatory disorders are reviewed here. The nonsalicylate NSAIDs, including nonspecific NSAIDs and cyclooxygenase (COX)-2 selective agents; the use of aspirin for primary and secondary prevention of cardiovascular disease; and the prevention of gastroduodenal and other toxicities from aspirin are discussed in detail elsewhere. (See "Nonselective NSAIDs: Overview of adverse effects" and "Overview of selective COX-2 inhibitors" and "NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity" and "NSAIDs (including aspirin): Secondary prevention of gastroduodenal toxicity" and "Nonselective NSAIDs: Adverse cardiovascular effects" and "NSAIDs (including aspirin): Allergic and pseudoallergic reactions" and "Aspirin in the primary prevention of cardiovascular disease and cancer" and "Aspirin for the secondary prevention of atherosclerotic cardiovascular disease".)
MECHANISM OF ACTION
Effect of dose — Aspirin's effects and respective mechanisms of action vary with dose:
●Low doses (typically 75 to 81 mg/day) are sufficient to irreversibly acetylate serine 530 of cyclooxygenase (COX)-1. This effect inhibits platelet generation of thromboxane A2, resulting in an antithrombotic effect.
●Intermediate doses (650 mg to 4 g/day) inhibit COX-1 and COX-2, blocking prostaglandin (PG) production, and have analgesic and antipyretic effects.
- Pillinger MH, Capodici C, Rosenthal P, et al. Modes of action of aspirin-like drugs: salicylates inhibit erk activation and integrin-dependent neutrophil adhesion. Proc Natl Acad Sci U S A 1998; 95:14540.
- Picot D, Loll PJ, Garavito RM. The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1. Nature 1994; 367:243.
- Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000; 284:1247.
- Abramson S, Korchak H, Ludewig R, et al. Modes of action of aspirin-like drugs. Proc Natl Acad Sci U S A 1985; 82:7227.
- Amin AR, Vyas P, Attur M, et al. The mode of action of aspirin-like drugs: effect on inducible nitric oxide synthase. Proc Natl Acad Sci U S A 1995; 92:7926.
- Kopp E, Ghosh S. Inhibition of NF-kappa B by sodium salicylate and aspirin. Science 1994; 265:956.
- MECHANISM OF ACTION
- Effect of dose
- Cyclooxygenase inhibition
- Other proposed mechanisms of action
- CLINICAL USE IN RHEUMATIC DISEASES
- Rheumatoid arthritis
- Giant cell arteritis
- Kawasaki disease
- Co-administration of salicylates with other NSAIDS
- OTHER USES OF ASPIRIN
- MAJOR SIDE EFFECTS AND OTHER CONCERNS
- Gastrointestinal toxicity
- Anticoagulant effects
- Use in pregnancy
- Other side effects
- Plasma salicylate levels and salicylate toxicity
- SUMMARY AND RECOMMENDATIONS