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 pharmacological 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 "Benefits and risks of aspirin in secondary and primary prevention of cardiovascular disease" 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".)
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 cyclooxygenase (COX)-1 and COX-2, blocking prostaglandin (PG) production, and have analgesic and antipyretic effects.
- High doses (between 4 and 8 g/day) are effective as antiinflammatory agents in rheumatic disorders; the mechanism(s) of action at these high doses may include both PG-dependent (particularly COX-2 dependent PGE2) and independent effects . However, the usefulness of aspirin at these high doses is limited by toxicity, including tinnitus, hearing loss, and gastric intolerance.
Cyclooxygenase inhibition — Cyclooxygenase (COX) inhibition is central to the mechanism of action of both aspirin and the nonsalicylate NSAIDs. The role of COX inhibition is reviewed briefly below, especially as it pertains to aspirin and other salicylates, and is discussed in further detail elsewhere. (See "NSAIDs: Mechanism of action", section on 'Cyclooxygenase inhibition'.)