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NSAIDs: Pharmacology and mechanism of action

Daniel H Solomon, MD, MPH
Section Editor
Daniel E Furst, MD
Deputy Editor
Paul L Romain, MD


More than 20 different nonsteroidal antiinflammatory drugs (NSAIDs) are available commercially, and these agents are used worldwide for their analgesic antipyretic and antiinflammatory effects in patients with multiple medical conditions. NSAIDs, including aspirin, do not generally change the course of the disease process in those conditions, where they are used for symptomatic relief.

The pharmacology and mechanisms of action of the NSAIDs will be reviewed here. The therapeutic variability and approach to the clinical use of NSAIDs, including their use in combination with other medications and in patients with comorbid conditions, the adverse effects of NSAIDs, an overview of cyclooxygenase (COX)-2 selective NSAIDs, and the mechanisms relevant to aspirin, its toxicities, and its uses in the rheumatic diseases are described in detail separately. (See "NSAIDs: Therapeutic use and variability of response in adults" and "Nonselective NSAIDs: Overview of adverse effects" and "Overview of selective COX-2 inhibitors" and "Aspirin: Mechanism of action, major toxicities, and use in rheumatic diseases".)


There are more than 20 different nonsteroidal antiinflammatory drugs (NSAIDs), from six major classes determined by their chemical structures, available for use worldwide. These drugs differ in their dose, drug interactions, and some side effects (table 1). Most NSAIDs are absorbed completely, have negligible first-pass hepatic metabolism, are tightly bound to serum proteins, and have small volumes of distribution.

NSAIDs undergo hepatic transformations variously by CYP2C8, 2C9, 2C19 and/or glucuronidation. Half-lives of the NSAIDs vary but in general can be divided into "short-acting" (less than six hours, including ibuprofen, diclofenac, ketoprofen and indomethacin) and "long-acting" (more than six hours, including naproxen, celecoxib, meloxicam, nabumetone, and piroxicam). Patients with hypoalbuminemia (due, for example, to cirrhosis or active rheumatoid arthritis) may have a higher free serum concentration of the drug.

Assessment of toxicity and therapeutic response to a given NSAID must take into account the time needed to reach the steady state plasma concentration (roughly equal to three to five half-lives of the drug). The pathogenesis of symptomatic peptic ulcer disease caused by exposure to NSAIDs is mainly a consequence of systemic (post-absorptive) inhibition of gastrointestinal mucosal cyclooxygenase (COX) activity. (See "NSAIDs (including aspirin): Pathogenesis of gastroduodenal toxicity".)

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Literature review current through: Nov 2017. | This topic last updated: Aug 29, 2017.
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