Non-steroidal anti-inflammatory drugs
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Non-steroidal anti-inflammatory drugs
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Non-steroidal anti-inflammatory drugs
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Anti-inflammatory drugs p. 499
Nonsteroidal anti-inflammatory drugs (NSAIDs) p. 499
Renal disorders/failure p. 626
NSAIDs p. 613
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Transcript
Content Reviewers
Yifan Xiao, MDContributors
Filip Vasiljević, MD
Ursula Florjanczyk, MScBMC
Sam Gillespie, BSc
Evan Debevec-McKenney
Non-steroidal anti-inflammatory drugs or NSAIDs are mainly used to treat inflammation, pain, and fever. These conditions are related to an increased production of pro-inflammatory chemicals called prostaglandins.
NSAIDs work by decreasing the production of prostaglandins, thereby reducing inflammation, relieving pain, and reducing fever.
In order to understand how NSAIDs work, first we need to talk briefly about inflammation, which is the body’s response to a harmful stimulus, such as infection or injury.
So, during inflammation, your immune cells use an enzyme called phospholipase A2 to take membrane phospholipids and make a 20-carbon polyunsaturated fatty acid, called arachidonic acid.
Arachidonic acid is a substrate for an enzyme called cyclooxygenase or COX.
The enzyme cyclooxygenase exists in two different isoforms: COX-1 and COX-2.
COX-1 is a constitutive enzyme, meaning that it’s always active, while on the other hand, COX-2 is an inducible enzyme, meaning that it must be turned on to function. This is usually triggered by immune cells and vascular endothelial cells during inflammation.
Both enzymes produce prostaglandin E2 (PGE2) and prostacyclin (PGI2), which cause vasodilation and attract different immune cells to the area.
They also act on neurons that detect pain, called nociceptors, and make them more sensitive to stimuli by lowering their threshold for activation.
Finally, they stimulate the hypothalamus to increase the body temperature, causing fever.
Prostaglandin E2 also has other effects like causing uterine contractions, decreasing the secretion of acid, and increasing the production of protective mucus in the stomach.
So, in conditions such as inflammation, pain, or fever, NSAIDs can be used to inhibit cyclooxygenase and decrease the production of prostaglandins.
Depending on how they interact with these enzymes, NSAIDs are subdivided into 2 main groups: irreversible COX inhibitors, like aspirin; and reversible COX inhibitors, or non-aspirin NSAIDs.
Sources
- "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
- "Rang and Dale's Pharmacology" Elsevier (2019)
- "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
- "Aspirin and NSAIDs; benefits and harms for the gut" Best Pract Res Clin Gastroenterol (2012)
- "Gastrointestinal safety of selective COX-2 inhibitors" Curr Pharm Des (2002)
- "Clinical pharmacology of selective COX-2 inhibitors" Int J Immunopathol Pharmacol (2003)
- "The Role of Human Carboxylesterases in Drug Metabolism: Have We Overlooked Their Importance?" Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy (2013)
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