Fever and NSAIDS


Q: What is the mechanism of the antipyretic action of NSAIDs like mefenamic acid and aspirin?

A: To understand the rationale for the use of NSAIDs in fever, it is helpful to start by understanding the febrile pathway.

Fever is initiated by lipid substances called pyrogens which can be biological (such as bacterial toxins and blood products) or chemical in origin.

These substances cause a release of a chemical messenger called Prostaglandin E2 or PGE2 in cells which raises the thermostat in the hypothalamus to increase the body’s temperature. This increase in the body’s temperature is achieved through:

a) release of hormones like norepinephrine that increases metabolism in brown adipose tissue to raise temperature.

b) constriction of blood vessels on skin surfaces, (this restricts blood to the inside of the vessels that prevents loss of heat) [NOTE: prostaglandins cause vasoconstriction only on vessels directly underlying skin and vasodilation where an infection occurs, which causes the characteristic redness and swelling due to extravasation of blood)

c) by shivering, where muscle contractions make you feel warmer

PGE2, a prostaglandin is produced from arachidonic acid primarily in the GI mucosa and kidney. This pathway requires an enzyme called cyclooxygenase (COX). Prostaglandins are essential chemical messengers for inflammation, the body's response to invading agents, as seen in this diagram.


NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) such as aspirin and mefenamic acid block COX (that's why they're called COX inhibitors). Because of this, pyrogens can no longer increase temperature via prostaglandins, and the fever breaks. It also contributes to pain relief and antiplatelet functions as per the image above and hence is used for headaches and patients with ischemic heart disease as well!

While aggressive treatment of fever remains a controversial topic, as fever is a useful defence mechanism against infections and augments immunity, NSAIDs can help the patient rest by relieving pain and making the patient feel more comfortable, for a better recovery.

Dr Prabhav Vasistha

References:
1. Ishiguro, Hitoshi & Kawahara, Takashi. (2014). Nonsteroidal Anti-Inflammatory Drugs and Prostatic Diseases. BioMed research international. 2014. 436123. 10.1155/2014/436123.

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