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Antipyretics: mechanisms of action and clinical use in fever suppression

  • David M Aronoff
    Correspondence
    Requests for reprints should be addressed to David M. Aronoff, MD, Division of Clinical Pharmacology, 514 RRB, 23rd Avenue at Pierce, Nashville, Tennessee 37232-6603.
    Affiliations
    Divisions of Infectious Diseases and Clinical Pharmacology and the Departments of Medicine and Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Search for articles by this author
  • Eric G Neilson
    Affiliations
    Divisions of Infectious Diseases and Clinical Pharmacology and the Departments of Medicine and Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Search for articles by this author

      Abstract

      Fever is a complex physiologic response triggered by infectious or aseptic stimuli. Elevations in body temperature occur when concentrations of prostaglandin E2 (PGE2) increase within certain areas of the brain. These elevations alter the firing rate of neurons that control thermoregulation in the hypothalamus. Although fever benefits the nonspecific immune response to invading microorganisms, it is also viewed as a source of discomfort and is commonly suppressed with antipyretic medication. Antipyretics such as aspirin have been widely used since the late 19th century, but the mechanisms by which they relieve fever have only been characterized in the last few decades. It is now clear that most antipyretics work by inhibiting the enzyme cyclooxygenase and reducing the levels of PGE2 within the hypothalamus. Recently, other mechanisms of action for antipyretic drugs have been suggested, including their ability to reduce proinflammatory mediators, enhance anti-inflammatory signals at sites of injury, or boost antipyretic messages within the brain. Although the complex biologic actions of antipyretic agents are better understood, the indications for their clinical use are less clear. They may not be indicated for all febrile conditions because some paradoxically contribute to patient discomfort, interfere with accurately assessing patients receiving antimicrobials, or predispose patients to adverse effects from other medications. The development of more selective fever-relieving agents and their prudent use with attention to possible untoward consequences are important to the future quality of clinical medicine.

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