Kauffman RE
Children's Mercy Hospital, University of Missouri-Kansas City, Kansas City, MO, USA

Objectives: 1) Review the physiology of normal thermoregulation; 2) Discuss biochemical mechanisms of the febrile response; 3) Review mechanisms of action of antipyretic drugs; and 4) Compare the pharmacologic characteristics of the commonly used antipyretics.
Methods: Current information regarding pathophysiology of fever and pharmacology of antipyretics will be provided.
Results: Fever is one of the most common presenting complaints in pediatric patients. It is a normal component of the acute phase host response to infection, and involves complex physiologic and biochemical processes. Fever is the result of a resetting of the thermostatic "set point" in the posterior hypothalamus. The pyretic response is mediated by release of cytokines, specifically IL-1, IL-6, and TNF. These cytokines act at the hypothalamus to induce local production of PGE2. Anti-pyretic drugs reduce fever by inhibition of cyclooxygenase to reduce production of PGE2. The most commonly used antipyretics around the world include dypyrone, aspirin, ibuprofen, and paracetamol. The selection of antipyretic drug of choice varies widely in different countries. Aspirin, ibuprofen, dipyrone and paracetamol all are effective antipyretics. Therefore the physician's choice of antipyretic is based primarily on safety considerations. The pharmacology of the several antipyretics will be discussed with a comparison of their relative safety profiles.
Conclusion: Fever is a normal part of the host response to pyretic stimuli. Pharmacologic reduction of fever may be desirable to improve patient comfort. The most commonly used antipyretic drugs around to world are dipyrone, aspirin, ibuprofen, and acetaminophen. All are effective antipyretics. The choice of antipyretic should be based on the safety profiles of the respective drugs.