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Many drugs can cause fever, by a variety of mechanisms. Drugs such as interferons can stimulate the production of endogenous pyrogens, and antibacterial agents such as penicillins can kill organisms and so release endotoxins, as in the Jarisch-Herxheimer reaction. Irritant drugs can produce local phlebitis. Alterations of thermoregulation by anticholinergic agents, amphetamines including Ecstasy, and serotoninergic agents are all important causes of druginduced fever. Antituberculous agents and anticonvulsants are implicated in fever due to hypersensitivity reactions; and some drugs can cause severe hyperthermia in susceptible individuals, for example anaesthetic agents in patients predisposed to malignant hyperthermia. Drugs should be suspected in any case of fever the cause of which is obscure.
The mechanism of fever Body temperature is usually controlled within a narrow range by a number of physiological processes. It rises when heat absorption or production exceeds heat loss. Heat is absorbed from the environment, and endogenous production depends on metabolic rate, muscular activity, and 'non- shivering thermogenesis'. Heat is lost from the body by convection and radiation from the surface and evaporation from the skin and lungs. The normal physiological response to a rising temperature is dilatation of skin blood vessels and increased sweating.
The balance between heat production and heat loss is controlled by a combination of mechanisms including the behaviour of the whole organism (avoiding heat, shedding clothes, etc.) and homoeostatic mechanisms. Infection results in the introduction of exogenous pyrogens like bacterial lipopolysaccharide, and inflammation results in the production of endogenous pyrogens, such as the cytokine interleukin-lb. These act on the preoptic region of the hypo thalamus, where they lead to the production of prostaglandin E2 (PGE2) which is the neural mediator of fever, stimulating the endogenous pyrogen receptor (EP3).
In this short review we will outline a classification of the various mechanisms of drug-induced fever and give a number of examples. Classification of drug-induced fever A drug can cause fever in the following ways:
Drugs acting as direct or indirect pyrogens Interferons commonly cause a
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