Hyperthermia Hypothalamus

Thermoregulation Note DA = dopaminergic. p may mediate hypothermia 8 may mediate hyperthermia Hypothalamus... 

Neuroleptic malignant syndrome is an acute iatrogenic condition caused by neuroleptics, characterized by tremor, catatonia, fluctuating consciousness, hyperthermia, and cardiovascular instability. It is relatively uncommon, occuring in 1-1.5% of patients but is fatal in 11-38%, most often due to cardiovascular collapse (Jahan et al. 1992). The pathogenesis of neuroleptic malignant syndrome is poorly understood, but it is believed to result from altered dopamine and serotonin transmission in the hypothalamus, spinal cord, and striatum. Treatment includes discontinuation of neuroleptics and administration of drugs that increase dopamine transmission bromocriptine or L-dopa (Jahan etal. 1992 Baldessarini 1996). 

Antipsychotic drugs directly affect the hypothalamus and suppress temperature regulation. Severe hyperthermia, rhahdomyolysis, renal failure, and death may result. A cool environment and adequate amounts of fluids are mandatory for patients taking antipsychotic agents. 

Homeostatic regulation of body temperature is mediated in part by the action of endogenous opioid peptides in the brain. This has been supported by experiments demonstrating that administration of -opioid receptor agonists such as morphine administered to the anterior hypothalamus produces hyperthermia, whereas administration of agonists induces hypothermia. 

First, changes in body temperature must reflect a central process, because body temperature is regulated centrally. To produce hyperthermia, psychotogens must somehow enhance sympathetic drive and/or block cholinergic drive on the thermoregulatory centers of the hypothalamus. 

Neuroleptic drugs interfere with the temperature regulatory function of the hypothalamus and peripherally with the sweating mechanism, resulting in poikilothermy. This can result in either hyperthermia or hypothermia, depending on the environmental temperature. 

Moderate doses. Pyrogens increase IL-1, which in the hypothalamus —>T PGE2 formation — temperature set-point. ASA lowers it back to normal in hyperthermia (no effect normally and may 4 temperature in hypothermia). 

Hyperthermia which is not responding to antipyretics (TRPV channels are found in the hypothalamus, where they may play a role in temperature regulation). 

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