$KIN Centrally acting fever reduction
Causes of fever
Both internal (endogenous) or external (exogenous) substances can cause a febrile response in the horse. Most commonly, bacteria and viruses initiate a cascade of events leading to fever. However, neoplastic cells and host-derived antigen antibody complexes also can cause fever.1
Temperature is centrally regulated
After a febrile response is triggered, a complex cascade of events occurs centrally, leading to thermal conservation and an elevated hypothalamic set point. The main pathway to elevation of the hypothalamic set point is through arachidonic acid conversion to prostaglandin E2 (PGE2) catalyzed by cyclo-oxygenase (COX).2,3
Fever is a clinical sign mediated by cytokines, which are short polypeptide segments involved with cell signaling.3 Cytokines are also the mediators of the septic process. When unchecked, pyrogenic cytokines have the potential to be both harmful and beneficial during processes that result in the body generating fever.4
Dipyrone’s mechanism of action
Dipyrone, the active ingredient in Zimeta, is a member of the pyrazolone class of non-steroidal anti-inflammatory drugs (NSAIDs) and has a centrally acting mechanism of action on the hypothalamus, where fever originates and is regulated.*
There are multiple postulated mechanisms of actions of dipyrone as an antipyretic. As with all NSAIDs, dipyrone may inhibit fever via inhibition of COX. Additionally, dipyrone may also act as an antipyretic by decreasing arachidonic acid levels via the endocannabinoid pathway. There may also be two, non-prostaglandin-dependent mechanisms: via the endothelin pathway and via the direct endocannabinoid pathway.*
