Replies to post #41 on Kindred Biosciences Inc (KIN)

[mick]

$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.*

[mick]

$KIN https://zimeta.com/about-fever-in-horses/

About Fever in Horses

Reasons why horses may experience elevated body temperature
In horses, elevated core body temperature (greater than 101.5°F) is the result of either hyperthermia or pyrexia (fever). Hyperthermia conditions include exercise-related hyperthermia, heat stroke, and reactions to certain toxins or drugs. In general, these conditions do not respond to antipyretic drugs.1

In a true fever, the set point for the physiologic core body temperature increases as a response to infection or inflammation. Although there are documented benefits of fever in many disease processes, managing fever also has benefits, particularly in the horse.1

Fever takes valuable energy
Nutrition is an important part of managing and treating sick horses. Fever increases caloric needs of horses, and inadequate nutrition may result in impaired immune system function, delayed wound or fracture healing, and/or muscle wasting.2

Fever can have serious secondary effects
Managing fever in a sick horse is important to help offset potential negative sequelae, including weakness, muscle wasting, and weight loss.1

Well-documented secondary effects of fever can include anorexia and decreased water intake, which may be associated with gastrointestinal impactions.1,3,4,5

Common causes of fever in horses
Fever is a clinical sign commonly associated with various underlying infectious and non-infectious diseases in the horse. Transportation of horses often results in fever, with incidence increasing with greater travel time and distances. One study showed fever occurred in 47.2% of clinically normal horses with no prior history of respiratory disease following transport.6

Diseases that may present with fever as a clinical sign include:
• Pneumonia/Pleuropneumonia7
• Acute diarrhea8
• Duodenitis/Proximal jejunitis8
• Internal infections10

These diseases are often associated with endotoxemia, a risk factor for sequelae including alminitis.11