pharmacology clinical pharmacology and medicinal drugs hypothermia mechanism of hypothermia

1. Therapeutic of hypothermia
The Pharmacologic Inhibition of Thermoregulation
Mohanad AlBayati
Mohanad AbdulSattar Ali Al-Bayati, BVM&S, MSc. Physiol., PhD.
Assistant Professor of Pharmacology and Toxicology
Department of Physiology and Pharmacology
College of Veterinary Medicine
University of Baghdad
Al Ameria, Baghdad
Phone: 0964 7802120391
E. Mail: aumnmumu@covm.uobaghdad.edu.iq
aumnmumu@yahoo.com

2. Hypothermia <35.0 °C (95.0 °F)
Normal 36.5–37.5 °C (97.7–99.5 °F)
Fever >37.5–38.3 °C (99.5–100.9 °F)
Hyperthermia >37.5–38.3 °C (99.5–100.9 °F)
Hyperpyrexia >40.0–41.5 °C (104–106.7 °F)

3. The external heat transfer mechanisms are
 Radiation
 Conduction
 Convection
 Evaporation of perspiration
The process is far more than the passive operation of
these heat transfer mechanisms, however. The body
takes a very active role in temperature regulation

4. Possible Mechanisms
Underlying The Beneficial
Effects of Hypothermia

6. Possible Mechanisms
Underlying The Risk
Factors of Hypothermia

8. The most obvious thermoregulatory responses are behavioral. When
the temperature of the preoptic area of the hypothalamus rises, this
produces the sense of being warm; cooling of the skin and possibly
other receptors produces the awareness of being cold. Effective
behavioral control of temperature depends on both an intact
sensory-motor system and an ability to communicate perceptions.
Regulation of body temperature is inadequate below the level at
which the sympathetic nerves leave the cord in spinal cord
transection. This occurs because the hypothalamus can no longer
control skin blood flow or the degree to which sweating is possible.
Critically ill infants and children have a limited ability to alter their
environment in response to their perception of temperature
variations. Moreover, their ability to communicate their perceptions
is often limited by their developmental stage and the severity of their
illness.
Control of Body Temperature

12. Excitotoxicity
a phenomenon that which was first described by Olney in the seventies,
implies the activation in the CNS of the so-called glutamate receptors.nineteen-
seventies1, involves the activation of glutamate receptors in the central nervous
system (CNS). Glutamate, an excitatory amino acid, activates different types of ion
channel forming receptors (named ionotropic) channel-forming receptors
(ionotropic) and G-protein-coupled receptors (named metabotropic) to develop
their essential role in the functional activity of the brain. However, high
concentrations of glutamate, or neurotoxins acting at the same receptors, cause
cell death through the excessive activation of these receptors. In physiological
conditions, the presence of glutamate in the synapse is highly regulated by very
active, ATP-dependent transporters in neurones and glia. For instance, in CNS
ischaemia a decrease in the levels of glucose exerts causes a decrease in ATP
production, leading to an impairment of glutamate uptake. Moreover, the
membrane potential of presynaptic neurones is lost and efflux of excitatory amino
acids occurs, contributing to the excessive activation of post-synaptic glutamate
postsynaptic receptors

13. Excitotoxicity

14. Glutamate receptors
As pointed out earlier, above, glutamate and other amino acids can
activate both ionotropic and metabotropic receptors (for review, 3). The latter are
subdivided into three main families, and can be coupled to phospholipase C (PLC)
or to adenylyl cyclase (AC). The ion channel forming channel-forming receptors
are subdivided into three different receptor classes that are named by their
selective agonists: AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)
receptors, kainate receptors and NMDA (N-methyl-D-aspartic acid) receptors.
AMPA and kainate receptors trigger rapid excitatory neurotransmission in the
CNS,CNS by promoting entry of Na+ into neurones. However, a subset of
neurones in the hippocampus, cortex and the retina express AMPA receptors that
are also permeable to Ca2+. NMDA receptors are associated to a high
conductance with a high-conductance Ca2+ channel that in resting, non-
depolarising conditions is blocked by Mg2+ in a voltage-dependent manner. Their
activation is secondary to AMPA or AMPA- or kainate-kainate receptor activation
that receptor activation, which depolarises the neurone, allowing for the relief
the release of the Mg2+ blockade.