Transcript Slide 1

KETAMINE
Ketamine’s Properties and
Effect on Brain Development
OVERVIEW
 Pharmacology of ketamine
 Brief history
 Effects of ketamine usage
 Ketamine & neuronal degeneration
in a rat brain
PHARMACOLOGY/HISTORY
 Structurally related to phencyclidine (PCP)
 Prevents the actions of excitatory amino
acids, such as glutamate and aspartate.
 Dissociative anesthetic first used during the
Vietnam War
 Currently still used for veterinary practices and
with children
 First choice for victims w/unknown medical
histories
 In recent years, drug users have discovered
its hallucinogenic properties
 Also used by sexual predators to incapacitate
their victims
EFFECTS OF KETAMINE
 Cardiovascular
 Respiratory
 Vision
 Gastrointestinal
 Immune system
 Psychoactive
BRAIN DEGENERATION
 Apoptosis (programmed cell death)
 Origin of control mechanism still undetermined
but stimulation of NMDA (N-methyl-D-aspartate)
seems vital to the survival of developing nerve
cells
 Need right amount of NMDA situation for sufficient
brain development
 Negative effects for both over and understimulation of NMDA receptors:
 Over-stimulation of NMDA receptors, known as
excitatory neurotoxicity, is known to exacerbate
neuronal damage
 Not enough NMDA stimulation triggers apoptosis
in an immature central nervous system
Table 1: The effect of ketamine on righting reflex
Table 2: The effect of ketamine on weight gain
This table shows the effect of a single dose
of ketamine on different parts of the brain.
This table shows the effect of multiple
ketamine doses on different parts of the
brain.
This table shows the effect of MK-801 doses
during a 24 hour duration.
BRAIN DEGENERATION (con’t)
 Ketamine = Noncompetitive NMDA receptor
antagonist
 Obvious evidence that it causes neurological
degeneration after prolonged exposure
 Duration of NMDA receptor blockage appears
crucial factor in triggering neuronal degeneration in
the developing rat brain
 However, results might not necessary mirror similar
effects in humans due to interspecies variability (i.e.
different duration of brain development)
 Probable that the capability of the human brain
can stand more damage than a rat brain
DEGENERATION FROM KETAMINE
Figure 1
Silver-cupric staining of brain slices from P7 rat treated
with saline (a) or ketamine (b) Degenerating neurones
(dark cells) are abundant in the brain of the rats
treated with ketamine.
DISCUSSION/CONCLUSION
 Ketamine has a balance of positive and
negative effects
 Excessive neuronal damage from
apoptosis after 24 hours of prolonged
exposure to ketamine
 More research is necessary to reveal
ketamine’s full effect on humans.
REFERENCES
 Dikkes P, Hayashi H, Soriano SG. Repeated
administration of ketamine may lead to
neuronal degeneration in the developing rat
brain. Paedriatric Anaesthesia 2002; 12: 770774.
 Copeland J, Dillon P. The health and psychosocial consequences of ketamine use. The
International Journal of Drug Policy 2005; 16:
122-131.