ketamine

Question 1

what is ketamine

Answer 1

phencyclidine derivative

Question 2

uses of ketamine

Answer 2

• induction of general anaesthesia,
  -as an analgesic agent
  -@ subanaesthetic dose- 0.2-0.5mg/kg

-to provide analgesia and sedation for short procedures,
-as an adjunct in epidural anaesthesia
- management of severe asthma.

Question 3

main mechanism of ketamine

Answer 3

-interaction with the phencyclidine binding site at the N-methyl-D-aspartate (NMDA) receptor, resulting in non- competitive antagonism of L-glutamate (a major excitatory neurotransmitter in
the central nervous system).
-Ketamine also has local anaesthetic properties in high doses (sodium channel blockade) along with interaction at opioid, monoaminergic, muscarinic and nicotinic receptors.
-typically causes dissociative anaesthesia and has a number of benefits, including analgesic properties, maintenance of airway tone and spontaneous ventilation with cardiovascular stability.

Question 4

major drawback of ketamine
as an anaesthetic agent

Answer 4

association with emergence reactions, delirium, hallucinations and vivid dreams.

Question 5

pharmacokinetics of ketamine

Answer 5

-a chiral centre with two optical stereoisomers: R- and S-ketamine.
-S-ketamine is the more potent enantiomer, with fewer side effects, shorter recovery time and greater affinity for the NMDA receptor
-The pKa of ketamine is 7.5.
-Ketamine is highly lipid soluble (up to 10 times more soluble than thiopentone) and penetrates the blood–brain barrier rapidly.
-Peak plasma-occur within 1 minute after IV administration and within 5 minutes after IM injection.
-PPB- Ketamine is not significantly bound to plasma proteins and leaves the blood rapidly to be distributed into tissues.
-Initially, ketamine is distributed to highly perfused tissues such as the brain, where the peak concentration may be 4 or 5 times that present in plasma.
- ketamine-induced increases in cerebral blood flow could facilitate delivery of drug and thus enhance rapid achievement of high brain concentrations
-Subsequently, ketamine is redistributed from the brain and other highly perfused tissues to less well-perfused tissues, the release of which results in late psychodynamic effects after emergence.
-Ketamine has a high hepatic clearance rate (1 L per minute) and a large Vd (3 L/kg), resulting in an elimination half-time of 2 to 3 hours.
-The high hepatic extraction ratio suggests that alterations in hepatic blood flow could influence ketamine’s clearance rate.

Metabolism
-metabolized extensively by hepatic microsomal enzymes.
-demethylation of ketamine by
cytochrome P450 enzymes to form norketamine and subsequently hydroxynorketamine
-active metabolite-norketamine is one-fifth to one-third as potent as ketamine
-contribute to prolonged effects of ketamine (analgesia), especially with repeated doses or a continuous IV infusion

can develop tolerance and dependence
-Accelerated metabolism of ketamine as a result of enzyme induction
-occurs in patients receiving repeated doses of this drug.