Dissociatives

Question 1

What is the original cyclohexylamine?

Answer 1

phencyclidine - it is the most potent

Question 2

What is the least potent dissociative?

Answer 2

Ketamine!

Question 3

Can you use tiletamine alone?

Answer 3

No - only used in combination with zolazepam (a benzodiazepine) to end up as telazol

Question 4

What control schedule are ketamine and telazol?

Answer 4

Schedule III

Question 5

How many enantiomers does ketamine have?

Answer 5

Two! S (+) and R (-)

Question 6

What are the differences between the two enantiomers?

Answer 6

S (+) is more potent, more rapid metabolism and recovery, less salivation, more analgesia, and lower incidence of emergency reactions

S (+) ketamine is twice as potent as racemic and 4 times as potent as R (-)

Question 7

What is the MoA of Ketamine?

Answer 7

Non-competitive antagonist at NMDA receptor

prevents the binding of glutamate and glycine
- this prevents conduction of ions and subsequent firing of second order neurons

Question 8

What is the result of the binding of a non-competitive antagonist at the NMDA receptor?

Answer 8

depressed activity at the thalamocortical and limbic systems as well as depression of nuclei in reticular activating system

Question 9

Ketamine is a muscarinic receptor antagonist - what does this result in?

Answer 9

bronchodilation, sympathomimetic action

(Additionally, it results in sodium channel blockade)

Question 10

Duration of action of ketamine is related to what?

Answer 10

redistribution to lean body tissues and fat. The duration of anesthetic action is shorter than elimination half-life

Question 11

What and how is ketamine metabolized to?

Answer 11

Metabolized by N-demethylation to norketamine (active metabolite) in the liver

Question 12

What and how is norketamine metabolized in dogs and horses?

Answer 12

metabolized via hydroxylation to INACTIVE metabolite (glucuronide derivative) which is excreted in urine

Question 13

What is different about cats and norketamine?

Answer 13

it is excreted unchanged in urine

Question 14

What are the known pharmacokinetics in dogs?

Answer 14

after 15mg/kg IV elimination was 61 minutes, clearance was 32.2 mL/min/kg with 53.5% protein binding

Question 15

What are the known pharmacokinetics in cats?

Answer 15

After 25mg/kg IV, elimination half-life was 78.7min and clearance was 21.3mL/min/kg with 53% protein binding

Question 16

What are the known pharmacokinetics in horses?

Answer 16

2.2mg/kg IV elimination half-life was 42 minutes and clearance was 26.6 mL/min/kg with 50% protein binding

Note: S (+) ketamine resulted in better recoveries compared to racemic ketamine

Question 17

Where in the CNS does dissociation occur secondary to ketamine administration?

Answer 17

the thalamocortical and limbic systems resulting in catalepsy and amnesia

Question 18

What cerebral things occur with ketamine?

Answer 18

• increased cerebral blood flow due to cerebral vasodilation and increased arterial blood pressure
• increased cerebral metabolism
• increased cerebral metabolic oxygen consumption
• increased intracranial pressure