Ketamine

Question 1

Drug class

Answer 1

Phencyclidine derivative

Question 2

Mechanism of action

Answer 2

Non-competitive binding to phencyclidine site on N-methyl-D-aspartate receptor (NMDA)
Weak actions at GABAa receptors

Question 3

Metabolism

Answer 3

Hepatic
CYP450 Demethylation of ketamine to Norketamine (active metabolite)
Norketamine is hydroxylated then conjugated to an inactive glucuronide
Excreted via the kidneys

Question 4

Describe the structure-activity relationship

Answer 4

Ketamine contains an asymmetric carbon atom resulting in an S and R enantiomer
S(+) ketamine produces more intense analgesia, more rapid metabolism (faster recovery), less salivation, less emergence phenomena

Question 5

What are the doses for induction of anaesthesia?

Answer 5

IV 1-2mg/kg

IM 4-8mg/kg

Question 6

Time to onset of anaesthesia for IV and IM dosing and the duration of effect

Answer 6

IV 30-60secs
IM 2-4mins
Duration 5-10mins

Question 7

Elimination half time

Answer 7

2-3hrs

Question 8

Volume of distribution

Answer 8

2.5-3.5L/kg

Question 9

Clearance

Answer 9

16-18mLs/kg/min

Question 10

Amount of protein binding

Answer 10

25%

Question 11

What is the dose for analgesia?

Answer 11

0.2-0.5mg/kg IV

Question 12

Describe the Cardiovascular effects

Answer 12

Inc systemic and pulmonary arterial BP
Inc HR
Inc CO
Inc myocardial O2 requirements
via direct stimulation of the CNS causing an increased SNS outflow
In critically ill pts with exhausted catecholamine stores Ketamine produces a direct myocardial depressive effect

Question 13

Describe the respiratory effects

Answer 13

Inc respiratory rate
Bronchodilator
Laryngeal reflexes are preserved
Inc airway secretions

Question 14

Describe the CNS effects

Answer 14

Dissociative anaesthesia
Analgesia
Sensory distortion
Emergence phenomena - hallucinations, delirium
Inc CMRO2
Inc CBF
Inc ICP
Inc IOP - pupillary dilation and nystagmus
Dec alpha, inc theta waves on EEG