Ketamine

Class	IV anaesthetic
Chemistry	Cyclohexylamine
Routes of administration	Intravenous, intramuscular, subcutaneous, oral (rarely), buccal, transdermal and rectal
Absorption	17% oral bioavailability
Solubility	pKa 7.5; relatively poor water solubility; 20-50% protein bound
Distribution	1-3L/kg VOD; 20-50% protein bound
Metabolism	Metabolised by CYP450 enzymes into multiple metabolites, of which only norketamine is mildly active.
Elimination	Elimination half-life is 2.5 hrs, but redistribution (alpha) half-life is ~ 7-11 minutes
Time course of action	Onset of anaesthetic effect, following an anaesthetic dose (~2mg/kg), is within 15-30 seconds. Duration of useful anaesthesia/analgesia is about 15-30 minutes.
Target receptor	NMDA receptor
Mechanism of action	Lodges in the pore of the NMDA cation channel, causing the receptor to become closed, and to stop binding glutamate. As a consequence, it prevents glutamate-simulated sodium and calicum influx into the cell, and potassium efflux. The result is a depressed excitatory neurotransmission
Clinical effects	Dissociative anaesthesia, analgesia, sialorrhoea, bronchorrhoea, bronchodilation, possible increased cerebral metabolic rate, reversal of opioid tolerance, and slightly increased skeletal muscle tone. Haemodynamic effects are largely indirect, i.e. the result of sympathetic stimulation. - Increased cardiac output - Markedly increased heart rate - Increased mean arterial pressure initially, which rapidly renormalises - Decreased pulmonary vascular resistance - Decreased peripheral vascular resistance - Decreased CVP Direct effects of ketamine on inotropy are negative.skeletal muscle tone
Literature reference	the Australian PI from Interpharma.
CICM details of understanding	Level 1
Mentioned around Deranged Physiology	Ketamine
Related SAQs	Question 11 from the first paper of 2022 Question 15 from the first paper of 2019 (NMDA receptor pharmacology) Question 4 from the second paper of 2018 (ketamine vs. midazolam) Question 22 from the first paper of 2015 (ketamine vs dexmedetomidine) Question 16 from the second paper of 2011 (ketamine and propofol effects on CMRO₂) Question 7 from the second paper of 2010 (ketamine vs propofol) Question 9(p.2) from the second paper of 2007 (ketamine vs. propofol)

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