Propofol

Class IV anaesthetic
Chemistry
Alkylphenol
Routes of administration

IV only

Absorption
Minimal oral bioavailability due to very high first-pass metabolism and high hepatic extraction ratio
Solubility
pKa 11; minimally soluble in water
Distribution
VOD=2-10 L/Kg; 98% protein-bound
Metabolism
Metabolism is by glucouronide and sulphate conjugation, which happens mainly in the liver.
Elimination
All the metabolites are inactive and excreted renally, which can give the urine a healthy green tinge.
Time course of action
Distribution half life = 120 seconds; elimination half-life from steady state during infusion = 5-12 hours
Target receptor

GABA-A chloride channels, where propofol acts as a GABA-agonist

Mechanism of action

Propofol binds to the β-subunit of the postsynaptic GABAA receptor, where it causes an inward directed chloride current that hyperpolarizes the postsynaptic membrane and inhibits neuronal depolarisation.

Clinical effects

Anaesthesia, respiratory depression, decreased CMRO2, depressed cardiovascular reflexes. Also antipruritic and antiemetic effects. Haemodynamic effects are largely indirect, i.e. the result of sympathetic depression.  - Stable cardiac output - Decreased heart rate (blunted baroreceptor reflex) - Decreased mean arterial pressure, mainly due to increased unstressed volume and decreased MSFP - Decreased peripheral vascular resistance - Decreased CVP Direct effects of propofol on inotropy are minimal, at normal therapeutic doses.

Literature reference

Sahinovich et al (2018)

CICM details of understanding Level 1
Mentioned around Deranged Physiology
Related SAQs

Question 9 from the second paper of 2019 (propofol vs midazolam)

Question 11 from the second paper of 2017 (propofol alone)

Question 14 from the second paper of 2015 (propofol alone)

Question 21 from the second paper of 2013 (propofol alone)

Question 5 from the first paper of 2012 (dexmedetomidine vs. propofol)

Question 7 from the second paper of 2010 (ketamine vs propofol)

Question 9(p.2) from the second paper of 2007 (ketamine vs propofol)