Question 11

Describe the pharmacology of propofol

Pharmacology of propofol

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College Answer

A structured approach proved a good basis to answer this question. It was expected candidates
would outline the uses such as anaesthesia, more prolonged sedation or possible additional
roles in patients with seizures or head injuries. Discussion of the presentation and
pharmaceutics, including a comment on antibacterial preservatives or lack thereof was
expected. The mechanism of action should have been described. It was expected candidates
could provide an indication of the usual dose (and how it differs in the more unwell / elderly
patient population). A maximal rate and possible toxicity was expected.

A discussion on the pharmacodynamics by major organ systems was expected and credit was
given for additional comments about hyperlipidaemia, urine colour changes or metabolic
alterations. It was expected that candidates would mention propofol infusion syndrome at some
point in their answer with some mention of clinical features or pathophysiology.

The important aspects of its pharmacokinetics should have been mentioned (high protein
binding, large volume of distribution, termination of effect by redistribution, hepatic metabolism,
context sensitive half life). A mention of adverse effects would complete the answer.


It is remarkable that the college asked for a usual dose here, because of how individually variable it is, and how distant from reality the textbook 2mg/kg induction dose of propofol can be. When you ask a senior anaesthetist, "how much propofol should I give this patient", the answer is usually "enough". That aside, the rest of the answer is fairly formulaic:

Class IV anaesthetic
Chemistry Alkylphenol
Presentation Oil emulsion. Vial contains:
  • 1% propofol (10mg/ml)
  • 10% soybean oil
  • 1.2% purified egg phospholipid
  • 2.25% glycerol, to adjust tonicity
  • Sodium hydroxide  to keep the pH between 6 and 8.5.
  • Sodium EDTA as an antimicrobial additive
Dose 1-2mg/kg, more in young children, much less in hemodynamically unstable, elderly or already obtunded patients
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
Target receptor GABA-A chloride channels, where propofol acts as a GABA-agonist
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 Bolus half life = 120 seconds
Half life from steady state = 5-12 hours
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.

Single best reference for further information Sahinovich et al (2018)


Sahinovic, Marko M., Michel MRF Struys, and Anthony R. Absalom. "Clinical pharmacokinetics and pharmacodynamics of propofol." Clinical pharmacokinetics 57.12 (2018): 1539-1558.