Question 21

Describe the pharmacology of propofol.

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College Answer

A high level of knowledge was expected as it is a commonly used drug in intensive care. Overall most 
candidates performed very well. Areas of weakness were those relating to propofol pharmacokinetics 
and pharmacodynamics.


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.