Question 14

Describe the pharmacology of propofol.

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College Answer

Those candidates who did poorly lacked any structure for answering a pharmacology question. 
Pharmacokinetics was generally poorly handled and many answers revealed a lack of 
knowledge about this drug. Adverse effects and mechanism of action were generally well 
known. Doses of the drug were often incorrectly stated.
Important aspects such as dose or pharmacodynamics were often omitted and a structured 
approach helps avoid this.


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.