Describe the pharmacology of propofol.
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:
|
| 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. 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.