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
|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.|
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.