Describe the pharmacology of propofol.
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.
|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.