Thiopentone Onset — FRCA Primary MCQ

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EasyPharmacology - Intravenous AnaestheticsThiopentone OnsetFRCA Primary

Which physicochemical property of thiopentone most directly accounts for its rapid onset of action after intravenous administration?

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Correct answer: A — High lipid solubility favouring blood–brain barrier penetration

Thiopentone has high lipid solubility, allowing its diffusible non-ionised form to cross the blood–brain barrier and enter the highly perfused brain rapidly. Unconsciousness therefore occurs within approximately 30 seconds after an intravenous induction dose. Redistribution from the brain to muscle and subsequently fat explains termination of the effect after a single bolus, not its onset. Low lipid solubility or predominant ionisation would impede membrane penetration. Thiopentone is extensively protein-bound, but protein binding limits the freely diffusible concentration and is not the property responsible for rapid onset. ([medicines.org.uk](https://www.medicines.org.uk/emc/product/9376/smpc))

Reference: Electronic Medicines Compendium. Thiopental 500 mg Powder for Solution for Injection, Summary of Product Characteristics, sections 5.1–5.2. Updated 8 January 2025. https://www.medicines.org.uk/emc/product/9376/smpc