Thiopentone GABA Mechanism — FRCA Primary MCQ
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Correct answer: A — Positive allosteric modulation of GABA-A receptors, prolonging chloride-channel opening
Thiopentone is a barbiturate that produces hypnosis principally by positively modulating GABA-A receptors. These ligand-gated chloride channels mediate inhibitory neurotransmission; barbiturates increase the probability of longer-duration channel openings, enhancing chloride conductance and neuronal inhibition. At sufficiently high concentrations, barbiturates can also activate GABA-A receptors in the absence of GABA. Alpha-2 agonism is characteristic of dexmedetomidine and clonidine, whereas non-competitive NMDA antagonism is the principal mechanism of ketamine. Glycine-receptor antagonism would reduce inhibitory transmission and promote excitation. Thiopentone can affect voltage-gated ion channels and excitatory glutamate transmission, but sodium-channel blockade is not the principal mechanism responsible for hypnosis.
Reference: Whyte IM, Dawson AH, Buckley NA. Should phenytoin or barbiturates be used as second-line anticonvulsant therapy for toxicological seizures? Clinical Toxicology. 2010;48(8):800-805. https://pubmed.ncbi.nlm.nih.gov/20923393/