Ketamine Pharmacology — FRCA Primary MCQ
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Correct answer: C — The S(+) enantiomer is approximately 3–4 times more potent than the R(−) enantiomer
Explanation lettering: D = shown as A · E = shown as D · A = shown as E
C is correct. S(+)-ketamine has greater affinity for the phencyclidine site within the NMDA receptor channel and is approximately three times, commonly quoted as 3–4 times, as potent as R(−)-ketamine for anaesthesia and analgesia. Norketamine remains pharmacologically active but is substantially less potent than ketamine, so A is false. Ketamine is predominantly a non-competitive NMDA receptor antagonist rather than a GABA-A receptor agonist, excluding D. Its pKa is approximately 7.5, whereas propofol has a pKa of approximately 11, so B is false. Protein-binding estimates vary by preparation and source, but the current esketamine SmPC reports about 50%; therefore, 75% is not correct. The previous explanation's specific claim of 25% binding has been removed because it conflicts with the current UK SmPC.
Reference: Electronic Medicines Compendium, Esketamine 5 mg/ml solution for injection/infusion, SmPC sections 5.1–5.2, updated 16 December 2024. https://www.medicines.org.uk/emc/product/13194/smpc