LA Lipid Solubility — MFDS Part 1 MCQ

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ModeratePharmacologyLA Lipid SolubilityMFDS Part 1

Two amide local anaesthetic agents have similar pKa values and degrees of protein binding, but one has substantially greater lipid solubility. Which property would be expected to be greater for the more lipid-soluble agent?

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Correct answer: C — Potency

The correct answer is C, potency. Greater lipid solubility facilitates partitioning of a local anaesthetic into the lipid-rich neural membrane and access to its voltage-gated sodium-channel binding site. Lipid solubility therefore correlates most closely with relative intrinsic potency. Duration of action is influenced principally by protein binding and removal from the injection site, including local vascular uptake. Onset is related mainly to pKa, formulation and tissue pH because these determine the proportion present as the membrane-permeable unionised form. Metabolic rate depends chiefly on whether the drug is an ester or amide and on the relevant enzymatic pathways. Renal excretion is not the primary clinical property determined by lipid solubility.

Reference: Covino BG. Pharmacology of local anaesthetic agents. British Journal of Anaesthesia. 1986;58(7):701–716. https://pubmed.ncbi.nlm.nih.gov/2425835/