Local Anaesthetic pKa — MFDS Part 1 MCQ

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HardPharmacologyLocal Anaesthetic pKaMFDS Part 1

Two weak-base local anaesthetics are identical in concentration, lipid solubility, protein binding and formulation. Local anaesthetic X has a pKa of 7.6 and local anaesthetic Y has a pKa of 8.1. They are deposited in tissue at pH 7.4. Using pH = pKa + log10([B]/[BH+]), where B is the non-ionised base, approximately how many times greater is the non-ionised fraction of X than that of Y?

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Correct answer: B — 2.3-fold

The correct answer is B. A local anaesthetic's pKa, relative to tissue pH, determines its equilibrium between non-ionised base and ionised cation. The calculated non-ionised fractions are approximately 38.7% for X and 16.6% for Y, making that of X about 2.3 times greater. The non-ionised form more readily crosses the lipid nerve membrane, so X would generally be expected to have the faster onset when other determinants are equal. Option A reverses the comparison. Option E incorrectly assumes equal ionisation. Option C compares the two base-to-cation ratios directly rather than calculating each drug's fraction of the total. Option D is the approximate ionised-to-non-ionised ratio for Y, not the requested comparison.

Reference: Kambuaya NN, Fuadi I, Yadi DF. Sodium bicarbonate alkalinization of local anesthetics for peripheral nerve blocks: A systematic review. Journal of Clinical Anesthesia. 2026;113:112268. https://pubmed.ncbi.nlm.nih.gov/42378735/