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LA Failure Infection pH — MFDS Part 1 MCQ

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ModeratePharmacologyLA Failure Infection pHMFDS Part 1

A patient with an acute odontogenic infection has incomplete anaesthesia following local infiltration into the inflamed tissues. Which pH-dependent physicochemical change most directly contributes to reduced local anaesthetic penetration into the nerve?

Educational content. Not a substitute for clinical judgement or local policy.

Reveal the answer and explanation

Correct answer: B — Greater protonation, reducing the unionised drug available to cross the lipid membrane

Explanation lettering: B = shown as A · A = shown as B · E = shown as C · C = shown as D · D = shown as E

A is correct. Most injectable local anaesthetics are weak bases. The lower extracellular pH associated with acute inflammation shifts the equilibrium towards the protonated, charged form, leaving less unionised lipid-soluble drug available to penetrate the nerve membrane. Once intracellular, protonated anaesthetic blocks voltage-gated sodium channels. Option B reverses the expected acid–base shift. Clinically relevant amide local anaesthetics are not rendered ineffective by rapid acid-catalysed cleavage or bacterial destruction, excluding C. Altered protein binding is not the principal pH-dependent explanation, excluding D, and hydrogen ions do not irreversibly inactivate sodium channels, excluding E. Acidosis is best regarded as one contributor: increased inflammatory perfusion and altered nociceptor excitability may also reduce anaesthetic success.

Reference: Pope RLE, Brown AM. A primer on tissue pH and local anesthetic potency. Advances in Physiology Education. 2020;44(3):305–308. https://pubmed.ncbi.nlm.nih.gov/22096346/