Which physicochemical property of a local anaesthetic primarily determines its speed of onset?
- A pKa relative to tissue pH ✓
- B Lipid solubility
- C Degree of protein binding
- D Molecular weight
Correct answer: A. pKa relative to tissue pH
Explanation
Only the unionised fraction diffuses across the nerve sheath and axonal membrane. C lower pKa means a larger unionised fraction at physiological pH, so the drug reaches its site of action faster. Lidocaine (pKa 7.8 to 7.9) has a faster onset than bupivacaine (pKa 8.1). Protein binding governs duration and lipid solubility governs potency, which is what makes those options tempting but incorrect for onset speed.
Reference: Morgan and Mikhail's Clinical Anesthesiology, 6th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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