Which property determines potency of local anesthetic?

• A. pH
• B. Color
• C. Molecular weight
• D. Lipid solubility

Answer: (D)

Potency is determined by how easily the drug can penetrate the nerve’s membrane to reach the site of action inside the neuron. That ability hinges on lipid solubility: the more lipid-soluble a local anesthetic is, the more readily it diffuses through the lipid bilayer, so a smaller amount is needed to achieve blockade. In other words, higher lipid solubility means higher potency.

These drugs are weak bases, so they exist in both ionized and nonionized forms; only the nonionized form crosses membranes readily, and the proportion available depends on pH and the drug’s pKa, which influences onset more than potency. Color is irrelevant, and while molecular weight can affect diffusion, it doesn’t determine potency as strongly as lipid solubility.