Which property determines the potency of a local anesthetic?

Which property determines the potency of a local anesthetic?

• A. Lipid solubility
• B. pKa
• C. Protein binding
• D. Molecular weight

Answer: (A)

Potency is driven mainly by how lipid-soluble the local anesthetic is. Drugs that are more lipid-soluble diffuse through the nerve membrane more readily and reach the intracellular site of action at lower concentrations, producing a stronger block with less drug—so they’re more potent. pKa influences the fraction that is nonionized at body pH, which affects the speed of onset rather than the ultimate potency. Protein binding and molecular weight affect duration and diffusion characteristics, respectively, but not the inherent strength of the block at a given concentration.

Potency is driven mainly by how lipid-soluble the local anesthetic is. Drugs that are more lipid-soluble diffuse through the nerve membrane more readily and reach the intracellular site of action at lower concentrations, producing a stronger block with less drug—so they’re more potent.

pKa influences the fraction that is nonionized at body pH, which affects the speed of onset rather than the ultimate potency. Protein binding and molecular weight affect duration and diffusion characteristics, respectively, but not the inherent strength of the block at a given concentration.