What determines potency of local anesthetic?

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

Answer: (B)

Potency is driven by lipid solubility. Local anesthetics must cross the nerve membrane to reach the intracellular site of action on sodium channels. More lipid-soluble (lipophilic) molecules penetrate that membrane more readily, so they achieve effective blockade at lower concentrations. That greater membrane penetration translates directly into higher potency.

Other factors influence how the drug works in other ways. pH affects the balance between ionized and nonionized forms and thus the rate at which the drug can cross membranes (in acidic environments, crossing is slower, affecting onset more than intrinsic potency). Molecular weight has only a minor influence compared with lipophilicity, and color has no bearing on potency.