Pharmacology  ·  Local Anesthetics

Mechanism of Action and Nerve Fiber Pharmacology

Sodium channel blockade, ionization, and differential nerve sensitivity

• Local anesthetics work by a two-step mechanism that depends on the drug's ability to exist in both un-ionized and ionized forms. The un-ionized form is lipid-soluble and crosses the nerve membrane; the ionized form is the species that actually binds the sodium channel from inside the axon. Neither form alone is sufficient — you need both the membrane-crossing step and the intracellular binding step.
• The step-by-step flow card in the mechanism section makes the sequence explicit because the two-form requirement is where examination questions about local anesthetics are built. The channel is blocked from inside, not outside. That single fact explains why infected tissue resistance occurs — low pH traps more drug in the ionized form before it can cross the membrane, so less drug reaches the binding site.
• The pH panel deserves attention because it shows a mechanistic prediction that matches a clinical reality every dentist encounters. An acidic abscess doesn't fail to respond to lidocaine because of some vague "inflammation effect" — it fails because the equilibrium between ionized and un-ionized drug shifts, and the membrane-crossing fraction drops below the level needed for a reliable block.
• The differential block table shows that nerve size and myelination, not fiber function per se, determine the sequence of blockade. C fibers (pain, temperature, autonomic) are blocked first because they are small and unmyelinated — not because the drug preferentially "recognizes" pain. The use-dependent blockade rule box adds the dynamic piece: rapidly firing pain fibers accumulate blockade faster because the open and inactivated channel states are the drug's preferred binding states.
• The recovery rule box at the bottom reverses the table. Motor returns first; pain returns last. That sequence is clinically observable in every patient recovering from a spinal anesthetic, and the rule box frames it as a diagnostic fact: a patient who can move but cannot feel pinprick is in differential recovery, not in a pathological state.