Regional anesthesia involves depositing local anesthetic near specific nerves or nerve plexuses to produce reversible blockade of neural conduction. Local anesthetics block voltage-gated sodium channels in neuronal membranes, preventing depolarization and action potential propagation. The order of nerve fiber blockade follows Gasser's classification: small unmyelinated C-fibers (pain, temperature) are blocked first, followed by small myelinated A-delta (sharp pain, temperature), B-fibers (autonomic), and finally large myelinated A-alpha/A-beta (motor, proprioception, touch). This differential blockade explains why pain relief precedes motor block. Two chemical classes: esters (chloroprocaine, procaine, tetracaine - metabolized by plasma cholinesterases, higher allergic potential from PABA metabolite) and amides (lidocaine, bupivacaine, ropivacaine - metabolized hepatically, allergic reactions extremely rare). Lipid solubility determines potency, protein binding determines duration, and pKa determines onset speed. The maximum safe doses must be calculated to prevent local anesthetic systemic toxicity (LAST): lidocaine 4.5 mg/kg without epinephrine, 7 mg/kg with; bupivacaine 2.5 mg/kg (most cardiotoxic - cardiac arrest from bupivacaine is notoriously difficult to resuscitate).