Anaes · Local anaesthetic pharmacology

Local anaesthetic chemistry: amide and ester

Also known as Amide vs ester local anaesthetics · Local anaesthetic structure-activity · Voltage-gated sodium channel blockers

Local anaesthetics reversibly block nerve conduction by inhibiting voltage-gated sodium channels in a use-dependent fashion (textbook framework), and every agent shares a three-part structure (a lipophilic aromatic ring, an ester or amide linkage, and a hydrophilic tertiary amine) that classifies it as an ESTER (cocaine, procaine, chloroprocaine, amethocaine), metabolised by plasma cholinesterases to para-aminobenzoate (PABA) and so taught as carrying a higher allergy risk, or an AMIDE (lidocaine, bupivacaine, ropivacaine, prilocaine), metabolised by hepatic CYP450 enzymes with rare true allergy. They are weak bases (taught pKa range): the un-ionised lipid-soluble form crosses the nerve membrane and the ionised form binds the channel from inside, so onset depends on pKa and tissue pH and is reduced in inflamed or acidotic tissue (ion trapping). Potency tracks lipid solubility and duration tracks protein binding (textbook structure-activity framework). Small myelinated and unmyelinated sensory fibres block before large motor fibres, and adrenaline prolongs duration (but must be avoided in end-arterial territories) — per local protocol. Owned evidence in this file is narrow: Galata (2026, n=101) on suspected LA hypersensitivity, Little (2026) AORN local-only guideline overview, Copur (2026, n=64) on volume-dose vs block onset/duration, Ogu (2026, n=190) on liposomal bupivacaine and obesity, Chooklin (2026) rectus-sheath narrative review, and de Souza (2026, n=138) on clonidine vs fentanyl adjuvants.