Local anaesthetics

Local anaesthetics (LAs) are applied to block nociception (pain perception) that is transmitted via peripheral Aδ and C nerve fibres to the brain. Chemically, LAs are amphiphilic molecules with a hydrophobic aromatic group and a basic amine group. They are weak bases that act in their ionised form, but which can only diffuse across the cell membrane to their site of action (at the intracellular face of voltage-gated sodium channels) in their un-ionised form. Docking to the channel blocks Na⁺ from entering nerve cells, and thereby prevents depolarisation and propagation of the action potential along the axon. Efficacy (potency and duration of action) is determined by both the hydrophobicity and pKa of ionisation of the LA compound. LAs are ineffective in inflamed tissue due to tissue acidosis.

Two main subfamilies of LAs are used clinically:

Ester-linked LAs e.g. procaine- rapidly metabolised by tissue and plasma cholinesterases (half-life <3 minutes)

Amide-linked LAs e.g. lidocaine- primarily metabolised slowly by liver p450 enzymes (half-life 1-3 hours)

Administration:

Topical- high concentration of LA in an oily vehicle > slow penetration through skin or mucous membrane.

Infiltration- the LA is injected intradermally or subcutaneously > effective more quickly than via topical application. Lidocaine is the most widely used injected LA.

Peripheral nerve block- the LA is injected around the nerve trunk, to produce anaesthesia distal to the injection site e.g. brachial plexus block anaesthesia can be used the numb the whole arm.

Central nerve block- the LA is injected near the spinal cord, to produce anaesthesia above and below the injection site e.g. epidural anaesthesia used during labour.

Intravenous regional anaesthesia- a tourniquet is used to restrict diffusion of the LA beyond the target area, for example in the arm. This procedure can be used to manipulate bones in limb fractures, or for minor surgical procedures.