Local Anaesthetics

Mechanism of Action

Local anaethetic drugs reversibly interfere with action potential generation and conduction in the neurons around which they are administered. To reach the neuronal plasma membrane where they act, local anaethetic drugs must first enter the nerve sheath. Only molecules lacking ionic charge may do this, and so local anaesthetic agents work more effectively in an alkaline pH when charge is neutral. Once inside the sheath, the drug gains charge and can then bind to voltage-gated Na⁺ channels, preventing depolarisation of the cell. Local anaesthetics also infiltrate and change the composition of the cell membrane to take effect.