6,502
edits
Changes
Jump to navigation
Jump to search
→Mechanism of Action
==Mechanism of Action==
==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<sup>+</sup> channels, preventing depolarisation of the cell. Local anaesthetics also infiltrate and change the composition of the cell membrane to take effect. However, they do NOT alter resting membrane potential.
Small diameter nerve fibres are blocked before large fibres by local anaesthetics, and fibres which are myelinated are blocked before those which are unmyelinated. Therefore, A-delta fibres are blocked before C fibres, and so the sensation of pain is eliminated before that of gentle touch.
The blocking effects of local anaethetics is more effective in neurons which are firing. This is because action potentials cause channels in the nerve sheath to cycle between open, resting inactive conformations. The drugspenetrate the sheath through open channels, and bind most readily to inactivated channels.
==Pharmacokinetic Considerations==
==Pharmacokinetic Considerations==