Block voltage-gated sodium channels from the inside of the axon
Expansion
Mechanism
- The un-ionised form crosses the axonal membrane
- Inside, it re-ionises and binds the voltage-gated sodium channel from within
- Depolarisation is blocked, so no action potential propagates
Two properties follow: pKa determines speed of onset (closer to physiological pH means more un-ionised drug and faster onset), and lipid solubility determines potency, while protein binding determines duration.
Use dependence: the drug binds preferentially to open and inactivated channels, so rapidly firing fibres are blocked more readily. This contributes to the differential block of small pain fibres before large motor fibres.
Failure in infection: inflamed tissue is acidic, so a greater proportion of drug is ionised and cannot cross the membrane. Hence the practice of blocking proximally or using a regional technique rather than infiltrating an abscess.
Systemic toxicity progresses from perioral tingling, tinnitus and metallic taste, to confusion and seizures, then cardiovascular collapse. Bupivacaine is the most cardiotoxic. Treatment is supportive plus intravenous lipid emulsion, which acts as a lipid sink.