Pharmacology · Local anesthetics
Lidocaine !
The most used local anesthetic: it numbs skin and nerves by blocking sodium channels. It is also a class Ib antiarrhythmic.
Updated 2026-11-01
There is no structure yet of a human Nav channel with lidocaine. The figure shows flecainide in the rat cardiac Nav1.5 channel: it occupies the same inner-pore site where lidocaine binds.
Mechanism of action
Lidocaine, an amide, crosses the axon membrane in its uncharged form and blocks the pore of the voltage-gated sodium channel from inside. It binds mainly to open or inactivated channels, so it curbs the generation and conduction of the action potential: the nerve stops carrying pain. In the heart it binds and leaves inactivated channels quickly (class Ib) and acts most on ischemic, depolarized ventricular tissue.
- The uncharged form crosses the axon membrane
- Inside, it blocks the pore of the open or inactivated Nav channel
- Without sodium current no action potential fires
- The pain signal stops: the area goes numb
Pharmacokinetics
- Absorption
- Absorbed from the injection site; a vasoconstrictor such as epinephrine reduces systemic absorption.
- Distribution
- Wide, with affinity for fat; crosses the blood-brain barrier and the placenta.
- Metabolism
- Liver, rapidly, to less potent active metabolites (MEGX and GX); heart or liver failure slows it.
- Elimination
- Kidney, as metabolites.
- Half-life
- 1.5 to 2 hours; longer in liver or heart failure.
Indications
- Local anesthesia for carpal tunnel release and other hand procedures Carpal tunnel syndrome →
- Infiltration for stitches, minor procedures and dentistry
- Peripheral nerve blocks and topical anesthesia of mucosa
- Ventricular arrhythmias, especially ischemia-related (class Ib antiarrhythmic)
- Postherpetic neuralgia (patch)
Adverse effects
Common
- Burning on injection
- Dizziness and drowsiness
- Perioral numbness and metallic taste as early signs of excess
Contraindications
- Allergy to amide-type anesthetics
- Adams-Stokes or Wolff-Parkinson-White syndrome (antiarrhythmic use)
- Severe sinoatrial, atrioventricular or intraventricular block
Key interactions
- Propranolol
- Lowers lidocaine clearance and can push it to toxic levels.
- Cimetidine
- Lowers lidocaine clearance.
- Amiodarone, phenytoin, procainamide and quinidine
- Additive or opposing cardiac effects and additive toxicity.
- Other local anesthetics
- Their toxicities add up.
What is monitored
- Early neurological signs of toxicity (perioral numbness, tinnitus)
- ECG and blood pressure with intravenous use
Test yourself
Think of the answer, then tap the question to see it.
From which side of the membrane does lidocaine block the sodium channel?
From the intracellular side: the uncharged form crosses the membrane and the charged form occupies the channel's inner pore.
Why does lidocaine act more on ischemic ventricular myocardium than on healthy tissue?
It binds preferentially to inactivated channels, plentiful in depolarized ischemic tissue, and leaves the channels of healthy tissue quickly.
Why does heart failure raise the risk of lidocaine toxicity?
Hepatic blood flow falls, the liver clears less lidocaine and its half-life lengthens.
Why is lidocaine mixed with epinephrine for infiltration?
Vasoconstriction reduces systemic absorption: the drug stays longer at the site and the risk of toxicity falls.
Related conditions
← Back to the class: Local anesthetics
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: LIDOCAINE HYDROCHLORIDE AND DEXTROSE- lidocaine hydrochloride anhydrous and dextrose monohydrate injection, solution (DailyMed (U.S. National Library of Medicine), 2026); Lidocaine (PubChem (NCBI), 2026); Lidocaine Transdermal Patch: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.