From the Guidelines
Lidocaine works as a local anesthetic by blocking sodium channels in nerve cell membranes, preventing the generation and conduction of nerve impulses, as supported by the most recent and highest quality study 1.
Mechanism of Action
When applied to a specific area, lidocaine temporarily numbs the tissue by inhibiting the flow of sodium ions into nerve cells, which stops pain signals from being transmitted to the brain.
- It comes in various formulations including injectable solutions (typically 1-2% concentration), topical creams or gels (usually 2-5%), patches (5%), and sprays.
- The onset of action is relatively quick, usually within minutes, with effects lasting 1-2 hours for injectable forms and up to 12 hours for patches.
- Lidocaine can be used for minor surgical procedures, dental work, skin conditions, and managing localized pain.
Key Points
- The medication works best when applied directly to the affected area, and its effectiveness stems from its ability to stabilize the neuronal membrane at a molecular level by binding to specific receptor sites within sodium channels, effectively raising the threshold for electrical excitation in the nerve 1.
- Lidocaine has anti-nociceptive, anti-hyperalgesic and anti-inflammatory actions, which explain the apparent prolonged effect hours after an infusion has been completed 1.
- The therapeutic index for i.v. lidocaine is low, with central nervous system toxicity starting at plasma levels only slightly higher than therapeutic levels 1.
Clinical Considerations
- Clinicians should remember the possibility of toxicity even though there may be other explanations for a given clinical presentation, and lipid emulsion 20% should be readily available wherever i.v. lidocaine is used 1.
- Ideal body weight should be used for dose calculation, and intravenous lidocaine should not be used in patients weighing < 40 kg 1.
- No more than 120 mg.h-1 should be infused, and a loading dose of no more than 1.5 mg.kg-1, given as an infusion over 10 min, is recommended 1.
From the FDA Drug Label
Mechanism of action: Lidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action. The mechanism of action of lidocaine is to stabilize the neuronal membrane by inhibiting ionic fluxes, which prevents the initiation and conduction of impulses, resulting in local anesthetic action 2.
- The key points of the mechanism of action are:
- Neuronal membrane stabilization
- Inhibition of ionic fluxes
- Prevention of impulse initiation and conduction
From the Research
Mechanism of Action of Lidocaine
The mechanism of action of lidocaine, a local anesthetic and antiarrhythmic drug, involves altering depolarization in neurons by blocking the fast voltage-gated sodium (Na+) channels in the cell membrane 3. This action is believed to exert its clinically important effects by blocking voltage-gated Na+ channels, which are essential for the generation and propagation of nerve impulses.
Blocking of Sodium Channels
Lidocaine binds to sodium channels from the inner side of the nerve membrane, preventing the normal sodium ion flux 4. The binding of lidocaine to sodium channels is selective, with a higher affinity for open channels than for closed channels. This selective binding provides a simple explanation for the use-dependent block of nerve impulses, where the block increases with the frequency of nerve impulses.
Subtypes of Sodium Channels
Studies have shown that lidocaine has distinct affinities for different subtypes of Na+ channels, with the cardiac sodium channel being intrinsically more sensitive to inhibition by lidocaine than the skeletal muscle sodium channel 5. This difference in sensitivity may contribute to the cardioselective effects of lidocaine.
Induction of Slow Inactivated State
Lidocaine has been shown to induce a slow inactivated state in rat skeletal muscle sodium channels, which is characterized by a long-lived quiescent state 6. This slow inactivated state is thought to be involved in the use-dependent block of nerve impulses by lidocaine.
Key Features of Lidocaine's Mechanism of Action
- Blocks fast voltage-gated sodium (Na+) channels in the cell membrane
- Binds to sodium channels from the inner side of the nerve membrane
- Selective binding to open sodium channels
- Induces a slow inactivated state in sodium channels
- Has distinct affinities for different subtypes of Na+ channels, with a higher affinity for cardiac sodium channels than for skeletal muscle sodium channels 3, 5, 6, 4