Local Anesthetics
How local anesthetics block sodium channels to produce reversible nerve conduction blockade, and clinical considerations for their use.
## Mechanism of Action
Local anesthetics (LAs) reversibly block voltage-gated sodium channels from the intracellular side, preventing action potential propagation. They preferentially bind the inactivated state of the channel (use-dependent blockade), so actively firing neurons are blocked more readily. LAs must be in their uncharged (base) form to cross the nerve membrane, then become protonated (charged) inside the cell to bind the sodium channel.
This explains why LAs work poorly in infected (acidic) tissue: low pH increases ionization, reducing membrane penetration.
## Chemical Classification
| Class | Linkage | Examples | Metabolism | Allergy Risk |
|-------|---------|---------|------------|-------------|
| Esters | Ester bond | Procaine, chloroprocaine, tetracaine | Plasma cholinesterases (rapid) | Higher (PABA metabolite) |
| Amides | Amide bond | Lidocaine, bupivacaine, ropivacaine, mepivacaine | Hepatic CYP enzymes | Very rare |
Memory aid: amides have two "i"s in the prefix (lidocaine, prilocaine, bupivacaine).
## Differential Nerve Blockade
Small-diameter, myelinated fibers (pain, temperature -- A-delta and C fibers) are blocked before large-diameter motor fibers (A-alpha). This allows pain relief before motor paralysis at appropriate concentrations. The order of blockade is typically: autonomic > pain > touch > motor.
## Clinical Properties
| Agent | Onset | Duration | Uses |
|-------|-------|----------|------|
| Lidocaine | Rapid | 1-2 hours | Infiltration, nerve blocks, epidural, topical, antiarrhythmic |
| Bupivacaine | Slow | 4-8 hours | Epidural, spinal, peripheral nerve blocks; cardiotoxic in overdose |
| Ropivacaine | Moderate | 4-6 hours | Similar to bupivacaine with less cardiotoxicity; less motor block |
| Chloroprocaine | Very rapid | 30-60 min | Epidural; rapid onset, short duration, very low systemic toxicity |
Adding epinephrine causes local vasoconstriction, slowing LA absorption, prolonging duration, and reducing systemic toxicity. Contraindicated in end-artery regions (digits, penis, ear tip).
## Systemic Toxicity (LAST)
Local anesthetic systemic toxicity results from inadvertent intravascular injection or excessive dosing. Progression: circumoral numbness and tinnitus -> seizures -> cardiac arrest. Bupivacaine is especially cardiotoxic (binds cardiac sodium channels tightly). Treatment of LAST includes IV lipid emulsion (Intralipid 20%), which acts as a lipid sink to sequester the drug.
## Key Takeaways
- LAs block sodium channels in their inactivated state, preferentially silencing active nociceptive fibers
- Amide LAs (lidocaine, bupivacaine) are more common and rarely cause allergic reactions
- Acidic (infected) tissue reduces LA efficacy by increasing ionization
- LAST is treated with IV lipid emulsion; bupivacaine overdose is the most dangerous scenario