Local Anesthetics in Pain Management

Definition and Mechanism of Action of LA and the minimum blockade needed for effective anesthesia

Definition and Mechanism of Action

• Definition: Drugs that block conduction of impulses in central and peripheral nerves by reversibly inhibiting sodium channels.

• Mechanism: Bind to Na⁺ channels → inhibit sodium influx → prevent depolarization → block action potential → loss of sensation.

• Minimum Blockade: For myelinated fibers (e.g., A fibers), at least 2–3 consecutive nodes of Ranvier must be blocked for effective anesthesia.

• Peripheral Nerve Layers:

• • Endoneurium: Surrounds individual axons; contains glial cells, fibroblasts, capillaries.

  • Perineurium: Dense collagen layer surrounding fascicles.

  • Epineurium: Outer connective tissue encasing nerve bundles.

• Myelination CNS vs PNS

• define nodes of ranvier

• Myelination:

  • CNS: Myelinated by oligodendrocytes.

  • PNS: Myelinated by Schwann cells.

  • Nodes of Ranvier: Gaps critical for action potential propagation and anesthesia efficacy.

Physiology of Nerve Conduction

• RMP

• key pump that maintains RMP

• AP

• Resting Potential: −70 to −90 mV due to ionic imbalance.

• Key Mechanism: Na⁺/K⁺ ATPase pump maintains membrane potential.

• Action Potential: Na⁺ channels play central role in depolarization and propagation.

Effect of Local Anesthetic: Blocks Na⁺ channels, preventing AP propagation

General structure of LA _______-

• Aromatic Ring: _____.

• Amine Group: ______.

• General Structure: Aromatic ring — Intermediate chain — Amine group.

  • Aromatic Ring: Lipophilic.

  • Amine Group: Hydrophilic.

LA classification

ester vs amide

• Amino Esters: Metabolized in plasma by pseudocholinesterase.

  • e.g., Procaine

• Amino Amides: Metabolized in liver.

  • e.g., Lidocaine, Mepivacaine

    “AmIdes have an extra I in their name.”

Property	Impact
Lipid Solubility
Diffusibility
Protein Binding
Ionization
pKa
pH Effect
Vasodilation
Epinephrine Use

• ↑ Potency (90% of nerve membrane is lipid)

• ↑ Onset speed

• ↑ Duration of action

• Only non-ionized form crosses membranes [ and non-ionized = active form]

• Closer to physiologic pH = faster onset

• ↓ pH (e.g., infection) → more ionized form → slower onset

• Most LAs are vasodilators → faster absorption → shorter duration

• Slows absorption → prolongs action, reduces toxicity risk

Toxicity and Adverse Effects of LA

• causes

• organ systems affected

• prevention

• Toxicity Causes:

  • Overdose

  • Intravascular injection

  • High vascular site injection

• Organ Systems Affected:

  • CNS: Seizures, altered mental status

  • Cardiovascular: Arrhythmias, hypotension, myocardial depression

  • Muscle: Myotoxicity

• Prevention:

  • Careful dose calculation

  • Use of epinephrine

  • Monitoring during administration

• _____: First local anesthetic used.

  • Extracted by Albert Niemann in 1860.

  • Clinical use by Carl Koller in 1884 (eye surgery).

• Cocaine