Local Anesthetics

Question 1

Describe the MOA for all local anesthetic drugs.

Answer 1

• reversible inhibition of nerve conduction
• block open sodium channels from cytosolic side (inside) during inactivated state
• bind at site R
• most effective on smaller, myelinated, high frequency nerves (pain)
• charged, cationic form is active at receptor site
• neutral form is important in crossing membranes

Question 2

Identify the various nerve fiber types. Compare how they respond to local anesthetic drugs.

Answer 2

TYPE A - myelinated, larger

• alpha - motor
• beta - tactile, proprioception
• gamma - muscle tone
• delta - pain, cold, temp (very small - easiest)

TYPE B - myelinated, small
- preganglionic sympathetics

TYPE C - unmyelinated
- visceral pain

order of sensitivity

• B => Ad => Aa => C
• more proximal effects first, moves distal
• more frequent firing leaves Na channels in inactivated/activated = easier

Question 3

Discuss the primary determinants of local anesthetics regarding the following:

• onset time
• duration
• potency

Answer 3

onset time - pH and pKa b/c need the neutral form to traverse the membrane, become charged, and then it is active (determines how quickly it will enter the cell)

duration - protein binding (gradual release)

potency - lipid solubility (easier to get in)

Question 4

Explain local anesthetic systemic toxicity (LAST). Demonstrate how to treat it.

Answer 4

LAST
- minimal respiratory effect
=> if respiratory arrest, NEVER due to phrenic nerve paralysis; usually due to hypoperfusion of the 4th ventricle
=> Rx = vasopressors and supportive ventilation
- inhibited sympathetics => vasodilation => hypotension, bradycardia

TX = intralipid that creates a sink for the LA to be trapped into

Question 5

Describe the structure of a prototypical local anesthetic molecule. Name the 2 classes of local anesthetics.

Answer 5

STRUCTURE = benzene ring + alkyl + amine

• ester OR amide linkage
• tertiary amine allows for shift between charged (H bonds to electron pair) and neutral (no H bonds)

CLASSES

• ester
• amide

Question 6

Name some common additives to local anesthetics. Describe why these drugs are given together.

Answer 6

SODIUM BICARB
- neutralizes charge on LA to allow faster intracellular transport

EPINEPHRINE - to combat vasodilation effects of some LAs (lidocaine)

• vasoconstriction => decreases local perfusion => decreases drug absorption to minimize toxicity and enhance duration
• less effective for highly protein bound drugs

A2 agonists

• epi
• clonidine => decrease release of substance P

Question 7

Recall some clinical uses for local anesthetics.

Answer 7

• topical anesthesia
• IV regional anesthesia
• peripheral nerve block
• spinal cord anesthesia
• epidural anesthesia
• anti-arrhythmics

Question 8

Describe how each class of local anesthetics are metabolized.

Answer 8

• ester anesthetic injection => metabolized by plasma cholinesterase => PABA
  => can lead to PABA allergy
• amide anesthetic injection => slower metabolism by liver microsomal enzymes
  => can produce CNS activation, seizures, CV toxicity

Question 9

What is the maximum recommended dose for lidocaine? bupivicaine?

Answer 9

LIDOCAINE

• 5 mg/kg plain
• 7 mg/kg with epi

BUPIVICAINE

• 3 mg/kg
• 2.5 mg/kg neonates