Local Anesthetics

Question 1

Structure

Answer 1

Weak base (pKa 8-9)

Lipophilic group on an aromatic ring, intermediate chain (ester or amide), ionizable group

**Non-ionized form penetrates cell membrane; ionized form occupies Na+ channels

Question 2

Pharmacokinetics

Answer 2

• often administered with epinephrine to reduce systemic absorption from the depot site (epi causes vasoconstriction)

Distribution:

• amides are widely distributed followed by uptake into muscle and gut
• esters have relatively short half lives

Elimination:

• amides are metabolized in the liver by N-dealkylation and hydrolysis
• Esters are rapidly inactivated by plasma cholinesterase and liver esterases

Question 3

Pharmacodynamics

Answer 3

• Bind to Na+ channels from the inside of the cell and block Na+ entry
• Binding is state dependent (higher affinity for activated and inactivated channel states, but not for the resting state)
• small nerves are blocked before large nerves, myelinated fibers are blocked before unmyelinated fibers, circumferential fibers are blocked before central fibers
• Anesthesia first develops proximally because proximal sensory fibers are located more superficially than distal sensory fibers

Question 4

Toxicity

Answer 4

• Systemic administration may depress CNS cortical inhibitory pathway and lead to excitation, colvulsion, and respiratory depression
• Block cardiac Na channels and depress cardiac function; cause vasodilation (except for cocaine)

Treatments:

• Thiopental or Diazepam for seizures
• Succinylcholine IV for muscular manifestations
• Atropine for bradycardia
• Bretylium for arrhythmias
• Epinephrine for hypotension

Question 5

Cocaine

Answer 5

Ester Anesthetic
- Reversibly block impulse conduction along nerve axons by blocking Na channels from the INSIDE

Tox: vasoconstriction; metabolite (p-aminobenzoic acid) can cause allergic reaction

Question 6

Procaine

Answer 6

Ester Anesthetic
- Reversibly block impulse conduction along nerve axons by blocking Na channels from the INSIDE

Tox: metabolite can cause allergic rxn

Short duration of action (~30 min)

Question 7

Tetracaine

Answer 7

Ester Anesthetic
- Reversibly block impulse conduction along nerve axons by blocking Na channels from the INSIDE

Long duration of action (~7 hours)

Question 8

Benzocaine

Answer 8

Ester Anesthetic
- Reversibly block impulse conduction along nerve axons by blocking Na channels from the INSIDE

Topical use

Question 9

Lidocaine

Answer 9

Amide Anesthetic
- Reversibly block impulse conduction along nerve axons by blocking Na channels from the INSIDE

Intermediate duration of action

Question 10

Bupivacaine

Answer 10

Amide Anesthetic
- Reversibly block impulse conduction along nerve axons by blocking Na channels from the INSIDE

Cardiac arrest if administered systemically

Long duration of action

Question 11

Ropivacaine

Answer 11

Amide Anesthetic
- Reversibly block impulse conduction along nerve axons by blocking Na channels from the INSIDE

Long duration of action

Question 12

Etidocaine

Answer 12

Amide Anesthetic
- Reversibly block impulse conduction along nerve axons by blocking Na channels from the INSIDE

Long duration of action

Question 13

Mepivacaine

Answer 13

Amide Anesthetic
- Reversibly block impulse conduction along nerve axons by blocking Na channels from the INSIDE

May become trapped in acidified neonate blood

Intermediate duration of action

Question 14

Prilocaine

Answer 14

Amide Anesthetic
- Reversibly block impulse conduction along nerve axons by blocking Na channels from the INSIDE

Large dose may lead to o-toluidine accumulation –> methemoglobinemia and cyanosis (tx with methylene blue)

Intermediate duration of action