Local Anesthetics

Question 1

Key/Most Effective Feature

Answer 1

Block AP

Question 2

Basic Structure

Answer 2

Hydrophobic Ring + ester/amide linkage + basic amine side chain (so weak bases)

Question 3

Main Ex.s for Ester and Amide Groups

Answer 3

Cocaine and Lidocaine, respectively

Question 4

Weak Base Important Features of Cycle

Answer 4

Ionizable w/ pKa ~ 8-9, so prepared at pH of 5-6 so majority will be charged and soluble. Blood/cells = 7.4, so most uncharged. However, you want to buffer to this pH beforehand to establish more base. Uncharged required to cross cell membranes (attack from inside), but charged form required to bind to target

Question 5

LA Mech

Answer 5

Binds to Vg Na channels (better bc first in AP) by binding “open channel” - use dependence. Have to be in open or inactivated state, so has to be stimulated before will have any effect

Question 6

Hydrophilic vs. Hydrophobic Pathway

Answer 6

Philic more common, attacks from inside. Phobic attacks laterally

Question 7

Order Nerves Get Blocked

Answer 7

Smaller (like pain Cs and Adeltas) and myelinated first

Question 8

Breakdown (2)

Answer 8

Esterases in plasma cleave esters

Amides metabolized in liver so problems for liver pts

Question 9

2 Side Effects

Answer 9

CNS depression -> respiratory failure or tremors (loss of inhibitory neurons)
Lidocaine is anti-arrythmia