LO8 Local Anesth [3]

Question 1

Local anesthetics have which type of structure?

Answer 1

Tripartite

1. lipophilic aromatic
2. intermediate alkyl chain
3. hydrophilic amine

(note: LA usually end in -caine)

Question 2

Are LA weak acids or bases? Why is that imp?

Answer 2

Weak bases, making them partly ionized

• can rapidly protonate (+ ch) /deprotonate (neutral) at the amino group.
• Cationic (+) binds better to binding site
• neutral can cross pm to reach site of action

Question 3

HH eq. describing degree of ionization

Answer 3

(neutral form)/(cationic form) = 10^ (pH-pKA)

Question 4

Blockage of AP occurs at the nodes of ranvier or in the internodal myelinated axons?

Answer 4

Node of ranvier

there are no Na+ channels int he internodal segs

Question 5

LA conduction block occurs in (pick one) smaller/larger diameter fibers at lower doses.
Why?

Answer 5

Smaller diameter
PAIN SENSATION IS THE FIRST FUNCTIONALITY LOST!
- because internodal distances is shorter in smaller diameter axons
- the Na+ channels of small-diameter axons are “used” more than large (fractional block of Na+ channels in sm diameter axons is greater)

(ie: C fibers)

Question 6

Generally speaking, LA with:
- Faster onset
- More potent
\_\_\_\_\_\_\_\_\_\_\_
- Longer lasting 

have. . .

Answer 6

↓er pKa
↑er lipid solubility
______________
↑er protein binding

Question 7

Rank potency
Procaine
Lidocaine
Bupivicaine

Answer 7

Procaine: low
Lidocaine: Med
Bupivicaine: high

Question 8

Rank onset

Procaine
Lidocaine
Bupivicaine

Answer 8

Procaine: slow
Lidocaine: Fast
Bupivicaine: med

Question 9

Amide LA are significantly bound to which plasma protein to increase duration of action?

Answer 9

α1- acid glycoprotein

• high protein binding capacity

Question 10

Diff betwn how esters and amides get broken down

Answer 10

Esters:

• pseudocholinesterase
• liver hydrolysis

Amides:
- only liver metabolism

(if indib have liver failure/hepatic insuff: amide LA are contraindicated)

Question 11

Why is the use of a vasoconstrictor (ie: epi) useful?

Answer 11

LA typically reduce SNS activity → vasodilation

Vasoconstrictors can Prolong the duration of conduction blockage by ↓ing blood flow
-also prevents plasma levels from getting toxic

Question 12

side effects of LA

Answer 12

1. convulsions
2. interfere with ANA fxn (↓ SNS)
3. Anti and Proarrythmic
4. cardiotoxic
5. a. vasodilation
6. cross placenta to baby
7. inhibit neuro transmission
8. allergy (esters)

Question 13

Saxitoxin + TTX MOA

Answer 13

bind and block extracellular entrance of VG Na+ channels → paralyze respiratory muscle (not by action on heart)

(not the same MOA as local anesth)