Local Anesthetics

Question 1

Benzocaine

Answer 1

Amino ester

pKa ~ 3.5. Exists solely as non-ionized base.

Question 2

Cocaine

Answer 2

Amino ester

Procedures requiring high surface activity and vasoconstriction

Question 3

Tetracaine

Answer 3

Amino ester
More potent (longer duration)

Question 4

Procaine

Answer 4

Amino ester
Transient neurological symptoms (TNS)
Very short procedures

Question 5

Amino ester

Answer 5

Benzocaine
Cocaine
Tetracaine
Procaine
ONE LETTER "i"

Question 6

Lidocaine

Answer 6

Amino amide
More water soluble (less potent) (small)
Transient neurological symptoms (TNS)
Short duration procedures.

Question 7

Prilocaine

Answer 7

Amino amide
More water soluble (less potent)
No TNS
Fastest metabolism of amide-linked agents

Question 8

Meprivacaine

Answer 8

Amino amide
More water soluble (less potent)
Transient neurological symptoms (TNS)

Question 9

Bupivacaine

Answer 9

Amino amide
More potent (longer duration) (more lipid soluble) (big)
No TNS
Longer duration procedures 
Slowest metabolism

Question 10

Amino amide

Answer 10

Lidocaine
Prilocaine
Meprivcaine
Bupivacaine
TWO LETTER "i"

Question 11

Pharmacological properties of local anesthetics

Answer 11

Weak bases (pKa 7.8 to 9.1) 
Physiological pH: positively charged (cationic form) 
Henderson-Hasselbalch: pKa = pH - log[base]/[conj acid]
Lower pKa = larger % uncharged

Question 12

Mechanism of Action

Answer 12

Block Na+ channels (along axons) 
--can only do so when channel is open 
--Voltage and time-dependent 
Blockade from inside of cell
Reversible 
Ionized (cationic) form = higher affinity for receptor 
Unionized form diffuses across membrane 
Critical length to block = 2-3 nodes of Ranvier

Question 13

Sodium channel

Answer 13

Large por-forming alpha subunit
Nine alpha-subunit isoforms
Two auxiliary Beta-subunits

Question 14

Efficacy on different nerve types

Answer 14

More efficacious on rapidly firing neurons
Small C and B fibers blocked first 
--> small type A-delta and A-gamma
--> A-alpha fibers blocked last 
C: pain [[BLOCKED FIRST]]
B: preganglionic autonomic
A-delta: pain, temp
A-gamma: muscle spindles
A-beta: touch, pressure
A-alpha: proprioception, motor 
Pain --> sensation --> motor 
Recovery: reverse of block (pain returns last)

Question 15

Types of blocks

Answer 15

Topical 
Infiltration (pH of wound might be acidic --> increased ionization--> increased time of onset)
Field (ring) block (faster onset) 
Peripheral 
Infiltration (spinal)

Question 16

Clearance

Answer 16

Patient age
Liver fxn
CV status
Ester hydrolyzed faster than amide

Question 17

Dibucaine number

Answer 17

Inhibits cholinesterase (butylcholinesterase)
Each patient has a different dibucaine #
–refers to speed at which ester drugs are cleared

Question 18

CYP 450

Answer 18

Amide-linked agents

Prilocaine > lidocaine > mepivicaine > ropivicaine ~ bupivaciane & levobupivocaine (slowest)

Question 19

Toxicity

Answer 19

Hypersensitivity
–benzoic acid
–para-aminobenzoic acid
Methyparaben (preservative)

Question 20

Transient neurologic symptoms (TNS)

Answer 20

Neuraxial (spinal and epidural)
transient pain or dysethesia
Not ask with sensory loss, motor weakness, or bowel and bladder dysfxn 
Pain can be quite severe 
Lidocaine, procaine, mepivacaine