3.6 Local Anesthesia

Question 1

What is an ester?

Answer 1

C=O
|
OR

Question 2

What is an amide?

Answer 2

Amine + carbonyl
C=O
|
NH - R

Question 3

What are the ester local anesthetics?

Answer 3

Cocaine and procaine

Question 4

What are the amide local anesthetics?

Answer 4

Lidocaine and bupivacaine

Question 5

What is the henderson-hasselbach equation?

Answer 5

Weak bases:
Log (cation/uncharged) = pKa - pH

Question 6

All local anesthetics have a pKa from…

Answer 6

8 - 9 (all greater than plasma 7.4)

Question 7

T/F: pKa is indirectly related to available drug

Answer 7

True, higher pKa means more cationic/acid form (unavailable form)

Question 8

What is the MOA of local anesthetics?

Answer 8

Block Na+ channels, more negative, increased threshold = -APs

Question 9

The subunits of the Na+ channel are…

Answer 9

2 beta, 1 alpha

Question 10

What are the 4 phases of AP firing?

Answer 10

1. Resting = Na+/K+ pump
2. Depolarization = Na+ open to enter
3. Repolarization = K+ open to leave
4. Return to resting = Na+/K+ pump

Question 11

Why are ionized drugs useless?

Answer 11

Ionized = non-lipid soluble, cannot cross phospholipid membrane into cells

Question 12

How do local anesthetics block Na+ channels?

Answer 12

Unionized passes through and reionizes in the cell, then enters the Na+ channel from the inside IF its open (use-dependent)

Question 13

Why is local anesthetic action use-dependent?

Answer 13

Channel needs to open to let the drug in from the inside, so the more active the nerve, the quicker the block

Question 14

Which enantiomer of bupivacaine is more cardiotoxic?

Answer 14

R

Question 15

Why are amide local anethetics more potent?

Answer 15

Amide = higher weight = higher lipid solubility

Question 16

Drug lipophilicity is ___ related to protein binding

Answer 16

Directly

Question 17

Protein binding is ___ related to duration of action

Answer 17

Directly

Question 18

What is pKa?

Answer 18

The pH at which ionized and unionized form are equal

Question 19

T/F: All local anesthetics are weak bases

Answer 19

True

Question 20

How would a lower pH affect local anesthetic efficacy?

Answer 20

They’re weak bases, so it would increase the ionized form, therefore reduced efficacy

Question 21

Why is adrenaline added in procedures using local anesthesia?

Answer 21

Cause vasoconstriction so systemic absorption is limited, increasing the drug at the site of action
(LA usually cause vasodilation anyway)

Question 22

Why is adrenaline not required if cocaine is administered?

Answer 22

It is a vasoconstrictor itself

Question 23

Local anesthetics bind to ____

Answer 23

alpha-1-acid glycoprotein and albumin

Question 24

T/F: albumin > alpha-1-acid glycoprotein binding due to greater potency

Answer 24

False, because of greater abundance

Question 25

What metabolizes esters?

Answer 25

Cholinesterases

Question 26

Esters –(cholinesterase)–> ?

Answer 26

PABA

Question 27

Why doesn’t cocaine cause anaphylaxis?

Answer 27

After cholinesterase there’s liver hydrolysis and renal excretion, so PABA doesn’t remain

Question 28

Why are amides more likely to accumulate than esters?

Answer 28

Liver metabolism is slower

Question 29

Which nerve fibres are more susceptible to local anesthetics?

Answer 29

The Ad (acute pain) and C (heat + chronic pain) fibres

Question 30

Why are the Ad and C fibres more susceptible to local anesthetics?

Answer 30

1. Thinner
2. Slower conduction = greater chance for drug entry

Question 31

What are the units of max safe doses of local anesthetics?

Answer 31

mg/kg

Question 32

0.25% bupivacaine = ___mg/mL

Answer 32

2.5mg/mL

Question 33

2g/kg bupivacaine = ___mg/mL

Answer 33

200mg/mL