Pharm of Local Anesthetics

Question 1

In general, how do LAs work?

Answer 1

Block the generation and propagation of APs along nerve fibers
Blockade of voltage-gated Na channels (stabilize the inactivated state of Na channels)

Question 2

Are LAs selective drugs?

Answer 2

No!!
They act on all excitable tissues (including heart, brain, smooth and skeletal muscle)
Interact with a whole range of membrane associated proteins

Question 3

Most LAs are weak acids or weak bases?

Answer 3

Weak bases

Question 4

2 classes of clinically used LAs

Answer 4

Aminoesters

Aminoamides

Question 5

Typical structure of LAs

Answer 5

Aromatic head (lipophilic)
Amine tail
Connected by alkyl chain (ester or amide linkage)
They’re amphoteric!

Question 6

Does lidocaine have a chiral center?

Answer 6

No

Question 7

Does bupivacaine have a chiral center?

Answer 7

Yes
Both isomers are similar in terms of efficacy
The R isomer is more toxic

Question 8

Is it the base or cation form that is responsible for the blocking action?

Answer 8

Cation

But it is the base that penetrates through lipid membranes

Question 9

What types of fibers are more resistant to LA blockade?

Answer 9

The thick, fast conducting fibers (motor)

Question 10

How many consecutive nodes need to be blocked to fully block impulse conduction along a myelinated fiber?

Answer 10

3

Question 11

Differential block definition

Answer 11

Allows preferential blockade of sympathetic and pain fibers while minimizing impairment of motor function

Question 12

Benzocaine (amide or ester, use, risk of what)

Answer 12

Aminoester
Used for topical anesthesia only
Risk of methemoglobin formation (can cause cyanosis)

Question 13

Lidocaine (amide or ester, speed, use)

Answer 13

Aminoamide
Fast onset and intermediate duration of action
Used IV as an anti-arrhythmic and in acute and chronic pain

Question 14

Bupivacaine (duration of action, good for, a problem)

Answer 14

Lipophilic and potent
Long duration of action
Racemate with high cardiotoxicity (R isomer)
Good sensory/motor block separation

Question 15

Ropivacaine (isomer, benefits over bupivacaine)

Answer 15

S isomer
Structurally similar but less potent
Lower cardiotoxicity but similar CNS toxicity
Even more motor sparing than bupivacaine

Question 16

Potency correlates to what property?

Answer 16

Lipid solubility

More soluble = more potent

Question 17

Onset of action is related to what property?

Answer 17

pKa

Lower pKa = faster onset

Question 18

Duration of action increases with what 2 properties

Answer 18

Lipid solubility

Protein binding

Question 19

LAs are mainly excreted through…

Answer 19

Urine

Question 20

Why do you add vasoconstrictors when giving LAs?

Answer 20

Delay absorption
Prolong LA effect
Reduce systemic toxicity

Question 21

Where should you NEVER inject an LA with a vasoconstrictor?

Answer 21

Peripheral body parts
Ex: fingers, toes, penis, ears, nose
Can cause tissue necrosis and gangrene

Question 22

Neurotoxicity from LAs

Answer 22

Concentration dependent neuronal injury
From all of the LAs
Most severe and devastating manifestations
Paraplegia or diffuse injury to cauda equina roots

Question 23

3 phases of systemic CNS toxicity

Answer 23

Inhibition (sedation/dizziness, numbness, tinnitus)
Excitation (tonic-clonic seizures)
Generalized depression (coma, cardiorespiratory arrest, death)

Question 24

Which LA is the worst for the heart?

Answer 24

Bupivacaine

In part due to its lipophilicy and potency, can accumulate in the heart

Question 25

Lipid rescue

Answer 25

Treatment for systemic local anesthetic toxicity and overdoses with other lipophilic drugs
Works through mitochondrial effects and oxidation