Pharm- Local Anesthetics

Question 1

how does local anesthetic hydrophobicity affect LA function?

Answer 1

increasing hydrophobicity increase anesthetic potency and duration but also increases side effects

Question 2

name the ester LA’s

Answer 2

procaine, tetracaine, benzocaine

Question 3

name the amide LAs

Answer 3

lidocaine, bupivacaine

Question 4

what is cocaine?

Answer 4

technically an ester LA but it acts differently from the rest

Question 5

how does cocaine affect catecholamine reuptake?

Answer 5

it inhibits it, especially dopamine

Question 6

potency and duration of the ester LAs?

Answer 6

procaine is low and short

tetracaine is potent and medium duration

benzocaine is highest potency and duration

Question 7

uses of lidocaine?

Answer 7

widely used LA, and a cardiac antiarrythmic

Question 8

how do LAs bind to target recpetors?

Answer 8

they can only bind the target receptors (Na channels) from the neuronal cytoplasmic side

means that only uncharged form can cross lipid bilayer and do this

LAs are weak bases and uncharged when they have not bound H+

Question 9

what’s differential block?

Answer 9

the property that LAs block pain before other neuronal pathways

dependent on: critical length (distance between Na channels/nodes of Ranvier, shorter is easier to block); firing frequency (pain neurons fire faster, and LAs bind preferentially to open Na channels);

Question 10

what affects systemic absorbption of LAs and their subsequent clearance?

Answer 10

the hydrophobicity of the LA, the vascularity of the injection site, the degree of vasoconstriction there, and dose

Question 11

describe metabolism of LAs

Answer 11

esters are metabolized quickly into PABA by plasma cholinesterase

amides are metabolized more slowly by CYP450 and are thus susceptible to more side effects and drug-drug interactions

Question 12

what’s a side effect of PABA?

Answer 12

inhibits potency of sulfa drugs (antibiotics)

Question 13

adverse toxicities of LAs?

Answer 13

overexcitation of CNS leading to seizures, depression and death; GABAergic neurons are also unmyelinated and have a high firing frequency (like pain fibers) and become blocked, leading to unopposed glutamatergic activity

all LAs are directly neurotoxic

in high doses, LAs decrease myocardial elecrical conduction

high doses of benzocaine can cause methemoglobinemia (decreases innate defense agents ROS)

risk of anaphylactic reaction (more susceptible to ester type)

Question 14

puffer fish toxin

Answer 14

tetrodotoxin

binds to the extracellular side of Na channel

reversible Na conduction block

potent, possibly fatal