local anaesthetics

Question 1

how did they discover the first local anasthetic?

Answer 1

chewed cocaine and found it to have numbing sensation- applied it topically and had the same effect

Question 2

what is the addictive functional groups in cocaine?

Answer 2

methyl ester

Question 3

why does procaine have a short duration of action?

Answer 3

due to its ester group which is abled to be broken down into an alcohol and a carboxylic acid by esterase’s- less potent

Question 4

how do local anasthetics work?

Answer 4

they work against sodium channels. they diffuse passively through a lipophilic membrane and find their target once through- has to be done this way as they are to big otherwise

Question 5

do we really need the amine in local anasthetics?

Answer 5

yes- if IV- need to be able to be polar

no- if topical- but will not be as potent

Question 6

what is the buchi model of anastetic binding

Answer 6

can only bind ortha or para NOT meta
- by doing this the substituent is able to donate el density through resonance- and making the bonding of the oxygen on the carbonyl more delta positive for stroonger binding.

Question 7

what compound displays a 50 fold increase in binding over procaine?

Answer 7

Tetracaine

Question 8

why does switching ester to amide increases stability?

Answer 8

as it is not efterified into an alcohol and carboxylic acid.- longer duration of action

Question 9

what are the toxic s/e of lidocaine?

Answer 9

some CNS s/e

N-dealkylation after passing BBB