local anaesthetics Flashcards
how did they discover the first local anasthetic?
chewed cocaine and found it to have numbing sensation- applied it topically and had the same effect
what is the addictive functional groups in cocaine?
methyl ester
why does procaine have a short duration of action?
due to its ester group which is abled to be broken down into an alcohol and a carboxylic acid by esterase’s- less potent
how do local anasthetics work?
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
do we really need the amine in local anasthetics?
yes- if IV- need to be able to be polar
no- if topical- but will not be as potent
what is the buchi model of anastetic binding
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.
what compound displays a 50 fold increase in binding over procaine?
Tetracaine
why does switching ester to amide increases stability?
as it is not efterified into an alcohol and carboxylic acid.- longer duration of action
what are the toxic s/e of lidocaine?
some CNS s/e
N-dealkylation after passing BBB