med chem (SAR)

Question 1

are LA molecules acidic, basic, or neutral

Answer 1

basic

Question 2

to exhibit faster onset and lower toxicity, how should the
- lipid solubility
- pKa value
be?

Answer 2

high lipid solubility
low pKa values

Question 3

the sodium blocking action of LA is dependent on the pKa value. why should pH = pKa?

Answer 3

Allows presence of both unionised and ionised forms.

Unionised form allows penetration of membranes of nerve cells.
Ionised form allow interaction with sodium channel of target molecule

Question 4

how to eliminate addiction in benzotropine from cocaine

Answer 4

Removing carbomethoxy (COOCH3)

Question 5

why is methadone less euphorigenic and has less withdrawal effect

Answer 5

presence of diphenylpropylamine ring

Question 6

how to eliminate toxicity in cocaine to form procaine

Answer 6

replace tropine with amine

Question 7

how to reduce side effect and lengthen duration of action in morphine

Answer 7

glucuronidation to morphine-6-O glucuronide

Question 8

how to derive pentazocine from morphine which is non addictive

Answer 8

omit ether bridge, cyclohexene ring replaced by methyl groups

Question 9

for a molecule to demonstrate LA property, why must it have both lipophilic and hydrophilic properties?

Answer 9

lipophilic portion -> facilitate permeation
hydrophilic portion -> facilitate injectable formulation

Question 10

for the lipophilic portion at the intermediate chain, what is the requirement?

Answer 10

ester/amide with 1 to 3 carbon chain

Question 11

for the hydrophilic portion at the terminal portion, what is the requirement?

Answer 11

needs to be basic and ionisable to give cation.

2 or 3 degree amine OR
N part of heterocycle.

Question 12

why does procaine have increased local anaesthetic activity?

Answer 12

addition of terminal amino alcohol to form a benzoyl ester

Question 13

why is fentanyl more lipophilic (better transport) and more potent than morphine?

Answer 13

replacement of 4-phenyl-piperidine in morphine with 4 anilino structure

Question 14

why does lidocaine have LA activity but isogramine (derivative) does not have?

Answer 14

formation of lipophilic amide group via ring opening from isogramine

Question 15

why is codeine less potent than morphine

Answer 15

mono-o-methylation at phenolic hydroxyl group

Question 16

why does diamorphine have better absorption and transport than morphine

Answer 16

addition of an acetyloxy group to the phenyl ring increasing lipophilicity

Question 17

how to reduce a drug’s chances of degradation

Answer 17

replace ester groups with amide , less prone to hydrolysis