Drug delivery to the lungs

Question 1

Suggest two limitations of using adrenaline for the treatment of asthma

Answer 1

Short duration of action AND
no selectivity for B2-receptor so side effects such as cardiovascular effects

Question 2

Compare the structures of adrenaline, isoprenaline and isoetharine and use this to identify structural features that have enhanced the selectivity between beta and alpha receptors, and between beta 2 and beta 1- receptors.

Answer 2

Adrenaline binds to both beta and alpha receptors
addition of an alkyl side chain was added to improve selectivity for beta over alpha receptors but not beta 2 over beta 1. (Isoprenaline)
extra alkyl was added which was selective to beta 2 but short acting. (Isoetharine)

Question 3

Metabolism of which functional group in isoetharine is responsible for the short duration of action?

Answer 3

Cathecol

Question 4

Why is salbutamol chosen over isoetharine

Answer 4

it has better selectivity to B2 over B1
it is not metabolised by COMT
it has better duration of action

Question 5

explain the difference in the use of adrenaline and salbutamol in the treatment of asthma

Answer 5

adrenaline is used in emergency in clinics wile salbutamol is used in the routine treatment of asthma

Question 6

what is chiral switching

Answer 6

where you initially take a racemic compound and develop a single enantiomer for use in the clinic.
(So they make a single drug with just one of the enantiomer)

Question 7

Give two advantages of chiral switching.

Answer 7

more business opportunity.
May offer better therapeutic properties if single enantiomer is more effective than the racemic drug

Question 8

Compare the structures of salbutamol and salmeterol and explain why salmeterol has a longer duration of action than salbutamol.

note : Salmeterol had longer chain in diagram with hydrophobic group which they labeled

Answer 8

The N-side chain is more lipophilic in salmeterol and so it binds more strongly to the tissue therefore longer duration of action of drug.

Question 9

Notes.( just to know)
- Antiasthmatic drugs are usually taken by inhalation, but with poor inhalation technique, the patient can instead swallow it leading to the drug getting into the blood supply instead of lungs , leading to side effects.
- Researchers are looking for tricks and functional groups that can be done so if a drug gets into the blood supply, it can be quicky metabolised instead of stgaying in the blood stream for long.
- E.g Esther groups as there’s esterase in the blood to destroy the active compound

Question 10

how can you increase activity of a drug

Answer 10

Increase the size of N-alky substituent to increase potency at b receptors.
Increasing the length of the N-alkyl substituent by Introducing hydrophobic chains, will increase lipophilicity of the drug (drug will bind more strongly to tissue) therefore longer duration of action of drug.

Question 11

Give an example of chiral switching

Answer 11

salbutamol is a racemate mixture
The R enantiomer is more active than S as the S accumulates more in the body and produces side effects pure R-enantiomer (levalbuterol) was eventually marketed.