E9 The chemical basis of drug action 2

Question 1

What does histamine stimulate and how does it do this?

Answer 1

acid secretion by binding to H2 receptors in the parietal cells

Question 2

In H2 antagonists what is the imidazole ring responsible for?

Answer 2

adverse drug actions

Question 3

In H2 antagonists what is the thiazole and furan responsible for when with a ring substituent that is basic?

Answer 3

increases selectivity and potency pf antagonism at H2 receptors and reduces interactions with cytochrome P450

Question 4

Are PPIs reversible or irreversible?

Answer 4

irreversible

Question 5

How does omeprazole reach the target proton pump?

Answer 5

1) in stomach protected by enteric coatings remains prodrug
2) in duodenum it is uncharged so easily absorbed
3) in blood it is uncharged
4) then reaches parietal cells so becomes ionised forms active drug, reacts with target

Question 6

Omeprazole is unstable in acid needs to undergo reaction to produce the active drug molecule, what is meant by prodrug?

Answer 6

needs to be activated to become the active drug species

Question 7

How does omeprazole bind to the proton pump?

Answer 7

forms covalent (disulfide) bond with cysteine amino acid