C6. The chemical basis of drug action 3

Question 1

Describe omeprazole

Answer 1

-Omeprazole inhibits the proton pump in the parietal cells
-Binds irreversibly to the proton pump
-Weak base with pKa = 4.0 and 0.79
-ionisation of omeprazole varies along the GI tract as pH varies along the GI tract
ONE NOTE

Question 2

how to predict percentage ionization from pKa and pH values?

Answer 2

-Rule of thumb: pKa +/- 1 pH unit ionisation is 10% / 90% or 90% / 10%
-Rule of thumb: pKa +/- 2 pH units ionisation is 1% / 99% or 99% / 1%
FOR IONISATION LOOK AT ONE NOTE

Question 3

Describe the journey of omeprazole. How does it reach the target proton pump?

Answer 3

one note

Question 4

Omeprazole is a prodrug, what does this mean?

Answer 4

-It needs to become activated to become the active drug species
-Omeprazole is unstable in acid, it undergoes a reaction to produce the active drug molecule
ONE NOTE

Question 5

what does activated omeprazole do?

Answer 5

Activated omeprazole forms covalent (disulfide) bond with an accessible cysteine amino acid in the proton pump
ONE NOTE

Question 6

Stereochemistry of omeprazole?

Answer 6

ONE NOTE

Question 7

What does urease enzyme do?

Answer 7

urease enzyme produced by H. pylori protects bacterium from acid by producing NH3 which neutralises stomach acid
ONE NOTE

Question 8

Describe 13C urea breath test

Answer 8

-Detection of 13C enriched carbon dioxide gas:
13CO2:12CO2 ratio measured in both breath samples obtained
Mass spectrometry
Infrared spectroscopy
ONE NOTE

Question 9

Describe NSAIDs and molecular interactions

Answer 9

ONE NOTE

Question 10

Describe hydrolysis of aspirin

Answer 10

ONE NOTE