C6 The chemical basis of drug action 3 Flashcards
(32 cards)
what does omeprazole inhibit and how?
- inhibits the proton pump in parietal cells
- binds irreversibly to the proton pump
which is more basic: pKa 4 or 0.79?
- pKa 4 is more basic
the pKa of omeprazole is 4. describe the percent ionisation at pH 2, 3, 4, 5 and 6.
- pH 2 = 99% therefore largely charged and minimally absorbed
- pH 6 = 1% and maximally absorbed
compare and explain absorption differences of omeprazole in the stomach and duodenum
- stomach: high extent of ionisation and minimal absorption
- duodenum: lower pH, less ionisation and more absorption
describe the pathway of omeprazole absorption starting at the stomach
- stomach
- duodenum
- blood
- parietal cells (extracellular space, adjacent to proton pumps)
explain what occurs at the stomach stage of omeprazole absorption
- pH 1-2
- protected by enteric coating
- remains as prodrug
explain what occurs at the duodenum stage of omeprazole absorption
- pH 6-6.5
- unchanged
- easily absorbed
explain what occurs at the blood stage of omeprazole absorption
- pH 7.4
- uncharged
- systemic circulation
explain what occurs at the parietal cells stage of omeprazole absorption
- pH ≤ 2
- ionised
- forms active drug
- reacts with target
explain the ion trapping of omeprazole
- omeprazole crosses into parietal cell (extracellular) when unionised
- then becomes ionised in the acidic environment of the parietal cell
- can then not cross back to intracellular environment
what kind of drug is omeprazole? (not PPI)
prodrug (needs to be activated to become the active drug species)
describe omeprazole in acid
- unstable
- undergoes a reaction to produce the active drug molecule
what does activated omeprazole form?
- covalent (disulphide) bond with an accessible cysteine amino acid in the proton pump
- disulphide bridge forms between cysteine residue in proton pump and activated omeprazole to block proton pump
explain the stereochemistry of omeprazole
- sulphur can be a chiral centre which allows for S and R configurations
what are me-too drugs?
similar to structural similarity in H2 receptor antagonist drugs
what is the chemical equation for the 13C urea breath test?
what is the urease enzyme produced by? what does it do?
- H. pylori
- protects bacterium from acid by producing NH3 which neutralises stomach acid
compare 12C and 13C
- both naturally occurring
- both non-radioactive isotopes of carbon
- slightly higher stomach pH from produced urea allows bacteria to survive
track the isotopic carbon in the equation for the urea breath test and describe the start and beginning
how is the 13C enriched carbon dioxide detected?
- 13CO2 : 12CO2 ratio measured in both breath samples obtained
- mass spectrometry
- infrared spectroscopy
- 2 above techniques can detect small difference in mass
what difference is detected between the 1st and 2nd breath samples in the urea breath test?
to see if 13C carbon dioxide proportion has increased
explain the hydrolysis of urea by the equations (3 equations). also state where the product is absorbed into and how its eliminated
what is a common feature of NSAIDs?
weak, organic acids
in this image, 2 NSAIDs are shown. describe them at physiological pH
these will be essentially completely ionised
