Lecture 3 - Chemistry & Targets of PPIs & H2 antagonists Flashcards
What was pyridylthioacetamide made to do?
Antiviral drug
showed to slow down gastric secretion as a side effect
What did timoprazole prevent?
Uptake of iodine by the thyroid
Why is omeprazole given as the unionised form?
This allows it to diffuse through the fatty secretory canals of the parietal cells
What happens once omeprazole is inside the cells?
The pyridine ring becomes protonated and that in turn enables the amine to be protonated and the whole molecule is ionised
What is the pH of the parietal cells?
~1
What happens once omeprazole is completely ionised?
It cannot diffuse back out of the cell, this is known as ion trapping
What does ion trapping cause?
A build up in concentration of omeprazole, the chemical conversion of omeprazole then occurs
What is omeprazole converted to?
Active sulphenamide
What causes maximal conversion to the sulphenamide?
the steep proton gradient caused by the H+/K+ATPase enzyme
There is then ion trapping of what?
Both omeprazole and the sulphenamide
What is the sulphenamide trapped in the cells as?
the permanently charged quaternary ammonium salt
Where does omeprazole act?
specifically in the parietal cells
What does sulphenamide react with?
irreversibly with thiol groups in H+/K+ATPase enzyme which forms stable disulphide complex (covalent bond)
very strong bond
What does the disulphide complex mean?
no more acid is produced until new enzyme is made
this results in long duration of inhibition of gastric acid production
what is omeprazole used to treat?
duodenal ulcers and erosive oesophagitis
