Terms in this set (125)

First in the blood, they are not ionized, the picture is the parietal cell that is in the stomach lining

The cytosol of the parietal cell ahs a pH of 7.1 almost neutral pH so they are NOT activated there

Once they enter this Canalicular lumen, which is the lumen that secretes the protons, it has the pumps, the pH of this lumen is 0.8, very acidic pH, 0.8; much lower than the stomach pH and because of that low pH the drugs gets ionized and they get concentrated because of ion trapping (they are trapped inside the cell), they get converted into the active form and they can inhibit the pump

So it gets activated and the S=O bond is broken and we have S—OH and it becomes ionized. This is good because it is at the active site, if this was in the stomach then the drug will be deactivated because they cannot inhibit the pump from the stomach, they have to enter the blood first then get to the site of action. So we get sulfuric acid

If you rearrange this, you form a cyclic form (cyclic sulfenamide) so sulfa again gets attached to the nitrogen here and we have a cyclic ring so we started with 3 cyclics and now we formed 4 cyclic forms and by doing that we lost the chirality of the drug and form the achiral, so now its achiral optically active. So whether you start with R or S isomer, you will only get one product which is not chiral, it is 4 cyclic ring. You only get one active drug which has free sulfur and the free sulfur can bind with the cysteine of the proton pump and form covalent bond (irreversible)

PPI's have delayed onset and longer DOA; it takes time to show effect because they can inhibit more than 90% of the pump, but it could be over a few days; and it is active for a longer time. Because it is irreversible, we have to resynthesize new pumps because these pumps are non-functional, they won't go back to the original state. So even if you stop taking PPIs, you will still have the effect of the drug for 4-5 days because of that covalent bond
At this stage we don't see any benefit of S omeprazole vs R
Remember this activation pathway