استعرض مصدر Review article: the clinical pharmacology of proton pump inhibitors




Review article: the clinical pharmacology of proton pump
inhibitors

G. SACHS* ,J.M.SHIN* &C.W.HOWDEN

Aliment  Pharmacol  Ther 23 (Suppl. 2), 2–8


SUMMARY

Proton pump inhibitors inhibit the gastric H+/K+-ATPase via covalent
binding to cysteine residues of the proton pump. All proton pump
inhibitors must undergo acid accumulation in the parietal cell through
protonation, followed by activation mediated by a second protonation
at the active secretory canaliculus of the parietal cell.
The relative ease with which these steps occur with different proton
pump inhibitors underlies differences in their rates of activation, which
in turn influence the location of covalent binding and the stability of
inhibition. Slow activation is associated with binding to a cysteine resi-
due involved in proton transport that is located deep in the membrane.
However, this is inaccessible to the endogenous reducing agents responsible for restoring H + /K + -ATPase activity, favouring a longer duration of gastric acid inhibition. Pantoprazole and tenatoprazole, a novel pro-
ton pump inhibitor which has an imidazopyridine ring in place of the
benzimidazole moiety found in other proton pump inhibitors, are acti-
vated more slowly than other proton pump inhibitors but their inhibi-
tion is resistant to reversal. In addition, tenatoprazole has a greatly
extended plasma half-life in comparison with all other proton pump
inhibitors.

The chemical and pharmacological characteristics of tenatoprazole
give it theoretical advantages over benzimidazole-based proton pump
inhibitors that should translate into improved acid control, particularly
during the night.

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2006.02943.x/pdf

[[تصنيف:Proton pump inhibitors and vision]]