Mini-Review on Proton Pump
Inhibitors PPI with Focus on their
Mechanism of Action
Maren Haslach-Häfner, B.A.
Berufsfachschule für Pflege Kronach, Helios Bildungszentrum Kronach, Germany
Proton pump inhibitors (PPI=are the most common medications utilized to treat
upper gastrointestinal bleeding resulting from acid-peptic disorders and
ingestion of non-steroidal anti-inflammatory agents (NSAIDs). The aim of this
mini review is to explain the mechanism of action in a practical manner. The
following figures show the PPI on the parietal cell of the stomach in a simplified
manner. The task of the proton pump is primarily to secrete hydrochloric acid
from the parietal cells of the gastric mucosa, in conjunction with food intake as a
stimulus. The H+K+ATPase is responsible for this active transport, i.e. proton
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exchange H+ from the cell for potassium ions K+ into the cell (Figures 1-4).
Figures 1-4: Pharmacokinetics of PPI (own presentation, graphics by Kirsten
Tucker, 2023). PPIs do not act immediately after ingestion. Once they have
passed through the stomach (Figure 1) and the enteric coating has dissolved in
the small intestine, PPIs are absorbed into the blood (Figure 2) where they have a
relatively short plasma half-life of 1 – 1.5 hours. After being absorbed from the
small intestine, they reach the bloodstream via the portal vein system, where
they undergo the first pass effect of the liver by CYP2C19 and CYP3A4 (1). Then
the PPI metabolites continue to travel in the bloodstream, and they are absorbed
from the bloodstream into the parietal cells of the stomach, the place where
they ultimately intervene in the final secretion process (Figure 3). Indeed, PPIs
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are prodrugs that activate their effect in the acidic environment of the secretory
canaliculi of the parietal cells (Figure 3). PPIs are referred to as weak bases with a
pKa of 3.89 to 4.9, which allows them to accumulate in the acinactivateidic space
of the secretory duct in the parietal cells (1). PPI then irreversibly the proton
pump by the covalent modification associated with cysteine residues on the
luminal side of the H+K+ATPase (Figure 4). This compound causes acid secretion
inhibition to be longer than the PPI half-life. This is preceded by protonation
into a tetracyclic sulfenamide or a sulfenic acid, which is now no longer
permeable to membranes (2). This acid inhibition represents a more specific
blockade than the H2 receptor or acetylcholine and gastrin blockade, regardless
of the type of acid stimulation (2).
References:
1. Shin JM, Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol
Rep. 2008 Dec;10(6):528-34. doi: 10.1007/s11894-008-0098-4. PMID: 19006606;
PMCID: PMC2855237.
2. Olbe L, Carlsson E, Lindberg P. A proton-pump inhibitor expedition: the case
histories of omeprazole and esomeprazole. Nat Rev Drug Discov. 2003
Feb;2(2):132-9. doi: 10.1038/nrd1010. PMID: 12563304.
Corresponding Author:
Maren Haslach-Häfner, B.A.
Berufsfachschule für Pflege der Helios
Gesellschaft für berufliche Bildung mbH in Kronach
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pi-with-focus-on-their-mechanism-of-action
(Berufsfachschule für Pflege Kronach, Bildungszentrum Kronach)
Friesener Str. 41
96317 Kronach
Germany
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entrum/
E-Mail: [Link]-haefner@[Link]
Editorial Office Comments: date submitted 29. August, 2024; peer reviewed 3.
September 2024; accepted for publication on 5. September, 2024; Author notified on 5.
September, 2024.
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