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 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 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 acidic space of the secretory duct in the parietal cells (1). PPI then irreversibly inactivate 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

(Berufsfachschule für Pflege Kronach, Bildungszentrum Kronach)

Friesener Str. 41
96317 Kronach

Germany

https://www.helios-gesundheit.de/karriere/standorte/kronach/ausbildung/bildungszentrum/

E-Mail: [email protected]

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.