The chemotherapeutic effects of H+/K+ inhibitors on Helicobacter pylori infection.
Helicobacter pylori's powerful urease enzyme is essential for colonisation and adaptation to the acid milieu of the stomach. Eradication of infection with "standard triple therapy" abolishes the chronic immunological and inflammatory responses to H. pylori and, thus, cures gastritis and peptic ulcer. In vitro, proton pump inhibitors (PPI) are active against H. pylori with minimum inhibitory concentrations that compare favourably with bismuth salts. PPIs are also potent urease inhibitors, but because PPIs are also active against urease-negative mutant Helicobacter spp., it is unlikely that urease inhibition alone accounts for their anti-H. pylori activity. Early reports suggested that omeprazole monotherapy was able to eradicate H. pylori. This has not been confirmed by more comprehensive studies, which have shown that treatment with omeprazole is associated with a shift of infection from the antrum to the corpus. The explanation for this observation is unclear, but does not appear to be due to bacterial overgrowth. Raising the intragastric pH with a PPI lowers the minimum inhibitory concentration of the many antimicrobials, while decreasing the acid storage pool increases the intramucosal concentration. Dual therapy (omeprazole with either amoxycillin or clarithromycin) is a more logical and highly effective alternative to standard triple therapy, with fewer side effects and better patient compliance. However, H. pylori eradication regimens based on a PPI and two antimicrobials will be the first-line treatment for H. pylori gastritis and peptic ulcer in the future.
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Parkside Helicobacter Study Group, Central Middlesex and St. Mary's Hospitals, London, UK.
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D015536:Down-Regulation; D004381:Duodenal Ulcer / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D064747:Lansoprazole; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011706:Pyloric Antrum / Q000201:enzymology*; D014510:Urease / Q000378:metabolism*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D004791:Enzyme Inhibitors; D064747:Lansoprazole; D014510:Urease; D009853:Omeprazole