Antimicrobial Properties of Proton Pump Inhibitors

Abstract

Proton pump inhibitors [PPI] are acid activated pro drugs which convert in to sulfenic acid and then in to tetracycline sulfenamide in the acidic pH of parietal cell canaliculi. They block H+K+ATPase proton pumps and reduce gastric acid secretion. They are used to treat acid peptic disorders and NSAID induced gastric mucosal injury. Activity of PPI against Helicobactor pylori [H.pylori] is proved undisputably. Lansoprazole is the most effective PPI against H.pylori due to its unique chemical structure.PPI inhibit urease activity of H. pylori. They affect respiration and energy metabolism of these organisms as result of decreased ATP synthesis. Structural similarity of benzimidazole PPI with imidazole like metronidazole and tinidazole may contribute for their antibacterial property. Omeprazole and lansoprazole have been found to have anti fungal activity by inhibition of fungal H+K+ATPase-vacuolar ATPase which are essential for fungal survival and to carry out essential physiological functions, the inhibition of which leads to fungicidal action. Recently anti tubercular action of lansoprazole was highlighted which is attributed to its intra mycobacterial sulfoxide reduction to lansoprazole sulfide. This acts on mycobacterial cytochrome bc1 complex and inhibits ATP synthesis and compromises energy metabolism threatening its survival. Cytochrome bc1 of plasmodium also forms a drug target for lansoprazole. Thus, lansoprazole can emerge as a potential drug to treat MDR tuberculosis and malaria. Antiviral action of lansoprazole was noted against rhinovirus. Gram positive and negative organisms other than H.pylori were found to be inhibited by omeprazole in vitro. But this is not supported by in vivo studies.