The hydrogen-potassium ATPase pump, which is found on the luminal surface of the parietal cell membrane, is irreversibly bound to and inhibited by Proton Pump Inhibitors (PPI), which effectively stop stomach acid secretion. For the treatment of erosive esophagitis and as maintenance therapy in patients with severe erosive esophagitis or Barrett's oesophagus, PPIs are appropriate in patients with gastroesophageal reflux disease. The first-line antisecretory therapy for peptic ulcer disease is PPIs.
Proton Pump Inhibitors fall into two categories: irreversible inhibitors and reversible inhibitors. The pump enzyme is inhibited by irreversible covalent inhibitors, such as substituted 2-(pyridinemethylsulfinyl)benzimidazoles or pyridylmethylsulfinyl pyrido-imidazoles, which bind covalently to the H+,K+-ATPase -subunit. Mostly K+-competitive inhibitors, reversible proton pump inhibitors reduce the activity of the gastric H+,K+-ATPase by out-competing potassium ions. Since the H+,K+-ATPase was initially shown to be inhibited by a substituted benzimidazole, numerous PPIs have been created and are currently being used in therapeutic settings.
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