16.01.2 Proton Pump Inhibitors (PPIs) and Antibiotics for Helicobacter Pylori

The most effective way to overcome excess acid, being produced from the parietal cells of the stomach, is to use proton pump inhibitors. This is because regardless of what is stimulating the acid secretion (histamine, gastrin and acetylcholine), inhibiting the proton pump will inhibit acid secretion. This makes the proton pump inhibitors the most effective inhibitors of acid secretion.

Omeprazole is the prototype proton pump inhibitor but there are other –prazoles in clinical use. The proton pump inhibitors are prodrugs, requiring activation in an acidic environment. To avoid activation of the omeprazole by the acid in the oesophagus and stomach, omeprazole is supplied as enteric-coated granules that dissolve only at an alkaline pH, which limits absorption to the intestine. Omeprazole is then carried in the blood stream until it is activated in the acid environment of the stomach.

The proton pump inhibitors inhibit the activity of some cytochrome P45O enzymes, and may decrease the clearance of benzodiazepines, phenytoin and warfarin, which will increase the concentration and increase the toxicity of these medicines. Proton pump inhibitors are used in the treatment of GERD and peptic ulcers, and in the prevention of NSAIDs-induced ulcers.

Up to 90% of peptic ulcers may be associated with Helicobacter pylori infections of the stomach leading to increased stimulation of acid secretion. H. pylori are Gram-negative rods. Unfortunately, single antibiotic regimens are ineffective as resistance has developed to H. pylori. Indeed, antibiotic resistance is preventing the elimination of H. pylori. The preferred combination of antibiotics used to kill H. pylori is amoxicillin and clarithromycin. These antibiotics are generally used in combination with a proton pump inhibitor. Besides reducing the acid secretion, the proton pump inhibitor enhances the effectiveness of pH-dependent antibiotics such as amoxicillin or clarithromycin.