Proton pump inhibitor

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Proton pump inhibitors (PPIs) are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar effects, but different mode-of-action, called H2-receptor antagonists. These drugs are among the most widely-selling drugs in the world and are generally considered effective.[1] The vast majority of these drugs are benzimidazole derivatives; however, promising new research indicates that imidazopyridine derivatives may be a more effective means of treatment.[2] High dose or long-term use of PPIs carry a possible increased risk of bone fractures.[3]

Contents

Clinical use

These drugs are utilized in the treatment of many conditions such as:

The effectiveness of proton pump inhibitors has not been demonstrated in every case, despite their widespread use for these conditions. For example, proton pump inhibitors do not change the length of Barrett's esophagus.[4] The most objective test to assess success of PPI therapy in patients with GERD is Esophageal pH Monitoring.

The FDA advises that no more than three 14-day treatment courses should be used in one year.[3]

Mechanism of action

Proton pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H+/K+ ATPase, or more common gastric proton pump) of the gastric parietal cells. The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H+ ions into the gastric lumen, making it an ideal target for inhibiting acid secretion. ("Irreversibility" refers to the effect on a single copy of the enzyme; the effect on the overall human digestive system is reversible, as the enzymes are naturally destroyed and replaced with new copies.)

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