Proton-pump inhibitor

Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump. They are the most potent inhibitors of acid secretion available. Proton-pump inhibitors have largely superseded the H2-receptor antagonists, a group of medications with similar effects but a different mode of action.

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Proton pump inhibitors mechanism

Introduction

Proton-pump inhibitors (PPIs) are a class of drugs designed to dramatically decrease the production of gastric acid in the stomach. They accomplish this by irreversibly inhibiting the functionality of the stomach's H+/K+ ATPase (proton pump), an enzyme responsible for acid secretion. PPIs are considered the most effective inhibitors of gastric acid secretion currently available, and have largely replaced H2-receptor antagonists, which also inhibit acid secretion, but by a different mechanism.

Mechanism of Action of Proton-pump Inhibitors

PPIs function by selectively and irreversibly binding to the H+/K+ ATPase enzyme on gastric parietal cells. This enzyme is responsible for the final step in the production of gastric acid, namely the exchange of potassium ions (K+) for hydronium ions (H3O+) in the stomach.

By inhibiting the activity of this enzyme, PPIs effectively stop the secretion of gastric acid into the stomach. This action is dose-dependent and affects both basal and stimulated acid secretion, making PPIs the most potent inhibitors of acid secretion available.

Clinical Uses of Proton-pump Inhibitors

Proton-pump inhibitors have various clinical applications primarily related to conditions caused by excessive gastric acid secretion. These include:

• Gastroesophageal reflux disease (GERD): This is the most common use of PPIs, providing relief from the heartburn symptoms of GERD and allowing the esophagus to heal from any acid damage.
• Peptic ulcer disease (PUD): PPIs aid in the healing of gastric and duodenal ulcers and are also used in combination with antibiotics for eradication of Helicobacter pylori, a bacterium often associated with PUD.
• Zollinger-Ellison syndrome: This is a rare disorder characterized by severe peptic ulcers due to overproduction of gastric acid. PPIs are used to control acid hypersecretion.
• Prevention of Nonsteroidal anti-inflammatory drug (NSAID)-induced ulcers: Long-term use of NSAIDs can lead to peptic ulcers. PPIs are often co-prescribed with NSAIDs to prevent this.

Side Effects and Precautions

Although PPIs are generally well-tolerated, they are associated with several side effects and risks, including an increased susceptibility to gastrointestinal infections (due to the lack of protective gastric acid), vitamin B12 deficiency, and potential kidney disease with long-term use. Some studies have also suggested possible links to dementia and bone fractures, though these associations require further investigation.

Conclusion

Proton-pump inhibitors have revolutionized the management of acid-related disorders. Their potent acid-suppressive effects, combined with their safety profile, have made them an essential tool in the therapeutic arsenal against gastric acid-related conditions.

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References

• Sachs, G., Shin, J. M., & Howden, C. W. (2006). Review article: the clinical pharmacology of proton pump inhibitors. Alimentary Pharmacology & Therapeutics, 23, 2–8.
• Forgacs, I., & Loganayagam, A. (2008). Overprescribing proton pump inhibitors. BMJ, 336(7634), 2-3.
• Strand, D. S., Kim, D., & Peura, D. A. (2017). 25 Years of Proton Pump Inhibitors: A Comprehensive Review. Gut and liver.