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Pharmacology of PPIs -- Therapeutic Implications

Authors: Philip O. Katz, MDFaculty and Disclosures

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Introduction

Proton-Pump Inhibitors and GERD

Gastroesophageal reflux disease (GERD) affects 30% to 40% of individuals in the United States in their lifetimes.[1] Studies suggest that 5% to 25% of the population has heartburn or regurgitation, with an unknown number having extraesophageal symptoms, such as cough, laryngitis, or wheezing.[2,3] It is now clear that chronic, frequent heartburn is a risk factor for the development of esophageal adenocarcinoma (the fastest rising cancer in white men in the United States).

Management is based on the concept that acid and pepsin are responsible for esophageal injury and most symptoms of reflux disease. Pharmacologic treatment is based on the principle that controlling intragastric pH will facilitate esophageal healing and, subsequently, symptom relief. Control of pH can be accomplished with H2-receptor antagonists and proton-pump inhibitors (PPIs), which have become the mainstay of therapy. Although the majority of patients respond to a single daily dose of a PPI, patients with reflux disease may require higher doses and some are even "refractory" to twice-daily dosing of these drugs. The success of these agents, and in fact reasons for "failure," are elucidated by understanding the mechanism of action of PPIs and the effect of dose timing and meals on their efficacy. This article reviews the pharmacologic properties of PPIs and the impact on the treatment of GERD.