Proton Pump Inhibitors (PPIs)

Contributed by: Eric Ngo, Baylor College of Medicine, 1 Baylor Plaza, Houston, Tx 77030
Overview
  • Proton pump Inhibitors (PPIs) are a class of drugs that irreversibly bind to and potently inhibit the H-K ATPase of gastric parietal cells responsible for gastric acid secretion. They are commonly used in treatment of peptic ulcer disease and GERD
Mechanism of Action
  • PPIs are coated prodrugs that remain inactive until they reach the alkaline environment of the duodenum where they are absorbed and transported to parietal cells. As mentioned they irreversibly bind and inhibit the parietal cell H-K ATPase, yielding nearly 90% reduction of acid secretion by these cells.
Clinical Use
  • PPIs are used for diseases such as peptic ulcer disease, GERD, dyspepsia, Barrett Esophagus, gastrinomas, and Zollinger-Ellison Syndrome. Each pathology benefits from having decreased amounts of acid in their respective anatomical region.
Adverse Affects
  • PPIs are extremely well-tolerated drugs; however, prolonged achlorydria, or elevated stomach acid pH, may yield several consequences. For example, there is a theorotical risk of increased carcinoid tumor due to increased compensatory gastrin secretion. Long-term PPI use may cause enterochromaffin-like cell (ECL) hyperplasia and neoplasia. Case studies have shown well-differentiated, neuroendocrine tumor growth in patients on long-term PPI regimens that have shown resolution after cessation of PPI treatment.
  • Additionally, because low gastric pHs are required for Vitamin B12 absorption, prolonged PPI use may yield Vitamin B12 deficiency.
  • Finally, omeprazole specifically inhibits CYP450 enzymes which may decrease metabolism of Warfarin.
Member Drugs
  • PPIs as a class end in the suffix, “prazole”
    • Omeprazole
    • Lansoprazole
    • Pantoprazole
    • Esomeprazole