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Proton pump inhibitors

Last updated: March 25, 2021

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Proton pump inhibitors (PPIs) are a group of drugs used primarily to inhibit gastric acid secretion. They have largely replaced H2 blockers such as ranitidine in the management of conditions caused by excessive gastroesophageal acidity (e.g., dyspepsia, GERD, Barrett's esophagus, peptic ulcers). PPIs act by completely and irreversibly inhibiting the H+/K+ ATPase enzyme system (gastric proton pump) in the parietal cells of the stomach, resulting in decreased acid production and an increase in gastric pH. PPIs are available in oral and intravenous forms, of which the oral form is more commonly administered. Intravenous PPIs are reserved for management of severe disease, since they can cause irreversible visual disturbances in rare cases. Other side effects are predominantly gastrointestinal, including symptoms such as nausea and abdominal pain, and usually decrease during the course of treatment. Significant drug interactions occur especially with anticoagulants (warfarin, clopidogrel) and should be considered before prescribing PPIs.

  • Commonly used PPIs
    • Omeprazole
    • Esomeprazole
    • Pantoprazole
    • Lansoprazole, dexlansoprazole
    • Rabeprazole
  • Administration
    • 1 Tablet/day taken in the morning on an empty stomach (see “Effects” below)
    • Duration
      • 1–12 weeks depending on the underlying condition
      • Long-term administration for complicated disease, but should generally be avoided (see “Side effects” below)

The individual PPIs differ in their pKa, bioavailability, peak plasma levels, and route of excretion. However, because these differences have not yet proven to be clinically relevant, PPIs are often used interchangeably.
References:[1][2][3]

References:[1]

References:[1][5]

We list the most important adverse effects. The selection is not exhaustive.

References:[1]

Although several drug interactions are suspected, those with omeprazole and esomeprazole have proven to be of clinical significance, mainly in CYP2C19-mediated interactions:

References:[9]

  1. Katzung B,Trevor A. Basic and Clinical Pharmacology. McGraw-Hill Education ; 2014
  2. McCarthy DM. Adverse effects of proton pump inhibitor drugs: clues and conclusions. Curr Opin Gastroenterol. 2010; 26 (6): p.624-631. doi: 10.1097/mog.0b013e32833ea9d9 . | Open in Read by QxMD
  3. Gomm W, Von holt K, Thomé F, et al. Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis. JAMA Neurol. 2016; 73 (4): p.410-416. doi: 10.1001/jamaneurol.2015.4791 . | Open in Read by QxMD
  4. Fohl AL, Regal RE. Proton pump inhibitor-associated pneumonia: Not a breath of fresh air after all?. World J Gastrointest Pharmacol Ther. 2011; 2 (3): p.17-26. doi: 10.4292/wjgpt.v2.i3.17 . | Open in Read by QxMD
  5. De jager CP, Wever PC, Gemen EF, et al. Proton pump inhibitor therapy predisposes to community-acquired Streptococcus pneumoniae pneumonia. Aliment Pharmacol Ther. 2012; 36 (10): p.941-949. doi: 10.1111/apt.12069 . | Open in Read by QxMD
  6. Giuliano C, Wilhelm SM, Kale-pradhan PB. Are proton pump inhibitors associated with the development of community-acquired pneumonia? A meta-analysis. Expert Rev Clin Pharmacol. 2012; 5 (3): p.337-344. doi: 10.1586/ecp.12.20 . | Open in Read by QxMD
  7. Baker DE. Intravenous proton pump inhibitors. Rev Gastroenterol Disord. 2006; 6 (1): p.22-34.
  8. Pang SH, Graham DY. A clinical guide to using intravenous proton-pump inhibitors in reflux and peptic ulcers. Therap Adv Gastroenterol. 2010; 3 (1): p.11-22. doi: 10.1177/1756283X09352095 . | Open in Read by QxMD
  9. Wedemeyer RS, Blume H. Pharmacokinetic drug interaction profiles of proton pump inhibitors: an update. Drug Saf. 2014; 37 (4): p.201-211. doi: 10.1007/s40264-014-0144-0 . | Open in Read by QxMD
  10. Herold G. Internal Medicine. Herold G ; 2014
  11. Proton pump inhibitor (PPI) dosage and administration. http://www.nps.org.au/medicines/digestive-system/indigestion-reflux-and-stomach-ulcer-medicines/heartburn-and-reflux-medicines/for-health-professionals/dosage-and-administration. Updated: March 30, 2015. Accessed: February 21, 2017.