Gastrointestinal Side Effects of Proton Pump Inhibitors and H2 Receptor Antagonists

Side Effect Profiles

• The British Society of Gastroenterology guidelines note that long-term PPI use requires consideration of gastrointestinal infections, which can manifest as diarrhea 3
• PPIs' mechanism of profound acid suppression can lead to bacterial overgrowth and increased risk of infectious diarrhea, particularly Clostridioides difficile infection 3
• PPIs as a class are known to have gastrointestinal side effects, including diarrhea 2

Mechanism and Clinical Context

• The key mechanistic difference is that PPIs cause more profound acid suppression than H2 receptor antagonists, leading to altered gut microbiome 3
• The profound acid suppression caused by PPIs can also lead to increased susceptibility to enteric infections 3
• Osmotic effects from undigested nutrients can occur due to PPI use 4

Drug Interactions

• Ranitidine interacts weakly with cytochrome P-450 and has minimal drug interaction potential 1, 2, 4
• Famotidine (another H2 blocker) does not bind to the cytochrome P-450 system at all, making H2 blockers generally safer from a drug interaction standpoint 2, 4