Does long-term medication with a proton pump inhibitor induce a tolerance to H2 receptor antagonist?

J Gastroenterol. 2007 Apr;42(4):275-8. doi: 10.1007/s00535-006-1946-3. Epub 2007 Apr 26.


Background: Previous reports suggest that complete tolerance to H2 receptor antagonists (H2RAs) in patients with regular H2RA medication may be due to hypergastrinemia-increased histamine synthesis or upregulation of H2 receptors. As proton pump inhibitors (PPIs) have been reported to induce hypergastrinemia (similar to H2RAs), patients receiving long-term medication with PPIs may show tolerance to preanesthetic H2RA. Therefore, we studied the efficacy of an H2RA, roxatidine, in patients receiving long-term PPI medication.

Methods: Effects of H2RA in 15 surgical patients receiving a regular PPI for more than 4 weeks (PPI+H2RA group) were compared with those in 30 patients not receiving regular PPIs or H2RAs (None+H2RA group and None+None group, n = 15 each). Oral roxatidine was given to both PPI+H2RA and None+H2RA group patients as an anesthetic premedication, while it was not given to None+None group patients. Gastric volume and pH were measured after induction of anesthesia.

Results: Gastric pH and volume (ml) in the PPI+H2RA group (5.79 +/- 1.61 and 9.1 +/- 16.7, respectively) were both similar to those in the None+H2RA group (5.54 +/- 2.20 and 9.7 +/- 10.8, respectively) but were significantly higher (gastric pH) and lower (volume) than in the None+None group (2.29 +/- 1.84 and 29.3 +/- 22.8, respectively, P < 0.01).

Conclusions: These data suggest that long-term PPI medication may not induce a tolerance to H2RAs.

MeSH terms

  • Drug Tolerance*
  • Female
  • Gastric Acid / metabolism
  • Gastric Acidity Determination
  • Histamine H2 Antagonists / pharmacology*
  • Humans
  • Male
  • Middle Aged
  • Piperidines / pharmacology*
  • Pneumonia, Aspiration / prevention & control
  • Proton Pump Inhibitors*
  • Time Factors


  • Histamine H2 Antagonists
  • Piperidines
  • Proton Pump Inhibitors
  • roxatidine acetate