title: Does long-term medication with a proton pump inhibitor induce a tolerance to H2 receptor antagonist?
abstract: 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.
authors.affiliation: Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki, Aomori 036-8563, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kushikata
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kudo
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hirota
mesh_terms: D004361:Drug Tolerance; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005745:Gastric Acidity Determination; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000494:pharmacology*; D011015:Pneumonia, Aspiration / Q000517:prevention & control; D054328:Proton Pump Inhibitors; D013997:Time Factors
chemical_list: D006635:Histamine H2 Antagonists; D010880:Piperidines; D054328:Proton Pump Inhibitors; C053742:roxatidine acetate