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

Background. Previous reports suggest that complete tolerance to H-2 receptor antagonists (H2RAs) in patients with regular H(2)RA medication may be due to hypergastrinemia-increased histamine synthesis or upregulation of H-2 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 H(2)RA. Therefore, we studied the efficacy of an H(2)RA, roxatidine, in patients receiving long-term PPI medication. Methods. Effects of H(2)RA in 15 surgical patients receiving a regular PPI for more than 4 weeks (PPI+H(2)RA group) were compared with those in 30 patients not receiving regular PPIs or H2RAs (None+H(2)RA group and None+None group, n = 15 each). Oral roxatidine was given to both PPI+H(2)RA and None+H(2)RA 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+H(2)RA group (5.79 +/- 1.61 and 9.1 +/- 16.7, respectively) were both similar to those in the None+H(2)RA 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.