| Theme | Comparison of PPIs and H2RAs in the Actions and Suitable Use for the Diseases | |
|---|---|---|
| Title | Histamine H2-Receptor Antagonists (H2RAs) or Proton Pump Inhibitors (PPIs) Do Not Necessarily Provide Sufficient Acid-suppressive Efficacy in All Cases | |
| Publish Date | 2005/07 | |
| Author | Tomohiko Shimatani | Department of General Medicine, Hiroshima University Hospital |
| Author | Masaki Inoue | Department of Geriatric Health Sciences, Graduate School of Health Sciences, Hiroshima University |
| [ Summary ] | The acid-suppressive efficacy of H2RAs significantly decreases with continuous administration, and is described as “tolerance”. During the long-term administration of H2RAs, the number of histamine H2-receptors on parietal cells increases significantly and endogenous histamine stimulates gastric acid secretion via H2RA-unbound histamine H2-receptors. Reduced gastric emptying interferes with the absorption of PPIs and results in insufficient inhibition of gastric acid secretion. Plasma concentrations of PPIs may increase after a change from single-unit enteric-coated PPI tablets to multiunit enteric-coated granules in capsules. In most patients treated with PPIs gastric acid secretion recovers at night and intragastric pH decreases below 4.0 for more than 1 h during the overnight period. This is defined as “nocturnal gastric acid breakthrough (NAB)”. The mechanisms associated with NAB are unclear, but endogenous histamine may play a major role in nocturnal gastric acid secretion during administration of PPIs. Plasma concentrations of PPIs depend on the cytochrome P 450 2C19 (CYP2C19) genotype status, therefore, inter-individual variations in acid-suppressive efficacy are great. Standard dosages of PPIs appear to be insufficient for patients with the homozygous extensive metabolizer genotype status of CYP2C19. Changing the formulation and / or doubling the dosage are both effective to compensate for reduced acid-suppressive efficacy in the treatment of H2RAs / PPIs-resistant ulcers and reflux esophagitis. |
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