| 特集名 | PPI・H2RAの使い分け | |
|---|---|---|
| 題名 | 作用特性 (2) 薬剤耐性におけるPPI・H2RAの比較 | |
| 発刊年月 | 2005年 07月 | |
| 著者 | 島谷 智彦 | 広島大学病院医系総合診療科 |
| 著者 | 井上 正規 | 広島大学大学院保健学研究科老年期健康学 |
| 【 要旨 】 | ヒスタミンH2受容体拮抗薬 (H2RA) には継続投与中に胃酸分泌抑制効果が減弱するトレランスという現象があり，壁細胞上のヒスタミンH2受容体のup-regulationによると考えられている． プロトンポンプ阻害薬 (PPI) は長時間，胃酸に接触すると失活する可能性があり，胃排出が遅延した症例では注意が必要である．また，チトクロームP 450 2C19 (CYP2C19) の遺伝子多型に基づく代謝酵素活性の個人差があり，胃酸分泌抑制に大きく影響する．さらに，深夜に胃酸分泌が一時的に回復するnocturnal gastric acid breakthrough (NAB) という現象があり，内因性のヒスタミン刺激による胃酸分泌と考えられている． |
|
| 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 | |
| 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. |
|