[Mechanisms of direct gastric mucosal damage by NSAIDs].

Since gastric mucosal membrane, that is the most important part of mucosal barrier, is a lipid-protein layer, ionized and water-soluble NSAIDs are restricted in their transport. In the highly acidic condition of gastric juice, however most of NSAIDs are non-ionized and fat-soluble, dissolve rapidly in lipid-protein layer, and is rapidly absorbed from the acid gastric contents. Within the gastric mucosal cells in neutral condition, NSAIDs are ionized and H+ ions are released. Intracellular NSAIDs cause impairment of gastric mucosal barrier by reduction and alteration of mucous secretion and/or reduction of mucosal ATP. Intracellular H+ ions provoke the mast cells to release histamine which causes mucosal micro-vascular damage. Finally, auto-digestion by gastric juice in this impaired mucosa makes the variegated mucosal lesions.

The pharmacodynamic effect of omeprazole 10 mg and 20 mg once daily in patients with nonerosive reflux disease in Japan.

BACKGROUND: To evaluate the pharmacodynamic effect, efficacy, and safety of omeprazole 10 mg and 20 mg once daily in patients with nonerosive reflux disease (NERD) in Japan. METHODS: A total of 37 patients were randomized to omeprazole 10 mg or omeprazole 20 mg once daily for 4 weeks. Eligible patients had a history of moderate-to-severe heartburn for 2 days or more per week during the last 1 month or longer prior to the study screening, grade M or grade N on Hoshihara's modification of the Los Angeles classification (i.e., no sign of mucosal break on esophagogastroduodenoscopy), and heartburn episodes for 2 days or more per week during the last week of the observation period while taking antacids. Ambulatory 24-h intraesophageal pH was monitored on the day before treatment and on the last day of treatment. The occurrence of a heartburn episode was recorded during pH monitoring. The primary endpoint was the change in the percentage of time with intraesophageal pH < 4 during the 24-h period before and after omeprazole treatment. RESULTS: Both omeprazole 10 mg and omeprazole 20 mg once daily reduced the percentage of time with intraesophageal pH < 4. The percentage reduction in time with intraesophageal pH < 4 after treatment with omeprazole was associated with a reduced number of heartburn episodes. Patients with grade M or grade N esophagus had similar pH profiles and NERD characteristics (e.g., pH holding time, symptom index) and comparable responses to omeprazole. No serious, drug-related adverse events were reported. CONCLUSIONS: Omeprazole 10 mg or 20 mg reduces the percentage of time with intraesophageal pH < 4, is efficacious, and is well tolerated in patients with NERD in Japan, regardless of the patient's endoscopic classification.