arbaprostil and Gastrointestinal-Hemorrhage

The deleterious effects of aspirin on gastric mucosa have been well documented in experimental and clinical studies. Prostaglandins offer a potential method by which this injury may be prevented. In these studies, we developed a single-dose endoscopic assay system of aspirin-induced gastric mucosal injury in normal volunteers. With this system, 27 of 30 volunteers (90%) demonstrated severe mucosal injury after ingestion of aspirin. Subsequently, we evaluated whether pretreatment with 15-R-15 methyl prostaglandin E2 prevented severe injury after ingestion of aspirin. Following an initial dose-response study, a double-blind crossover trial was performed using pretreatment with placebo or with 10-micrograms doses of 15-R-15 methyl prostaglandin E2 for 24 h before treatment with aspirin. The results of this trial indicate that prostaglandin pretreatment significantly prevented the occurrence of endoscopically visible severe gastric mucosal injury after single-dose aspirin administration.

Topics: Adolescent; Adult; Arbaprostil; Aspirin; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Endoscopy; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Male; Prostaglandins E, Synthetic

A prospective, randomized trial was designed to compare the relative efficacy of 15 (R)-15-methyl prostaglandin E2 with antacid (usually Mylanta II) in 46 patients admitted to a respiratory-surgical intensive care unit. Bleeding was assessed by a modification of the Hemoccult slide test. Three of 22 patients in the antacid group bled, and 12 of 24 patients in the prostaglandin group bled, for a highly significant difference (p = 0.008). Patients in whom prophylaxis failed tended to have a greater number of risk factors. Other prostaglandin analogues that do not require conversion from an inactive to an active form, may be more useful than the agent we studied. Based on currently available data, the hourly titration of the gastric juice to a pH of greater than 3.5 remains the preferred method of prophylaxis for acute bleeding from the stomach in seriously ill patients.

Topics: Aged; Aluminum Hydroxide; Antacids; Arbaprostil; Clinical Trials as Topic; Drug Combinations; Female; Gastric Acid; Gastric Acidity Determination; Gastrointestinal Hemorrhage; Humans; Magnesium Hydroxide; Male; Postoperative Complications; Prospective Studies; Prostaglandins E, Synthetic; Random Allocation; Risk; Simethicone

Thirteen patients who had rheumatoid arthritis and gastroduodenal lesion (erosions, ulcers) received 200 micrograms/d of 15(R)-15-methyl prostaglandin E2 (MPGE2) for one month in a controlled, randomized, double-blind crossover study. The patients continued their usual arthritis medications. Serial assessments were made with endoscopy and multiple antral biopsies. Seven patients improved on MPGE2 and 3 improved on placebo. Two patients worsened on MPGE2 compared with 3 on placebo. No dramatic benefit was observed after one month of therapy with MPGE2, although a moderate benefit could have been missed in a small study of this type. Our experience with this study suggests that future studies in rheumatoid arthritis should first establish the natural history of lesions in a given group of patients, that a cross-over design may actually hamper interpretation and that therapy should be more prolonged.

Topics: Adult; Aged; Anti-Inflammatory Agents; Arbaprostil; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Gastrointestinal Hemorrhage; Humans; Middle Aged; Prostaglandins E, Synthetic

The efficacy of sucralfate, 15(R)15-methyl prostaglandin E2, and cimetidine in protecting against ethanol injury in rat stomachs was examined. Rats that had been fasted were pretreated intragastrically with either sucralfate 160 mg/kg, 15(R)15-methyl prostaglandin E2 16 micrograms/kg, cimetidine 100 mg/kg, or an equal amount of vehicle alone (control). One hour later, all rats received 1 ml of 99.5 percent ethanol orally and were killed 15 minutes or 24 hours later. Stomachs were removed, and mucosal damage was assessed macroscopically as well as by scanning electron microscopy. Pretreatment with either 15(R)15-methyl prostaglandin E2 or sucralfate significantly reduced the number and extent of ethanol-induced mucosal gastric lesions; pretreatment with cimetidine, however, failed to produce positive results. It is concluded that the abilities of 15(R)15-methyl prostaglandin E2 and sucralfate in protecting against ethanol injury are comparable.

Topics: Animals; Arbaprostil; Basement Membrane; Cimetidine; Drug Interactions; Epithelium; Ethanol; Gastric Mucosa; Gastrointestinal Hemorrhage; Male; Microscopy, Electron, Scanning; Prostaglandins E, Synthetic; Rats; Stomach Ulcer; Sucralfate

A 19-yr-old male developed severe hemorrhagic gastritis following three abdominal operations. Treatment with intravenous cimetidine and hourly antacids to maintain his gastric pH above 5 failed to affect gastrointestinal bleeding. Also, peripheral venous vasopressin, propantheline bromide, and glucagon were without effect. Total gastrectomy was considered to control his bleeding. However, since a number of prostaglandin analogs prevent gastric lesions produced by many noxious agents (e.g., aspirin, alcohol, strong acid or alkali, etc.) in animals and humans, the patient was treated with 50 micrograms of 15(R)-15 methyl prostaglandin E2 intragastrically every 6 h for 10 days. To epimerize the 15(R) form to the more active 15(S) form, 50-100 ml of 50-mN HCl was placed into the patient's stomach immediately before each dose. Bleeding ceased within 24 h of the onset of 15(R)-15 methyl prostaglandin E2 therapy and did not recur. The prompt response to 15(R)-15 methyl prostaglandin E2 in combination with hourly antacids in this patient with persistent and severe hemorrhagic gastritis suggests a therapeutic effect and the need for a prospective double-blind clinical trial.

Topics: Abdomen; Administration, Oral; Adult; Arbaprostil; Gastritis; Gastrointestinal Hemorrhage; Humans; Male; Postoperative Complications; Prostaglandins E, Synthetic