misoprostol and Duodenal-Diseases

The association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the development of upper gastrointestinal (GI) damage is well established. Studies have indicated that 12-30% of NSAID users will develop gastric ulcers and that 2-19% will develop duodenal ulcers. Furthermore, many NSAID-induced ulcers are "silent" and are only discovered when complications occur. When possible, the most effective method of preventing NSAID-induced gastropathy is discontinuation of NSAIDs or a reduction in the NSAID dosage. For patients who require continued NSAID therapy, four classes of drugs have been evaluated for their potential protective effects against NSAID-induced gastroduodenal damage:H2-receptor antagonists (eg, ranitidine), proton pump inhibitors (eg, omeprazole), acid-barrier compounds (eg, sucralfate), and prostaglandin E1 analogues (eg, misoprostol). H2-receptor antagonists have not been shown to be effective in preventing NSAID-induced gastric ulcers, and sucralfate has not been shown to be effective in preventing NSAID-induced gastric or duodenal ulcers. Similarly, newer proton pump inhibitors, such as omeprazole, do not appear to protect the stomach against NSAID-induced damage. In contrast, misoprostol has proven its efficacy in preventing both gastric and duodenal ulcers in arthritis patients taking NSAID therapy.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Duodenal Diseases; Humans; Misoprostol; Stomach Diseases

Advanced age is an established risk factor for gastrointestinal toxicity of nonsteroidal antiinflammatory drugs, and the duration of use of these agents in elderly patients should be kept as short as possible. A multicenter, double-blind, placebo-controlled trial was conducted to evaluate the efficacy of misoprostol in preventing gastrointestinal toxicity in elderly patients (> or = 65 years) given nonsteroidal antiinflammatory agents for no more than ten days. Patients who were to receive a nonsteroidal antiinflammatory agent for ten days to treat an acute rheumatic condition were randomly allocated to treatment with either a placebo or misoprostol in a dose of 200 micrograms bid. The primary efficacy criterion was the result of a gastroduodenal endoscopic evaluation done on day 10. The outcome of the rheumatic condition, changes in serum creatinine levels, and clinical safety were also evaluated. The study population included 208 subjects with a mean age of 81.4 +/- 6.4 years, of whom 81.3% were women. The misoprostol group (n = 104) and the placebo group (n = 104) were comparable at baseline. The incidence of endoscopically visible gastric lesions after ten days of nonsteroidal antiinflammatory drug therapy was significantly lower in the misoprostol group (25%) than in the placebo group (43%) (P = 0.001). In contrast, no statistically significant difference was found for the incidence of duodenal lesions between the two groups. The incidence of gastroduodenal ulcers was significantly lower (P < 0.021) in the misoprostol group (4.1%) than in the placebo group (13.5%). Changes in serum creatinine levels on day 10 versus baseline were similar in the two groups. The nonsteroidal antiinflammatory drug was well tolerated clinically when given alone or in combination with misoprostol.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Cohort Studies; Creatinine; Double-Blind Method; Duodenal Diseases; Female; Gastrointestinal Diseases; Humans; Male; Misoprostol; Placebos; Time Factors; Treatment Outcome

Ninety-one normal, healthy volunteers participated in a single-center, double-blind, placebo-controlled, randomized, parallel group study: 1) to compare the prostaglandin E1 analog, misoprostol, given at a dose of 200 micrograms bid, with the recommended dose of 200 micrograms qid in protecting the gastroduodenal mucosa against injury due to anti-inflammatory doses of aspirin (3900 mg/day); and 2) to determine whether the reduced dose was associated with a lesser incidence of gastrointestinal (GI) side effects, particularly diarrhea. All subjects received 975 mg of aspirin qid with meals and at bedtime. They were concurrently administered either misoprostol 200 micrograms qid, misoprostol 200 micrograms bid and placebo bid, or placebo qid. All subjects were endoscopically normal at the onset of the study and were re-endoscoped on the morning of the 7th day of therapy, 2 h after the morning dose of medications. Gastric and duodenal mucosa were assessed separately on a 0-7 scale which gave a greater weight to erosions than to hemorrhages. GI symptoms, especially bowel habits, were assessed by means of diary cards. Subjects in both misoprostol groups had significantly less gastric and duodenal mucosal injury than subjects who received placebo (p less than 0.007 for each pairwise comparison). There was no statistically significant difference between the two misoprostol groups (p less than 0.093). Subjects in the misoprostol 200 micrograms qid group had significantly more loose and watery bowel movements than the subjects in the misoprostol 200 micrograms bid group (p less than 0.013), whereas there were no significant differences in bowel habits between the misoprostol 200 micrograms bid and placebo groups (p less than 0.122). More subjects in the misoprostol 200 micrograms qid group reported abdominal pain, loose stools, watery stools, flatulence, dyspepsia, and nausea than in the misoprostol 200 micrograms bid and placebo groups. In conclusion, the adverse events in the misoprostol 200 micrograms bid group were not significantly different from those in the placebo group, and were significantly better than in the misoprostol 200 micrograms qid group. The lower dose retained mucosal protective activity that was statistically indistinguishable from that of misoprostol 200 micrograms qid.

Topics: Adult; Aspirin; Diarrhea; Double-Blind Method; Duodenal Diseases; Duodenoscopy; Female; Gastric Mucosa; Gastroscopy; Humans; Intestinal Mucosa; Male; Middle Aged; Misoprostol; Stomach Diseases