https://www.gastrojournal.org/article/S0016-5085(01)38079-4/pdf

Approaches to nonsteroidal anti-inflammatory drug use in the high-risk patient.

Evidence has accumulated that nonsteroidal anti-inflammatory drugs (NSAIDs) cause clinically important gastroduodenal ulcers. The pathogenesis, which involves the impairment of mucosal resistance to injury in an acid-peptic environment, is multifactorial and controversial. Ulcers caused by NSAIDs can occur either in mucosa inflamed because of infection with Helicobacter pylori or in histologically normal mucosa. The use of these drugs has been linked to an unexpectedly high incidence of ulcer complications, and a history of peptic ulcer disease is common in such cases. Nonsteroidal anti-inflammatory drugs thus appear both to exacerbate an underlying peptic diathesis and to cause de novo ulcers. The association between the use of these drugs and ulcer complications is supported by ulcer prevalence data from cross-sectional studies, and by data from case-controlled and cohort studies, and from randomized, experimental trials. Drug-induced gastric ulcers have been prevented by misoprostol, but not by H2 blocker therapy. Several therapies have been reported to promote ulcer healing despite continued use of NSAIDs, but adequate controlled trials have not been done. Small gastric and duodenal ulcers readily heal, whereas larger gastric ulcers require vigorous and prolonged therapy. The relative efficacies of various therapies in preventing ulcers, healing ulcers, or preventing complications remain to be established.

Nonsteroidal anti-inflammatory drugs and peptic ulcer disease

OBJECTIVE: To evaluate the prophylactic effect of ranitidine 150 mg twice daily in patients requiring one of the following non-steroidal anti-inflammatory drugs: naproxen, piroxicam, diclofenac, and indomethacin. In addition, risk factors were studied in order to help in targeting of such treatment to specific groups of patients. DESIGN: Double blind, placebo controlled, randomised, parallel group with endoscopic assessments at 0, 4, and 8 weeks. SETTING: Multicentre outpatient study at secondary referral centres in five European countries. PATIENTS--297 patients with rheumatoid arthritis or osteoarthritis over the age of 18 without lesions in the stomach and duodenum at baseline endoscopy (after one week without taking non-steroidal anti-inflammatory drugs). Those taking other antirheumatic agents, concomitant ulcerogenic drugs, or treatment for peptic ulcers within the previous 30 days were excluded. Age, sex, arthritic disease, and type of non-steroidal anti-inflammatory drug used were comparable in the two treatment groups. In all, 263 patients completed the trial. INTERVENTIONS: Ranitidine 150 mg twice daily or placebo (plus the selected non-steroidal anti-inflammatory drug) was prescribed within five days after the baseline endoscopy for two consecutive periods of four weeks. Paracetamol was permitted during the study, but not antacids. Patients were withdrawn if the most severe grade of damage (including ulceration) was found at the four week endoscopy or when indicated, or with lesser damage at the investigator's discretion. END POINT: Frequency of gastric and duodenal ulceration or lesions, or both. MEASUREMENTS AND MAIN RESULTS: The cumulative incidence of peptic ulceration by eight weeks was 10.3% (27/263); 2 out of 135 (1.5%) developed duodenal ulceration in the ranitidine group, compared with 10 out of 126 (8%) taking placebo. The frequency of gastric ulceration was the same (6%) for the two groups at eight weeks. Though significantly fewer gastric lesions developed in the ranitidine group by eight weeks. The frequency of non-ulcerative lesions in the duodenum did not differ greatly for the two groups at either time point. Twelve out of 75 (16%) patients taking piroxicam developed peptic ulceration, of whom two thirds had duodenal ulceration. Patients with a history of peptic ulcer were particularly susceptible to recurrent ulceration, against which ranitidine offered some protection. CONCLUSIONS: Ranitidine 150 mg twice daily significantly reduced the incidence of duodenal ulceration but not gastric ulceration when prescribed concomitantly with one of four commonly used non-steroidal anti-inflammatory drugs.

https://www.bmj.com/content/bmj/297/6655/1017.full.pdf

Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine.

Background: Chronic fatigue syndrome (CFS), fibromyalgia (FM), and multiple chemical sensitivities (MCS) are conditions associated with fatigue and a variety of other symptoms that appear to share many clinical and demographic features. Our objectives were to describe the similarities and differences among patients with CFS, FM, and MCS. Additional objectives were to determine how frequently patients with MCS and FM met the criteria for CFS and if they differed in their health locus of control. Methods: Demographic, clinical, and psychosocial measures were prospectively collected in 90 patients, 30 each with CFS, FM, and MCS. Patients were recruited from a university-based referral clinic devoted to the evaluation and treatment of chronic fatigue and three private practices. Variables included demographic features, symptoms characteristic of each condition, psychological complaints, a measure of health locus of control, and information on health care use. Results: Overall, the three patient groups were remarkably similar in demographic characteristics and the presence of specific symptoms. Patients with CFS and FM frequently reported symptoms compatible with MCS. Likewise, 70% of patients with FM and 30% of those with MCS met the criteria for CFS. Health care use was substantial among patients with CFS, FM, and MCS, with an average of 22.1, 39.7, and 23.3 visits, respectively, to a medical provider during the prior year. Health locus of control did not differ among the three populations. Conclusions: In general, demographic and clinical factors and health locus of control do not clearly distinguish patients with CFS, FM, and MCS. Symptoms typical of each disorder are prevalent in the other two conditions. (Arch Intern Med. 1994;154:2049-2053)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=INTEMED&articleId=619352&pdfFileName=archinte_154_18_007.pdf

Comparison of Patients With Chronic Fatigue Syndrome, Fibromyalgia, and Multiple Chemical Sensitivities

https://www.gastrojournal.org/article/0016-5085(85)90225-2/pdf

Prostaglandins and the gastrointestinal mucosa: Are they important in its function, disease, or treatment?

Endoscopy has become a standard method to evaluate drug-induced damage to the gastroduodenal mucosa; however, studies defining the time course, extent, and duration of the injury in man are unavailable. We report a systematic endoscopic evaluation of the effect of aspirin administration on the gastric mucosa in normal volunteers. Aspirin (2.6 g/day) or placebo was administered for 1 or 7 days. Gastroscopy was performed after 1, 2, 4, and 8 days, and every other day thereafter until the lesions resolved. Submocosal hemorrhages and/or focal erosions were present within 24 hr in all subjects. With continuous aspirin administration, injury was maximal within 3 days and then lessened, ie, damage present after 7 days of aspirin was significantly less than after 1 day of therapy. The time to resolution of the damage was also longer following 1 day than after 7 days of aspirin (median 8 days for 1 day of aspirin vs median 3 days for 7 days of aspirin). Thus, gastric mucosal adaptation occurred and was associated both with less damage and with an accelerated healing process. Acute administration of aspirin produced well-defined areas of submucosal hemorrhages within 2 hr of administration; additional doses increased the area of involvement but not necessarily the severity of involvement.

Gastric adaptation occurs with aspirin administration in man

https://www.giejournal.org/article/S0016-5107(82)72961-X/pdf

Stuart M. Dobbs

Papers

Gastric adaptation occurs with aspirin administration in man

Vascular-enteric fistula: diagnosis by colonoscopy