sulindac and Gastritis

Patients with osteoarthritis were entered into a single-blind trial comparing the effects on the gastric mucosa of a four week course of indomethacin, sulindac and a compound of paracetamol and dextropropoxyphene (Distalgesic). The presence and severity of both acute and chronic gastritis were assessed by histological examination of endoscopic biopsy specimens taken from five standard sites in th stomach of each patient before and at the end of the four week period. The presence and severity of chronic gastritis was not affected by the treatment in any of the groups. The pattern of acute gastritis was complex, many of the patients having acute inflammatory changes in their initial biopsy specimens. At least one patient in each treatment group developed marked acute gastritis during the treatment period, but a significant overall increase in the severity of these changes was only found in the group treated with sulindac.

Topics: Acetaminophen; Acute Disease; Adult; Anti-Inflammatory Agents; Chronic Disease; Dextropropoxyphene; Drug Combinations; Female; Gastric Mucosa; Gastritis; Humans; Indenes; Indomethacin; Male; Middle Aged; Osteoarthritis; Sulindac

Newer nonsteroidal antiinflammatory agents (NSAI's) such as ibuprofen, neproxen, fenoprofen, and tolmetin have broadened the therapeutic choice and increased the chances of providing optimum arthritis control, but require careful assessment of the possibilities for unwanted drug effects when long-term therapy is required. A review of the literature on the gastrointestinal effects of the promising newer NSAIs, as compared with the older agents, aspirin, indomethacin, and phenylbutazone, is presented, highlighting animal toxicology and human adverse reaction surveillance data and the evidence for various suggested pathophysiological mechanisms.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Diclofenac; Double-Blind Method; Drug Evaluation; Fenoprofen; Gastric Mucosa; Gastritis; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Ibuprofen; Ketoprofen; Naproxen; Phenylbutazone; Registries; Sulindac; Tolmetin

Helicobacter pylori infection causes severe dysplasia manifested as gastrointestinal intraepithelial neoplasia (GIN) after 28 weeks post-H. pylori infection (WPI) in cancer-prone, hypergastrinemic male INS-GAS mice. We examined the efficacy of the nonsteroidal anti-inflammatory drug sulindac (400 ppm in drinking water) alone, the CCK2/gastrin receptor antagonist YM022 (45 mg/kg/wk) alone, and sulindac or YM022 combined with H. pylori eradication therapy to prevent H. pylori-associated gastric cancer in male INS-GAS mice. Treatments started at 22 WPI, and mice were euthanized at 28 WPI. In uninfected mice, all treatments significantly delayed development of spontaneous GIN (P < 0.05). In H. pylori-infected mice, sulindac alone or YM022 alone had no protective effect on H. pylori-associated GIN. Importantly, sulindac exacerbated the severity of H. pylori-associated gastritis despite decreased gastric prostaglandin E(2) levels. However, sulindac combined with H. pylori antimicrobial eradication reduced the incidence of GIN (P < 0.05), whereas YM022 combined with antimicrobial eradication did not reduce GIN. In infected mice, sulindac or YM022 treatment did not alter gastric expression of the proinflammatory cytokines Ifn-gamma and Tnf-alpha and mucosal cell proliferation. Sulindac or YM022 combined with antimicrobial eradication down-regulated mRNA levels of Ifn-gamma and Tnf-alpha and mucosal cell proliferation (P < 0.05). We conclude that sulindac enhances H. pylori gastritis and may promote inflammation-mediated gastric carcinogenesis. The combination of sulindac and antimicrobial H. pylori eradication was beneficial for reducing proinflammatory cytokine mRNA in the stomach and preventing progression from severe dysplasia to gastric cancer in H. pylori-infected INS-GAS mice.

Topics: Animals; Anti-Infective Agents; Antineoplastic Agents; Benzodiazepines; Blotting, Western; Cell Proliferation; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Drug Therapy, Combination; Gastritis; Helicobacter Infections; Helicobacter pylori; Hormone Antagonists; Hydrogen-Ion Concentration; Interferon-gamma; Male; Membrane Proteins; Mice; Precancerous Conditions; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stomach Neoplasms; Sulindac; Tumor Necrosis Factor-alpha

We report the first case in a preterm infant given oral sulindac for treatment of symptomatic patent ductus arteriosus who subsequently developed severe acute haemorrhagic gastritis leading to disseminated intravascular coagulation, massive pulmonary haemorrhage and death. The postmortem examination suggested that the mechanism was likely a direct irritant insult causing ischaemia on the gastric mucosa. Although sulindac is supposed to be a renal-sparing non-steroidal anti-inflammatory prodrug associated with minimal renal and gastrointestinal adverse effects, clinicians should be alerted to this potential life-threatening complication in preterm infants. Until the question of safety could be adequately addressed, the use of sulindac for ductal closure should remain experimental.

Topics: Cyclooxygenase Inhibitors; Diseases in Twins; Ductus Arteriosus, Patent; Fatal Outcome; Gastritis; Gastrointestinal Hemorrhage; Humans; Infant, Newborn; Infant, Premature; Irritants; Sulindac