Gastroduodenal ulcers

Polymorphisms of CYP2C19 cause differences in metabolism of omeprazole, a proton pump inhibitor used for treatment of gastroduodenal ulcers or reflux esophagitis. Such polymorphisms result in resistance to treatment at a standard dose regimen in nearly 20% of European Caucasians, and in an even higher percentage of Asians [12]. 

Rostom A, Dube C, Wells G, Tugwell P, Welch V, Joli-coeur E et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev 2002. 

It is a sclerosing agent for bleeding oesophageal varices, varicose veins, bleeding gastroduodenal ulcers etc. 

Use of celecoxib is associated with a reduced incidence of gastroduodenal ulcers in comparison to naproxen (Goldstein et al., 2001) ibuprofen, or diclofenac (Silverstein et al., 2000) in patients with arthritis. 

Reduced incidence of gastroduodenal ulcers with celecoxib, a novel cyclooxygenase-2 inhibitor, compared to naproxen in patients with arthritis, Am. J. Gastroenterol. 2001, 96, 1019-1027. 

Misoprostol, an analogue of PGE1 is licensed for use in the management of gastroduodenal ulceration. It is an effective myometrial stimulant of the pregnant uterus and is used for the induction of labor and as abortifacient, both alone and in combination with other substances (for example mifepristone). It provides an effective alternative to gemeprost, the most widely used prostaglandin pessaries in combination with mifepristone. 

Flaten TP, Glattre E, Viste A, et al. 1991. Mortality from dementia among gastroduodenal ulcer patients. J Epidemiol Commun Health 45 203-206. 

Ernst, P.B., Gold, B.D. The disease spectrum of H. pylori the immunopathogenesis of gastroduodenal ulcer and gastric cancer. Annu Rev Microbiol 54 (2000) 615-640. 

Pecha RE, Prindiville T, Pecha BS, Camp R, Carroll M, Trudeau W. Association of cocaine and methamphetamine use with giant gastroduodenal ulcers. Am J Gastroenterol 1996 91(12) 2523-7. 

Bll. Bayer, A. E., Plummer, K., and Bradley, S., A clinical and experimental evaluation of the effect of diphenmethanil methylsuUate (Prantal) on gastroduodenal ulcer and gastric secretion. Gastroenterology 22, 112-118 (1952). 

Idelson, L. I., Castromucoprotein and vitamin Bjig in gastroduodenal ulcer. Therap. Arch. (Russ.) 31, 26-32 (1959). 

Czarnobilski Z, Bern S, Czarnobilski K, Konturek SJ. Carprofen and the therapy of gastroduodenal ulcerations by ranitidine. Hepatogastroenterology 1985 32(l) 20-3. 

In the VIGOR study, 8076 patients with rheumatoid arthritis were randomly assigned to receive rofecoxib 50 mg/day or naproxen 500 mg bd. The primary endpoint was a confirmed clinical upper gastrointestinal event (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcer). 

The H2 receptor antagonists do not prevent gastroduodenal ulceration by non-steroidal anti-inflammatory drugs, but they do prevent stress-induced ulceration and bleeding. In intensive care units there is evidence of a beneficial effect, but in patients with hematemesis and melena there is little evidence that H2 receptor antagonists reduce rates of transfusion, surgical intervention, or mortality (SEDA-19, 326). 

Further evidence of the unfavorable benefit-to-harm balance of ketorolac compared with other NSAIDs has been provided by another case-control study on first-time hospitalization for gastroduodenal ulcer (documented by endoscopy, radiology, surgery, or autopsy), with or without bleeding or perforation. Of all the NSAIDs used in outpatients the highest rate ratio for lesions of any degree of severity was seen with piroxicam (4.6 95% Cl = 1.4,... 

The role of Helicobacter pylori Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) account for nearly all gastroduodenal ulcers and serious ulcer complications, but the interaction between infection with H. pylori and the use of NSAIDs in the pathogenesis of NSAID-induced gastropathy is controversial. In fact, studies that have examined these two susceptibility factors have yielded conflicting results about whether H. pylori infection increases the risk of toxicity in NSAID users, has no effect, or may even be protective (70-72). 

Clinical use Treatment of dyspepsia, gastroduodenal ulcers, gastroesophageal reflux disease (GERD), and Zollinger-Ellison syndrome. 

One of the side effects of adrenocorticotropic hormone (ACTH) and corticoid therapy in humans is the development or reactivation of gastroduodenal ulcers. Daily subcutaneous administration of cortisol or A -cortisol to rats for 4 days results in the regular development of gastric ulcers (38). This procedure has been adapted to testing antiulcer activity (39). There are certain differences between steroid ulcers and "natural" ulcers in localization, rate of development, and severity (40). 

Misoprostol has several therapeutic uses, including the treatment of gastroduodenal ulceration and labor induction and has the advantage of being relatively inexpensive and stable enough to be stored at room temperature. Prostaglandin therapy for the induction of labor is a well-established practice, and misoprostol has been compared with dinoprostone and also oxytocin. It was found to be equieffective with oxytocin (325)and more effective than dinoprostone (326). It was also shown to be effective in 92% of women in combination with tamoxifen (327). However, mi-... 

The most common adverse effect seen with the use of misoprostol is diarrhea, but abdominal pain has also been reported, limiting the use of this and other similar compounds in the management of gastroduodenal ulceration. Effects on uterine contraction have also been reported, suggesting that misoprostol should not be given to pregnant women (335). 

There is little evidence to support clinically important differences with regard to the frequency of ulcers and upper GI complications among most available nonaspirin, nonselective NSAIDs (see Table 33-3) when used in equipotent anti-inflammatory dosages. However, the nonacetylated salicylates (e.g., salsalate) and newer NSAIDs (e.g., etodolac, nabumetone, and meloxicam) may be associated with a decreased incidence of GI toxicity. NSAIDs that selectively inhibit cyclooxygenase-2 (COX-2) decrease the incidence of gastroduodenal ulcers and related GI complications when compared to the nonselective NSAIDs. The use of buffered or enteric-coated aspirin confers no added protection from ulcer or GI complications. ... 

Standard PPI dosages (e.g., omeprazole 20 mg/day and lansoprazole 30 mg/day) reduce the risk of NSAID-induced gastric ulcer and duodenal ulcer. " In a large comparative multicenter trial, omeprazole 20 mg/day was superior to ranitidine 150 mg twice daily in preventing NSAID-induced gastroduodenal ulcers. Two randomized controlled trials have compared PPIs with misoprostol and placebo. 

The incidence of endoscopically observed gastroduodenal nlcers in RA patients taking valdecoxib 20 mg daily (6%) and valdecoxib 40 mg daily (4%) was reduced compared to that in patients receiving diclofenac 75 mg sustained-release twice daily (16% p < 0.001). Valdecoxib 20 mg daily was also associated with significantly improved GI tolerability (p = 0.035) compared with diclofenac. Four safety studies and two reviews of clinical trials indicated decreased rates of gastroduodenal ulceration with valdecoxib versus ibuprofen, naproxen, and diclofenac (p < 0.001 to < 0.05). ... 

Pavelka K, Recker DP, Verburg KM. Valdecoxib is as effective as diclofenac in the management of rheumatoid arthritis with a lower incidence of gastroduodenal ulcers Results of a 26-week trial. Rheumatology 2003 42 1207-1215. 

H5. Hellstrom, J, Hyperparathyroidism and gastroduodenal ulcer. Acta Chit. Scand. 116, 207-221 (1959). 

Simethicone, a surfactant that may decrease foaming and hence esophageal reflux, is included in many antacid preparations. However, other fixed combinations that are marketed for acid indigestion , particularly those with aspirin, are potentially unsafe in patients predisposed to gastroduodenal ulcers and should not be used. 

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