Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D00446 (Sucralfate)
 278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mucosal lesions in the g.i. tract due to ASA and other nonsteroidal anti-inflammatory drugs are well-known in clinical practice. Though the gastroduodenal mucosa is the area most commonly investigated, several recent reports focus on lesions in the small and large intestine as well. Despite considerable efforts in the field, none of the new substances developed in the past few years have proven convincingly superior to existing drugs. Instead, other approaches are being evaluated: Bypassing of the gastroduodenal mucosa through enteric coating and slow release formulations have been suggested, but the possibility of transferring the deleterious effects to distal parts of the gastrointestinal tract by such formulation modifications calls for extensive evaluation of this area, before these formulations can be applauded as advantageous in this group of patients. Co-administration of protective substances has also been advocated, and, despite somewhat contradictory results, protection has been reported by H2-antagonists alone or in combination with antacids, as well as by cytoprotective agents like Sucralfate, and prostaglandin analogues.
 ...
PMID:Management of NSAID-induced gastrointestinal lesions. 290 80

Sucralfate promotes the healing of peptic ulcers and, in large doses, increases gastric mucosal prostaglandins. The present study was designed to further elucidate the protective effect of sucralfate and to evaluate the role of prostaglandins in this action. Eight chair-adapted rhesus monkeys received a subcutaneous injection of either 150 mg/kg of aspirin or vehicle in combination with either a therapeutic oral dose of sucralfate (50 mg/kg X day) or water. Gastric soluble mucus concentration was determined in samples of gastric juice by Alcian blue dye binding of acidic glycoproteins, and mucus output was determined using a technetium 99m-diethylenetriaminepentaacetic acid dilution technique. Monkeys underwent endoscopy to assess gastric mucosal damage, which was ranked blindly on a scale of 0-5, and to obtain biopsy specimens for determination of mucosal prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha. Aspirin did not alter soluble mucus but did significantly increase gastric mucosal damage and suppress tissue levels of all prostaglandins. Sucralfate significantly increased the output of soluble mucus, even after aspirin treatment, and protected against aspirin-induced damage, although it did not modify aspirin-induced suppression of prostaglandins. These results suggest that the gastric protection afforded by sucralfate is related to a prostaglandin-independent increase in mucus production.
 ...
PMID:Gastric protection by sucralfate. Role of mucus and prostaglandins. 346 Sep 26

Sucralfate, an agent that heals peptic ulcers in humans, has been shown to reduce aspirin-induced gastric mucosal damage in experimental animals. It has been suggested that the protective effect of sucralfate is due to stimulation of local prostaglandin production. The purpose of this study was to establish whether sucralfate was capable of reducing aspirin-induced gastric damage in humans. The effect of 1 g of sucralfate or identical placebo was studied in random order in eight healthy subjects. To determine if the effect of sucralfate was related to local prostaglandin synthesis, a second series of studies was performed in which prostaglandin production was inhibited with indomethacin 50 mg given orally eight hours before sucralfate. In each subject, all studies were performed at least one week apart. Following an overnight fast, upper gastrointestinal endoscopy was performed, with sucralfate or placebo given orally 30 minutes before ingestion of 1,200 mg of soluble aspirin in 50 ml of water. Both endoscopist and subject were unaware of the test agent. Ninety minutes after aspirin ingestion, endoscopy was again performed and gastric mucosal lesions were counted and graded to derive an erosion score. Results are expressed as mean +/- SEM. Aspirin produced endoscopic changes (score of 2.75 +/- 0.49) that were significantly (p less than 0.05) inhibited by sucralfate (score of 1.13 +/- 0.44). The protective effect of sucralfate was abolished by pretreatment with indomethacin (scores of 2.88 +/- 0.55 and 1.88 +/- 0.40, respectively). These results demonstrate that sucralfate significantly protects the human gastric mucosa against the acute damaging effects of aspirin. This effect is abolished by indomethacin, suggesting that the protective action of sucralfate on the gastric mucosa of humans may be related to stimulation of endogenous prostaglandins.
 ...
PMID:Protective effect of sucralfate against aspirin-induced damage to the human gastric mucosa. 366 13

Sucralfate, an aluminum salt of sulfated sucrose, is a new drug designed for the treatment of peptic ulcer. Sucralfate has been reported to be useful in a variety of situations including prevention of aspirin-induced gastric mucosal damage. We investigated the in vitro adsorption of bile salts or aspirin to sucralfate in environments simulating the stomach (pH 1.5), small intestine (pH 7), and colon (pH 7.8). Bile salts were incubated with sucralfate, and the quantity of bile salt adsorbed was calculated by subtraction from the amount remaining in solution after centrifugation at 12,500g for 30 min. Adsorption experiments were performed in bile salt solutions at pH 1.5 and 7.0 with 0-10 g/dl sucralfate using glycocholate, glycochenodeoxycholate, taurocholate, taurodeoxycholate, or taurochenodeoxycholate. The dihydroxy-unconjugated bile salts, deoxycholic, and chenodeoxycholic salts were tested at pH 7.8. Binding capacity (micromoles per gram sucralfate) was calculated from the linear regression of micromoles bound vs grams sucralfate incubated. Sucralfate adsorbed all bile salts tested (except taurocholic acid at pH 1.5) but was less effective than cholestyramine. Sucralfate does not adsorb sufficient bile salts at neutral pH to cause bile salt depletion. Aspirin was minimally adsorbed by sucralfate [7.5 mumol (1.4 mg)/g sucralfate, pH 1.5], and thus adsorption of aspirin does not explain the protective effect of sucralfate against aspirin injury.
 ...
PMID:In vitro adsorption of bile salts and aspirin to sucralfate. 654 15

The proton pump inhibitors omeprazole and lansoprazole and the histamine H2 receptor antagonists ranitidine and nizatidine were investigated for their effects on gastric transmucosal potential difference (PD) in the rat, in comparison with the gastroprotective compound sucralfate. Omeprazole (1-3 mg kg-1, i.v.) and lansoprazole (1-3 mg kg-1, i.v.) did not modify basal PD, but significantly reduced (by approx. 50-60%) the drop in PD caused by intragastric administration of acetylsalicylic acid (ASA, 60 mg kg-1). Ranitidine (3-100 mg kg-1, i.v.) and nizatidine (10-30 mg kg-1, i.v.) behaved similarly to proton pump inhibitors, being ineffective on basal PD, while significantly reducing the effect of ASA. The antisecretory compounds did not change basal pH values. Sucralfate (0.5-1.5 g kg-1 intragastrically) caused a slight increase (approx. 20%) of basal PD and a dose-dependent reduction of ASA-induced fall in PD, with a maximum effect (65% reduction) comparable to that caused by the antisecretory agents. These results showed that ASA-induced disruption of the mucosal barrier can be reduced to the same extent by various antiulcer drugs, irrespective of their effects on gastric acid secretion.
 ...
PMID:Effects of different antisecretory drugs on gastric potential difference in the rat: comparison with sucralfate. 999 Jun 56

The efficacy of antacids in the short- and long-term treatment of peptic ulcers, has suggested a possible use in the prevention and in the treatment of non-steroidal anti-inflammatory drug related gastroduodenal lesions. In short-term prevention studies, significant protection against ASA-related lesions was observed when antacids at high-dose were given before the administration of the offending drug. To the contrary, antacids at low dose did not prevent ASA-induced lesions of gastric and duodenal mucosa. As for long-term prophylaxis, no clinical effect was observed. In the treatment of non-steroidal anti-inflammatory drug-related mucosal lesions in patients who were able to discontinue the offending drugs, antacids proved of some use, when compared with placebo, but were significantly less effective than H2 blockers, as cimetidine. Sucralfate is an effective antiulcer drug thought to provide cytoprotective action. Although initial studies utilizing sucralfate for protection against short-term aspirin administration were encouraging, longer term studies (more than 7 days) were generally disappointing. A comparative study with misoprostol demonstrated that the PGE1 analogue was far superior for the prevention of non-steroidal anti-inflammatory drugs ulcers, and that ulceration rates in the sucralfate group were equivalent to rates in the placebo group. As far as the treatment of non-steroidal anti-inflammatory drug-related mucosal lesions is concerned, sucralfate proved superior to placebo, similar to ranitidine, but significantly less effective than omeprazole.
 ...
PMID:Non-steroidal anti-inflammatory drug gastropathy: clinical results with antacids and sucralfate. 1037 70

Allophylus serratus is known to possess various therapeutic properties. We evaluated the anti-ulcerogenic property of crude ethanolic extract of Allophylus serratus (AS) in different ulcer models in Sprague-Dawley rats. The extract at 400 mg/kg body weight, once daily, orally has a significant effect in cold restraint (CRU, 2 h cold restraint stress), aspirin (ASA, 150 mg/kg body weight, orally), alcohol (AL, 1 ml/200 gm of absolute alcohol) and pyloric ligation (PL, 4h ligation) induced gastric ulcer models as it showed protection index of 71.28, 62.50, 90.84 and 64.29% protection, respectively whereas, standard drug omeprazole (OMZ, 10mg/kg body weight) has shown protection index of 85.70, 74.99 and 74.99 in CRU, ASA and PL model respectively. Sucralfate (SUC, 500 mg/kg body weight) as a standard drug in AL model has 93.20% protection. Furthermore, AS has significantly decreased the free acidity (72.41%), total acidity (47.97%) and peptic activity (24.59%), respectively as well as has significantly increased the mucus secretion (29.41%). Conclusively the ulcer protective effect of AS may be due to its anti-secretory along with cytoprotective mechanism.
 ...
PMID:Allophylus serratus: a plant with potential anti-ulcerogenic activity. 1587 49