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

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.
Gastroenterology 1986 Sep
PMID:Gastric protection by sucralfate. Role of mucus and prostaglandins. 346 Sep 26

This study investigated the relationship between the protective effect of sucralfate against ethanol-induced gastric mucosal injury in the rat and the effects of sucralfate on prostaglandin and mucus synthesis and secretion. Sucralfate at 200, 400, and 800 mg/kg significantly reduced gastric ulceration. Intragastric administration of sucralfate increased luminal mucus and prostaglandin E2 levels but did not affect prostaglandin or mucus synthesis in gastric mucosal biopsy specimens from sucralfate-treated animals. Pretreatment with indomethacin partially reduced the protective effect of sucralfate. However, sucralfate 200 mg/kg, a dose that completely prevented ulceration, did not increase the levels of luminal prostaglandin E2. In vitro incubation with sucralfate did not stimulate mucosal prostaglandin synthesis. Longer-term administration of sucralfate for 48 or 96 hours did not stimulate mucus or prostaglandin synthesis but did increase luminal prostaglandin E2 and mucus. Although sucralfate increased the gastric juice content of prostaglandin E2 and mucus, the two did not appear to be mechanistically related, and only mucus release was consistently associated with mucosal protection.
Am J Med 1987 Sep 28
PMID:Role of mucus and prostaglandins in the gastric mucosal protective actions of sucralfate against ethanol-induced injury in the rat. 347 59

Rats pretreated with dilute ethanol, dilute hydrochloric acid, or dilute sodium hydroxide had significantly less gastric mucosal damage when they were exposed 15 or 30 minutes later to strong irritants. The dilute agents, known as mild irritants, also caused an increase in the production of gastric mucosal prostaglandin E2 at the 15- and 30-minute dosing intervals. This suggests that the mild irritants are only effective in providing gastric mucosal protection when they increase gastric production of prostaglandin E2. Sucralfate treatment also caused an increase in gastric mucosal production of prostaglandin E2 at only the 15- and 30-minute dosing intervals. In contrast, pretreatment with sucralfate protected against the damaging effects of the strong irritants for at least 480 minutes. Therefore, prostaglandin E2 may play a role in sucralfate's protective effect at short dosing intervals, but at longer intervals, when prostaglandin E2 changes were not observed, sucralfate was still found to be very effective in reducing the severity of gastritis. This suggests that sucralfate acts, at least in part, through some other mechanism(s) besides increasing gastric mucosal prostaglandin E2 production.
Am J Med 1987 Sep 28
PMID:Effects of sucralfate or mild irritants on experimental gastritis and prostaglandin production. 347 60

It has been suggested that an acidic medium is required for the action of sucralfate in providing mucosal protection. We have examined the effect of sucralfate (300 mg/kg) at an acidic pH of 1.5 and a near-neutral pH of 6.5 on the occurrence of mucosal damage induced in rats by aspirin alone and aspirin combined with bile acids. Fasting Sprague-Dawley rats received test solutions by oral intubation, and their stomachs were examined four hours later for the presence of hemorrhagic erosions. Sucralfate significantly reduced mucosal erosions induced by aspirin alone and aspirin combined with bile acids at pHs of both 1.5 and 6.5. These results indicate that the protective effect of sucralfate against mucosal injury induced by aspirin and bile acids is not dependent on an acidic medium.
Am J Med 1987 Sep 28
PMID:Is an acid pH medium required for the protective effect of sucralfate against mucosal injury? 349 73

Seventy-four medical and surgical patients having a minimum of two risk factors for stress-related gastric mucosal bleeding were prospectively selected randomly to receive prophylaxis by antacid titration (to maintain a gastric pH of more than 4) or with sucralfate suspension (1 g/10 ml every four hours). Gastric aspirates were monitored every two hours for pH and overt and occult bleeding. Despite a significantly greater severity of illness in the sucralfate group (p less than 0.01), no significant difference in overt or occult bleeding between the groups could be demonstrated. Low-grade occult blood loss occurred frequently in both groups, but only one of the 74 patients (four risk factors, sucralfate group) had significant stress-related bleeding as defined by preset criteria and documented by endoscopy. The effectiveness of sucralfate appeared unrelated to acid neutralization in keeping with its classification as a cytoprotective agent. There were eight antacid-related side effects (four severe diarrhea, four hypermagnesemia), and none related to sucralfate. Sucralfate suspension was safe and effective and had fewer side effects than antacid titration for the prophylaxis of stress-related bleeding in critically ill patients.
Am J Med 1987 Sep 28
PMID:Sucralfate suspension versus titrated antacid for the prevention of acute stress-related gastrointestinal hemorrhage in critically ill patients. 349 74

In order to study whether sucralfate or cimetidine may protect human gastric mucosa against alcohol injury, 28 healthy volunteers were pretreated with either: (1) placebo 1 g; (2) cimetidine (Tagamet) 300 mg; or (3) sucralfate (Carafate) 1 g. One hour later, 100 ml of 40 percent ethanol was sprayed directly on the gastric mucosa of the greater curvature during an endoscopic examination. Gastric mucosal changes were assessed by endoscopic appearance (according to grading scale) and by histology. In placebo-pretreated subjects, alcohol produced prominent mucosal damage (endoscopic score, 3.9 +/- 0.3, histologic score, 4.0 +/- 1.1 at 30 minutes). Cimetidine alkalinized gastric pH but did not prevent alcohol-induced damage (endoscopic score, 4.0 +/- 0.6; histologic score, 3.8 +/- 1.1, at 30 minutes). Sucralfate reduced endoscopic and histologic features of alcohol injury (endoscopic score, 1.8 +/- 0.6; histologic score, 1.8 +/- 1.1, at 30 minutes) without affecting gastric luminal pH. Reduction of alcohol-induced injury of the human gastric mucosa by sucralfate but not cimetidine demonstrates that effective protection of the gastric mucosa can be achieved without neutralization or inhibition of gastric acid secretion and points out another clinical application for sucralfate.
Am J Med 1987 Sep 28
PMID:Efficacy of sucralfate and cimetidine in protection of the human gastric mucosa against alcohol injury. 366 9

Sucralfate has been evaluated in reflux esophagitis, based on its protective adherence to denuded surfaces, its bile salt-binding properties, and its cytoprotective properties. Histamine (H2)-receptor blockers are currently considered the standard therapy. The goal of this study was to compare the potential efficacy of sucralfate with that of cimetidine. A single-blind, randomized, multicenter study was performed in 42 patients with endoscopically documented reflux esophagitis. Patients were randomly given 1 g of sucralfate suspension four times daily or 400 mg of cimetidine four times daily for eight weeks. Forty patients were evaluated after eight weeks. Symptomatic improvement was good and comparable in both groups. In two patients given sucralfate and one given cimetidine, side effects were noted but did not necessitate withdrawal from the study. Endoscopy showed improvement in 53 percent of patients and healing of esophagitis in 31 percent after sucralfate treatment. With cimetidine, improvement was seen in 67 percent and healing occurred in 14 percent. In one patient receiving cimetidine, distal esophageal stenosis developed, requiring dilatation therapy. It is concluded that treatment with sucralfate improves the symptomatology and severity of reflux esophagitis. The results obtained with sucralfate appear comparable to those with cimetidine. Sucralfate may therefore be considered as a valid alternative to H2-receptor antagonist therapy in treating reflux esophagitis.
Am J Med 1987 Sep 28
PMID:Clinical efficacy of sucralfate in reflux esophagitis. Comparison with cimetidine. 366 10

Sucralfate has been reported to protect the gastroduodenal mucosa against a variety of agents and is known to adsorb bile salts. Since gastrointestinal side effects can seriously compromise the efficacy of nonsteroidal anti-inflammatory drug therapy, and since it seems reasonable to assume that sucralfate may adsorb nonsteroidal anti-inflammatory drugs, the influence of sucralfate on the pharmacokinetic parameters of naproxen was assessed in 12 healthy volunteers. To do so, the pharmacokinetic profile of naproxen, administered alone or with sucralfate, singly or repeatedly (twice daily for five days), was compared. No significant difference was observed with any pharmacokinetic parameter between the single administration of naproxen alone or with sucralfate. However, a significantly lower maximum plasma concentration was attained with the repeated administration of naproxen in combination with sucralfate, compared with the repeated administration of naproxen alone. When single- and multiple-dose administration were compared, significant differences were observed in the maximum plasma concentration and the cumulative area under the curve. These results suggest an accumulation of naproxen after five days' administration. This accumulation, however, is not altered by the administration of sucralfate. The results of this study suggest that when naproxen is administered with sucralfate, only a delay in naproxen's absorption may occur, confirmed by a lower maximum plasma concentration, a longer time to reach the maximum plasma concentration, a similar elimination half-life, and equivalence in bioavailability. The clinical importance of such a delay has yet to be proved; however, it is unlikely that the clinical efficacy of naproxen will be altered, since the amount of drug absorbed remains the same.
Am J Med 1987 Sep 28
PMID:Effects of concurrent sucralfate administration on pharmacokinetics of naproxen. 366 12

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.
Am J Med 1987 Sep 28
PMID:Protective effect of sucralfate against aspirin-induced damage to the human gastric mucosa. 366 13

Fifty-nine patients who had duodenal ulcers that were healed following sucralfate administration in a dose of 1 g four times a day were randomly entered into a double-blind, placebo-controlled, 12-month maintenance study to determine whether sucralfate 1 g twice daily prevents recurrence of duodenal ulceration. Patients were assessed endoscopically at four, eight, and 12 months after healing or earlier if clinical relapse occurred. Of the original 59 patients, 53 showed healing with six weeks of therapy, and the remaining six patients required 10 weeks of treatment. Nine patients were subsequently lost to follow-up because of non-compliance, leaving 50 patients for the analysis, 24 who received sucralfate and 26 who received placebo. There were 10 ulcer recurrences in the sucralfate group and the ulcers in 14 (58 percent) patients remaining healed at the end of 12 months. In contrast, there were 21 recurrences in the placebo group with the ulcers in five patients (19 percent) remaining healed at 12 months. Patients who received placebo experienced recurrence more quickly than those who received sucralfate and there was no difference between the two groups in terms of symptomatic and asymptomatic recurrence. There was no alteration in serum aluminium and phosphate levels throughout the study. Smoking seemed to have no adverse effect on recurrence once initial healing had been achieved. Sucralfate is, therefore, an effective and safe maintenance treatment for duodenal ulcer disease.
Am J Med 1987 Sep 28
PMID:Role of maintenance sucralfate in prevention of duodenal ulcer recurrence. 366 14


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