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)

Until 1950 the clinical treatment of peptic ulcer disease relied on dieting and antacids. However, recent controlled studies suggest that the natural course of peptic ulcer disease is not affected by diet. Antacids are primarily used to relieve distress, although high- and low-dose antacid regimens have been reported to promote duodenal ulcer healing. Initial favorable reports following the introduction of synthetic anticholinergic drugs have not been confirmed. Pirenzepine is an anticholinergic compound with a specific action on the muscarinic receptors of the parietal cells. Although pirenzepine appears effective in peptic ulcer, the results obtained in different centers have not been uniform. Sucralfate and tripotassium dicitrato bismuthate both act locally by coating the ulcer crater, the latter agent also liberating prostaglandins. Most prospective studies suggest that both drugs are effective when compared with placebo. Carbenoxolone heals 70% of gastric ulcers but is less effective against duodenal ulcers, and has a high incidence of side-effects. Treatment of peptic ulcer in the 1980s has been dominated by the advent of the H2-blockers, cimetidine and ranitidine. Peptic ulcer healing rates are similar with both drugs, and the main problem is how often and how much should be given in order to provide acceptable healing and to prevent ulcer recurrence. Other H2-blockers are being tested and they may be more effective either by healing more ulcers or healing them earlier. The clinical treatment of peptic ulcers will in future be advanced by the addition of two new classes of drugs, the prostaglandins and the benzimidazole derivatives, which are currently being investigated and appear extremely promising.
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PMID:Anti-ulcer therapy. Past to present. 286 91

Stress-related mucosal damage (SRMD) of the upper gastrointestinal tract is being increasingly recognized in critically ill patients. Its precise pathogenesis is unknown. Acid is a prerequisite for the development of mucosal injury. However, mucosal defense factors that maintain the integrity of the gastric mucosal barrier are equally important. Therapy is directed toward reducing the intraluminal acid concentration. Since histamine H2-receptor antagonists became available in 1977, they have been used for the prevention and treatment of SRMD. They offer the potential for use as an effective parenteral as well as oral agent that could obviate the need for frequent antacid administration and eliminate some of the troublesome side effects that accompany an intensive antacid regimen. Although the beneficial effects of H2 blockers are probably related to their ability to inhibit acid secretion, recent evidence suggests that they may also act by mechanisms independent of their antisecretory effect. Numerous controlled studies have confirmed that cimetidine, being superior to placebo and equivalent to antacids, is effective therapy for SRMD. Sucralfate, a basic aluminum salt of sucrose octasulfate, has been shown to protect animal and human gastric mucosa from a variety of injurious agents. However, few clinical trials have evaluated the efficacy of sucralfate in SRMD. Exogenous prostaglandins also have been shown to protect gastric mucosa from a variety of insults. Although exogenous prostaglandins may work by augmenting mucosal defense mechanisms, most clinical studies have used antisecretory doses of prostaglandin drugs, making it difficult to discount the antisecretory component as being responsible for efficacy.
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PMID:Stress-related mucosal damage. 287 27

Critically ill patients are prone to stress-induced ulcerations in the upper gastrointestinal tract, which might lead to life-threatening bleeding. Therefore, an effective stress ulcer prophylaxis is absolutely indicated and H2-blocking agents, anticholinergics, antacids, sucralfate, enteral nutrition and prostaglandin E analoges are recommended. H2-blocking agents seem to provide effective prophylaxis, but severe side effects seem to limit their application. Most of all, as they are less effective as antacids and as they cause considerable costs. Additionally H2-blocking agents elevate gastric pH, thereby favouring microbic colonisation of gastric juice. Microorganism from gastric juice may reach the tracheobronchial system and lead to nosocomial pneumonias. The contaminated gastric juice may also be considered as endogenous source for sepsis and entero-colitis. The anticholinergic agent pirenzepine does not increase gastric pH and seems to be effective in neurological and neurosurgical intensive care patients. Antacids are effective in stress ulcer bleeding prophylaxis, but favour bacterial overgrowth, are badly tolerated by patients and cause a high amount of nursing time. Sucralfate seems to be as effective as antacids, is better tolerated and does not elevate gastric pH. The remaining acidity of gastric juice blocks bacterial contamination. After all, the smallest costs of effective stress ulcer prophylaxis, makes sucralfate to the medicament of first choice. However, in severely ill patients, a combined stress ulcer prophylaxis with two or more agents seems to be necessary.
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PMID:[Prevention of stress ulcer in intensive care patients]. 288 1

The aim of this study was to analyze the results and the quality of methodology of 51 controlled double blind trials in the medical treatment of gastroesophageal reflux. The results of H2 receptor antagonist treatment were evaluated by the pooling method. Evaluation of methodology was carried out by using a special form filled in by two independent observers. The major criticisms in methodology were: small sample size, unblind evaluation of end-points, inappropriate statistical tests for small samples, and inaccurate handling of the withdrawals. There were only two trials concerning antacids versus placebo: one showed that Novaluzid improved symptoms and another that Maalox did not differ from placebo. The effectiveness of alginic acid and domperidone on either symptoms or endoscopic lesions was not demonstrated. Metoclopramide and bethanechol produced significant relief of reflux symptoms. Sucralfate and bethanechol were better than placebo in improvement of esophagitis endoscopic lesions. The H2-inhibitors efficiently relieved symptoms and esophagitis. Pooling analysis showed that H2-inhibitors were superior to placebo in the healing of esophagitis; the odds ratios were 2.5 for cimetidine and 3.3 for ranitidine, without significant difference. Omeprazole was better than ranitidine in relief of symptoms and esophagitis. The comparison of cimetidine alone with cimetidine plus metoclopramide showed that combined therapy was better in one trial out of two. New controlled trials are necessary to compare these different drugs and their association.
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PMID:[Treatment of gastroesophageal reflux: analysis of randomized double-blind trials]. 289 80

All nonsteroidal anti-inflammatory drugs (NSAIDs) used in the treatment of rheumatic diseases may cause gastric mucosal damage. Although the best-studied agent is aspirin, the mechanisms by which it damages the gastric mucosa are not fully understood. However, it is thought that the drug impairs mucosal defenses by penetrating the protective mucous and bicarbonate layers and damaging the epithelial lining cells. In turn, gastric acid is permitted to pour through the breached defenses. This "back-diffusion" of acid further injures cells and destroys capillaries and venules. This local damaging effect is pH dependent and is contributed to by the acid secretion of the stomach. Other mechanisms by which aspirin may induce or contribute to mucosal injury include inhibition of mucosal prostaglandin synthesis, reduction and alteration of mucus secretion, reduction of bicarbonate secretion, interference with cell turnover, as well as systemic effects such as platelet dysfunction. The mechanism by which nonaspirin NSAIDs cause gastrointestinal damage is uncertain. All are known to inhibit prostaglandin synthesis, which could contribute to their toxicity since prostaglandins found in the stomach both inhibit acid secretion and have mucosal defensive effects. Partial protections against aspirin-induced or other NSAID-induced gastric mucosal damage has been demonstrated, at least in some studies, by sucralfate, prostaglandins, omeprazole and histamine (H2)-receptor antagonists. Sucralfate appears to act primarily on local defensive mechanisms; its antisecretory effects are minimal. Prostaglandins exert a protective effect at both antisecretory and nonantisecretory (cytoprotective) doses, indicating that either or both mechanisms may be involved. The most recently studied agent, omeprazole, is the most potent of all acid inhibitors; it may also be cytoprotective, possibly as a result of its effects on sulfhydryl groups. Prostaglandins and omeprazole are not available in the United States and their potential side effects may limit their use in patients with chronic rheumatic diseases. Protection by H2-receptor antagonists is mostly related to reduction of acid secretion, though a cytoprotective effect may occur.
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PMID:Mechanisms of nonsteroidal anti-inflammatory drug-induced gastric damage. Actions of therapeutic agents. 289 63

Syrup of ipecac (SOI) is a commonly used emetic for toxic ingestions. A preliminary study was undertaken to quantify the efficacy of SOI-induced emesis. Three groups of adult subjects fasted overnight before ingestion of 1 mCi of Tc-99m human serum albumin-sucralfate. Sucralfate is minimally absorbed from the gastrointestinal tract and has a gastric clearance half-time of 90 minutes, approximately equal to that of solid foods. At 5, 30, and 60 minutes after ingestion of radiolabeled sucralfate (RSC), subjects were given a standard dose of 30 ml SOI and 240 ml of water. Gastrointestinal tract images were obtained both at the time of ingestion of RSC and 60 minutes after ingestion of SOI. Regions-of-interest were drawn and activity measured over the stomach and small bowel with correction for physical decay. Those subjects (N = 10) treated at 5 minutes after ingestion retained a mean value of 17% of the administered RSC by 60 minutes. The group (N = 5) treated at 30 minutes after ingestion retained a mean value of 41%, while those (N = 5) treated at 60 minutes retained a mean value of 56%. The results tend to confirm the efficacy of SOI-induced emesis when SOI is given promptly (i.e., 5 minutes) following ingestion, and generally support efforts to assure widespread immediate availability of SOI for toxic ingestions.
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PMID:Efficacy of syrup of ipecac-induced emesis for emptying gastric contents. 290 46

Both genetic and nongenetic factors predispose to ulcer diathesis. At the mucosal level ulcers result from an imbalance between aggressive factors and mucosal defense. Ulcer therapy reduces aggressive forces, bolsters defense, or both. Gastric acid, the major aggressive factor, may have its secretion inhibited or it may be partially neutralized by antacids. H2 receptor antagonists competitively block histamine occupancy of H2 receptors on parietal cells, thereby preventing stimulation of adenylate cyclase, cAMP rises, and activation of protein kinase and H+/K+ATPase. Prostaglandins inhibit acid secretion largely by preventing histamine-induced cAMP rises. Proton pump inhibitors bind H+/K+ATPase. Antimuscarinics inhibit acetylcholine receptors on the parietal cell, thereby blocking Ca2+ entry and subsequent activation of protein kinase and the proton pump. Mucosal defense is enhanced by certain prostaglandins, colloidal bismuth subcitrate and sucralfate. Prostaglandins stimulate secretion of bicarbonate and mucus, among other effects. Colloidal bismuth and sucralfate bind to proteins in the ulcer base and stimulate bicarbonate and mucus secretion, partially, in the case of sucralfate, by increasing endogenous prostanoid synthesis. Sucralfate also binds pepsin and bile acids. Colloidal bismuth temporarily eradicates mucosal colonization by Campylobacter pylori, another putative agent in ulcer diathesis.
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PMID:The pathophysiological and pharmacological basis of peptic ulcer therapy. 290 42

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.
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PMID:Management of NSAID-induced gastrointestinal lesions. 290 80

Sucralfate has been reported to reduce serum phosphate concentration in patients with chronic renal failure. To evaluate whether sucralfate could be used to treat hyperphosphatemia secondary to chronic renal failure and whether this treatment resulted in a reduced exposure to aluminum, an open-label crossover study was designed to determine the efficacy, relative potency, safety, and cost of sucralfate v aluminum hydroxide. Of the 21 hemodialysis patients completing both phases of the crossover study, serum phosphate could be maintained below 4.5 mg/dL (1.45 mmol/L) in 16 with sucralfate and in 14 with aluminum hydroxide. The 16 patients controlled on sucralfate consumed 1,694 +/- 190 mg/d of aluminum to maintain a serum phosphate concentration of 3.91 +/- 0.17 mg/dL (1.27 +/- 0.05 mmol/L) compared with the 14 patients controlled on aluminum hydroxide with an aluminum intake of 2,678 +/- 294 mg/d (P less than 0.025) and a serum phosphate concentration of 3.94 +/- 0.13 mg/dL (1.27 +/- 0.04 mmol/L). Thus sucralfate was an effective, albeit expensive, alternative to aluminum hydroxide for the treatment of hyperphosphatemia associated with chronic renal failure. Although the difference in aluminum intake was significant, use of sucralfate did not result in lower serum aluminum concentrations.
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PMID:Phosphate-binding effects of sucralfate in patients with chronic renal failure. 291

The efficacy of orally administered sucralfate suspension in preventing and treating chemotherapy-induced mucositis was evaluated in a double-blind trial. Forty-eight children and adolescents with newly diagnosed acute nonlymphocytic leukemia were randomized to receive suspensions of either sucralfate or placebo orally every 6 hours during the first 10 weeks of intensive remission-induction chemotherapy. Patients given sucralfate suspension were less likely than subjects receiving placebo to acquire colonization with potentially pathogenic microorganisms: 14 (58%) of 24 versus 22 (92%) of 24, respectively (p = 0.008). However, no effect on preexisting colonization was noted. Subjective reporting of discomfort, objective scoring of the severity of mucositis, and the maximal percent of body weight lost during therapy were similar; 58% of patients receiving sucralfate reported no oral pain compared with 25% receiving placebo (p = 0.06). Ten episodes of gastrointestinal bleeding, 25 documented infections, and 886 days with fever were also equally distributed between sucralfate and placebo groups. We conclude that sucralfate suspension is of limited, if any efficacy, in the prevention and treatment of chemotherapy-induced mucositis. Sucralfate administration can, however, reduce acquisition of alimentary colonization with potential pathogens, perhaps by interfering with adherence to mucosal membranes.
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PMID:Efficacy of oral sucralfate suspension in prevention and treatment of chemotherapy-induced mucositis. 305 5


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