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, a basic aluminum salt of sucrose octasulfate, was developed to counteract the activities of both acid and pepsin. It differs chemically from other sulfated anionic inhibitors of pepsin in being a base and a derivative of pure disaccharide sucrose. The development of sucralfate was guided by the observations that sulfated disaccharides do not exhibit the anticoagulant activity of sulfated polysaccharides, and that the inhibition of peptic activity and the protection against experimental ulceration depend only on the degree of sulfation. Sucralfate has been found to protect pylorusligated animals from peptic ulceration more effectively than a mixture of sucrose octasulfate and aluminum hydroxide. Sucralfate has several unusual properties. On encountering gastric acid, it becomes a highly condensed, viscous substance with the capacity to buffer acid. These properties are retained in the duodenum. Sucralfate forms stable complexes with proteins and inhibits their hydrolysis by preventing pepsin-substrate interaction. Sucralfate also inhibits peptic activities by direct adsorption of pepsin. In addition, sucralfate adsorbs bile salts. The sum of these properties implies that sucralfate provides a comprehensive defense against identified aggressive factors, acid, pepsin, and bile salts.
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PMID:Development and characteristics of sucralfate. 679 99

Sucralfate, a complex salt of polyaluminum hydroxide with a sulfated disaccharide skeleton, has recently been approved by the Food and Drug Administration for the short-term treatment of duodenal ulcer. The drug is nonsystemic in action and apparently exerts its antiulcer effects by bonding with proteinaceous exudates in the ulcer crater, thereby protecting it from insult. In vitro and clinical studies have shown that the drug is not an antacid but does block the diffusion of acid. Inhibition of pepsin and bile acid activities have also been demonstrated. In double-blind clinical trials where patients used antacids as needed for pain, sucralfate 1 g 4 times a day was significantly more effective than placebo and as effective as cimetidine. No serious adverse effects have been caused by this locally-acting agent.
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PMID:Pharmacology, clinical efficacy, and adverse effects of sucralfate, a nonsystemic agent for peptic ulcer. 692 35

Sucralfate inhibits activity of certain Helicobacter pylori enzymes, implying that this medication may limit gastric cell injury associated with H pylori infection. This study evaluates the ability of sucralfate and its two major structural components, sucrose octasulfate and aluminum hydroxide, to reduce the cytotoxic effects of H pylori and to inhibit binding of H pylori to human gastric epithelial cells. Experiments were performed using human gastric epithelial cells isolated from gastric biopsy tissue taken at upper gastrointestinal endoscopy. Primary cultures of human gastric epithelial cells, when exposed to broth-culture supernatant from a vacuolating cytotoxin-positive H pylori strain, were shown to form cytoplasmic vacuoles. Preexposing H pylori brothculture supernatant to sucralfate reduced vacuole formation in human gastric epithelial cells; however, preexposure of H pylori broth-culture supernatant to aluminum hydroxide or sucrose octasulfate did not reduce vacuolation in human gastric epithelial cells. H pylori binding to human gastric epithelial cells was significantly reduced when H pylori was exposed to sucralfate prior to incubating the bacterium with human gastric epithelial cells. These data show that sucralfate, but not its two major components, reduces the toxicity of an H pylori-produced cytotoxin (VacA) and decreases H pylori adherence to human gastric epithelial cells. This reduction in H pylori cytotoxicity may contribute to sucralfate's ulcerhealing properties and to the lower ulcer recurrence rates seen in patients treated with this medication.
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PMID:Effects of sucralfate on vacuolating cytotoxin activity and adherence of Helicobacter pylori to human gastric epithelial cells. 893 34

We have established models of cell damage induced by acid and pepsin using rat gastric epithelial cells (RGM1). In the present study, the effects of aluminum hydroxide [Al(OH)3] and potassium sucrose octasulfate (KSOS), which are components of sucralfate, and sucralfate on cell damage and peptic activity of pepsin were examined. Pretreatment of cells with sucralfate (0.1-3 mg/ml) or Al(OH)3 (0.1-1 mg/ml) for 2 hr prevented both acid- (pH 4.0) and pepsin- (pH 4.5) induced cell damage. However, KSOS (0.1-1 mg/ml) did not show any effects on two different types of cell damage. The peptic activity of pepsin at pH 4.5 was about 10% of that at pH 2.0. Sucralfate and KSOS slightly inhibited peptic activity at pH 4.5. Al(OH)3 inhibited peptic activity by approximately 50%; however, no concentration-dependent pattern was observed. Pepstatin (0.003-0.1 mg/ml), a specific inhibitor of pepsin, inhibited the peptic activity in a concentration-dependent manner. Here, we confirmed that sucralfate and Al(OH)3 have cytoprotective effects against acid- and pepsin-induced cell damage. The mechanism behind the cytoprotective effects of sucralfate seems to relate to adhesion of the cell surface and neutralization of hydrogen ion by aluminum that prevents the penetration of hydrogen ions into the cells.
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PMID:Effects of sucralfate and its components on acid- and pepsin-induced damage to rat gastric epithelial cells. 933 82

Sucralfate, a complex of aluminium hydroxide with sulfated sucrose, forms a strong gastrointestinal tract (GIT) mucosal barrier with excellent anti-ulcer property. Because sucralfate does not undergo any significant oral absorption, sucralfate resides in the GIT for a considerable length of time. The unabsorbed sucralfate may alter the pharmacokinetics of the oral drugs by impeding its absorption and reducing the oral bioavailability. Because of the increased use of sucralfate, it was important to provide a reappraisal of the published clinical drug-drug interaction studies of sucralfate with scores of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along with study design, objectives and key remarks. While the loss of oral bioavailability was significant for the fluoroquinolone class, it generally varied for other classes of drugs, suggesting that impact of the co-administration of sucralfate is manageable in clinical situations. Given the technology advancement in formulation development, it may be in order feasible to develop appropriate formulation strategies to either avoid or minimize the absorption-related issues when co-administered with sucralfate. It is recommended that consideration of both in vitro and preclinical studies may be in order to gauge the level of interaction of a drug with sucralfate. Such data may aid in the development of appropriate strategies to navigate the co-administration of sucralfate with other drugs in this age of polypharmacy.
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PMID:Clinical Drug-Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs: Review and Perspectives. 2708 59


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