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)

Pharmacologic management of peptic ulcer disease continues to evolve with the introduction of diverse types of new therapeutic agents. The ideal aims of treatment of peptic ulcer disease are to relieve pain, heal the ulcer, and delay ulcer recurrence. This article provides a broad perspective on the pharmacology and therapeutic actions of antiulcer drugs. To date, no drug meets all goals of therapy. Drug treatment of peptic ulcers is targeted at either counteracting aggressive factors or stimulating the mucosal defense. Drugs that inhibit or neutralize gastric acid secretion include histamine H2-receptor antagonists, proton pump inhibitors, anticholinergics, prostaglandins, and antacids. H2-receptor antagonists have become first-line drugs for treatment of uncomplicated duodenal ulcers, gastric ulcers, prevention of ulcer relapse, and mild esophagitis. However, H2-receptor antagonists, like other gastric antisecretory/antiulcer drugs, have high rates of ulcer recurrence following discontinuation of therapy. They therefore need to be administered continuously in patients prone to such recurrences. Omeprazole has emerged as a major drug for the treatment of severe erosive esophagitis, refractory ulcers, and Zollinger-Ellison syndrome. The major disadvantage of proton pump inhibitors is the concern for their long-term safety. The roles of M1-antimuscarinic agents and antacids have not been fully defined. Misoprostol, effective for the treatment of gastric and duodenal ulcers, is now the only drug that prevents ulcers induced by nonsteroidal anti-inflammatory drugs. Mucosal protective drugs that do not inhibit gastric acid secretion include sucralfate and organic bismuth salts. Sucralfate is a nonsystemic, well-tolerated, effective drug for treatment of duodenal ulcers and prevention of duodenal ulcer relapse. The organic bismuth salt bismuth subcitrate is efficacious in the treatment of duodenal and gastric ulcers. Furthermore, it has also been established that it alters the course of ulcer recurrence. However, bismuth encephalopathy is a major toxicity concern that needs to be addressed.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Drugs for treatment of peptic ulcers. 135 99

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.
 ...
PMID:The pathophysiological and pharmacological basis of peptic ulcer therapy. 290 42

Absorption of ketoconazole is impaired in subjects with an increased gastric pH due to administration of antacids, H2-receptor antagonists, proton pump inhibitors, or the presence of hypochlorhydria. Sucralfate could provide an attractive alternative in patients receiving ketoconazole who require therapy for acid-peptic disorders. Twelve healthy human volunteers were administered a single 400-mg oral dose of ketoconazole in each of three randomized treatment phases. In phase A, ketoconazole was administered orally with 240 ml of water. In phase B, ketoconazole and sucralfate (1.0 g) were administered simultaneously with 240 ml of water. In phase C, ketoconazole was administered with 240 ml of water 2 h after administration of sucralfate (1.0 g) orally with 240 ml of water. A 680-mg oral dose of glutamic acid hydrochloride was administered 10 min prior to and with each dose of ketoconazole, sucralfate, or ketoconazole plus sucralfate. Simultaneous administration of ketoconazole and sucralfate led to a significant reduction in the area under the concentration-time curve and maximal concentration of ketoconazole in serum (78.12 +/- 12.20 versus 59.32 +/- 13.61 micrograms.h/ml and 12.34 +/- 3.07 versus 8.92 +/- 2.57 micrograms/ml, respectively; P < 0.05). When ketoconazole was administered 2 h after sucralfate, the observed ketoconazole area under the concentration-time curve was not significantly decreased compared with that of ketoconazole alone. The time to maximal concentrations in serum and the ketoconazole elimination rate constant were not significantly different in any of the three treatment phases. In patients receiving concurrent administration of ketoconazole and sucralfate, doses should be separated by at least 2 h.
 ...
PMID:In vivo interaction of ketoconazole and sucralfate in healthy volunteers. 791 Jul 24

Medical therapy for reflux esophagitis is designed to provide symptom relief and esophageal healing, and to prevent complications. Life-style modifications serve as an adjunct to drug therapy. Sucralfate, prokinetic agents, and H2-receptor antagonists promote symptom relief and esophageal healing in mild esophagitis, but are less effective in the treatment of moderate to severe esophagitis. For patients with mild to severe (erosive) esophagitis, rapid symptom relief and esophageal healing have been achieved with proton pump inhibitors such as omeprazole and lansoprazole.
 ...
PMID:Therapeutic approaches to healing esophagitis. 912 23

Coprescription of gastroprotective agents is a common practice for patients requiring nonsteroidal anti-inflammatory drug (NSAID) therapy, although there is limited evidence that some of these agents are effective. The prostaglandin analog misoprostol and the proton pump inhibitor omeprazole appear to be efficacious in decreasing NSAID-associated ulcers. Misoprostol has also been shown to decrease NSAID-associated gastrointestinal (GI) complications by 40% compared with placebo. Despite the efficacy of these drugs, their effectiveness in the general population has not yet been adequately determined with respect to reduction of symptoms and improvement in patient quality of life. Sucralfate and bismuth appear to be largely ineffective, and histamine receptor antagonists, when given at traditional ulcer-healing doses, decrease symptoms and duodenal ulcers only. The issue of outcomes research, therefore, needs to be more fully incorporated into any analysis of the effectiveness or cost-effectiveness of the widespread clinical use of such gastroprotective drugs.
 ...
PMID:Agents used in the prevention and treatment of nonsteroidal anti-inflammatory drug-associated symptoms and ulcers. 985 74

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

Non-ulcer dyspepsia is common and is often confused with other diagnoses. It remains a condition identified by exclusion, and continues to be a challenge to manage. Currently, only a limited number of pharmacological options are available. Antacids are no more effective than placebo in treating nonulcer dyspepsia. H2-receptor antagonists appear to be superior to placebo in efficacy, but many of the studies suggesting this finding have had a suboptimal study design. Proton pump inhibitors have been shown to be superior to placebo, although questions remain as to whether the only subgroup that responds is comprised of patients with unrecognized gastroesophageal reflux disease. Studies have found that prokinetic agents are superior to placebo, but currently only a very limited number of agents within this class can be prescribed in the United States. Sparse data support the role of metoclopramide and its side effects limit its use even further. The eradication of Helicobacter pylori has a small but positive therapeutic benefit in non-ulcer dyspepsia, and can be considered in those confirmed to be infected. Sucralfate is unlikely to be effective, and misoprostol is ineffective. Bismuth alone is probably not efficacious. Tricyclic antidepressants may have a therapeutic role, but this is not firmly established and this class of medication should be reserved for resistant cases. Emerging therapies include drugs that relax the gastric fundus, such as buspirone or sumatriptan, and the new prokinetic tegaserod. Psychological therapies may play a role but studies of these therapies are limited. Therapy for non-ulcer dyspepsia remains challenging and is usually empiric; it will remain so until the mechanisms that induce symptoms of dyspepsia are better understood.
 ...
PMID:Update on the role of drug therapy in non-ulcer dyspepsia. 1268 90

Although the incidence of stomach hemorrhage is declining, stress-related gastric bleeding remains an important source of morbidity and mortality in cancer patients undergoing major surgical procedures to remove tumor. Prevention of stress-related bleeding is desirable; however, the optimal use of drugs to prevent gastric bleeding is unclear. Prophylaxis is recommended for surgical patients who require prolonged mechanical ventilation or have a coaguloathy. Histamine-2 receptor antagonists and sucralfate will reduce the likelihood of clinically important gastric-bleeding. Sucralfate appears to be less effective than H-2 blockers, but it is associated with fewer side effects such as nosocomial pneumonia. Preliminary studies show that proton pump inhibitors are most effective, have few side effects, but are most expensive. Intravenous proton pump inhibitors may be the drugs of choice for stress ulcer prophylaxis (SUP) in high-risk patients.
 ...
PMID:Evidence-based analysis: postoperative gastric bleeding: etiology and prevention. 1268 66

It has been documented that sucralfate, a basic aluminum salt, enhances the efficacies of antibiotics against Helicobacter pylori, resulting in eradication rates comparable to those associated with the use of proton pump inhibitors. However, its mechanism of action remains unclear. The aim of the present study was to investigate sucralfate's ability to complement antibiotic treatment of H. pylori infection in vivo. Four weeks following induced H. pylori infection, clarithromycin (CAM) and amoxicillin (AMPC) were administered orally to C57BL/6 mice for 5 days, both with and without sucralfate or lansoprazole. When sucralfate was concurrently given with CAM and AMPC at the maximum noninhibitory doses for the treatment of H. pylori infection, the bacterial clearance rates were comparable to those achieved by treatment with lansoprazole plus those antibiotics. The results of pharmacokinetic studies showed that lansoprazole delayed gastric clearance and accelerated the absorption of CAM, whereas sucralfate suppressed both gastric clearance and absorption. AMPC was undetectable in all samples. Scanning electron microscopy with a microscope to which a energy dispersive spectrometer was attached revealed that aluminum-containing aggregated substances coated the mucosa surrounding H. pylori in mice receiving sucralfate plus antibiotics, whereas the gastric surface and pits where H. pylori had attached were clearly visible in mice receiving lansoprazole plus antibiotics. The addition of sucralfate to the antibiotic suspension resulted in a more viscous mixture that bound to the H. pylori-infected mucosa and that inhibited the loss of CAM bioavailability in the acidic environment. Sucralfate delays gastric clearance of CAM and physically captures H. pylori through the creation of an adherent mucus, which leads to bacterial clearance.
 ...
PMID:Effect of sucralfate on antibiotic therapy for Helicobacter pylori infection in mice. 1556 29