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, an aluminum hydroxide complex of sulfated sucrose used in the treatment of gastric ulcer, was shown to prevent irradiation-induced diarrhea and bowel discomfort significantly in patients treated for pelvic cancer with external radiotherapy with intent to cure. The double-blind placebo-controlled study included 70 patients with carcinoma of the prostate and urinary bladder without distant metastasis (T1-4NO1xMO) and performance status of greater than or equal to 90% Karnofsky scale. Radiotherapy was administered in a conventional manner with MeV photons and a four-field technique. The total dose was 62-66 Gy and total treatment time of 6.5 weeks. Dose granules of sucralfate or placebo were dispensed to each patient 2 weeks after radiation started and continued for 6 weeks. All analyses were performed blindly. Seven of 34 evaluable patients in the placebo group and 18 of 32 evaluable patients in the sucralfate group did not present with diarrhea during the observation period. The frequency of defecation and stool consistency were significantly improved by sucralfate. Fourteen patients in the placebo group and only three in the sucralfate group required symptomatic therapy with loperamide. There was no evidence of adverse effects associated with the use of sucralfate. Sucralfate can be of beneficial value in diminishing the bowel discomfort during radiotherapy of pelvic malignancies, and the earlier proposed mechanisms of action (e.g., protection of denuded mucosa, cytoprotective properties, binding bile acids) can also be valid for the current effects of sucralfate.
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PMID:Prevention of irradiation-induced bowel discomfort by sucralfate: a double-blind, placebo-controlled study when treating localized pelvic cancer. 188 3

Viable bacteria in the gut of thermally injured patients may be translocated through the gut mucosa, causing widespread infection. Increased flora from optimization of bacterial growth by pH elevation, coupled with the decreased intestinal motility common among patients whose mucosal integrity has been compromised, may increase the incidence of translocation. Gastric pH in these patients is monitored and maintained around pH 6 by various agents to reduce susceptibility to stress ulceration. Whole milk, given as a nutrient source, also raises pH. An in vitro trial simulating gastric fluid under conditions found in patients with burns was conducted to evaluate the growth of commonly ingested bacteria. Bicarbonate buffer containing pepsin and adjusted to pH 2, 4, or 7 with HCl was dosed with magnesium and aluminum hydroxide antacid (Maalox) (10 ml), sucralfate (Carafate) (0.4 gm), or prostaglandin E2 (PGE2) (10 ng) before inoculation with Escherichia coli (3 x 10(2) organisms), Pseudomonas aeruginosa (3 x 10(2) organisms), or Staphylococcus aureus (2 x 10(1) organisms). Bacterial growth and pH were determined periodically over the 24-hour trial. Milk was added at intervals in half the samples to simulate patient feeding. Maalox increased pH in all samples containing milk (initially pH 2, 4, or 7) to over 7.0 in 2 hours, and increased pH more slowly without milk. Carafate had a moderating effect, increasing pH 2 and pH 4 and decreasing pH 7, with a narrower pH range found in the milk groups. PGE2 treatments combined with milk also increased pH 2 and pH 4, but slightly elevated pH 7 within 24 hours. Without milk, PGE2 did not alter pH from initial values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antacid, sucralfate, and prostaglandin E2 effects on the growth and potential for translocation of Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus in an in vitro gastric simulation. 190 78

The present study evaluated the effect of sucralfate and its components, sucrose octasulfate and aluminum hydroxide, on: (1) damage to rat cultured gastric mucosal cells induced by sodium taurocholate in a neutral environment and in conditions independent of systemic factors, (2) prostaglandin E2 and on 6-keto prostaglandin F1 alpha release by cultured cells, and (3) sulfhydryl content of cultured cells. Cell damage was quantitated by chromium-51 release assay. Prostaglandin E2 and 6-keto prostaglandin F1 alpha were measured by radioimmunoassay. Total sulfhydryl content of cultured cells was determined calorimetrically. Microscopically, sucralfate was found to adhere tightly to epithelial cell surfaces despite frequent washings. Sucralfate 2 mg/ml and 5 mg/ml significantly decreased taurocholate-induced damage, reducing taurocholate-induced specific 51Cr release by 11.8 points (equal to 29% decrease in cell damage, P less than 0.01) and 22.9 points (equal to 56% decrease in cell damage, P less than 0.001), respectively. Sucrose octasulfate and aluminum hydroxide did not exert significant protection against damage induced by sodium taurocholate. The protective effect of sucralfate was not prevented by indomethacin, nor was it counteracted by the sulfhydryl blocker, iodoacetamide. Sucralfate, but not its components, significantly and dose-dependently stimulated prostaglandin E2 (r = 0.94, P less than 0.05) and 6-keto prostaglandin F1 alpha (r = 0.89, P less than 0.05) production by cultured cells. Neither sucralfate nor its components affected sulfhydryl content of cultured cells. In conclusion, sucralfate, but not its components, (1) protects rat gastric mucosal cells against taurocholate-induced damage in conditions independent of systemic factors and in a neutral environment and (2) significantly stimulates prostaglandin production by cultured cells. (3) The protection by sucralfate in vitro does not seem to depend on its stimulatory effect on endogenous prostaglandin synthesis.
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PMID:Effect of sucralfate and its components on taurocholate-induced damage to rat gastric mucosal cells in tissue culture. 231 93

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

We have validated a method to measure bile salt binding by Maalox (aluminum hydroxide and magnesium hydroxide), Carafate (sucralfate), and Questran (cholestyramine) in vitro. The method used in this study involves a correction for adherent water volume and thus provides a correct measure of bile salt binding. With this approach, we described the binding properties of Maalox, Carafate, and Questran. The bile salt binding capacities of Carafate and Maalox are limited and do not have physiological or pharmacological significance. On the other hand, we found that Questran has substantial bile salt binding capacity. At the recommended dosage, Questran could deplete the total bile salt pool. We also found that Carafate, although not used as an antacid, has buffering capacity (maintaining a pH of solution in the range 4.2-4.8) which might contribute to its effectiveness as an ulcer treatment drug.
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PMID:Bile salt binding properties of commonly used gastrointestinal drugs: maalox, carafate, and questran. 317 34

Sucralfate, one of the newer drugs shown to be effective in the treatment of peptic ulcer and esophagitis; cholestyramine, a known bile acid binder; and commercial antacid preparations of pure aluminum hydroxide, pure magnesium hydroxide, and a combination of aluminum hydroxide, magnesium hydroxide, and magnesium carbonate were tested in vitro for bile acid-binding capacity. Cholestyramine was found to be the most effective bile acid binder, with more than 90% of bile acids adsorbed at all of the pH values studied. Sucralfate proved efficacious at pH 4, 6, and 8, adsorbing about 50% of the bile acids, but its binding capacity decreased at pH 2. Pure aluminum hydroxide was the most effective of the various antacid preparations; it adsorbed about 90% of bile acids at pH 2, although this percentage was significantly reduced at pH 6 and 8. Sucralfate was significantly more effective as a bile acid absorbent at pH 4 than either the magnesium hydroxide or aluminum-magnesium hydroxide plus magnesium carbonate antacids, as effective as the aluminum hydroxide antacid, and significantly less effective than cholestyramine.
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PMID:Adsorption of bile acids by sucralfate, antacids, and cholestyramine in vitro. 344 Feb 73

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.
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PMID:Effects of sucralfate or mild irritants on experimental gastritis and prostaglandin production. 347 60

Sucralfate has been reported to protect the esophageal epithelium of the rabbit and cat against acid injury. To determine the contribution of its components, aluminum hydroxide and sucrose octasulfate (SOS), rabbit esophageal epithelia were mounted in Ussing chambers to monitor changes in electrical resistance (R) upon exposure to HCl (pH 1.4-1.6). In untreated tissues, acidification of the luminal bath produced a progressive decline in R, indicating increased epithelial permeability. Sucralfate added to the luminal bath 45 min after acidification increased R to preexposure levels--an effect accompanied by increased luminal pH. Similar to sucralfate, aluminum hydroxide added to the acidified bath increased R and luminal pH. However, the effect of aluminum hydroxide could be abolished by titration with HCl to maintain pH similar to acid-treated control tissues. Tissues treated with sucralfate and whose luminal solutions were titrated with HCl to maintain pH similar to controls no longer exhibited an increase in R but, in contrast to aluminum hydroxide treatment, the acid-induced decline in R was prevented. This action of sucralfate was shown to be a property of its other component, SOS. Sucrose octasulfate, like acid-titrated sucralfate solutions, did not increase luminal bath pH, yet prevented the acid-induced decline in R. Confirmation of protection by SOS was shown by additional morphologic and flux studies. Thus 1 h after luminal bath acidification in the Ussing chamber, SOS-treated tissues demonstrated less damage (injury score 0.6 +/- 0.4 vs. 1.6 +/- 0.3, p less than 0.05) and lower permeability to mannitol (0.003 +/- 0.001 vs. 0.013 +/- 0.005 mumol/h X cm2, p less than 0.05) than untreated tissues. Similarly, 1 h of luminal perfusion with HCl in vivo produced less damage (injury score 1.3 +/- 0.5 vs. 3.5 +/- 0.4, p less than 0.05) and less H+ efflux from the lumen in SOS-treated than untreated tissues. These results indicate that sucralfate can protect against acid injury in esophagus and that this protection is mediated by (a) intraluminal pH buffering through its content of aluminum hydroxide and (b) enhancing mucosal defense against H+ entry and injury through its content of SOS.
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PMID:Mucosal protection by sucralfate and its components in acid-exposed rabbit esophagus. 359 73

It is known that antacids containing aluminum hydroxide inhibit peptic activity by raising intragastric pH and by adsorbing pepsin. Since sucralfate contains aluminum hydroxide moieties, the possibility that this drug might inhibit peptic activity by these same mechanisms was examined. Sucralfate was incubated at a concentration of 10 mg/ml with samples of human gastric juice having pH values between 1.5 and 4 for 30 minutes at 37 degrees C. The proteolytic activity of the supernatant was then determined at a pH of 2.2 against a bovine hemoglobin substrate. When the initial pH of the gastric juice sample was 1.5, sucralfate was converted to a viscous gel and the pH of the incubation mixture rose to 2.9. However, there was no decrease in the peptic activity of the supernatant. In contrast, when the pH of the gastric juice sample was more than 2, the drug remained in suspension, but there was a graded rise in pH to a maximum of 4.1 and a progressive decrease in peptic activity (determined at a pH of 2.2) to a nadir of 65 percent of the control value. However, because peptic activity declines rapidly at a pH of more than 3, peptic activity at the ambient pH of the samples was reduced to only 25 percent of the control value. The results indicate that at pH values of more than 2, sucralfate inhibits peptic activity by both adsorbing pepsin and buffering hydrogen ions.
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PMID:Inhibition of peptic activity by sucralfate. 392 1

In an attempt to discover a phosphate binding agent for use in uraemia that would not lead to appreciable systemic absorption of aluminium the effect of sucralfate was evaluated after three weeks and compared with that of the existing standard agent aluminium hydroxide. Sucralfate caused a decrease in serum phosphate concentration comparable with that obtained with aluminium hydroxide, but similar absorption of aluminium resulted. Sucralfate may be the phosphate binder of choice in patients with uraemia and peptic ulceration; care should be taken in using large doses of the drug in patients with normal renal function.
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PMID:Aluminium hydroxide versus sucralfate as a phosphate binder in uraemia. 640 68


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