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)

Drugs used in the treatment of peptic ulcer disease may interact with the renal system in a variety of ways. Since many agents are eliminated by renal excretion, clearance of these agents may be reduced and half-life extended in the presence of renal insufficiency. The histamine H2-receptor antagonists may interfere with renal tubular excretion of creatinine and cationic drugs, resulting in elevated serum concentrations and reduced renal clearance. The prostaglandin E1 analogue misoprostol is used as a cytoprotective agent but has renal effects. The renal effects differ between systems studied. In the rat, misoprostol reduces cyclosporin-induced renal tubular toxicity, whereas in humans it has been shown to attenuate renal allograft rejection. Sucralfate is the aluminium salt of sucrose octasulfate. It permits the absorption of aluminium in amounts similar to aluminium-containing antacids, and toxicity has been demonstrated in the presence of renal insufficiency. Bismuth compounds are used increasingly to treat peptic ulcer disease, and bismuth toxicity has been described in association with renal insufficiency. Aluminium-, calcium- and magnesium-containing antacids are used as oral phosphate binders in patients with renal insufficiency in addition to their usual indications. Cation absorption and accumulation with all of these antacid preparations has been described and may lead to toxicity.
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PMID:Renal effects of peptic ulcer therapy. 152

In the United States, the drugs most commonly used to treat peptic ulcer disease are antacids and the H2-receptor antagonists cimetidine and ranitidine. Other available agents include anticholinergics and the coating agent sucralfate. Investigational drugs such as colloidal bismuth, carbenoxolone, prostaglandins, the tricyclic compound pirenzepine, and substituted benzimidazoles are not available for use in the United States. Most of the commercially available and investigational compounds have similar efficacy; therefore the optimal drug may be the one associated with the fewest adverse effects and the most convenient dosing regimen. Cimetidine causes a small number of adverse effects, including neuropsychiatric disorders, gynecomastia, impotence, loss of libido, elevation of serum creatinine and serum transaminases concentrations, and drug interactions. Some of these reactions have been of clinical significance. Presently, there are rare reports of gynecomastia, bradycardia, inhibition of acetylcholinesterase, headache, lethargy, diarrhea, and rash in patients receiving ranitidine. Antacids can produce either diarrhea or constipation and have been associated with low serum phosphorus concentrations, and metabolic alkalosis. Anticholinergics, especially in elderly or debilitated patients, can cause central nervous system disorders, intestinal atony, or urinary retention. Sucralfate may cause constipation, diarrhea, nausea, and headache. The investigational agents have their own side effect profiles. The adverse effects of anticholinergics make them unattractive therapeutic choices, and antacids and sucralfate have inconvenient dosing requirements compared with some equally efficacious alternatives. In addition, clinical experience with sucralfate in the United States is limited. The safety record of cimetidine is admirable. As clinical experience with ranitidine increases, currently unrecognized adverse effects may be reported. However, based on current data, ranitidine is as effective as cimetidine and is associated with a lower incidence of side effects.
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PMID:Problems associated with medical treatment of peptic ulcer disease. 609 62

Elevated aluminum concentrations have been implicated in several disease states in the elderly. We examined the effects of sucralfate, a basic aluminum salt of sucrose sulfate, and ranitidine, administered individually and in combination, on plasma and urine aluminum concentrations in the elderly in a prospective, randomized, three-arm crossover study. Subjects were 20 healthy volunteers over age 65 years, with no clinically significant comorbidities or recent use of aluminum-containing drugs or histamine (H)2-antagonists. The three regimens were ranitidine 300 mg at bedtime, sucralfate 1 g 4 times/day, and ranitidine 300 mg at bedtime plus sucralfate 1 g 4 times/day, administered for 4 weeks, with a washout period of at least 1 week between regimens. Plasma and urine aluminum concentrations were measured on days 0, 1, 7, 14, and 28 of each regimen. After 28 days, mean plasma aluminum concentrations were significantly higher in subjects receiving sucralfate alone (8.5 +/- 1.8 micrograms/L) and sucralfate plus ranitidine (5.1 +/- 1.3 micrograms/L) compared with those receiving ranitidine alone (2.4 +/- 0.7 micrograms/L). Urine aluminum concentrations were significantly higher in subjects receiving sucralfate alone (133.2 +/- 32.8 micrograms/g creatinine) and sucralfate plus ranitidine (148.1 +/- 51.9 micrograms/g creatinine) compared with those receiving ranitidine alone (11.0 +/- 3.7 micrograms/g creatinine). There was no significant difference in plasma or urine aluminum concentrations between subjects who received sucralfate alone versus those who received sucralfate plus ranitidine. Sucralfate 4 g/day in elderly subjects produces a significant increase in both plasma and urine aluminum concentrations, compared with ranitidine 300 mg/day. This increase most likely is secondary to gastrointestinal absorption of aluminum in the sucralfate formulation. The clinical relevance of this increase requires further evaluation.
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PMID:Effects of sucralfate and ranitidine on aluminum concentrations in elderly volunteers. 860 82

BACKGROUND: Sucralfate, used in stress ulcer prophylaxis, contains aluminum, which can be absorbed from the gut. OBJECTIVE: To determine whether toxic serum aluminum levels can develop after short-term sucralfate therapy in critically ill children. DESIGN: Retrospective clinical study. SETTING: Pediatric intensive care unit of a pediatric university hospital. PATIENTS: Nineteen patients receiving mechanical ventilatory support (median age, 5 yrs [range, 0.25-16 yrs]; median weight, 17 kg [range, 3.5-60 kg]). INTERVENTIONS: All patients received sucralfate suspension nasogastrically. Measurements and RESULTS: Serum aluminum concentrations were measured after a short period on sucralfate therapy (median time, 7 days [range, 3-14 days]). There was no correlation between total sucralfate dose received (p =.35) or dose of sucralfate per unit of body weight (p =.55) and serum aluminum. Nine patients received peritoneal dialysis. Serum aluminum levels were higher in the nine patients who received peritoneal dialysis (median aluminum concentration, 2.86 &mgr;mol/L [range, 0.19-12.3 &mgr;mol/L]) than the ten patients not dialyzed (median aluminum concentration, 0.55 &mgr;mol/L [range, 0.18-0.94 &mgr;mol/L]) (p =.001). The peak serum creatinine levels were higher in the dialyzed patients (median creatinine level, 500 &mgr;mol/L [range, 163-910 &mgr;mol/L]) than those not dialyzed (median creatinine level, 98 &mgr;mol/L [range, 36-415 &mgr;mol/L]) (p =.006). There was a trend toward correlation between peak serum creatinine and serum aluminum (p =.06). CONCLUSION: Aluminum accumulation occurs in children with acute renal failure on sucralfate, especially those receiving dialysis. If sucralfate is used in children in renal failure, serum aluminum concentrations should be monitored regularly.
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PMID:Aluminum accumulation in critically ill children on sucralfate therapy. 1279 50