Sucralfate

Description

Sucralfate is a complex of the sulfuric acid ester of sucrose and aluminum hydroxide. Secondary polymerization with aluminum hydroxide forms intermolecular bridges between molecules of sulfate esters with aluminum. Limited dissociation of the complex occurs in gastric acid, but these anionic sulfate esters form insoluble adherent complexes with the proteinaceous exudate at the abraded surface of a crater of the ulcerated area in the stomach. This physical complex protects the ulcer from the erosive action of pepsin and bile salts. Sucralfate also stimulates synthesis and release of prostaglandins, bicarbonate, and epidermal and fibroblast growth factors. Significant ulcer healing effects are noted in placebo-controlled trials. Only small amounts of sucralfate are absorbed systemically. In renal impairment, there is a risk of accumulation of absorbed aluminum from the drug. Sucralfate reduces absorption of other drugs, including H2 antihistamines, quinolone antibiotics, phenytoin, and perhaps, warfarin

Description

Sucralfate is a basic aluminum sucrose sulfate complex that has gastroprotective activity. It inhibits rat pepsin in a concentration-dependent manner and pepsin activity in isolated human gastric juice. It also inhibits ulcer formation induced by pyloric ligation, indomethacin , or cysteamine in rats. Sucralfate (5,600 mg/animal) is protective against neutral ethanol and acidified taurocholic acid-induced damage in a rat model of hydrochloric acid-induced gastric mucosal damage, increasing the pH and reducing the disappearance of hydrogen ions. Formulations containing sucralfate have been used as antacids in the treatment of duodenal ulcer.

Chemical Properties

White Powder

Originator

Antepsin,Baldacci,Italy,1975

Uses

antineoplastic, antileukemia

Uses

An inhibitor of peptic hydrolysis and stomach acidity. Used as an antiulcerative

Uses

Sucralfate, an aluminum salt of sucrose octasulfate, is used as an antacid and antiulcer medication. Bis- and tris-platinum complexes of sucrose show promise as antitumor agents. Sucrose monoesters are used in some pharmaceutical preparations.

Indications

Sucralfate (Carafate) is an aluminum hydroxide–sulfated sucrose complex that is only minimally absorbed from the GI tract. After exposure to gastric acid, the compound becomes negatively charged, creating a viscous adherent complex. This complex is believed to inhibit back-diffusion of H .Other effects are a direct reduction in pepsin activity and a slight rise in tissue prostaglandin levels. Stimulation of a cytoprotection mechanism may therefore assist mucosal healing. The drug has no acid-buffering capacity.

Manufacturing Process

A disaccharide is added to a pyridine SO3 complex solution, which is prepared by reacting 5 to 6 times the molar amount of liquid SO3 as much as that of disaccharide with 5 to 10 times the amount of pyridine as that of the disaccharide at 0°C to 5°C, for sulfation at 50°C to 70°C for 3 to 7 hours. After the completion of sulfation, the greater part of pyridine is removed by decantation. The obtained solution exhibits an acidity that is so strong that it is improper to apply the reaction with aluminum ion and, therefore, sodium hydroxide is added for neutralization. After the remaining pyridine is removed by concentration, 100 unit volumes of water per unit volume of the residue is added thereto. To the solution is then added aluminum ion solution mainly containing aluminum dihydroxychloride, the pH of which is 1.0 to 1.2, in such an amount that the aluminum ion is present in an amount of 4 to 6 molar parts of the amount of disaccharide to provide a pH of 4 to 4.5. The mixture is reacted under stirring at room temperature and the formed disaccharide polysulfate-aluminum compound is allowed to precipitate. After filtration, the residue is washed with water and dried.

brand name

Carafate (Axcan Scandipharm).

Therapeutic Function

Antiulcer

General Description

Sucralfate, 3,4,5,6-tetra-(polyhydroxyaluminum)-α-D-glucopyranosyl sulfate-2,3,4,5-tetra-(polyhydroxyaluminum)-β-D-fructofuranoside sulfate (Carafate), isthe aluminum hydroxide complex of the octasulfate ester ofsucrose. It is practically insoluble in water and soluble instrong acids and bases. It has a pKa value between 0.43 and1.19.
Sucralfate is minimally absorbed from the GI tract by design,and thus exerts its antiulcer effect through local ratherthan systemic action. It has negligible acid-neutralizing orbuffering capacity in therapeutic doses. Although its mechanismof action has not been established, studies suggestthat sucralfate binds preferentially to the ulcer site to form aprotective barrier that prevents exposure of the lesion to acidand pepsin. In addition, it adsorbs pepsin and bile salts.Either would be very desirable modes of action.
The simultaneous administration of sucralfate may reducethe bioavailability of certain agents (e.g., tetracycline, phenytoin,digoxin, or cimetidine). It further recommends restorationof bioavailability by separating administration of theseagents from that of sucralfate by 2 hours. Presumably, sucralfatebinds these agents in the GI tract. The most frequentlyreported adverse reaction to sucralfate is constipation (2.2%).Antacids may be prescribed as needed but should not be takenwithin 0.5 hour before or after sucralfate.

Clinical Use

Sucralfate is frequently used for prophylaxis of stress-induced gastritis in patients in intensive care units. It has also been successfully used in small numbers of patients as a suspension enema to treat radiation proctitis.

Veterinary Drugs and Treatments

Sucralfate has been used in the treatment of oral, esophageal, gastric, and duodenal ulcers. It has also been employed to prevent drug-induced (e.g., aspirin) gastric erosions, but efficacy for this is somewhat sporadic. Sucralfate has been used in human patients with hyperphosphatemia secondary to renal failure and potentially could be useful for this in animals as well.

Drug interactions

Potentially hazardous interactions with other drugs
Reduced absorption of digoxin, tetracyclines, quinolones, coumarins, fosphenytoin and phenytoin - give 2 hours after sucralfate.

Metabolism

Sucralfate is only slightly absorbed from the gastrointestinal tract after oral doses. However, there can be some release of aluminium ions and of sucrose sulphate; small quantities of sucrose sulphate may then be absorbed and excreted, mainly in the urine; some absorption of aluminium may also occur.