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.
Production Methods
Sucralfate is produced by mixing sucrose octasulfate sodium salt with polyaluminum chloride, followed by precipitation with sodium hydroxide[3].
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.
References
[1] L E BORELLA W L K Seethaler. Sucralfate: antipeptic, antiulcer activities and antagonism of gastric emptying.[J]. Arzneimittel-Forschung-Drug Research, 1979, 29 5: 793-798.
[2] S J HARRINGTON C F C J F Schlegel. The protective effect of sucralfate on the gastric mucosa of rats.[J]. Journal of clinical gastroenterology, 1981, 3 Suppl 2: 129-134.
[3] Ispas-Szabo, P., Friciu, M. M., Nguyen, P., Dumoulin, Y., & Mateescu, M. A. (2015). Novel self-assembled mesalamine–sucralfate complexes: preparation, characterization, and formulation aspects. Drug Development and Industrial Pharmacy, 42(7), 1183–1193.
https://doi.org/10.3109/03639045.2015.1118493
