What is the mechanism of action of Carafate (sucralfate)?

Mechanism of Action of Carafate (Sucralfate)

Sucralfate works primarily through local action at the ulcer site by forming a protective barrier that adheres to proteinaceous exudate in damaged mucosa, while also inhibiting pepsin activity, adsorbing bile salts, and stimulating mucosal defense mechanisms—all without significantly affecting gastric pH. 1

Primary Mechanisms

Local Barrier Formation

• Sucralfate forms an ulcer-adherent complex with proteinaceous material at the ulcer site, creating a physical barrier that protects against further damage from acid, pepsin, and bile salts 1
• The drug binds selectively and durably to lesions through electrostatic interactions between negatively charged sucralfate polyanions and positively charged proteins exuding from damaged mucosa 2
• This sucralfate-albumin film provides a barrier to hydrogen ion diffusion in vitro 1

Pepsin Inhibition

• At therapeutic doses, sucralfate inhibits pepsin activity in gastric juice by approximately 32% 1
• The drug both adsorbs pepsin and interferes with pepsin binding to mucosal lesions 2, 3

Bile Salt Adsorption

• Sucralfate adsorbs bile salts in vitro, contributing to mucosal protection 1
• This binding of bile acids helps protect the mucosa from bile-induced injury 4, 3

Secondary Cytoprotective Effects

Enhancement of Mucosal Defense

• Sucralfate stimulates the synthesis and release of gastric mucosal prostaglandins, which enhance natural defensive mechanisms 4, 3
• The drug promotes bicarbonate secretion and stimulates release of epidermal growth factor, which facilitates healing 4, 3
• It has a trophic effect on gastric mucosa, increasing both quantitative and qualitative aspects of surface epithelial and proliferative zone cells 3

Minimal Acid Effects

• Sucralfate has only 14 to 16 mEq of acid-neutralizing capacity per 1 gram dose, which is minimal 1
• The drug exerts its effect through local rather than systemic action, as it is only minimally absorbed from the gastrointestinal tract (approximately 3-5% absorption) 1, 5

Clinical Implications

Duration of Action

• Sucralfate remains at the site of gastric ulcers for up to six hours after administration 5
• The small amounts absorbed are excreted primarily in the urine, while more than 90% is excreted unchanged in feces 5

Important Caveat

• Sucralfate should be administered at least 2 hours apart from drugs that decrease gastric acidity (PPIs or H2-blockers) to avoid interaction, as recommended by the American Gastroenterological Association 6, 7