Mechanism of Action of Sucralfate
Sucralfate works primarily through local action at ulcer sites by forming a protective barrier that adheres to damaged mucosa and shields it from acid, pepsin, and bile salts, rather than through systemic absorption or acid suppression. 1
Primary Mechanism: Ulcer-Adherent Barrier Formation
- Sucralfate forms an ulcer-adherent complex with proteinaceous exudate at the ulcer site, creating a physical barrier that protects damaged tissue from further injury 1
- The drug binds selectively to ulcerated and damaged mucosa through formation of polyvalent bridges between negatively charged sucralfate polyanions and positively charged proteins that are present in high concentrations at mucosal lesions 2
- This sucralfate-albumin film provides a barrier to diffusion of hydrogen ions, effectively protecting the ulcer from acid penetration 1
Secondary Protective Mechanisms
- Pepsin inhibition: Sucralfate inhibits pepsin activity in gastric juice by approximately 32% at therapeutic doses, and directly adsorbs and inactivates pepsin 1, 2
- Bile salt binding: The drug adsorbs bile salts both in vitro and in vivo, preventing bile-mediated mucosal damage 1, 2
- Minimal acid neutralization: Sucralfate has approximately 14-16 mEq of acid-neutralizing capacity per 1g dose, though this is not its primary mechanism 1
Cytoprotective and Healing Enhancement
- Sucralfate stimulates synthesis and release of gastric mucosal prostaglandins, bicarbonate, and epidermal growth factor, which collectively enhance mucosal defense and stimulate healing 3, 4
- The drug maintains mucosal blood flow and enhances epithelial restitution (cell migration) and regeneration (cell proliferation) at injury sites 4
- It binds growth factors at the ulcer site, concentrating them where healing is needed 4
Pharmacokinetic Properties
- Sucralfate is only minimally absorbed from the gastrointestinal tract, with small absorbed amounts excreted primarily in urine 1
- The drug exerts its therapeutic effect through local rather than systemic action 1
- Its viscous adhesiveness allows sustained action at the ulcer site, with slow reaction with acid and high affinity for defective mucosa 2
Clinical Context
Important caveat: While sucralfate has these multiple mechanisms of action, current guidelines recommend PPIs as first-line agents for ulcer treatment due to superior efficacy and convenience, with sucralfate relegated to second-line status 5, 6. Sucralfate should be administered at least 2 hours apart from PPIs or H2-blockers to avoid interaction 7, 6.