Mechanism of Action of Sucralfate
Sucralfate exerts its therapeutic effect primarily through formation of an ulcer-adherent complex that covers the ulcer site and protects it against further attack by acid, pepsin, and bile salts. 1
Primary Mechanisms
- Sucralfate forms an ulcer-adherent complex with proteinaceous exudate at the ulcer site, creating a protective barrier against acid, pepsin, and bile salts 1, 2
- When exposed to gastric acid, sucralfate becomes a viscous adhesive substance that selectively binds to damaged mucosa through electrostatic interactions between its negatively charged polyanions and positively charged proteins in mucosal lesions 2, 3
- Sucralfate provides a barrier to diffusion of hydrogen ions, inhibiting their penetration into the ulcer site 1, 4
- It inhibits pepsin activity in gastric juice by approximately 32% when given in therapeutic doses 1
- Sucralfate effectively adsorbs bile salts, further protecting the ulcer from damaging agents 1, 4
Secondary Mechanisms
- Sucralfate enhances natural defensive mechanisms of the gastric mucosa by stimulating:
- Mucus secretion
- Bicarbonate release
- Prostaglandin production
- Mucosal cell renewal 5
- It has a trophic effect on the entire mucosa, facilitating healing and re-epithelialization 5
- Sucralfate provides minimal acid neutralization capacity (approximately 14-16 mEq per 1g dose) 1
Pharmacokinetic Properties
- Sucralfate is minimally absorbed from the gastrointestinal tract (only 3-5% of an orally administered dose) 1, 4
- The small amounts absorbed are excreted primarily in the urine 1
- More than 90% of the dose is excreted unchanged in the feces 4
- Sucralfate remains at the site of gastric ulcers for up to six hours 4
- Its action is local rather than systemic, explaining its excellent safety profile and minimal side effects 1, 6
Clinical Applications
- Sucralfate is effective for treating duodenal and gastric ulcers 4, 6
- It can be used for stress ulcer prophylaxis in critically ill patients 5
- Sucralfate enemas have shown efficacy in controlling bleeding from radiation proctitis by stimulating epithelial healing and forming a protective barrier 7, 8
- When used for stress ulcer prophylaxis, sucralfate may be associated with a lower risk of ventilator-associated pneumonia compared to acid-suppressive therapies 7, 8
Important Considerations
- Sucralfate should be administered 1 hour before meals and at bedtime for optimal effect 4
- It should be administered at least 2 hours apart from drugs that decrease gastric acidity (PPIs or H2-blockers) to avoid interaction 9
- The most common side effect is constipation, occurring in approximately 2-4% of patients 4, 6
- Sucralfate can cause feeding tube blockage when administered through tubes, especially when combined with crushed tablets 9