Sucralfate mechanism of action
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Sucralfate Mechanism of Action: Key Protective and Healing Pathways
Barrier Formation and Mucosal Protection
Sucralfate acts primarily by forming a protective barrier over ulcers and erosions in the stomach and duodenum. This barrier is created through the drug’s viscous adhesiveness and the formation of bridges between negatively charged sucralfate molecules and positively charged proteins in damaged mucosa. This layer prevents acid, pepsin, and bile salts from penetrating and further injuring the tissue, effectively shielding both injured and regenerating mucosa from harmful agents 3457.
Enhancement of Mucosal Defense Mechanisms
Sucralfate stimulates the secretion of mucus and bicarbonate, which are crucial for both acute and chronic protection of the gastroduodenal lining. These secretions help maintain the mucosal barrier and pH gradient, making the tissue more resistant to injury from substances like ethanol and aspirin 168910. Sucralfate also increases the hydrophobicity of the mucus gel, further enhancing its protective function .
Maintenance of Vascular Integrity and Blood Flow
A key acute action of sucralfate is the preservation of microvascular integrity and blood flow in the gastric mucosa. By maintaining blood flow, sucralfate supports rapid epithelial restitution, which is essential for repairing superficial defects and preventing further injury 129. This vascular protection is a critical component of its immediate gastroprotective effects.
Stimulation of Growth Factors and Tissue Repair
For chronic ulcer healing, sucralfate enhances the binding of growth factors such as fibroblast growth factor and epidermal growth factor. This stimulation promotes angiogenesis (formation of new blood vessels), granulation tissue development, and re-epithelialization, all of which are vital for the healing of chronic ulcers 129. Sucralfate also stimulates cell proliferation and the regeneration of epithelial cells 56.
Modulation of Prostaglandins and Other Mediators
Sucralfate increases the synthesis and release of protective prostaglandins, which play a role in maintaining mucosal integrity and promoting healing. It also stimulates endogenous sulfhydryl compounds and inhibits the release of thromboxane, further contributing to its protective and reparative actions 6910.
Additional Actions
While sucralfate does not significantly affect gastric acid production or pH, it can buffer acid, inhibit pepsin activity, and adsorb bile salts, all of which contribute to its overall protective effect on the gastric and duodenal mucosa 345. There is also evidence that sucralfate may reduce parietal cell responsiveness after ulcer healing, possibly through increased somatostatin release, which may help prevent ulcer relapse .
Conclusion
Sucralfate’s mechanism of action is multifactorial, involving the formation of a protective barrier, enhancement of mucosal defenses, maintenance of vascular integrity, stimulation of tissue repair, and modulation of protective mediators. These combined actions make sucralfate effective in both the prevention and healing of gastric and duodenal ulcers.
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