Mechanisms of gastroduodenal protection by sucralfate.

Over the past 5-10 years, a number of studies have shown that topical sucralfate enhances a number of gastric and duodenal mechanisms, e.g., the "mucus-bicarbonate barrier," mucosal hydrophobicity, mucosal blood flow, cell viability, and local production of prostaglandins, as well as endogenous mediators of tissue injury and repair. It seems likely that the complex actions of sucralfate are in part related to direct interaction between the drug or its components (aluminum, sucrose, and sulfate) and gastric mucosal tissues, and in part related to effects of the drug on the various mucosal mediators of tissue injury and repair. Local actions may play a role in accelerating healing of ulcer-damaged mucosa, but this does not explain the protective actions of sucralfate on normal mucosa. Thus sucralfate appears to enhance the protective function of the "mucus-bicarbonate" barrier by actions on both components. This may depend in part on an interaction with the unstirred layer overlying gastric epithelium. Sucralfate has also been shown to increase the hydrophobicity of mucus gel. There is little doubt that sucralfate increases local production and release of protective prostaglandins (PGs), but the precise role played by these agents in mediating mucosal protection and in chronic ulcer healing remains uncertain. Currently, the mechanism of action of sucralfate on vascular integrity remains unknown and the role of PGs in this protective function is unclear. There is little evidence that epidermal growth factor plays any role in mediating mucosal protection by sucralfate, but it may be important in its ulcer-healing action. Sucralfate has been shown to be truly "cytoprotective" in that it protects isolated epithelial cells from damage by noxious agents. In animals treated with sucralfate, the surface epithelial cells were disrupted, but necrotic lesions in the deep proliferative zone were virtually absent. It seems likely that investigations of the actions of sucralfate and its components will move ever closer to defining the target cells, the intracellular events, and the mediators that bring about its protective and ulcer-healing activity.