Sucralfate is administered in a dosage of 1 g four times daily on an empty stomach (at least 1 hour before meals). At present, its clinical uses are limited. Sucralfate (administered as a slurry through a nasogastric tube) reduces the incidence of clinically significant upper gastrointestinal bleeding in critically ill patients hospitalized in the intensive care unit, although it is slightly less effective than intravenous H2 antagonists. Sucralfate is still used by many clinicians for prevention of stress-related bleeding because of concerns that acid inhibitory therapies (antacids, H2 antagonists, and PPIs) may increase the risk of nosocomial pneumonia.
Because it is not absorbed, sucralfate is virtually devoid of systemic adverse effects. Constipation occurs in 2% of patients due to the aluminum salt. Because a small amount of aluminum is absorbed, it should not be used for prolonged periods in patients with renal insufficiency.
Sucralfate may bind to other medications, impairing their absorption.
The human gastrointestinal mucosa synthesizes a number of prostaglandins (see Chapter 18); the primary ones are prostaglandins E and F. Misoprostol, a methyl analog of PGE1, has been approved for gastrointestinal conditions. After oral administration, it is rapidly absorbed and metabolized to a metabolically active free acid. The serum half-life is less than 30 minutes; hence, it must be administered 3–4 times daily. It is excreted in the urine; however, dose reduction is not needed in patients with renal insufficiency.
Misoprostol has both acid inhibitory and mucosal protective properties. It is believed to stimulate mucus and bicarbonate secretion and enhance mucosal blood flow. Misoprostol can reduce the incidence of NSAID-induced ulcers to less than 3% and the incidence of ulcer complications by 50%. It is approved for prevention of NSAID-induced ulcers in high-risk patients; however, misoprostol has never achieved widespread use owing to its high adverse-effect profile and need for multiple daily dosing.
Two bismuth compounds are available: bismuth subsalicylate, a nonprescription formulation containing bismuth and salicylate, and bismuth subcitrate potassium. In the USA, bismuth subcitrate is available only as a combination prescription product that also contains metronidazole and tetracycline for the treatment of H pylori. Bismuth subsalicylate undergoes rapid dissociation within the stomach, allowing absorption of salicylate. Over 99% of the bismuth appears in the stool. Although minimal (<1%), bismuth is absorbed; it is stored in many tissues and has slow renal excretion. Salicylate (like aspirin) is readily absorbed and excreted in the urine.
The precise mechanisms of action of bismuth are unknown. Bismuth coats ulcers and erosions, creating a protective layer against acid and pepsin. It may also stimulate prostaglandin, mucus, and bicarbonate secretion. Bismuth subsalicylate reduces stool frequency and liquidity in acute infectious diarrhea, due to salicylate inhibition of intestinal prostaglandin and chloride secretion. Bismuth has direct antimicrobial effects and binds enterotoxins, accounting for its benefit in preventing and treating traveler’s diarrhea. Bismuth compounds have direct antimicrobial activity against H pylori.
Despite the lack of comparative trials, nonprescription bismuth compounds (eg, Pepto-Bismol, Kaopectate) are widely used by patients for the nonspecific treatment of dyspepsia and acute diarrhea. Bismuth subsalicylate also is used for the prevention of traveler’s diarrhea (30 mL or two tablets four times daily).