Mucosal Protective Drugs

Mucosal protective drugs strengthen the mucosal barrier or its defences without relying mainly on acid suppression. The group includes sucralfate, bismuth compounds and misoprostol, a prostaglandin E1 analogue.

Mechanism. Sucralfate polymerises in acid into a paste that binds ulcer bases and bile salts. Bismuth coats ulcers and has direct antibacterial activity against H. pylori. Misoprostol raises mucus and bicarbonate secretion, mucosal blood flow and reduces acid secretion.

• Sucralfate 1 g four times daily, 1 hour before meals and at bedtime, or 2 g twice daily; maximum 8 g daily.
• Colloidal bismuth subcitrate 120 mg four times daily for 4 to 8 weeks; dose of other bismuth salts varies by product.
• Misoprostol 200 microgram two to four times daily with food.

Differences. Sucralfate and bismuth act locally; misoprostol acts systemically and is the only one with proven prevention of NSAID-related ulcers.

• Sucralfate: duodenal ulcer when a proton pump inhibitor is unsuitable; radiation oesophagitis or proctitis (enema).
• Bismuth: part of quadruple H. pylori therapy for 14 days.
• Misoprostol: NSAID ulcer prevention in high-risk patients intolerant of proton pump inhibitors; also in obstetric use under specialist direction.

Selection. Each is second-line to a proton pump inhibitor for ulcers.

Contraindications. Misoprostol in pregnancy (uterine contraction, miscarriage, congenital malformation) and in women of childbearing age without effective contraception. Bismuth subsalicylate in children, aspirin allergy and anticoagulation. Sucralfate in severe kidney failure.

Adverse effects. Sucralfate: constipation, aluminium accumulation in kidney impairment, bezoar with enteral feeding. Bismuth: black stools and tongue; encephalopathy with prolonged high doses. Misoprostol: diarrhoea, cramping, vaginal bleeding.

Interactions. Sucralfate binds fluoroquinolones, tetracyclines, levothyroxine, phenytoin and warfarin: give other drugs at least 2 hours apart. Bismuth reduces tetracycline absorption.

Special groups.

• Pregnancy: misoprostol contraindicated; sucralfate acceptable.
• Breastfeeding: misoprostol may cause infant diarrhoea; avoid.
• Kidney impairment: avoid sucralfate and bismuth.
• Children: bismuth subsalicylate avoided because of Reye syndrome.

Monitoring. Renal function and aluminium or bismuth exposure when given for more than 4 weeks.

Referral and escalation. Ulcer not healing after 8 weeks, gastric ulcer needing biopsy, bleeding.