Enhancing mucosal resistance

Drugs can increase mucosal resistance by:

• protecting the base of a peptic ulcer (bismuth chelate, sucralfate)

• 'cytoprotection' (misoprostol).

Bismuth chelate

Tripotassium dicitratobismuthate, bismuth subcitrate, (De-Nol) This substance was originally thought to act mainly by chelating with protein in the ulcer base to form a coating, which protects the ulcer from the adverse influences of acid, pepsin and bile. Subsequently, bismuth chelate was found to possess an additional valuable action, namely activity against Helicobacter pylori, especially when combined with an antimicrobial (see below).

Bismuth chelate is used for benign gastric and duodenal ulcer and has a therapeutic efficacy approximately equivalent to histamine H2 receptor antagonists. Ulcers remain healed for longer after bismuth chelate than after the histamine H2 receptor antagonists, and this may relate to the ability of the former but not the latter to eradicate Helicobacter pylori.

Adverse effects. Bismuth chelate, particularly as a liquid formulation, darkens the tongue, teeth and stool; the effect is less likely with the tablet, which is thus more acceptable. There is little systemic absorption of bismuth from the chelated preparation, but bismuth is excreted by the kidney and it is prudent to avoid giving the drug to patients with impaired renal function. Urinary elimination continues for months after bismuth is discontinued.

Sucralfate

This is a complex salt of sucrose sulphate and aluminium hydroxide. In the acid environment of the stomach, the aluminium moiety is released so that the compound develops a strong negative charge and binds to positively charged protein molecules that transude from damaged mucosa. The result is a viscous paste that adheres selectively and protectively to the ulcer base. It also binds to and inactivates pepsin and bile acids. Sucralfate has negligible acid neutralising capacity, which explains why it is ineffective in gastro-oesophageal reflux disease (see below). Its therapeutic efficacy in healing gastric and duodenal ulcers is approximately equal to that of the histamine H2 receptor antagonists.

Adverse effects. Sucralfate may cause constipation but is otherwise well tolerated. The concentration of aluminium in the plasma may be elevated but this appears to be a problem only with long-term use by uraemic patients, especially those undergoing dialysis. As the drug is effective only in acid conditions, an antacid should not be taken 30 min before or after a dose of sucralfate. Sucralfate interferes with absorption of co-administered ciprofloxacin, theophylline, digoxin, phenytoin and amitriptyline, possibly by binding due to its strong negative charge.

Misoprostol

Endogenous prostaglandins contribute importantly to the integrity of the gastrointestinal mucosa by a number of related mechanisms (see Chapter 15). Misoprostol is a synthetic analogue of prostaglandin Ej which protects against the formation of gastric and duodenal ulcers in patients who are taking NSAIDs, presumably by these 'cytoprotective' mechanisms (see below). The drug also heals chronic gastric and duodenal ulcers unrelated to NSAIDs, but here the mechanism appears related to its antisecretory properties rather than to a cytoprotective action.

Adverse effects. Diarrhoea and abdominal pain, transient and dose-related, are the commonest. Women may experience gynaecological disturbances such as vaginal spotting and dysmenorrhoea; the drug is contraindicated in pregnancy or for women planning to become pregnant, for the products of conception may be aborted. Indeed, women have resorted to using misoprostol (illicitly) as an abortifacient in parts of the world where provision of contraceptive services is poor.1

Liquorice derivatives (carbenoxolone) and degly-cyrrhizinised liquorice, formerly used for peptic ulcer, are now obsolete.

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Blood Pressure Health

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