Antidiarrhoeal Drugs

There are two types of drug which are often used in combination.

Antimotility drugs

These act on bowel muscle to delay the passage of gut contents so allowing time for more water to be absorbed.

Codeine (t1/ 3 h) activates opioid receptors on the smooth muscle of the bowel to reduce peristalsis and increase segmentation contractions. Tolerance may develop with prolonged use, as may dependence (rarely). It should be avoided in patients with

9 Solutions with lower sodium content and thus reduced total osmolarity (250 mmol/1) are associated with less need for unscheduled intravenous fluid infusion, lower stool volume and less vomiting, and may now be preferred. Hahn S et al 2001 British Medical Journal 323: 81-85.

10 The higher sodium content of the WHO/UNICEF formulation is based on sodium concentrations in diarrhoeal stools, but low-sodium, high-glucose formulations may be preferred for infants, whose faecal losses of sodium are less.

diverticular disease as it increases intraluminal pressure.

Diphenoxylate (t1/, 3 h) is structurally related to pethidine and affects the bowel like codeine. The drug is offered mixed with a trivial dose of atropine (to discourage abuse) as co-phenotrope (Lomotil). The drug can cause nausea, vomiting, abdominal pain and CNS depression. Following overdose with Lomotil respiratory depression may be serious, and can occur up to 16 h after ingestion because gastric emptying is delayed.

Loperamide (t/2 10 h) is structurally similar to diphenoxylate. Its precise mode of action remains obscure but it impairs propulsion of gut contents by effects on intestinal circular and longitudinal muscle that are at least partly due to an action on opioid receptors. Loperamide may cause nausea, vomiting and abdominal cramps. Its potential for abuse appears to be low.

The actions of codeine, diphenoxylate and loperamide are antagonised by naloxone.

Warning. Antimotility drugs should not be used for acute diarrhoea in children, especially babies, or in patients with active inflammatory bowel disease, for there is danger of causing paralytic ileus and, in babies, respiratory depression.

Drugs that directly increase the viscosity of gut contents

Kaolin and chalk are adsorbent powders. Their therapeutic efficacy is marginal as is shown by the fact that they are often combined with an opioid. Bulk-forming agents such as ispaghula, methylcellulose and sterculia (see above) are useful for diarrhoea in diverticular disease, and for reducing the fluidity of faeces in patients with ileostomy and colostomy.

TRAVELLERS' DIARRHOEA

So familiar is diarrhoea to travellers that it has acquired regional popular names: the Aztec 2-step, Montezuma's Revenge, Delhi Belly, Rangoon Runs, Tokyo Trots, Gyppy Tummy, Hong-Kong Dog, Estomac Anglais and Casablanca Crud, all indicate some of the areas deemed dangerous by visitors. The Mexican name 'turista' indicates the principal sufferers.

Most cases are infective, and up to half of the diarrhoea that afflicts visitors to tropical and subtropical countries is associated with enterotoxigenic strains of Escherichia coli; other bacteria including Shigella and Salmonella spp, viruses including the Norwalk family, and parasites (particularly Giardia lamblia) have also been implicated. Recognition that transmission is almost invariably by ingestion of contaminated food and water points to the most effective way of reducing the risk.

Acute watery diarrhoea in adults can usually be controlled by oral rehydration solutions and one of the antimotility drugs, although in mild cases the abdominal bloating produced by the latter may be less acceptable than the loose stools. While diarrhoea usually lasts only 2-3 days, this may still be socially inconvenient, and if symptomatic remedies fail, an aminoquinolone, e.g. ciprofloxacin 500 mg b.d. will be effective. The use of antimicrobials for travellers' diarrhoea continues to evoke controversy (see below) but most sufferers will appreciate the relief that even one or two tablets can bring.

Prophylactic antimicrobial therapy has been shown to reduce the incidence of attacks of diarrhoea but its routine use carries the risk of hindering the diagnosis of serious infection. A wider issue is the possible development and spread of antibiotic-resistant organisms. Thus any benefits to the individual must be weighed against the risk to the community in the future. In most instances prophylactic antimicrobials should not be used but ciprofloxacin (500 mg once daily) may be justified for individuals who must remain well while travelling for short periods to high-risk areas.

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