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Alan Nathan discusses the options for managing diarrhoea – a common but distressing condition

WHAT’S AVAILABLE?

• Oral rehydration therapy (ORT)
• Opioids – loperamide and morphine
• Adsorbents.

ORT

Fluid and electrolyte replacement by oral rehydration salts is generally regarded as the first line of treatment for acute diarrhoea; it is particularly important for the very young and the elderly.

How does it act?

Oral rehydration salts (ORS) are designed to replace water and electrolytes lost through diarrhoea and vomiting, but they are not intended to relieve symptoms. They contain sodium and potassium salts to replace these essential ions, and citrate and/or bicarbonate to correct acidosis. Glucose is also an important ingredient, acting as a carrier for the transport of sodium ions, and hence water, across the mucosa of the small intestine. The composition of ORS preparations varies between products, but all are designed to correct fluid loss and electrolyte imbalance associated with mild-to-moderate diarrhoea. ORT can be recommended for patients of any age, even when referral to a doctor is considered necessary.

One oral rehydration product contains powdered rice starch in place of glucose. It is claimed to achieve even greater rehydration than glucose over time and the rice starch is claimed to help produce firmer stools, leading to faster recovery compared with glucose. A Cochrane Review found that polymer (including rice)-based ORS showed some advantages compared to glucose-based ORS for treating diarrhoea of any cause¹. A ready-made drink, containing ORS in natural mineral water, is also available.

Cautions and contraindications

There are no contraindications to ORT unless the patient is vomiting frequently and unable to keep the solution down, in which case intravenous fluid and electrolyte replacement may be necessary. Fluid overload from excessive administration of ORS is highly unlikely, but is possible if it is continued in babies and young children for more than 48 hours. Fluid overload is recognised by the eyelids becoming puffy, and is rapidly corrected by withholding ORS and other liquids.

OTC dosages

The contents of one sachet of ORS should be dissolved in 200ml water; for infants the water should be freshly boiled and cooled. It is important to make up the solution exactly to the recommended volume, as too concentrated a solution will be hyperosmolar, drawing more water into the intestine and exacerbating the diarrhoea and dehydration. To avoid any risk of exposure to further infection, the solution should be discarded not later than one hour after reconstitution, or it may be kept for up to 24 hours if stored in a refrigerator.

The recommended dose of ORS for an adult is 200-400ml after every loose motion, or 2-4l over 4-6 hours. Diabetic patients can use ORS, but they should be reminded to monitor blood glucose levels carefully. Patients may prefer to sip one or two teaspoonfuls every few minutes rather than drink large quantities less frequently. Children over two years of age should be offered a cupful (200ml) of solution after each loose stool; children under two years of age should be offered a quarter to half a cupful. Infants should be given one to one-and-a-half times the normal feed volume. Both breast-fed and formula-fed babies should be fed normally during diarrhoea; formula feed should not be diluted.

OPIODS – LOPERAMIDE AND MORPHINE

How do they act?

Opioid drugs counteract diarrhoea by increasing the tone of both the small and large bowel and reducing intestinal motility. They also increase sphincter tone and decrease secretory activity along the gastrointestinal tract. Decreased motility enhances fluid and electrolyte reabsorption and decreases the volume of intestinal contents.

Loperamide has a high affinity for, and exerts a direct action on, opiate receptors in the gut wall. It also undergoes extensive first-pass metabolism so very little reaches the systemic circulation and, at the restricted dosage permitted for non-prescription use, is unlikely to cause any of the side effects associated with opiates. Several controlled trials have shown it to be effective in reducing the duration of diarrhoea². Loperamide is available as 2mg tablets, dispersible tablets and capsules. One product contains loperamide with simeticone, the latter included to relieve gas-related abdominal symptoms that may accompany diarrhoea. A study carried out by the manufacturers showed that it considerably reduced the duration of diarrhoea and relieved gas-related discomfort in comparison with loperamide alone³.

The recommended dose of loperamide is 4mg initially, followed by 2mg after each loose bowel movement, up to a maximum of eight capsules (16mg) in 24 hours. If symptoms have not subsided within 24 hours, the patient should be referred.

Morphine acts promptly on the intestine, within one hour of administration, because of its direct action on intestinal smooth muscle and quick absorption from the gastrointestinal tract. Its action peaks within 2-3 hours and lasts about four hours. Morphine is not well absorbed orally and in combination products its availability may be reduced because of adsorption onto other constituents. The only products available are kaolin and morphine mixture, containing less than 1mg/10ml, and a proprietary liquid preparation containing 1mg morphine/5ml.

Cautions and contraindications

The content of morphine in antidiarrhoeal preparations is very low, so at recommended doses the risk of opioid adverse effects is low. The main potential problem is misuse. Loperamide is not licensed, and kaolin and morphine mixture not recommended, for non-prescription use in children aged under 12. Loperamide should not be recommended to pregnant or breastfeeding women.

ADSORBENTS – KAOLIN AND BISMUTH SUBSALICYLATE

How do they act?

The rationale behind the use of adsorbents is that they are capable of adsorbing microbial toxins and microorganisms onto their surfaces. Because the drugs are not absorbed from the gastrointestinal tract, adsorbed toxins and microorganisms are ultimately excreted in the stool.

Kaolin is a natural hydrated aluminium silicate. It is not absorbed from the gastrointestinal tract, and about 90 per cent of the drug is metabolised in the gut and excreted in the faeces. There appears to be no proof that it is effective, but as is it largely unabsorbed it is relatively harmless and safe to use.

Bismuth subsalicylate is claimed to possess adsorbent properties and some studies have shown it to be effective in treating diarrhoea^4-6. Large doses are required, however, and salicylate absorption may occur. It should therefore be avoided by individuals sensitive to aspirin. 

References

1. Gregorio GV, Gonzales MLM, Dans LF, Martinez EG. Polymer-based oral rehydration solution for treating acute watery diarrhoea. Cochrane Database of Systematic Reviews 2009, Issue 2.
2. De Bruyn G. Diarrhoea in adults (acute). BMJ Clin Evid. 2008; 0901.
3. Du Pont HL. Bismuth subsalicylate in the treatment and prevention of diarrheal disease. Drug Intell Clin Pharm 1987; 21:687–693.
4. Kaplan MA, Prior MJ, Ash RR, et al. Loperamide-simethicone vs loperamide alone, simethicone alone, and placebo in the treatment of acute diarrhoea with gas-related abdominal discomfort. A randomized controlled trial. Arch Fam Med 1999; 8:243–248.
5. Du Pont HL, Sullivan P, Pickering LK. Symptomatic treatment of diarrhoea with bismuth subsalicylate. Gastroenterology 1977; 73:715–718.
6. Ericsson CD, Du Pont HL, Johnson PC. Non-antibiotic therapy for travellers’ diarrhoea. Rev Infect Dis 1986; 8 (Suppl. 2):S202–S206.