Treating acute diarrhoea in adults
Diarrhoea is one of the most common problems on which pharmacists are consulted: about one in five people in the UK suffer an episode at least once a year. Alan Nathan gives an overview of the symptom and looks at the advice pharmacists can give
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The Royal Pharmaceutical Society’s areas of competence for pharmacists are listed in “Plan and record”.
This article relates to “common disease states” (see appendix 4 of “Plan and record”).
Diarrhoea is defined as a change in bowel habit that results in substantially more frequent and looser stools than usual. The consistency of the stools is more significant than the number — passing formed stools frequently is not defined as diarrhoea — but the symptom has also been described as the passage of at least 200g of stool in 24 hours or at least three defecations a day.1 Diarrhoea has also been categorised as acute, chronic or travellers’.
Types and causes
In adults, rotavirus infection is uncommon (infection in childhood confers long-lasting immunity) but norovirus is a common cause of gastroenteritis (immunity is short-lived). It is this virus that is responsible for winter vomiting disease. The bacteria most commonly implicated in acute diarrhoea are campylobacter, Escherischia coli and salmonella.
Damage to intestinal mucosa cells causes inflammation and prevents absorption of water from the intestine into the bloodstream. The fluid is evacuated in watery stools, taking electrolytes with it (see below).
Gastroenteritis means, literally, inflammation of the lining of the stomach and small and large intestines but the term “acute gastroenteritis” describes diarrhoea of rapid onset and of less than 14 days’ duration, with or without nausea, vomiting, fever and abdominal pain.
In most cases, the condition is self-limiting (normally resolving spontaneously within about 72 hours) and pharmacists can recommend over-the-counter symptomatic relief.
However, diarrhoea is also a symptom of more serious conditions with causes, both infective and pathophysiological, that require investigation and medical treatment. It is, therefore, important that pharmacists are able to distinguish diarrhoea as a result of a trivial cause from that with a potentially more serious cause.
Dysentery Acute infectious gastroenteritis characterised by loose, small-volume stools with blood and mucus, often accompanied by pyrexia and abdominal cramps.
Causative organisms include
Enterohaemorrhagic E coli E coli that cause bleeding in the intestines. These are also called verocytotoxin-producing (VTEC) E coli or E coli 0157:H7.
Gastroenteritis caused by these strains are relatively rare in the UK but haemorrhagic colitis can be fatal.
For example, dysentery (see Glossary) is a notifiable disease and, if suspected, must be referred. Food poisoning (see Panel 1) is also notifiable.
Panel 1: Food poisoning
Food poisoning is defined by the UK Government’s Advisory Committee on the Microbiological Safety of Food as “any disease of an infectious or toxic nature caused by or thought to be caused by the consumption of food or water”.
Gastroenteritis due to food poisoning can be caused by ingesting either food contaminated with bacteria (enterotoxic) or toxins (exotoxic), often produced by bacteria. Organisms most commonly involved in enterotoxic infection include campylobacter (most common), norovirus, salmonella, giardia, cryptosporidium, E coli O157:H7 and shigella. Symptoms due to enterotoxins are usually slow in onset and last for more than 12 hours.
The bacteria most commonly implicated in exotoxic food poisoning are Staphylococcus aureus and Bacillus cereus.
Foods and contaminants that are commonly responsible for exotoxic poisoning include:
Diarrhoea and vomiting due to exotoxic food poisoning are usually rapid in onset and last for less than 12 hours.
If poisoning is suspected to be caused by food from a specific shop, takeaway or restaurant, the local environmental health department should be informed.
Chronic diarrhoea is recurrent or persistent diarrhoea for over two weeks. There are many potential causes, including irritable bowel syndrome, Crohn’s disease, ulcerative colitis, malabsorption syndromes (eg, coeliac disease and lactose intolerance), bowel tumour, metabolic disease (including diabetes and hyperthyroidism) and laxative abuse.
Travellers’ diarrhoea is the term applied to diarrhoea experienced by travellers or holidaymakers. Attacks are normally short-lived, lasting up to seven days, but some infections, such as giardiasis and amoebic dysentery, can cause persistent or recurrent diarrhoea and systemic complications. Further information is given in Panel 2.
Panel 2: Travellers’ diarrhoea
Between 30 per cent and 80 per cent of all travellers are estimated to suffer from travellers’ diarrhoea. In up to about 60 per cent of cases no pathogenic cause is found2 and the diarrhoea could simply be attributed to a change in diet or gut flora. Of the rest, the causative organisms are:
The main features of travellers’ diarrhoea are:
People who are going travelling may request an antibiotic to treat gastroenteritis. Ciprofloxacin (500mg bd for three days) is sometimes prescribed for gastroenteritis of no confirmed cause.
The use of antibiotics for prophylaxis is rarely recommended (exceptions have included people with inflammatory bowel disease). There is some evidence that bismuth subsalicylate is an effective prophylactic but the US study involved taking tablets four times a day3 and use for more than three weeks is not recommended.
In addition, bismuth subsalicylate can interfere with the absorption of antimalarials, particularly doxycyline. What is most important is attention to hygiene and food and drink, and pharmacists can give the following advice to travellers:
Symptoms in the pharmacy
To distinguish between types and causes of diarrhoea, pharmacists should consider asking about the frequency and nature of stools (eg, any blood or mucus), occurrence (isolated or recurrent), duration, onset, timing (eg, early in the morning and during the night can indicate inflammatory bowel disease), food that has been eaten (food additives, such as sorbitol, can cause diarrhoea) and any recent travel.
Pharmacists should also ask people about medicines they are taking. Diarrhoea accounts for about 7 per cent of all adverse effects and more than 700 drugs have been implicated.4 There are often several mechanisms involved (Panel 3 lists these and gives examples of causative drugs).
Panel 3: Mechanisms of drug-induced diarrhoea
Osmotic Caused mainly by inorganic salts or organic compounds that are poorly absorbed and create a hypertonic state in the intestine (eg, acarbose, antibiotics and magnesium salts). Water is drawn into the lumen, increasing the volume of the contents, thus stimulating peristalsis and promoting evacuation.
Secretory Caused by drugs that increase small intestine ion secretion or inhibit normal active ion absorption, with the same result as in osmotic diarrhoea (eg, antibacterials, antineoplastics, digoxin, metformin, non-steroidal anti-inflammatory drugs, misoprostol and olsalazine).
Impaired fluid absorption Caused by drugs that act by activating adenylate cyclase within enterocytes, increasing the level of cyclic adenosine monophosphate (eg, misoprostol). This leads to active secretion of chloride and bicarbonate ions, and efflux of sodium, potassium and water into the intestine.
Disturbed intestinal motility This leads to shortened transit time. (Drugs include macrolide antibiotics and thyroxine.)
Exudative Caused by drugs that cause inflammation and ulceration in the intestine (eg, antineoplastics, NSAIDs and simvastatin).
Malabsorption or maldigestion of fat or carbohydrates Caused by drugs such as aminoglycosides, colestyramine, metformin, orlistat and tetracyclines.
Microscopic colitis Some drugs cause a thick submucosal band of collagen in the intestine to be produced, resulting in a watery diarrhoea (eg, antineoplastics, budesonide, carbamazepine, ciclosporin, levodopa-benserazide, NSAIDs, ranitidine and simvastatin)
Antibiotics are responsible for 25 per cent of drug-induced diarrhoea (see Panel 4). If long-term medication is identified as the cause of diarrhoea, a suitable replacement should be found because the loss of fluid and electrolytes can have serious consequences, particularly in elderly patients.
Panel 4: Antibiotic-associated diarrhoea
Taking co-amoxiclav is associated with a 25 per cent risk of symptoms and cefixime and ampicillin with up to 20 per cent and 10 per cent risk, respectively. No figure has been found for amoxicillin in adults, but in children an incidence of up to 30 per cent has been reported.5 Other antibiotics causing diarrhoea include other cephalosporins, the macrolides and tetracycline.
In most cases, symptoms are mild and self-limiting and unless the diarrhoea is severe patients can be advised to continue their course of treatment. There is evidence that taking a probiotic in advance of a course of an antibiotic reduces the risk of diarrhoea (PJ, 31 March 2007, pp373–6).
The most serious type of antibiotic-associated diarrhoea is that caused by the overgrowth of Clostridium difficile as a result of antibiotics changing the balance of gut flora. Those most at risk include the elderly or immunocompromised and those who have recently been in hospital or live in a nursing home.
It has been suggested that taking antacids might increase risk because a reduction in stomach acid might ease the passage of C difficile in the intestine.
Although acute diarrhoea is officially defined as symptoms lasting for up to 14 days, pharmacists should refer normally healthy adults for medical advice if diarrhoea persists for more than 72 hours. For patients in high risk groups the referral threshold is shorter. Panel 5 lists referral criteria.
Panel 5: Diarrhoea in adults — when to refer
Symptoms lasting over 72 hours in healthy adults; more than 48 hours in elderly people and more than 24 hours in people with diabetes
Guidelines for treatment of diarrhoea are inconsistent and sometimes contradictory. One view is to regard diarrhoea as the body’s way of flushing out the causative organisms and toxins from the bowel, and the use of anti-diarrhoeals is considered unnecessary and, sometimes, undesirable.
On the other hand, it is recognised that sufferers often wish to curtail diarrhoea for reasons of comfort or convenience, and there is no evidence that this is either unsafe or prolongs the condition.6 What is accepted is that oral rehydration is recommended in most cases.
Oral rehydration therapy In diarrhoea, the normal mechanisms of intestinal transport are altered. Normal faeces contain 60–85 per cent water, and 70–200ml water per day is lost from the body through defecation. In diarrhoea, water loss of up to four times this volume per loose stool can occur. The primary consideration in diarrhoea management is, therefore, to prevent dehydration.
However, along with water, sodium and potassium alkaline salts are also excreted, leading to a fall in plasma pH (ie, acidosis). Reduction in blood volume resulting from excessive loss of fluid through diarrhoea may stimulate the secretion of aldosterone from the adrenal cortex, also causing excretion of potassium, leading to hypokalaemia.
Excessive fluid loss can also lead to renal failure through reduction of renal artery blood flow, making acidosis more likely. Signs of acidosis are deep and rapid breathing and increased vomiting.
The elderly are particularly sensitive to the effects of fluid and electrolyte loss, especially if they are taking diuretics. Fluid and electrolyte losses are increased further if vomiting also occurs.
Oral rehydration salts (ORSs) are designed to replace water and electrolytes lost through diarrhoea and vomiting. They contain sodium and potassium to replace these essential ions, and citrate or bicarbonate, or both, to correct acidosis. Glucose is also an important ingredient because it acts as a carrier for the transport of sodium ions, and hence water, across the intestinal mucosa.
The composition of the ORSs available in the UK varies between products, but all are designed to correct fluid loss and electrolyte imbalance associated with mild-to-moderate diarrhoea. Oral rehydration therapy can be recommended for patients of any age, even when referral to a doctor is considered necessary.
ORSs are presented in sachets to be dissolved in water. It is important to make up the solution exactly to the recommended volume (usually 200ml) because too concentrated a solution will be hyperosmolar, drawing more water into the intestine and exacerbating the diarrhoea and dehydration.
To avoid risk of possible 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 ORSs for an adult is 200–400ml after every loose motion, or 2–4L over four to six hours.
If preferred, one or two teaspoonfuls of the solution can be sipped every few minutes rather than drunk in large amounts. Patients with diabetes can use ORSs, but they should be reminded to monitor blood glucose levels carefully.
There are no contraindications to oral rehydration therapy unless the patient is vomiting frequently and unable to keep the solution down, in which case intravenous replacement may be necessary. Fluid overload from excessive administration of ORSs is highly unlikely in adults. It can be recognised by puffy eyelids, and is rapidly corrected by withholding ORSs and other liquids.
Opioids Opioid drugs cause constipation by increasing the tone of both the small and large bowel and by reducing intestinal motility. They also increase sphincter tone and decrease secretory activity along the gastrointestinal tract. This decreased motility enhances fluid and electrolyte reabsorption and reduces the volume of intestinal contents.
Non-prescription medicines containing loperamide, morphine and diphenoxylate are available for the symptomatic treatment of acute diarrhoea. However, the use of opioids as antidiarrhoeals is limited by their actions on the central nervous system (CNS), which include CNS depression and the risk of dependence.
Although, the risk of dependence at usual dosages for episodes of acute diarrhoea is low, the abuse of over-the-counter products containing morphine is an acknowledged problem.
Opioids can be recommended in certain situations, such as to make travel easier or to allow a person to attend an important event.
Loperamide Loperamide, a synthetic opioid analogue, 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 little reaches the systemic circulation and, at the dosage permitted for non-prescription use, it is unlikely to cause any of the side effects associated with opiates.
Several controlled trials4 have shown loperamide to be effective in reducing the duration of diarrhoea. The dose for adults is two 2mg capsules initially, followed by one after each loose bowel movement, up to a maximum of eight capsules in 24 hours. If symptoms have not subsided within 24 hours, the patient should be referred.
Side effects are abdominal cramps and dizziness. Loperamide should not be recommended to pregnant or breastfeeding women.
Morphine Morphine acts promptly on the intestine (within an hour of administration) because of its direct action on intestinal smooth muscle. Its action peaks within two to three 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 morphine content per recommended dose of products available for OTC treatment of diarrhoea ranges between 0.5 and 1mg. The effectiveness of these small amounts in controlling diarrhoea is debatable.
Diphenoxylate Diphenoxylate is a synthetic derivative of pethidine acting selectively on gastrointestinal smooth muscle. It is available in combination with atropine as co-phenotrope (diphenoxylate hydrochloride 2.5mg/atropine 25µg).
Although atropine has an effect on smooth muscle, it is included at a subtherapeutic dose to discourage abuse of the opioid, on the premise that unpleasant antimuscarinic effects will be experienced if higher-than-recommended doses are taken.
Limited clinical evidence shows that co-phenotrope can reduce the duration of diarrhoea if taken for more than 24 hours, but appears to be no more effective than placebo in the first 24 hours.7
Adsorbents The adsorbents used in anti-diarrhoeals include kaolin, attapulgite and bismuth subsalicylate. The rationale for their use is that they are capable of adsorbing microbial toxins and micro-organisms onto their surfaces, and because these substances are not absorbed from the gastrointestinal tract, they are excreted.
This lack of absorption also means that adsorbents are relatively harmless and safe to use, but there is little evidence that they are effective and, according to the British National Formulary, adsorbents are not recommended for acute diarrhoea.
Some studies have shown bismuth subsalicylate to be effective in treating diarrhoea. However, large doses are required and salicylate absorption can occur (products should be avoided by people sensitive to aspirin).
Adsorption is non-specific and, as well as adsorbing toxins, bacteria and water, adsorbents might also affect the absorption of drugs from the intestine.
Antibiotics Antibiotics are unnecessary in acute diarrhoea because the condition is self-limiting. They are also of no use for exotoxic infections.
According to the British Society for Antimicrobial Chemotherapy (BSAC), the gastrointestinal side effects of many antibiotics could prolong symptoms and unnecessary treatment could predipose patients to Clostridium difficile infection.
In addition, there is a theory that antibiotics that act through cell lysis may worsen gastroenteritis by causing the release of toxins from cells. The BSAC does, however, recommend antibiotics for severe infections, typically involving a fever over 39C and prolonged symptoms, in the elderly or immunocompromised.
Stool samples should be taken and the causative organism identified before an antibiotic is given — empirical treatment before identification is generally not recommended, not least because indiscriminate antibiotic use encourages resistance.
When giving advice about diarrhoea, pharmacists should bear in mind that it can reduce the absorption of medicines. Drugs that are slowly absorbed, including anti-epileptics and modified release formulations, are particularly affected. Antidiabetics, anti-coagulants, antimalarials and oral contraceptives can also be affected.
In addition to recommendations for the management of acute diarrhoea, pharmacists can also give the following advice:
- Drink plenty of clear fluids, such as water and diluted fruit squash
- Avoid drinks high in sugar (these can prolong diarrhoea)
- Avoid milk and milky drinks (a temporary lactose intolerance occurs due to damage done by infecting organisms to the cells lining the intestine, making diarrhoea worse)
- Many people with acute diarrhoea do not feel like eating, but those who do will probably benefit from eating light, easily digested food
- All cases of gastroenteritis should be regarded as potentially infectious. This means that people who work with food or who have contact with high risk groups (eg, work in nursing homes) should be advised not to return to work until they have been symptom-free for 48 hours. In addition, close attention should be paid to hygiene, for example, thorough hand washing and cleaning of toilet seats, flush handles and basin taps with detergent.
1. Thielman NM, Guerrant RL. Clinical practice: acute infectious diarrhea. New England Journal of Medicine 2004;350:38–47.
2. Wingate D, Phillips SF, Lewis SJ, Malagelada JR, Speelman P, Steffen R et al. Guidelines for adults on self-medication for the treatment of acute diarrhoea. Alimentary Pharmacology and Therapeutics 2001;15:773–82.
3. DuPont HL, Ericsson CD, Johnson PC, Bitsura JM, DuPont MW, de la Cabada FJ. Prevention of travellers’ diarrhea by the tablet formulation of bismuth subsalicylate. Journal of the American Medical Association 1987;257:1347–50.
4. Chassany O, Michaux A, Bergmann JF. Drug-induced diarrhoea. Drug Safety 2000;22:53–72.
5. OME in children. Available at http://clinicalevidence.bmj.com (accessed on 7 August 2008).
6. The Mayo Clinic. C. Difficile. Available at www.mayoclinic.com (accessed on 13 August 2008).
7. Clinical Knowledge Summaries. Gastroenteritis. Available at http://cks.library.nhs.uk (accessed on 13 August 2008).
Further information on travellers’ diarrhoea is available in an article by Larry Goodyer (PJ, 9 October 1999, pp571–5).
Alan Nathan, BPharm, FRPharmS, is a freelance pharmacy writer and consultant
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