• define the term diarrhea;
• describe the causes of diarrhea and the organisms frequently associated with traveller’s diarrhea;
• discuss the drug treatments used in diarrhea and their mechanisms of action;
• describe the actions of intestinal flora.
Sixty-year-old Mrs Kaye was a very healthy lady who never missed her daily walk to the park and went swimming twice a week. She had never experienced any health problems, except occasional indigestion, for which she usually took ranitidine. Sadly, a year ago she lost her husband, who died quite suddenly. Mrs Kaye sold her house and moved in with her daughter and two grandchildren. She decided to take them all abroad for the first time, to enjoy a package holiday in the sun. Everybody was having an enjoyable time; however, two days before coming back home, Mrs Kaye developed acute diarrhea. Her daughter took her to a local medical centre and Mrs Kaye was prescribed loperamide hydrochloride. She had a rather uncomfortable few days but recovered soon after returning home.
What do you understand by the term diarrhea?
A basic definition of diarrhea is an increase in frequency and/or volume of the faeces: in an adult the average quantity of faeces passed per day is 200 g. Ninety-nine percent of the fluid ingested each day plus the gastric and intestinal fluid secreted into the gut (7-81 daily) is usually reabsorbed in the intestine, and only 150 ml is excreted via the faeces.
There are three underlying causes of diarrhea: osmotic, secretory and motility.
Osmotic diarrhea occurs when a non-absorbable substance draws fluid into the intestine by osmosis, for example lactase deficiency, when unabsorbed lactose remains in the intestine. This type of problem also occurs in malabsorption disorders, for example in celiac disease. Secretory diarrhea may be caused by excessive secretion of fluid and electrolytes into the intestinal lumen as a result of a bacterial toxin or a tumour producing a secretory stimulant.
An increase in intestinal motility also causes diarrhea; because of very rapid transit of material through the gut, there is insufficient time to fully reabsorb gastric and intestinal secretions. Causes of motility change include impaired autonomic control, for example in peripheral neuropathy of diabetes or following some surgical procedures which shorten the intestine.
Comment on the pathophysiology of diarrhea.
Diarrhoea can be acute or chronic. Acute diarrhea has a sudden onset and, if it is due to a viral agent, usually lasts 24-48 hours. Acute diarrhea may also be due to unwise food consumption or to food poisoning. Traveller’s diarrhea, which affects people travelling outside their own countries, usually lasts two to five days. A working definition of the latter type of diarrhea is three or more unformed stools in 24 hours and at least one other symptom, such as: faecal urgency, fever, nausea, vomiting, abdominal pain or cramps. Chronic diarrhea may be due to: enteric infection with parasitic or fungal organisms, drugs, malabsorption or inflammatory bowel disease. If the diarrhea is severe, the major problem is loss of fluid and electrolytes which results in severe dehydration and electrolyte imbalance. This can be a particular problem in infants, young children and the elderly.
Which organisms are most frequently associated with traveller’s diarrhea?
The most common agent is Escherichia coli, but other bacterial causes include: Campylobacter jejuni and Salmonella species. A minority of cases appear to involve viral infection, such as rotavirus.
What factors might have made Mrs Kaye more likely than some other travellers to develop diarrhea?
Mrs Kaye may be at risk because this was her first visit abroad and possibly she was particularly affected by a change in diet or did not take the usual precaution of drinking bottled water and avoiding salads and unwashed fruit. Mrs Kaye also takes ranitidine for indigestion and there is some evidence that patients with reduced gastric acid, including those who take H2 antagonists such as ranitidine, are at increased risk of traveller’s diarrhea.
Comment on the pharmacological management of diarrhea.
Different treatments can be prescribed depending on the type or cause of diarrhea. These include oral rehydration, absorbents, antimotility agents such as opioids or intestinal flora modifiers. In all cases maintaining fluid intake helps to improve symptoms.
Oral rehydration therapy consists of a mixture of salt and glucose, or another carbohydrate, in clean, preferably boiled, water. Commercial sachets of the materials are available and form the most suitable treatment for children and the elderly.
Absorbents such as kaolin are not recommended for traveller’s acute diarrhea.
The most useful antimotility agent for adults is loperamide because it has specific effects on the gastrointestinal (GI) tract. It is not recommended for children as it decreases the clearance of the pathological organism from the gut and so prolongs the problem.
Very occasionally, an antibiotic may be necessary, depending on the organism involved.
To which category of drugs does loperamide hydrochloride belong and what is its mechanism of action?
Loperamide hydrochloride is an opioid. The starting dose will be 4mg, which can be reduced to 2 mg, three times a day for five days if necessary. Opioids act on i opiate receptors in the myenteric plexus of the intestine and may modulate acetylcholine release to reduce peristalsis. They trigger mucosal transport of ions and water out of the lumen and cause a reduction in secretion. The absorption of fluid and electrolytes is increased since the stool remains in the colon for a longer period. Loperamide does not produce sedation or other central effects associated with opiates, since it does not cross the blood-brain barrier.
What is an intestinal flora modifier? Comment on its mechanism of action.
Intestinal flora modifiers include Lactohacillus acidophilus or Lactohacillus bulgaricus. They help to establish and maintain the balance of the intestinal flora by enhancing or replacing the normal flora. Millions of bacteria normally exist in the gastrointestinal tract, particularly in the colon. In the colon, these bacteria help to produce vitamins K, Bi2, thiamine and riboflavin, and also digest small amounts of cellulose, producing gases. Following administration of antibiotics or after diarrhea, the normal flora of the intestine may be reduced or changed, which can then lead to secondary diarrhea and gas production. The presence of’good’ bacteria such as Lactohacillus spp helps to prevent the growth of unfavourable bacteria in the colon.
• Acute diarrhea has a sudden onset and, if it is due to a viral agent, usually lasts 24-48 hours. It maybe due to unwise food consumption, food poisoning or an infectious agent such as a virus.
• Traveller’s diarrhea, which affects people travelling outside their own countries, usually lasts two to five days. It involves three or four unformed stools in 24 hours and at least one other symptom, such as: faecal urgency, fever, nausea, vomiting, abdominal pain or cramps.
• Chronic diarrhea may be due to: enteric infection with parasitic or fungal organisms, drugs, malabsorption or inflammatory bowel disease. In severe cases it can lead to severe dehydration and electrolyte imbalance. This can be a particular problem in infants, young children and the elderly.
• The most frequent cause of traveller’s diarrhea is E. coli but other bacterial causes include: C. jejuni and Salmonella species. A minority of cases appear to involve viral infection, such as rotavirus.
• Therapies include oral rehydration, absorbents, antimotility agents such as opioids or intestinal flora modifiers. In all cases maintaining fluid intake helps to improve symptoms. Very occasionally, an antibiotic maybe necessary, depending on the organism involved.