Diarrhea: Treatment

Non-pharmacologic

Adult individuals with acute diarrhea who are otherwise healthy are not likely to develop dehydration. Lost fluids and electrolytes can be replaced with virtually any beverage plus a source of sodium chloride (salted crackers, etc.). Patients can rest the bowel by avoiding high-fiber foods, fats, milk and other dairy products, caffeine and alcohol. A bland diet emphasizing such foods as bananas, clear soups, juice, gelatin and boiled vegetables may be helpful. The diet can gradually be returned to normal as tolerated and as stools become formed. For less than severe diarrhea, an oral glucose-electrolyte solution may be given if nausea and vomiting are not severe. Intravenous fluid therapy is necessary for the treatment of severe dehydration or diarrhea that is accompanied by severe vomiting.

The degree of dehydration present determines the treatment of a child with diarrhea. Children with diarrhea who are not dehydrated should continue to be fed age-appropriate diets. Oral rehydration therapy (ORT) is the preferred treatment of fluid and electrolyte losses caused by diarrhea in children with mild to moderate dehydration. Several glucose-electrolyte or rice-based physiologic solutions (Pedialyte, Infalyte, etc.) are commercially available for children who require ORT.

Parents should be discouraged from using nonphysiologic solutions (cola, apple juice, chicken broth and sports beverages) to treat their children with diarrhea. These solutions are hypertonic and have low electrolyte concentrations. While commercially available pre-mixed solutions are recommended for ORT, several recipes exist for homemade oral replacement solutions. One example is noted in Table 4.

In the majority of patients, diarrhea is mild and self-limited and responds within five days to simple rehydration therapy or antidiarrheal agents. Symptoms that suggest the need for prompt medical attention include high fever (>38.5C), bloody diarrhea, abdominal pain, diarrhea that does not subside after 4-5 days or dehydration.

The goals of treatment are to maintain hydration, treat the underlying causes and relieve the symptoms of diarrhea. Rehydration and correction of any electrolyte imbalance is critical in the treatment of diarrhea. Symptomatic relief is a second therapeutic goal.

Pharmacologic Treatment

Several agents can be used as adjunctive therapy in the management of acute nonspecific diarrhea and acute exacerbations of chronic functional diarrhea. These agents are not curative and are palliative at best. The antimotility agents (e.g., loperamide), adsorbents (e.g., attapulgite) and antisecretory compounds (e.g., bismuth subsalicylate) are not recommended for preschool patients.Table 5 contains a list of antidiarrheal agents along with their common doses and contraindications.

Prescription Agents

The opiate analgesics as a class have an antimotility effect on the gastrointestinal tract. Agents such as paregoric (camphorated tincture of opium) and paregoric-containing products have been used for many years. They rely on their content of morphine, which exerts its effect by decreasing the hyperperistaltic movements of the small intestine and colon, thereby slowing down the passage of intestinal contents.

Related agents diphenoxylate HCl with atropine sulfate (Lomotil, Logen, etc.) and difenoxin HCl with atropine sulfate (Motofen) are specifically indicated for the treatment of diarrhea. Both of these agents are chemically related to meperidine (Demerol), but they lack analgesic activity. Difenoxin is the principal active metabolite of diphenoxylate and is effective at one fifth the dosage of diphenoxylate. The atropine has been added in subtherapeutic doses to discourage deliberate abuse. At the recommended doses, anticholinergic activity is usually not a concern.

Diphenoxylate and difenoxin appear to provide an antidiarrheal effect by slowing intestinal motility through a local effect on the gastrointestinal wall. Because of these agents’ structural relationship to traditional opiates, potential side effects include dizziness, drowsiness and sedation in a few patients. Addiction to (physiological dependence on) diphenoxylate and difenoxin is theoretically possible at high doses and after chronic use but this is rare. It is particularly important that these two agents not be used in the management of invasive bacterial diarrhea. These agents may prolong or aggravate the diarrhea associated with these organisms that penetrate the intestinal mucosa (i.e., toxigenic E. coli, Salmonella, Shigella) or in pseudomembranous enterocolitis associated with broad-spectrum antibiotic therapy.

Agents that slow intestinal motility may induce toxic megacolon. Therefore, patients who have ulcerative colitis should be monitored carefully and these agents should be discontinued promptly if abdominal distention occurs or if other untoward symptoms develop.

Because of the opiate-related agents’ depressant effects on the central nervous system, barbiturates, tranquilizers and alcohol should not be used concomitantly. Patients should be warned about the potential for causing drowsiness or dizziness and should use caution when driving or performing other tasks requiring alertness, coordination or physical dexterity. When these agents are used for acute diarrhea, clinical improvement is usually seen within 48 hours and treatment beyond that time frame is usually not necessary.

Non-prescription Agents

As part of the FDA OTC Review process, three agents—attapulgite, polycarbophil and calcium polycarbophil—are considered safe and effective for diarrhea treatment in the Tentative Final Monograph. Loperamide was approved by the FDA for OTC status via a new drug application (NDA) procedure which was not part of the FDA OTC Review process. The FDA continues to review data for kaolin-pectin combination (the old Kaopectate formulation), kaolin alone, bismuth subsalicylate and additional data regarding attapulgite and calcium polycar-bophil.

It is likely that the Final Monograph will contain a significant number of changes from the Tentatative Final Monograph. The Final Monograph for antidiarrheals had been originally planned to be released in 1994, but is now not expected to be completed for another six months to one year. .For this final monograph, one of the FDA advisory committees has recommended a reversal in the Tentative Final Monograph published in 1986 to place attapulgite in Category III (data insufficient to permit classification) and to place kaolin-pectin in Category I (safe and effective).

Because of concerns regarding significant dehydration and electrolyte imbalances, OTC agents available for diarrhea must not be used if the diarrhea has lasted for more than two days or in patients less than three years of age.Patients who should be under a physician’s care are those who are under three years of age, are over 60 years of age with multiple medical problems, are pregnant and those who have a history of chronic diseases, bloody stools, abdominal tenderness, fever, dehydration, a weight loss of more than 5% of total body weight and diarrhea for longer than 48 hours.

Loperamide HCl (Imodium AD, Maalox Antidiarrheal and Pepto Diarrhea Control) is an agent which slows intestinal motility and affects water and electrolyte movement through the bowel. It appears to inhibit intestinal motility by a direct effect on the circular and longitudinal muscles of the intestinal wall. The bulk density and viscosity of a bowel movement is increased with a concomitant reduction in daily fecal volume and a decrease in a loss of fluid and electrolytes.

The same contraindication concerning the use of this agent in the presence of invasive bacterial diarrhea applies as noted for diphenoxylate HCl with atropine sulfate and difenoxin HCl with atropine sulfate. As an OTC drug, loperamide is indicated for control and symptomatic relief of acute nonspecific diarrhea, including traveler’s diarrhea. As a prescription drug, loperamide may be prescribed for the control and symptomatic relief of chronic diarrhea associated with inflammatory or functional bowel diseases. It may also be used to reduce the volume of discharge from ileostomies.

The adverse effects of this agent are generally minor and self-limiting and are more commonly observed during the treatment of chronic diarrhea. CNS penetration of the drug is minimal and it therefore does not usually produce the CNS side effects noted with opiate use and it lacks potential for abuse. The agent may cause some drowsiness or dizziness and patients should observe caution while driving or performing other tasks requiring alertness, coordination or physical dexterity. Dry mouth, constipation, nausea and vomiting may also occur. For the treatment of acute diarrhea, clinical improvement is usually observed within 48 hours.

Attapulgite, Activated (Kaopectate Advanced Formula, Donnagel, Diasorb and Rheaban Maximum Strength) has been considered by the FDA as a Category 1 agent (safe and effective) for the treatment of acute diarrhea. It is considered an adsorbent agent and is a naturally occurring hydrous magnesium aluminum silicate that adsorbs about eight times its weight in water. Attapulgite is not absorbed systemically, therefore side effects are minimal. The adsorbent effect reduces the liquidity of the stool. The primary problem with attapulgite is that adsorption is not selective; the systemic absorption of nutrients and other drugs may be disrupted. Because of this effect, patients should be counseled not to take any other medications within two to three hours of taking attapulgite.

OTC labeling indicates that patients should not use this agent for more than two days unless directed to do so by their physician, nor should it be used if blood or mucus is present in the stool or in infants or children less than three years of age. In June, 1994, two FDA advisory committees recommended reversing the status of attapulgite from Category I (generally recognized as safe and effective) to Category III (data insufficient to permit classification). After reviewing four clinical studies on attapulgite, the committees determined that the trials were inconclusive in supporting the efficacy of the ingredient. The Nonprescription Drug Manufacturers Association (NDMA) is currently sponsoring a clinical study to provide data to support monograph status of attapulgite, but the final results from this study have not been completed.

Calcium polycarbophil (Mitrolan, Equalactin, FiberCon, Fiberall) is a hydrophilic polyacrylic resin that possesses absorbent properties. In addition to its use as a bulk-forming laxative, in diarrhea when the intestinal mucosa is incapable of absorbing water at normal rates, it absorbs free fecal water, forming a gel to aid in the production of formed stools. Like attapulgite, polycarbophil is not absorbed systemically so no systemic side effects are produced. It can absorb up to sixty times its weight in water.

Studies have demonstrated that polycarbophil decreases the frequency of bowel movements and improves stool consistency in patients with acute as well as chronic diarrhea. Epigastric pain and bloating may occur which may be somewhat minimized by giving smaller doses spaced more evenly throughout the day. Minimal fluid intake is encouraged and the tablets should be chewed well and not swallowed whole. Because calcium in this product can inhibit the absorption of tetracycline, this antibiotic should not be given at the same time as the calcium polycarbophil. It is indicated for acute nonspecific diarrhea or diarrhea that is associated with conditions such as irritable bowel syndrome and diverticulosis.

Bismuth subsalicylate (Pepto-Bismol) has been sold OTC for the treatment of diarrhea in the U.S. for more than 75 years. It appears to have antisecretory and antimicrobial effects. Studies have confirmed its efficacy in pediatrics protocols with intravenous rehydration and also in adults for the prevention and treatment of traveler’s diarrhea and against Norwalk viral gastroenteritis. It has been shown to enhance the effects of oral rehydration by shortening the episodes of diarrhea in infants (mean age 13.5 months) in a study in Peru. The salicylate portion of this agent provides the antisecretory effect while the bismuth portion may exert antimicrobial effects.

It is especially important to consider the amount of salicylate that a patient is receiving, as two of the bismuth subsalicylate tablets yield 204 mg of salicylate and 30 mL of the suspension yields 258 mg of salicylate. This would be especially important to consider in patients who are on long-term high doses of salicylate, such as patients who have rheumatoid arthritis. One must simply consider the total amount of salicylate the patient will receive. This agent is indicated for the control of diarrhea, including traveler’s diarrhea. If the diarrhea is accompanied by a high fever or continues for more than two days, a physician should be consulted. The stool may temporarily appear gray-black with use of this agent. The tongue may also be partially discolored.

Lactobacillus preparations (e.g., Lactinex, Bacid) have been available for years. These products contain lactobacillus organisms (Lactobacillus acidophilus and Lactobacillus bulgaricus). They have been touted as effective in restoring normal bowel flora when diarrhea is thought to be caused by the administration of antibiotics, but there is no solid documented evidence to support this claim. Milk, yogurt and buttermilk have been reported to be equally effective in re-establishing normal intestinal flora.

John Buducci

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