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Treatment of IBS. Antidiarrheal Agents

Treatment of IBS. Antidiarrheal AgentsMorphine analogs such as diphenoxylate and codeine have been used for their antiperistaltic actions to counter frequent stools in irritable bowel syndrome (IBS). Although these medications are effective, the accompanying central nervous system (CNS) side effects, potential for addiction, and controlled-substance status make these less desirable in light of other agents, such as loperamide. Although structurally related to morphine, loperamide does not share the same adverse-effect profile.

Loperamide regulates stool frequency and urgency by slowing motility via the peripheral opiate receptors and mitigating spasms of the large bowel, as well as improving rectal sphincter tone. One result is increased intestinal transit time, which allows for increased water reabsorption and improved stool consistency. These actions may also account for decreased abdominal and intestinal pain.

Cann et al describe a study in which loperamide 2 mg was administered with breakfast and in the evening. Patients were allowed to titrate downward or upward (to a maximum of 12 mg per day in divided doses, breakfast, lunch, and dinner), balancing relief of symptoms and adverse effects. The small bowel and whole gut transit times were significantly increased as compared to placebo, as was the number of formed stools passed. At the same time, the incidence of urgency decreased significantly. Significant improvements for all symptoms evaluated (diarrhea, urgency, constipation, pain, borborygmi [GI sounds], distension, belching, flatulence, regurgitation, and nausea) occurred during treatment with loperamide and with placebo. Improvements in diarrhea, urgency, and borborygmi were significant for loperamide as compared to placebo.

Treatment of IBS. Antidiarrheal AgentsHovdenak evaluated loperamide 4 mg taken at bedtime versus placebo in irritable bowel syndrome (IBS) patients with painless diarrhea, alternating bowel habits with pain, and alternating bowel habits without pain. The first two subgroups had significant improvement in both stool frequency and consistency. Those with alternating bowel habits with pain had a significant decrease in number of painful days. No improvement in symptoms was observed in subjects with alternating bowel habits and no pain.

In a study by Efskind et al, patients were titrated up to 6 mg per day (three 2-mg capsules) of loperamide or placebo, in the evening, as needed, and as tolerated for one week. Patients who did not respond to placebo in the first week were titrated on active drug during week 2. For the remainder of the trial, patients could decrease their dose based on symptoms of abdominal pain or constipation. The average maintenance dose was 3 mg in the active group and 4 mg for the placebo group. As with the other studies, significant improvements in stool frequency and consistency were noted with loperamide. No differences were found in the incidence of borborygmi, distension, incomplete defecation, or intensity of pain related to meals, defecation, posture, or time of day. Though pain intensity was significantly reduced in the active group as compared to baseline, this same group experienced significantly higher pain intensity in the evening as compared to the placebo group, leading the authors to recommend dividing the daily dose.

Common adverse effects from loperamide include constipation, abdominal distention, and pain. Other adverse effects include drowsiness, dizziness, dry mouth, and fatigue. Hovdenak did not note any adverse effects in study patients, and the remaining studies did not report on specific adverse effects.

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