pigmentation of the colon. Castor oil is a powerful stimulant laxative hydrolyzed in the upper small intestine to form recinoleic acid, which stimulates intestinal motility. Once commonly used, it has now fallen out of favor for purgative action. Drugs for the treatment of irritable bowel syndrome (IBS) Irritable bowel syndrome is a chronic, recurring disorder in which the individual experiences abdominal cramping and bloating with diarrhea, constipation, or both. Abdominal pain is usually associated with increased frequency of bowel movements. Treatments are typically focused on the relief of pain and normalization of bowel function. IBS may be associated with recurrent abdominal cramping, pain, and/or diarrhea/constipation cycle. IBS may be may be stress-induced or exacerbated. In some cases, gentle clockwise massage may be helpful in reducing symptoms; massage of the lumbar, gluteal, and thigh muscles may reduce referred pain. Individuals suffering from constipation can use fiber supplements to soften the stools, but this may result in excessive bloating and gas, increasing abdominal discomfort. Instead, osmotic laxatives are often used to soften and increase stool frequency. Individuals experiencing diarrhea may find loperamide (see below) offers some relief, reducing urgency and frequency of bowel movements. Anticholinergic drugs Atropine, belladonna alkaloids tincture, dicyclomine, glycopyrrolate (Robinul); I-hyoscyamine (Anaspaz); methscopolamine (Pamine); propantheline; scopolamine; tridihexethyl (Pathilon). Anticholinergic medications block or slow nerve impulses at parasympathetic nerve endings. This prevents muscle contraction and gland secretion in the organs involved. These medications are thought to slow the action of the bowel and relieve spasms (antispasmodic) through relaxation of the muscles. Dicyclomine and hyoscayamine are sometimes considered antispasmodics, but typically relieve abdominal pain through anticholinergic activity (small and large bowel spasms are not typically associated with IBS). These anticholinergic properties sometimes increase gastrointestinal motility and secretion, and reduce bowel movement frequency and liquidity. These medications are used infrequently due to the incidence of side effects including visual disturbances, urinary dysfunction, and constipation. Antidiarrheal drugs Bismuth subsalicylate (Pepto Bismol), difenoxin (Motofen), diphenoxylate (Lomotil), kaolin/pectin (Kaopectate), loperamide* (Imodium). Colloidal bismuth compounds, like bismuth subalicylate, are classified as both antidiarrheals and mucosal protective agents. Antidiarrheals are typically used to control chronic diarrhea caused by irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD). In general, antidiarrheal drugs should only be used in cases of mild to moderate diarrhea, and should not be used by individuals with blood in their stool, a high fever, or other condition that might cause systemic toxicity or worsen the pre-existing condition. They also should not be used in individuals with diarrhea that worsens after administration of any antidiarrheal drug. Two main opioids are used as anti-diarrheal agents: loperamide and diphenoxylate. Both have constipating effects, leading to increased transit time and greater absorption of water by the fecal matter. At the same time, opioids inhibit the gastrocolic reflex slowing colonic movements. Over longer periods of time or larger doses, opioids can have effects on the central nervous system and create the potential risk of addiction. Opioids and anticholinergics, like diphenoxylate and atropine, are used together to slow the action of the bowel, relieving diarrhea. Loperamide is a nonprescription opioid that does
not cross the blood-brain barrier, and appears to have no analgesic properties or potential for addiction. Diphenoxylate also has no analgesic properties at normal doses, but may have central nervous effects or potential for addiction with higher or prolonged usage. Some opioid preparations also have atropine, which has anticholinergic properties that assist in antidiarrheal action. Altered parasympathetic action (abnormal relaxation response) may be a concern for massage. Kaolin is hydrated magnesium aluminum silicate, a natural clay like substance known as attapulgite . Pectin is indigestible carbohydrate made from apples. Both absorb bacteria, toxins, and fluid into the stool, increasing their production and liquidity. Useful in acute diarrhea, neither should be used for prolonged periods. Kaolin/pectin solutions are not absorbed and have a low incidence of side effects like constipation. Because they may bind to other medications, they should be carefully timed around the ingestion of other drugs. Antiemetic drugs Alosetron (Lotronex), granisetron (Kytril), ondansetron (Zofran), prochlorperazine (Compazine), tegaserod (Zelnorm). Alosetron is a powerful 5-HT3 antagonist that works by inhibiting 5-HT3 receptors in the gastrointestinal tract, minimizing visceral afferent pain and intestinal motility. Alosetron is approved for individuals with severe IBS with diarrhea. Alosetron is highly specific to the 5-HT3 receptor that is rapidly absorbed from the gastrointestinal tract with a bioavailability near 55 percent, and a half-life of 1½ hours, with effects that typically last much longer. Alosetron is subject to hepatic metabolism and is excreted in urine. Alosetron inhibits distention-induced sensory and motor reflex activation as well as central response to visceral stimulation due to the fact that it blocks 5-HT3 receptors on enteric afferent neutrons inhibiting colonic motility, particularly in the left colon, and increasing the duration of transit time in the colon. While alosetron is currently approved for the treatment of women experiencing IBS with diarrhea as the primary symptom, efficacy in use among men has not been supported by research data. Among women, about one-half of individuals taking alosetron find relief from pain or discomfort and a reduction in bowel movements compared with 30-40 percent of individuals treated with placebo. Because alosetron is associated, in rare cases, with gastrointestinal toxicity, it should be discontinued if constipation occurs (about 30 percent of users). In very rare cases (1 out of 1000 users), constipation has resulted in complications requiring hospitalization or surgery, and ischemic colitis in as many as 3 out of 1000 users. Due to the seriousness of these side effects, alosetron is only approved in women with diarrhea-prone IBS who have not responded to other strategies and are aware of the risks. Alosetron appears to have no significant interactions with other drugs. Tegoserod is a partial seratonin 5-HT4 receptor agonist with a similar structure to seratonin. Tegaserod has a bioavailability of about 10 percent and should be taken before meals, as food can further reduce its bioavailability. About 2/3 of the drug is excreted virtually unchanged in fecal matter, while 1/3 is eliminated as a metabolite in the urine. Tegoserod should not be used by individuals with hepatic or renal dysfunction. Research suggests that stimulation of 5-HT4 receptors on mucosal afferent nerve fibers triggers the release of neurotransmitters, stimulating the peristaltic reflex (bowel contraction and bowel relaxation) and promoting gastric emptying, increasing movement through the small and large bowel. Stimulation of the 5-HT4 receptors also leads to increased liquidity of the stool. Tegaserod was recently approved for the treatment of IBS associated with constipation. Tegaserod appears to reduce pain and bloating, increases the number of bowel movements while decreasing stool hardness compared to the placebo. Diarrhea occurs in less than 10 percent of users within the first few days
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Book Code: MGA1224
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