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February 9, 2012

Constipation (cont.)

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What treatments are available for constipation?

There are many treatments for constipation, and the best approach relies on a clear understanding of the underlying cause.

Dietary fiber (bulk-forming laxatives)

The best way of adding fiber to the diet is increasing the quantity of fruits and vegetables that are eaten. This means a minimum of five servings of fruits or vegetables every day. For many people, however, the amount of fruits and vegetables that are necessary may be inconveniently large or may not provide adequate relief from constipation. In this case, fiber supplements can be useful.

Fiber is defined as material made by plants that is not digested by the human gastrointestinal tract. Fiber is one of the mainstays in the treatment of constipation. Many types of fiber within the intestine bind to water and keep the water within the intestine. The fiber adds bulk (volume) to the stool and the water softens the stool.

There are different sources of fiber and the type of fiber varies from source to source. Types of fiber can be categorized in several ways, for example, by their source.

The most common sources of fiber include:

  • fruits and vegetables,

  • wheat or oat bran,

  • psyllium seed (for example, Metamucil, Konsyl),

  • synthetic methyl cellulose (for example, Citrucel), and

  • polycarbophil (for example, Equilactin, Konsyl Fiber).

Polycarbophil often is combined with calcium (for example, Fibercon). However, in some studies, the calcium-containing polycarbophil was not as effective as the polycarbophil without calcium.

A lesser known source of fiber is an extract of malt (for example, Maltsupex); however, this extract may soften stools in ways other than increasing fiber.

Increased gas (flatulence) is a common side effect of high-fiber diets. The gas occurs because the bacteria normally present within the colon are capable of digesting fiber to a small extent. The bacteria produce gas as a byproduct of their digestion of fiber. All fibers, no matter what their source, can cause flatulence. However, since bacteria vary in their ability to digest the various types of fiber, the different sources of fiber may produce different amounts of gas. To complicate the situation, the ability of bacteria to digest one type of fiber can vary from individual to individual. This variability makes the selection of the best type of fiber for each person (for example, a fiber that improves the quality of the stool without causing flatulence) more difficult. Thus, finding the proper fiber for an individual becomes a matter of trial and error.

The different sources of fiber should be tried one by one. The fiber should be started at a low dose and increased every one to two weeks until either the desired effect on the stool is achieved or troublesome flatulence interferes. (Fiber does not work overnight.) If flatulence occurs, the dose of fiber can be reduced for a few weeks and the higher dose can then be tried again. (It generally is said that the amount of gas that is produced by fiber decreases when the fiber is ingested for a prolonged period of time; however, this has never been studied.) If flatulence remains a problem and prevents the dose of fiber from being raised to a level that affects the stool satisfactorily, it is time to move on to a different source of fiber.

When increasing amounts of fiber are used, it is recommended that greater amounts of water be consumed (for example, a full glass with each dose). In theory, the water prevents "hardening" of the fiber and blockage (obstruction) of the intestine. This seems like simple and reasonable advice. However, ingesting larger amounts of water has never been shown to have a beneficial effect on constipation, with or without the addition of fiber. (There is already a lot of water in the intestine and extra water that is digested is absorbed and excreted in the urine.) It is reasonable to drink enough fluids to prevent dehydration because with dehydration there may be reduced intestinal water.

Because of concern about obstruction, persons with narrowings (strictures) or adhesions (scar tissue from previous surgery) of their intestines should not use fiber unless it has been discussed with their physician. Some fiber laxatives contain sugar, and patients with diabetes may need to select sugar-free products.

Lubricant laxatives

Lubricant laxatives contain mineral oil as either the plain oil or an emulsion (combination with water) of the oil. The oil stays within the intestine, coats the particles of stool, and presumably prevents the removal of water from the stool. This retention of water in the stool results in softer stool. Mineral oil generally is used only for the short-term treatment of constipation since its long-term use has several potential disadvantages.

The oil can absorb fat-soluble vitamins from the intestine and, if used for prolonged periods, may lead to deficiencies of these vitamins. This is of particular concern in pregnancy during which an adequate supply of vitamins is important for the fetus. In the very young or very elderly in whom the swallowing mechanism is not strong or is impaired by strokes, small amounts of the swallowed oil may enter the lungs and cause a type of pneumonia called lipid pneumonia. Mineral oil also may decrease the absorption of some drugs such as warfarin (Coumadin) and oral contraceptives, thereby decreasing their effectiveness. Despite these potential disadvantages, mineral oil can be effective when short-term treatment is necessary.

Emollient laxatives (stool softeners)

Emollient laxatives are generally known as stool softeners. They contain a compound called docusate (for example, Colace). Docusate is a wetting agent that improves the ability of water within the colon to penetrate and mix with stool. This increased water within the stool softens the stool. Although studies have not shown docusate to be consistently effective in relieving constipation. Stool softeners often are used in the long-term treatment of constipation. It may take a week or more for docusate to be effective. The dose should be increased after one to two weeks if no effect is seen.

Although docusate generally is safe, it may increase the absorption of mineral oil and some medications from the intestine. Absorbed mineral oil collects in tissues of the body, for example, the lymph nodes and the liver, where it causes inflammation. It is not clear if this inflammation has any important consequences, but it generally is felt that prolonged absorption of mineral oil should not be allowed. The use of emollient laxatives is not recommended together with mineral oil or with certain prescription medications. Emollient laxatives are commonly used when there is a need to soften the stool temporarily and make defecation easier (for example, after surgery, childbirth, or heart attacks). They are also used for individuals with hemorrhoids or anal fissures.

Hyperosmolar laxatives

Hyperosmolar laxatives are undigestible, unabsorbable compounds that remain within the colon and retain the water that already is in the colon. The result is softening of the stool. The most common hyperosmolar laxatives are lactulose (for example, Kristalose), sorbitol, and polyethylene glycol (for example, MiraLax). and are available by prescription only. These laxatives are safe for long-term use and are associated with few side effects.

Hyperosmolar laxatives may be digested by colonic bacteria and turned into gas, which may result in unwanted abdominal bloating and flatulence. This effect is dose-related and less with polyethylene glycol. Therefore, gas can be reduced by reducing the dose of the laxative. In some cases, the gas will decrease over time.

Saline laxatives

Saline laxatives contain non-absorbable ions such as magnesium, sulfate, phosphate, and citrate [for example, magnesium citrate (Citroma), magnesium hydroxide, sodium phosphate). These ions remain in the colon and cause water to be drawn into the colon. Again, the effect is softening of the stool.

Magnesium also may have mild stimulatory effects on the colonic muscles. The magnesium in magnesium-containing laxatives is partially absorbed from the intestine and into the body. Magnesium is eliminated from the body by the kidneys. Therefore, individuals with impaired kidney function may develop toxic levels of magnesium from chronic (long duration) use of magnesium-containing laxatives.

Saline laxatives act within a few hours. In general, potent saline laxatives should not be used on a regular basis. If major diarrhea develops with the use of saline laxatives and the lost fluid is not replaced by the consumption of liquids, dehydration may result. For constipation, the most frequently-used and mildest of the saline laxatives is milk of magnesia. Epsom Salt is a more potent saline laxative that contains magnesium sulfate.

Stimulant laxatives

Stimulant laxatives cause the muscles of the small intestine and colon to propel their contents more rapidly. They also increase the amount of water in the stool, either by reducing the absorption of the water in the colon or by causing active secretion of water in the small intestine.

The most commonly-used stimulant laxatives contain cascara (castor oil), senna (for example, Ex-Lax, Senokot), and aloe. Stimulant laxatives are very effective, but they can cause severe diarrhea with resulting dehydration and loss of electrolytes (especially potassium). They also are more likely than other types of laxatives to cause intestinal cramping. There is concern that chronic use of stimulant laxatives may damage the colon and worsen constipation, as previously discussed. Bisacodyl (for example, Dulcolax, Correctol) is a stimulant laxative that affects the nerves of the colon which, in turn, stimulate the muscles of the colon to propel its contents. Prunes also contain a mild colonic stimulant.

Tegaserod (Zelnorm)

Tegaserod (Zelnorm) was approved in 2002 by the FDA specifically for the treatment of abdominal pain and constipation in women with irritable bowel syndrome. In March of 2007, the FDA asked Novartis, the company manufacturing tegaserod, to suspend sales of tegaserod in the U.S. because a retrospective analysis of data by Novartis from more than 18,000 patients showed a slight difference in the incidence of cardiovascular events (heart attacks, strokes and angina) among patients taking tegaserod compared to placebo. The data showed that cardiovascular events occurred in 13 out of 11,614 patients treated with tegaserod (.11%), compared to one cardiovascular event in 7,031 (.01%) placebo-treated patients. However, it is unclear whether tegaserod actually causes heart attacks and strokes. Doctors and scientists will be scrutinizing the data to determine the long-term safety of tegaserod.

The mechanism whereby tegaserod relieves constipation (and abdominal bloating and pain) is interesting and is related to its effects on the intestinal serotonin, a chemical that controls contractions of intestinal muscles. The contractions of the intestinal muscles control transit of digesting food through the intestine. More contractions speed transit, fewer contractions slow transit. In constipated patients, contractions are fewer.

Serotonin is a chemical manufactured by nerves in the intestine that is released and then binds to muscle cells. Depending on which receptor it binds to on the muscle, serotonin can either promote or prevent contractions. The serotonin 5-HT4 receptor is a receptor that prevents contractions when serotonin binds to it. Tegaserod blocks the 5-HT4 receptor, prevents serotonin from binding to it, and thereby increases contractions of the intestinal muscles. The increased contractions speed the transit of digesting food and reduces constipation. In addition, tegaserod reduces the sensitivity of the intestinal pain-sensing nerves and can thereby reduce abdominal pain.

In large placebo controlled trials involving men and women with chronic constipation, tegaserod was more effective than placebo in increasing the number of spontaneous bowel movements and reducing straining, abdominal bloating, abdominal pain, and abdominal discomfort. The most common side effect of tegaserod was diarrhea, which was usually mild or moderate and generally resolved within a few days while continuing treatment.

Lubiprostone (Amitiza)

Lubiprostone (Amitiza) is a selective chloride channel activator that increases secretion of chloride ions from the cells of the intestinal lining into the intestinal lumen. Sodium ions and water then follow the chloride ions into the lumen, and the water softens the stool. The FDA approved lubiprostone for the treatment of chronic constipation in both men and women in February 2006. At a dose of 24 micrograms twice a day, lubiprostone significantly and promptly increased bowel movements, improved stool consistency, and decreased straining. The most common side effect of initial clinical studies was mild to moderate nausea in 32% of patients treated with lubiprostone, compared to 3% of the controls. More long term studies of efficacy and side effects are needed to determine the place of lubiprostone in the treatment of constipation.

Enemas

There are many different types of enemas. By distending the rectum, all enemas (even the simplest type, the tap water enema) stimulate the colon to contract and eliminate stool. Other types of enemas have additional mechanisms of action. For example, saline enemas cause water to be drawn into the colon. Phosphate enemas (for example, Fleet phosphosoda) stimulate the muscles of the colon. Mineral oil enemas lubricate and soften hard stool. Emollient enemas (for example, Colace Microenema) contain agents that soften the stool.

Enemas are particularly useful when there is impaction, which is hardening of stool in the rectum. In order to be effective, the instructions that come with the enema must be followed. This requires full application of the enema, appropriate positioning after the enema is instilled, and retention of the enema until cramps are felt. Defecation usually occurs between a few minutes and one hour after the enema is inserted.

Enemas are meant for occasional rather than regular use. The frequent use of enemas can cause disturbances of the fluids and electrolytes in the body. This is especially true of tap water enemas. Soapsuds enemas are not recommended because they can seriously damage the rectum.

Suppositories

As is the case with enemas, different types of suppositories have different mechanisms of action. There are stimulant suppositories containing bisacodyl (for example, Dulcolax). Glycerin suppositories are believed to have their effect by irritating the rectum. The insertion of the finger into the rectum when the suppository is placed may itself stimulate a bowel movement.

Combination products

There are many products that combine different laxatives. For example, there are oral products that combine senna and psyllium (Perdiem), senna and docusate (Senokot-S), and senna and glycerin (Fletcher's Castoria). One product even combines three laxatives, senna-like casanthranol, docusate, and glycerin (Sof-lax Overnight). These products may be convenient and effective, but they also contain stimulant laxatives. Therefore, there is concern about permanent colonic damage with the use of these products, and they probably should not be used for long-term treatment unless non-stimulant treatment fails.

Miscellaneous drugs

Several prescribed drugs that are used to treat medical diseases consistently cause (as a side effect) loose stools, even diarrhea. There actually are several small studies that have examined these drugs for the treatment of constipation.

Colchicine

Colchicine is a drug that has been used for decades to treat gout. Most patients who take colchicine note a loosening of their stools. Colchicine has also been demonstrated to relieve constipation effectively in patients without gout.

Misoprostol (Cytotec)

Misoprostol (Cytotec) is a drug used primarily for preventing stomach ulcers caused by nonsteroidal antiinflammatory drugs such as ibuprofen. Diarrhea is one of its consistent side-effects. Several studies have shown that misoprostol is effective in the short term treatment of constipation. Misoprostol is expensive, and it is not clear if it will remain effective and safe with long-term use. Therefore, its role in the treatment of constipation remains to be determined.

Orlistat (Xenical)

Orlistat (Xenical) is a drug that is used primarily for reducing weight. It works by blocking the enzymes within the intestine that digest fat. The undigested fat is not absorbed, which accounts for the weight loss. Undigested fat is digested by bacteria within the intestine and the products of this bacterial digestion promote the secretion of water. The products of digestion also may affect the intestine in other ways, for example, by stimulating the intestinal muscles. In fact, in studies, orlistat has been shown to be effective in treating constipation. Orlistat has few important side effects, which is consistent with the fact that only very small amounts of the drug are absorbed from the intestine.

It is unclear if these prescribed drugs should be used for the treatment of constipation. Although it is difficult to recommend them specifically just for the treatment of constipation, they might be considered for constipated individuals who are overweight, have gout, or need protection from nonsteroidal antiinflammatory drugs.

Exercise

People who lead sedentary lives are more frequently constipated than people who are active. Nevertheless, limited studies of exercise on bowel habit have shown that exercise has minimal or no effect on the frequency of bowel movements. Thus, exercise can be recommended for its many other health benefits, but not for its effect on constipation.

Biofeedback

Most of the muscles of the pelvis surrounding the anus and rectum are under some degree of voluntary control. Thus, biofeedback training can teach patients with pelvic floor dysfunction how to make their muscles work more normally and improve their ability to defecate. During ano-rectal biofeedback training, a pressure-sensing catheter is placed through the anus and into the rectum. Each time a patient contracts the muscles, the muscles generate a pressure that is sensed by the catheter and recorded on a screen. By watching the pressures on the screen and attempting to modify them, patients learn how to relax and contract the muscles more normally.

Surgery

For individuals with problematic constipation that is due to diseases of the colon or laxative abuse, surgery is the ultimate treatment. During surgery, most of the colon, except for the rectum (or the rectum and part of the sigmoid colon), is removed. The cut end of the small intestine is attached to the remaining rectum or sigmoid colon. In patients with colonic inertia, surgery is reserved for those who do not respond to all other therapies. If the surgery is to be done, there must be no disease of the small intestinal muscles. Normal small intestinal muscles are evidenced by normal motility studies of the small intestine itself.

Electrical pacing

Electrical pacing is still in its experimental phases. Electrical pacing may be done using electrodes implanted into the muscular wall of the colon. The electrodes exit the colon and are attached to an electrical stimulator. Alternatively, stimulation of the sacral skin can be used to stimulate nerves going to the colon. These techniques are promising, but much more work lies ahead before their role in treating constipation, if any, has been defined.


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