William C. Shiel Jr., MD, FACP, FACR
Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.
In this Article
- Constipation facts
- What is constipation?
- What causes constipation?
- Medications that cause constipation
- Other causes of constipation
- How is constipation evaluated (diagnosed)?
- What treatments are available for constipation?
- Home remedies and OTC medications to treat constipation
- Prescription drugs to treat constipation
- Other treatments for constipation
- What is the approach to the evaluation and treatment of constipation?
- When should I seek medical care for chronic constipation?
- What's new in the treatment of constipation?
- Pictures of Constipation Myths and Facts - Slideshow
- Pictures of Irritable Bowel Syndrome (IBS) - Slideshow
- Pictures of What's Causing Your Pelvic Pain - Slideshow
Prescription drugs to treat constipation
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) 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.
Linaclotide (Linzess) is an oral drug that is not absorbed from the intestine. It stimulates the cells lining the small intestine to secrete fluid into the intestine. The increase in fluid secretion leads to an increased number of bowel movements. In addition, when constipation is associated with the abdominal pain of IBS, the pain also is reduced. Although the improvement in pain may be due to the improvement in constipation, linaclotide has been shown also to reduce the sensitivity of intestinal pain nerves, and this mechanism of action also may account for the decrease in pain.
Linaclotide is moderately effective, and it's effectiveness depends on how a favorable response is defined. In the studies leading up to its approval, linaclotide was associated with a predefined response of an increase in bowel movements and a decrease in pain in approximately one-third (33%) of patients as compared with 17% of patients who received placebo. The response was better when pain and constipation were considered separately, with responses of approximately 50% for either.
The only common side effect of linaclotide is diarrhea. It should not be used in children below the age of six because of serious toxicity (death) to very young mice in animal studies, and should be avoided in children ages six through 17.
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 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) 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) 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.
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