Update on constipation: One treatment does not fit all
ABSTRACTConstipation is a common clinical problem that can be difficult to manage. It has a variety of identifiable causes, but even idiopathic constipation has different possible mechanisms. Often, the key to improvement and patient satisfaction is to understand the mechanism and the patient.
KEY POINTS
- A high-fiber diet often improves functional constipation, but it may worsen slow-transit constipation or dyssynergia (a failure of the pelvic floor muscles to relax). Nevertheless, fiber remains a mainstay of treatment for its ability to provide homogeneous stool consistency.
- Drugs approved for treating constipation increase fluid in the lumen, speed intestinal transit, and improve stool consistency, while tegaserod (Zelnorm) additionally acts as a serotonin agonist.
- Colonoscopy and other tests are reserved for patients with refractory constipation and those with symptoms suggesting colon cancer.
- Prebiotics (short-chain carbohydrates that stimulate activity of beneficial colonic bacterial flora) and probiotics (live bacterial preparations) are under evaluation as treatments for chronic constipation.
OSMOTIC LAXATIVES
Osmotic laxatives are molecules that are either not absorbed or poorly absorbed and that draw water into the intestinal lumen to maintain isotonicity between the intestinal contents and the serum. Examples are polyethylene glycol, sodium phosphate (Fleet phosphosoda), magnesium hydroxide, magnesium citrate, the sugars lactulose and sorbitol, and glycerin.
Certain formulations of this class of laxative can cause bloating, diarrhea, electrolyte disturbances, volume overload, or dehydration. These effects limit their use, and these medications should be used with caution in patients prone to renal insufficiency or cardiac abnormalities.
Polyethylene glycol
Polyethylene glycol is an exception. It is not absorbed and lacks electrolytes, making it an attractive option in patients with underlying renal or cardiac dysfunction. In several placebo-controlled trials,50–52 various formulations significantly increased stool frequency while significantly decreasing straining, use of other laxatives, and colonic transit. No increase in adverse effects was noted compared with placebo.
Compared with lactulose, polyethylene glycol at about 21 g/day significantly increased bowel movement frequency while significantly decreasing the sense of straining with bowel movements and flatus due to laxative use.51 Both polyethylene glycol and lactulose accelerate colonic transit, although polyethylene glycol does so to a greater extent.53
Polyethylene glycol has been safe and effective when used for up to 6 months.54
Lactulose and sorbitol
Carbohydrate or sugar-based laxatives, if taken in sufficient doses, have a cathartic effect through two mechanisms: a primary osmotic effect of the sugar itself and a secondary osmotic effect as a substrate for colonic bacteria to cleave to acid metabolites, which exert an osmotic effect in the colon. This secondary effect will be discussed in a later section.
Lactulose and sorbitol are sugars that are poorly absorbed by the intestine. Lactulose has been shown to be more effective than placebo in increasing stool frequency, volume, weight, and consistency in chronically constipated patients.55 In a head-to-head comparison between sugar laxatives, 70% sorbitol was as effective as lactulose in increasing the frequency of bowel movements, and it was similar in its adverse effects56; 70% sorbitol is a cost-effective alternative to lactulose in the elderly nursing home population.57
Compared with fiber alone, lactulose use leads to a significantly higher number of bowel movements and better stool consistency.58 However, when lactulose was compared with a combination of fiber and a stimulant laxative, it was less effective than the combination therapy.59,60
Sugar laxatives, while effective, may have dose-limiting or use-limiting adverse effects such as abdominal bloating and flatulence.
Phosphate, magnesium
Sodium phosphate, like polyethylene glycol, is often used as a bowel preparation before colonoscopy, for which it is about as good or slightly better than polyethylene glycol.61,62
Although magnesium and sodium phosphate preparations are effective, there are multiple reports of clinically significant electrolyte abnormalities, renal failure, and congestive heart failure occurring with these preparations. Therefore, they must be used with discretion and caution in appropriate patients with frequent monitoring.
STIMULANT (IRRITANT) LAXATIVES
Stimulant laxatives are usually reserved for use when bulking agents and osmotic laxatives fail. Their mechanism of action involves the alteration of intestinal motility and intestinal fluid secretion.
Anthraquinones (cascara, aloe, and senna), castor oil, and diphenylmethanes (bisacodyl) are the most commonly used stimulant laxatives. They work relatively quickly, often eliciting a bowel movement 2 to 8 hours after they are taken.
This class of laxatives has historically been underused or given for only short periods of time, owing to concern about impairing colonic function, damaging the enteric nervous system, causing laxative dependency, causing cathartic colon, and even causing colon cancer. However, there is very little evidence to support these concerns. Stimulant laxatives can be used on a more regular basis when bulking or osmotic agents fail.63
Possibly of greatest concern is the potential for the overuse and abuse of stimulant laxatives. Excessive use can cause electrolyte disturbances brought about by high-volume watery diarrhea. Risk factors for overuse and abuse include underlying psychiatric disturbances and eating disorders. Prescribing other types of laxatives or cathartic agents may reduce risk, but the potential for abuse exists with all categories of laxatives.
TEGASEROD: GONE BUT STILL AVAILABLE, ON A CONTROLLED BASIS
Tegaserod (Zelnorm), a serotonin (5-HT4) agonist, was used predominantly in women with constipation-predominant irritable bowel syndrome and in men and women with chronic constipation. However, it was suspended from the market in the United States in March 2007 owing to concern about a high risk of adverse cardiovascular effects compared with placebo.
In a double-blind, randomized controlled trial, men with chronic constipation who received tegaserod 6 mg twice a day for 12 weeks had more spontaneous bowel movements than those receiving placebo (P = .04).64
Lin et al65 evaluated the use of tegaserod 6 mg twice daily for 4 weeks in both men and women with chronic constipation. Those receiving tegaserod had significantly more spontaneous bowel movements per week, less straining, and better stool consistency than those receiving placebo.
Tegaserod can still be obtained for appropriate patients via a treatment investigational new drug application. Safety data are under further review by the US Food and Drug Administration. Studies of other serotonin agonists are under way.
