GENERAL APPROACH TO TREATMENT

The patient should be asked about the frequency of bowel movements and the chronicity of constipation. Constipation occurring recently in an adult may indicate significant colon pathology such as malignancy; constipation present since early infancy may be indicative of neurologic disorders. The patient also should be carefully questioned about usual diet and laxative regimens. Does the patient have a diet consistently deficient in high-fiber items and containing mainly highly refined foods? What laxatives or cathartics has the patient used to attempt relief of constipation? The patient should be questioned about other concurrent medications, with interest focused on agents that might cause constipation.

Table: Constipation Treatment Algorithm

History

• Stool frequency

• Stool consistency

• Difficulty of defecation

Possible causes

• Diet deficient in high-fiber items and consisting mainly of highly refined foods

• GI disorders

• Metabolic and endocrine disorders

• Pregnancy

• Neurogenic

• Psychogenic

• Drug-Induced

• Laxative abusers

Symptoms seen with chronic constipation

• Fluid and electrolyte imbalances (hypokalemia)

• Protein-losing gastroenteropathy with hypoalbuminemia

• Syndromes resembling colitis

Select appropriate diagnostic studies

• Protoscopy

• Sigmoidoscopy

• Colonoscopy

• Barium enema

Diagnosis

1. Treat specific cause

2. No diagnosis, symptomatic therapy

A. Bulk-forming agents

B. Dietary modification

C. Alter lifestyle (exercise)

D. Increase fluid intake

E. Discontinue potential drug inducer

For most patients complaining of constipation, a thorough physical examination is not required after it is established that constipation (a) is not a chronic problem, (b) is not accompanied by signs of significant GI disease (e.g., rectal bleeding or anemia), and (c) does not cause severe discomfort. In these circumstances, the patient may be referred directly to the first-line therapies for constipation described in the next section (mainly bulk-forming laxatives and dietary fiber with occasional use of saline or stimulant laxatives). Table: Constipation Treatment Algorithm presents a general treatment algorithm for the management of constipation.

The proper management of constipation requires a number of different modalities; however, the basis for therapy should be dietary modification. The major dietary change should be an increase in the amount of fiber consumed daily. In addition to dietary management, patients should be encouraged to alter other aspects of their lifestyles if necessary. Important considerations are to encourage patients to exercise (achieved even by brisk walking after dinner) and to adjust bowel habits so that a regular and adequate time is made to respond to the urge to defecate. Another general measure is to increase fluid intake. This is generally recommended and believed beneficial, although there is little objective evidence to support this measure.

If an underlying disease is recognized as the cause of constipation, attempts should be made to correct it. GI malignancies may be removed via surgical resection. Endocrine and metabolic derangements should be corrected by the appropriate methods. For example, when hypothyroidism is the cause of constipation, cautious institution of thyroid-replacement therapy is the most important treatment measure.

As discussed earlier, many drug substances may cause constipation. If a patient is consuming medications well known to cause constipation, consideration should be given to alternative agents. For some medications (e.g., antacids), nonconstipating alternatives exist. If no reasonable alternatives exist to the medication thought to be responsible for constipation, consideration should be given to lowering the dose. If a patient must remain on constipating medications, then more attention must be given to general measures for prevention of constipation, as discussed in the next section.

NONPHARMACOLOGIC THERAPY

DIETARY MODIFICATION AND BULK-FORMING AGENTS

The most important aspect of therapy for constipation for the majority of patients is dietary modification to increase the amount of fiber consumed. Fiber, the portion of vegetable matter not digested in the human GI tract, increases stool bulk, retention of stool water, and rate of transit of stool through the intestine. The result of fiber therapy is an increased frequency of defecation. Also, fiber decreases intraluminal pressures in the colon and rectum, which is thought to be beneficial for diverticular disease and for irritable bowel syndrome. The specific physiologic effects of fiber are not well understood. Patients should be advised to include at least 10 g of crude fiber in their daily diets. Fruits, vegetables, and cereals have the highest fiber content. Bran, a by-product of milling of wheat, is often added to foods to increase fiber content. Raw bran is generally 40% fiber. Medicinal products, often called “bulk-forming agents,” such as psyllium hydrophilic colloids, methylcellulose, or polycarbophil, have properties similar to those of dietary fiber and may be taken as tablets, powders, or granules (Table: Dosage Recommendations for Laxatives and Cathartics). A trial of dietary modification with high-fiber content should be continued for at least 1 month before effects on bowel function are determined. Most patients begin to notice effects on bowel function 3 to 5 days after beginning a high-fiber diet, but some patients may require a considerably longer period of time. Patients should be cautioned that abdominal distention and flatus may be particularly troublesome in the first few weeks of fiber therapy, particularly with high bran consumption. In most cases these problems resolve with continued use.

Bulk-forming laxatives have few adverse effects. The only major caution in the use of bulk-forming laxatives is that obstruction of the esophagus, stomach, small intestine, and colon has been reported when the agents have been consumed without sufficient fluid or in patients with intestinal stenosis.

Table: Dosage Recommendations for Laxatives and Cathartics

Agent	Recommended Dose
Agents that cause softening of feces in 1-3 days
Bulk-forming agents
Methylcellulose	4-6 g/day
Polycarbophil	4-6 g/day
Psyllium	Varies with product
Emollients
Docusate sodium	50-360 mg/day
Docusate calcium	50-360 mg/day
Docusate potassium	100-300 mg/day
Lactulose	15-30 mL orally
Sorbitol	30-50 g/day orally
Mineral oil	15-30 mL orally
Agents that result in soft or semifluid stool in 6-12 h
Bisacodyl (oral)	5-1 5 mg orally
Phenolphthalein	30-270 mg orally
Cascara sagrada	Dose varies with formulation
Senna	Dose varies with formulation
Magnesium sulfate (low dose)	<10 g orally
Agents that cause watery evacuation in 1-6 h
Magnesium citrate	1 8 g 300 mL water
Magnesium hydroxide	2.4-4.8 g orally
Magnesium sulfate (high dose)	10-30 g orally
Sodium phosphates	Varies with salt used
Bisacodyl	10 mg rectally
Polyethylene glycol-electrolyte preparations	4 L

SURGERY

In a small percentage of patients presenting with complaints of constipation, surgical procedures are necessary due to the presence of colonic malignancies or GI obstruction from a number of other causes. In each case, the involved segment of intestine may be resected or revised. Surgery may be required in some endocrine disorders causing constipation, such as pheochromocytoma, which requires removal of a tumor.

BIOFEEDBACK

The majority of patients with constipation related to pelvic floor dysfunction can benefit from electromyogram-guided biofeedback therapy. The value of biofeedback in children with chronic constipation has not been well demonstrated.

PHARMACOLOGIC THERAPY

DRUG REGIMENS OF CHOICE

Treatment and prevention of constipation should consist of bulk-forming agents in addition to dietary modifications that increase dietary fiber. A variety of products are available that provide adequate bulk. Whichever agent is chosen, it should be used daily and continued indefinitely in most patients, particularly those with chronic constipation. Bulk-forming agents available in combination with diphenylmethane or anthraquinone derivatives should not be used on a routine basis.

For most persons with acute constipation, infrequent use (less than every few weeks) of laxative products is acceptable. Acute constipation may be relieved by the use of a tap-water enema or a glycerin suppository; if neither is effective, the use of oral sorbitol, low doses of diphenylmethane or anthraquinone laxatives, or saline laxatives (e.g., milk of magnesia) may provide relief. If laxative treatment is required for longer than 1 week, the person should be advised to consult a physician to determine if there is an underlying cause of constipation that requires treatment with other modalities.

For some bedridden or geriatric patients, or others with chronic constipation, bulk-forming laxatives remain the first line of treatment, but the use of more potent laxatives may be required relatively frequently. Fiber should be avoided in bedridden patients who are cognitively impaired. When other than bulk-forming laxatives are used, they should be administered in the lowest effective dose and as infrequently as possible to maintain regular bowel function (more than three stools per week). Agents that may be used in these situations include diphenylmethane and anthraquinone derivatives, milk of magnesia, and sorbitol or lactulose. Mineral oil should be avoided, particularly in bedridden patients, because of the risk of aspiration and lipoid pneumonia. Some patients with chronic constipation may present with fecal impactions. Before vigorous oral laxatives can be used, the impaction needs to be removed using mechanical methods, including tap water or saline enemas and digital extraction.

In the hospitalized patient without GI disease, constipation may be related to the use of general anesthesia and/or opiate substances. Most orally or rectally administered laxatives may be used in these situations. For prompt initiation of bowel evacuation, either a tap-water enema, glycerin suppository, or oral milk of magnesia are recommended.

With infants and children, constipation may occur commonly. In patients with persistent problems, the underlying etiology may be neurologic, metabolic, or secondary to anatomic abnormalities. Managementof constipation in this age group should consist of dietary modification with an emphasis on high-fiber foods.

For acute constipation in most age groups, a tap-water enema or glycerin suppository may be helpful. Occasional use of milk of magnesia or an anthraquinone laxative in low doses is justified as well.

DRUG CLASSES

The traditional classification system for laxatives and cathartics by suspected mode of action is not very useful, as this is not clearly understood for many agents. In general, most of these products induce bowel evacuation by one or more of the mechanisms associated with the etiology of diarrhea, including active electrolyte secretion, decreased water and electrolyte absorption, increased intraluminal osmolarity, and increased hydrostatic pressure in the gut. Laxatives convert the intestine from primarily an organ that absorbs water and electrolytes to an organ that secretes these substances.

The various classes of laxatives are discussed in this section. These agents are divided into three general classifications: (a) those causing softening of feces in 1 to 3 days (bulk-forming laxatives, docusates, and lactulose); (b) those that result in soft or semifluid stool in 6 to 12 hours (diphenylmethane derivatives and anthraquinone derivatives); and (c) those causing water evacuation in 1 to 6 hours (saline cathartics, castor oil, and polyethylene glycol-electrolyte lavage solution).

EMOLLIENT LAXATIVES

Emollient laxatives are surfactant agents, docusate in its various salts, which work by facilitating mixing of aqueous and fatty materials within the intestinal tract. They may increase water and electrolyte secretion in the small and large bowel. These products are generally given orally, although docusate potassium has also been used rectally. These products result in a softening of stools within 1 to 3 days of therapy.

Emollient laxatives are ineffective in treating constipation, but are used mainly to prevent this condition. They may be helpful in situations in which straining at stool should be avoided, such as after recovery from myocardial infarction, with acute perianal disease, or after rectal surgery. It is unlikely that these agents would be very effective in preventing constipation if major causative factors (e.g., heavy opiate use, uncorrected pathology, or inadequate dietary fiber) are not concurrently addressed.

Although docusates are generally safe, a few adverse effects have been noted. They may increase the intestinal absorption of agents administered concurrently and alter toxic potential.

LUBRICANTS

Mineral oil is the only lubricant laxative in routine use. This agent, obtained from petroleum refining, acts by coating stool and allowing for easier passage. It inhibits colonic absorption of water, thereby increasing stool weight and decreasing stool transit time. Mineral oil may be given orally or rectally in a dose of 15 to 45 mL. Generally, the effect on bowel function is noted after 2 or 3 days of use.

Mineral oil is helpful in situations similar to those suggested for docusates: to maintain a soft stool and to avoid straining for relatively short periods of time (a few days to 2 weeks); however, it possesses a much greater potential for adverse effects and its routine use should be discouraged. Mineral oil may be absorbed systemically and can cause a foreign-body reaction in lymphoid tissue. Also, in debilitated or recumbent patients, mineral oil may be aspirated, causing lipoid pneumonia. Mineral oil may decrease the absorption of fat-soluble vitamins (A, D, E, and K) with chronic use by causing retention in the GI tract. Finally, even when given orally, mineral oil may leak from the anal sphincter, causing pruritus and soiling of clothing.

LACTULOSE AND SORBITOL

Lactulose is a disaccharide that is used orally or rectally. It is metabolized by colonic bacteria to low-molecular-weight acids, resulting in an osmotic effect whereby fluid is retained in the colon. The fluid retained in the colon lowers the pH and increases colonic peristalsis. Lactulose is generally not recommended as a first-line agent for the treatment of constipation because it is costly and not necessarily more effective than such agents as sorbitol or milk of magnesia. It may be justified as an alternative for acute constipation, and has been particularly useful in elderly patients. Occasionally, the use of lactulose may result in flatulence, cramps, diarrhea, and electrolyte imbalances. Sorbitol, a monosaccharide, exerts its effect by osmotic action and has been recommended as a primary agent in the treatment of functional constipation in cognitively intact patients. It is as effective as lactulose and much less expensive.

DIPHENYLMETHANE DERIVATIVES

The two commonly used diphenylmethane derivatives are bisacodyl and phenolphthalein. Bisacodyl exerts its therapeutic effect by stimulating the mucosal nerve plexus of the colon. Phenolphthalein is thought to inhibit active glucose and sodium absorption, resulting in fluid accumulation in the colon by osmotic action. With both of these agents, significant interpatient variability exists with dosing. A dose that causes no effect in one patient may result in excessive cramping and fluid evacuation in others. With phenolphthalein, a small portion of the dose undergoes enterohepatic recirculation, which may result in a prolonged laxative action.

These agents are not recommended for regular daily use. Their use is acceptable intermittently (every few weeks) to treat constipation or as a bowel preparation before diagnostic procedures in which cleansing of the colon is necessary. These agents may sometimes cause severe abdominal cramping as well as significant fluid and electrolyte imbalances with chronic use. They should not be used for patients in whom appendicitis is a possibility (perforation of the appendix may result) or during pregnancy or lactation. Finally, patients using phenolphthalein-containing laxatives should be cautioned that their urine might turn pink.

ANTHRAQUINONE DERIVATIVES

Anthraquinone derivatives include cascara sagrada, sennosides, and casanthrol. Gut bacteria metabolizes these agents to their active compounds, but the exact mechanisms of action are not understood. Effects are limited to the colon, and stimulation of Auerbach’s plexus may be involved. Recommendations for the use of these agents are similar to those for the diphenylmethane derivatives. In most cases, intermittent use is acceptable; daily use should be strongly discouraged.

Most of the concerns with the use of diphenylmethane derivatives apply to the anthraquinone derivatives. In addition, the anthraquinone derivatives may cause melanosis coli, an accumulation of dark pigment, mainly in the cecum and rectum, that is evident after 4 to 13 months of use. A pathologic effect of melanosis coli has not been demonstrated, and it appears to be reversible after anthraquinones have been discontinued for 3 to 6 months.

SALINE CATHARTICS

Saline cathartics are composed of relatively poorly absorbed ions such as magnesium, sulfate, phosphate, and citrate, which produce their effects primarily by osmotic action in retaining fluid in the GI tract. Magnesium stimulates the secretion of cholecystokinin, a hormone that causes stimulation of bowel motility and fluid secretion. These agents may be given orally or rectally. A bowel movement may result within a few hours after oral doses and in 1 hour or less after rectal administration.

These agents should be used primarily for acute evacuation of the bowel, which may be necessary before diagnostic examinations, after poisonings, and in conjunction with some anthelmintics to eliminate parasites. Such agents as milk of magnesia (an 8% suspension of magnesium hydroxide) may be used occasionally (every few weeks) to treat constipation in otherwise healthy adults. Saline cathartics should not be used on a routine basis. The enema formulations of these agents may be useful in fecal impactions.

As with most laxatives, these agents may cause fluid and electrolyte depletion. Also, magnesium or sodium accumulation may occur when magnesium-containing cathartics are used in patients with renal dysfunction or when sodium phosphate is used in patients with congestive heart failure.

CASTOR OIL

Castor oil is metabolized in the GI tract to an active compound, ricinoleic acid, which stimulates secretory processes, decreases glucose absorption, and promotes intestinal motility, primarily in the small intestine. Castor oil usually results in a bowel movement within 1 to 3 hours of administration. Because the agent has such a strong purgative action, it should not be used for the routine treatment of constipation.

GLYCERIN

Glycerin is usually administered as a 3-g suppository and exerts its effect by osmotic action in the rectum. As with most agents given as suppositories, the onset of action is usually less than 30 minutes. Glycerin is considered a very safe laxative, although it may occasionally cause rectal irritation. Its use is acceptable on an intermittent basis for constipation, particularly in children.

POLYETHYLENE GLYCOL-ELECTROLYTE LAVAGE SOLUTION

Whole-bowel irrigation with polyethylene glycol-electrolyte lavage solution (PEG-ELS) has become popular for colon cleansing before diagnostic procedures or colorectal operations.

Four liters of this solution is administered over 3 hours to obtain complete evacuation of the GI tract. The solution is not recommended for the routine treatment of constipation and its use should be avoided in patients with intestinal obstruction.

OTHER AGENTS

Tap-water enemas may be used to treat simple constipation. The administration of 200 mL of tap water by enema to an adult often results in a bowel movement within 30 minutes. Soap-suds enemas are no longer recommended as their use may result in proctitis or colitis.

PREVENTION

For certain groups of patients, such as those recovering from myocardial infarction or rectal surgery, straining at defecation is to be avoided. The basis of preventive therapy in these patients should be bulk-forming laxatives. Additionally, the use of docusate is popular, although its effectiveness is debated. In pregnant patients, constipation may result because of alterations in anatomy or iron supplementation. As described earlier, bulk-forming laxatives and docusates should be the first line of prevention.

LAXATIVE ABUSE SYNDROME

Misconceptions about normal bowel patterns and the effect of laxatives have contributed to a syndrome of laxative abuse that is relatively common in the United States. The availability of laxatives as chocolates or gums conveys to the public that the use of these agents is without adverse consequences. Abuse of laxatives has occurred traditionally in persons trying to maintain daily bowel function, but more recently has extended to others who use laxatives for the purpose of controlling weight. In either case, the consistent abuse of strong laxatives and cathartics may lead to serious illness.

Laxative abuse for the purpose of maintaining daily bowel function begins with misconceptions about the frequency, quantity, or consistency of stools. With the use of strong purgatives, the colon may be so thoroughly cleansed that a bowel movement may not occur normally until a few days later. This delay reinforces the need for more purgatives and the cycle of laxative dependence is begun. Eventually the patient may require daily laxatives to maintain bowel function.

The laxative abuser may present with contradictory findings of diarrhea and weight loss. In addition, long-term abusers of laxatives tend to have vomiting, abdominal pain, lassitude, weakness, thirst, edema, and bone pain (caused by osteomalacia). With prolonged use of laxatives a number of serious illnesses may arise. These include fluid and electrolyte imbalances (including acid-base imbalances and hypokalemia), protein-losing gastroenteropathy with hypoalbuminemia, and syndromes resembling colitis.

The determination of laxative abuse syndrome can be difficult because many laxative abusers vigorously deny laxative use. Middle-aged women tend to be the most common laxative abusers. The chronic laxative abuse problem should be addressed by a combination of measures, including psychiatric evaluation, dietary modification with reliance on bulk-forming laxatives, and specific guidelines to the patient for the withdrawal of stimulant laxatives.

A variation of laxative abuse is seen in persons who use them as a means of weight loss. It appears from the medical literature and daily news sources that this type of abuse is on the increase. Treatment of patients who abuse laxatives in this way has proven very difficult.

EVALUATION OF THERAPEUTIC OUTCOMES

The ultimate goal of treatment for constipation is alteration of lifestyle (particularly diet) to prevent further episodes of constipation. Short-term goals include alleviation of acute constipation with relief from symptoms. For patients with chronic constipation, the goals are more long-term and include use of proper diet and decreased reliance on laxatives. Effective treatment of constipation requires the patient to become more knowledgeable about the causes of constipation, proper diet, and appropriate use of laxatives.



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