to 
adult dose
Adults: 1250 mg 1–4 times a day
Children 6–12 yr: 625 mg 1–4 times a day
Adults and children older than 12 yr: 50–500 mg/day
Children 6–12 yr: 40–120 mg/day (All doses taken with a full glass of water)
Adults: 10–15 mg (tablets) or 10-mg suppository once daily
Children: 5-mg tablet or 5-mg suppository once daily
Adults: 2 tablets once or twice a day
Children 6–12 yr: 1 tablet once or twice a day
Adults: 15–30 mL daily, increased to 60 mL if needed
Children 6 mo–1 yr: 40 mg/kg PO daily
Children 2–5 yr: 400–1200 mg PO daily
Children 6–11 yr: 1200–2400 mg PO daily
Children >12 yr: 2400–4800 mg PO daily
Adults: 15–45 mL daily; may take in divided doses
Children: 5–45 mL daily; may take in divided doses
Surfactant Laxatives
Actions
The surfactants (e.g., docusate sodium) are group III laxatives: they produce a soft stool several days after the onset of treatment. Surfactants alter stool consistency by lowering surface tension, which facilitates penetration of water into the feces. The surfactants may also act on the intestinal wall to (1) inhibit fluid absorption and (2) stimulate secretion of water and electrolytes into the intestinal lumen. In this respect, surfactants resemble the stimulant laxatives (see later).
Preparations, Dosage, and Administration
The surfactant family consists of two docusate salts: docusate sodium and docusate calcium. The dosage for docusate sodium [Colace], the prototype surfactant, is shown in Table 63.4. Administration should be accompanied by a full glass of water.
Stimulant Laxatives
The stimulant laxatives (e.g., bisacodyl, senna, castor oil) have two effects on the bowel. First, they stimulate intestinal motility—hence their name. Second, they increase the amount of water and electrolytes within the intestinal lumen by increasing secretion of water and ions into the intestine and by reducing water and electrolyte absorption. Most stimulant laxatives are group II agents: they act on the colon to produce a semifluid stool within 6 to 12 hours.
Stimulant laxatives are widely used—and abused—by the general public and are of concern for this reason. They have few legitimate applications. Two applications that are legitimate are (1) treatment of opioid-induced constipation and (2) treatment of constipation resulting from slow intestinal transit. Properties of individual agents are discussed next.
Bisacodyl
Bisacodyl [Correctol, Dulcolax] is unique among the stimulant laxatives in that it can be administered by rectal suppository as well as by mouth. Oral bisacodyl acts within 6 to 12 hours. Hence tablets may be given at bedtime to produce a response the following morning. Bisacodyl suppositories act rapidly (in 15–60 minutes). Dosages for bisacodyl are shown in Table 63.4.
Bisacodyl tablets are enteric coated to prevent gastric irritation. Accordingly, patients should be advised to swallow them intact, without chewing or crushing. Because milk and antacids accelerate dissolution of the enteric coating, the tablets should be administered no sooner than 1 hour after ingesting these substances.
Bisacodyl suppositories may cause a burning sensation and, with continued use, proctitis may develop. Accordingly, long-term use should be discouraged.
Senna
Senna [Senokot, Ex-Lax] is a plant-derived laxative that contains anthraquinones as active ingredients. The actions and applications of senna are similar to those of bisacodyl. Anthraquinones act on the colon to produce a soft or semifluid stool in 6 to 12 hours. Systemic absorption followed by renal secretion may impart a harmless yellow-brown or pink color to the urine. Dosages are presented in Table 63.4.
Castor Oil
Castor oil is the only stimulant laxative that acts on the small intestine. As a result, the drug acts quickly (in 2–6 hours) to produce a watery stool. Hence, unlike other stimulant laxatives, which are all group II agents, castor oil belongs to group I. Use of castor oil is limited to situations in which rapid and thorough evacuation of the bowel is desired (e.g., preparation for radiologic procedures). The drug is far too powerful for routine treatment of constipation. Because of its relatively prompt action, castor oil should not be administered at bedtime. The drug has an unpleasant taste that can be improved by chilling and mixing with fruit juice.
Osmotic Laxatives
Laxative Salts
Actions and Uses
The laxative salts (e.g., sodium phosphate, magnesium hydroxide) are poorly absorbed salts whose osmotic action draws water into the intestinal lumen. Accumulation of water causes the fecal mass to soften and swell, thereby stretching the intestinal wall, which stimulates peristalsis. When administered in low doses, the osmotic laxatives produce a soft or semifluid stool in 6 to 12 hours. In high doses, these agents act rapidly (in 2–6 hours) to cause a fluid evacuation of the bowel. High-dose therapy is employed to empty the bowel in preparation for diagnostic and surgical procedures. High doses are also employed to purge the bowel of ingested poisons and to evacuate dead parasites after anthelmintic therapy.
Preparations
We have two groups of laxative salts: (1) magnesium salts (magnesium hydroxide, magnesium citrate, and magnesium sulfate) and (2) one sodium salt (sodium phosphate). Dosages for magnesium hydroxide solution (also known as milk of magnesia) and sodium phosphate are shown in Table 63.4.
Adverse Effects
Osmotic laxatives can cause substantial loss of water. To avoid dehydration, patients should increase fluid intake. Although the osmotic laxatives are poorly and slowly absorbed, some absorption does take place. In patients with renal impairment, magnesium can accumulate to toxic levels. Accordingly, magnesium salts are contraindicated in patients with kidney disease. Sodium absorption (from sodium phosphate) can cause fluid retention, which in turn can exacerbate heart failure, hypertension, and edema. Accordingly, sodium phosphate is contraindicated for patients with these disorders. Sodium phosphate can also cause acute renal failure in vulnerable patients, especially those with kidney disease and those taking drugs that alter renal function (e.g., diuretics, angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs]). The mechanism involves dehydration and precipitation of calcium and phosphate in renal tubules. Accordingly, sodium phosphate should be avoided in this vulnerable group.
Polyethylene Glycol
Polyethylene glycol (PEG) [MiraLax, GlycoLax, Peglax 
] is an osmotic laxative used widely for chronic constipation. Like the laxative salts, PEG is a nonabsorbable compound that retains water in the intestinal lumen, causing the fecal mass to soften and swell. The most common adverse effects are nausea, abdominal bloating, cramping, and flatulence. High doses may cause diarrhea. For management of chronic constipation, PEG is superior to lactulose with regard to relief of abdominal pain and improvements in stool consistency and frequency per week, although side effects are similar. The recommended dosage is 17 g once a day, dissolved in 4 to 8 ounces of water, juice, soda, coffee, or tea. Bowel movement may not occur for another 2 to 4 days. As discussed later, products that contain PEG plus electrolytes can be used to cleanse the bowel before colonoscopy and other procedures.
Lactulose
Lactulose [Constulose, Enulose] is a semisynthetic disaccharide composed of galactose and fructose. Lactulose is poorly absorbed and cannot be digested by intestinal enzymes. In the colon, resident bacteria metabolize lactulose to lactic acid, formic acid, and acetic acid. These acids exert a mild osmotic action, producing a soft, formed stool in 1 to 3 days. Although lactulose can relieve constipation, this agent is more expensive than equivalent drugs (bulk-forming laxatives) and causes more unpleasant side effects (flatulence and cramping are common). Accordingly, lactulose should be reserved for patients who do not respond adequately to a bulk-forming agent.
In addition to its laxative action, lactulose can enhance intestinal excretion of ammonia. This property has been exploited to lower blood ammonia content in patients with portal hypertension and hepatic encephalopathy secondary to chronic liver disease.
Other Laxatives
Lubiprostone
Lubiprostone [Amitiza] is the first representative of a new class of drugs: the selective chloride channel activators. By activating (opening) chloride channels in epithelial cells lining the intestine, lubiprostone (1) promotes secretion of chloride-rich fluid into the intestine and (2) enhances motility in the small intestine and colon. The result is spontaneous evacuation of a semisoft stool, usually within 24 hours. Lubiprostone has three indications: (1) chronic idiopathic constipation in adults, (2) irritable bowel syndrome with constipation (IBS-C) in women at least 18 years old, and (3) treatment of opioid-induced constipation in chronic noncancer pain. In clinical trials, the drug reduced constipation severity, abdominal bloating, and discomfort.
Lubiprostone is taken orally, and very little is absorbed. Nausea is the most common side effect and can be reduced by taking lubiprostone with food and water. Other GI effects include diarrhea, abdominal distention, abdominal pain, gas, vomiting, and loose stools. Headache is the major non-GI effect. A small percentage of patients experience difficulty breathing in association with a sense of tightness in the chest, starting 30 to 60 minutes after the first dose and resolving in a few hours. Lubiprostone is categorized in U.S. Food and Drug Administration (FDA) Pregnancy Risk Category C and hence should be used only if benefits are deemed to outweigh potential risks to the fetus. (In animal studies, lubiprostone was not teratogenic. However, when given to guinea pigs in doses more than 100 times the human dose, lubiprostone did cause fetal loss.) Interactions with other drugs have not been studied but seem unlikely because lubiprostone is poorly absorbed and does not alter the activity of cytochrome P450 drug-metabolizing enzymes.
Lubiprostone is available in 8- and 24-mcg soft-gelatin capsules that should be taken with food and water. The recommended dosage is 24 mcg twice daily for constipation and 8 mcg twice daily for IBS-C. The role of lubiprostone in IBS-C is discussed in Chapter 64.
Mineral Oil
Mineral oil is a mixture of indigestible and poorly absorbed hydrocarbons. Laxative action is produced by lubrication. Mineral oil is especially useful when administered by enema to treat fecal impaction.
Mineral oil can produce a variety of adverse effects. Aspiration of oil droplets can cause lipid pneumonia. Anal leakage can cause pruritus and soiling. Systemic absorption can produce deposition of mineral oil in the liver. Excessive dosing can decrease absorption of fat-soluble vitamins. Dosages for adults and children are shown in Table 63.4.
Glycerin Suppository
Glycerin is an osmotic agent that softens and lubricates inspissated (hardened, impacted) feces. The drug may also stimulate rectal contraction. Evacuation occurs about 30 minutes after suppository insertion. Glycerin suppositories have been useful for reestablishing normal bowel function after termination of chronic laxative use.
Bowel Cleansing Products for Colonoscopy
Colonoscopy is the most effective method for early detection of colorectal cancer, the second leading cause of cancer deaths in the United States. Before the procedure, the bowel must be cleansed to permit good visualization. Three kinds of bowel cleansers are used: (1) sodium phosphate; (2) a combination of sodium picosulfate, magnesium oxide, and citric acid; and (3) PEG plus electrolytes (ELS). The PEG-ELS products are isotonic with body fluids and hence do not alter water or electrolyte status. In contrast, the sodium phosphate and combination products are hypertonic and can cause dehydration and electrolyte disturbances. In addition, the sodium phosphate products can cause kidney damage. However, despite their greater potential for harm, the sodium phosphate products have better patient acceptance because the PEG-ELS products require ingestion of a large volume of liquid, whereas the sodium phosphate products do not. Nonetheless, sodium phosphate products should be avoided by patients at risk, including those with electrolyte abnormalities, renal impairment, and hypovolemia. Representative bowel cleansers are shown in Table 63.5.
TABLE 63.5
Oral Bowel Cleansing Products for Colonoscopy
| Product Type and Brand Name | Adult Dosage | Total Volume to Swallow | |
| Bowel Cleanser | Clear Liquid | ||
| SODIUM PHOSPHATE TABLETS | |||
| Visicol | 20 tablets with clear liquid in the evening plus 12 tablets with clear liquid the next day | 3.4 L | |
| OsmoPrep | 20 tablets with clear liquid in the evening plus 20 tablets with clear liquid the next day | 1.9 L | |
| POLYETHYLENE GLYCOL PLUS ELECTROLYTES | |||
| GoLYTELY, NuLytely, CoLyte, TriLyte | 240 mL every 10 min until 4 L is ingested or until rectal effluent is clear | 4 L | |
| HalfLytely and bisacodyl | 240 mL every 10 min until 2 L is ingested* | 2 L | |
| MoviPrep† | 240 mL every 15 min unti1 1 L is ingested, then repeat 1.5 hr later, then drink 1 more L of clear liquid‡ | 2 L | 1 L |
| COMBINATION PRODUCT | |||
| Prepopik | 1 package (16.1 g) mixed in 5 ounces of water the evening before the colonoscopy and 1 package mixed in 5 ounces of water the morning of the colonoscopy.§ | 2.5 L | |
Polyethylene Glycol–Electrolyte Solutions
These bowel-cleansing solutions [CoLyte, GoLYTELY, others] contain PEG, a nonabsorbable osmotic agent, together with ELS (usually potassium chloride, sodium chloride, sodium sulfate, and sodium bicarbonate). The mixture is isosmotic with body fluids, and hence water and electrolytes are neither absorbed from nor secreted into the intestinal lumen. As a result, dehydration does not occur and electrolyte balance is preserved. Because effects on water and electrolytes are minimal, PEG-ELS solutions can be used safely by patients who are dehydrated and by those who are especially sensitive to alteration of electrolyte levels (e.g., patients with renal impairment or cardiovascular disease).
With traditional PEG-ELS products (e.g., CoLyte, GoLYTELY), the volume administered is huge, typically 4 L. Patients must ingest 250 to 300 mL every 10 minutes for 2 to 3 hours. With two newer products—HalfLytely and MoviPrep—the volume is cut in half. Patients using HalfLytely take a stimulant laxative—bisacodyl—along with the PEG-ELS solution and hence don’t need the full 4-L dose. Volume reduction with MoviPrep is possible owing to addition of ascorbic acid and sodium ascorbate to the PEG-ELS solution. With all PEG products, bowel movements commence about 1 hour after the first dose.
PEG-ELS products are generally well tolerated. The most common adverse effects are nausea, bloating, and abdominal discomfort. These effects are less intense with the reduced-volume formulations. Because PEG-ELS products don’t alter water and electrolyte status, they are safer than sodium phosphate products for patients with electrolyte imbalances, heart failure, kidney disease, or advanced liver disease.
Sodium Phosphate Products
As discussed previously, sodium phosphate is an osmotic laxative that draws water into the intestinal lumen, which then softens and swells the fecal mass, which then stretches the intestinal wall to stimulate peristalsis. Dosing consists of swallowing tablets along with a large volume of water or some other clear liquid. Because the clear liquid is more palatable than the PEG-ELS solutions, patients find the sodium phosphate regimens more appealing.
Like the PEG-ELS products, the sodium phosphate products can cause nausea, bloating, and abdominal discomfort. In addition, the sodium phosphate products can cause adverse effects not seen with the PEG-ELS products, especially dehydration, electrolyte disturbances, and kidney damage. By drawing a large volume of fluid into the intestinal lumen, sodium phosphate can cause dehydration. To prevent dehydration, patients must drink a large volume of clear fluid before, during, and after dosing.
Rarely, phosphate is absorbed in amounts sufficient to cause hyperphosphatemia, which can cause acute, reversible renal damage, and possibly chronic, irreversible renal damage. Risk factors for hyperphosphatemia and kidney damage include hypovolemia, advanced age, delayed bowel transit, active colitis, preexisting kidney disease, and use of drugs that can alter kidney function, including diuretics, ACE inhibitors, ARBs, and nonsteroidal antiinflammatory drugs. Patients who have these risk factors should probably use a PEG-ELS product rather than sodium phosphate.
Combination Products
One combination product—magnesium oxide/anhydrous citric acid/sodium picosulfate [Prepopik]—is approved for preparation for colonoscopy in adults. Sodium picosulfate is a stimulant laxative, and magnesium oxide and citric acid combine to form magnesium citrate, an osmotic laxative. When given in a split-dose regimen, results were superior to colon preparation with PEG-ELS.
Prepopik is given in a split-dose regimen. It is supplied in 2 packets containing 16.1 g each of powder that must be mixed with water for consumption. The first dose is taken the evening before the colonoscopy and the second dose the next morning before the procedure.
As with sodium phosphate products, Prepopik can cause electrolyte and fluid imbalances, renal impairment, seizures, and dysrhythmia secondary to electrolyte abnormalities. Caution must be employed in patients with reduced renal function. The most common adverse reactions are nausea, headache, and vomiting.
Laxative Abuse
Causes
Many people believe that a daily bowel movement is a requisite of good health and that any deviation from this pattern merits correction. Such misconceptions are reinforced by aggressive marketing of over-the-counter laxative preparations. Not infrequently, the combination of tradition supported by advertising has led to habitual self-prescribing of laxatives by people who don’t need them.
Laxatives can help perpetuate their own use. Strong laxatives can purge the entire bowel. When this occurs, spontaneous evacuation is impossible until bowel content has been replenished, which can take 2 to 5 days. During this time, the laxative user, having experienced no movement of the bowel, often becomes convinced that constipation has returned. In response, he or she takes yet another dose, which purges the bowel once more, and thereby sets the stage for a repeating cycle of laxative use and purging.
Consequences
Chronic exposure to laxatives can diminish defecatory reflexes, leading to further reliance on laxatives. Laxative abuse may also cause more serious pathologic changes, including electrolyte imbalance, dehydration, and colitis.
Treatment
The first step in breaking the laxative habit is abrupt cessation of laxative use. After drug withdrawal, bowel movements will be absent for several days; the patient should be informed of this fact. Any misconceptions that the patient has regarding bowel function should be corrected: the patient should be taught that a once-daily bowel movement may not be normal for him or her and that stool quality is more important than frequency or quantity. Instruction on bowel training (heeding the defecatory reflex, establishing a consistent time for bowel movements) should be provided. Increased consumption of fiber (bran, fruits, vegetables) and fluid should be stressed. The patient should be encouraged to exercise daily, especially after meals. Finally, the patient should be advised that, if a laxative must be used, it should be used briefly and in the smallest effective dose. Agents that produce catharsis must be avoided.
