Constipation Medication

Medications to treat constipation include bulk-forming agents (fibers), emollient stool softeners, rapidly acting lubricants, prokinetics, laxatives, osmotic agents, and prosecretory drugs. Fiber is arguably the best and least expensive medication for long-term treatment, although enthusiasm for the use of polyethylene glycol as first-line therapy in chronic constipation is increasing.

Emollient stool softeners are easier to use, but they lose their effectiveness with chronic administration. These drugs are best used for prophylaxis in a short-term setting, such as in patients receiving a postoperative narcotic prescription.

Rapidly acting lubricants and laxatives, including over-the-counter products, are often used to treat acute and chronic constipation.

Polyethylene glycol is simple to use and is more effective than placebo in the management of chronic constipation; however, the effects of chronic therapy with polyethylene glycol over decades are still not well studied.

Newer therapies for constipation include the prokinetic agent prucalopride and the osmotic agents lubiprostone and linaclotide. These drugs may be useful in chronic constipation when fiber, water, and polyethylene glycol fail, either alone in combination with simpler interventions.

Class Summary

Bulk-forming agents are used for long-term prophylaxis, treatment of constipation, or both in patients without anatomic outlet obstruction.

Psyllium (Metamucil, Fiberall, Bulk-K, Fibro-XL)

Psyllium dosages vary depending on whether the preparations contain sugar or are sugar-free (the former are 50% sugar). These preparations must be taken with water, or they may cause obstruction.

Methylcellulose (Citrucel)

Theoretically, nonfermentable products such as methylcellulose, which produce less gas, are better tolerated than psyllium. Occasionally, patients who cannot tolerate one preparation may do well with another product.

Class Summary

Emollient stool softeners are used for prophylaxis against constipation in acute and subacute settings.

Docusate (Colace, Correctol, Docu-Soft, Dok)

Docusate is indicated for patients who should avoid straining during defecation. It allows incorporation of water and fat into stools, causing stools to soften. Tachyphylaxis develops with long-term use. Docusate is effective acutely. It does not induce defecation.

Class Summary

Emollient stool softeners cause stool to soften; stimulants increase peristaltic activity in the gastrointestinal (GI) system.

Senna concentrate/docusate (Peri-Colace, Dok Plus, Senokot-S)

Docusate sodium allows incorporation of water and fat into stool, causing stool to soften. Sennosides induce defecation by acting directly on the intestinal mucosa or nerve plexus, which stimulates peristaltic activity, increasing intestinal motility. The combination usually produces action 8-12 hours after administration.

Class Summary

Saline laxatives are used for acute treatment of constipation in the absence of bowel obstruction.

Magnesium hydroxide (Phillips Milk of Magnesia, Fleet Pedia-Lax Chewable)

Magnesium hydroxide causes osmotic retention of fluid, which distends the colon and increases peristaltic activity; it also promotes emptying of the bowel.

Magnesium citrate (Citroma)

Magnesium citrate causes osmotic retention of fluid, distending the colon and increasing peristaltic activity; it promotes emptying of the bowel. The drug works within 3 hours given orally (PO) or 15 minutes given rectally (PR). It may cause electrolyte imbalance, especially in young children or patients with renal insufficiency.

Magnesium sulfate

Magnesium sulfate causes osmotic retention of fluid, which distends the colon and increases peristaltic activity; it promotes emptying of the bowel.

Class Summary

Lubricant laxatives are used for acute or subacute management of constipation. They lubricate the intestine and facilitate passage of stool by decreasing water absorption from the intestine.

Mineral oil (Fleet, Kondremul)

Mineral oil is more gentle than some other rapidly acting laxatives. It generally works within 8 hours. Long-term use is accompanied by concerns about lipid pneumonia, lymphoid hyperplasia, and foreign body reactions.

Lubiprostone (Amitiza)

Lubiprostone is a locally acting chloride channel activator that enhances a chloride-rich intestinal fluid secretion without altering sodium and potassium concentrations in the serum. It specifically activates C1C-2, an apical membrane in the human intestine. It increases intestinal fluid secretion to assist in GI motility, thereby decreasing symptoms of chronic idiopathic constipation (eg, abdominal pain, bloating, straining, and hard stools).

Class Summary

Osmotic agents are useful for long-term treatment of constipated patients with slow colonic transit who are refractory to dietary fiber supplementation.

Lactulose (Constulose, Enulose, Generlac, Kristalose)

Lactulose produces an osmotic effect in the colon, resulting in bowel distention and stimulation of peristalsis.

Sorbitol

Sorbitol is a hyperosmotic laxative that has a cathartic action in the GI tract.

Polyethylene glycol solution (Miralax)

Polyethylene glycol solution (Miralax)

Polyethylene glycol is typically used in large volumes for bowel preparation and washout before surgical or endoscopic procedures. It is now being used in smaller volumes as an osmotic (but not hyperosmotic) agent.

In theory, there is a lower risk of dehydration or electrolyte imbalance with isotonic polyethylene glycol than with hypertonic sugar solutions. The laxative effect is generated because polyethylene glycol is not absorbed and continues to hold water by osmotic action through the small bowel and the colon, resulting in mechanical cleansing.

Class Summary

Stimulant laxatives are commonly employed to treat acute constipation and are the most common class of laxatives used over the long term by individuals taking over-the-counter products. The latter represents an inappropriate choice, at least as first- or second-line therapy, given concerns about development of tolerance.

Senna (Senokot, Ex-Lax, Senexon, Senna-Gen)

Sennosides induce defecation by acting directly on the intestinal mucosa or nerve plexus, which stimulates peristaltic activity, increasing intestinal motility. Senna usually produces its action 8-12 hours after administration.

Bisacodyl (Bisac-Evac, Biscolax, Dulcolax, Dacodyl)

Bisacodyl stimulates peristalsis by possibly stimulating the colonic intramural neuronal plexus. It alters water and electrolyte secretion, resulting in net intestinal fluid accumulation and laxation. It provokes defecation within 24 hours and may cause abdominal cramping.

Cascara sagrada

Cascara sagrada irritates the intestinal mucosa, resulting in increased colonic motility and altered fluid and electrolyte secretion.

Castor oil

Castor oil is reduced to ricinoleic acid. It decreases net absorption of fluid and electrolytes and stimulates peristalsis. It acts on the small intestine.

Class Summary

Prokinetics are promotility agents proposed for use with severe constipation-predominant symptoms.^[26]

Tegaserod (Zelnorm)

Tegaserod is available in the United States on a restricted treatment investigational new drug (IND) protocol for irritable bowel syndrome (IBS) with constipation (IBS-C) or chronic idiopathic constipation (CIC) in women younger than 55 years who meet specific guidelines. It is indicated for treatment of chronic idiopathic constipation. It is also indicated for short-term treatment of women with IBS in whom constipation is the predominant symptom.

Tegaserod is a serotonin type 4 (5-HT4) receptor partial agonist with no affinity for 5-HT3 receptors. It may trigger peristaltic reflex via 5-HT4 activation, which enhances basal motor activity and normalizes impaired GI motility. Research studies have shown inhibitory activity of the drug on visceral activity in the GI tract.

Class Summary

Peripherally selective opioid antagonists are now available. Methylnaltrexone is indicated for treating constipation in patients who have advanced illness requiring long-term opioid analgesia and who are unresponsive to laxatives. Alvimopan is indicated to prevent postoperative ileus after bowel resection.

Methylnaltrexone (Relistor)

Methylnaltrexone is a peripherally acting mu-opioid receptor antagonist. It selectively displaces opioids from mu-opioid receptors outside the central nervous system (CNS), including those located in the GI tract, thereby decreasing constipating effects. It is indicated for opioid-induced constipation in patients with advanced illness receiving palliative care, when response to laxatives has not been sufficient. It is available as a 12 mg/0.6 mL injectable solution for subcutaneous use.

Alvimopan (Entereg)

Alvimopan is a peripherally acting mu-opioid receptor antagonist. It binds mu-opioid receptors in the gut, thereby selectively inhibiting negative opioid effects on GI function and motility. It is indicated for postoperative ileus after bowel resection with primary anastomosis.

In 5 clinical studies that enrolled more than 2500 patients, alvimopan demonstrated accelerated recovery time of upper and lower tract GI function compared with placebo. A decrease of hospital days was also observed in the alvimopan group.

Alvimopan is only available to hospitals after they complete a registration process designed to maintain the benefits associated with short-term use and prevent long-term outpatient use (Entereg Access Support and Education [EASE] program).