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©2013 UpToDate ® Print Email Agents used for chronic opioid-induced constipation Class Mechanism Use Problems Bulk-forming laxatives (cellulose or psyllium seeds) Increases mass and water content of stool Decreases transit time Should always be considered; may be useful in changing character of the effluent from a functioning stoma May worsen flatulence and distention. Should be avoided in patients who are severely debilitated or suspected of early bowel obstruction. Osmotic cathartics (magnesium salts, sodium salts, lactulose, and sorbitol, and polyethylene glycol) Increases water in the bowel Decreases transit time Lactulose/sorbitol attracts water into colon, acidifies contents Polyethylene glycol attracts water into the colon Often used for bowel cleansing before medical procedures Lactulose and sorbitol have a slower onset and are commonly selected for long-term use; dose must be adjusted to effect Polyethylene glycol is not absorbed, has a slower onset, and the powder formulation also is commonly used for long-term therapy; dose must be adjusted to effect Severe diarrhea and dehydration may occur with overuse Rarely, causes serious electrolyte disorders or volume overload Patients with renal insufficiency or cardiac failure must be carefully monitored if sodium or magnesium salts are used Lactulose or sorbitol may increase flatulence. Lactulose should be avoided in patients who are lactose-intolerant. Surfactants (docusate sodium) Facilitates mixture of fat and stool Usually combined with a contact cathartic as a first-line therapy for opioid-induced constipation Minimal risks Contact cathartics diphenylmethane drugs (bisacodyl) Anthraquinone drugs (cascara, senna) Increases peristalsis Reduces absorption of water and electrolytes from intraluminal contents May be used for acute or chronic therapy. Often a first-line approach for long-term management, including prophylaxis when opioid therapy is initiated. Risks associated with short term use are minimal "Laxative bowel", a condition characterized by dependence on laxatives for bowel function has been reported but is presumably rare Allergies to these substances have been reported Prokinetic agents Metoclopramide Promotes transit through gastrointestinal tract Experience is limited and trial should be considered only when constipation has responded poorly to more conventional measures Opioid antagonists Subcutaneous methylnaltrexone Oral naloxone Opioid antagonist

"Laxative bowel", a condition characterized by dependence on laxatives for bowel function has been reported but is presumably rare Allergies to these substances have been reported Prokinetic agents Metoclopramide Promotes transit through gastrointestinal tract Experience is limited and trial should be considered only when constipation has responded poorly to more conventional measures Opioid antagonists Subcutaneous methylnaltrexone Oral naloxone Opioid antagonist Goal is "bowel withdrawal" without concurrent systemic withdrawal Methylnaltrexone is approved for the indication of opioid-induced constipation in refractory cases. Available currently as an injectable, which may be useful when administered as a "rescue," should routine therapies be ineffective, or every few days for long-term treatment of constipation. Does not cause systemic abstinence. Limited evidence supporting efficacy of oral naloxone and some patients will absorb sufficient naloxone to develop uncomfortable signs of abstinence May cause abdominal cramping