Opioid-Induced Constipation

Publication Date: January 1, 2019

Key Points

Key Points

  • Based on a thorough assessment of the current evidence, the American Gastroenterological Association (AGA) strongly recommends traditional laxative therapy as first line agents given established efficacy and benefits of safety and cost.
  • When an adequate trial of laxatives results in suboptimal symptom control, AGA recommends escalation of therapy to peripherally acting µ-opioid receptor antagonists (PAMORA) drugs with high or moderate quality evidence of efficacy, namely naldemedine and naloxegol.
  • AGA also conditionally recommends use of methylnaltrexone for laxative-refractory opioid-induced constipation (OIC).
  • Due to insufficient evidence, AGA did not issue a recommendation regarding use of either lubiprostone or prucalopride in OIC.

Introduction

Three different classes of opioid receptors mediate the gastrointestinal effects of opioid medications: µ (mu), d (delta), and k (kappa). Opioids exert their GI effects via kappa receptors in the stomach and small intestine and mu receptors located in the small intestine and proximal colon. OIC occurs primarily via activation of enteric mu receptors, which results in increased tonic nonpropulsive contractions in the small and large intestine, increased colonic fluid absorption and stool desiccation. Opioids are also thought to increase the minimum sensory threshold of the rectum and increase anal sphincter tone. The sum of these effects results in harder stool and less frequent and less effective defecation. Because OIC results from the specific effects of opioids, it differs mechanistically from other forms of constipation, and therefore, medical management of this disorder deserves dedicated attention.

  • It is estimated that 4–5% of the U.S. population use prescription opioids regularly, and opioid prescribing has increased over the past several decades, particularly for non-cancer pain.
  • The true number of those affected by opioid dependence and opioid-induced side effects is larger due to nonmedical or illicit use, which is also on the rise.
  • Opioid induced bowel dysfunction refers to the set of gastrointestinal adverse effects associated with opioid therapy, including constipation, gastroesophageal reflux disease, nausea and vomiting, bloating, and abdominal pain.
    • Constipation is by far the most common and debilitating gastrointestinal effect of opioids, and some degree of constipation is near universal in patients taking opioid medications.

Table 1. Definitions

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ROME IV

New or worsening symptoms of constipation when initiating, changing, or increasing opioid therapy that must include 2 or more of the following:
  • Straining during more than one-fourth (25%) of defecations
  • Lumpy or hard stools more than one-fourth (25%) of defecations
  • Sensation of incomplete evacuation more than one-fourth (25%) of defecations
  • Sensation of anorectal obstruction/blockage more than one-fourth (25%) of defecations
  • Manual maneuvers to facilitate more than one-fourth (25%) of defecations (e.g., digital evacuation, support of the pelvic floor)
  • Fewer than three spontaneous bowel movements per week

A Consensus Definition

A change when initiating opioid therapy from baseline bowel habits that is characterized by any of the following:
  • Reduced bowel movement frequency
  • Development or worsening of straining to pass bowel movements
  • A sense of incomplete rectal evacuation
  • Harder stool frequency

Treatment

...eatment

...mmary of Recommendations of AGA Clinic...

...itional laxatives...

...OIC, AGA recommends use of laxatives as first-lin...

...pherally-acting µ-opioid receptor antago...

...patients with laxative refractory OI...

...atients with laxative refractory OIC, AGA recommen...

...th laxative refractory OIC, AGA suggests methyln...

...tinal secretagogue...

...OIC, AGA makes no recommendation for the use...

...lective 5-HT agoni...

...nts with OIC, AGA makes no recommendation for the...


...-Opioid Receptor Antagonists for OICHaving troub...


Table 3. Different Classes of Agents...


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...Clinical Decision Support Tool for the Medical...