Opioid-induced constipation

Over the past 20 years, the use of opiates and opioids for the management of chronic pain has significantly increased. Approximately 40% to 90% of patients treated with opioids experience gastrointestinal adverse effects, including constipation. Most of the activity that causes these adverse effects occurs through μ receptors located in the gut and central nervous system. Thus, medications for OIC have focused on blocking the μ receptors in the gut.

Methylnaltrexone bromide (12 mg, subcutaneous), a μ-opioid receptor agonist, has been approved by the FDA for OIC in patients who take opioids for non-cancer pain. Researchers are investigating the safety and efficacy of other μ-opioid receptor agonists and lubiprostone for the treatment of OIC.


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Another approach to treating OIC is to combine a strong opioid with an opioid receptor agonist that does not counteract the opioid’s function as a pain reducer. Combination oxycodone/naloxone has been approved by the FDA for this purpose.

A similar treatment is the FDA-approved naloxegol, a derivative of naloxone that only acts on peripheral μ-opioid receptors and does not affect the gut.

Defecation disorders

If a patient responds poorly or does not respond to standard CIC treatment, it is likely that he or she has a defecation disorder. These are often caused by a functional disorder, including dyssynergic defecation or inadequate propulsive forces during defection. In some cases, defecation disorders can result from anatomic causes such as a large rectocele or enterocoele.

Defecation disorders can be diagnosed using a colon transit study with radio-opaque markers or a wireless capsule, which can determine if the patient has slow colonic transit. Patients can also be tested with an anorectal manometry (ARM) with balloon expulsion testing (BET) to determine a functional defecation disorder.

If a patient is diagnosed with a functional defection disorder, biofeedback is the recommended treatment.

American Gastroenterological Association (AGA) constipation treatment algorithm

The AGA’s main recommendations are as follows: “An algorithmic treatment approach is recommended. For clinical assessment of constipation, if feasible, discontinue medications that can cause constipation before further testing (strong recommendation, low-quality evidence). A digital rectal examination including assessment of pelvic floor motion during simulated evacuation should be performed before referral for anorectal manometry (strong recommendation, moderate-quality evidence).”

Table 1. Tests to assess for medical causes of chronic constipation (adapted from AGA Medical Position Statement on Constipation1)

Test When to perform test Recommendation strength Quality of evidence
Complete blood cell count In the absence of other indications Strong Low
Metabolic tests Not recommended for chronic constipation alone Strong Moderate
Colonoscopy Not advised in patients lacking alarm features Strong Moderate
Anorectal manometry and rectal balloon expulsion If patient does not respond to laxatives Strong Moderate
Defecography If results of anorectal manometry and rectal balloon expulsion are inconclusive Strong Low
Colonic transit If anorectal test results do not show a defecatory disorder or if symptoms persist despite treatment of a defecatory disorder Strong Low

After ruling out medications that may be causing constipation and performing clinical tests, the AGA recommends trying to treat the patient’s constipation with therapeutics such as fiber supplements, osmotic laxatives, or stimulant laxatives before anorectal testing.

Patients with normal-transit constipation and slow-transit constipation can be treated with the long-term use of laxatives.

If a patient has a defecatory disorder, the AGA recommends pelvic floor retraining through biofeedback rather than laxatives to treat the disorder.

References

  1. Stern T, Davis AM. Evaluation and Treatment of Patients With Constipation. JAMA. 2016; 315(2):192-193.
  2. Wald A. Constipation: Advances in Diagnosis and Treatment. JAMA. 2016; 315(2):185-191.