Opioids and Constipation

Up to 100 million American adults have chronic pain.¹ Once patients need specialized pain care, approximately 90% of them will receive opioids.² Opioid use is widespread: in 2010, US physicians prescribed enough opioid analgesics to medicate every American adult around-the-clock for 1 month.³ The large quantities of prescribed opioids in circulation have attracted national attention, incited regulatory concern, and created widespread potential for opioid-induced constipation (OIC).²

When patients develop severe cancer-related, noncancer, and end-of-life pain, opioids are the most effective treatment; however, they have several adverse effects.^4,5 OIC is predictable: up to 90% of opioid-treated patients in clinical trials experience constipation, and real-world studies report constipation rates of 40% to 62%.⁶ OIC is manageable, but prescribing clinicians often fail to anticipate, identify, or treat it.^7-14 In addition, OIC pain may rival that caused by the conditions for which opioids are prescribed.¹⁵

OIC: A DIFFERENT CONSTIPATION

Many clinicians are surprised to learn that OIC is physiologically different than functional constipation. Regular constipation usually occurs subsequent to poor dietary choices, inactivity, or dehydration. OIC follows interrupted receptor activity. The gastrointestinal tract’s enteric neurons synthesize and release many neurotransmitters, including endogenous opioids. Endogenous opioids bind to 3 opioid receptors—mu, kappa, and, to a lesser extent, delta—to provide analgesia and control bowel function.^16,17 Endogenous opioids slow the overactive gut to maintain homeostatic gut function. However, they have shorter half-lives than exogenous opioids: all endogenous opioids (except endorphin) are rapidly metabolized after performing their intended functions.

OIC develops when long-lived exogenous opioids create several changes—slower motility, altered fluid balance, sluggish mental status (leading to hampered mobility), and increased luminal fluid absorption¹⁸—when opioid agonists bind to mu-opioid receptors in the enteric nervous system.^16,17 OIC creates needless suffering (Figure^19-22).

ADDRESS OIC IMMEDIATELY

Clinicians should address potential constipation in all patients who start long-term opioids. Unfortunately, clinicians often fail to address constipation. Consider this: of 489 patients treated with opioid analgesics in 2015, 27% reported no laxative use, 25% had insufficient laxative use, and 48% had sufficient laxative use. During follow-up, 21% to 28% of patients used no or insufficient laxatives.⁶

Data from a recent study show that patients and their health care providers have different interpretations of the impact of OIC, the effectiveness of laxative treatment, and the impact of OIC on pain control. This study looked at patients treated with a daily morphine-equivalent dose of 30 mg for 4 weeks or longer. At baseline, 25% of health care providers were unaware of their patients’ laxative treatment status, and only 55% of patient—health care provider pairs reported the same plan for laxative use. Twenty-four weeks later, the majority of patients were dissatisfied with their OIC care, but their health care providers believed their patients were “moderately satisfied.” These discordant perceptions complicated pain management and demonstrated a need for greater communication.²³

The economics of untreated OIC in the United States are noteworthy. Patients with noncancer pain who develop OIC have significantly higher (more than double) total health care costs than patients who do not develop OIC, regardless of age or residing in a community or a long-term care facility.²⁴

TREATMENT OPTIONS FOR OIC

Prescribers and pharmacists should advise patients to maintain adequate hydration and, if possible, increase their physical activity. Increasing dietary fiber may help some patients, but it is not appropriate for all. Patients who are debilitated, have a suspected bowel obstruction, or cannot hydrate adequately should not fiber-load. Most patients should also be treated prophylactically with a stool softener and a laxative.

Among the traditional laxatives, no one agent is more effective than another. Patients may need to try different laxative classes, use more than 1 laxative type, or adjust their dosing schedule to reach the desired effect. When traditional laxatives are inadequate, clinicians should consider adding an agent specifically indicated for treating OIC²⁵ (Table^26-28).

Pharmacists need to advise patients to use prophylactic and intensive bowel management regimens, and pharmacy staff should be vigilant in identifying patients who need counseling. Coordinating care among health care professionals proactively manages the burden of OIC in patients with chronic pain.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy.

References

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