Overview and Treatment of Opioid-Induced Constipation

Abstract

Opioid analgesics have a central place in the management of both chronic and acute moderate-to-severe pain. However, their potential benefits may be compromised by constipation and other related bowel adverse effects mediated by gastrointestinal μ-opioid receptors. These adverse effects occur in up to 90% of patients treated with opioids, and may be sufficiently debilitating to cause patients to discontinue or modify opioid therapy, thereby compromising effective analgesia. Thorough assessment and treatment to prevent or ameliorate opioid-induced constipation (OIC) is therefore an essential component of pain management. Current treatment options include lifestyle and dietary alterations and pharmacologic interventions, such as laxatives. However, laxatives do not affect opioid binding to μ-opioid receptors in the gastrointestinal tract and, hence, treatment of OIC with these agents is often unsatisfactory to patients. Although μ-receptor blockade with naloxone has been shown to relieve OIC, this compound readily crosses the blood-brain barrier and may reduce the analgesic effects of opioids. Unlike naloxone, methylnaltrexone is a peripherally acting μ-receptor antagonist that does not cross the blood-brain barrier. Therefore, it inhibits OIC without negatively affecting opioid-induced analgesia. Clinical trials in opioid-treated patients with constipation have shown that methylnaltrexone produces a bowel movement within 4 hours in approximately 50% to 65% of patients without affecting pain scores or inducing opioid withdrawal symptoms. The most common adverse effects in methylnaltrexone-treated patients were abdominal pain and flatulence, both possibly associated with the experience of having a bowel movement. Other potential treatment options for OIC are in clinical development and include oral peripherally acting μ-opioid receptor antagonists.