Most prescribed
opioids exert their
analgesic effects via activation of central μ-
opioid receptors. However, μ-
opioid receptors are also located in the gastrointestinal (GI) tract, and activation of these receptors by
opioids can lead to GI-related adverse effects, in particular
opioid-induced constipation (OIC). OIC has been associated with increased use of healthcare resources, increased healthcare costs, and decreased quality of life for patients. Nonpharmacologic (e.g., increased fiber uptake) and pharmacologic agents (e.g., laxatives) may be considered for the treatment and prevention of OIC. However, many interventions, such as laxatives alone, are generally insufficient to reverse OIC because they do not target the underlying cause of OIC,
opioid activation of μ-
opioid receptors in the GI tract. Therefore, there has been keen interest in antagonism of the μ-
opioid receptor in the periphery to inhibit the effects of
opioids in the GI tract. In this review, currently available pharmacologic
therapies for the treatment and prevention of OIC are summarized briefly, with a primary focus on the administration of the peripheral μ-
opioid receptor antagonist methylnaltrexone bromide in patients with OIC and advanced illness who are receiving
palliative care. Also, clinical trial data of
methylnaltrexone treatment in patients with OIC and other
pain conditions (i.e., chronic noncancer
pain and
pain after
orthopedic surgery) are reviewed. Data support that
methylnaltrexone is efficacious for the treatment of OIC and has a favorable tolerability profile.