Chronic opioid induced constipation in patients with nonmalignant pain: challenges and opportunities

Abstract

With the recent introduction and approval of medications directed at the treatment of opioid induced constipation (OIC) in patients with nonmalignant pain, there is increased interest and understanding of the unmet need and opportunities to enhance patient management. The high incidence of OIC is associated with rapid increase of narcotic analgesic prescriptions for nonmalignant chronic pain. This review addresses briefly the mechanisms of action of opioids that lead to OIC, the differential tolerance of gastrointestinal organs to the effects of opioids, the size and scope of the problem, the definition and outcome measures for OIC, current differential diagnosis and management algorithms, and the pharmacology and efficacy of treatments for OIC in patients with nonmalignant pain.

Keywords: constipation; opioids; pain.

Conflict of interest statement

Conflict of interest statement: M.C. has performed consulting with AstraZeneca regarding naloxegol for the treatment of opioid induced constipation. A.D. declares no conflicts of interest in preparing this article.

Figures

Figure 1.

Rates of opioid sales and opioid substance abuse treatment admissions in the United States, 1999–2010. Reproduced from ‘Addressing Prescription Drug Abuse in the United States: Current Activities and Future Opportunities’, http://www.cdc.gov/HomeandRecreationalSafety/pdf/HHS_Prescription_Drug_Abuse_Report_09.2013.pdf.

Figure 2.

Intracellular signaling following activation of opioid receptors involves G proteins which result in activation of K+ channels, inhibition of Ca++ channels, and inhibition of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA). The results are generally membrane hyperpolarization or neurotransmitter release. Reproduced with permission from Galligan and Akbarali [2014].