Meeting the Challenges of Opioid-Induced Constipation in Chronic Pain Management – A Novel Approach

Abstract

Opioid analgesics are the cornerstone of pain management for moderate-to-severe cancer pain and, increasingly, chronic noncancer pain. Despite proven analgesic efficacy, the use of opioids is commonly associated with frequently dose-limiting constipation that seriously impacts on patients’ quality of life. Agents currently used to manage opioid-induced constipation (OIC), such as laxatives, do not address the underlying opioid receptor-mediated cause of constipation and are often ineffective. A significant need therefore exists for more effective treatment options. A novel approach for selectively and locally antagonizing the gastrointestinal effects of opioids involves the coadministration of a μ-opioid receptor antagonist with negligible systemic availability, such as oral naloxone. Combination therapy with prolonged-release (PR) oxycodone plus PR naloxone has been shown to provide effective analgesia while preventing or reducing constipation. The current article highlights this novel strategy in its potential to significantly improve the quality of life of patients suffering from chronic pain, affording patients the benefit of full analgesia, without the burden of OIC.

Prolonged‐release oxycodone/naloxone for chronic pain

“…12 Prior to its hepatic metabolism, however, naloxone acts locally in the gut to block gut opioid receptors. 3 By this mechanism of action, oral naloxone improves OIBD. 17 Therefore oral naloxone administered with oxycodone may allow selective blockade of intestinal opioid receptors without blocking the analgesic effects of oxycodone within the central nervous system.…”

“…The World Health Organization (WHO) recommends opioids for managing moderate-tosevere cancer pain, but the role of opioids in chronic non-cancer pain is less established; they are increasingly being used to treat chronic non-cancer pain. 3 Breivik et al found that only 5% of those taking prescription medications for pain were taking a strong opioid. 2 There may be a need to optimise opioid use for those patients who do not respond to other analgesic regimens including pharmacological and non-drug therapies.…”

“…7 OIBD has a serious impact on patients' daily function and quality of life. 3 It is not a benign complication as it can lead to faecal impaction and bowel perforation. Its treatment increases costs to patients, healthcare providers and society, eg laxative prescriptions, increased use of resources and GP/hospital visits/admission.…”

Are we able to Manage Effectively Opioid-Induced Bowel Dysfunction?

“…The peripheral opioid effect on µ-opioid receptors in the gut wall plays the main role here [3]. High density of µ-opioid receptors was found in neurons of myenteric and submucosal plexus and immune cells in the lamina propria [4].…”

Les récepteurs µ-opioïdes de la veine porte

“…Fait intéressant, les deux organes du corps dans lesquels les récepteurs -opioïdes sont le plus largement exprimés sont le cerveau, en particulier dans les régions impliquées dans le contrôle de la prise alimentaire lié au système de récompense [9], et l'intestin grêle où ils contrôlent la motilité intestinale [10]. De plus, la naloxone (Nalox), un antagoniste des récepteurs -opioïdes, diminue l'apport alimentaire lorsqu'elle est administrée par voie orale chez l'homme [8], alors qu'elle est activement dégradée par le foie [11]. Ceci suggérait que les modulateurs des récepteurs -opioïdes d'origine alimentaire pourraient agir sur un site portal, gastro-intestinal ou mésentérique.…”