Opioid-Induced Bowel Dysfunction

Abstract

Opioids are the most commonly prescribed medications to treat severe pain in the Western world. It has been estimated that up to 90% of American patients presenting to specialized pain centres are treated with opioids. Along with their analgesic properties, opioids have the potential to produce substantial side effects, such as nausea, cognitive impairment, addiction and urinary retention. In the gut, opioids exert their action on the enteric nervous system, where they bind to the myenteric and submucosal plexuses, causing dysmotility, decreased fluid secretion and sphincter dysfunction, which all leads to opioid-induced bowel dysfunction (OIBD). In the clinic, this is reported as nausea, vomiting, gastro-oesophageal reflux-related symptoms, constipation, etc. One of the most severe symptoms is constipation, which can be assessed using different scales for subjective assessment. Objective methods such as radiography and colonic transit time can also be used, together with manometry and evaluation of anorectal function to explore the pathophysiology. Dose-limiting adverse symptoms of OIBD can lead to insufficient pain treatment. Even though several treatment strategies are available, the side effects are still a major challenge. Traditional laxatives are normally prescribed but they are often insufficient to alleviate symptoms, especially those from the upper gastrointestinal tract. Newer prokinetics, such as prucalopride and lubiprostone, may be more effective in alleviating OIBD. Another treatment approach is co-administration of opioid antagonists, which either cannot cross the blood-brain barrier or selectively target opioid receptors in the gastrointestinal tract. However, although these new agents have proved to be more efficacious than placebo, clinical trials still need to prove their superiority to standard co-prescribed laxative regimes.

Opioid-induced constipation: Pathophysiology, treatment and management

“…Opioid receptors are an inhibitory group of G-protein-coupled receptors (GPCR) with opioids as ligands that sense molecules outside the cell, activating signal transduction pathways inside the cell which produce cellular responses , Holzer, 2009and Brock et al, 2012. Both the sympathetic and parasympathetic nervous systems are regulated by GPRC pathways.…”

“…Endogenous opioids are dynorhins, enkephalins, endorphins, endomorphins and nociception. In the intestine, met-enkephalin, leu-enkephalin, β-endorphin and dynorphin occur in both neurons and endocrine cells Brock et al, 2012).…”

“…However they also bind to these receptors peripherally in areas such as the gastrointestinal (GI) tract , Holzer, 2009and Brock et al, 2012. The GI tract is densely packed with mu-opioid receptors.…”

“…When released, opioid peptides activate the opioid receptors on the enteric system that controls motility and secretion. OIC is therefore caused by mu-opioid receptor agonists binding to mu-receptors in the myenteric and submucosal plexus (Brock et al, 2012 andSharma andJamal, 2013) tissues within the GI tract, this leads to inhibition of the propulsive activity of the intestine and slower gut transit time. Additionally centrally acting opioids may reduce intestinal peristalsis.…”

“… Reduced gastric emptying  Reduced propulsion of chime through the intestine. , Holzer, 2009, Brock et al, 2012and and Sharma and Jamal, 2013 Assessment Many patients with constipation will not inform clinicians of their symptoms (Prichard., Norton and Bharucha, 2016). Therefore healthcare practitioners need to pro-actively ask patients receiving opioid medications at each opportunity if they are experiencing any symptoms.…”