Novel opioid antagonists for opioid-induced bowel dysfunction

Diego, Laura; Atayee, Rabia S.; Helmons, Pieter J.; Hsiao, Grace; Gunten, Charles F. von

doi:10.1517/13543784.2011.592830

Cited by 67 publications

(64 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Full descriptions of these are beyond the scope of this review, and readers are referred to a number of reviews (Cicero, 1980;Reisine and Pasternak, 1996;Pattinson, 2008;Diego et al, 2009Diego et al, , 2011Cox, 2011;Elliott et al, 2011;Wald, 2012). However, it is worthwhile to highlight several aspects of these additional functions.…”

Section: E Other Actionsmentioning

confidence: 99%

Mu Opioids and Their Receptors: Evolution of a Concept

2013

View full text Add to dashboard Cite

Section: E Other Actionsmentioning

confidence: 99%

Mu Opioids and Their Receptors: Evolution of a Concept

2013

View full text Add to dashboard Cite

“…Together, these effects result in the formation of dry, hard stools that are difficult to pass. 2,14 Opioids may also inhibit bowel motility through immunomodulatory effects involving recruitment of leukocytes and production of inhibitory neurotransmitters, such as inducible nitric oxide. 1 In addition to these peripheral effects, opioids may decrease intestinal motility by stimulating central µ-opioid receptors, leading to changes in the autonomic outflow to the gut.…”

Section: Pathophysiology Of Oicmentioning

confidence: 99%

Overview and Treatment of Opioid-Induced Constipation

McCarberg

2013

Postgraduate Medicine

View full text Add to dashboard Cite

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.Constipation and other gastrointestinal (GI) issues (eg, nausea) are common adverse effects of opioid therapy, and the burden of these conditions is likely to increase given the increasing use of opioids in the United States. 2 Opioidinduced constipation (OIC) can be severely debilitating and can substantially impair patient quality of life. 2 Indeed, OIC may be sufficiently severe as to reduce patient adherence to therapy, compromising effective analgesia. Data from the Patient Reports of Opioid-Related Bothersome Effects (PROBE 1) study, an internet-based survey of 322 patients who were using opioids at least twice weekly for long-term or persistent cancer or noncancer pain, reported that 33% of patients had reduced or discontinued opioid treatment because of GI-related adverse effects. Furthermore, 92% of these patients reported that they had experienced more severe pain as a result of limiting opioid use. 7 With the increasing use of opioids for pain management, including for noncancer pain, it is important to understand the impact of these medications on the GI tract, how GIrelated adverse effects can negatively affect patient adherence to treatment and effective anal...

show abstract

“…Two representative polymer conjugated opioid derivatives are shown in Figure 8. These compounds consist of naloxol analogs linked to PEG chains through hydrolytically stable ether linkage [71,72]. In preclinical studies, these pegylated opioid derivatives were found to maintain their centrally mediated analgesia, while antagonizing peripherally mediated constipation.…”

Section: Polymer-opioid Conjugates and Polymeric Opioid Derivativesmentioning

confidence: 99%