Opioid-induced bowel disorders and narcotic bowel syndrome in patients with chronic non-cancer pain

Tuteja, Ashok K.; Biskupiak, Joseph; Stoddard, Gregory J.; Lipman, Arthur G.

doi:10.1111/j.1365-2982.2009.01458.x

Cited by 155 publications

(113 citation statements)

References 31 publications

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“…In the same study gastroesophageal reflux related symptoms were reported by 33% of all patients, nausea by 27% and vomiting by 9%. Furthermore, chronic abdominal pain was reported by 58% [Tuteja et al 2010]. Similar results have been found in a population-based survey along with increased frequency of constipation-related symptoms (including straining, hard stools, bloating and infrequent bowel movements) [Choung et al 2009].…”

Section: Prevalence Of Opioid-induced Bowel Dysfunctionsupporting

confidence: 73%

Evolving paradigms in the treatment of opioid-induced bowel dysfunction

Poulsen

Brock

Olesen

et al. 2015

Therap Adv Gastroenterol

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Abstract:In recent years prescription of opioids has increased significantly. Although effective in pain management, bothersome gastrointestinal adverse effects are experienced by a substantial proportion of opioid-treated patients. This can lead to difficulties with therapy and subsequently inadequate pain relief. Collectively referred to as opioid-induced bowel dysfunction, these adverse effects are the result of binding of exogenous opioids to opioid receptors in the gastrointestinal tract. This leads to disturbance of three important gastrointestinal functions: motility, coordination of sphincter function and secretion. In the clinic this manifests in a wide range of symptoms such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation, although the most known adverse effect is opioid-induced constipation. Traditional treatment with laxatives is often insufficient, but in recent years a number of novel pharmacological approaches have been introduced. In this review the pathophysiology, symptomatology and prevalence of opioid-induced bowel dysfunction is presented along with the benefits and caveats of a suggested consensus definition for opioid-induced constipation. Finally, traditional treatment is appraised and compared with the latest pharmacological developments. In conclusion, opioid antagonists restricted to the periphery show promising results, but use of different definitions and outcome measures complicate comparison. However, an international working group has recently suggested a consensus definition for opioid-induced constipation and relevant outcome measures have also been proposed. If investigators within this field adapt the suggested consensus and include symptoms related to dysfunction of the upper gut, it will ease comparison and be a step forward in future research.

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Section: Prevalence Of Opioid-induced Bowel Dysfunctionsupporting

confidence: 73%

Evolving paradigms in the treatment of opioid-induced bowel dysfunction

Poulsen

Brock

Olesen

et al. 2015

Therap Adv Gastroenterol

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“…Clinical reports suggest that, of the several adverse effects of long-term opiate use, constipation is one of the most debilitating (Grond et al, 1994;Kurz and Sessler, 2003;Droney et al, 2008;Tuteja et al, 2010). Studies in several species, including the mouse and guinea pig, have demonstrated that morphine alters gastrointestinal motility and produces constipation via its effect on -opioid receptors (Roy et al, 1998;Sternini et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Side effects to morphine treatment include nausea and vomiting, abdominal pain, and constipation, which collectively are referred to as "opioid-induced bowel dysfunction." Although tolerance develops toward many of the effects of morphine, including analgesia, constipation remains resistant to tolerance such that in many cases patients choose to limit or discontinue opioid treatment (Moore and McQuay, 2005;Holzer et al, 2009;Tuteja et al, 2010). Consistent with the persistence of morphine-induced constipation in humans, tolerance to morphine-induced retardation of colonic transit does not develop in either moderate (5.5-fold) or high (52-fold) antinociceptive tolerance mice .…”

Section: Introductionmentioning

confidence: 99%

The Role of β-Arrestin2 in the Mechanism of Morphine Tolerance in the Mouse and Guinea Pig Gastrointestinal Tract

Kang¹,

Maguma²,

Smith³

et al. 2011

J Pharmacol Exp Ther

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␤-Arrestin2 has been reported to play an essential role in analgesic tolerance. Analgesic tolerance without concomitant tolerance to constipation is a limiting side effect of chronic morphine treatment. Because tolerance to morphine develops in the mouse ileum but not the colon, we therefore examined whether the role of ␤-arrestin2 in the mechanism of morphine tolerance differs in the ileum and colon. In both guinea pig and mouse, chronic in vitro exposure (2 h, 10 M) to morphine resulted in tolerance development in the isolated ileum but not the colon. The IC 50 values for morphine-induced inhibition of electrical field stimulation contraction of guinea pig longitudinal muscle myenteric plexus shifted rightward in the ileum from 5.7 Ϯ 0.08 (n ϭ 9) to 5.45 Ϯ 0.09 (n ϭ 6) (p Ͻ 0.001) after morphine exposure. A significant shift was not observed in the colon. Similar differential tolerance was seen between the mouse ileum and the colon. However, tolerance developed in the colon from ␤-arrestin2 knockout mice. ␤-Arrestin2 and extracellular signal-regulated kinase 1/2 expression levels were determined further by Western blot analyses in guinea pig longitudinal muscle myenteric plexus. A time-dependent decrease in the expression of ␤-arrestin2 and extracellular signalregulated kinase 1/2 occurred in the ileum but not the colon after 2 h of morphine (10 M) exposure. Naloxone prevented the decrease in ␤-arrestin2. In the isolated ileum from guinea pigs chronically treated in vivo with morphine for 7 days, neither additional tolerance to in vitro exposure of morphine nor a decrease in ␤-arrestin2 occurred. We conclude that a decrease in ␤-arrestin2 is associated with tolerance development to morphine in the gastrointestinal tract.

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“…OIC can occur even at low dosages of opioids [Shook et al 1987] and can occur at any time after initiation of opioid therapy [Choi and Billings, 2002]. Nausea, vomiting and gastroesophageal reflux are the other symptoms associated with OIC [Tuteja et al 2010]. …”

Section: Clinical Presentation Of Oicmentioning

confidence: 99%

Opioid-induced constipation: advances and clinical guidance

Nelson

Camilleri

2016

Therapeutic Advances in Chronic Disease

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Currently opioids are the most frequently used medications for chronic noncancer pain. Opioid-induced constipation is the most common adverse effect associated with prolonged use of opioids, having a major impact on quality of life. There is an increasing need to treat opioid-induced constipation. With the recent approval of medications for the treatment of opioid-induced constipation, there are several therapeutic approaches. This review addresses the clinical presentation and diagnosis of opioid-induced constipation, barriers to its diagnosis, effects of opioids in the gastrointestinal tract, differential tolerance to opiates in different gastrointestinal organs, medications approved and in development for the treatment of opioid-induced constipation, and a proposed clinical management algorithm for treating opioid-induced constipation in patients with noncancer pain.

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Opioid-induced bowel disorders and narcotic bowel syndrome in patients with chronic non-cancer pain

Abstract: Bowel disorders including chronic abdominal pain and NBS are common in patients taking opioids for CNCP. Decreased HRQoL in patients with CNCP is driven by chronic abdominal pain.

Cited by 155 publications

References 31 publications

Evolving paradigms in the treatment of opioid-induced bowel dysfunction

Evolving paradigms in the treatment of opioid-induced bowel dysfunction

The Role of β-Arrestin2 in the Mechanism of Morphine Tolerance in the Mouse and Guinea Pig Gastrointestinal Tract

Opioid-induced constipation: advances and clinical guidance

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