Opioid misuse in gastroenterology and non-opioid management of abdominal pain

Szigethy, Eva; Knisely, Mitchell R.; Drossman, Douglas A.

doi:10.1038/nrgastro.2017.141

Cited by 90 publications

(66 citation statements)

References 194 publications

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“… 123 Worsening symptoms of abdominal pain with opioid use may be multifactorial and due to narcotic bowel syndrome, opioid-induced constipation, worsening psychopathology, and addiction. 124 In addition, opioids can further delay GE in patients with GP and lead to worsening symptoms. 119 , 121 , 125 …”

Section: Qol and Biopsychosocial Factors In Dmgpmentioning

confidence: 99%

Diabetic gastroparesis: current challenges and future prospects

Avalos¹,

Sarosiek²,

Loganathan³

et al. 2018

CEG

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Diabetic gastroparesis (DMGP) is a condition of delayed gastric emptying after gastric outlet obstruction has been excluded. Symptoms of nausea, vomiting, early satiety, bloating, and abdominal pain are associated with DMGP. Uncontrolled symptoms can lead to overall poor quality of life and financial burdens on the healthcare system. A combination of antiemetics and prokinetics is used in symptom control; metoclopramide is the main prokinetic available for clinical use and is the only U.S. Food and Drug Administration-approved agent in the United States. However, a black box warning in 2009 reporting its association with tardive dyskinesia and recommending caution in chronically using this agent beyond 3 months has decreased its role in clinical practice. There is an unmet need for new prokinetics with good efficacy and safety profiles. Currently, there are several new drugs with different mechanisms of action in the pipeline that are under investigation and show promising preliminary results. Surgically combining gastric electrical stimulation with pyloroplasty is considered “gold” standard. Advances in therapeutic endoscopic intervention with gastric per-oral endoscopic pyloromyotomy have also been shown to improve gastric emptying and gastroparesis (GP) symptoms. In this review, we will comment on the challenges encountered when managing patients with DMGP and provide an update on advances in drug development and endoscopic and surgical interventions.

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Section: Qol and Biopsychosocial Factors In Dmgpmentioning

confidence: 99%

Diabetic gastroparesis: current challenges and future prospects

Avalos¹,

Sarosiek²,

Loganathan³

et al. 2018

CEG

View full text Add to dashboard Cite

show abstract

“…Such patients may present repeatedly to secondary and tertiary services, with significant psychological co‐morbidity, multiple repeated negative investigations and heavy socioeconomic costs including healthcare utilisation and the burden of loss of working days due to illness . These patients may be subjected to futile or counter‐productive treatments including opioid analgesia . Indeed, the detrimental effects of opioids in this setting are increasingly being recognised and include nausea, vomiting, constipation and the development of opioid‐induced hyperalgesia …”

Section: Introductionmentioning

confidence: 99%

Chronic continuous abdominal pain: evaluation of diagnostic features, iatrogenesis and drug treatments in a cohort of 103 patients

Kilgallon

Vasant

Green

et al. 2019

Aliment Pharmacol Ther

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Summary Background Chronic continuous abdominal pain (CCAP) is characteristic of centrally mediated gastrointestinal pain disorders. It consumes significant healthcare resources yet is poorly understood, with minimal cohort‐specific data in the literature. Aims To examine in a large cohort of CCAP patients, (a) diagnostic features, (b) iatrogenic impact of opioids and surgery, (c) drug treatment effects and tolerance. Methods Consecutive tertiary CCAP referrals to a neurogastroenterology clinic (2009‐2016) were reviewed for Rome IV and neuropathic pain criteria. Medical, surgical and drug histories, interventions and outcomes were correlated with clinical diagnosis and associated opioid use. Results Of 103 CCAP patients (mean age 40 ± 14, 85% female), 50% had physiological exacerbations precluding full Rome IV Centrally Mediated Abdominal Pain Syndrome criteria. However, there were no significant differences between patients who satisfied Rome IV criteria and those who did not. Overall, 81% had allodynia (a nonpainful stimulus evoking pain sensation). Opioid use was associated with allodynia (P = 0.003). Prior surgery was associated with further operations post CCAP onset (P < 0.001). Although 68% had undergone surgical interventions, surgery did not resolve pain in any patient and worsened pain in 35%. Whilst duloxetine was the most effective neuromodulator (P = 0.003), combination therapy was superior to monotherapy (P = 0.007). Conclusions This is currently the largest cohort CCAP dataset that supports eliciting neuropathic features, including allodynia, for a positive clinical diagnosis, to guide treatment. Physiological exacerbation of CCAP may represent visceral allodynia, and need not preclude central origin. Use of centrally acting neuromodulators, and avoidance of detrimental opioids and surgical interventions appear to predict favourable outcomes.

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“…Development of analgesic tolerance pose challenges for compliance and is particularly problematic in long-term chronic pain users ( Benyamin et al, 2008 ; Severino et al, 2018 ). Opioid-induced constipation is one of the most common and most bothersome side effect of opioid analgesics, and can significantly impact the quality of life ( Szigethy et al, 2018 ). The incidence of constipation is reported in 40–95% of opioid treated patients ( Imam et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo Pharmacological Activities of 14-O-Phenylpropyloxymorphone, a Potent Mixed Mu/Delta/Kappa-Opioid Receptor Agonist With Reduced Constipation in Mice

et al. 2018

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Pain, particularly chronic pain, is still an unsolved medical condition. Central goals in pain control are to provide analgesia of adequate efficacy and to reduce complications associated with the currently available drugs. Opioids are the mainstay for the treatment of moderate to severe pain. However, opioid pain medications also cause detrimental side effects, thus highlighting the need of innovative and safer analgesics. Opioids mediate their actions via the activation of opioid receptors, with the mu-opioid receptor as the primary target for analgesia, but also for side effects. One long-standing focus of drug discovery is the pursuit for new opioids exhibiting a favorable dissociation between analgesia and adverse effects. In this study, we describe the in vitro and in vivo pharmacological profiles of the 14-O-phenylpropyl substituted analog of the mu-opioid agonist 14-O-methyloxymorphone (14-OMO). The consequence of the substitution of the 14-O-methyl in 14-OMO with a 14-O-phenylpropyl group on in vitro binding and functional activity, and in vivo behavioral properties (nociception and gastrointestinal motility) was investigated. In binding studies, 14-O-phenylpropyloxymorphone (POMO) displayed very high affinity at mu-, delta-, and kappa-opioid receptors (Ki values in nM, mu:delta:kappa = 0.073:0.13:0.30) in rodent brain membranes, with complete loss of mu-receptor selectivity compared to 14-OMO. In guinea-pig ileum and mouse vas deferens bioassays, POMO was a highly efficacious and full agonist, being more potent than 14-OMO. In the [35S]GTPγS binding assays with membranes from CHO cells expressing human opioid receptors, POMO was a potent mu/delta-receptor full agonist and a kappa-receptor partial agonist. In vivo, POMO was highly effective in acute thermal nociception (hot-plate test, AD50 = 0.7 nmol/kg) in mice after subcutaneous administration, with over 70- and 9000-fold increased potency than 14-OMO and morphine, respectively. POMO-induced antinociception is mediated through the activation of the mu-opioid receptor, and it does not involve delta- and kappa-opioid receptors. In the charcoal test, POMO produced fourfold less inhibition of the gastrointestinal transit than 14-OMO and morphine. In summary, POMO emerges as a new potent mixed mu/delta/kappa-opioid receptor agonist with reduced liability to cause constipation at antinociceptive doses.

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Opioid misuse in gastroenterology and non-opioid management of abdominal pain

Cited by 90 publications

References 194 publications

Diabetic gastroparesis: current challenges and future prospects

Diabetic gastroparesis: current challenges and future prospects

Chronic continuous abdominal pain: evaluation of diagnostic features, iatrogenesis and drug treatments in a cohort of 103 patients

In vitro and in vivo Pharmacological Activities of 14-O-Phenylpropyloxymorphone, a Potent Mixed Mu/Delta/Kappa-Opioid Receptor Agonist With Reduced Constipation in Mice

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