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New developments in the treatment of opioid-induced gastrointestinal symptoms.

ABSTRACT: Chronic pain affects a large part of the global population, leading to an increase of opioid use. Opioid-induced constipation (OIC), a highly prevalent adverse effect of opioid use, has a major impact on patients' quality of life. Thanks to the introduction of new drugs for chronic constipation, which can also be used in OIC, and the development of peripherally acting mu-opioid receptor blockers, specifically for use in OIC, therapeutic options have seen major development. This review summarises current and emerging treatment options for OIC based on an extensive bibliographical search. Efficacy data for laxatives, lubiprostone, prucalopride, linaclotide, oxycodone/naloxone combinations, methylnaltrexone, alvimopan, naloxegol, naldemedine, axelopran, and bevenopran in OIC are summarised.

SUBMITTER: Pannemans J

PROVIDER: S-EPMC6169055 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

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New developments in the treatment of opioid-induced gastrointestinal symptoms.

Pannemans Jasper J Vanuytsel Tim T Tack Jan J

United European gastroenterology journal 20180827 8

Chronic pain affects a large part of the global population, leading to an increase of opioid use. Opioid-induced constipation (OIC), a highly prevalent adverse effect of opioid use, has a major impact on patients' quality of life. Thanks to the introduction of new drugs for chronic constipation, which can also be used in OIC, and the development of peripherally acting mu-opioid receptor blockers, specifically for use in OIC, therapeutic options have seen major development. This review summarises ...[more]

PMID: 30288274

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Project description:PURPOSE:Constipation can be a significant problem in critically unwell patients, associated with detrimental outcomes. Opioids are thought to contribute to the mechanism of bowel dysfunction. We tested if methylnaltrexone, a pure peripheral mu-opioid receptor antagonist, could reverse opioid-induced constipation. METHODS:The MOTION trial is a multi-centre, double blind, randomised placebo-controlled trial to investigate whether methylnaltrexone alleviates opioid-induced constipation (OIC) in critical care patients. Eligibility criteria included adult ICU patients who were mechanically ventilated, receiving opioids and were constipated (had not opened bowels for a minimum 48 h) despite prior administration of regular laxatives as per local bowel management protocol. The primary outcome was time to significant rescue-free laxation. Secondary outcomes included gastric residual volume, tolerance of enteral feeds, requirement for rescue laxatives, requirement for prokinetics, average number of bowel movements per day, escalation of opioid dose due to antagonism/reversal of analgesia, incidence of ventilator-associated pneumonia, incidence of diarrhoea and Clostridium difficile infection and finally 28 day, ICU and hospital mortality. RESULTS:A total of 84 patients were enrolled and randomized (41 to methylnaltrexone and 43 to placebo). The baseline demographic characteristics of the two groups were generally well balanced. There was no significant difference in time to rescue-free laxation between the groups (Hazard ratio 1.42, 95% CI 0.82-2.46, p?=?0.22). There were no significant differences in the majority of secondary outcomes, particularly days 1-3. However, during days 4-28, there were fewer median number of bowel movements per day in the methylnaltrexone group, (p?=?0.01) and a greater incidence of diarrhoea in the placebo group (p?=?0.02). There was a marked difference in mortality between the groups, with ten deaths in the methylnaltrexone group and two in the placebo group during days 4-28 (p?=?0.007). CONCLUSION:We found no evidence to support the addition of methylnaltrexone to regular laxatives for the treatment of opioid-induced constipation in critically ill patients; however, the confidence interval was wide and a clinically important difference cannot be excluded.

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New developments in the treatment of opioid-induced gastrointestinal symptoms.

Publications

New developments in the treatment of opioid-induced gastrointestinal symptoms.

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