Opioids and GI Motility—Friend or Foe?

Lee, Allen; Hasler, William L.

doi:10.1007/s11938-016-0112-0

Cited by 24 publications

(23 citation statements)

References 92 publications

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“…Opioids are known to interfere with normal gastrointestinal (GI) motility by delaying transit, resulting in adverse effects such as bowel dysfunction [ 34 ]. These effects are primarily mediated by peripheral μ-opioid receptors, which are widely distributed in the submucosa [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolomics analysis of serum in a rat heroin self-administration model undergoing reinforcement based on 1H-nuclear magnetic resonance spectra

et al. 2018

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BackgroundUnderstanding the process of relapse to abused drugs and ultimately developing treatments that can reduce the incidence of relapse remains the primary goal for the study of substance dependence. Therefore, exploring the metabolite characteristics during the relapse stage is valuable.MethodsA heroin self-administered rat model was employed, and analysis of the 1H-nuclear magnetic resonance-based metabolomics was performed to investigate the characteristic metabolite profile upon reintroduction to the drug after abstinence.ResultsSixteen metabolites in the serum of rats, including phospholipids, intermediates in TCA (Tricarboxylic Acid Cycle) cycle, keto bodies, and precursors for neurotransmitters, underwent a significant change in the reinstatement stage compared with those in the control group. In particular, energy production was greatly disturbed as evidenced by different aspects such as an increase in glucose and decrease in intermediates of glycolysis and the TCA cycle. The finding that the level of 3-hydroxybutyrate and acetoacetate increased significantly suggested that energy production was activated from fatty acids. The concentration of phenylalanine, glutamine, and choline, the precursors of major neurotransmitters, increased during the reinstatement stage which indicated that an alteration in neurotransmitters in the brain might occur along with the disturbance in substrate supply in the circulatory system.ConclusionsHeroin reinforcement resulted in impaired energy production via different pathways, including glycolysis, the TCA cycle, keto body metabolism, etc. A disturbance in the substrate supply in the circulatory system may partly explain heroin toxicity in the central nervous system. These findings provide new insight into the mechanism underlying the relapse to heroin use.Electronic supplementary materialThe online version of this article (10.1186/s12868-018-0404-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Metabolomics analysis of serum in a rat heroin self-administration model undergoing reinforcement based on 1H-nuclear magnetic resonance spectra

et al. 2018

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“…Physiologic effects of opioids on the bowel include the appearance of nonperistaltic contractions and increased absorption of fluids, resulting in harder stools. [ 89 90 91 92 ] Therefore, opioids may help prolong bacterial spore contact with the colonic mucosa and thus promote CD colonization. [ 88 ] Consequently, it is not surprising that opioid use has been associated with 3-fold increase in CDI risk [ 27 ] as well as 2.5 times the odds of severe and CCDI.…”

Section: Discussionmentioning

confidence: 99%

Early results of fecal microbial transplantation protocol implementation at a community-based university hospital

Duarte-Chavez

Wojda

Zanders

et al. 2018

J Global Infect Dis

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Introduction:Clostridium difficile (CD) is a serious and increasingly prevalent healthcare-associated infection. The pathogenesis of CD infection (CDI) involves the acquisition of CD with a concurrent disruption of the native gut flora. Antibiotics are a major risk although other contributing factors have also been identified. Clinical management combines discontinuation of the offending antibiotic, initiation of CD-specific antibiotic therapy, probiotic agent use, fecal microbiota transplantation (FMT), and surgery as the “last resort” option. The aim of this study is to review short-term clinical results following the implementation of FMT protocol (FMTP) at our community-based university hospital.Methods:After obtaining Institutional Review Board and Infection Control Committee approvals, we implemented an institution-wide FMTP for patients diagnosed with CDI. Prospective tracking of all patients receiving FMT between July 1, 2015, and February 1, 2017, was conducted using REDCap™ electronic data capture system. According to the FMTP, indications for FMT included (a) three or more CDI recurrences, (b) two or more hospital admissions with severe CDI, or (c) first episode of complicated CDI (CCDI). Risk factors for initial infection and for treatment failure were assessed. Patients were followed for at least 3 months to monitor for cure/failure, relapse, and side effects. Frozen 250 mL FMT samples were acquired from OpenBiome (Somerville, MA, USA). After 4 h of thawing, the liquid suspension was applied using colonoscopy, beginning with terminal ileum and proceeding distally toward mid-transverse colon. Monitored clinical parameters included disease severity (Hines VA CDI Severity Score or HVCSS), concomitant medications, number of FMT treatments, non-FMT therapies, cure rates, and mortality. Descriptive statistics were utilized to outline the study results.Results:A total of 35 patients (mean age 58.5 years, 69% female) were analyzed, with FMT-attributable primary cure achieved in 30/35 (86%) cases. Within this subgroup, 2/30 (6.7%) patients recurred and were subsequently cured with long-term oral vancomycin. Among five primary FMT failures (14% total sample), 3 (60%) achieved medical cure with long-term oral vancomycin therapy and 2 (40%) required colectomy. For the seven patients who either failed FMT or recurred, long-term vancomycin therapy was curative in all but two cases. For patients with severe CDI (HVCSS ≥3), primary and overall cure rates were 6/10 (60%) and 8/10 (80%), respectively. Patients with CCDI (n = 4) had higher HVCSS (4 vs. 3) and a mortality of 25%. Characteristics of patients who failed initial FMT included older age (70 vs. 57 years), female sex (80% vs. 67%), severe CDI (80% vs. 13%), and active opioid use during the initial infection (60% vs. 37%) and at the time of FMT (60% vs. 27%). The most commonly reported side effect of FMT was loose stools.Conclusions:This pilot study supports the efficacy and safety of FMT administration for CDI in the setting of a community-based university ho...

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“…In the bowel wall, opioids bind to opioid μ-receptors and give abnormal motility, decreased secretion of fluids, and increased sphincter tone. 3,4 This may cause a cluster of gastrointestinal (GI) symptoms referred to as opioid-induced bowel dysfunction, which embraces symptoms like gastroesophageal reflux, abdominal discomfort, vomiting, bloating, borborygmi, and constipation. Opioid-induced constipation (OIC) is the most burdensome and common adverse effect of opioid treatment and affects around 40%-70% of patients taking opioids continuously; symptoms typically manifest as infrequent bowel movements or defecation difficulties.…”

Section: Introductionmentioning

confidence: 99%

Ambulatory assessment of colonic motility using the electromagnetic capsule tracking system: Effect of opioids

Mark

Klinge

Grønlund

et al. 2019

Neurogastroenterology Motil

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Background Opioid treatment often causes debilitating constipation. However, it is not well described how opioids affect colonic motility and whether opioid‐induced constipation is due to either a decrease of powerful peristaltic contractions or “uncoordinated” peristalsis. The present study aims to investigate the effect of oxycodone on parameters of colonic motility and to determine whether motility is normalized by the opioid antagonist naloxegol. Methods In two randomized, double‐blind crossover trials, oxycodone or placebo was administered to 25 healthy males (Trial A), while another 24 healthy males were administered oxycodone with naloxegol or placebo (Trial B). Colonic motility was assessed by tracking the progression of an electromagnetic capsule throughout the large intestine. Segmental colonic transit times and capsule movements were calculated using displacement distance and velocity. Key Results In Trial A, colonic transit time increased during oxycodone treatment compared with placebo (39 vs 18 hours, P < .01). Displacement during long fast antegrade movements was shorter during oxycodone treatment than with placebo (10 vs 20 cm, P = .03). In Trial B, colonic transit time was faster during oxycodone + naloxegol than during oxycodone + placebo (40 vs 55 hours, P = .049), mainly caused by an increase of the percentwise fraction of distance covered by fast movements in the left colon (P = .001). Conclusion & Inferences Oxycodone treatment impaired colonic motility, manifested as increased transit time, specifically decreased long fast antegrade movements, and addition of naloxegol improved motility dynamics. In humans, the increased transit time during opioid treatment is caused by a decrease in long fast movements rather than uncoordinated peristalsis.

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Opioids and GI Motility—Friend or Foe?

Cited by 24 publications

References 92 publications

Metabolomics analysis of serum in a rat heroin self-administration model undergoing reinforcement based on 1H-nuclear magnetic resonance spectra

Metabolomics analysis of serum in a rat heroin self-administration model undergoing reinforcement based on 1H-nuclear magnetic resonance spectra

Early results of fecal microbial transplantation protocol implementation at a community-based university hospital

Ambulatory assessment of colonic motility using the electromagnetic capsule tracking system: Effect of opioids

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