Prevention of constipation during treatment with opioids: magnesiumoxide versus macrogol/elektrolytes
Ontology highlight
ABSTRACT:
DISEASE(S): Palliative Care Cancer Patients Starting With Opioids,Constipation
PROVIDER: 2523670 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:RATIONALE: Naloxone may be effective in treating constipation that may be caused by opioid pain medications such as morphine.
PURPOSE: Phase III trial to determine the effectiveness of naloxone in relieving constiption in patients who are receiving opioids for chronic pain.
| 2006458 | ecrin-mdr-crc
Project description:Opioid use is associated with worse outcome in HIV-infected patients. The exacerbated disease progression by opioids is mainly driven by increased epithelial damage and less regenerative response. The present study investigates how opioids potentiate HIV disease progression by impairing intestinal epithelial self-repair. Abnormal intestinal morphology and reduced epithelial proliferation were observed in HIV-infected humanized mice, which were exposed to opioids. For this study, we had 4 groups of BLT humanized mice- (A) Untreated, (B) Morphine treated, (C) HIV infected and (D) HIV infected + Morphine treated. HIV infection was done for 4 weeks and Morphine treatment was done for 7 days. Morphine treatment was done via subcutaneous implantation of slow-release morphine pellet in individual mouse in the appropriate groups. In other groups, a matching Placebo pellet was implanted.
2020-01-11 | E-MTAB-7883 | biostudies-arrayexpress
Project description:More than 70% of patients with cancer in the palliative phase have pain that often requires treatment with opioids (morphine-like agents). Constipation occurs in 59% of patients treated with opioids. Opioid-induced constipation (OIC) has consequences that range from daily discomfort with social insecurity and disability to intestinal obstruction. It leads to limitations in self-management, a reduced quality of life and a risk of the need for more care. In the guideline "Diagnosis and treatment of pain in patients with cancer" it is recommended to start preventively with an osmotic laxative such as macrogol/electrolytes or magnesium hydroxide when starting opioids. Macrogol/electrolytes has been proven to be effective for OIC, but is sometimes perceived by patients as unpleasant due to its taste. Magnesium hydroxide, which is less commonly prescribed for OIC, has a neutral taste. Although it is mentioned in the guideline, it is not studied for the treatment of OIC and also not officially registered for this. To support the advice of the guideline and to prove that a choice is possible, it is important to investigate whether there are differences in effectiveness and/or side effects between macrogol/electrolytes and magnesium hydroxide in the prevention of OIC.
The aim of this study is to compare macrogol/electrolytes with magnesium hydroxide in the prevention of opioid-induced constipation in patients with cancer in the palliative (incurable) phase, who start opioids because of pain. The choice of laxative is determined by drawing lots (randomisation). After two weeks, its effect will be assessed and will be presented as the percentage of patients who have not developed constipation after starting opioids. If the laxative, as assigned by lot, is described as satisfactory by the patient, the patient can continue with the drug that the patient used, after the study through regular prescription.
The investigators will ask the patients in the study about their satisfaction with the laxative used, any side effects and the degree of pain. Furthermore, the appeal to care for possible constipation will be examined. Because the best attainable quality of life in the palliative phase is the objective of all care, the investigators will also measure this perceived quality with a questionnaire in this study. The results of this study will lead to the best achievable prevention of opioid constipation in patients with cancer in the palliative phase.
| 2402873 | ecrin-mdr-crc
Project description:Opioids are powerful analgesics but carry many contingencies that can lead to opioid-use disorder. Significant energy has been invested in understanding the molecular actions of the opioid alkaloids, particularly their relationship with the opioid receptors at the cell surface. However, there is growing awareness of the opioid-receptor-independent and intracellular actions of opioids that may contribute to their overall pharmacology. The investigation of these interactions is stymied by a lack of relevant opioid chemical tools to probe intracellular actions of the opioids. To investigate the intracellular interactions of the opioids, we designed and developed two opioid probes: photo-click morphine (PCM-2) as a photo-affinity probe for morphine and dialkynyl-acetyl morphine (DAAM) as a metabolic acetate reporter for heroin. Application of these probes to SH-SY5Y, HEK293T, and U2OS cells revealed that PCM-2 and DAAM primarily localize to the lysosome by confocal microscopy and chemical proteomics studies. Interaction site identification by mass spectrometry revealed the mitochondria phosphate carrier protein, solute carrier family 25 member 3, SLC25A3, and histone H2B as acetylation targets of DAAM. This study provides the first chemical probes for the study of the intracellular targets of opioid alkaloids.
2024-05-07 | PXD045676 | Pride
Project description:Evaluate the effect of short-term use of precribed opioids on DNA methylation
2020-05-30 | GSE151485 | GEO
Project description:This is a study to compare the efficacy and tolerability of two laxatives for treatment of opioid-induced constipation in adult outpatients with cancer treated at the British Columbia Cancer Pain and Symptom Management/Palliative Care clinics. Each participating patient will be randomly assigned to one of two treatment groups.
| 2094150 | ecrin-mdr-crc
Project description:Abstract Background Chronic constipation is prevalent and involves both colon sensitivity and various changes in intestinal bacteria, particularly mucosa-associated microflora. Here we examined regulatory mechanisms of TRPV4 expression by co-culturing colon epithelial cell lines with intestinal bacteria and their derivatives. We also investigated TRPV4 expression in colon epithelium from patients with constipation. Methods Colon epithelial cell lines were co-cultured with various enterobacteria (bacterial components and supernatant), folate, LPS, or short chain fatty acids (SCFAs). TRPV4 expression levels and promoter DNA methylation were assessed using pyrosequencing, and microarray network analysis. For human samples, correlation coefficients were calculated and multiple regression analyses were used to examine the association between clinical background, rectal TRPV4 expression level and mucosa-associated microbiota. Results Co-culture of CCD841 cells with P. acnes, C. perfringens, or S. aureus transiently decreased TRPV4 expression but did not induce methylation. Co-culture with clinical isolates and standard strains of K. oxytoca, E. faecalis, or E. coli increased TRPV4 expression in CCD841 cells, and TRPV4 and TNF-alpha expression were increased by E. coli culture supernatants but not bacterial components. Although folate, LPS, IL-6, TNF-alpha, or SCFAs alone did not alter TRPV4 expression, TRPV4 expression following exposure to E. coli culture supernatants was inhibited by butyric acid or TNF-alphaR1 inhibitor and increased by p38 inhibitor. Microarray network analysis showed activation of TNF-alpha, cytokines, and NOD signaling. TRPV4 expression was higher in constipated patients from the terminal ileum to the colorectum, and multiple regression analyses showed that low stool frequency, frequency of defecation aids, and duration were associated with TRPV4 expression. Meanwhile, incomplete defecation, time required to defecate, and number of defecation failures per 24 hours were associated with increased E. faecalis frequency. Conclusions Colon epithelium cells had increased TRPV4 expression upon co-culture with K. oxytoca, E. faecalis, or E. coli supernatants, as well as TNFα-stimulated TNFαR1 expression via a pathway other than p38. Butyrate treatment suppressed this increase. Epithelial TRPV4 expression was increased in constipated patients, suggesting that TRPV4 together with increased frequency of E. faecalis may be involved in the pathogenesis of various constipation symptoms.
2022-07-15 | GSE208164 | GEO
Project description:To pinpoint a distinctive gene associated with constipation resulting from C3 deficiency, we conducted microarray hybridization using total RNA extracted from the mid colon of C3 knockout (C3 KO) mice. Identification of causal genes through comparison of gene expression levels in mice induced with C3 deficiency.
2024-04-17 | GSE261184 | GEO
Project description:In order to characterize the changes in global gene expression in the distal colon of constipated SD rats in response to the laxative effects induced by aqueous extract of Liriope platyphylla (AEtLP) including isoflavone, saponin, oligosaccharide, succinic acid and hydroxyproline, total RNA extracted from the distal colon of AEtLP-treated constipation rats was hybridized to oligonucleotide microarrays.Overall, 581 genes were up-regulated and 216 genes were down-regulated by constipation induced by loperamide, while 67 genes were up-regulated and 421 genes were down-regulated by AEtLP treatment in constipated rats compared to controls. Among the transcripts up-regulated by constipation, 89 were significantly down-regulated and 20 were recovered to normal levels by AEtLP treatment. The major genes in the down-regulated categories included Slc9a5, klk10, Fgf15 and Alpi, while the major genes in the recovered categories were Cyp2b2, Ace, G6pc and Setbp1. However, nine of these genes that were down-regulated by constipation were significantly up-regulated and four were recovered to normal levels by AEtLP treatment. The major genes in the up-regulated categories included Serpina3n, Lcn2 and Slc5a81, while the major genes in the recovered categories were Tmem45a, Rerg and Rgc32. Constipation was induced in SD rats by subcutaneous injection of loperamide for 3 days. At 15 hr after the final treatment of loperamide, each animal were received a consistent volume of water or 15 uL/g body weight of AEtLP (1,000 mg/kg weight) via oral administration for once at 9 AM.
2014-10-04 | E-GEOD-62041 | biostudies-arrayexpress
Project description:In order to characterize the changes in global gene expression in the distal colon of constipated SD rats in response to the laxative effects induced by aqueous extract of Liriope platyphylla (AEtLP) including isoflavone, saponin, oligosaccharide, succinic acid and hydroxyproline, total RNA extracted from the distal colon of AEtLP-treated constipation rats was hybridized to oligonucleotide microarrays.Overall, 581 genes were up-regulated and 216 genes were down-regulated by constipation induced by loperamide, while 67 genes were up-regulated and 421 genes were down-regulated by AEtLP treatment in constipated rats compared to controls. Among the transcripts up-regulated by constipation, 89 were significantly down-regulated and 20 were recovered to normal levels by AEtLP treatment. The major genes in the down-regulated categories included Slc9a5, klk10, Fgf15 and Alpi, while the major genes in the recovered categories were Cyp2b2, Ace, G6pc and Setbp1. However, nine of these genes that were down-regulated by constipation were significantly up-regulated and four were recovered to normal levels by AEtLP treatment. The major genes in the up-regulated categories included Serpina3n, Lcn2 and Slc5a81, while the major genes in the recovered categories were Tmem45a, Rerg and Rgc32.
2014-10-04 | GSE62041 | GEO