RESUMEN
Dietary micronutrients are integral to the development and progression of constipation; however, the specific relationship between dietary copper intake and constipation has not been thoroughly investigated. This study aims to examine the correlation between dietary copper intake and constipation among U.S. adults, thereby offering novel insights and recommendations for the clinical management and prevention of constipation. Bowel health data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2010 were analyzed. Subjects' dietary information was collected through questionnaire records. Multivariate logistic regression analysis, subgroup analysis, and curve fitting analysis were used to assess the correlation between dietary copper intake and chronic constipation. After adjusting for all possible confounders, each unit increase in dietary copper intake (converted to natural logarithms) was associated with a 20% reduction in the prevalence of constipation (OR = 0.80; 95% CI 0.65-0.98; P = 0.037). The interaction P-values for all subgroups were greater than 0.05, indicating that the findings were stable and consistent across subgroups. The present study showed a significant negative association between dietary copper intake and chronic constipation in adults. This finding raises clinical and healthcare professionals' awareness of the impact of dietary trace elements on intestinal health and has important implications for the development of personalized meal plans and rational supplementation of trace copper in patients with constipation.
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Estreñimiento , Cobre , Encuestas Nutricionales , Humanos , Estreñimiento/epidemiología , Estreñimiento/inducido químicamente , Cobre/administración & dosificación , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estados Unidos/epidemiología , Dieta/efectos adversos , Anciano , Prevalencia , Adulto JovenRESUMEN
This study aimed to investigate the ameliorating effects of peach blossom soluble dietary fiber (PBSDF) and polyphenol (PBP) combinations on loperamide (Lop)-induced constipation in mice, together with the possible mechanism of action. The results demonstrated that the combined use of PBSDF and PBP could synergistically accelerate the gastrointestinal transit rate and gastric emptying rate, shorten first red fecal defecation time, accelerate the frequency of defecation, regulate the abnormal secretion of gastrointestinal neurotransmitters and pro-inflammatory cytokines, and down-regulate the expressions of AQP3 and AQP8. Western blotting and RT-qPCR analysis confirmed that PBSDF + PBP up-regulated the protein and mRNA expressions of SCF and C-kit in SCF/C-kit signaling pathway, and down-regulated pro-inflammatory mediator expressions in NF-κB signaling pathway. 16S rRNA sequencing showed that the diversity of gut microbiota and the relative abundance of specific strains, including Akkermansia, Bacteroides, Ruminococcus, Lachnospiraceae_NK4A136_group, and Turicibacter, rehabilitated after PBSDF + PBP intervention. These findings suggested that the combination of a certain dose of PBSDF and PBP had a synergistic effect on attenuating Lop-induced constipation, and the synergistic mechanism in improving constipation might associated with the regulating NF-κB and SCF/C-kit signaling pathway, and modulating the specific gut strains on constipation-related systemic types. The present study provided a novel strategy via dietary fiber and polyphenol interactions for the treatment of constipation.
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Estreñimiento , Fibras de la Dieta , Microbioma Gastrointestinal , Loperamida , FN-kappa B , Polifenoles , Proteínas Proto-Oncogénicas c-kit , Prunus persica , Transducción de Señal , Factor de Células Madre , Animales , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Polifenoles/farmacología , FN-kappa B/metabolismo , Factor de Células Madre/metabolismo , Masculino , Prunus persica/química , Proteínas Proto-Oncogénicas c-kit/metabolismo , Proteínas Proto-Oncogénicas c-kit/genética , Acuaporina 3/metabolismo , Acuaporina 3/genética , Tránsito Gastrointestinal/efectos de los fármacos , Modelos Animales de EnfermedadRESUMEN
PURPOSE: In this study, we aimed to evaluate the safety and effectiveness of naldemedine for treating opioid-induced constipation (OIC) in patients with advanced cancer, who are receiving palliative care, and particularly explored its early effects. METHODS: Palliative care teams and inpatient palliative care units across 14 institutions in Japan were included in this multicenter, prospective, observational study. Patients who were newly prescribed a daily oral dose of 0.2 mg naldemedine were enrolled. The spontaneous bowel movement (SBM) within 24 h after the first dose of naldemedine was considered the primary outcome, whereas, the secondary outcomes included weekly changes in SBM frequency and adverse events. RESULTS: A total of 204 patients were enrolled and 184 completed the 7-day study. The average age of the participants (103 males, 101 females) was 63 ± 14 years. The primary cancer was detected in the lungs (23.5%), gastrointestinal tract (13.7%), and urological organs (9.3%). A considerable proportion of patients (34.8%) had ECOG performance status of 3-4. Most patients were undergoing active cancer treatment, however, 40.7% of the patients were receiving the best supportive care. Within 24 h of the first naldemedine dose, 146 patients (71.6%, 95% CI: 65.4-77.8%) experienced SBMs. The weekly SBM counts increased in 62.7% of the participants. The major adverse events included diarrhea and abdominal pain, detected in 17.6% and 5.4% of the patients, respectively. However, no serious adverse events were observed. CONCLUSION: Conclusively, naldemedine is effective and safe for OIC treatments in real-world palliative care settings. TRIAL REGISTRATION NUMBER: UMIN000031381, registered 20/02/2018.
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Analgésicos Opioides , Naltrexona , Antagonistas de Narcóticos , Neoplasias , Estreñimiento Inducido por Opioides , Cuidados Paliativos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Cuidados Paliativos/métodos , Anciano , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Estreñimiento Inducido por Opioides/tratamiento farmacológico , Naltrexona/análogos & derivados , Naltrexona/uso terapéutico , Naltrexona/administración & dosificación , Naltrexona/efectos adversos , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/uso terapéutico , Antagonistas de Narcóticos/efectos adversos , Japón , Adulto , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico , Anciano de 80 o más Años , Dolor en Cáncer/tratamiento farmacológico , Resultado del TratamientoRESUMEN
INTRODUCTION: Immune-related adverse events (irAE) secondary to immune checkpoint inhibitors (ICI) have gastrointestinal (GI) manifestations, including gastritis, enteritis, and/or colitis. The long-term sequelae of ICI-associated GI toxicities (GI-irAE), particularly the development of disorders of gut-brain interaction, are not well known. We characterized the incidence of persistent GI symptoms after GI-irAE. METHODS: This is a retrospective study of adults with melanoma treated with ICI and diagnosed with GI-irAE at our institution from 2013 to 2021. All patients had endoscopic and histologic evidence of GI-irAE. The primary outcome was incidence of persistent GI symptoms (diarrhea, abdominal pain, bloating, constipation, fecal incontinence, nausea, vomiting) after resolution of GI-irAE. Hazard ratios evaluated the association between parameters and time to persistent GI symptoms. RESULTS: One hundred four patients with melanoma (90% stage IV disease) and GI-irAE met inclusion criteria. Thirty-four percent received anti-cytotoxic T lymphocyte-associated protein-4 therapy, 33% anti-programmed death-1, and 34% dual therapy. Patients were treated for GI-irAE for an average of 9 ± 6 weeks. Twenty-eight (27%) patients developed persistent GI symptoms 1.6 ± 0.8 years after GI-irAE. The most common symptom was constipation (17%), followed by bloating (8%) and diarrhea (5%). Over 453 person-years, the incident rate was 6.2% per 100 person-years. Use of cytotoxic T lymphocyte-associated protein-4 single or dual therapy was associated with a 3.51× risk of persistent GI symptoms (95% confidence interval 1.20-10.23). DISCUSSION: In this cohort of melanoma patients who experienced GI-irAE, 26% developed persistent GI symptoms, most frequently constipation. Future studies should characterize the GI sequelae after GI-irAE, which may shed light on disorders of gut-brain interaction pathogenesis and improve the lives of cancer survivors.
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Enfermedades Gastrointestinales , Inhibidores de Puntos de Control Inmunológico , Melanoma , Humanos , Melanoma/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/epidemiología , Incidencia , Adulto , Diarrea/inducido químicamente , Diarrea/epidemiología , Estreñimiento/inducido químicamente , Estreñimiento/epidemiologíaRESUMEN
Berberine (BBR) is used to treat cancer, inflammatory conditions, and so on. But the side effects of BBR causing constipation should not be ignored. In clinical application, the combination of Amomum villosum Lour. (AVL) and BBR can relieve it. However, the effective ingredients and molecular mechanism of AVL in relieving constipation are not clear. A small intestine propulsion experiment was conducted in constipated mice to screen active ingredients of AVL. We further confirmed the molecular mechanism of action of the active ingredient on BBR-induced constipation. Quercetin (QR) was found to be the effective ingredient of AVL in terms of relieving constipation. QR can efficiently regulate the microbiota in mice suffering from constipation. Moreover, QR significantly raised the levels of substance P and motilin while lowering those of 5-hydroxytryptamine and vasoactive intestinal peptide; furthermore, it also increased the protein expression levels of calmodulin, myosin light-chain kinase, and myosin light chain. The use of QR in combination with BBR has an adverse effect-reducing efficacy. The study provides new ideas and possibilities for the treatment of constipation induced by BBR.
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Berberina , Estreñimiento , Microbioma Gastrointestinal , Quercetina , Animales , Berberina/farmacología , Berberina/uso terapéutico , Quercetina/farmacología , Estreñimiento/tratamiento farmacológico , Estreñimiento/inducido químicamente , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Masculino , Modelos Animales de Enfermedad , Motilina/metabolismoRESUMEN
Constipation is a major gastrointestinal (GI) symptom worldwide, with diverse causes of formation, and requires effective and safe therapeutic measures. In the present study, we used loperamide hydrochloride to establish a constipation model and assessed the effect of Bifidobacterium on constipation and its possible mechanism of relief. The results showed that B. longum S3 exerted a constipation-relieving effect primarily by improving the gut microbiota, enriching genera including Lactobacillus, Alistipes, and Ruminococcaceae UCG-007, and decreasing the bacteria Lachnospiraceae NK4B4 group. These changes may thereby increase acetic acid and stearic acid (C18:0) levels, which significantly increase the expression levels of ZO-1 and MUC-2, repair intestinal barrier damage and reduce inflammation (IL-6). Furthermore, it also inhibited oxidative stress levels (SOD and CAT), decreased the expression of water channel proteins (AQP4 and AQP8), significantly elevated the Gas, 5-HT, PGE2, and Ach levels, and reduced nNOS and VIP levels to improve the intestinal luminal transit time and fecal water content. Collectively, these changes resulted in the alleviation of constipation.
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Ácido Acético , Bifidobacterium longum , Estreñimiento , Microbioma Gastrointestinal , Loperamida , Probióticos , Ácidos Esteáricos , Loperamida/efectos adversos , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico , Estreñimiento/metabolismo , Animales , Ratones , Probióticos/farmacología , Ácidos Esteáricos/metabolismo , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Modelos Animales de Enfermedad , Intestinos/microbiologíaRESUMEN
BACKGROUND: Garlic polysaccharides (GPs) constitute over 75% of the dry weight of garlic. They are characterized by fructan with a 2,1-ß-d-Fruf backbone and 2,6-ß-d-Fruf branches. Studies have suggested a role for GPs in regulating gut microbiota but whether they possess a comprehensive function in maintaining intestinal well-being and can serve as effective prebiotics remains unknown. To explore this, varied doses of GPs (1.25-5.0 g kg-1 body weight) and inulin (as a positive control) were administered to Kunming mice via gavage, and their effects on the intestinal epithelial, chemical, and biological barriers were assessed. A constipation model was also established using loperamide to investigate the potential effects of GPs on the relief of constipation. RESULTS: Administration of GPs significantly upregulated expression of tight-junction proteins and mucins in Kunming mouse small-intestine tissue. Garlic polysaccharides elevated cecal butyric acid content, reduced the abundance of Desulfobacterota, and decreased the ratio of Firmicutes to Bacteroidetes (the F/B ratio). Garlic polysaccharides also promoted the growth of Bacteroides acidifaciens and Clostridium saccharogumia. Tax4Fun functional predictions suggested the potential of GPs to prevent human diseases, reducing the risk of insulin resistance, infectious diseases, and drug resistance. Garlic polysaccharides also exhibited a beneficial effect in alleviating loperamide-induced constipation symptoms by enhancing small intestinal transit, softening stool consistency, accelerating bowel movements, and promoting the release of excitatory neurotransmitters. CONCLUSIONS: These findings highlight the important role of GPs in maintaining gut fitness by enhancing intestinal barrier function and peristalsis. Garlic polysaccharides are promising prebiotics, potentially contributing to overall intestinal well-being and health. © 2024 Society of Chemical Industry.
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Estreñimiento , Fructanos , Ajo , Microbioma Gastrointestinal , Oligosacáridos , Extractos Vegetales , Prebióticos , Animales , Estreñimiento/tratamiento farmacológico , Estreñimiento/inducido químicamente , Ratones , Ajo/química , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/farmacología , Prebióticos/administración & dosificación , Fructanos/química , Oligosacáridos/administración & dosificación , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/genética , Humanos , Mucosa Intestinal/metabolismo , Intestinos/efectos de los fármacos , Intestinos/microbiología , Polisacáridos/farmacología , Polisacáridos/administración & dosificación , Polisacáridos/química , Intestino Delgado/metabolismo , Intestino Delgado/microbiología , Intestino Delgado/efectos de los fármacos , Animales no ConsanguíneosRESUMEN
Probiotics exert beneficial effects by regulating the intestinal microbiota, metabolism, immune function and other ways of their host. Patients with constipation, a common gastrointestinal disorder, experience disturbances in their intestinal microbiota. In the present study, we investigated the effectiveness of two microbial ecological agents (postbiotic extract PE0401 and a combination of postbiotic extract PE0401 and Lacticaseibacillus paracasei CCFM 2711) in regulating the makeup of the intestinal microbiota and alleviating loperamide hydrochloride-induced constipation in mice. We also preliminarily explored the mechanism underlying their effects. Both microbial ecological agents increased the abundance of the beneficial bacteria Lactobacilli and Bifidobacterium after administration and were able to relieve constipation. However, the degree of improvement in constipation symptoms varied depending on the makeup of the supplement. The postbiotic extract PE0401 increased peristalsis time and improved faecal properties throughout the intestinal tract of the host. PE0401 relieved constipation, possibly by modulating the levels of the constipation-related gastrointestinal regulatory transmitters mouse motilin, mouse vasoactive intestinal peptide, and 5-hydoxytryptamine in the intestinal tract of the host and by increasing the levels of the short-chain fatty acids (SCFAs) acetic acid, propionic acid, and isovaleric acid. It also increased the relative abundance of Lactobacillus and Bifidobacterium and reduced that of Faecalibaculum, Mucispirillum, Staphylococcus, and Lachnoclostridium, which are among the beneficial microbiota in the host intestine. Furthermore, PE0401 decreased the levels of constipation-induced host inflammatory factors. Therefore, the two microbial ecological agents can regulate the intestinal microbiota of constipation mice, and PE0401 has a stronger ability to relieve constipation.
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Estreñimiento , Ácidos Grasos Volátiles , Microbioma Gastrointestinal , Loperamida , Probióticos , Animales , Loperamida/efectos adversos , Estreñimiento/tratamiento farmacológico , Estreñimiento/inducido químicamente , Estreñimiento/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Ácidos Grasos Volátiles/metabolismo , Ratones , Probióticos/administración & dosificación , Probióticos/farmacología , Probióticos/uso terapéutico , Masculino , Bifidobacterium , Lacticaseibacillus paracasei , Modelos Animales de Enfermedad , Lactobacillus , Motilina/metabolismo , Heces/microbiología , Heces/química , Péptido Intestinal Vasoactivo/metabolismoRESUMEN
BACKGROUND: Opioid-induced constipation (OIC) is the most prevalent side effect of methadone maintenance therapy (MMT). Naloxone could reduce the OIC. METHOD: Fifty-six MMT cases (< 75 mg/day methadone, > 3 months) were entered randomly into four groups of a trial. They received placebo or naloxone tablets (0.5, 2, or 4 mg/day) once a day for 2 weeks. They continued their conventional laxative. Their constipation and opiate withdrawal (OWS) were evaluated by the Bristol Stool Form Scale (stool consistency and frequency), Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire, Constipation Scoring System (CSS), and the Subjective Opiate Withdrawal Scale (SOWS) before starting treatment and at the end of the first and second weeks. RESULTS: The dose of 4 mg/day naloxone was excluded from the study due to severe OWS. The precipitants of groups had similar ages, methadone dose and duration, laxative use, and constipation scores at the start of the trial. However, 2 mg of naloxone could change the stool consistency (PV = 0.0052) and frequency (P = 0.0133), 0.5 mg/day dose only improved the stool consistency (P = 0.0016). The patients' CSS and PAC-SYM scores were reduced by naloxone after the 1st week of treatment. However, there was no significant difference in the mean score of SOWS at different assessment times and groups. Also, 3 and 4 cases of 0.5 and 2 mg/day groups, respectively, withdrew from the study due to OWS. CONCLUSION: Oral naloxone at doses of 0.5 and 2 mg/day was significantly more effective than placebo on OIC in MMT. However, the dose of 4 mg induced intolerable OWS.
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Metadona , Naloxona , Antagonistas de Narcóticos , Humanos , Naloxona/uso terapéutico , Naloxona/administración & dosificación , Metadona/uso terapéutico , Metadona/administración & dosificación , Metadona/efectos adversos , Método Doble Ciego , Femenino , Adulto , Masculino , Antagonistas de Narcóticos/uso terapéutico , Antagonistas de Narcóticos/administración & dosificación , Administración Oral , Persona de Mediana Edad , Estreñimiento Inducido por Opioides/tratamiento farmacológico , Estreñimiento/tratamiento farmacológico , Estreñimiento/inducido químicamente , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Tratamiento de Sustitución de Opiáceos/métodosRESUMEN
OBJECTIVE: The purpose of this study is to evaluate the safety and efficacy of linaclotide and polyethylene glycol (PEG) electrolyte powder in patients with chronic constipation undergoing colonoscopy preparation. PATIENTS AND METHODS: We included 260 patients with chronic constipation who were scheduled to undergo a colonoscopy. They were equally divided into 4 groups using a random number table: 4L PEG, 3L PEG, 3L PEG+L, and 2L PEG+L. The 4 groups were compared based on their scores on the Boston Bowel Preparation Scale (BBPS) and Ottawa Bowel Preparation Quality Scale (OBPQS), adverse reactions during the bowel preparation procedure, colonoscope insertion time, colonoscope withdrawal time, detection rate of adenomas, and their willingness to repeat bowel preparation. RESULTS: In terms of the score of the right half of the colon, the score of the transverse colon, the total score using BBPS, and the total score using OBPQS, the 3L PEG (polyethylene glycol)+L group was superior to groups 3L PEG and 2L PEG+L ( P <0.05), but comparable to the 4L PEG group ( P >0.05). The incidence rate of vomiting was higher in the 4L PEG group than in the 2L PEG+L group ( P <0.05). There was no statistically significant difference in the insertion time of the colonoscope between the 4 groups. The colonoscope withdrawal time in the 3L PEG+L group was shorter than in groups 4L PEG and 3L PEG ( P <0.05) and comparable to that in the 4L PEG group ( P >0.05). There was no statistically significant difference in the rate of adenoma detection among the 4 groups ( P >0.05). The 4L PEG group was the least willing of the 4 groups to undergo repeated bowel preparation ( P <0.05). CONCLUSION: The 3L PEG+L is optimal among the 4 procedures. It can facilitate high-quality bowel preparation, reduce the incidence of nausea during the bowel preparation procedure, and encourage patients to undertake repeated bowel preparation.
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Catárticos , Estreñimiento , Péptidos , Humanos , Catárticos/efectos adversos , Polvos , Estreñimiento/diagnóstico , Estreñimiento/inducido químicamente , Polietilenglicoles , Colonoscopía/métodos , ElectrólitosRESUMEN
BACKGROUND: Opioids are pain relievers that are often associated with opioid-induced constipation (OIC) that worsens with age. We performed a multicenter, retrospective analysis on the efficacy and safety of naldemedine, an opioid receptor antagonist, in treating OIC in patients with cancer (age >75 years). METHODS: The electronic medical records of cancer patients who received naldemedine at 10 Japanese institutions between 7 June 2017 and August 31, 2019, were retrieved. Patients aged ≥75 years who were treated with naldemedine for the first time and hospitalized for at least 7 days before and after initiating naldemedine therapy were included in this analysis. RESULTS: Sixty patients were observed for at least 7 days before and after starting naldemedine. The response rate was 68.3%, and the frequency of bowel movements increased significantly after naldemedine administration in the overall population ( P â <â 0.0001) and among those who defecated <3 times/week before naldemedine administration ( P â <â 0.0001). Diarrhea was the most frequent adverse event in all grades, observed in 45% of patients, of which 92.6% were Grade 1 or 2. Grade 4 or higher adverse events, including death, were not observed. CONCLUSION: Naldemedine exhibits significant efficacy and safety in OIC treatment in older patients with cancer.
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Naltrexona/análogos & derivados , Neoplasias , Estreñimiento Inducido por Opioides , Humanos , Anciano , Analgésicos Opioides/efectos adversos , Estudios Retrospectivos , Estreñimiento Inducido por Opioides/tratamiento farmacológico , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológicoRESUMEN
BACKGROUND: Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients. METHODS: A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed. RESULTS: Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I2 = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I2 = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I2 = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I2 = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates. CONCLUSIONS: Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.
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Analgésicos Opioides , Laxativos , Antagonistas de Narcóticos , Estreñimiento Inducido por Opioides , Humanos , Estreñimiento Inducido por Opioides/tratamiento farmacológico , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Laxativos/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Dolor en Cáncer/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico , Estreñimiento/prevención & control , Oxicodona/uso terapéutico , Oxicodona/efectos adversosRESUMEN
OBJECTIVES: The goal of this quality improvement project (QIP) was to increase awareness of the serious medical consequences of clozapine-associated constipation to front line nursing staff and patients with schizophrenia. METHODS: The QIP was developed iteratively by psychiatric nurses, psychiatrists and pharmacists with input from patients. The processes involved a literature review, development of educational materials for staff and patients, and the creation of a daily bowel movements log (BML). Implementation involved review of the BML at treatment team meetings, and deployment of pharmacological and non-pharmacological interventions to resolve constipation and increase awareness and knowledge of this clinical concern. OUTCOMES: The initial pilot screened for symptoms of constipation in patients receiving clozapine and non-clozapine antipsychotic agents and intervening as necessary during multidisciplinary team meetings. Patients benefited from relief of constipation and improved bowel habits. Staff benefited from improved knowledge and making requisite changes in workflow and practice. Feedback allowed refinements to be made to the educational materials for patients and staff. Since full implementation, bowel habits are routinely monitored, and interventions are reviewed for effectiveness. Staff satisfaction with this QIP is reflected in answers to a structured questionnaire and in patient reports (n = 50). CONCLUSIONS: Clozapine, the only approved and efficacious medication for treatment-resistant schizophrenia is significantly underutilized. Medically consequential constipation can be a serious barrier to retention of patients benefiting from clozapine. Increased awareness and use of educational materials for patients and staff, routine monitoring of bowel habits combined with pharmacological and non-pharmacological interventions can successfully address this clinical problem.
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Antipsicóticos , Clozapina , Esquizofrenia , Humanos , Clozapina/efectos adversos , Mejoramiento de la Calidad , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico , Antipsicóticos/efectos adversos , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/diagnósticoAsunto(s)
Antagonistas de Narcóticos , Estreñimiento Inducido por Opioides , Receptores Opioides mu , Humanos , Receptores Opioides mu/antagonistas & inhibidores , Niño , Antagonistas de Narcóticos/uso terapéutico , Antagonistas de Narcóticos/efectos adversos , Estreñimiento Inducido por Opioides/tratamiento farmacológico , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Estreñimiento/tratamiento farmacológico , Estreñimiento/inducido químicamente , Resultado del TratamientoRESUMEN
Each year, over 1.3 million patients visit the emergency department for constipation. Most cases are benign, but serious complications, such as fecal impaction and stercoral colitis, must be ruled out. Evidence to guide the evaluation and treatment of constipation in the emergency department is limited, and many of the decades-old treatments have not been studied in modern, rigorous, controlled trials. In the emergency department, constipation is a clinical diagnosis, and ideal management includes excluding dangerous mimics or complications and, for most patients, discharging the patient with a bowel regimen tailored to the likely cause of their constipation, with appropriate referral to primary or specialty care. This review evaluates consensus guidelines on management of constipation as well as the early data on the newer prescription medications for chronic and opioid-induced constipation.
Asunto(s)
Analgésicos Opioides , Estreñimiento , Humanos , Estreñimiento/inducido químicamente , Estreñimiento/diagnóstico , Estreñimiento/terapia , Analgésicos Opioides/uso terapéutico , Servicio de Urgencia en HospitalRESUMEN
BACKGROUND: Adverse anticholinergic drug reactions are common, yet evidence on how to reduce exposure to anticholinergic activity and reliably measure successful deprescribing is still scant. This study proposes an algorithm-based approach to evaluate and reduce anticholinergic load, and reports the results of its pilot testing. METHODS: Based on published evidence and expert opinion, a list of 85 anticholinergic drugs and 21 algorithms for reducing anticholinergic load, e.g., by recommending alternative drugs with lower risk, were developed. An accompanying test battery was assembled by focusing on instruments that sensitively reflect anticholinergic load and may be sensitive to depict changes (Neuropsychological Assessment Battery to measure memory and attention, validated assessments for constipation, urinary symptoms, and xerostomia, as well as blood biomarkers). The approach was pilot-tested in a geriatric rehabilitation unit, with clinician feedback as the primary outcome and characterization of anticholinergic symptoms as the secondary outcome. The intervention was delivered by a pharmacist and a clinical pharmacologist who used the algorithms to generate personalized recommendation letters. RESULTS: We included a total of 20 patients, 13 with anticholinergic drugs and 7 without. Recommendations were made for 22 drugs in nine patients from the intervention group, of which seven letters (78%) were considered helpful and 8/22 (36%) anticholinergic drugs were discontinued, reducing anticholinergic load in seven patients. In contrast to patients without drug change, memory assessment in patients with reduced anticholinergic load improved significantly after 2 weeks (6 ± 3 vs. -1 ± 6 points). CONCLUSIONS: The approach was well received by the participating physicians and might support standardized anticholinergic deprescribing.