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Obesity Reviews : An Official Journal... Nov 2023This systematic review collates studies of dietary or bariatric surgery interventions for obesity using positron emission tomography and single-photon emission computed... (Review)
Review
Effects of bariatric surgery and dietary interventions for obesity on brain neurotransmitter systems and metabolism: A systematic review of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies.
This systematic review collates studies of dietary or bariatric surgery interventions for obesity using positron emission tomography and single-photon emission computed tomography. Of 604 publications identified, 22 met inclusion criteria. Twelve studies assessed bariatric surgery (seven gastric bypass, five gastric bypass/sleeve gastrectomy), and ten dietary interventions (six low-calorie diet, three very low-calorie diet, one prolonged fasting). Thirteen studies examined neurotransmitter systems (six used tracers for dopamine DRD2/3 receptors: two each for C-raclopride, F-fallypride, I-IBZM; one for dopamine transporter, I-FP-CIT; one used tracer for serotonin 5-HT receptor, F-altanserin; two used tracers for serotonin transporter, C-DASB or I-FP-CIT; two used tracer for μ-opioid receptor, C-carfentanil; one used tracer for noradrenaline transporter, C-MRB); seven studies assessed glucose uptake using F-fluorodeoxyglucose; four studies assessed regional cerebral blood flow using O-H O (one study also used arterial spin labeling); and two studies measured fatty acid uptake using F-FTHA and one using C-palmitate. The review summarizes findings and correlations with clinical outcomes, eating behavior, and mechanistic mediators. The small number of studies using each tracer and intervention, lack of dietary intervention control groups in any surgical studies, heterogeneity in time since intervention and degree of weight loss, and small sample sizes hindered the drawing of robust conclusions across studies.
Topics: Humans; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon; Bariatric Surgery; Brain; Obesity; Neurotransmitter Agents
PubMed: 37699864
DOI: 10.1111/obr.13620 -
Tramadol for the Management of Opioid Withdrawal: A Systematic Review of Randomized Clinical Trials.Cureus Jul 2020The increase in the prescription of opioid medications has resulted in a wildfire of misuse of opioids, both for medical and non-medical reasons, with over 1.7 million... (Review)
Review
The increase in the prescription of opioid medications has resulted in a wildfire of misuse of opioids, both for medical and non-medical reasons, with over 1.7 million people in the United States (US) suffering from distinct disorders owing to opioid use. While various medications, such as methadone, buprenorphine, and naloxone, among others, have been used in treating opioid withdrawal symptoms, concerns of the potential abuse of these drugs, the cost of procurement, legislations, and prescription policies have risen. In recent times, tramadol has been considered a viable replacement for some of these treatment regimes. Tramadol is a synthetic analgesic that acts centrally, possessing opioid-like effects due to the binding of its metabolite with the mu (µ)-opioid receptor, yet with low potential for abuse. Several clinical studies conducted in the past ten years have identified the effects of tramadol in opioid withdrawal cases. The results showed that it exhibits better efficacy and tolerance with fewer side effects in specific clinical scenarios as compared to existing available detox management. We aim to examine the properties of tramadol in opioid withdrawal through this systematic review of clinical studies on humans.
PubMed: 32789069
DOI: 10.7759/cureus.9128 -
JMIR Dermatology May 2022
PubMed: 37632854
DOI: 10.2196/30737 -
Pharmacy (Basel, Switzerland) Mar 2024Opioid-induced constipation (OIC) is a pervasive and distressing side effect of chronic opioid therapy in patients with cancer pain, significantly impacting their... (Review)
Review
BACKGROUND
Opioid-induced constipation (OIC) is a pervasive and distressing side effect of chronic opioid therapy in patients with cancer pain, significantly impacting their quality of life. Peripherally acting μ-opioid receptor antagonists (PAMORAS) were developed for treatment-resistant OIC but most studies were conducted with non-cancer patients.
OBJECTIVE
to discuss two oral formulations of PAMORAs, naldemedine and naloxegol, and to review available evidence of the effectiveness of these drugs for OIC in cancer patients.
METHODS
a comprehensive search to identify primary literature for either naldemedine or naloxegol for OIC in cancer patients.
RESULTS
Only three prospective randomized, double-blind, placebo-controlled clinical trials for naldemedine enrolling cancer patients were identified; the results of a subgroup analysis of two of those studies and two non-interventional post marketing surveillance studies of these trials are also reported here. For naloxegol, only two randomized controlled trials were identified; both were unsuccessful in enrolling sufficient patients. An additional four prospective non-interventional observational studies with naloxegol were found that enrolled cancer patients. There were significantly higher rates of responders in the PAMORA groups than in the placebo groups. The most common side effect for both PAMORAs was diarrhea.
LIMITATIONS
All studies were industry-funded, and given that only three trials were randomized controlled studies, the overall quality of the studies was lacking.
CONCLUSION
Naldemedine or naloxegol appeared safe and useful in the treatment of OIC in cancer patients and may improve their quality of life. Larger-scale randomized placebo-controlled studies of PAMORAs in cancer patients would strengthen existing evidence.
PubMed: 38525728
DOI: 10.3390/pharmacy12020048 -
Medicine Jan 2021While irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal diseases in clinical practice, it has diverse pathogenesis. Because of its... (Meta-Analysis)
Meta-Analysis
BACKGROUND
While irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal diseases in clinical practice, it has diverse pathogenesis. Because of its sudden and lingering intractable symptoms, it seriously affects patients work and life. Opioid receptors are G protein-coupled receptors distributed across the brain, spinal cord, skin, and gastrointestinal tract, and each of the subtypes has a unique role and specific distribution. They play a role in regulating gastrointestinal motility, secretion, and visceral sensations in the gastrointestinal tract. Therefore, this meta-analysis aims to evaluate the effects of opioid receptor modulators on improving the symptoms of IBS.
METHODS
Searching the key words (Irritable Bowel Syndromes or Syndrome, Irritable Bowel OR Syndromes, Irritable Bowel OR Colon, Irritable OR Irritable Colon OR Colitis, Mucous OR Colitides, Mucous OR Mucous Colitides OR Mucous Colitis) AND (opioid receptor modulators OR eluxadoline OR Viberzi OR asimadoline OR loperamide), a preliminary search on PubMed (English), EMBASE (English), Cochrane Library (English), China National Knowledge Infrastructure Database (CNKI, Chinese), WanFang (Chinese), VIP citation databases (Chinese) and SinoMed (Chinese) databases yielded 1023 papers published in English and Chinese from inception to July 1, 2019. Nine studies were included in the final meta-analysis. Because this is a systematic review and meta-analysis, ethical approval is not necessary.
RESULTS
The random-effects meta-analysis based on these 9 studies and their 4156 patients found that opioid receptor modulators have a statistically significant beneficial effect on IBS global symptoms (RR = 0.85, 95%CI = 0.79-0.92, P < .01) and bowel movement frequency (SMD = -1.26, 95%CI = -2.49--0.04, P < .05), and while there was an improvement trend in stool consistency and quality of life, these findings were not statistically significant.
CONCLUSIONS
This is the first meta-analysis to examine the use of opioid receptor modulators in IBS, and few adverse events were reported in the available trials. Compared with the control group, eluxadolin has a better effect in improving IBS global symptoms and abdominal pain and has statistical significance and showed a low rate of constipation development in IBS patients in comparison with known effects of other opioid receptor modulators. However, current findings are based on a considerably limited evidence base with marked heterogeneity. Future studies should aim to identify subpopulations of patients with IBS and need to evaluate the long-term safety of these therapies.PROSPERO registration number: CRD42020141597.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Irritable Bowel Syndrome; Male; Middle Aged; Narcotic Antagonists; Treatment Outcome; Young Adult
PubMed: 33530231
DOI: 10.1097/MD.0000000000024361 -
International Review of Psychiatry... Oct 2018There are several biological factors that might play a role in physiological response to opioids and/or the onset of problematic opioid use; however, sex-based...
There are several biological factors that might play a role in physiological response to opioids and/or the onset of problematic opioid use; however, sex-based differences in non-analgesic opioid-based effects are poorly understood. The goal of this review is to provide a current analysis of the pre-clinical literature on sex-based differences in response to endogenous and exogenous opioids, including the interplay between sex hormones and opioid receptor-mediated neuronal activity and associated behaviours. A systematic search was performed on the following terms within PubMed between March and April 2018: 'opioid oestrogen', 'opioid progesterone', 'opioid oestradiol', and 'opioid testosterone'. Pre-clinical research on the non-analgesic, sex-based effects of opioids is disparate, both in terms of methodology and outcomes, which prohibits a cohesive summary of the results. Themes from the pre-clinical literature suggest that opioid receptor binding, coupling, and density vary as a function of hormone exposure. Findings also suggest that interactions between endogenous opioid and stress systems may differ between males and females as a function of ovarian hormones. Given the current opioid-related public health crisis, there is a pressing need to increase systematic pre-clinical and clinical research on sex-based differences in opioid-effects and opioid use disorder.
Topics: Analgesics, Opioid; Animals; Gonadal Steroid Hormones; Humans; Models, Animal; Receptors, Opioid; Sex Characteristics
PubMed: 30522374
DOI: 10.1080/09540261.2018.1514295 -
Cureus Jul 2021In treating chronic and acute pain, opioids are widely used. Although they do provide analgesia, their usage does come with adverse events (AEs). One of the most... (Review)
Review
In treating chronic and acute pain, opioids are widely used. Although they do provide analgesia, their usage does come with adverse events (AEs). One of the most burdensome is opioid-induced bowel dysfunction, and more specifically opioid-induced constipation (OIC). The pathogenesis of these AEs is well known as the consequence of the action of opioids on m-receptors in the enteric nervous system. In recent years, medicines counteracting this specific action at the receptors have been registered for clinical use: the peripherally acting μ-opioid receptor antagonists (PAMORAs). The knowledge of their comparative efficacy and tolerability is very important for physicians and patients in opioid therapy. This systematic review of the existing literature on PAMORAs aimed to study the relative clinical advantages and disadvantages. The most important data banks, including "PubMed," "Embase," "CT.gov," "ICTRP" and "CINAHL" were used to find the published material on PAMORAs. The selected publications were examined to systematically analyze the efficacy and safety of the four existing PAMORAs. All of the medications are superior to placebo in reducing OIC. There are few published data on alvimopan used to treat OIC, and it is only indicated for the treatment of post-abdominal surgery ileus. Methylnaltrexone is studied mainly in its subcutaneous (SC) formulation. When used in its oral formulation, it seems more rapid than naloxegol and placebo in the reduction of OIC. Naldemedine is able to produce more spontaneous bowel movements (SBMs) when compared to alvimopan and naloxegol. Tolerability was found to be similar for all of them. In particular, they affect the gastrointestinal tract (GI), with flatulence and diarrhea, especially at high dosages. For some of them, nasopharyngitis and abdominal pain were observed as treatment adverse effects (TEAs). Several cardiovascular TEAs were reported after methylnaltrexone use, but it is not clear whether they were consequences of the drug or related to the general conditions of the patients. Considering the existing data, naloxegol and naldemedine seem to be the best choices, with a higher number of spontaneous bowel movements following naldemedine administration.
PubMed: 34367804
DOI: 10.7759/cureus.16201 -
Journal of Clinical Medicine Apr 2023Chiari Malformation Type I (CM) includes a range of cranial abnormalities at the junction of the skull with the spine, with common symptoms including pain and headaches.... (Review)
Review
Chiari Malformation Type I (CM) includes a range of cranial abnormalities at the junction of the skull with the spine, with common symptoms including pain and headaches. Currently, CM pain is managed medically through anti-inflammatory drugs, muscle relaxants, and opioids, while surgical management includes posterior fossa decompression. Given the adverse effects of opioid use, and an ongoing opioid epidemic, there is a need for safe, non-opioid alternatives for clinical pain management. This systematic review was performed to provide an update on the current literature pertaining to the treatment of CM pain with non-opioid alternatives. A literature search was performed in June 2022 utilizing the PubMed and Google Scholar databases, and articles were identified that included information regarding non-opioid pain management in CM patients. A total of 90 articles were obtained from this search, including 10 relevant, drug-specific studies. Two independent reviewers selected and included all relevant articles based on the chosen search criteria to minimize bias risk. Currently available treatments for neurosurgical pain management include anticonvulsants, corticosteroids, NSAIDs, anti-inflammatory drugs, NMDA receptor antagonists, local anesthetics, nerve blocks, scalp blocks, and neuromuscular blocks. While more information is needed on the use of non-opioid pain management, the present literature provides potential evidence of its efficacy amongst the CM patient population, on account of the success that non-opioid pain management has demonstrated within other neurological pain syndromes. Further research into non-pharmacological pain management would also benefit the CM population and could be generalized to related conditions.
PubMed: 37176505
DOI: 10.3390/jcm12093064 -
The Cochrane Database of Systematic... Jun 2018Opioid-induced bowel dysfunction (OIBD) is characterised by constipation, incomplete evacuation, bloating, and gastric reflux. It is one of the major adverse events of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Opioid-induced bowel dysfunction (OIBD) is characterised by constipation, incomplete evacuation, bloating, and gastric reflux. It is one of the major adverse events of treatment for pain in cancer and in palliative care, resulting in increased morbidity and reduced quality of life.This is an update of two Cochrane reviews. One was published in 2011, Issue 1 on laxatives and methylnaltrexone for the management of constipation in people receiving palliative care; this was updated in 2015 and excluded methylnaltrexone. The other was published in 2008, Issue 4 on mu-opioid antagonists (MOA) for OIBD. In this updated review, we only included trials on MOA (including methylnaltrexone) for OIBD in people with cancer and people receiving palliative care.
OBJECTIVES
To assess the effectiveness and safety of MOA for OIBD in people with cancer and people receiving palliative care.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, and Web of Science to August 2017. We also searched clinical trial registries and regulatory websites. We contacted manufacturers of MOA to identify further data.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that assessed the effectiveness and safety of MOA for OIBD in people with cancer and people at a palliative stage irrespective of the type of terminal disease they experienced.
DATA COLLECTION AND ANALYSIS
Two review authors assessed risk of bias and extracted data. The appropriateness of combining data from the trials depended upon sufficient homogeneity across the trials. Our primary outcomes were laxation, impact on pain relief, and adverse events. Impact on pain relief was a primary outcome because a possible adverse effect of MOAs is a reduction in pain relief from opioids. We assessed the evidence on these outcomes using GRADE.
MAIN RESULTS
We identified four new trials for this update, bringing the total number included in this review to eight. In total, 1022 men and women with cancer irrespective of stage or at a palliative care stage of any disease were randomised across the trials. The MOAs evaluated were oral naldemedine and naloxone (alone or in combination with oxycodone), and subcutaneous methylnaltrexone. The trials compared with MOA with a placebo or with the active intervention administered at different doses or in combination with other drugs. The trial of naldemedine and the two of naloxone in combination with oxycodone were in people with cancer irrespective of disease stage. The trial on naloxone alone was in people with advanced cancer. The four trials on methylnaltrexone were undertaken in palliative care where most participants had cancer. All trials were vulnerable to biases; four were at a high risk as they involved a sample of fewer than 50 participants per arm.In the trial of naldemedine compared to placebo in 225 participants, there were more spontaneous laxations over the two-week treatment for the intervention group (risk ratio (RR) 1.93, 95% confidence intervals (CI) 1.36 to 2.74; moderate-quality evidence). In comparison with higher doses, lower doses resulted in fewer spontaneous laxations (0.1 mg versus 0.2 mg: RR 0.73, 95% CI 0.55 to 0.95; 0.1 mg versus 0.4 mg: RR 0.69, 95% CI 0.53 to 0.89; moderate-quality evidence). There was moderate-quality evidence that naldemedine had no effect on opiate withdrawal. There were five serious adverse events. All were in people taking naldemedine (low-quality evidence). There was an increase in the occurrence of other (non-serious) adverse events in the naldemedine groups (RR 1.36, 95% CI 1.04 to 1.79, moderate-quality evidence). The most common adverse event was diarrhoea.The trials on naloxone taken either on its own, or in combination with oxycodone (an opioid) compared to oxycodone only did not evaluate laxation response over the first two weeks of administration. There was very low-quality evidence that naloxone alone, and moderate-quality evidence that oxycodone/naloxone, had no effect on analgesia. There was low-quality evidence that oxycodone/naloxone did not increase the risk of serious adverse events and moderate-quality evidence that it did not increase risk of adverse events.In combined analysis of two trials of 287 participants, we found methylnaltrexone compared to placebo induced more laxations within 24 hours (RR 2.77, 95% CI 1.91 to 4.04. I² = 0%; moderate-quality evidence). In combined analysis, we found methylnaltrexone induced more laxation responses over two weeks (RR 9.98, 95% CI 4.96 to 20.09. I² = 0%; moderate-quality evidence). The proportion of participants who had a rescue-free laxation response within 24 hours of the first dose was 59.1% in the methylnaltrexone arms and 19.1% in the placebo arm. There was moderate-quality evidence that the rate of opioid withdrawal was not affected. Methylnaltrexone did not increase the likelihood of a serious adverse event; there were fewer in the intervention arm (RR 0.59, 95% CI 0.38 to 0.93; I² = 0%; moderate-quality evidence). There was no difference in the proportion of participants experiencing an adverse event (RR 1.17, 95% CI 0.94 to 1.45; I² = 74%; low-quality evidence). Methylnaltrexone increased the likelihood of abdominal pain and flatulence.Two trials compared differing methylnaltrexone schedules of higher doses with lower doses. For early laxation, there was low-quality evidence of no clear difference between doses on analgesia and adverse events. Both trials measured laxation response within 24 hours of first dose (trial one: RR 0.82, 95% CI 0.41 to 1.66; trial two: RR 1.07, 95% CI 0.81 to 1.42).
AUTHORS' CONCLUSIONS
In this update, the conclusions for naldemedine are new. There is moderate-quality evidence to suggest that, taken orally, naldemedine improves bowel function over two weeks in people with cancer and OIBD but increases the risk of adverse events. The conclusions on naloxone and methylnaltrexone have not changed. The trials on naloxone did not assess laxation at 24 hours or over two weeks. There is moderate-quality evidence that methylnaltrexone improves bowel function in people receiving palliative care in the short term and over two weeks, and low-quality evidence that it does not increase adverse events. There is a need for more trials including more evaluation of adverse events. None of the current trials evaluated effects in children.
Topics: Constipation; Defecation; Female; Gastrointestinal Agents; Humans; Intestinal Diseases; Male; Nalbuphine; Naloxone; Naltrexone; Narcotic Antagonists; Neoplasms; Opioid-Related Disorders; Oxycodone; Palliative Care; Piperidines; Quaternary Ammonium Compounds; Randomized Controlled Trials as Topic; Receptors, Opioid, mu
PubMed: 29869799
DOI: 10.1002/14651858.CD006332.pub3 -
Pharmaceuticals (Basel, Switzerland) Jul 2022Chronic kidney disease-associated pruritus (CKD-aP) is a chronic condition that significantly reduces the quality of life of patients with end-stage renal disease. The... (Review)
Review
Chronic kidney disease-associated pruritus (CKD-aP) is a chronic condition that significantly reduces the quality of life of patients with end-stage renal disease. The etiology is not fully understood, but imbalance in the activity of the opioid pathways, including downregulation of the kappa-opioid receptor, may contribute to itching sensation. Difelikefalin is a selective, peripherally acting kappa-opioid receptor (KOR) agonist. Recently, difelikefalin has been approved as a first drug for the treatment of pruritus associated with chronic kidney disease (CKD) in adult hemodialysis patients. A systematic review of currently available clinical trials was performed to assess the efficacy and safety of difelikefalin in patients with uremic pruritus. A literature review was conducted in May 2022 based on the PRISMA 2020 guidelines. The analyzed clinical trials showed that difelikefalin was effective in reducing pruritus in patients as assessed by the Worst Itching Intensity Numerical Rating Scale. Improvement in quality of life assessed on the basis of the Skindex score and the 5-D itch scale was also noticed. The most commonly reported side effects were mild and included nausea, vomiting, dizziness, and diarrhea. Due to its proven efficacy and good safety profile, difelikefalin is a promising drug for the treatment of pruritus in patients with chronic kidney disease.
PubMed: 36015082
DOI: 10.3390/ph15080934