Cardiovascular Risk of Opioids: A Real-World Study Based on FAERS

Objective:This research utilizes the FAERS for data mining to identify heart-related side effects caused by opioids,ensuring the safe use of these medications.Methods:Data from 79 quarters(Q12004 to Q32023)involving adverse event(AE)reports for opioids like morphine and oxycodone was reviewed.We applied the MedDRA system to categorize events and used statistical tools,ROR and BCPNN,for signal detection.These findings were cross-checked with drug labels and SIDER 4.1 for accuracy.Identified risks were then categorized by severity using DME and IME classifications.Results:Analysis of adverse events(AEs)for the five examined drugs(35359,14367,144441,10592,and 28848)identified 33,6,12,37,and 34 cardiovascular AEs,and 16,5,7,25,and 21 instances of important medical events(IMEs)respectively.Each drug was linked to cases of cardiac and cardiopulmonary arrest.The cardiovascular AEs varied widely in occurrence and severity,with methadone notably presenting diverse and potent risks,including sudden cardiac death as a distinct medical event(DME).A comparison with SIDER 4.1 showed 11 opioid-related cardiovascular AEs in line with our findings.Standardized MedDRA Queries(SMQs)confirmed these results,indicating stronger signals for methadone and tramadol,while morphine,hydromorphone,and oxycodone exhibited fewer and weaker signals.Conclusion:The study revealed numerous heart-related adverse effects(AEs)not listed on drug labels and identified new AE patterns.Recognizing these differences in AE profiles and risks across different opioids is crucial for safer prescription practices to minimize cardiac complications.

Guidance on opioids prescribing for the management of persistent non-cancer pain in older adults

Many older adults suffer from persistent pain but prevalence studies consistently showed high levels of untreated or under-treated pain in old population.Both persistent pain and pain under-treatment adversely affect independence and quality of life in geriatric patients.Pain management is challenging in this age-group because of the declining organ function,the presence of concurrent diseases and polypharmacy.For all the above reasons,persistent pain in the elderly should be considered a geriatric syndrome per se and effective approaches are warranted.Current guidelines and consensus statements recommend opioid therapy for older adults with moderateto-severe persistent pain or functional impairment and diminished quality of life due to pain.However clinicians and patients themselves have some concerns about opioids use.Age-related decline in organs functions and warnings about risk of addiction and drug misuse/abuse also in geriatric patients need particular attention for safe prescribing.On the basis of clinical evidence,these practical recommendations will help to improve the competence on opioid role in persistent pain management and the likelihood of a successful analgesic trial in older patients.

Research progress on the influence of opioids on fetal neurodevelopment during pregnancy

Women usually suffer from chronic pain due to pregnancy or have an increased level of chronic pain.In view of the definite curative effect of opioids on chronic pain and opioid use disorders,opioids have attracted much attention in the treatment of bone,joint,neuropathic and other chronic pain and opioid use disorders in pregnant women.Considering that the unreasonable use of opioids by pregnant women will lead to risks such as drug accumulation and increased neural sensitivity in the fetus,the correct and reasonable use of opioids is the key to the treatment.In recent years,it has been found that opioids can cross the blood fetal barrier into the fetal circulation,and damage fetal nerve development to varying degrees.However,the studies on the typical diseases such as neonatal neural tube defects and neonatal abstinence syndrome are not comprehensive.Therefore,this article has clarified the unreasonable use of opioids during pregnancy and its effect on fetal nerve development,and put forward relevant measures in order to provide reference for clinicians/pharmacists in obstetrics and gynecology.

Effects of propofol combined with different types of opioids on inflammatory stress response in painless gastroscopy

Objective:To study the effects of propofol combined with different types of opioids on inflammatory stress response in painless gastroscopy.Methods: Patients who underwent painless gastroscopy in our hospital between August 2014 and January 2018 were retrospectively analyzed, divided into those with nalbuphine hydrochloride, dezocine and sufentanil according to different choice of opioids and included in group A, group B and group C of the study respectively. The contents of inflammatory cytokines and oxidative stress products in serum as well as the expression levels of inflammatory pathway molecules and antioxidant pathway molecules in peripheral blood were measured before and 6 h after gastroscopy.Results: HMGB-1, TNF-α, IFN-γ, CRP, MDA, OH- and O2- contents in serum as well as RhoA, ROCK, Wnt3a,β-catenin, JNK, ERK1/2, Nrf2, ARE, HO-1,γ-GCS and Prx1 expression in peripheral blood of three groups of patients after gastroscopy were higher than those before gastroscopy, and HMGB-1, TNF-α, IFN-γ, CRP, MDA, OH- and O2- contents in serum as well as RhoA, ROCK, Wnt3a,β-catenin, JNK and ERK1/2 expression in peripheral blood of group A after gastroscopy were lower than those of group B and group C whereas Nrf2, ARE, HO-1,γ-GCS and Prx1 expression in peripheral blood were higher than those of group B and group C.Conclusion: Propofol combined with nalbuphine hydrochloride can be more effective than dezocine and sufentanil to reduce the inflammatory stress response in painless gastroscopy.

Polysubstance Use and Overdose Visualized via Maps: Opioids

Polysubstance (combinations of substances) abuse and overdose deaths now surpass mono-substance abuse and overdose deaths. Several international and governmental organizations such as the WHO (World Health Organization), CDC (Centers for Disease Control and Prevention), several of the Institutes of the NIH (National Institutes of Health), Regulators, and Enforcement Agencies, among others, track and provide a valuable source of statistical information about drug (prescription and illicit) (mis)use and overdose. The information is disseminated free to stakeholders and the general public for use. Although the numeric presentations of the data are helpful and adequate for professionals, the non-expert and the visual learner often find visual representation more clear and more compelling. With this in mind, the aim of this study was to present polysubstance use and overdose using visual maps of the available data. This article considers the opioids.

Impact of adding opioids to paravertebral blocks in breast cancer surgery patients:A systematic review and meta-analysis

BACKGROUND Several breast cancer studies have reported the use of adjuvant opioids with the paravertebral block(PVB)to improve outcomes.However,there is no level-1 evidence justifying its use.AIM To elucidate if the addition of opioids to PVB improves pain control in breast cancer surgery patients.METHODS We conducted an electronic literature search across PubMed,Embase,Scopus,and Google Scholar databases up to October 20,2020.Only randomized controlled trials(RCTs)comparing the addition of opioids to PVB with placebo for breast cancer surgery patients were included.RESULTS Six RCTs were included.Our meta-analysis indicated significantly reduced 24-h total analgesic consumption with the addition of opioids to PVB as compared to placebo[standardized mean difference(SMD)-1.57,95%confidence interval(CI):-2.93,-0.21,I2=94%].However,on subgroup analysis,the results were nonsignificant for studies using single PVB(SMD:-1.76,95%CI:-3.65,0.13 I2=95.09%)and studies using PVB infusion(SMD:-1.30,95%CI:-4.26,1.65,I2=95.49%).Analysis of single PVB studies indicated no significant difference in the time to first analgesic request between opioid and placebo groups(mean difference-11.28,95%CI:-42.00,19.43,I2=99.39%).Pain scores at 24 h were marginally lower in the opioid group(mean difference-1.10,95%CI:-2.20,0.00,I2=0%).There was no difference in the incidence of postoperative nausea and vomiting between the two groups.CONCLUSION Current evidence suggests a limited role of adjuvant opioids with PVB for breast cancer surgery patients.Further homogenous RCTs with a large sample size are needed to clarify the beneficial role of opioids with PVB.

REGULATION OF ANTI-SRBC ANTIBODY PRODUCTION BY OPIOIDS AND THEIR MECHANISMS

This study focused on the influences of opioids on the generation of antibody against sheep erythrocyte in vitro, It was found that morphine. a-CAO, DADLE, MENK were able to inhibit the capacity of murine spleen cells to generate antibody and leukotriene C4 and conversely. dynorphin was able to stimulate the capacity of murine spleen cells to generate antibody and leukotriene C4. Morphine, a-CAO, MENK, DADLE, dynorphin decreased intracellular cAMP level, increased [Ca(2+)]i and calmodulin activity. The effects were completely blocked by naloxone, the specific opioid antagonist. Our results showed that opioids regulate the production of antibody in murine spleen cells, and alter intracellular cAMP, [Ca(2+)]i calmodulin activity. and leukotriene C4 production by way of binding to different receptor types.

“New-Look” Opioids: Biased Ligands

Between the illicit use of opioids and attendant overdoses, and accidental overdoses with prescribed drugs, overuse of opioids has become a serious problem. At the same time, finding that fine balance between minimizing the risk of opioid misuse and abuse while at the same time providing access to treatment for patients who need pain control presents an ongoing challenge. Efforts to discover and develop better agents have led to what we term “new-look” opioids. We summarize here one such approach—known as biased ligands. By targeting a subset of GPCR signal transduction, this approach attempts to increase the separation between therapeutic and adverse effects.

Study on Opioids Diffusion Based on Improved SIR Model

The abuse of opioids is harmful to the national economy and health.The U.S.government has spent a lot of time,energy and money to deal with this phenomenon.Based on the topic background and team discussion,we deeply excavated the data and information provided in the topic,determined the current use of opioids,and constructed an improved SIR model to determine the source of drug abuse,the mechanism of drug abuse diffusion and the origin of each state through reverse derivation,which provided guidance for the government in the context of opioid abuse.Based on the above results,we simulated and analyzed the improved SIR model and determined the accuracy and stability of the model in the data set.

Chronic opioids in gastroparesis: relationship with gastrointestinal symptoms, healthcare utilization and employment

AIM To examine the relationship of chronic scheduled opioid use on symptoms, healthcare utilization and employment in gastroparesis(Gp) patients. Methods Patients referred to our tertiary care academic center from May 2016 to July 2017, with established diagnosis or symptoms suggestive of Gp filled out the Patient Assessment of Upper GI Symptoms, abdominal pain and demographics questionnaires, and underwent gastric emptying and blood tests. They were asked about taking pain medicines and the types, doses, and duration. We used Mann Whitney U test, Analysis of Variance, Student's t test and χ2 tests where appropriate for data analyses.RESULTS Of 223 patients with delayed gastric emptying, 158(70.9%) patients were not taking opioids(Gp NO), 22(9.9%) were taking opioids only as needed, while 43(19.3%) were on chronic(> 1 mo) scheduled opioids(Gp CO), of which 18 were taking opioids forreasons that included gastroparesis and/or stomach pain. Median morphine equivalent use was 60 mg per day. Gp CO reported higher severities of many gastrointestinal symptoms compared to Gp NO including nausea(mean ± SE of mean of 4.09 ± 0.12 vs 3.41 ± 0.12, P = 0.011), retching(2.86 ± 0.25 vs 1.98 ± 0.14, P = 0.003), vomiting(2.93 ± 0.24 vs 2.07 ± 0.15, P = 0.011), early satiety(4.17 ± 0.19 vs 3.57 ± 0.12, P = 0.004), post-prandial fullness(4.14 ± 0.18 vs 3.63 ± 0.11, P = 0.022), loss of appetite(3.64 ± 0.21 vs 3.04 ± 0.13, P = 0.039), upper abdominal pain(3.86 ± 0.20 vs 2.93 ± 0.13, P = 0.001), upper abdominal discomfort(3.74 ± 0.19 vs 3.09 ± 0.13, P = 0.031), heartburn during day(2.55 ± 0.27 vs 1.89 ± 0.13, P = 0.032), heartburn on lying down(2.76 ± 0.28 vs 1.94 ± 0.14, P = 0.008), chest discomfort during day(2.42 ± 0.20 vs 1.83 ± 0.12, P = 0.018), chest discomfort at night(2.40 ± 0.23 vs 1.61 ± 0.13, P = 0.003), regurgitation/reflux during day(2.77 ± 0.25 vs 2.18 ± 0.13, P = 0.040) and bitter/acid/sour taste in the mouth(2.79 ± 0.27 vs 2.11 ± 0.14, P = 0.028). Gp CO had a longer duration of nausea per day(median of 7 h vs 4 h for Gp NO, P = 0.037), and a higher number of vomiting episodes per day(median of 3 vs 2 for Gp NO, P = 0.002). Their abdominal pain more frequently woke them up at night(78.1% vs 57.3%, P = 0.031). They had a lower employment rate(33.3% vs 54.2%, P = 0.016) and amongst those who were employed less number of working hours per week(median of 23 vs 40, P = 0.005). They reported higher number of hospitalizations in the last 1 year(mean ± SE of mean of 2.90 ± 0.77 vs 1.26 ± 0.23, P = 0.047). CONCLUSION Gp CO had a higher severity of many gastrointestinal symptoms, compared to Gp NO. Hospitalization rates were more than 2-fold higher in Gp CO than Gp NO.Gp CO also had lower employment rate and working hours, when compared to Gp NO.

The neuroimmunopharmacology of opioids and the CNS drug discovery

Opioids have been used for treated pain for thousands of years. Meanwhile, opioids induce drug addic- tion, which causes serious medical and social problems. Most opioids research have been concentrated on neurons in the central nerve system （CNS） , however, the action of glia, which accounts for 90% cells in CNS have been long neglected. Unlike the classical opioid-neuron stereoselective interaction opioids were found to non-stereose- lectively bind the accessory protein myeloid differentiation factor 2 （MD-2） of innate immune Toll- like receptor 4 （TLR4） , which induces glial activation and pro-inflammatory factors production, therefore contributing to opioid hyper-analgesia, drug tolerance, dependence and addiction. A series of TLR4 antagonists have been discovered by multiple drug discovery strategies for inhibiting the opioids＇ side effects and treating drug abuse, among which （ ＋ ）-naltrexone and T-5342126 have been transferred to Xalud and BioLineRx respectively, for further pre-clini- cal/clinical drug development.

Dimethyltyrosine, the Viagra of Opioids

Introduction The introduction of 2＇ ,6＇-dimethyl-L＇tyrosine （Dmt） at the N-terminus of Tyr-Tic （1,2,3,4-tetra-hydroisoquinoline-3-carboxylic acid ）-containing δ-opioid antagonists enhances receptor affinity and in vitro bioactivity to several orders of magnitude and its application in the formation of ligands with new properties, such as potent inverse agonism. For example, the δ2 agonist,

Blockade of the Dopamine D3 Receptor Attenuates Opioids-Induced Addictive Behaviours Associated with Inhibiting the Mesolimbic Dopamine System

Opioid use disorder(OUD)has become a considerable global public health challenge;however,potential medications for the management of OUD that are effective,safe,and nonaddictive are not available.Accumulating preclinical evidence indicates that antagonists of the dopamine D3 receptor(D3R)have effects on addiction in different animal models.We have previously reported that YQA14,a D3R antagonist,exhibits very high affinity and selectivity for D3Rs over D2Rs,and is able to inhibit cocaine-or methamphetamine-induced reinforcement and reinstatement in self-administration tests.In the present study,our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats,also attenuated heroin-induced reinstatement of drug-seeking behavior.On the other hand,YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice.Moreover,we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system.These findings suggest that D3R might play a very important role in opioid addiction,and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.

Understanding the eff ect of recreational drug use on bone health and musculoskeletal disease in the establishment of pain regimens

BACKGROUND:The widespread use of recreational drugs has raised concerns regarding their eff ects on various organ systems.The use of cannabis and opioids in chronic pain management increases their prevalence among patients with musculoskeletal conditions whose bone health may already be compromised.This article aims to review the pathophysiology and toxic eff ects of recreational drug use on musculoskeletal health to establish appropriate pain regimens for patients with substance use.METHODS:Medical literature published from 1970 until 2022 was identifi ed utilizing MEDLINE/PubMed and the Cochrane Library.In addition to the databases,references were obtained through the use of reference lists of published articles identifi ed by the aforementioned databases.The initial search terms included opioids,inhalants,hallucinogens,cannabis,stimulants,and bone health.There were no methodological limitations in relation to the initial acquisition and analysis of data.RESULTS:A total of 55 research articles were included in this review.Cannabis,stimulants,opioids,and inhalants impact bone maintenance,specifically osteoblast and osteoclast activity,as well as impede hormone production.These substances inhibit bone remodeling and development,manifesting as lower bone mineral density and increased fracture risk in chronic users.CONCLUSION:Although the current literature suggests a deleterious effect of recreational drugs on bone health and musculoskeletal disease,further research is warranted to evaluate the clinical effects of long-term substance use.The evaluation of such effects will aid in establishing appropriate pain regimens,as well as appropriate screening and treatment plans for recreational drug users.

Advances in epidural labor analgesia:Effectiveness and treatment strategies of butorphanol

In this editorial,we provide a critical review of the article by Tang et al published in the World J Clin Cases,focusing on the utilization of butorphanol for epidural analgesia during labor.Our discussion encompasses recent research developments in epidural labor analgesia,specifically highlighting the current status of clinical applications of butorphanol and associated treatment approaches.Epidural analgesia is widely acknowledged as the primary method for pain management during labor,offering effective and prolonged pain relief while allowing mothers to remain alert and actively participate in the delivery process.Among the various drugs utilized for epidural labor analgesia,butorphanol has received increasing attention due to its potential efficacy and distinctive pharmacological properties.As a synthetic opioid analgesic,butorphanol exhibits both agonistic and antagonistic activity on opioid receptors,striking a balance between analgesia and minimizing side effects.Nevertheless,the safety and efficacy of butorphanol in epidural labor analgesia remains controversial.While certain studies have reported positive outcomes with butorphanol,including effective pain relief and a reduced incidence of side effects,others have raised concerns about its safety and efficacy compared to traditional opioids or alternative analgesics.In addition,the optimal dosing strategy and regimen of butorphanol as an adjuvant in epidural labor analgesia still need to be verified.Through comprehensive synthesis and analysis of existing literature,we aim to evaluate the current evidence regarding the use of butorphanol for epidural labor analgesia,delineate areas of consensus and controversy,and propose future avenues for research and clinical practice in this domain.

The Impact of Opioid Drugs on Memory and Other Cognitive Functions: A Review

Background and Purpose: Opioids, used for centuries to alleviate pain, have become a double-edged sword. While effective, they come with a host of adverse effects, including memory and cognition impairment. This review delves into the impact of opioid drugs on cognitive functions, explores underlying mechanisms, and investigates their prevalence in both medical care and illicit drug use. The ultimate goal is to find ways to mitigate their potential harm and address the ongoing opioid crisis. Methods: We sourced data from PubMed and Google Scholar, employing search combinations like “opioids,” “memory,” “cognition,” “amnesia,” “cognitive function,” “executive function,” and “inhibition.” Our focus was on English-language articles spanning from the inception of these databases up to the present. Results: The literature consistently reveals that opioid use, particularly at high doses, adversely affects memory and other cognitive functions. Longer deliberation times, impaired decision-making, impulsivity, and behavioral disorders are common consequences. Chronic high-dose opioid use is associated with conditions such as amnesiac syndrome (OAS), post-operative cognitive dysfunction (POCD), neonatal abstinence syndrome (NAS), depression, anxiety, sedation, and addiction. Alarming trends show increased opioid use over recent decades, amplifying the risk of these outcomes. Conclusion: Opioids cast a shadow over memory and cognitive function. These effects range from amnesiac effects, lessened cognitive function, depression, and more. Contributing factors include over-prescription, misuse, misinformation, and prohibition policies. Focusing on correct informational campaigns, removing punitive policies, and focusing on harm reduction strategies have been shown to lessen the abuse and use of opioids and thus helping to mitigate the adverse effects of these drugs. Further research into the impacts of opioids on cognitive abilities is also needed as they are well demonstrated in the literature, but the mechanism is not often completely understood.

Wastewater analysis for nicotine,cocaine,amphetamines,opioids and cannabis in New York City

According to current surveys and overdoses data,there is a drug crisis in the USA.Wastewater-based epidemiology(WBE)is an evolving discipline that analyses wastewater samples to detect drugs and metabolites to estimate drug consumption in a certain community.This study demonstrates how drug relative presence could be tracked by testing wastewater,providing real-time results,in different boroughs in New York City throughout 1 year.We developed and fully validated two analytical methods,one for 21 drugs and metabolites,including nicotine,cocaine,amphetamines,opioids and cannabis markers;and another for the normalization factor creatinine.Both methods were performed by liquid chromatography tandem mass spectrometry(LC-MS/MS)using positive electrospray ionization,achieving a limit of quantification of 5–10 ng/L for drugs and metabolites,and 0.01 mg/L for creatinine.These methods were applied to 48 one-time grab wastewater samples collected from six wastewater treatment plants in New York City(Manhattan,The Bronx,Queens and Brooklyn),eight different times throughout 2016,before and after major holidays,including Memorial Day,4th of July,Labour Day and New Year’s.In this study,the drug group normalized concentrations present in the wastewater samples,in decreasing order,were cocaine,nicotine,opioids,cannabis and amphetamines.When looking at individual compounds,the one with the highest normalized concentration was benzoylecgonine(BE),followed by cotinine,morphine and 11-nor-9-carboxy-tetrahydrocannabinol(THCCOOH).To estimate community use,these concentrations were multiplied by the corresponding correction factor,and the most present were THCCOOH,followed by BE,cotinine and morphine.When comparing the treatment plants by drug group(nicotine,cocaine,amphetamines,opioids and cannabis),samples collected from The Bronx had the highest normalized concentrations for nicotine,cocaine and opioids;The Bronx and Manhattan for cannabis;and Manhattan and Queens for amphetamines.In most of the cases,no effect due to holiday was observed.This study provides the first snapshot of drug use in New York City and how that changes between key calendar dates employing wastewater analysis.

Fatalities caused by novel opioids:a review

Drugs related to morphine represent not only large range of important therapeutic applications for the relief of moderate to severe pain but also give rise to a relatively large series of novel opioids that mimic the action of this naturally occurring analgesic.Most of these are based on fentanyl structures that are much more potent,and dangerous,than fentanyl itself.This publication reviews reports of fatalities attributed to 15 novel opioids with the view to assessing mortality associated with their misuse as well as reviewing published analytical procedures that would be able to detect these and other novel opioids.These drugs include reports of deaths to acetylfentanyl,acrylfentanyl,butr(yl)fentanyl,carfentanil,2-and 4-fluorofentanyls,4-fluorobutyrfentanyl,4-fluoroisobutyrfentanyl,furanylfentanyl,a-and 3-methylfentanyls,4-methoxyfentanyl,ocfentanil,as well as AH-7921,U-47700 and MT-45.Most of these cases reporting a drug-caused death involved other drugs in addition to the opioid.No obvious minimum fatal concentration was discerned for any of the opioids for which details were provided,however,the more potent members required detection limits well under 1 ng/mL and often even well below 0.1 ng/mL requiring use of the most sensitive mass spectral detection procedures,particularly when screening specimens using a non-targeted mode.Four other novel opioids have been reported in admissions to hospitals include 4-chloroisobutryfentanyl,cyclopentylfentanyl and tetrahydrofuranfentanyl,all of which are likely to have the potential to cause death.It is also likely that other analogues will appear with time.

Novel synthetic opioids-toxicological aspects and analysis

Over the past few years,there has been an emerging number of new psychoactive drugs.These drugs are frequently mentioned as“legal highs”,“herbal highs”,“bath salts”and“research chemicals”.They are mostly sold and advertised on online forums and on the dark web.The emerging new psychoactive substances are designed to mimic the effects of psychoactive groups,which are often abused drugs.Novel synthetic opioids are a new trend in this context and represent an alarming threat to public health.Given the wide number of fatalities related to these compounds reported within the last few years,it is an important task to accurately identify these compounds in biologic matrices in order to administer an effective treatment and reverse the respiratory depression caused by opioid related substances.Clinicians dealing with fentanyl intoxication cases should consider that it could,in fact,be a fentanyl analogue.For this reason,it is a helpful recommendation to include synthetic opioids in the routine toxicological screening procedures,including analysis in alternative matrices,if available,to investigate poly-drug use and possible tolerance to opioids.To address this public health problem,better international collaboration,effective legislation,effective investigation,control of suspicious“research chemicals”online forums and continuous community alertness are required.This article aims to review diverse reported fatalities associated with new synthetic opioids describing them in terms of pharmacology,metabolism,posology,available forms,as well as their toxic effects,highlighting the sample procedures and analytical techniques available for their detection and quantification in biological matrices.

Fentanyl and xylazine crisis:Crafting coherent strategies for opioid overdose prevention

The United States is in the throes of a severe opioid overdose epidemic,primarily fueled by the pervasive use of fentanyl and the emerging threat of xylazine,a veterinary sedative often mixed with fentanyl.The high potency and long duration of fentanyl is compounded by the added risks from xylazine,heightening the lethal danger faced by opioid users.Measures such as enhanced surveillance,public awareness campaigns,and the distribution of fentanylxylazine test kits,and naloxone have been undertaken to mitigate this crisis.Fentanyl-related overdose deaths persist despite these efforts,partly due to inconsistent policies across states and resistance towards adopting harm reduction strategies.A multifaceted approach is imperative in effectively combating the opioid overdose epidemic.This approach should include expansion of treatment access,broadening the availability of medications for opioid use disorder,implementation of harm reduction strategies,and enaction of legislative reforms and diminishing stigma associated with opioid use disorder.