Hard Drugs Research Articles

Discovery, Multiparametric Optimization, and Solid-State Driven Identification of CHF-6550, a Novel Soft Dual Pharmacology Muscarinic Antagonist and β2 Agonist (MABA) for the Inhaled Treatment of Respiratory Diseases.

Clinical guidelines for COPD and asthma recommend inhaled β-adrenergic agonists, muscarinic antagonists, and, for frequent exacerbators, inhaled corticosteroids, with the challenge of combining them into a single device. The MABA (muscarinic antagonist and β2 agonist) concept has the potential to simplify this complexity while increasing the efficacy of both pharmacologies. In this article, we report the outcome of our solid-state driven back-up program that led to the discovery of the MABA compound CHF-6550. A soft drug approach was applied, aiming at high plasma protein binding and high hepatic clearance, concurrently with an early stage assessment of crystallinity through a dedicated experimental workflow. A new chemotype was identified, the diphenyl hydroxyacetic esters, able to generate crystalline material. Among this class, CHF-6550 demonstrated in vivo efficacy, suitability for dry powder inhaler development, favorable pharmacokinetics, and safety in preclinical settings and was selected as a back-up candidate, fulfilling the desired pharmacological and solid-state profile.

Two-Dimensional Deep Learning Frameworks for Drug-Induced Cardiotoxicity Detection.

The identification of drug-induced cardiotoxicity remains a pressing challenge with far-reaching clinical and economic ramifications, often leading to patient harm and resource-intensive drug recalls. Current methodologies, including in vivo and in vitro models, have severe limitations in accurate identification of cardiotoxic substances. Pioneering a paradigm shift from these conventional techniques, our study presents two deep learning-based frameworks, STFT-CNN and SST-CNN, to assess cardiotoxicity with markedly improved accuracy and reliability. Leveraging the power of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) as a more human-relevant cell model, we record mechanical beating signals through impedance measurements. These temporal signals were converted into enriched two-dimensional representations through advanced transformation techniques, specifically short-time Fourier transform (STFT) and synchro-squeezing transform (SST). These transformed data are fed into the proposed frameworks for comprehensive analysis, including drug type classification, concentration classification, cardiotoxicity classification, and new drug identification. Compared to traditional models like recurrent neural network (RNN) and 1-dimensional convolutional neural network (1D-CNN), SST-CNN delivered an impressive test accuracy of 98.55% in drug type classification and 99% in distinguishing cardiotoxic and noncardiotoxic drugs. Its feasibility is further highlighted with a stellar 98.5% average accuracy for classification of various concentrations, and the superiority of our proposed frameworks underscores their promise in revolutionizing drug safety assessments. With a potential for scalability, they represent a major leap in drug safety assessments, offering a pathway to more robust, efficient, and human-relevant cardiotoxicity evaluations.

Prevalence and correlates of alcohol and drug harms to others: Findings from the 2020 U.S. National Alcohol Survey.

Measure prevalence and overlap of secondhand harms from other people's use of alcohol, cannabis, opioid, or other drugs and examine sociodemographic and other correlates of these secondhand harms. This cross-sectional analysis used data from 7,799 respondents (51.6% female; 12.9% Black, 15.6% Hispanic/Latiné; mean age: 47.6) in the 2020 U.S. National Alcohol Survey. Secondhand harms included family/marriage difficulties, traffic accidents, vandalism, physical harm, and financial difficulties. Weighted prevalence estimates provided nationally representative estimates of these harms. Logistic regression assessed associations between individual characteristics and secondhand harms. Lifetime prevalence of secondhand harms from alcohol, cannabis, opioid, or other drugs was 34.2%, 5.5%, 7.6%, and 8.3%, respectively. There was substantial overlap among lifetime harms: almost 30% of those reporting secondhand alcohol harms also reported secondhand drug harms. Significant correlates of secondhand substance harms included female sex (alcohol, other drug); white (alcohol, opioid), American Indian/Alaska Native (opioid), and Black (cannabis) race/ethnicity; and separated/divorced/widowed marital status (opioid). Those reporting family history of alcohol problems had significantly higher odds of reporting secondhand harms across substance types. Individuals who reported frequent cannabis use had higher odds of reporting secondhand alcohol and opioid harms compared to those with no cannabis use, (aOR=1.55; aOR=2.38), but lower odds of reporting secondhand cannabis harms (aOR=0.51). Although less prevalent than secondhand alcohol harms, 14% of participants reported secondhand harms from someone else's drug use and frequently experienced secondhand harms attributed to multiple substances. Population-focused interventions are needed to reduce the total burden of alcohol and drug use.

Hard drugs use and tooth wear: a scoping review.

This study aims to map evidence on the relationship between hard drug use and dental wear. The scoping review is guided by the question: What is the relationship between hard drug consumption and dental wear? Adhering to PRISMA-ScR guidelines, searches were conducted across PubMed, Embase, and four databases in March 2024. Inclusion criteria included studies investigating the association between hard drug use and dental wear, regardless of publication date or language. Data were presented through narrative exposition, tables, and a conceptual framework. Twenty-eight studies (four case-control, three cross-sectional, five case reports, and sixteen literature reviews) were included. Among case-control studies, 75% observed an association between drug use and dental erosion; however, no cross-sectional studies demonstrated this association. Despite questionable quality, reviews established connections between drug use and dental erosion. Studies aimed to elucidate potential causes for dental erosion. Analysis suggests a potential link between hard drug use and dental wear, though indirect. Factors like bruxism and reduced salivary pH may contribute to dental wear among drug users. Further investigation through primary studies exploring this relationship is necessary. Dentists should focus not only on clinical characteristics of dental wear but also on mediating factors such as bruxism and decreased salivary pH associated with drug use. This holistic approach allows for a deeper understanding of dental wear mechanisms, enabling targeted preventive and therapeutic interventions.

Emerging Aspects of Triazole in Organic Synthesis: Exploring its Potential as a Gelator.

Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) - commonly known as the "click reaction" - serves as the most effective and highly reliable tool for facile construction of simple to complex designs at the molecular level. It relates to the formation of carbon heteroatomic systems by joining or clicking small molecular pieces together with the help of various organic reactions such as cycloaddition, conjugate addition, ring-opening, etc. Such dynamic strategy results in the generation of triazole and its derivatives from azides and alkynes with three nitrogen atoms in the five-membered aromatic azole ring that often forms gel-assembled structures having gelating properties. These scaffolds have led to prominent applications in designing advanced soft materials, 3D printing, ion sensing, drug delivery, photonics, separation, and purification. In this review, we mainly emphasize the different mechanistic aspects of triazole formation, which includes the synthesis of sugar-based and non-sugar-based triazoles, and their gel applications reported in the literature for the past ten years, as well as the upcoming scope in different branches of applied sciences.

Synthesis and study of organo-modified silica based hydrogels: Rheological properties and drug release kinetics.

The method of synthesis of unmodified and organo-modified silica hydrogels and their composites with orotic acid as a model drug was developed. The hydrogels had a pH of 6.5-7.8. The particulate nature and highly porous structures of the hydrogel materials were revealed using scanning electron and optical microscopy methods. The content of aqueous phase in the hydrogels was 99% or more. In order to evaluate the possibility of their application as a basis for development of novel soft drug formulations and cosmetic compositions, rheological properties of the hydrogels and in vitro release kinetics of the drug were studied. The effects of synthesis conditions (increasing concentration of catalyst of silica sol formation, drug loading) and the silica matrix modification with various organic groups on the indicated properties were investigated. It was found that all synthesized hydrogels exhibited pseudoplasticity, thixotropy and controlled release of the drug, which are important for their potential application. However, in general, the indicated effects led to worsening the properties of the hydrogel materials in comparison with the unmodified silica hydrogels.

Contribution to the harm assessment of darknet markets: topic modelling drug reviews on Dark0de Reborn

Amid the global opioid crisis, the volume of drug trade via darknet markets has risen to an all-time high. The steady increase can be explained by the reliable operation of darknet markets, affected by community-building trust factors reducing the risks during the process of the darknet drug trade. This study was designed to explore the risk reduction efforts of the community of a selected darknet market and therefore contribute to the harm assessment of darknet markets. We performed Latent Dirichlet Allocation topic modelling on customer reviews of drug products (n = 25,107) scraped from the darknet market Dark0de Reborn in 2021. We obtained a model resulting in 4 topics (coherence score = 0.57): (1) feedback on satisfaction with the transaction; (2) report on order not received; (3) information on the quality of the product; and (4) feedback on vendor reliability. These topics identified in the customer reviews suggest that the community of the selected darknet market implemented a safer form of drug supply, reducing risks at the payment and delivery stages and the potential harms of drug use. However, the pitfalls of this form of community-initiated safer supply support the need for universally available and professional harm reduction and drug checking services. These findings, and our methodological remarks on applying text mining, can enhance future research to further examine risk and harm reduction efforts across darknet markets.

Evaluating a Controlled Electromagnetic Launcher for Safe Remote Drug Delivery

Biologists and veterinarians rely on dart projectors to inject animals with drugs, take biopsies from specimens, or inject tracking chips. Firearms, air guns, and other launchers are limited in their ability to precisely control the kinetic energy of a projectile, which can injure the animal if too high. In order to improve the safety of remote drug delivery, a lidar-modulated electromagnetic launcher and a soft drug delivery dart were prototyped. A single-stage revolver coilgun and soft dart were designed and tested at distances up to 8 m. With a coil efficiency of 2.25%, the launcher could consistently deliver a projectile at a controlled kinetic energy of 1.00 ± 0.006 J and an uncontrolled kinetic energy of 2.66 ± 0.076 J. Although modifications to charging time, sensors, and electronics could improve performance, our launcher performed at the required level at the necessary distances. The precision achieved with commercial components enables many other applications, from law enforcement to manufacturing.

How do we understand the value of drug checking as a component of harm reduction services? A qualitative exploration of client and provider perspectives

BackgroundMortality related to opioid overdose in the U.S. has risen sharply in the past decade. In California, opioid overdose death rates more than tripled from 2018 to 2021, and deaths from synthetic opioids such as fentanyl increased more than seven times in those three years alone. Heightened attention to this crisis has attracted funding and programming opportunities for prevention and harm reduction interventions. Drug checking services offer people who use drugs the opportunity to test the chemical content of their own supply, but are not widely used in North America. We report on qualitative data from providers and clients of harm reduction and drug checking services, to explore how these services are used, experienced, and considered.MethodsWe conducted in-depth semi-structured key informant interviews across two samples of drug checking stakeholders: “clients” (individuals who use drugs and receive harm reduction services) and “providers” (subject matter experts and those providing clinical and harm reduction services to people who use drugs). Provider interviews were conducted via Zoom from June-November, 2022. Client interviews were conducted in person in San Francisco over a one-week period in November 2022. Data were analyzed following the tenets of thematic analysis.ResultsWe found that the value of drug checking includes but extends well beyond overdose prevention. Participants discussed ways that drug checking can fill a regulatory vacuum, serve as a tool of informal market regulation at the community level, and empower public health surveillance systems and clinical response. We present our findings within three key themes: (1) the role of drug checking in overdose prevention; (2) benefits to the overall agency, health, and wellbeing of people who use drugs; and (3) impacts of drug checking services at the community and systems levels.ConclusionThis study contributes to growing evidence of the effectiveness of drug checking services in mitigating risks associated with substance use, including overdose, through enabling people who use and sell drugs to test their own supply. It further contributes to discussions around the utility of drug checking and harm reduction, in order to inform legislation and funding allocation.

Distribution Deviation Of Limited Over-The-Counter Medicines And Prescription Medicines In Grocery Storesin X Village, Tarakan

Regarding the distribution of medicines to pharmaceutical facilities, there are several problems that are often found in the community, namely, there are still many places such as grocery stores that do not have permits to sell medicines, in fact quite a few of these stalls sell hard medicines without service and information about good treatment. This research aims to obtain an overview of irregularities in the distribution of restricted over-the-counter medicines including precursors and Obat-Obat Tertentu (OOT) and hard medicines in grocery stores in the amal beach area. This study used descriptive qualitative method. The sample for this research was all grocery stores in the X sub-district area that were willing to be respondents, namely 28 stores. The research results showed that all respondents sold limited over-the-counter drugs including precursors and OOTs as well as hard drugs. The most limited over-the-counter drug sold is Paramex, the most common precursor and oot drug is Mixagrip flu, and the most hard drug is mefenamic acid with various types of brand names. Based on the results of interviews with shop owners, it is known that most drugs are obtained by purchasing directly from pharmacies, sales and drug stores. Based on the results of this research, it can be concluded that there are irregularities in drug distribution in the X Village area, Tarakan City, because there are still grocery stores selling limited over-the-counter drugs, OOT, precursors and hard drugs.

A guide to precise measurements of isotope abundance by ESI-Orbitrap MS.

Stable isotopes of carbon, hydrogen, nitrogen, oxygen and sulfur are widespread in nature. Nevertheless, their relative abundance is not the same everywhere. This is due to kinetic isotope effects in enzymes and other physical principles such as equilibrium thermodynamics. Variations in isotope ratios offer unique insights into environmental pollution, trophic relationships in ecology, metabolic disorders and Earth history including climate history. Although classical isotope ratio mass spectrometry (IRMS) techniques still struggle to access intramolecular information like site-specific isotope abundance, electrospray ionization-Orbitrap mass spectrometry can be used to achieve precise and accurate intramolecular quantification of isotopically substituted molecules ('isotopocules'). This protocol describes two procedures. In the first one, we provide a step-by-step beginner's guide for performing multi-elemental, intramolecular and site-specific stable isotope analysis in unlabeled polar solutes by direct infusion. Using a widely available calibration solution, isotopocules of trifluoroacetic acid and immonium ions from the model peptide MRFA are quantified. In the second approach, nitrate is used as a simple model for a flow injection routine that enables access to a diverse range of naturally occurring isotopic signatures in inorganic oxyanions. Each procedure takes 2-3 h to complete and requires expertise only in general mass spectrometry. The workflows use optimized Orbitrap IRMS data-extraction and -processing software and are transferable to various analytes amenable to soft ionization, including metabolites, peptides, drugs and environmental pollutants. Optimized mass spectrometry systems will enable intramolecular isotope research in many areas of biology.

LIFE EXPERIENCES OF PATIENTS USING ORAL ANTICOAGULANTS

Abstract Objective: The aim of the study is to examine the life experiences of individuals receiving oral anticoagulant therapy. Material and Methods: The research was carried out with face-to-face semi-structured interviews (n = 16) using the qualitative research method from the qualitative research design. All interviews were recorded by mobile phone audio record programme and the interviews were transcribed into the text and evaluated in the Nvivo 8.0 packet program. Results: The average age of the participants in the study was 58 ± 10.56 . In the research, themes related to drug use knowledge and awareness, drug benefit perception, drug harm perception, treatment satisfaction, and its effect on daily life were determined. Conclusion: Awareness/knowledge, benefit and harm perception, impact on daily life and treatment satisfaction defined within the scope of five main themes. It is recommended that healthcare professionals consider these themes determined in the training programs they will plan for patients. Keywords: Oral Anticoagulant, heart disease, qualitative research.

Epidemiology of Substance Abuse Among the Youths in Makueni County, Kenya

Introduction: Majority of youths all over the world ignorantly rely on one or more types of drugs for their everyday activities, including Mandrax, Cocaine, Tobacco, Heroine, Khat, Morphine, Alcohol, Amphetamines, Ephedrine, and Glue among others. This study’s purpose was to evaluate the epidemiology of substance abuse among the youths in Makueni County, Kenya. The broad objectives that guided the study was; to determine the epidemiology of substance abuse among the youths in Makueni County, Kenya. Methodology: -A Cross-sectional mixed-method study design was undertaken, with the target population consisting of all youths from Makueni County's eight main marketplaces. Purposive sampling was employed to obtain the 8 Major urban centres while simple random selection approach was employed to obtain respondents in each market. Qualitative data was collected using 8 key informants to supplement the quantitative data collected from the youths. A self-administered questionnaire was employed. Quantitative data was analysed using Descriptive as well as inferential statistics while qualitative narrative data was grouped into themes and was presented inform of texts with verbatim quotes used to amplify the voice of the informants. Results: The study sampled 384 respondents from Makueni County. Prevalence of Drug/Substance abuse stood at 62.3 % with alcohol (58.3%) being the most commonly abused drug/Substance. Hard Drugs were the least abused with 96.9% reporting they had never abused. Pearson correlation between gender, age and education level on prevalence of drug abuse in Makueni showed a weak positive relationship(r=0.032), weak negative relationship (r=-0.064) and a significant negative relationship (r=-0.212) respectively. High unemployment rates 62.3%, easy availability of drugs 34.3%, Peer pressure 72.3%, cheap cost of drugs 28.3% and poverty level 15.1% are main contributory factors to drug abuse. A chi-square run on the factors contributing to drug abuse also indicated a significant positive relationship between the local music, TV programs, friends, and social media with prevalence of drug abuse in Makueni County. The chi-square results also revealed a weak positive relationship between parents and prevalence of drug abuse in Makueni County. Faith-based organizations, local leaders, religious leaders, and non-governmental organizations had a strong negative relationship with prevalence of drug abuse in Makueni County. Conclusion & Recommendations: There is high prevalence of Drug/Substance abuse among the youths in Makueni County and both the County Government, national Government and the community in general must put stringent measures to curb the easy availability, sale and buying of abusive Drugs and other substances in the county.

Enhancing the SUSTAINable uptake of evidence to minimise harms from alcohol and other drugs in New South Wales, Australia.

Although alcohol and other drug use is increasingly the focus of policy and research efforts, there are challenges identifying and applying evidence-based strategies to minimise harms for alcohol and other drugs in health care and community settings. These challenges include limited available research, variability across settings, and lack of 'fit' between research evidence and their intended settings. In this commentary, we describe a novel approach to develop and evaluate tailored, sustainable strategies to enhance the uptake of evidence-based activities into health services and community settings. Our approach involves four key principles: (i) identifying evidence-based alcohol and other drug harm minimisation strategies; (ii) partnering with local experts to identify and tailor strategies; (iii) implementing strategies into existing practice/infrastructure to build in sustainability; and (iv) using sustainable co-designed outcome measures including value-based health-care principles to measure uptake, feasibility and acceptability, health outcomes and economic implications. We propose that this approach offers a way forward to enhance the relevance and suitability of research in health services and community settings and has potential to be applied in other sectors.

Addiction in the Age of the Internet: The Case of E-drugs in the UAE

Preventing and protecting youth and society from drug harm is a goal that everyone seeks to achieve. In the first place, the legislative authority is entrusted with enacting laws and regulations to curb the new crimes, as the legislator succeeded in addressing in terms of criminalization and punishment for the crime of narcotic drugs and psychotropic substances. However, there is a legislative vacuum to stipulate a crime Digital drug, which the prosecution stands in front of confronting this crime in the absence of a text criminalizing this act based on the legal element of the crime (There is no crime and no punishment except by a text) which exacerbated the problem and made the matter more complicated. This study lies in shedding light on the possibility of providing digital drugs as reliable evidence to the investigation authorities, just like other types of drugs. The Results It's hard to criminalize digital drugs, because the Public Prosecution‘s reliance on the hormone dopamine in criminalization only, leads to the loss of the criminal case in proof by the Public Prosecution Office in the face of the accused, due to the difficulty of determining.

Scoping review of interventions to de-implement potentially harmful non-steroidal anti-inflammatory drugs (NSAIDs) in healthcare settings

ObjectivesPotentially harmful non-steroidal anti-inflammatory drugs (NSAIDs) utilisation persists at undesirable rates worldwide. The purpose of this paper is to review the literature on interventions to de-implement potentially harmful NSAIDs in...

Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials

Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs. This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678. 14 605 citations were identified by our search, of which 132 eligible trials enrolled 48 209 participants. All drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·98, 95% CI -9·27 to -6·69) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·79, 95% CI -6·34 to -5·25). Naltrexone-bupropion (OR 2·69, 95% CI 2·10 to 3·44), phentermine-topiramate (2·40, 1·68 to 3·44), GLP-1 receptor agonists (2·22, 1·74 to 2·84), and orlistat (1·71, 1·42 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·40, 95% CI -12·51 to -10·29). In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective. 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.

International Narcotics Crime Status and Countermeasures: Focusing on Thailand and new drugs

creasing every year. According to the Supreme Prosecutors' Office, the number of drug offenders exceeded 10,000 in 2015 and increased to 18,395 in 2022. In particular, the number of teenagers using drugs nearly tripled from 119 in 2017 to 481 in 2022. In addition, with the revitalization of international exchange and the Internet, illegal distribution of drugs on the dark web and other Internet drugs has increased. New supply methods such as illegal distribution of medical narcotics have emerged, and drugs developed as analogues or inducers that avoid existing sanctions are being distributed as new types of narcotics, making it difficult to solve the problem. The country that has the greatest influence on drug crimes in Korea is Thailand. As of 2022, among foreign drug offenders, Thais accounted for the largest number at 779, and the largest number were smuggling offenders at 301. Meanwhile, the harmfulness of drugs causes various social problems such as crimes due to arousal, tolerance, and withdrawal symptoms. In particular, the number of drug offenders under the age of 29 is increasing, raising concerns about the future of the country. Drug crime measures to be taken together with Thailand include establishing measures by drug type, establishing and implementing an early response system for new drugs such as a temporary drug designation system, and operating a cooperation system to investigate and arrest drug crime distribution networks.

The Rise of Remimazolam: A Review of Pharmacology, Clinical Efficacy, and Safety Profiles.

Anesthesiologists often use benzodiazepines (BZDs) due to their remarkable amnestic and anxiolytic capabilities. Because of this, they are perfect for use during the perioperative phase, when patients' anxiety levels are already high. Remimazolam has replaced certain commonly used intravenous (IV) anesthetics due to its excellent safety profile, rapid onset of action, and short half-life. The four classes of BZDs, 2-keto-benzodiazepines, 3-hydroxy-benzodiazepines, triazolobenzodiazepines, and 7-nitro-benzodiazepines based on chemical structure, provide various levels of drowsiness, forgetfulness, and anxiolysis. Based on their elimination half-life, short-acting BZDs typically have a half-life ranging from one to 12 hours, e.g., oxazepam; intermediate-acting BZDs have an average elimination half-life of 12 to 40 hours, e.g., alprazolam; and long-acting BZDs have an average elimination half-life of more than 40 hours, e.g., diazepam. The chloride ion channel is conformationally shifted by the benzodiazepine molecule resulting in central nervous system (CNS) inhibition and hyperpolarization. Each type of benzodiazepine has a favored use. For example, diazepam is used to treat anxiety. Midazolam is used for its anxiolytic and anterograde amnestic effects during the perioperative phase. Anxiety and epilepsy are two conditions that lorazepam effectively treats. There are now phase II and III clinical studies investigating remimazolam. It is not sensitive to alterations in its surroundings and has a brief half-life so that it may be removed rapidly, even after extensive infusion. Being a soft drug means the body easily breaks it down via metabolism, which explains many features. Remimazolam is hydrolyzed into methanol and its carboxylic acid metabolite CNS 7054 by esterase metabolism. Therefore, remimazolam has a shorter onset time and faster recovery than other BZDs. Remimazolam is metabolized independently of any particular organ. Patients with hepatic and renal problems will not see any changes in metabolism or excretion since the drug's ester moiety makes it a substrate for general tissue esterase enzymes. Like its predecessor, midazolam, it has a high potential for addiction. Some side effects that could occur during infusion include headaches and drowsiness. In clinical trials, hypotension, respiratory depression, and bradycardia were noted in participants. BZDs are helpful when used in conjunction with anesthesia. Remimazolam stands out, thanks to its unique pharmacokinetics, pharmacodynamics, safety profile, and potential medical applications. Its desirable properties make it a potential surgical premedication and sedative in the critical care unit. Anesthesiologists and other doctors could have access to more consistent and safer medication. However, additionalcomprehensive clinical trials are necessary to understand remimazolam's advantages and disadvantages.

Synergic fabrication of dual drug-loaded polymeric nanoparticles system to improve the in vitro treatment of glioma metastasis specific targeting therapy

ABSTRACT Poor drug delivery to the tumour site and harmful drug effects on the nearby healthy tissue are the two main issues with chemotherapeutic treatments for glioma. This study tests the efficacy of a chitosan dual delivery system loaded with rutin and aucubin to treat glioma. It was shown in vitro that rutin/aucubin loaded chitosan nanoparticlesignificantly inhibited U87 cells and promoted apoptosis, and the combination therapy results were superior to those of each compound used alone. The rutin-aucubin combination decreased the glioma cell’s ability to migrate. The chitosan rutin-aucubin nanocomposites showed time dependent cell uptake in U87 cells when labelled with RBITC ANG. At a low dose of 0.156 μg/mL chitosan rutin-aucubin successfully inhibited tumour growth and adhesion and ~ 43% necrosis was observed in mitochondrial membrane potential (ΔΨm) assay. In conclusion, rutin and aucubin drugs were codelivered which inhibited tumour proliferation by inducing cellular apoptosis at a low dose. This showed the system’s potential to effectively enhance glioma therapy.