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

World Journal of Psychiatry 2024年第6期14卷 760-766页

作者： Lakshit Jain Jasleen Kaur Shahana Ayub Danya Ansari Rizwan Ahmed Abdul Qadir Dada Saeed Ahmed Department of Psychiatry University of ConnecticutFarmingtonCT 06032United States Addiction Services Division Connecticut Valley HospitalMiddletownCT 06457United States Department of Psychiatry Institute of LivingHartfordCT 06102United States Department of Medicine Islamabad Medical and Dental CollegeIslamabad 44000Pakistan Department of Medicine Liaquat College of Medicine and DentistryKarachi 75290Pakistan Department of Medicine Trinity School of MedicineRoswellGA 30075United States Addiction Services and Dual Diagnosis Unit Saint Francis Hospital and Medical CenterHartfordCT 06105United States

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.

关键词： Fentanyl xylazine Opioid overdose Epidemic Opioid use disorder Buprenorphine Medications for opioid use disorder

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Pharmacokinetic Characterization of xylazine in Goats with Simultaneous Anesthesia Studies

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Journal of Northeast Agricultural University(English Edition) 2024年第2期31卷 86-96页

作者： Gao Tiantian Liu Yongti Zhou Lulu Li Yanan Ruan Hongri Wei Chengwei Gao Xiang College of Veterinary Medicine Northeast Agricultural UniversityHarbin 150030China Animal Clinical Teaching Hospital Northeast Agricultural UniversityHarbin 150030China

The aim was to study the pharmacokinetics of xylazine as a stable anesthetic in goats.In this study,goats were injected with xylazine at the rate of 0.3 mL·kg-1 intramusculally,and blood samples were collected at 1,3,5,10,20,30,45,60,90,120,180,and 240 min after administration,respectively.xylazine was extracted by liquid-liquid extraction and separation method,and blood concentration was determined by high performance liquid chromatography(HPLC).The pharmacokinetic characteristics of xylazine in healthy goats were analyzed by pharmacokinetic software.The results showed that the chromatographic peak time of xylazine chromatography was 9-11 min.The specificity of the method was good.The linear correlation coefficient R2 of the standard curve was 0.9982 when the concentration of xylazine was in the range of 10-1×1000 ng.The pharmacokinetic model of xylazine in goats was a one-chamber model with first-order rate absorption,distribution half-life t1/2Ka was(0.49±0.041)min,elimination half-life t1/2Ke was(23.3±2.5)min,and the peak time(Tp)of the highest concentration was(2.8±0.2)min.The total drug clearance CL/F was(0.00016±0.000016)mg·kg-1·min-1(ng·mL-1),and the minimum effective blood concentration was 56.6 ng·mL-1,which was consistent with the clinical anesthetic effect.The results showed that xylazine had the characteristics of rapid absorption,wide distribution,short peak time,slow clearance rate,and long anesthetic time in goats,which could be used as the basic drug for the development of goat complex anesthetic preparation.

关键词： xylazine anesthesia goat pharmacokinetics

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Effect of different anesthetic mixtures——ketamine-xylazine, ketamine-acepromazine and tiletamine-zolazepam——on the physiological and blood biochemistry parameters of male rhesus monkeys(Macaca mulatta) at different ages

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Animal Models and Experimental Medicine 2019年第2期2卷 83-97页

作者： Braulio Hernández‐Godínez Herlinda Bonilla Jaime Adrián Poblano Marcela Arteaga‐Silva Ameyalli Medina Hernández Armando Contreras‐Uribe Alejandra Ibanez-Contreras Posgrado en Ciencias Biológicas y de la Salud Unidad Iztapalapa Universidad Autónoma Metropolitana Ciudad de México México Investigación Biomédica Aplicada (INBIOMA) S.A.S. de C.V. Ciudad de México México Alimentos y Camas Zoosanitarias (ACAZOO) S. de R.L. Ciudad de México México Departamento Biología de la Reproducción Unidad Iztapalapa Universidad Autónoma Metropolitana Ciudad de México México Laboratorio de Neurofisiología Cognoscitiva Instituto Nacional de Rehabilitación Ciudad de México México

Background: Anesthetic agents are commonly utilized in the handling of non‐human primates for prevent the stress caused in physical exploration or physical restrain. For this reason, the objective of this work was to describe the effect of age and dissociative anesthetics (ketamine and tiletamine), and their combinations with acepromazine, xylazine and zolazepam, on the physiological and blood biochemical parameters in Macaca mulatta. Methods: Eighty male Macaca mulatta were divided into four experimental groups depending on the anesthetic mixture applied. Each group of 20 males was divided into five sub‐groups according to age. Physiological parameters were recorded every five minutes during a 30‐minute period. A blood sample was drawn to analyze blood biochemistry. Results: Statistical analyses revealed significant differences in the physiological parameters between the ketamine‐acepromazine and ketamine‐xylazine groups compared to the control group. The analysis of blood biochemistry found significant differences by age and by anesthetic mixture among all groups. Conclusion: These findings contribute to standardizing this animal model in biological research.

关键词： acepromazine anesthesia blood biochemistry ketamine Macaca mulatta physiologic parameters tiletamine xylazine zolazepam

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Anesthesia protocol for ear surgery in Wistar rats(animal research)

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Animal Models and Experimental Medicine 2022年第2期5卷 183-188页

作者： Abhijeet Bhatia Pranjal Pratim Saikia Barilin Dkhar Haphidasara Pyngrope Department of ENT North Eastern Indira Gandhi Regional Institute of Health&Medical Sciences(NEIGRIHMS)ShillongIndia Department of Pharmacology(Animal House) North Eastern Indira Gandhi Regional Institute of Health&Medical Sciences(NEIGRIHMS)ShillongIndia

Objective:To formulate an anesthesia protocol for safe and satisfactory anesthesia for ear surgery in rats.Methods:The rats were anesthetized with xylazine(10 mg/kg body weight)and keta-mine at doses of 80,50,40,and 30 mg/kg body weight or with isoflurane anesthesia(2%-3.5%in 100%oxygen;maintenance dose 1.5%-3.5%).The anesthesia induction,surgery,and recovery time were recorded.Results:In total,17 rats were induced by varying doses of ketamine-xylazine and 28 rats with isoflurane.Mean induction time with ketamine-xylazine was 6±2.9 min compared with 3.8±1.1 min with isoflurane.Mean recovery time with ketamine-xylazine was 142.6±49.3 min compared with 4.1±1.2 min with isoflurane.A mortal-ity of 4 animals after developing dyspnea was recorded with ketamine-xylazine.Conclusion:Isoflurane anesthesia offers appropriate induction and recovery times and low mortality rates for the surgeries performed.Isoflurane anesthesia offers reli-able results for ear surgery in rats.However,more equipment and technical skills are needed.

关键词： isoflurane ketamine otology Wistar rat xylazine

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Effect of xylazine Anesthesia on Glu and GABA Amino Acid Neurotransmitters in Rat

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Journal of Northeast Agricultural University(English Edition) 2019年第1期26卷 46-52页

作者： Zhang Xin-tong Li Li-na Wang Qi Chang Tian Wen Ya-jing Yuan Rui Du Xue-man Tang Sai-nan Gao Li Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine College of Veterinary Medicine Northeast Agriculture University

Neurotransmitters of the central nervous system were the important way to study the mechanism of anesthesia. The effect of different doses of xylazine anesthetic on the glutamate(Glu) and γ-aminobutyric-acid(GABA) were investigated and the mechanism of xylazine anesthetic on the central nervous system were explored in this study. A total of 88 rats were randomly divided into three groups, including normal saline control group, group with low dose of xylazine and group with high dose of xylazine.Cerebrum, cerebellum, hippocampus, thalamus and brainstem were collected. The results showed that the concentration of Glu in the hippocampus, thalamus and brainstem decreased first and then increased, but it increased first and then decreased in the cerebrum and cerebellum during the period of anesthesia. The concentration of GABA in the cerebrum, thalamus, brainstem and hippocampus increased first and then decreased. The results showed that xylazine inhibited Glu and promoted GABA with different dose dependence. The results and methods could provide guides for the clinical use of xylazine.

关键词： brain glutamate γ-aminobutyric acid rat xylazine

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Effect of Atipamzole on Fos Protein Expression Induced by Telazol/ xylazine in Rat Cerebral Cortex and Thalamencephal

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Journal of Northeast Agricultural University(English Edition) 2016年第4期23卷 61-66页

作者： Yin Bai-shuang Gao Li Fu Lian-jun LI Hong-jin Wang Hong-bin Department of Veterinary Science College of Jilin Agriculture Science and Technology Jilin 132101 Jilin China Key Laboratory of Preventive Veterinary Medicine Jilin 132101 Jilin China College of Veterinary Medicine Northeast Agricultural University Harbin 150030 China

The aim of the study was to assess effect of the atipamezolc on talezol/xylazine induced expression of c-fos in rat brain. Rats were injected with the mixture of 13.81 mg· kg^-1 telazol and 5.21 mg· kg^-1 xylazine, following 10 min later 0.522 mg· kg^-1 atipamezole injected, and then the cerebral cortex and thalamencephal were removed at 1 h after injected. Level of Fos protein was measured in the brain tissue by westem-blot. The results revealed that telazol/xylazine induction Fos protein expression in the thalamencephal and cerebral cortex during the period of anesthesia, atipamezole attenuated tclazol/ xylazine induction Fos protein expression in the thalamencephal and cerebral cortex. The results indicated that atipamezolc could inhibite telazol/xylazine-induced c-los expression in the rat brain, and played a protective role of neuronal injury.

关键词： atipamzole tclazol xylazine Fos brain

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Electrophysiological responses to imidazoline/α2-receptor agonists in rabbit sinoatrial node pacemaker cells

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Acta Pharmacologica Sinica 2003年第12期24卷 43-49页

作者： ZHAO Ding, REN Lei-Ming Department of Pharmacology, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China Department of Pharmacology School of Pharmacy Hebei Medical University Shijiazhuang 050017

AIM: To compare the effects of moxonidine (Mox), clonidine (Clo), agmatine (Agm), and xylazine (Xyl) on action potentials (AP) of the rabbit sinoatrial node (SAN) pacemaker cells and investigate the contribution of α-adrenoceptors to the cardiac electrophysiologic responses induced by the agonists. METHODS: Intracellular microelectrode technique was used to record AP in the rabbit SAN pacemaker cells. Vasoconstrictive responses to norepinephrine (NE), Mox, Clo, Agm and Xyl were observed in the thoracic aorta and ear vein isolated from rabbits. RESULTS: (1) In the rabbit thoracic aorta, a rank order of potency producing vasoconstrictive responses was NE>Clo>Mox; and a rank order of potency in ear vein was Clo>NE>Xyl=Mox. Agm did not produce any vascular responses in both preparations, and Xyl did not produce vascular responses in the thoracic aorta. (2) Mox, Clo, Xyl, and Agm concentration-dependently decreased the rate of pacemaker firing (RPF), and prolonged APD50and APD90in the rabbit SAN pac

关键词： moxonidine clonidine agmatine xylazine adrenergic alpha-1 receptors adrenergic alpha-2 receptors action potentials sinoatrial node vasoconstriction rabbits

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咪唑啉受体及α2受体非选择性激动剂对兔离体窦房结电生理效应的分析

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中国药理通讯 2003年第2期20卷 60-60页

作者：赵丁任雷鸣河北医科大学药学院药理研究室石家庄050017

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