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Journal of Addiction MedicineXylazine is an alpha-2 adrenergic agonist commonly used as a large animal anesthetic. It is used as an adulterant in illicit opioids, and it is now well established that...
BACKGROUND
Xylazine is an alpha-2 adrenergic agonist commonly used as a large animal anesthetic. It is used as an adulterant in illicit opioids, and it is now well established that its synergistic effect with opioids increases lethality. The amount of xylazine adulterating illicit opioids is growing at an alarming rate, present in almost one-third of opioid overdose deaths reported in Philadelphia in 2019. Despite this, there are no reports considering the management of patients using xylazine chronically. In particular, there are no reported cases detailing the management of xylazine withdrawal or exploring the potential for ongoing treatment for those in recovery from xylazine use.
CASE SUMMARY
We present the case of a 29 year old female with opioid use disorder and chronic xylazine use, admitted to the intensive care unit for treatment of chronic lower extremity wounds thought to be due to xylazine injection. Her xylazine withdrawal was managed with a combination of dexmedetomidine infusion, phenobarbital and tizanidine, later transitioned to clonidine. By hospital day 4 she was no longer experiencing withdrawal symptoms. She was transitioned from full-agonist opioids for pain to buprenorphine via a buprenorphine "micro-induction" and was ultimately discharged on buprenorphine, clonidine, and gabapentin on day 19 of admission.
CLINICAL SIGNIFICANCE
This case illustrates a potential treatment pathway that allows for safe and comfortable xylazine withdrawal in hospitalized patients. It also provides an introduction into several medical concerns affecting this patient population specifically, including xylazine-mediated soft tissue wounds.
Topics: Adrenergic Agonists; Analgesics, Opioid; Animals; Buprenorphine; Clonidine; Dexmedetomidine; Female; Gabapentin; Humans; Opioid-Related Disorders; Phenobarbital; Substance Withdrawal Syndrome; Xylazine
PubMed: 35020700
DOI: 10.1097/ADM.0000000000000955 -
Clinical Toxicology (Philadelphia, Pa.) Aug 2022Xylazine is an alpha-2-adrenergic agonist used for its sedative and analgesic properties in veterinary medicine. While not approved by the Food and Drug Administration...
PURPOSE
Xylazine is an alpha-2-adrenergic agonist used for its sedative and analgesic properties in veterinary medicine. While not approved by the Food and Drug Administration for use in humans, anecdotal evidence suggests that exposures in humans is on the rise. We sought to systematically review and synthesize the evidence on xylazine exposure in humans focusing on the clinical presentation, management, and outcomes.
METHODS
We conducted a systematic review of the literature including PubMed, Embase, and Scopus from their inception to September 9, 2021. We searched abstracts from selected emergency medicine and toxicology conferences from 2011 through 2021. We included clinical reports of xylazine exposure in humans. We excluded animal studies, studies, laboratory studies, or articles in a language other than English. From each included article, we extracted subjective and objective data that focused on clinical presentation, management, and outcomes of patients exposed to xylazine.
RESULTS
We evaluated a total of 1409 records, rendering a final set of 17 articles and 2 abstracts meeting inclusion criteria. We identified a total of 98 patients amongst reports ranging from 1979 to 2020 and across nine countries. The most common types of xylazine exposures reported were unintentional exposure and intentional misuse/abuse. Common symptoms on presentation included hypotension, bradycardia, drowsiness, lethargy, while apnea with intubation and death were less frequently reported.
CONCLUSION
Human exposure to xylazine appears to be a rising concern within the prehospital and emergency medicine setting. Although a standardized treatment algorithm cannot be recommended at this time, further research is needed to improve the care of patients exposed to xylazine.
Topics: Adrenergic Agonists; Bradycardia; Humans; Hypnotics and Sedatives; Hypotension; United States; Xylazine
PubMed: 35442125
DOI: 10.1080/15563650.2022.2063135 -
Methods in Molecular Biology (Clifton,... 2022Pineal gland secretes the hormone melatonin at night with a circadian rhythm. The synthesis and secretion of melatonin are stimulated at night by norepinephrine released...
Pineal gland secretes the hormone melatonin at night with a circadian rhythm. The synthesis and secretion of melatonin are stimulated at night by norepinephrine released by sympathetic postganglionic neurons projecting from the superior cervical ganglia. Norepinephrine simultaneously activates α- and β-adrenoceptors, triggering melatonin synthesis.To study the regulation of melatonin production and secretion, it is very convenient to use an ex vivo preparation. Thus, it is possible to keep intact pineal glands in culture and to study the actions of agonists, antagonists, modulators, toxic agents, etc., in melatonin synthesis. Artificial melatonin synthesis stimulation in vitro is usually achieved by using a β-adrenergic agonist alone or in association with an α-adrenergic agonist. In this chapter, the methodology of cultured pineal glands will be described. Several papers were published by our group using this methodology, approaching the role played in melatonin synthesis control by angiotensin II and IV, insulin, glutamate, voltage-gated calcium channels, anhydroecgonine methyl ester (AEME, crack-cocaine product), monosodium glutamate (MSG), signaling pathways like NFkB, pathophysiological conditions like diabetes, etc.
Topics: Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Angiotensin II; Calcium Channels; Circadian Rhythm; Cocaine; Insulins; Melatonin; Norepinephrine; Pineal Gland; Receptors, Adrenergic, beta; Sodium Glutamate
PubMed: 36180681
DOI: 10.1007/978-1-0716-2593-4_12 -
Handbook of Experimental Pharmacology 2017History suggests β agonists, the cognate ligand of the β adrenoceptor, have been used as bronchodilators for around 5,000 years, and β agonists remain today the... (Review)
Review
History suggests β agonists, the cognate ligand of the β adrenoceptor, have been used as bronchodilators for around 5,000 years, and β agonists remain today the frontline treatment for asthma and chronic obstructive pulmonary disease (COPD). The β agonists used clinically today are the products of significant expenditure and over 100 year's intensive research aimed at minimizing side effects and enhancing therapeutic usefulness. The respiratory physician now has a therapeutic toolbox of long acting β agonists to prophylactically manage bronchoconstriction, and short acting β agonists to relieve acute exacerbations. Despite constituting the cornerstone of asthma and COPD therapy, these drugs are not perfect; significant safety issues have led to a black box warning advising that long acting β agonists should not be used alone in patients with asthma. In addition there are a significant proportion of patients whose asthma remains uncontrolled. In this chapter we discuss the evolution of β agonist use and how the understanding of β agonist actions on their principal target tissue, airway smooth muscle, has led to greater understanding of how these drugs can be further modified and improved in the future. Research into the genetics of the β adrenoceptor will also be discussed, as will the implications of individual DNA profiles on the clinical outcomes of β agonist use (pharmacogenetics). Finally we comment on what the future may hold for the use of β agonists in respiratory disease.
Topics: Adrenergic beta-2 Receptor Agonists; Animals; Asthma; Bronchodilator Agents; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Pulmonary Disease, Chronic Obstructive
PubMed: 27878470
DOI: 10.1007/164_2016_64 -
Profiles of Drug Substances,... 2017Clenbuterol (Broncodil and trade) is a direct-acting sympathomimetic agent with mainly beta-adrenergic activity and a selective action on β2 receptors (a β2 agonist)....
Clenbuterol (Broncodil and trade) is a direct-acting sympathomimetic agent with mainly beta-adrenergic activity and a selective action on β2 receptors (a β2 agonist). It has properties similar to those of salbutamol. It is used as a bronchodilator in the management of reversible airways obstruction, as in asthma and in certain patients with chronic obstructive pulmonary disease. The uses, applications, and the synthetic pathways of this drug are outlined. Physical characteristics including: ionization constant, solubility, X-ray powder diffraction pattern, thermal methods of analysis, UV spectrum, IR spectrum, mass spectrum are all produced. This profile also includes the monograph of British Pharmacopoeia, together with several reported analytical methods including spectrophotometric, electrochemical, chromatographic, immunochemical methods, and capillary electrophoretic methods. The stability, the pharmacokinetic behavior, and the pharmacology of the drug are also provided.
Topics: Adrenergic beta-Agonists; Animals; Asthma; Bronchodilator Agents; Clenbuterol; Humans; Molecular Structure; Pulmonary Disease, Chronic Obstructive; Sympathomimetics
PubMed: 28431781
DOI: 10.1016/bs.podrm.2017.02.002 -
Paediatric Drugs Jul 2021Mirabegron (MYRBETRIQ), a beta-3 adrenergic agonist developed by Astellas Pharma Inc., is well established as a treatment for overactive bladder in adults and is... (Review)
Review
Mirabegron (MYRBETRIQ), a beta-3 adrenergic agonist developed by Astellas Pharma Inc., is well established as a treatment for overactive bladder in adults and is available as extended-release (ER) tablets administered once daily. More recently, mirabegron has been investigated in pediatric patients with neurogenic detrusor overactivity (NDO) and received its first approval in this indication in pediatric patients aged ≥ 3 years on 25 March 2021 in the USA. In addition to mirabegron ER tablets (which can be used in pediatric patients weighing ≥ 35 kg), mirabegron is available as an ER oral suspension (MYRBETRIQ Granules) for pediatric patients; in those weighing < 35 kg, only the ER oral suspension formulation should be used. The ER tablet and ER oral suspension formulations are not substitutable on a mg-by-mg basis. This article summarizes the milestones in the development of mirabegron for NDO leading to this pediatric first approval.
Topics: Acetanilides; Administration, Oral; Adolescent; Adrenergic beta-3 Receptor Agonists; Child; Child, Preschool; Clinical Trials, Phase III as Topic; Drug Approval; Female; Humans; Male; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents
PubMed: 34056686
DOI: 10.1007/s40272-021-00452-4 -
Pediatrics International : Official... 2023Nocturnal enuresis is defined as intermittent urinary incontinence during sleep in children 5 years of age and older, occurring at least once a month for at least... (Review)
Review
Nocturnal enuresis is defined as intermittent urinary incontinence during sleep in children 5 years of age and older, occurring at least once a month for at least 3 months. In Japan, pediatricians who do not specialize in nocturnal enuresis have become more proactive in treating the condition since 2016, when the guidelines for treating it were revised for the first time in 12 years. For monosymptomatic nocturnal enuresis, the first step is lifestyle guidance, with a focus on the restriction of fluid intake at night; however, if lifestyle guidance does not decrease the frequency of nocturnal enuresis, aggressive treatment should be added. The first choice of aggressive treatment is oral desmopressin, an antidiuretic hormone preparation, or alarm therapy. However, there remain patients whose wet nights do not decrease with oral desmopressin or alarm therapy. In such cases, it is necessary to reconfirm the method of desmopressin administration and check for factors that may decrease the efficacy of desmopressin. If alarm therapy does not increase the number of dry nights, it is possible that the patient is fundamentally unsuitable for alarm therapy. If dry nights do not increase with oral desmopressin or alarm therapy, the next treatment strategy should be considered immediately to keep the patient motivated for treatment.
Topics: Nocturnal Enuresis; Humans; Cholinergic Antagonists; Adrenergic beta-3 Receptor Agonists; Deamino Arginine Vasopressin; Antidiuretic Agents
PubMed: 37428825
DOI: 10.1111/ped.15573 -
Drug Testing and Analysis Feb 2021Higenamine was included in the World Anti-Doping Agency (WADA) Prohibited Substances and Methods List as a β -adrenoceptor agonist in 2017, thereby resulting in its... (Review)
Review
Higenamine was included in the World Anti-Doping Agency (WADA) Prohibited Substances and Methods List as a β -adrenoceptor agonist in 2017, thereby resulting in its prohibition both in and out of competition. The present mini review describes the physiology and pharmacology of adrenoceptors, summarizes the literature addressing the mechanism of action of higenamine and extends these findings with previously unpublished in silico and in vitro work. Studies conducted in isolated in vitro systems, whole-animal preparations and a small number of clinical studies suggest that higenamine acts in part as a β -adrenoceptor agonist. In silico predictive tools indicated that higenamine and possibly a metabolite have a high probability of interacting with the β -receptor as an agonist. Stable expression of human β -receptors in Chinese hamster ovary (CHO) cells to measure agonist activity not only confirmed the activity of higenamine at β but also closely agreed with the in silico prediction of potency for this compound. These data confirm and extend literature findings supporting the inclusion of higenamine in the Prohibited List.
Topics: Adrenergic beta-Agonists; Alkaloids; Animals; Athletic Performance; Doping in Sports; Humans; Performance-Enhancing Substances; Receptors, Adrenergic, beta-2; Tetrahydroisoquinolines
PubMed: 33369180
DOI: 10.1002/dta.2992 -
Drugs Jun 2019Tiotropium/olodaterol (Stiolto Respimat; Spiolto Respimat) is an inhaled fixed-dose combination of the long-acting muscarinic antagonist tiotropium bromide (hereafter... (Review)
Review
Tiotropium/olodaterol (Stiolto Respimat; Spiolto Respimat) is an inhaled fixed-dose combination of the long-acting muscarinic antagonist tiotropium bromide (hereafter referred to as tiotropium) and the long-acting β-adrenergic agonist olodaterol. It is available in several countries, including the USA, Japan, China and those of the EU, where it is indicated for the long-term maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). The efficacy of tiotropium/olodaterol 5/5 μg/day in patients with COPD was evaluated in phase III or IV trials of 6-52 weeks' duration. Tiotropium/olodaterol improved lung function to a greater extent than each of its individual components or placebo in 12- and 52-week trials. In 6-week trials, tiotropium/olodaterol provided greater lung function benefits over 24 h than the individual components, placebo or twice-daily fluticasone propionate/salmeterol. Tiotropium/olodaterol also demonstrated beneficial effects on health-related quality of life (HR-QoL), dyspnoea, inspiratory capacity, exercise endurance and the need for rescue medication. In an 8-week open-label trial, umeclidinium/vilanterol was superior to tiotropium/olodaterol for the primary endpoint of trough forced expiratory volume in 1 s. The tolerability profile of tiotropium/olodaterol was generally similar to that of the individual components. In conclusion, tiotropium/olodaterol provides a useful option for the maintenance treatment of COPD, with the convenience of once-daily administration via a single inhaler.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Benzoxazines; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Drug Combinations; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quality of Life; Tiotropium Bromide; Treatment Outcome
PubMed: 31119643
DOI: 10.1007/s40265-019-01133-w -
Current Neuropharmacology 2023Congenital myasthenic syndromes (CMS) refer to a series of inherited disorders caused by defects in various proteins. Mutation in the collagen-like tail subunit of... (Review)
Review Meta-Analysis
BACKGROUND
Congenital myasthenic syndromes (CMS) refer to a series of inherited disorders caused by defects in various proteins. Mutation in the collagen-like tail subunit of asymmetric acetylcholinesterase () is the second-most common cause of CMS. However, data on pharmacological treatments are limited.
OBJECTIVE
In this study, we reviewed related reports to determine the most appropriate pharmacological strategy for CMS caused by mutations. A literature review and meta-analysis were also performed. PubMed, MEDLINE, Web of Science, and Cochrane Library databases were searched to identify studies published in English before July 22, 2022.
RESULTS
A total of 42 studies including 164 patients with CMS due to 72 different mutations were selected for evaluation. Most studies were case reports, and none were randomized clinical trials. Our meta-analysis revealed evidence that β-adrenergic agonists, including salbutamol and ephedrine, can be used as first-line pharmacological treatments for CMS patients with mutations, as 98.7% of patients (74/75) treated with β-adrenergic agonists showed positive effects. In addition, AChEIs should be avoided in CMS patients with mutations, as 90.5% (105/116) of patients treated with AChEIs showed either no or negative effects.
CONCLUSION
(1) β-adrenergic agonist therapy is the first pharmacological strategy for treating CMS with mutations. (2) AChEIs should be avoided in patients with CMS with mutations.
Topics: Humans; Myasthenic Syndromes, Congenital; Acetylcholinesterase; Muscle Proteins; Mutation; Adrenergic beta-Agonists; Collagen
PubMed: 36703579
DOI: 10.2174/1570159X21666230126145652