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Korean Journal of Anesthesiology Aug 2019Dexmedetomidine is a potent, highly selective α-2 adrenoceptor agonist, with sedative, analgesic, anxiolytic, sympatholytic, and opioid-sparing properties.... (Review)
Review
Dexmedetomidine is a potent, highly selective α-2 adrenoceptor agonist, with sedative, analgesic, anxiolytic, sympatholytic, and opioid-sparing properties. Dexmedetomidine induces a unique sedative response, which shows an easy transition from sleep to wakefulness, thus allowing a patient to be cooperative and communicative when stimulated. Dexmedetomidine may produce less delirium than other sedatives or even prevent delirium. The analgesic effect of dexmedetomidine is not strong; however, it can be administered as a useful analgesic adjuvant. As an anesthetic adjuvant, dexmedetomidine decreases the need for opioids, inhalational anesthetics, and intravenous anesthetics. The sympatholytic effect of dexmedetomidine may provide stable hemodynamics during the perioperative period. Dexmedetomidine-induced cooperative sedation with minimal respiratory depression provides safe and acceptable conditions during neurosurgical procedures in awake patients and awake fiberoptic intubation. Despite the lack of pediatric labelling, dexmedetomidine has been widely studied for pediatric use in various applications. Most adverse events associated with dexmedetomidine occur during or shortly after a loading infusion. There are some case reports of dexmedetomidine-related cardiac arrest following severe bradycardia. Some extended applications of dexmedetomidine discussed in this review are promising, but still limited, and further research is required. The pharmacological properties and possible adverse effects of dexmedetomidine should be well understood by the anesthesiologist prior to use. Moreover, it is necessary to select patients carefully and to determine the appropriate dosage of dexmedetomidine to ensure patient safety.
Topics: Adrenergic alpha-2 Receptor Agonists; Delirium; Dexmedetomidine; Dose-Response Relationship, Drug; Humans; Hypnotics and Sedatives; Patient Selection
PubMed: 31220910
DOI: 10.4097/kja.19259 -
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 -
Drug Design, Development and Therapy 2023Peripheral nerve block technology is important to balanced anesthesia technology. It can effectively reduce opioid usage. It is the key to enhance clinical... (Review)
Review
Peripheral nerve block technology is important to balanced anesthesia technology. It can effectively reduce opioid usage. It is the key to enhance clinical rehabilitation as an important part of the multimodal analgesia scheme. The emergence of ultrasound technology has accelerated peripheral nerve block technology development. It can directly observe the nerve shape, surrounding tissue, and diffusion path of drugs. It can also reduce the dosage of local anesthetics by improving positioning accuracy while enhancing the block's efficacy. Dexmedetomidine is a highly selective drug α-adrenergic receptor agonist. Dexmedetomidine has the characteristics of sedation, analgesia, anti-anxiety, inhibition of sympathetic activity, mild respiratory inhibition, and stable hemodynamics. Numerous studies have revealed that dexmedetomidine in peripheral nerve blocks can shorten the onset time of anesthesia and prolong the time of sensory and motor nerve blocks. Although dexmedetomidine was approved by the European Drug Administration for sedation and analgesia in 2017, it has not yet been approved by the US Food and Drug Administration (FDA). It is used as a non-label drug as an adjuvant. Therefore, the risk-benefit ratio must be evaluated when using these drugs as adjuvants. This review explains the pharmacology and mechanism of dexmedetomidine, the effect of dexmedetomidine on various peripheral nerve block as an adjuvant, and compare it with other types of adjuvants. We summarized and reviewed the application progress of dexmedetomidine as an adjuvant in nerve block and look forward to its future research direction.
Topics: United States; Dexmedetomidine; Adjuvants, Immunologic; Anesthetics, Local; Nerve Block; Adrenergic alpha-2 Receptor Agonists; Peripheral Nerves
PubMed: 37220544
DOI: 10.2147/DDDT.S405294 -
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 -
Profiles of Drug Substances,... 2023Brimonidine is a highly selective 2-adrenoceptor agonist that lowers intraocular pressure (IOP) by decreasing aqueous humor production and increasing aqueous humor...
Brimonidine is a highly selective 2-adrenoceptor agonist that lowers intraocular pressure (IOP) by decreasing aqueous humor production and increasing aqueous humor outflow via the uveoscleral route. Brimonidine is used to treat glaucoma and other eye conditions. Brimonidine is a topical medication that is used mainly to treat open-angle glaucoma and ocular hypertension in the eyelids. The purpose of this chapter is to provide a comprehensive discussion of Brimonidine's nomenclature, physiochemical properties, preparation methods, identification procedures, and numerous qualitative and quantitative analytical techniques, as well as its ADME profiles and pharmacological effects. In addition, the chapter contains numerous approaches for separating brimonidine from other medications in combination formulations utilizing chromatographic techniques and other spectroscopic approaches.
Topics: Humans; Brimonidine Tartrate; Glaucoma, Open-Angle; Adrenergic alpha-Agonists; Quinoxalines; Ophthalmic Solutions; Glaucoma; Antihypertensive Agents
PubMed: 37061271
DOI: 10.1016/bs.podrm.2022.11.001 -
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 -
Neurobiology of Learning and Memory Dec 2020The selective norepinephrine (NE) α2A-adrenoceptor (α2A-AR) agonist, guanfacine (Intuniv™), is FDA-approved for treating Attention Deficit Hyperactivity Disorder... (Review)
Review
The selective norepinephrine (NE) α2A-adrenoceptor (α2A-AR) agonist, guanfacine (Intuniv™), is FDA-approved for treating Attention Deficit Hyperactivity Disorder (ADHD) based on research in animals, a translational success story. Guanfacine is also widely used off-label in additional mental disorders that involve impaired functioning of the prefrontal cortex (PFC), including stress-related disorders such as substance abuse, schizotypic cognitive deficits, and traumatic brain injury. The PFC subserves high order cognitive and executive functions including working memory, abstract reasoning, insight and judgment, and top-down control of attention, action and emotion. These abilities arise from PFC microcircuits with extensive recurrent excitation through NMDAR synapses. There is powerful modulation of these synapses, where cAMP-PKA opening of nearby potassium (K) channels can rapidly and dynamically alter synaptic strength to coordinate arousal state with cognitive state, e.g. to take PFC "offline" during uncontrollable stress. A variety of evidence shows that guanfacine acts within the PFC via post-synaptic α2A-AR on dendritic spines to inhibit cAMP-PKA-K channel signaling, thus strengthening network connectivity, enhancing PFC neuronal firing, and improving PFC cognitive functions. Although guanfacine's beneficial effects are present in rodent, they are especially evident in primates, where the PFC greatly expands and differentiates. In addition to therapeutic actions in PFC, stress-related disorders may also benefit from additional α2-AR actions, such as weakening plasticity in the amygdala, reducing NE release, and anti-inflammatory actions by deactivating microglia. Altogether, these NE α2-AR actions optimize top-down control by PFC networks, which may explain guanfacine's benefits in a variety of mental disorders.
Topics: Adrenergic alpha-2 Receptor Agonists; Animals; Attention Deficit Disorder with Hyperactivity; Cognition; Cognition Disorders; Guanfacine; Humans; Macaca mulatta; Memory, Short-Term; Mice; Nerve Net; Neurons; Prefrontal Cortex; Rats; Synapses
PubMed: 33075480
DOI: 10.1016/j.nlm.2020.107327 -
Molecular Medicine Reports Jul 2020Cardiac dysfunction resulting from sepsis may cause significant morbidity and mortality, and ferroptosis plays a role in this pathology. Dexmedetomidine (Dex), a...
Cardiac dysfunction resulting from sepsis may cause significant morbidity and mortality, and ferroptosis plays a role in this pathology. Dexmedetomidine (Dex), a α2‑adrenergic receptor (α2‑AR) agonist exerts cardioprotective effects against septic heart dysfunction, but the exact mechanism is unknown. In the present study, sepsis was induced by cecal ligation and puncture (CLP) in male C57BL/6 mice. Dex and yohimbine hydrochloride (YOH), an α2‑AR inhibitor, were administered before inducing CLP. Then, 24 h after CLP, serum and heart tissue were collected to detect changes of troponin‑I (TN‑I), interleukin 6 (IL‑6), superoxide dismutase (SOD), malonaldehyde (MDA) and glutathione (GSH) levels, and iron release. Ferroptosis‑targeting proteins, apoptosis and inflammatory factors were assessed by western blotting or ELISA. It was found that, 24 h after CLP, TN‑I, a biomarker of myocardial injury, was significantly increased compared with the control group. Furthermore, the levels of MDA, 8‑hydroxy‑2'‑deoxyguanosine and the inflammatory factors IL‑6 and monocyte chemoattractant protein‑1 were also significantly increased. It was demonstrated that treatment with Dex reverted or attenuated these changes (CLP + Dex vs. CLP; P<0.05), but these protective effects of Dex were reversed by YOH. Moreover, CLP significantly decreased the protein expression levels of glutathione peroxidase 4 (GPX4), SOD and GSH. However, CLP increased expression levels of heme oxygenase‑1 (HO‑1), transferrin receptor, cleaved caspase 3, inducible nitric oxide synthase and gasdermin D, and iron concentrations. It was found that Dex reversed these changes, but YOH abrogated the protective effects of Dex (CLP + Dex + YOH vs. CLP + Dex; P<0.05). Therefore, the present results suggested that the attenuation of sepsis‑induced HO‑1 overexpression and iron concentration, and the reduction of ferroptosis via enhancing GPX4, may be the major mechanisms via which Dex alleviates sepsis‑induced myocardial cellular injury.
Topics: Adrenergic alpha-2 Receptor Agonists; Animals; Dexmedetomidine; Ferroptosis; Heart; Heart Injuries; Male; Mice, Inbred C57BL; Myocardium; Sepsis
PubMed: 32377745
DOI: 10.3892/mmr.2020.11114 -
British Journal of Anaesthesia Dec 2019Dexmedetomidine (DEX) is a highly selective alpha2 adrenoceptor agonist with broad pharmacological effects, including sedation, analgesia, anxiolysis, and sympathetic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dexmedetomidine (DEX) is a highly selective alpha2 adrenoceptor agonist with broad pharmacological effects, including sedation, analgesia, anxiolysis, and sympathetic tone inhibition. Here we report a systematic review and meta-analysis of its effects on stress, inflammation, and immunity in surgical patients during the perioperative period.
METHODS
We searched MEDLINE, METSTR, Embase, and Web of Science for clinical studies or trials to analyse the effects of DEX on perioperative stress, inflammation, and immune function.
RESULTS
Sixty-seven studies (including randomised controlled trials and eight cohort studies) with 4842 patients were assessed, of which 2454 patients were in DEX groups and 2388 patients were in control (without DEX) groups. DEX infusion during the perioperative period inhibited release of epinephrine, norepinephrine, and cortisol; decreased blood glucose, interleukin (IL)-6, tumour necrosis factor-α, and C-reactive protein; and increased interleukin-10 in surgical patients. In addition, the numbers of natural killer cells, B cells, and CD4 T cells, and the ratios of CD4:CD8 and Th1:Th2 were significantly increased; CD8 T-cells were decreased in the DEX group when compared with the control group.
CONCLUSIONS
DEX, an anaesthesia adjuvant, can attenuate perioperative stress and inflammation, and protect the immune function of surgical patients, all of which may contribute to decreased postoperative complications and improved clinical outcomes.
Topics: Adrenergic alpha-2 Receptor Agonists; Dexmedetomidine; Humans; Immunity; Inflammation; Intraoperative Complications; Postoperative Complications; Preoperative Period; Stress, Physiological
PubMed: 31668347
DOI: 10.1016/j.bja.2019.07.027 -
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