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Toward Developing Alternative Opioid Antagonists for Treating Community Overdose: A Model-Based Evaluation of Important Pharmacological Attributes.
Clin Pharmacol Ther
January 2025
Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food & Drug Administration, Silver Spring, Maryland, USA.
In response to increased illicit use of synthetic opioids, various μ-receptor antagonist formulations, with varied pharmacological characteristics, have been and are being developed. To understand how pharmacologic characteristics such as absorption rate and clearance rate affect reversal in treating community opioid overdose, we used our previously published translational opioid model. We adapted this model with in vitro receptor binding data and clinical pharmacokinetic data of three intranasal nalmefene formulations along with an intranasal naloxone formulation to study the reversal of fentanyl and carfentanil-induced respiratory depression in chronic opioid users.
View Article and Find Full Text PDFRemote Ischemic Preconditioning Attenuates Ischemia-Reperfusion Injury Induced Reductions in Vascular Function through Release of Endogenous Opioids.
J Appl Physiol (1985)
January 2025
Department of Kinesiology, Health Promotion and Recreation, University of North Texas, Denton, Texas, USA.
Remote Ischemic Preconditioning (RIPC) is a therapy characterized by repeated bouts of limb ischemia and reperfusion. RIPC protects against ischemia-reperfusion injury (IRI), and preclinical studies suggest that this is mediated through release of endogenous opioids. We aimed to interrogate the role of endogenous opioids in RIPC-signaling in humans, using an arm model of IRI.
View Article and Find Full Text PDFManaging xylazine-involved overdoses in a community harm reduction setting: lessons from Tijuana, Mexico.
Harm Reduct J
January 2025
Asociación Bajacaliforniana de Salud Pública A.C, Tijuana, Baja California, Mexico.
Background: Xylazine is a α2-adrenergic receptor agonist, used for sedation in veterinary contexts. Although it is increasingly found in overdose deaths across North America, the clinical management of xylazine-involved overdoses has not been extensively studied, especially in community-based harm reduction settings. Here we present a clinical series of xylazine-involved overdose and share the clinical approach and lessons learned by a community overdose response team in Tijuana, Mexico amidst the arrival of xylazine.
View Article and Find Full Text PDFEffect of a best practice advisory activated "kit in hand" naloxone distribution program in the emergency department.
Am J Emerg Med
November 2024
Departments of Emergency Medicine and Environmental Medicine, University of Rochester Medical Center, Rochester, NY, United States of America.
Purpose: We implemented a "kit in hand" naloxone distribution program at emergency department (ED) discharge activated by electronic health record Best Practice Advisory (BPA). The purpose of this study was to evaluate naloxone kit distribution before and after implementation.
Methods: Retrospective observational study of adult ED patients with unintentional opioid overdose conducted over a six-month period.
Leveraging Implementation Factors and Policy to Improve the Effectiveness of Naloxone.
J Addict Med
November 2024
From the New York State Office of Addiction Services and Supports, New York, NY.
More than 50 years of high-quality data demonstrate that naloxone is an efficacious and cost-effective overdose reversal agent. Intranasal naloxone is now available in the United States as an over-the-counter and generic medication for the first time since the start of the overdose crisis more than 20 years ago. As the overdose crisis continues to contribute to substantial loss of life, there is an historic opportunity for jurisdictions to expand equitable and sustained access to intranasal naloxone.
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