2026-10-12T09:36:42Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33872800 2026-09-17T07:11:04Z category_19 portal_316 item_type_3 month_year_09_2026

Supplementary file 2_The effects of fentanyl and dexmedetomidine on cardiorespiratory activity: implications for morbidity and mortality associated with adulterated fentanyl products.pdf Mark A. Smith (21079) Emma M. Thomas (25002613) Stephanie G. Hockett (25002616) Kirsten J. Folger (25002619) Pharmacology alpha-2 adrenergic agonist cardiorespiratory toxicity fentanyl medetomidine opioid overdose respiratory depression Introduction<p>A recent driver of opioid-related overdose deaths has been the adulteration of illicitly manufactured fentanyl with alpha-2 (α₂)-adrenergic agonists; however, little research has examined their toxicity when combined with fentanyl. The purpose of this study was to examine the effects of fentanyl and the α₂-adrenergic agonist, dexmedetomidine, on cardiorespiratory measures that may contribute to the toxicity of these drug combinations (i.e., respiratory rate, heart rate, oxygen (O₂) saturation, and pulse distention).</p>Methods<p>Male and female rats were administered fentanyl (0.01–0.1 mg/kg) and dexmedetomidine (0.003–0.01 mg/kg) intravenously, and pulse oximetry was used to measure respiratory and cardiovascular activity.</p>Results<p>When administered alone, both drugs decreased respiratory rate and heart rate relative to baseline, albeit with different time courses. Fentanyl, but not dexmedetomidine, decreased O₂ saturation. Dexmedetomidine enhanced the suppression of respiratory rate and heart rate produced by fentanyl in a time-dependent manner. The effects of the drug combination on O₂ saturation and pulse distention were less consistent. Although not a primary endpoint, mortality occurred in 3 of 16 rats after the high-dose drug combination, suggesting that increases in lethality can be observed in the absence of explicit pharmacological synergy.</p>Discussion<p>These data indicate that dexmedetomidine exacerbates the cardiorespiratory effects of fentanyl in a manner that may contribute to the morbidity and mortality associated with α₂-adrenergic adulteration of illicitly manufactured fentanyl.</p> 2026-09-17T07:11:04Z Dataset Dataset 10.3389/fphar.2026.1885956.s007 https://figshare.com/articles/dataset/Supplementary_file_2_The_effects_of_fentanyl_and_dexmedetomidine_on_cardiorespiratory_activity_implications_for_morbidity_and_mortality_associated_with_adulterated_fentanyl_products_pdf/33872800 CC BY 4.0