Date of Award

2025

Degree Name

Pharmaceutical Sciences

College

School of Pharmacy

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Dr. Michael Hambuchen

Second Advisor

Dr. Cynthia B. Jones

Third Advisor

Dr. Eric R. Blough

Abstract

XYL is becoming more prevalent in opioid intoxication, which not only exacerbates the overdose impact by intensifying the drowsiness and respiratory depression caused by FENT but also increases other toxicities such as cardiovascular and thermoregulatory function. Coexposure to FENT and XYL can have enhanced detrimental effects on human health. In mice, XYL enhances the likelihood of death from FENT exposure. Clinical findings are conflicting as one retrospective study found that patients exposed to both drugs had lower rates of cardiac arrest and coma, but other studies indicate that using XYL together increases the risk of overdose, naloxone administration, and blood levels of Fentanyl. This study examined the effects of α2 antagonist ATI in combination with NLX in reversing XYL-FENT-induced sedation while NLX alone can only partially counteract this effect by targeting on FENT alone. ATI also lessened bradycardia and hyperglycemia, two further consequences of FENT-XYL intoxication and ATI also helped reverse the hypothermia caused by XYL to some extent. This evidence supports the use of the ATI-NLX combination as a safe and effective treatment for FENT and XYL intoxication concurrently.

Subject(s)

Fentanyl.

Xylazine.

Opioids.

Naloxone.

Intoxication.

Available for download on Sunday, May 02, 2027

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