Date of Award

2024

Degree Name

Pharmaceutical Sciences

College

School of Pharmacy

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Dr. Michael Hambuchen, Committee Chairperson

Second Advisor

Dr. Cynthia Jones

Third Advisor

Dr. Eric R. Blough

Abstract

Agitation is common amongst individuals who have taken methamphetamine (METH) when they arrive at the emergency room (ER). Fentanyl (FENT) and other opioids can mask this agitation which could then unexpectedly present after the reversal of these drugs by naloxone (NLX). Commonly used medications for agitation caused by METH include benzodiazepine sedatives (like alprazolam and similar drugs), but these drugs can produce dangerous sedation and inhibition of breathing when combined with opioids such as FENT. Therefore, the purpose of this MS thesis project was to use a rat model of METH-FENT overdose to test the ability of opioid antagonist NLX and d2 agonist sedative dexmedetomidine (DEXMED) which has minimal effect on breathing (even when combined with opioids) to safely and effectively inhibit the effects of both FENT and METH. Experiments tested for a reduction in agitation by measuring animal movement and safety by monitoring heart and breathing function. METHinduced locomotor activity was significantly reduced after the NLX administration at all DEXMED doses tested (p<0.05) to a level similar to rats not administered METH. Blood oxygenation was not reduced by NLX-adjunctive DEXMED in METH treated rats, but it was significantly reduced in the absence of METH. Heart rate was significantly reduced in both DEXMED treated groups, but METH partially attenuated this effect.

Subject(s)

Methamphetamine.

Fentanyl.

Opioids -- Overdose.

Naloxone.

Benzodiazepine.

Sedatives.

Stimulants.

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