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Full-Text Articles in Pharmacy and Pharmaceutical Sciences

Buprenorphine Utilization Following Removal Of Prior Authorization Requirements In The Kentucky Medicaid Population, Dustin K. Miracle, Lindsey R. Hammerslag, Svetla Slavova, Michelle R. Lofwall, Sharon L. Walsh, Jeffery Talbert, Patricia R. Freeman Jan 2026

Buprenorphine Utilization Following Removal Of Prior Authorization Requirements In The Kentucky Medicaid Population, Dustin K. Miracle, Lindsey R. Hammerslag, Svetla Slavova, Michelle R. Lofwall, Sharon L. Walsh, Jeffery Talbert, Patricia R. Freeman

Pharmacy Practice and Science Faculty Publications

Purpose: To evaluate changes in buprenorphine dispensing for treatment of opioid use disorder (OUD) among Kentucky Medicaid enrollees following the removal of prior authorization (PA) requirements for the transmucosal buprenorphine combination product.

Methods: We analyzed Kentucky Medicaid claims from 1/1/2016 through 6/30/2023 to identify enrollees with OUD during each quarter (Q1/2017–Q2/2023), using a 12-month lookback window. Segmented regression analysis was used for statistical modeling of an interrupted time series (ITS) design to assess changes in the quarterly proportion of enrollees with OUD receiving buprenorphine for OUD treatment, focusing on the effect of PA removal. The effective date of the PA …


Contemporary Trends In High-Potency P2y12 Receptor Inhibitor Use Among Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention, Ayman R. Fath, Binish Qureshi, Amro Aglan, Osamah Altaee, Hend Mansoor, Ahmed Almomani, Karim Al-Azizi, Marwan Saad, Andrew M. Goldsweig, Hani Jneid, Islam Y. Elgendy Jan 2026

Contemporary Trends In High-Potency P2y12 Receptor Inhibitor Use Among Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention, Ayman R. Fath, Binish Qureshi, Amro Aglan, Osamah Altaee, Hend Mansoor, Ahmed Almomani, Karim Al-Azizi, Marwan Saad, Andrew M. Goldsweig, Hani Jneid, Islam Y. Elgendy

Pharmacy Practice and Science Faculty Publications

Background: High‐potency P2Y12 receptor inhibitors (ticagrelor and prasugrel) reduce ischemic outcomes compared with clopidogrel among patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). This study aims to examine contemporary trends and identify predictors of their use among patients with AMI undergoing PCI in the United States.   Methods: This observational study used electronic health records from >95 US‐based health care organizations. Adults with AMI who underwent PCI between 2016 and 2023 were included. The primary outcome was the prescription of high‐potency P2Y12 receptor inhibitors versus clopidogrel. Multivariable logistic regression was used to identify independent predictors of P2Y12 inhibitor …


Contraceptive Method Provision Patterns Among Rural And Urban Kentucky Medicaid Enrollees, Dustin K. Miracle, Svetla Slavova, Jeffery Talbert, Daniela C. Moga, Patricia R. Freeman Jan 2026

Contraceptive Method Provision Patterns Among Rural And Urban Kentucky Medicaid Enrollees, Dustin K. Miracle, Svetla Slavova, Jeffery Talbert, Daniela C. Moga, Patricia R. Freeman

Pharmacy Practice and Science Faculty Publications

Purpose: To characterize contraceptive provision among the Kentucky Medicaid population and assess for rural−urban disparities.

Methods: Kentucky Medicaid claims from the calendar year 2019 were used to identify females at risk for unintended pregnancy (via a modified version of the criteria defined by the US Department of Health and Human Services Office of Population Affairs). Multinomial logistic regression was used to assess the impact of rural−urban residence on contraceptive outcomes, while adjusting for relevant covariates. Outcomes for the multinomial regression model were provision of a: (1) less effective method (i.e., condoms) or no contraceptive; (2) moderately effective method (oral, transdermal, …


The Dietary Burden Of Phosphorus And Aluminum In Ready-To-Eat Wheat Flour Tortillas Exceeds That Of Corn Tortillas: Implications For Patients With Chronic Kidney Disease, Kate Chander Chiang, Robert Yokel, Jason M. Unrine, Kamyar Kalantar-Zadeh, Ajay Gupta Jan 2026

The Dietary Burden Of Phosphorus And Aluminum In Ready-To-Eat Wheat Flour Tortillas Exceeds That Of Corn Tortillas: Implications For Patients With Chronic Kidney Disease, Kate Chander Chiang, Robert Yokel, Jason M. Unrine, Kamyar Kalantar-Zadeh, Ajay Gupta

Pharmaceutical Sciences Faculty Publications

Background: Ready-to-eat, shelf-stable tortillas contain several phosphorus- and aluminum-containing additives that may increase the risk of adverse events in patients with chronic kidney disease (CKD).

Objective: The present study aimed to measure the dietary aluminum and phosphorus burden in store-bought corn and wheat flour tortillas. Design: This cross-sectional study analyzed the elemental content of commercially available corn and wheat flour tortillas collected from 2019 to 2020.

Setting: Twenty-one elements were quantified by ICP-MS and ICP-OES from 14 corn and 13 wheat flour tortilla brands purchased from local supermarkets in Southern California in 2019–2020.

Statistical analyses performed: Multiple group comparisons were …


Altered Bile Acid Transport In Liver Disease, Sarah Cayton, Lindsay C. Czuba Jan 2026

Altered Bile Acid Transport In Liver Disease, Sarah Cayton, Lindsay C. Czuba

Pharmaceutical Sciences Faculty Publications

Background/Objectives: Bile acids, synthesized from cholesterol in the liver, are amphipathic molecules that play an integral role in lipid digestion and absorption, while also serving as systemic endocrine hormones. They continuously undergo enterohepatic circulation, where they interact with various transporter proteins. Dysregulated bile acid transport is associated with the pathogenesis of liver disease. This review summarizes the key findings relating to bile acid transport expression and activity in the pathogenesis of liver disease.

Methods: A review of the literature was performed using PubMed and relevant terms including, but not limited to, “bile acid transporters”, “liver disease”, and “bile acid uptake …


Chronic Alcohol Consumption Disrupts The Gut Microbial And Metabolic Landscapes, Madison B. Blanton, Ethan G. Napier, Katelyn E. Keen, Ethan V. Stuart, Isaac R. Cinco, Hami Hemati, Ronald C. Bruntz, Landon Wilson, Stephen Barnes, Rupak Khadka, Kathleen A. Grant, Ilhem Messaoudi Jan 2026

Chronic Alcohol Consumption Disrupts The Gut Microbial And Metabolic Landscapes, Madison B. Blanton, Ethan G. Napier, Katelyn E. Keen, Ethan V. Stuart, Isaac R. Cinco, Hami Hemati, Ronald C. Bruntz, Landon Wilson, Stephen Barnes, Rupak Khadka, Kathleen A. Grant, Ilhem Messaoudi

Pharmaceutical Sciences Faculty Publications

Introduction: Alcohol use disorder (AUD) increases incidence of infections, organ damage, and cancers. Aberrant inflammation is likely a driver of these adverse outcomes. Indeed, chronic alcohol consumption (CAC) rewires macrophages/monocytes toward a hyper-inflammatory phenotype. Prior studies showed increased gut permeability and dysbiosis. Translocation of host- and microbial-derived metabolites could trigger the hyper-inflammatory responses generated by macrophages/monocytes. However, the exact changes in these metabolites remain poorly defined due to confounders that complicate clinical studies and the differences between human and rodent gut microbiomes.

Methods: Here, we utilized a non-human primate model of ethanol self-administration to characterize alcohol-induced alterations in gut microbes …


Curriculum In Pharmacoepidemiology Training Programs: A Cross-Sectional Study To Assess Educational Needs And Alignment With Core Competencies, Amie Goodin, Deborah Layton, Ryan Chung, Vicki Osborne, Chioma Ejekam, Xiaojuan Li, Xuerong Wen, Kristian B. Filion, Luciane Cruz Lopes, Daniela C. Moga Jan 2026

Curriculum In Pharmacoepidemiology Training Programs: A Cross-Sectional Study To Assess Educational Needs And Alignment With Core Competencies, Amie Goodin, Deborah Layton, Ryan Chung, Vicki Osborne, Chioma Ejekam, Xiaojuan Li, Xuerong Wen, Kristian B. Filion, Luciane Cruz Lopes, Daniela C. Moga

Pharmacy Practice and Science Faculty Publications

Purpose: Pharmacoepidemiology is a key discipline for evidence-based decision-making, yet its educational programs have not been systematically assessed for alignment with international core competencies. Our objectives were to evaluate curricula alignment of pharmacoepidemiology training programs with ISPE-recommended core competency themes and identify key curriculum content development areas.

Methods: The ISPE Core Competencies Workgroup and ISPE leadership developed a curriculum and needs assessment survey, incorporating feedback from global members. The survey was electronically distributed to leaders of pharmacoepidemiology training programs (e.g., department chairs and program directors) using the ISPE contact database, followed by snowball sampling to enhance representation. Institutional respondent characteristics …


Comparative In Vitro Activity Of Aztreonam–Avibactam And Aztreonam Plus Ceftazidime–Avibactam Against Stenotrophomonas Maltophilia Complex, Ashlan J. Kunz Coyne, Rachel Gray, Pavani Gonnabathula, Elizabeth S. May, Pranita A. Tamma, Alex Do Jan 2026

Comparative In Vitro Activity Of Aztreonam–Avibactam And Aztreonam Plus Ceftazidime–Avibactam Against Stenotrophomonas Maltophilia Complex, Ashlan J. Kunz Coyne, Rachel Gray, Pavani Gonnabathula, Elizabeth S. May, Pranita A. Tamma, Alex Do

Pharmacy Practice and Science Faculty Publications

Members of the Stenotrophomonas maltophilia complex are intrinsically multidrug-resistant pathogens that disproportionately affect critically ill patients. Aztreonam–avibactam (ATM–AVI), FDA approved in 2025, combines aztreonam (ATM; stable to L1 β-lactamase) with avibactam (AVI; an L2 β-lactamase inhibitor). Aztreonam plus ceftazidime–avibactam (ATM–CZA) has been used as a surrogate for ATM–AVI, but direct comparisons between the two regimens are lacking. Twenty-three clinical S. maltophilia complex isolates underwent broth microdilution (BMD) testing for ATM, ceftazidime, ATM–AVI, and ATM–CZA, with gradient diffusion performed in parallel for ATM–AVI and ATM–CZA. Static 24-h time-kill assays at humanized steady-state Cmax concentrations evaluated bactericidal activity (≥3-log₁₀ reduction). Semi-mechanistic pharmacodynamic …


Social Engagement Moderates The Relationship Between Cognitive Functioning, Depressive Symptoms, And Restless Sleep In Older Black Adults, Sunkanmi Folorunsho, Olufunmilola Abraham, Darlingtina K. Esiaka Jan 2026

Social Engagement Moderates The Relationship Between Cognitive Functioning, Depressive Symptoms, And Restless Sleep In Older Black Adults, Sunkanmi Folorunsho, Olufunmilola Abraham, Darlingtina K. Esiaka

Pharmacy Practice and Science Faculty Publications

INTRODUCTION: Older Black adults face higher dementia risk, but it is unclear whether social engagement offsets the effects of depression and restless sleep.

METHODS: We analyzed 1,905 Black adults aged 50+ from the 2016-2020 Health and Retirement Study (HRS). Linear mixed-effects models tested how depressive symptoms, restless sleep, and social engagement predicted baseline cognition and cognitive decline.

RESULTS: Higher depressive symptoms and restless sleep were associated with lower baseline cognition (about 0.2 and 0.5 points lower) and faster decline (β×time ≈ −0.07 and −0.05). Greater social engagement predicted higher baseline cognition (about 0.6 points higher) and slower decline (β×time ≈ …


A Deimplementation Framework For Curricular Hoarding In Pharmacy Education, Mary E. Fredrickson, Ashleigh Barrickman, Krista L. Donohoe, Angela L. Goodhart, Caroline Lindsay Ko, Daniel R. Malcom, Frank Romanelli, Marissa C. Salvo Jan 2026

A Deimplementation Framework For Curricular Hoarding In Pharmacy Education, Mary E. Fredrickson, Ashleigh Barrickman, Krista L. Donohoe, Angela L. Goodhart, Caroline Lindsay Ko, Daniel R. Malcom, Frank Romanelli, Marissa C. Salvo

Pharmacy Practice and Science Faculty Publications

Objective: To propose a holistic approach to managing curricular transformation that addresses various curricular obligations, incorporates the emotional component of curricular overload, and utilizes deimplementation science to reframe curricular change decisions. Findings: Given the need to codify processes and interventions that continually seek to ensure curricula are modernized, contemporary, and free of outdated teaching materials, we have developed a systematic deimplementation approach to address curricular overload. Its intent is to free space for more impactful learning and practices within pharmacy curricula that can lead to measurable improvements in workload, satisfaction, and learning outcomes for both students and faculty. Summary: By …


Behavioral And Transcriptomic Markers Of Susceptibility To Escalate Fentanyl Intake, Jack V. Keady, Richard Charnigo, Jakob D. Shaykin, Emily Prantzalos, Mengfan Xia, Emily D. Denehy, Cody Bumgardner, Justin Miller, Pavel I. Ortinski, Michael Thomas Bardo, Jill R. Turner Jan 2026

Behavioral And Transcriptomic Markers Of Susceptibility To Escalate Fentanyl Intake, Jack V. Keady, Richard Charnigo, Jakob D. Shaykin, Emily Prantzalos, Mengfan Xia, Emily D. Denehy, Cody Bumgardner, Justin Miller, Pavel I. Ortinski, Michael Thomas Bardo, Jill R. Turner

Pharmacy Practice and Science Faculty Publications

The “loss of control” over drug consumption, known as escalation of intake in opioid use disorder (OUD), is well-established in preclinical rodent models. However, little is known about how antecedent behavioral characteristics, such as valuation of hedonic reinforcers prior to drug use, influence fentanyl intake trajectories. Moreover, it is unclear if distinct escalation phenotypes are driven by transcriptomic markers predictive of OUD susceptibility. Male and female Sprague-Dawley rats (n = 72) were trained in a sucrose reinforcement task using a progressive ratio schedule. Individual differences in responsivity to sucrose were hypothesized to predict escalation of fentanyl intake. Rats underwent daily …


The Immune Hangover: Understanding The Influence Of Alcohol Use, Abstinence, And Post-Abstinence Drinking On Monocyte Plasticity, Madison B. Blanton Jan 2026

The Immune Hangover: Understanding The Influence Of Alcohol Use, Abstinence, And Post-Abstinence Drinking On Monocyte Plasticity, Madison B. Blanton

Theses and Dissertations--Pharmacy

Alcohol consumption is widespread in the United States, with 80% of individuals aged 12 and older reporting alcohol use and 1-in-4 engaging in risky drinking behaviors. Alcohol misuse heightens susceptibility to infections and delays wound healing, indicating a disrupted immune system. Previous studies show alcohol rewires immune cells, especially monocytes and macrophages, which play critical roles in tissue homeostasis and host defense.

Using a rhesus macaque model of ethanol self-administration, we demonstrate that after 6-months of drinking, monocytes exhibit decreased cytokine production and significant transcriptomic changes, indicating a hypo-inflammatory state. In contrast, 12-months of chronic alcohol use induces hyperinflammatory responses, …


Metabolomics Driven Discovery Of Bioactive Natural Products Leads From Marine And Terrestrial Sources For The Development Of Analgesics, Sahar Mofidi Tabatabaei Jan 2026

Metabolomics Driven Discovery Of Bioactive Natural Products Leads From Marine And Terrestrial Sources For The Development Of Analgesics, Sahar Mofidi Tabatabaei

University of Kentucky Doctoral Dissertations

Natural products remain a rich source of structurally diverse bioactive compounds for drug discovery, particularly for pain therapeutics. However, the chemical complexity of natural product extracts presents significant challenges for the efficient identification and prioritization of bioactive metabolites. This dissertation integrates untargeted LC-MS/MS-based metabolomics, molecular networking, classical natural products chemistry, and neurobiological assays to accelerate the discovery of analgesic lead compounds targeting the emerging pain-associated receptor σ₂R/TMEM97.

An untargeted metabolomics workflow was developed to systematically profile complex biological extracts and guide bioactive compound isolation. High-resolution LC-MS/MS data were analyzed using molecular networking (GNPS/GNPS2) to visualize chemical space, dereplicate known metabolites, …


Unintentional Medication Discrepancies In Outpatient Cardiac Procedures: Identifying Modifiable Barriers, Julie M. Turner Jan 2026

Unintentional Medication Discrepancies In Outpatient Cardiac Procedures: Identifying Modifiable Barriers, Julie M. Turner

DNP Projects

Background: Medication reconciliation (MR) reduces medication errors during care transitions; however, unintentional medication discrepancies (UMDs) remain common due to variable practices and lack of standardization. Patients undergoing elective cardiac procedures are particularly vulnerable given complex medication regimens.

Purpose: This quality improvement project evaluated implementation of a Medication Reconciliation Barrier Identification Checklist (MRBIC) in the cardiac catheterization laboratory to identify patient, staff, and system-level contributors to UMDs.

Methods: A quasi-experimental pre–post design was conducted at a large academic medical center. During a six-week intervention, nurses and providers completed the MRBIC during pre-procedure MR. Barrier scores were compared with …


Implementing A Standardized App-Led Multidisciplinary Medication Review And Reconciliation To Improve Medication Safety Before Systemic Cancer Therapy: An Ambulatory Oncology Quality Improvement Initiative, Sarah R. Hines Jan 2026

Implementing A Standardized App-Led Multidisciplinary Medication Review And Reconciliation To Improve Medication Safety Before Systemic Cancer Therapy: An Ambulatory Oncology Quality Improvement Initiative, Sarah R. Hines

DNP Projects

Background

Adult patients initiating systemic cancer therapy frequently present with pre-existing polypharmacy related to chronic comorbidities and cancer-related symptom management. The addition of anticancer therapies and supportive care medications further increases medication burden and the risk of medication-related harm. Although national organizations and institutional policies recommend comprehensive medication review before treatment initiation, implementation remains inconsistent in ambulatory oncology practice.

Purpose

To implement and evaluate a standardized Advanced Practice Provider (APP)-led multidisciplinary medication review and reconciliation process designed to identify medication medication-related safety risks before initiation of systemic cancer therapy in adult oncology patients receiving care in an ambulatory infusion center. …


Antibiotic Alternatives And Next-Generation Therapeutics For Salmonella Control: A One Health Approach To Combating Antimicrobial Resistance, Mohamed Saleh, Ashutosh Verma, Khaled A. Shaaban, Yosra A. Helmy Jan 2025

Antibiotic Alternatives And Next-Generation Therapeutics For Salmonella Control: A One Health Approach To Combating Antimicrobial Resistance, Mohamed Saleh, Ashutosh Verma, Khaled A. Shaaban, Yosra A. Helmy

Veterinary Science Faculty Publications

The growing prevalence of antimicrobial resistance has significantly compromised the efficacy of conventional antibiotic-based interventions in controlling Salmonella infections across human and veterinary settings. This growing challenge necessitates a strategic rethinking of pathogen control, prompting the integration of next-generation therapeutics capable of disrupting Salmonella pathogenesis through novel, antibiotic-sparing mechanisms. In this context, a diverse array of emerging alternatives, including bacteriophages, antimicrobial peptides, probiotics, prebiotics, short-chain fatty acids, nanoparticles, and host-directed immunomodulators, have gained prominence as a promising frontier in non-antibiotic therapeutics. These modalities offer targeted approaches to inhibit Salmonella colonization, virulence expression, and persistence, while minimizing collateral damage to the …


Crystal Structures And Low-Affinity Complex Formation Of Halogenase Ctcp And Fad Reductase Ctcq From The Chlortetracycline Biosynthetic Pathway, Caixia Hou, Sylvie Garneau-Tsodikova, Oleg V. Tsodikov Jan 2025

Crystal Structures And Low-Affinity Complex Formation Of Halogenase Ctcp And Fad Reductase Ctcq From The Chlortetracycline Biosynthetic Pathway, Caixia Hou, Sylvie Garneau-Tsodikova, Oleg V. Tsodikov

Pharmaceutical Sciences Faculty Publications

Enzymatic halogenation in natural products has been intensely investigated due to its potential utility as a tool to improve pharmacological and pharmaceutical properties of drug leads. Chlortetracycline (CTC), the first tetracycline (TC) antibiotic discovered nearly eight decades ago, contains a chlorine group. This chlorine is installed enzymatically by the flavin adenine dinucleotide (FAD)-dependent halogenase CtcP. CtcP and the FAD reductase CtcQ, which is also encoded in the CTC biosynthetic gene cluster, function as a two-component system. Structural information on CtcP and CtcQ has been lacking. In this study, we determined crystal structures of CtcP from Kitasatospora aureofaciens in a complex …


Aluminum In Beverages And Foods: A Comprehensive Compilation Of Regulations; Concentrations In Raw, Prepared, And Stored Beverages And Foods; And Intake, Robert Yokel Jan 2025

Aluminum In Beverages And Foods: A Comprehensive Compilation Of Regulations; Concentrations In Raw, Prepared, And Stored Beverages And Foods; And Intake, Robert Yokel

Pharmaceutical Sciences Faculty Publications

The history and controversy concerning aluminum use in beverage and food preparation and storage are reviewed. This review on aluminum in drinking water, foods, and beverages updates and exceeds prior reviews. Country and international organization regulations that permit incorporation of aluminum containing food additives, their use limit, and purposes are presented. The aluminum concentration in beverages and foods consumed worldwide was gleaned from approximately 2100 sources available to the author. The approximately 17700 values are compiled in 175 tables by beverage or food category that include the analytical method used, sample source, and reference. The tables are posted on the …


A Cocaine Hydrolase Engineered From Human Butyrylcholinesterase As A Medical Countermeasure For Aldicarb Poisoning, Johnathan E. Lesaint, Nellore Bhanu Chandar, Annet Kyomuhangi, Huimei Wei, Fang Zheng, Chang-Guo Zhan Jan 2025

A Cocaine Hydrolase Engineered From Human Butyrylcholinesterase As A Medical Countermeasure For Aldicarb Poisoning, Johnathan E. Lesaint, Nellore Bhanu Chandar, Annet Kyomuhangi, Huimei Wei, Fang Zheng, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Publications

Aldicarb is known to be the most toxic carbamate pesticide and could be used easily by terrorists to cause a mass casualty incident. It is highly desired to discover a medical countermeasure for aldicarb poisoning. Based on structural insights from molecular modeling and in vitro experimental validation, CocH3-Fc(M3), a potent cocaine hydrolase engineered from human butyrylcholinesterase (BChE), has a ~4-fold improved binding affinity with aldicarb compared to wild-type human acetylcholinesterase (AChE) and BChE and a 9-28-fold improved bimolecular rate constant for the carbamylation with aldicarb compared to AChE. CocH3-Fc(M3) also has significant catalytic activity for aldicarb hydrolysis and, hence, is …


Development Of A Ghrelin Deacylase To Attenuate Drug Reward And Associated Effects Of Methamphetamine, Madeline J. Stewart, Huimei Wei, Nellore Bhanu Chandar, Fang Zheng, Chang-Guo Zhan Jan 2025

Development Of A Ghrelin Deacylase To Attenuate Drug Reward And Associated Effects Of Methamphetamine, Madeline J. Stewart, Huimei Wei, Nellore Bhanu Chandar, Fang Zheng, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Publications

All addictive substances directly or indirectly interact with the dopamine reward system to alter the brain’s dopamine receptor activities. It is essential for a truly effective addiction medication to attenuate substance reward and normalize the brain’s physiological functions. Conventional pharmacological intervention approaches to the treatment of substance addiction usually aim to develop and deliver a potential therapeutic agent to the brain to directly block or decrease actions of the substance or its therapeutic target in the brain. However, it is a grand challenge to attenuate the substance reward without affecting the normal physiological functions of brain receptors or transporters. Here, …


Effects Of Biased Analogues Of The Kappa Opioid Receptor Agonist, U50,488, In Preclinical Models Of Pain And Side Effects, Ross Van De Wetering, Loan Y. Vu, Lindsay D. Kornberger, Dan Luo, Brittany Scouller, Sheein Hong, Kelly F. Paton, Thomas E. Prisinzano, Bronwyn M. Kivell Jan 2025

Effects Of Biased Analogues Of The Kappa Opioid Receptor Agonist, U50,488, In Preclinical Models Of Pain And Side Effects, Ross Van De Wetering, Loan Y. Vu, Lindsay D. Kornberger, Dan Luo, Brittany Scouller, Sheein Hong, Kelly F. Paton, Thomas E. Prisinzano, Bronwyn M. Kivell

Pharmaceutical Sciences Faculty Publications

Kappa opioid receptor (KOR) agonists have well-established antinociceptive effects. However, many KOR agonists have negative side effects, which limit their therapeutic potential. Some researchers have suggested that the development of biased agonists that preferentially stimulate KOR G-protein pathways over β-arrestin pathways may yield drugs with fewer adverse side effects. This was investigated in the current study. We describe the synthesis and characterization of three U50,488 analogues, 1, 2, and 3. We evaluated the acute and chronic antinociceptive effects of these compounds in mice using the warm-water tail flick assay and in a paclitaxel-induced neuropathic pain model. Side …


Effects Of Fentanyl-Adulterated Methamphetamine On Circulating Ghrelin In Rats, Huimei Wei, Elise C. Maul, Shawn Park, Kaniz Fatema, Daniel J. Peter, Chang-Guo Zhan, Fang Zheng Jan 2025

Effects Of Fentanyl-Adulterated Methamphetamine On Circulating Ghrelin In Rats, Huimei Wei, Elise C. Maul, Shawn Park, Kaniz Fatema, Daniel J. Peter, Chang-Guo Zhan, Fang Zheng

Pharmaceutical Sciences Faculty Publications

The appetite hormone ghrelin influences biological processes that are responsible for substance use disorder, which is related to alcohol and most abused drugs including cocaine, methamphetamine, nicotine, etc. In general, upregulation of the ghrelin system enhances drug cravings and substance use. Studies reported in the literature consistently demonstrated that the ghrelin system is associated with stimulants. However, research on opioids in combination with methamphetamine has not been reported. In this study, we examined the relationship of circulating ghrelin with the polydrug use of fentanyl and methamphetamine in male Sprague-Dawley rats, demonstrating for the first time that concurrent use of fentanyl …


Effects Of Fentanyl-Laced Cocaine On Circulating Ghrelin, Insulin, And Glucose Levels In Rats, Huimei Wei, Elise C. Maul, Annet Kyomuhangi, Shawn Park, Maddilynn L. Mutchler, Chang-Guo Zhan, Fang Zheng Jan 2025

Effects Of Fentanyl-Laced Cocaine On Circulating Ghrelin, Insulin, And Glucose Levels In Rats, Huimei Wei, Elise C. Maul, Annet Kyomuhangi, Shawn Park, Maddilynn L. Mutchler, Chang-Guo Zhan, Fang Zheng

Pharmaceutical Sciences Faculty Publications

Opioid mixed with cocaine has been increasingly implicated in overdose deaths, including both intentional co-use of opioid and cocaine and fentanyl-adulterated drug supply. As ghrelin plays an important role in drug reward and can also influence insulin, this study aimed to assess responses of the circulating ghrelin, insulin, and glucose levels to the combined use of fentanyl and cocaine (a polydrug) in rats by performing combined animal behavioral experiments and biochemical analysis. The experimental data consistently revealed that the fentanyl and cocaine co-use can significantly elevate both the acyl-ghrelin and desacyl-ghrelin levels and significantly decrease the insulin level without significant …


Fluorescence-Guided Resection Of Gl261 Red-Fluc And Trp-Mcherry-Fluc Mouse Glioblastoma Tumors, Louis T. Rodgers, Bryan J. Maloney, Anika M. S. Hartz, Björn Bauer Jan 2025

Fluorescence-Guided Resection Of Gl261 Red-Fluc And Trp-Mcherry-Fluc Mouse Glioblastoma Tumors, Louis T. Rodgers, Bryan J. Maloney, Anika M. S. Hartz, Björn Bauer

Pharmaceutical Sciences Faculty Publications

Background: Most preclinical studies on glioblastoma (GBM) fail to provide translational utility in the clinic. Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) improves tumor resection, disease prognosis, and, thus, patient outcomes. Given the critical role of surgery in managing recurrent GBM, it is essential to incorporate surgical elements into preclinical models to accurately reflect clinical scenarios and enhance translational success. However, existing protocols for 5-ALA-guided resection in preclinical models are limited and often lack clinical relevance.

Methods: To address this gap, we developed a novel protocol for the 5-ALA-guided resection in two mouse GBM models: TRP-mCherry-FLuc and GL261 Red-FLuc.

Results: The …


Development Of Zafirlukast Analogues For Improved Antithrombotic Activity Through Thiol Isomerase Inhibition, Justine A. Keovilay, Kaitlind C. Howard, Kirk A. Taylor, Sabeeya Khan, Sienna E. Wurl, Melanie K. Szahaj, Tanya Sage, Nishad Thamban Chandrika, Caixia Hou, Oleg V. Tsodikov, Jonathan M. Gibbins, Sylvie Garneau-Tsodikova, Daniel R. Kennedy Jan 2025

Development Of Zafirlukast Analogues For Improved Antithrombotic Activity Through Thiol Isomerase Inhibition, Justine A. Keovilay, Kaitlind C. Howard, Kirk A. Taylor, Sabeeya Khan, Sienna E. Wurl, Melanie K. Szahaj, Tanya Sage, Nishad Thamban Chandrika, Caixia Hou, Oleg V. Tsodikov, Jonathan M. Gibbins, Sylvie Garneau-Tsodikova, Daniel R. Kennedy

Pharmaceutical Sciences Faculty Publications

Background:   Thiol isomerases play essential and nonredundant roles in platelet activation, aggregation, and thrombus formation. Thiol isomerase inhibitors have the potential to overcome the 2 major drawbacks of current antithrombotic therapies, as they target both arterial and venous thrombosis without enhancing bleeding risks. Recently, a Food and Drug Administration–approved drug, zafirlukast (ZAF), was shown to be a promising pan-thiol isomerase inhibitor. The objective of this study is to develop analogues of ZAF with optimized thiol isomerase inhibition and antithrombotic activity.   Methods:   Thirty-five ZAF analogues were tested in an insulin turbidometric assay for thiol isomerase inhibition. Analogues were tested for platelet …


Functional And Structural Studies On The Esperamicin Thioesterase And Progress Toward Understanding Enediyne Core Biosynthesis, Erome D. Hankore, Mitchell D. Miller, Abigael J. Kosgei, Weijun Xu, Kemin Tan, Michael Endres, Minakshi Bhardwaj, Grazyna Joachimiak, Andrzej Joachimiak, George N. Phillips Jr., Jon S. Thorson, Steven G. Van Lanen Jan 2025

Functional And Structural Studies On The Esperamicin Thioesterase And Progress Toward Understanding Enediyne Core Biosynthesis, Erome D. Hankore, Mitchell D. Miller, Abigael J. Kosgei, Weijun Xu, Kemin Tan, Michael Endres, Minakshi Bhardwaj, Grazyna Joachimiak, Andrzej Joachimiak, George N. Phillips Jr., Jon S. Thorson, Steven G. Van Lanen

Pharmaceutical Sciences Faculty Publications

Enediynes are among the most potent antitumor and antibacterial natural products. Studies on their biosynthetic pathways have identified a shared, linear polyene precursor generated from an iterative type I polyketide synthase (PKSE) as the source of the enediyne warhead. A key step is the release of this polyene from the PKSE by a discrete thioesterase (TE). Here, we used X-ray crystallography, site-directed mutagenesis, and heterologous coexpression of PKSEs and TEs to elucidate how enediyne TEs mediate the production of the polyene. We solved the structure of wild-type EspE7 from esperamicin producer Actinomodura verrucosospora. The substrate binding pocket was also …


Residual Next-Day Effects Of Alprazolam On Psychomotor Performance And Simulated Driving In Healthy Normal Adults, Stevie C. Roszkowski, Shanna Babalonis, Marion A. Coe, Paul Nuzzo, Michelle R. Lofwall, Laura C. Fanucchi, Sharon L. Walsh Jan 2025

Residual Next-Day Effects Of Alprazolam On Psychomotor Performance And Simulated Driving In Healthy Normal Adults, Stevie C. Roszkowski, Shanna Babalonis, Marion A. Coe, Paul Nuzzo, Michelle R. Lofwall, Laura C. Fanucchi, Sharon L. Walsh

Center on Drug and Alcohol Research Faculty Publications

The prevalence of drugged driving has increased in the United States. Some drugged driving may be unintentional as prescription medications used as sleeping aids, like zolpidem, cause impairment after the predicted duration of therapeutic action has elapsed. The aim of this study was to determine if nighttime administration of alprazolam, a drug commonly prescribed off-label as a sleeping aid, impacts driving performance the following day. Participants were healthy adults (n = 15) who completed a double-blind, double-dummy, within-subjects inpatient study examining the effects of nighttime administration of alprazolam (0.5, 1, and 2 mg), zolpidem (10 mg), and placebo on driving …


Adolescents’ And Parents’ Perspectives On Using The Medsmarxt Families Intervention In Emergency Departments For Opioid Medication Safety Education: Mixed Methods Study, Olufunmilola Abraham, Sara Nadi, Irene Hurst Jan 2025

Adolescents’ And Parents’ Perspectives On Using The Medsmarxt Families Intervention In Emergency Departments For Opioid Medication Safety Education: Mixed Methods Study, Olufunmilola Abraham, Sara Nadi, Irene Hurst

Pharmacy Practice and Science Faculty Publications

Background: The opioid crisis has significantly impacted adolescents and their families. This is attributed in part to increased opioid prescriptions in pediatric emergency departments (EDs) due to acute pain conditions and injuries. Although EDs frequently prescribe opioids, no effective preventative interventions have been implemented to educate adolescents and their families on safe opioid use. This study evaluates the MedSMA℞T Families intervention, which consists of an engaging serious game, Adventures in PharmaCity, and a personalized Family Medication Safety Plan (FMSP) with the aim of reducing opioid misuse and promoting opioid medication safety. The MedSMA℞T Families intervention was developed to educate adolescents …


Barriers To And Facilitators Of Buprenorphine Dispensing For Opioid Use Disorder: Evidence From Focus Groups In Appalachian Kentucky, Douglas R. Oyler, Dustin K. Miracle, Hannah Hesener, Laura Stinson, Monica Roberts, Adrienne Matson, Patricia R. Freeman Jan 2025

Barriers To And Facilitators Of Buprenorphine Dispensing For Opioid Use Disorder: Evidence From Focus Groups In Appalachian Kentucky, Douglas R. Oyler, Dustin K. Miracle, Hannah Hesener, Laura Stinson, Monica Roberts, Adrienne Matson, Patricia R. Freeman

Pharmacy Practice and Science Faculty Publications

Background: As efforts to increase buprenorphine prescribing continue to intensify, pharmacy dispensing plays an important role in access to essential medications for opioid use disorder. Existing survey research suggests stigma and regulatory concerns are barriers to pharmacists dispensing buprenorphine, but facilitators are less clear, as are in-depth perceptions of pharmacists regarding buprenorphine.

Objective: To assess barriers and facilitators to buprenorphine dispensing in Appalachian Kentucky using a series of focus groups with pharmacy employees.

Methods: Between September and October 2023, 5 structured focus groups were conducted with a total of 19 pharmacists and pharmacy technicians across a mixture of high- and …


Understanding The Impact Of Pharmacist Prescriptive Authority On Hiv Pre-Exposure Prophylaxis At The State Level, Cameron G. King Jan 2025

Understanding The Impact Of Pharmacist Prescriptive Authority On Hiv Pre-Exposure Prophylaxis At The State Level, Cameron G. King

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

HIV transmission, with relative risk reductions of up to 99%. However, real world data have revealed that even with large increases in PrEP use, new HIV diagnoses may only slightly decline. This disparity suggests that access to PrEP may be suboptimal, especially among high-risk subgroups, who are often hard to maintain on the continuum of HIV care. Pharmacists, because of their accessibility, trusted role in their communities, and growing scope of practice, could serve as an intervention point to improve access to PrEP.

A previously validated algorithm using National Drug Codes (NDCs) and the International Classification of Disease, 10th …