Pharmacology Commons^™

Misused And Misunderstood: Examining The Inappropriate Use Of Stimulant Medications, Connor Dains, Madilyn Paphanchith, Makayla Eversole, Chaehyeon Jin, Minhwan Yang, Joshua Honaker, Samantha Mccord, Kayla Petkus

Pharmacy and Wellness Review

Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in children, characterized by inattention, hyperactivity, and impulsivity. The American Academy of Pediatrics (AAP) endorses stimulant medications as the first-line treatment option. When combined with behavioral therapy, this pharmacologic class can improve focus, executive functioning, and the overall quality of life. While stimulant prescriptions can have a positive effect when used as directed, there is concern for the potential of provider overprescription and patient misuse related to these medications. Consequently, the Food and Drug Administration (FDA) revised the boxed warning and prescribing information for stimulant medications. Healthcare providers must educate …

Variability In Methotrexate Metabolites In A Cohort Of Jia Patients, Nuria Lara Castillo, Mara Becker, Marc Sudman, Susan Thompson, Laura Ramsey

Research Days

Background: Methotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug for the treatment of Juvenile Idiopathic Arthritis (JIA). While most patients receiving MTX have a favorable outcome, approximately 30% do not respond, and several experience toxic events, suggesting interindividual difference. Furthermore, evaluation of MTX response takes several months, with the risk of missing the early “window of opportunity” for treatment. Predicting MTX response prior to administration would greatly benefit these patients and their treating physicians by saving valuable time during the early stages of the disease onset. MTX is a folate antagonist and, similar to folate, it undergoes polyglutamation inside the …

Fc Gamma Receptors Facilitate Antigenic Modulation Of Lilrb4 And Function As Predictive Biomarkers In Acute Monocytic Leukemia, Joshua Morse

Dissertations and Theses (Open Access)

Acute monocytic leukemia (monocytic AML) is a subtype of AML marked by a proliferation of abnormal monoblasts. This subtype represents approximately 10% of AML cases. The prognosis of monocytic AML is poor, with a 5-year survival of ~30%. Most patients are diagnosed at an age when they are unlikely to survive first-line non-targeted cytotoxic chemotherapy as a bridge to hematopoietic stem cell transplant (HSCT). Even patients who achieve remission commonly relapse. This population of patients would greatly benefit from precision-targeted therapies but currently there are none approved for monocytic AML.

Leukocyte immunoglobulin-like receptor B4 (LILRB4) is an immune checkpoint expressed …

Investigating Prefrontal Cortex Neuronal Signatures Of Opioid-Induced Risk-Taking Behavior, Cana Quave

Dissertations and Theses (Open Access)

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed an approach-avoidance conflict task using a modified conditioned place preference procedure to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision-making. Following morphine conditioned place preference, rats underwent a conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline-exposed control group avoided cat odor, the morphine group included two subsets of rats that either maintained a preference for the paired side despite the presence of …

Investigating The Role Of The Hypocretin/Orexin System In A Novel Model Of Polysubstance Dependence, Tyler Zarin

Electronic Theses and Dissertations

Substance use disorders (SUD) in the United States are steadily increasing. Potent and dangerous substances such as methamphetamine (MA) and fentanyl (FEN) are often co-used as a polysubstance (POLY), either intentionally or unknowingly as FEN is a common adulterant. SUD is characterized by physiological and psychological dependence involving the negative reinforcement of anhedonia and withdrawal which drive hypermotivated drug-taking behaviors. Current theory suggests that recruitment of hypocretin/orexin (HCRT) neuropeptide in reward and stress associated brain regions contributes to drug dependence. Despite strong evidence for HCRT’s role in mono-drug dependence, a relevant model for POLY dependence has yet to be developed, …

Assessing The Behavioral Impact Of Pyridostigmine Bromide In Rats, Noah A. Martin

Honors Theses

Pyridostigmine bromide (PB) is an organophosphate (OP) nerve agent prophylactic used to protect warfighters against chemical warfare agents. OPs inhibit the neural enzyme acetylcholinesterase (AChE) in the brain. This leads to the buildup of acetylcholine, causing respiratory failure, seizures, and death. PB functions by inhibiting ~30% of peripheral AChE temporarily, protecting the enzymes so that the body is able to restore sufficient cholinergic function post-exposure. PB does not cross the blood-brain barrier, though it may still indirectly affect toxicity in the brain due to repeated AChE inhibition throughout treatment, or by inhibition of non-target ChE’s in the blood. The aim …

5-Ht Receptors: Pharmacology And Functional Selectivity, Benjamin R. Cummins, Gerald B. Billac, David E. Nichols, Charles D. Nichols

School of Medicine Faculty Publications

Serotonin 5-HT receptors were one of the first serotonin receptors to be pharmacologically characterized. In mammals, they are expressed throughout the body in nearly every cell and tissue type, with the highest density in cortical layer V of the brain. They are involved in several aspects of normal physiological processes and behaviors and have been implicated in the etiology of neuropsychiatric diseases such as schizophrenia. Atypical antipsychotics have targeted blockade of 5-HT receptors as part of their therapeutic mechanism. More recently, 5-HT receptors have come to prominence for their role as the primary target for psychedelic drugs, which activate this …

Psilocybin Impairs The Extinction Of Contextual Fear In Adult Female, But Not Male, Rats, Lillianna P. Puppel, Aleece K. Al-Olimat, Kylie M. King, Marisa J. Savini, Claire E. Miller, Colin R. Del Valle, Heather R. Sparkman, Brooke E. Bramlage, Phillip R. Zoladz

ONU Student Research Colloquium

Fear-related disorders are often treated with exposure therapy, a technique based on the concept of extinction. However, this type of therapy is ineffective for many individuals, so finding a pharmacological adjunct that augments the extinction of fear could lead to better treatment outcomes. In recent preclinical work, investigators have shown that psychedelics can accelerate the extinction of fear, potentially through their impact on neurotrophic signaling. We previously found that psilocybin exerted sex-dependent effects on the extinction of conditioned fear to an isolated cue (i.e., a tone). Specifically, psilocybin enhanced the extinction of cue fear in male rats but impaired it …

Enhancing Topical Drug Delivery Of Apremilast Through Niosomal Gel Formulation: Ex Vivo Skin Permeation And In Vivo Evaluation For Psoriasis, Megha Shyam Matlapudi, Anka Rao Areti, Yukti Jaiswal, Veeresh Bantal, Raghavender Medishetti

The Thai Journal of Pharmaceutical Sciences

Background: Psoriasis is a dynamic and chronic disease characterized by inflammatory changes and an increased rate of keratinocyte proliferation leading to the formation of erythematous scleroderma plaques with a silvery sheen. The existing therapies come with shortcomings in terms of effectiveness and leave behind a trail of side effects. Hence, there is a need of alternative therapeutic measures. Objectives: This study aimed to assess the therapeutic potential of Apremilast Niosomal Gel (APR Nio Gel) in treating psoriasis, comparing its effectiveness with conventional gel (APR Gel) and oral suspension (APR Oral) formulations. Materials and Methods: Apremilast niosomes were prepared by thin …

Editorial: Old Drugs: Confronting Recent Advancements And Challenges, Anna Wiktorowska-Owczarek, Diego Iacono, Magdalena Jasińska-Stroschein

Department of Neurology Faculty Papers

No abstract provided.

Putting The Substance In Substantial Evidence: An Evidence-Based Approach To Flexible Drug Regulation, Emanuel Krebs, Tania M. Bubela, Melanie Mcphail, Christopher Mccabe, Dean A. Regier

Office of the Provost

For new drugs or indications, substantial evidence of clinical effectiveness is required for market authorization. In most jurisdictions, substantial evidence is not explicitly defined. Health regulators exercise discretion and are increasingly tolerant of earlier or less mature evidence. To align with flexible evidentiary standards, we argue for the adoption of a principle and, context-based approach to the evidence threshold. Our approach aims to balance the potential benefits and harms of accelerated authorization, low therapeutic value, and safety, based on a value of information (VoI) framework. In our VoI framework, substantial evidence exists when the expected net health value of further …

Overexpression And Biophysical And Functional Characterization Of A Recombinant Fgf21, Phuc Phan, Jason Hoang, Thallapuranam Krishnaswamy Suresh Kumar

Chemistry & Biochemistry Faculty Publications and Presentations

Fibroblast growth factor 21 (FGF21) is an endocrine FGF that plays a vital role in regulating essential metabolic pathways. FGF21 increases glucose uptake by cells, promotes fatty acid oxidation, reduces blood glucose levels, and alleviates metabolic diseases. However, detailed studies on its stability and biophysical characteristics have not been reported. Herein, we present the overexpression, biophysical characterization, and metabolic activity of a soluble recombinant FGF21 (rFGF21). The far-UV circular dichroism spectra of rFGF21 show a negative trough at 215 nm, indicating that the protein’s backbone predominantly adopts a β sheet conformation. rFGF21 shows intrinsic tyrosine fluorescence at 305 nm. Thermal …

Pharmacodynamics Of Aspirin Through Gestation: Predictors Of Aspirin Response And Association With Pregnancy Outcome, A Prospective Cohort Study, Rupsa C. Boelig, Emily Foecke Munden, Tingting Zhan, Steven E. Mckenzie, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Low-dose aspirin is recommended for prevention of hypertensive disorders of pregnancy (HDP) and preterm birth (PTB) in high-risk pregnancies. There is limited data on factors impacting aspirin response in pregnancy. We aimed to evaluate predictors of aspirin response and association with pregnancy outcome with a prospective study of high-risk pregnancies taking 81 mg aspirin daily. Aspirin response was evaluated with Platelet Function Assay-100 (PFA-100) epinephrine closure time at baseline (< 16 weeks' gestation), follow-up 1 (2-4 weeks after aspirin initiation), and follow-up 2 (28-32 weeks gestation). Multivariable regression was used to identify factors associated with PFA-100 at each visit, and results presented with beta coefficient (B) and confidence interval. The median difference (MD) in PFA-100 in those with and without HDP or PTB was compared. Results included 108 who completed follow-up 1 and 96 who completed both visits with > 75% adherence. PFA-100 was increased from baseline at follow-ups 1 and 2 (MD 37 (27-49); MD 26 (15.5-38.5) respectively). At follow-up 1, obesity (B = -30 (-53 to -7) seconds), …

Antiseizure Medications And Their Differing Effects On Cardiovascular Risk, Aleena Abbasi, Bassil Abbasi, Scott Mintzer, Carla Lopinto-Khoury

Department of Neurology Faculty Papers

This review discusses the differing effects of enzyme-inducing and non-inducing antiseizure medications on cardiovascular risk and their implications for the management strategies of epilepsy patients. Traditional risk markers, including low density lipoprotein, high density lipoprotein and triglycerides, can be altered by both enzyme induction and inhibition. Other markers of vascular risk, including c-reactive protein, non-high-density lipoprotein and homocysteine, are affected by antiseizure medications, although adults and children may have different responses. The overall atherosclerotic risk picture is more complex due to indirect effects such as neuroendocrine function and the metabolic syndrome. Large scale data shows an evolving understanding of cardiovascular …

Pulmonopoly: A Game-Based Approach To Teach And Reinforce Basic Concepts Of Pulmonary Medicine To Medical Students, Michael Dong, James Uricheck, Urvashi Vaid

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

INTRODUCTION: Pulmonopoly is an innovative active-learning medical board game addressses core pulmonary concepts in an engaging, competitive style. The strength of Pulmonopoly lies in its ability to combine ease of setup and play with comprehensive content coverage that comprises a significant proportion of national board examinations, offering a gamification experience that can be readily applied in different settings and modified for learner levels.

METHODS: We created an instructional game, Pulmonopoly, based on pulmonary content delivered to preclinical medical students and required for national board examinations. We invited first-year medical students to participate in 60-minute small-group sessions. Content addressed pulmonary subject …

Retrospective Analysis Of Angiotensin Receptor Blockers And Knee Cartilage Volume In Osteoarthritis: Evidence From The Osteoarthritis Initiative, Parv Kale, Vijay Kale

Annual Research Symposium

No abstract provided.

Bayesian Population Pharmacokinetic Modeling Of Ondansetron For Neonatal Opioid Withdrawal Syndrome, Kevin Lam, John Mondick, Gary Peltz, Manhong Wu, Walter Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Ondansetron is an anti-emetic 5-HT3 receptor antagonist being investigated for treating neonatal opioid withdrawal syndrome (NOWS). Sparse PK data were analyzed from a multicenter, double-blind clinical trial with 98 mother/neonate dyads. Pregnant women with opioid use disorder were randomized to receive either placebo or ondansetron 8 mg intravenously within 4 h of delivery. Neonates born to mothers who were randomized to ondansetron received 0.07 mg/kg orally once every 24 h for up to five doses. Using current PK data, model parameters from a two-compartmental structural model from the literature (i.e., a priori model) were updated with the Metropolis-Hastings Markov-chain Monte …

Metformin In Overcoming Enzalutamide Resistance In Castration-Resistant Prostate Cancer, Kendall Simpson, Derek B. Allison, Daheng He, Jinpeng Liu, Chi Wang, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Androgen deprivation is the standard treatment for patients with prostate cancer. However, the disease eventually progresses as castration-resistant prostate cancer (CRPC). Enzalutamide, an androgen receptor inhibitor, is a typical drug for treating CRPC and with continuous reliance on the drug, can lead to enzalutamide resistance. This highlights the necessity for developing novel therapeutic targets to combat the gain of resistance. Metformin has been recently investigated for its potential antitumorigenic effects in many cancer types. In this study, we used enzalutamide and metformin in combination to explore the possible rescued efficacy of enzalutamide in the treatment of enzalutamide-resistant CRPC. We first …

Investigating The Role Of Dynamic Signaling Of Nrg3-Erbb4 In The Prefrontal Cortex In Mediating Nicotine Withdrawal Phenotypes, Emily Prantzalos

Theses and Dissertations--Pharmacy

While several pharmacotherapies are currently available for nicotine use disorder (NUD), smoking cessation success rates remain below 10% each year. The molecular mechanisms underlying failed quit attempts continue to represent a critical gap in our knowledge. However, recent advances in understanding the genetic contributions to nicotine dependence offer a promising avenue for developing more effective cessation therapies. Prior research has identified genetic variation in Neuregulin 3 (Nrg3) and its cognate receptor ErbB4 as potential contributors to affective nicotine withdrawal (WD) phenotypes and cessation outcomes. Therefore, this dissertation aims to systematically investigate the region-specific, functional role of the Neuregulin Signaling Pathway …

Impact Of Tetrahydrocannabinol (Thc) On Daphnia Magna Heart Rate, Ashley Cosgrave

Williams Honors College, Honors Research Projects

Marijuana (Cannabis) is currently federally illegal within the United States and classified as a Schedule I drug. This leaves a large research gap on the impacts of Tetrahydrocannabinol (THC) use. Daphnia magna are frequently used as a model organism for the human heart and toxicology screenings due to their myogenic heart, similarities in physiological pathways, and sensitivity to toxins. As such, in order to bridge the research gap and uncover potential use of Daphnia magna as a model organism for humans in regard to impact on heart rate, we hypothesized that if Daphnia magna possess CB1 receptors or an equivalent …

Scopolamine-Induced Modulation Of Serotonin And Dopamine Transporters Activity: Behavioral And Molecular Insights Into Rapid Antidepressant Action, Deepak Karunakaran

Theses and Dissertations

Major depressive disorder (MDD) affects over 350 million individuals worldwide and is characterized by profound dysregulation of serotonin (5-HT) and dopamine (DA) systems that govern mood, reward processing, and motivation. The serotonin transporter (SERT) and dopamine transporter (DAT), both dynamically regulated through phosphorylation, serve as critical determinants of synaptic monoamine signaling. Despite decades of therapeutic development, current antidepressants require 4-6 weeks to achieve efficacy, and approximately one-third to half of patients develop treatment-resistant depression. The emergence of rapid-acting antidepressants like ketamine represents a paradigmatic shift, demonstrating symptom relief within hours; however, ketamine's therapeutic potential remains constrained by abuse liability, dissociative …

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …

The Effects Of Plx 3397 On Fentanyl Escalation In Male And Female Sprague-Dawley Rats, Jakob Shaykin

Theses and Dissertations--Psychology

Purpose: A hallmark characteristic of opioid use disorder (OUD) is a persons’ ‘loss of control’, which leads to the compulsion to seek and obtain opioids, resulting in increased consumption. This phenomenon is known as ‘escalation of drug intake’. Chronic opioid use causes microglial reactivity and subsequent release of proinflammatory cytokines leading to neuroinflammation, weakening one’s executive control over drug taking and ultimately leading to greater use. Previous research in our laboratory has explored heterogeneity of fentanyl intake in extended access (6-hr) sessions and identified distinct endophenotypes of fentanyl intake. Moreover, we have observed a positive correlation between Treml1 expression …

Ccr5-Ligand Decorated Rilpivirine Lipid-Based Nanoparticles For Sustained Antiretroviral Responses, Milankumar Patel

Theses & Dissertations

Antiretroviral therapy (ART) is the standard remedy to improve the health-related quality of life of people living with human immunodeficiency virus (HIV). However, limited access to the viral reservoir has significantly hindered its effectiveness in fully eradicating HIV. Therefore, to improve HIV therapy, here we propose a C-C chemokine receptor type 5 (CCR5)-targeted theranostic lipid Based Nanoparticles (LBNPs) to noninvasively track and specifically deliver the antiretroviral drugs (ARVs) to the viral reservoir. A multi-modular radioactive nanoprobe was synthesized and co-encapsulated with rilpivirine (RPV, an ARV) into the LBNP to achieve a theranostic LBNP that can be tracked by positron emission …

Pediatric Flecainide Pharmacogenomics: A Roadmap To Delivering Precision-Based Care To Pediatrics Arrhythmias., Ronald Palmen, Mollie Walton, Jonathan B. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Flecainide acetate is a Class 1c anti-arrhythmic with a potent sodium voltage gated channel blockade which is utilized for the second-line treatment of tachyarrhythmias in children and adults. Given its narrow therapeutic index, the individualization of drug therapy is of utmost importance for clinicians. Despite efforts to improve anti-arrhythmic drug therapy, there remain knowledge gaps regarding the impact of variation in the genes relevant to flecainide's disposition and response. This variability is compounded in developing children whose drug disposition and response pathways may remain immature. The purpose of this comprehensive review is to outline flecainide's disposition and response pathways while …

Population-Based Cross-Sectional Analysis Of Cannabis Use Among Kentucky Adults, 2020– 21, Sydney Shafer, Gunnar Kennedy, W. Jay Christian

UK CARES Faculty Publications

Purpose We conducted this study to assess cannabis use rates in the state of Kentucky relative to socioeconomic, demographic, and geographic factors, as well as reasons for use and modes of use, before the legal medical marijuana market commences in 2025.

Methods We pooled Kentucky Behavioral Risk Factor Surveillance System (BRFSS) data for 2020–2021 and used weighted responses for all analyses. We estimated current cannabis use (at least once in the past 30 days), and heavy use (at least 20 of the past 30 days) prevalence rates for Appalachian, Delta, and Central geographic regions of Ken- tucky. We tabulated descriptive …

Γ -Aapeptides Targeting Amyloid-Β Pathway And Neural Repair For Alzheimer’S Disease Treatment, Ning Shen

USF Tampa Graduate Theses and Dissertations

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) plaques and progressive neuronal degeneration. Despite extensive research, no treatments have been able to effectively halt or reverse the progression of the disease. This study aimed to evaluate the therapeutic potential of two novel γ-AApeptides, HW-C9 and 125-6b, in AD treatment, assessing both their individual and combined effects. HW-C9 was designed to inhibit Aβ aggregation, while 125-6b was developed to promote neuronal growth and repair. Initially, the therapeutic effects of HW-C9 and 125-6b were assessed both in vitro and in vivo. The results showed that HW-C9 …

Tak1 Blockade Plus Azacitidine Induces Apoptosis, Augments Cytarabine, And Ablates Clonogenicity In Mll-Af9+ Human Aml Cell Lines, Austin P. Runde, Cameron Lewis, Peter Breslin Sj, Jiwang Zhang

School of Medicine

Acute myeloid leukemia (AML) encompasses a diverse group of cancers that originate in the blood-forming tissues of the bone marrow [1]. Aside from the PML-RARA⁺ subtype, AML carries a 5-year survival rate of 28% for patients 20+ years of age. AML is the most common cancer of the hematopoietic system and is slightly more common in biological males; the average age at diagnosis is 68 years. Standard frontline treatment for AML is a two-phase regimen of intensive chemotherapy (CTx) employing daunorubicin and cytarabine; etoposide may also be added in select regimens. Despite 60-70% of patients achieving complete remission (CR), …

Pharmacokinetics And Tissue Distribution Of A Lipid-Based Extended-Release Nano-Formulation Of Mo-Oh-Nap Tropolone To Enhance Pulmonary Delivery For The Treatment Of Pulmonary Metastatic Osteosarcoma, Wafaa N. Aldhafiri

Theses & Dissertations

Osteosarcoma is the most common primary bone tumor in children and adolescents. Metastasis is prevalent in 25% of patients, at diagnosis, with the lungs being the most common metastatic site. Pulmonary metastatic osteosarcoma is a significant therapeutic challenge with a 5-year survival rate of ≤30%. Patients with pulmonary metastatic disease at diagnosis receive the same standard of care as patients with local disease, which hasn’t changed over the past 30 years. The treatment and prevention of pulmonary metastatic osteosarcoma represents a significant critical and unmet need.

MO-OH-Nap tropolone is a novel small molecule with cytotoxic activity across multiple human osteosarcoma …

Bridging The Gap: Psychopharmacologic Education And Side Effect Screening For Non-Prescribing Mental Health Professionals, Elaine Fitzgerald

Dissertations

Abstract

Problem: The United States is experiencing a growing demand for pediatric mental health support. Surges in mental health diagnoses and psychotropic medication prescriptions have occurred, compounded by a shortage of psychiatric providers. Non-prescribing mental health professionals are well-positioned to recognize psychotropic medication side effects. However, psychologists and counselors lack formal pharmacology education.

Methods: The quality improvement (QI) initiative was guided by the Plan-Do-Study-Act (PDSA) model. The evidence-based psychopharmacologic education for non-prescribers utilized a quasi-experimental pre- and post- test design. Data collected from clinicians included knowledge, confidence, and skill concerning psychotropic medications. The Psychotropic Medication Monitoring Checklist (PMMC) screen clients …