Pharmaceutical Preparations Commons^™

The Efficacy Of Transversus Abdominis Plane Block As An Adjunct To Spinal Anesthesia For Cesarean Delivery: An Evidence Synthesis And Implementation Toolkit, Alyssa Hebert, Alex Potts, Gabriela Robertson

Graduate Theses, Dissertations, and Capstones

Postoperative pain hinders cesarean delivery recovery and overall patient experience. Although spinal anesthesia with intrathecal opioids remains the standard of practice, associated side effects and concerns regarding opioid exposure highlight the need for effective opioid-sparing strategies. Anesthesia providers play a critical role in advancing postoperative pain management through evidence-based protocol development, provider education, and interdisciplinary collaboration to optimize maternal outcomes. The transversus abdominis plane (TAP) block provides somatic analgesia to the anterior abdominal wall by targeting the thoracolumbar nerves (T6–L1) and has increasingly been incorporated into multimodal postoperative pain management strategies for abdominal surgery. Nevertheless, a gap remains in obstetric …

Quality Improvement Initiative To Improve Adherence To Ob Hemorrhage Policy And Standardize Pitocin Administration During Cesarean Sections To Reduce Postpartum Hemorrhage Risk, Lauren R. Litz, Monica Blauser

Doctor of Nurse Anesthesia Practice (DNAP) Manuscripts

Postpartum hemorrhage remains a leading cause of maternal morbidity and mortality, and Pitocin administration is an important component of hemorrhage prevention and management during cesarean delivery. Variation in Pitocin timing, dosing, method of administration, and adherence to evidence-based recommendations may compromise patient safety and create barriers to standardized obstetric anesthesia care. The purpose of this Doctorate of Nurse Anesthesia Practice quality improvement project was to evaluate current anesthesia provider practices for Pitocin administration during cesarean delivery, compare observed practices with the California Maternal Quality Care Collaborative hemorrhage toolkit and Society for Obstetric Anesthesia and Perinatology Enhanced Recovery After Cesarean recommendations, …

Independent And Combined Effects Of Early-Life Iron Deficiency And Antibiotic Exposure On Growth And Hematological Outcomes In A Piglet Model, Ginger M. Fitzpatrick

Master's Theses

Iron deficiency (ID) affects over 2 billion individuals globally. Children under 5 are at increased risk of ID due to rapid growth and are especially vulnerable to its negative consequences because of iron’s essential role in cognitive development and immune maturation. ID is the leading cause of iron deficiency anemia (IDA), with IDA affecting approximately 40% of children in this age group. Antibiotic (abx) exposure is also prevalent during early life and may disrupt growth and through gut dysbiosis, with increasing use posing additional risk in younger populations. Geographically, there is overlap in regions with high anemia prevalence and those …

Quality Improvement (Qi) Project Aimed At Reducing Unnecessary Antibiotic Usage Among Older Adult Patients By Addressing Inappropriate Antibiotic Prescribing In Primary And Long-Term Care Settings, Pamela M. Thomas

Seton Hall University Dissertations and Theses (ETDs)

Antibiotic overuse among older adults remains a significant patient safety and public health concern. Recent national data indicate that approximately 30%–50% of outpatient antibiotic prescriptions may be unnecessary, particularly for viral or self-limiting conditions (Chua et al., 2021). Antimicrobial resistance has been associated with more than 1.27 million deaths globally (Murray et al., 2022). This quality improvement project evaluated a multifaceted antimicrobial stewardship intervention in primary and long-term care settings. Baseline review of 167 antibiotic cases revealed 37.1% were inappropriate or questionable, and 28.7% lacked adequate diagnostic documentation. The intervention incorporated provider education, electronic health record decision-support tools, audit and …

Evaluation Of The Effectiveness Of Antihypertensive Therapy Chosen Through Maternal Hemodynamic Profile Analysis, Margaret Weimer

Honors Theses

Medication choice is tightly regulated in most situations, but in the field of obstetric medicine, the American College of Obstetricians and Gynecologists (ACOG) recommends both labetalol and nifedipine as oral treatments for emergent hypertension, with no preference shown between the two. Studies have suggested that consideration of hemodynamic profile may be an effective way to determine medication, but have not considered the Rule of 55, a simple calculation to predict hemodynamic profile. The goals of this study were to determine whether tailoring the oral hypertensive medication to a patient’s hemodynamic profile is associated with better blood pressure control within 72 …

The Impact Of Glucose Exposure On Organic Cation Transporters (Oct) Function In A Corneal Epithelial Cell Line, David A. Garza

Theses & Dissertations

Organic cation transporters (OCT) facilitate the movement of neurochemicals and medications, contribute to the removal of cellular waste, and facilitate neuronal communication. Three subtypes of these high-capacity, low-affinity transporters (OCT1, OCT2, and OCT3) are differently expressed in peripheral tissues such as the liver, kidneys, as well as the central nervous system. OCTs are also expressed in ocular tissues. Chronic hyperglycemia is a complication commonly associated with diabetes that can lead to ocular diseases such as diabetic keratopathy, which affects the cornea. In this project, we expose immortalized human corneal epithelial cells (HCE-S) to various glucose concentrations to study their impact …

Development Of Tunable Rose Bengal Based-Nanogumbos As Potential Selective Chemotherapeutic Agents, William J.A. Russell

Honors College Theses

As cancer remains one of the greatest threats to the global population, the development of chemotherapeutic agents that are selective and tunable is of critical importance. Herein, a series of Rose Bengal (RB)-based GUMBOS, a group of uniform materials based on organic salts, were synthesized via counterion exchange between [Na]₂[RB] and three organic cations: tetrabutylphosphonium bromide [TBP][Br], tetraphenylphosphonium chloride [TPP][Cl], and 1-dodecyl-3-methylimidazolium chloride [C₁₂MIm][Cl]. The resulting GUMBOS were characterized through FT-IR, ESI-MS, NMR, and UV-Vis Spectroscopy. Partition coefficient studies indicated all GUMBOS exhibited hydrophobic physiochemical characteristics. These hydrophobic RB-based GUMBOS …

Absolute Quantification And Identification Of Rna From Rna-Lipid Nanoparticles Using High Resolution Mass Spectrometry, Jason C. Funderburk

Theses and Dissertations

RNA therapeutics are a rising drug category with potential use for a range of conditions encompassing infectious diseases to therapies for cancer, diseases, and genetic disorders. RNA-lipid nanoparticles (RNA-LNPs) are the prominent delivery method for these therapeutics approved products include mRNA vaccines and polyneuropathy treatments. The emergency use authorizations and orphan drug status of current RNA-LNP drugs has allowed approval without finalization of the regulatory analytical procedures for quality monitoring. The objective of the study was to develop an LC-MS assay to simultaneously measure identity and concentration of two therapeutically relevant intact RNA constructs extracted from RNA-LNPs to enhance quality …

Synthesis And Characterization Of Succinate Dehydrogenase Inhibitors H2/Z14 And C6/Z96 In Order To Combat Small Cell Lung Cancer, Lauren M. Graves

Honors Undergraduate Theses

The use of ubiquinone inhibitors to combat cancer is a recent development in medicinal science and procedures to efficiently synthesize these drugs remain limited. C6/Z96 and H2/Z14, two succinate dehydrogenase inhibitors, have been previously tested in vitro against NSCLC with positive results. Their similarity to ubiquinone is what makes them a strong candidate for a succinate dehydrogenase inhibitor at the ubiquinone binding site. The heterocyclic scaffolds and substituents are proposed to bind strongly through a combination of electronics, hydrogen-bonding, and fit, allowing them to bind well and prove to be more favorable than ubiquinone when competing for the Q-site. By …

Safety Evaluation Of Epicertin, An Oral Biotherapeutic Candidate For Treating Ulcerative Colitis: A 28-Day Repeated Dose Toxicity Study., Jimmy Fernando Cifuentes Jimenez

Electronic Theses and Dissertations

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic, relapsing inflammation of the colon and rectum with limited treatment options. Among them, immunosuppressive agents have a high rate of adverse side effects and do not cure the disease. EPICERTIN (EPT), a recombinant variant of the cholera toxin B subunit (CTB) with a C-terminal hexapeptide extension consisting of a KDEL endoplasmic reticulum (ER) retention motif, is a promising oral biotherapeutic candidate for the treatment of UC. EPT has demonstrated mucosal healing activity in mouse models of colitis and human colonic explants. EPT's mechanism of action involves binding to GM1 …

Effect Of Histidine Tag On The Enzymatic Activity Of Pseudolysin And Its Interaction With The Streptomyces Metalloprotease Inhibitor (Smpi) Protein, Adewale Adeboye Adewole

Electronic Theses and Dissertations

Pseudolysin (PLN) protein is a major virulent factor in Pseudomonas aeruginosa infection. PLN belongs to the family of zinc-dependent metalloproteases. It is naturally inhibited by a smaller protein called streptomyces metalloprotease inhibitor (SMPI), secreted by Streptomyces nigrescens. Previous and current studies demonstrate that the interaction between PLN and SMPI offers unique mechanistic insights for drug development against infections caused by P. aeruginosa. This study investigated the effect of N-terminal Histidine (His) tag on the enzymatic activity of PLN and its interaction with SMPI. His-tagged PLN and SMPI proteins were expressed in bacteria and purified by affinity chromatography …

Cbl Regulation Of C-Met Signaling In Corneal Epithelial Cells., Kate Elise Tarvestad Laise

Electronic Theses and Dissertations

The cornea is the most anterior portion of the eye and permits light passage through to retina, allowing formation of a clear image as long as it remains healthy. If the cornea sustains damage, it creates and entrance for foreign body invasion, infection, and ultimately blindness in the immunocompromised eye. Healing the corneal tissue is critical for vision restoration and pain alleviation, as it is the most densely innervated tissue in the body. Growth factors and their cognate receptors are currently under investigation as tools to restore proper corneal physiology. We hypothesize that manipulating the hepatocyte growth factor (HGF) /c-Met …

Determining The Bioaccumulation Of Minor Cannabinoids In Zebrafish Larvae, Kamdyn A. Holt

Honors Theses

Due to the increasing prevalence of cannabis product availability and usage in the modern United States, particularly among pregnant individuals, evaluating the bioaccumulation of minor cannabinoids to further understand the adverse effects of cannabinoids during early development is critical. This study quantitated the uptake of eight minor cannabinoids ((∆8-tetrahydrocannabinol (∆8-THC), ∆9-THC, ∆10-THC, cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), tetrahydrocannabivarin (THCV), and hexahydrocannabinol (HHC)) in zebrafish larvae following water-borne 2 µM exposures from 6 to 96 hours post fertilization (hpf). Larvae were homogenized at 96 hpf and analyzed using a gas chromatography- mass spectrometry (GC-MS) method developed in this study. Bioconcentration …

Synthesis, Characterization, And Biological Activity Of Ni(Ii) And Co(Iii) Thiosemicarbazone Complexes As Potential Anticancer Agents, Jack Martin

Pitzer Senior Theses

The mechanics by which Reactive Oxygen Species work is an area of great interest given ROS’s wide range of biological applications. From cell signaling and mitochondrial regulation to pathogenesis and tumor cell death, varying concentrations of ROS in a system can lead to a whole host of positive and negative effects. In a similar vein, thiosemicarbazones are known to be equally useful for their myriad of antibacterial, antifungal, antiviral, and antitumoral effects. They have been at the core of the pharmaceutical world or the better part of the last century. The purpose of this work is to synthesize, characterize and …

Synthesis Of Tu100 Analogs And Biological Assays, Feyisope Tonye Oladapo

College of Graduate Studies: Theses & Dissertations

TU100 (14-methyl-5H-5,12-epiminobenzo[4,5]cyclohepta[1,2-b]naphthalene-6,11,13(12H)-trione) exhibits exceptional chemotherapeutic properties. It operates via a distinct mechanism that triggers cell death to create cytotoxic effects while concurrently inhibiting topoisomerase I and II. Its efficacy rivals that of well-known chemotherapeutic drugs like Daunorubicin. The distinctive characteristics of TU100 have led to initiatives aimed at creating structurally similar compounds to discover even more effective bioactive alternatives.

The analog synthesis incorporated quinoxaline or its derivatives (diphenyl quinoxaline, dipyridinyl quinoxaline, and dibenzophenazine-10,13-dione) that have been shown to have promising chemotherapeutic effects. Synthesizing the hetero naphthoquinones required a multi-step synthetic process, so quinoxaline/ derivatives intermediates are first prepared, then the …

Asymmetric Synthesis Of The Hiv Protease Inhibitor Tmc-126 And An Anti-Malarial Agent Via A Titanium Tetrachloride Mediated Asymmetric Glycolate Aldol Addition Reaction. Redefining The Curtius Rearrangement Reaction Via Dehomologation Of Carboxylic Acids Bearing Alpha-Leaving Groups, Kweku Amaning Affram

Theses and Dissertations

Acquired Immune Deficiency Syndrome (AIDS) and malaria are two devastating infectious diseases caused by HIV and Plasmodium parasites. AIDS is caused by HIV-1 and HIV-2, transmitted through sexual contact, blood transfusions, needle sharing, and perinatal routes. Malaria, caused by plasmodium parasites through mosquito bites. Today, millions of people around the world have been infected with HIV and malaria and much research has been done to treat it. However, despite advancements in therapeutic options, these diseases remain a significant global health threat, particularly in developing countries due to the emergence of drug-resistant strains for both HIV and malaria complicating eradication efforts. …

Opioid Tolerance And Withdrawal In The Mouse Colon, James Fune

Theses and Dissertations

Constipation is a major clinical obstacle associated with opioids, prompting patients to discontinue treatment due to pain, discomfort, and psychosocial stressors. Moreover, chronic users become tolerant to the analgesic effects of opioids, but not to their constipating effects. Upon cessation of long-term treatment, serious diarrhea–among other somatic signs of withdrawal–may ensue. These symptoms become a driving factor for relapse, causing patients to restart opioid treatment. In this study, we aim to understand mechanisms that contribute to opioid tolerance and withdrawal in the colon. Previous findings suggest that constipation occurs partly due to the colon’s lack of tolerance to opioids’ inhibitory …

Synthesis Of Photocleavable Molecules For Neurological Applications, Nishal Madujith Egodawaththa Arachchilage Don

Theses and Dissertations

In recent biomedical research, the precise control of molecular dynamics through light activation has emerged as a powerful tool, particularly in the field of neurobiology. This approach involves the use of photocleavable cages or photoprotective groups (PPGs) that are chemically tethered to biologically active molecules such as neurotransmitters or calcium chelators. These cages remain inert until exposed to specific wavelengths of light, typically in the visible range, triggering the release of the active compound with high spatiotemporal precision.

For neurotransmitter systems, such as glutamate (Glu), which plays a critical role in synaptic transmission and memory formation, researchers have developed novel …

A Third Generation Long-Acting Dimeric Dolutegravir Prodrug Nanoformulation, Bhoomika Suresh Gowda

Theses & Dissertations

Dolutegravir (DTG) is an integrase strand transfer inhibitor (INSTI) widely used as a part of first-line combination antiretroviral therapy. DTG has a high barrier to resistance However, one therapeutic challenge centers on its life-long daily use. Sub-optimal adherence to daily oral pills underscore the need for long-acting formulations. To these ends, our research activities have focused on the development and translation of ultra-long-acting ART. Monomeric ester prodrugs provided initial success in extending the apparent half-life of DTG and other INSTIs. One is the DTG prodrug formulation called NM2DTG. NM2DTG’s significantly extended the parent drug’s apparent half-life [Nature Communications, 3226 (2022)]. …

Novel Mechanisms For The Neural Control Of Breathing In Acute Lung Injury, Kajal Kamra

Theses & Dissertations

Acute lung injury (ALI) triggers inflammation that disrupts the normal alveolar-capillary endothelial barrier, impairing gas exchange and causing hypoxemia, which reflexively increases respiration. An elevated respiratory rate (fR) usually develops within hours to days following ALI. This acute respiratory failure disorder affects approximately 200,000 new cases annually in the US and accounts for 10% of ICU admissions, with high morbidity and mortality. The neural mechanisms underlying respiratory dysfunction post-ALI are not fully understood. My doctoral dissertation aimed to investigate the mediators of abnormal ventilation during ALI. Systemic hypoxia stimulates the carotid body (CB) chemoreflex, a crucial protective reflex that maintains …

Translational Pathways For Ultra Long-Acting Medicines For Chronic Disease: From Hiv To Substance Use Disorders, Suyash Sanjay Deodhar

Theses & Dissertations

Human immunodeficiency virus (HIV) and opioid use disorder (OUD) are among the top global public health challenges, with a significant overlap in the number of cases and higher mortality risks compared to the general population. Treatment and recreational opioid use lead to addictive disorders. Both conditions require repeated dosing of therapy where adherence to a strict lifelong regimen remains a major challenge. Notably, people living with HIV/AIDS (PLWHA) and struggling with opioid use disorders (OUD) show suboptimal adherence to antiretroviral drugs (ARVs). Also, the risk of transmitting HIV and other blood-borne infections through the sharing of needles and other injection …

Development Of Long-Acting Antiviral And Antimicrobial Prodrug Nanoformulations, Srijanee Das

Theses & Dissertations

Over the past decade, the global burden of infectious diseases has increased substantively, underscoring the need for more effective treatment strategies. However, the discovery and development of new drugs with desirable safety, pharmacokinetics, and efficacy is a time consuming and costly process with great uncertainty around success rate. As an alternative to new drug development, prodrugs and novel drug delivery systems have increasingly been explored. Both serve to overcome the drug development challenges. Such drug formulations that permit extended dosing intervals of potent native drugs serve multiple purposes by promoting patient adherence to in improving treatment outcomes. This is especially …

Pharmacodynamic Effects Of Zsj-0228 On Complement Protein Deposition In The Kidneys Of Focal Segmental Glomerulosclerosis-Afflicted Mice., Braeden Pinkerton

Theses & Dissertations

Chronic inflammation, when left untreated, may result in significant morbidity and in severe cases, mortality. While glucocorticoids (GCs) are still being extensively used clinically as a class of very potent anti-inflammatory agents, they are also notorious for diverse adverse side effects. To mitigate these side effects, we have developed a polyethylene glycol (PEG)-based prodrug (ZSJ-0228) of dexamethasone (Dex). When tested on rodent models of Lupus Nephritis and Focal Segmental Glomerulosclerosis (FSGS), ZSJ-0228 was found to provide potent and sustained therapeutic efficacy without any detectable typical GC-associated side effects. Given ZSJ-0228’s transient renal exposure after systemic administration, it is yet to …

Epiregulin As A Novel Target For Antibody-Drug Conjugate Development For The Treatment Of Colorectal Cancer, Joan Jacob

Dissertations and Theses (Open Access)

Antibody-drug conjugates (ADCs) are a fast-growing class of molecularly targeted therapies with 13 currently approved and over a 100 in clinical trials. ADCs consist of a monoclonal antibody (mAb) conjugated to a potent cytotoxic payload to selectively target tumor antigens highly expressed on the cell surface. ADC development has been limited in colorectal cancer (CRC) by the lack of novel and effective therapeutic targets. Epiregulin (EREG), is an epidermal growth factor receptor (EGFR) ligand that is highly expressed in CRCs of different subtypes and mutational statuses with low expression in normal tissues. Here, we have characterized the role of EREG …

Education Of The Effects Of Obesity Medications And A Stepwise Approach To Mitigate Prevalence And Encourage Lifestyle Medicine For Primary Care Physicians, Kiely M. Curran

Department of Nutrition Student Projects

My Capstone project is an Educational Manual that emphasizes a healthcare team approach to the treatment and management of obesity. The Educational Manual consists of a standardized protocol in management of obesity in patients and a document with summarized references for primary care providers; and a simplified document for patient education. There is a growing interest in the usage of obesity medications. The purpose of my Capstone project is to provide a simplified manual for the primary care provider to reference to make knowledgeable and patient-centered decisions in the prescription of obesity medications and decisions in weight-management. My methodology included …

From Cough To Crip: The Development Of Codeine From A Purely Medical Substance Into A Popular Recreational Drug, Rhett C. Vaughn

Senior Theses

The research that was conducted aimed to elicit the influence that pop culture has on recreational drug consumption. Specifically, the usage of the drug codeine has become very popular in social media among many influencers. The research focuses on the prevalence of this drug across several media platforms, alongside the growing rate of consumption globally. Research was conducted primarily through combining various databases at various organizations and this study aims to compile the data into one coherent paper regarding codeine in pop culture. While, it cannot be solely attributed to one specific outlet or influence, this study found that alongside …

Developing Radiosensitizers To Enhance Radiotherapy In Treating Gastroenteropancreatic Neuroendocrine Tumor, Zeta Chow

Theses and Dissertations--Clinical and Translational Science

Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) is a heterogeneous group of malignancies arising from multipotent neuroendocrine stem cells in the gastrointestinal tract. The incidence of GEP-NET continues to rise, possibly due to the advancement of imaging and biomarkers available for diagnosis. However, even though the majority of patients are diagnosed with low-grade and localized disease, a significant percentage of patients present with advanced-stage metastatic disease with poor prognosis in months to a few years. These advanced-stage GEP-NET patients can also present with a variety of debilitating symptoms that significantly impact their quality of life. The role of palliative-intent surgery is limited, and …

Continuous, Platform Purification Of Viral Products Using Aqueous Two-Phase Extraction, Natalie M. Nold

Dissertations, Master's Theses and Master's Reports

Cell and gene therapies, a ground-breaking class of drugs that can heal genetic diseases and cure cancer, often have treatment costs over $1 million. Most cell and gene therapies are delivered using virus-based delivery vectors, which are incredibly expensive to manufacture. Liquid chromatography is the favored method of viral vector purification since it is easily scalable and can be functionalized to purify by biospecificity, charge, hydrophobicity, or size. However, chromatography-based purification processes are highly expensive and usually only recover 20-50% of the viral vectors. There is currently no platform purification strategy for viral vectors due to differences in their surface …

Continuous Flow As A Process Intensification Tool For The Preparation Of Pharmaceutically Relevant N-Heterocycles, John W. Tomlin Jr

Theses and Dissertations

Continuous flow as a process intensification tool for the preparation of pharmaceutically relevant N-heterocycles

John W. Tomlin

Thesis Defense: 17 January 2024

Committee: B. Frank Gupton, Ph.D. (Advisor), Suzanne M. Ruder, Ph.D. (Chair), Heather R. Lucas, Ph.D., James K. Ferri, Ph.D., Matthew C.T. Hartman, Ph.D.

A dissertation submitted in partial fulfillment of the requirements of Doctor of Philosophy at Virginia Commonwealth University

© 2024 John W. Tomlin Jr All Rights Reserved

Abstract

Essential medicines must be produced in large quantities to accommodate large global demand. The preparation of these active pharmaceutical ingredients (API) must therefore strive to be both cost-effective …

Evaluating Outcomes Post-Adoption Of Reck Solution For Total Shoulder Arthroplasties: A Retrospective Quality Analysis, Benjamin Levi Tillis

Graduate Theses, Dissertations, and Problem Reports (ETD)

Abstract

Evaluating Outcomes Post-adoption of RECK Solution for Total Shoulder Arthroplasties: A Retrospective Quality Analysis

Benjamin Tillis

Introduction: Local infiltration analgesia (LIA) has become an integral part of postoperative pain relief for West Virginia University (WVU) Medicine’s total joint arthroplasty procedures. However, not all LIAs are the same. Liposomal bupivacaine has a unique mechanism of delivery which could potentially lead to longer lasting effects. Ropivacaine, epinephrine, clonidine, and ketorolac (RECK) solution offers a multimodal approach to enhancing the duration of effect for the LIA. In 2022, WVU Medicine switched from liposomal bupivacaine to the RECK solution for total joint …