Pharmaceutical Preparations Commons^™

Case Report And Review: Promethazine ("Purple Drank") Abuse, Riya Tandra, James Espinosa, Alan Lucerna

Rowan-Virtua Research Day

A 23 year old female was brought to the Emergency Department by EMS for confusion and aggressive behavior. The friends told EMS that the patient had been ingesting "purple drank" and that she had told her friends that she made the concoction with promethazine and opiate cough syrup with some vodka added. She mixed it in a carbonated soda. “Purple Drank” or “Lean” is a combination of codeine promethazine hydrochloride and soda or alcohol that has frequently been misused since the 1990s. This paper aims to highlight the recent resurgence of promethazine abuse occurring in the United States as well …

Brief Review: Iv Fluid Choice In The Emergency Department, Kaywan Saed, James Espinosa, Alan Lucerna

Rowan-Virtua Research Day

Normal saline and balanced crystalloids, such as lactated Ringer's (LR) and Plasma-Lyte A, are commonly used in the emergency setting for fluid resuscitation. However, there has been growing interest in recent years in whether balanced crystalloids may be superior to normal saline, particularly in critically ill patients.

Normal saline has been the traditional fluid of choice for decades due to its widespread availability, low cost, and presumed safety. However, normal saline has a high chloride concentration (154 mmol/L), which can lead to hyperchloremic metabolic acidosis and other adverse effects, such as renal vasoconstriction and reduced renal blood flow.

In contrast, …

Perioperative Ketamine Use For Post Mastectomy Pain, Alessia Cooney, Jaylyn Thompson, Naomi Watkins-Granville

Rowan-Virtua Research Day

PMPS is defined as chronic neuropathic pain following breast cancer procedures in the ipsilateral arm, chest wall, axilla or shoulder.1-3 Approximately 20 to 50% of post mastectomy patients suffer from Post Mastectomy Pain Syndrome (PMPS).1 With more than 3.8 million breast cancer survivors, due to advances in treatment, there is increased importance in findings ways to better manage the quality of life of breast cancer survivors.1,4 Ketamine induces analgesic effects through its non-competitive antagonism of NDMA receptors.5 Low doses of ketamine infusion (20–30 mg x h−1) have been shown to produce analgesia in neuropathic pain states with benefits lasting up …

Characterization Of Differential Rearing And Sex On 5-Ht2ar Receptor Activation, Kelsey Lowe

Theses/Capstones/Creative Projects

The prevalence of substance use disorders (SUDs) continues to rise while the number of medications to combat this deadly disorder remains stagnant. Entirely new thinking about what exemplifies a possible therapeutic is needed. Hallucinogens are continually being studied more as possible treatments for many psychological conditions, including SUDs. Classic hallucinogens engage many serotonin and monoamine systems, but the hallucinogenic effects are driven by serotonin 5-HT_2A receptor (5-HT_2AR) activation. Forced social isolation induces chronic stress, increases 5-HT_2AR expression in the cortex and have been suggested to play a role in the comorbidity between stress, maladaptive coping, …

The Application Of Continuous Stationary Phase Gradients To High-Performance Liquid Chromatography And Its Potential To Improve Pharmacological Research, Hannah Klose

Senior Honors Theses

The separation of mixtures into different components is integral to experimentation and analysis in a multitude of fields. Chromatography is one of the most popular, well-developed, and well-studied methods used to examine the makeup of a mixture. Thus, the improvement of chromatographic procedures directly benefits research across many scientific disciplines. The application of a continuous stationary phase gradient to High-Performance Liquid Chromatography (HPLC) methods has been proposed to improve the separation of complex mixtures that are difficult to achieve with existing separation techniques. By incorporating a gradient stationary phase, analysts will create a more selective mode of separation to improve …

March / April 2023, Randy Curry, Cindy Brooks

RURAL ROCKS

This is the March & April 2023 issue of Rural Rocks from the SWOSU College of Pharmacy.

Gh-05 Exploring Drug Efficacy In The Pediatric Population: Determining The Differences Among Various Drug Classes, William F. Gardner Ii, Brooks T. Mcphail

SC Upstate Research Symposium

Exploring Drug Efficacy in the Pediatric Population: Determining the Differences Among Various Drug Classes

William F. Gardner II¹, M. Jacob Wurst¹, Brooks McPhail, PhD^1,2

¹University of South Carolina School of Medicine Greenville, Greenville, SC,

²Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Introduction: Pharmacodynamics is commonly defined as what the drug does to the body. The pharmacodynamic effects of a drug are required to determine its efficacy and safety. Due to the unique nature of pediatric development, and the challenges in doing research on children, the efficacy and safety of many drugs are …

Second Generation Phenyloxadiazolyl Methyl Sulfones For Thiol-Specific Bioconjugations, Guillaume Dewaele-Le Roi

Dissertations, Theses, and Capstone Projects

The role of antibody-based molecular agents for diagnosis and therapy of cancer has expanded significantly over the past decades. However, most of these constructs are synthesized using traditional bioconjugation methods based on the random ligations between the molecular cargo and lysine residues within the protein. These non-specific approaches can create poorly defined conjugates with suboptimal immunoreactivity and in vivo performance while Site-specific approaches to antibody bioconjugation based on ligations between maleimides and free cysteine residues have long stood as attractive alternatives. Yet the inherent instability of the thiol-maleimide linkage has fueled the search for new, more stable thiol-reactive prosthetic groups. …

January / February 2023, Randy Curry, Cindy Brooks

RURAL ROCKS

This is the January & February 2023 issue of Rural Rocks from the SWOSU College of Pharmacy.

Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson

Dissertations, Theses, and Capstone Projects

A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed …

Engineered Plga Nanofibers For Drug Delivery, Andrew Mancuso

Dissertations, Theses, and Capstone Projects

Poly-lactic-co-glycolic acid (PLGA) polymers are rapidly gaining momentum as a platform for next-generation drug delivery systems due to their ease and low cost of synthesis, favorable biocompatibility and biodegradability, and lack of toxicity. In particular, the application of drug-loaded PLGA nanofibers directly to a target tissue may represent a promising alternative to traditional routes of drug administration (e.g., oral, injectable) as they offer the potential to greatly improve bioavailability, increase efficacy, and reduce off-target toxicity. Furthermore, the use of such a system may potentially allow for greater flexibility in clinical drug development, by enabling the use of compounds which have …

Characterization, Antibacterial, Antioxidant, Antidiabetic, And Anti-Inflammatory Activities Of Green Synthesized Silver Nanoparticles Using Phragmanthera Austroarabica A. G. Mill And J. A. Nyberg Extract, Shady Swidan, Dina Khodeer, Sarah Shabayek, Ali Nasr, Roaa Khinkar, Mohammed Aldurdunji, Maryam Ramadan, Jihan Badr

Pharmacy

Introduction: Diabetes mellitus is a chronic metabolic disorder that exhibited great expansion all over the world. It is becoming an epidemic disease adding a major burden to the health care system, particularly in developing countries.

Methods: The plant under investigation in the current study Phragmanthera austroarabica A. G. Mill and J. A. Nyberg is traditionally used in Saudi Arabia for the treatment of diabetes mellitus. The methanolic extract (200 mg/kg) of the plant and pure gallic acid (40 mg/kg), a major metabolite of the plant, as well as their silver nanoparticle formulae (AgNPs) were evaluated for their antidiabetic activity.

Results …

Effects Of Disulfiram On The Metabolome Of Mrsa, Surya Teja Naidu

Theses, Dissertations and Capstones

Disulfiram, known as Antabuse®, is an oral drug for the treatment of alcohol dependence. Previous studies have indicated that disulfiram (DSF) exhibits antibacterial effects, particularly against Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Our study delves into the antibacterial mechanism of DSF in MRSA through High-Pressure Liquid Chromatography (HPLC) metabolomics, investigating the underlying mechanism of DSF effects on thiamine and amino acid metabolism. Thiamine pyrophosphate (TPP) plays a crucial role as a cofactor for critical enzymes such as transketolase, pyruvate dehydrogenase, and 2-oxoglutarate dehydrogenase. These enzymes are integral to the carbohydrate metabolism process within bacterial cells. TPP also contributes …

Self-Assembled Ternary Polypeptide Nanoparticles With Improved Biostability For Drug Delivery In Cancer Therapy, Preye Mike Agbana

Theses and Dissertations--Pharmacy

Cancer remains a real and present threat to global health. In the United States, according to cancer statistics, almost 40% of people will be diagnosed with cancer at some point in their lifetime. Conventional chemotherapy has become the mainstay for cancer treatment option. However, chemotherapeutic agents are plagued with problems such as poor aqueous solubility, chemical degradation, Bio instability, and off-site toxicity due to non-specificity. New drug modalities are needed to tackle the ever-growing burden on cancer. In recent times, the promise of nanotechnology has aided to develop drug delivery vehicles to facilitate the administration of potent chemotherapeutics. Nanoformulations such …

Enhancing Dna-Damaging Therapy Through The Inhibition Of Dntp Synthesis Using A Synergistic Drug Combination To Treat Pancreatic Neuroendocrine Neoplasms, Jennifer Castle Md

Theses and Dissertations--Clinical and Translational Science

Despite clinical advances, pancreatic neuroendocrine neoplasms (pNEN) remain a difficult clinical entity to treat and can carry a poor prognosis. Systemic therapy is used to treat pNENs which are not amenable to surgical resection. Peptide receptor radionuclide therapy, a form of radiation therapy (RT) and cisplatin are two different forms of DNA-damaging therapy in current use to treat pNENs. However, their efficacy remains poor as single agents. This study aimed to increase the sensitivity of pNENs to the DNA-damaging agents, RT and cisplatin, by inhibiting deoxynucleotide triphosphate (dNTP) synthesis. Triapine, a ribonucleotide reductase inhibitor (RNRi), and ataxia telangiectasia and Rad3-related …

Efficacy And Safety Of Vibegron For The Treatment Of Overactive Bladder In Women: A Subgroup Analysis From The Double-Blind, Randomized, Controlled Empowur Trial, Diane K. Newman Dnp, Elizabeth Thomas Ms, Heather Greene Mph, Cornelia Haag-Molkenteller Md, Susann Varano Md

Physician Associate Studies Faculty Publications

Importance The international phase 3 EMPOWUR trial demonstrated efficacy and safety of vibegron, a newer b3-adrenergic receptor agonist, in adults with overactive bladder (OAB). Women are disproportionately affected by OAB, especially those with bothersome symptoms, such as urge urinary incontinence (UUI). Objective This subgroup analysis from EMPOWUR assessed efficacy and safety of vibegron in women. Study Design In EMPOWUR, patients with OAB were randomized 5:5:4 to 12 weeks of treatment with once-daily vibegron 75 mg, placebo, or tolterodine 4-mg extended release. Efficacy end points included change from baseline at week 12 in mean daily number of micturitions, UUI episodes, and …

An Acute Respiratory Distress Syndrome Drug Development Collaboration Stimulated By The Virginia Drug Discovery Consortium, John S. Lazo, Ruben M.L. Colunga-Biancatelli, Pavel A. Solopov, John D. Catravas

Bioelectrics Publications

The genesis of most older medicinal agents has generally been empirical. During the past one and a half centuries, at least in the Western countries, discovering and developing drugs has been primarily the domain of pharmaceutical companies largely built upon concepts emerging from organic chemistry. Public sector funding for the discovery of new therapeutics has more recently stimulated local, national, and international groups to band together and focus on new human disease targets and novel treatment approaches. This Perspective describes one contemporary example of a newly formed collaboration that was simulated by a regional drug discovery consortium. University of Virginia, …

Testing The Efficacy And Synergistic Components Of Sesamol And Black Rice Extract On Human Colon Cancer Cells, Sera Lim, Philip M. Gerk

UROP Posters

Purpose: Systemic treatment of colorectal cancer involves chemotherapeutic agents which elicit serious and negative side effects from the toxicity of the drug. To address this issue, we are testing dietary supplements for their efficacy against human colon cancer cell lines and also their potential synergistic effects when combined with conventional chemotherapy. Dietary supplements (specifically sesamol and black rice extract) exhibit anticancer, anti-inflammatory, and chemo-preventive properties. Meanwhile, one of the cancer resistance mechanisms is the upregulation of drug elimination mechanisms, leading to multi-drug resistance. We hypothesize that dietary compounds will act as chemo-enhancers, thus enhancing potency of the chemotherapy drug(s) on …

Identifying The Serious Clinical Outcomes Of Adverse Reactions To Drugs By A Multi-Task Deep Learning Framework, Haochen Zhao, Peng Ni, Qichang Zhao, Xiao Liang, Di Ai, Shannon Erhardt, Jun Wang, Yaohang Li, Jiianxin Wang

Computer Science Faculty Publications

Adverse Drug Reactions (ADRs) have a direct impact on human health. As continuous pharmacovigilance and drug monitoring prove to be costly and time-consuming, computational methods have emerged as promising alternatives. However, most existing computational methods primarily focus on predicting whether or not the drug is associated with an adverse reaction and do not consider the core issue of drug benefit-risk assessment-whether the treatment outcome is serious when adverse drug reactions occur. To this end, we categorize serious clinical outcomes caused by adverse reactions to drugs into seven distinct classes and present a deep learning framework, so-called GCAP, for predicting the …

Evaluation Of Antibody Response To Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Vaccination In Patients With Lymphoid And Solid Organ Malignancies, Mukul Singal, Sanjana Kalvehalli Kashinath, S. Shahzad Mustafa, Edward Walsh, Karthik Vadamalai, Saad Jamshed

Advances in Clinical Medical Research and Healthcare Delivery

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. There is emerging evidence regarding suboptimal response to vaccination against COVID-19 in patients with hematologic and solid organ malignancies.

We conducted a single-center prospective study assessing seroconversion in response to vaccination against COVID-19 in 53 patients with chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM), and solid organ malignancies.

A quantitative immunoassay of IgG antibodies to SARS-CoV-2 Spike (S) protein was measured prior to vaccination and at 2 weeks after completion of two-dose vaccination series. A fourfold increase in antibody titers was considered positive …

Prophylactic Intravenous Prehydration With Sodium Bicarbonate Or Sodium Chloride In The Prevention Of Contrast Induced Acute Kidney Injury, Briana Lockett, Caroline Dong

Physician Assistant Capstones, 2020-current

Introduction: Iodinated contrast media is a crucial component in the diagnostic work up of many life-threatening illnesses. However, it has been reported to cause acute kidney injury after administration, especially in patients with pre-existing renal disease. Several prophylactic treatments have been studied in hopes of minimizing these adverse events. The current standard of care in this patient population is prophylactic intravenous volume administration with either sodium chloride or sodium bicarbonate. Objective: The goal of this literature review is to determine if prophylactic intravenous volume administration with either saline or sodium bicarbonate prior to contrast administration decreases the incidence of contrast …

November / December 2022, Randy Curry, Cindy Brooks

RURAL ROCKS

This is the November & December 2022 issue of Rural Rocks from the SWOSU College of Pharmacy.

Effects Of Chronic Cirrhosis Induced By Intraperitoneal Thioacetamide Injection On The Protein Content And Michaelis–Menten Kinetics Of Cytochrome P450 Enzymes In The Rat Liver Microsomes, Devaraj Venkatapura Chandrashekar, Barent N. Dubois, Mamunur Rashid, Reza Mehvar

Pharmacy Faculty Articles and Research

Chronic intraperitoneal injection of thioacetamide (TAA) in rats has been used as an animal model of human cirrhosis to study the effects of the disease on drug metabolism. However, TAA inhibits P450 enzymes directly and independently of cirrhosis. We investigated the effects of chronic cirrhosis in rats, induced by 10 weeks of intraperitoneal TAA, on the P450 enzymes after a 10-day washout period to eliminate TAA. Liver histology and serum biomarkers of hepatic function confirmed cirrhosis in all animals. Microsomal total P450 content, P450 reductase activity and ethoxycoumarin O-deethylase activity, a general marker of P450 activity, were significantly reduced by …

Differential Expression And Activities Of Cytochrome P450 3a In The Rat Brain Microsomes And Mitochondria, Nouf Alshammari, Devaraj Venkatapura Chandrashekar, Mamunur Rashid, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ), a benzodiazepine derivative, is metabolized to 1′- and 4-hydroxylated metabolites (1′-OH-MDZ and 4-OH-MDZ, respectively) by cytochrome P450 3A (CYP3A). The purpose of this study was to investigate the CYP3A-mediated hydroxylation of MDZ in the rat brain mitochondria (MT). Brain microsomes (MC) and MT fractions were prepared from rats (n = 8) using differential and density gradient centrifugations, and the purity of the fractions was evaluated using VDAC1 and calreticulin as markers of MT and MC, respectively. The formation rates of 1′-OH-MDZ and 4-OH-MDZ in the rat brain MC and MT samples were determined using an LC–MS/MS method …

September / October 2022, Randy Curry, Cindy Brooks

RURAL ROCKS

PLS presents the 7^th Annual Substance Use Disorder Seminar with Dr. Jake Nichols.

The Effects Of Cannabidiol On Aqueous Humor Outflow And Trabecular Meshwork Cell Signaling., Alyssa S. Aebersold, Zhao-Hui Song

Faculty and Staff Scholarship

Intraocular pressure (IOP) is regulated primarily through aqueous humor production by ciliary body and drainage through uveoscleral and trabecular meshwork (TM) tissues. The goal of this study was to measure the effect of non-psychotropic cannabidiol (CBD) on aqueous humor outflow through TM and assess the effect of CBD on the TM cell signaling pathways that are important for regulating outflow. Perfused porcine eye anterior segment explants were used to investigate the effects of CBD on aqueous humor outflow. Cultured porcine TM cells were used to study the effects of CBD on TM cell contractility, myosin light chain (MLC) and myosin …

Prazosin Dosed 3 Times A Day To Treat Flashbacks Related To Ptsd: A Case Report, Christie Richardson, Alexander Swartz, Martin Forsberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Prazosin is an alpha-1 adrenergic receptor antagonist widely known by mental health providers for its off-label use for nightmares in patients with PTSD. Prazosin is lipophilic and crosses the blood-brain barrier to antagonize alpha-1 receptors in the central nervous system, potentially reducing autonomic arousal caused by PTSD. There have been numerous case reports describing the reduction of nightmares and daytime flashbacks due to PTSD with prazosin dosed at night and during the day, respectively. This case report illustrates the resolution of flashbacks related to chronic PTSD with prazosin dosed 3 times a day. As the half-life of prazosin is only …

Clinical Characteristics And Implications Of Bradycardia In Covid‐19 Patients Treated With Remdesivir: A Single‐Center Retrospective Cohort Study, Ariyon Schreiber, Justin S. Bauzon, Kavita Batra, Salman Mohammed, Kevin Lee, Nazanin Houshmand, Uyen Pham, Celica Cosme, Kim Inciong, Omar Al‑Taweel, Keaton Nasser, Jibran Rana, Chris Sossou, Ariel Go, Dalia Hawwass, Jimmy Diep, Chowdhury H. Ahsan

School of Medicine Faculty Research

Background and Objectives: Remdesivir is an antiviral drug used to treat coronavirus disease 2019 (COVID-19) with a relatively obscure cardiac efect profle. Previous studies have reported bradycardia associated with remdesivir, but few have examined its clinical characteristics. The objective of this study was to investigate remdesivir associated bradycardia and its associated clinical characteristics and outcomes. Methods: This is a single-institution retrospective study that investigated bradycardia in 600 patients who received remdesivir for treatment of COVID-19. A total of 375 patients were included in the study after screening for other known causes of bradycardia (atrioventricular [AV] nodal blockers). All patients were …

Identification And Quantitation Of Unspecified Impurities Discovered In Novel Oral Irinotecan By Lc-Ms/Ms And Uhplc, Laura B. Miller

Forensic Science Master's Projects

Irinotecan is a cancer medication approved for medical use in the United States in 1996. It is currently administered via intravenous injection. However, intravenous dosing has disadvantages such as requirement of administration by a trained professional in a medical facility, possible severe adverse effects, pain at the injection site, and possible hemolysis if injected too rapidly. Previously oral administration was not feasible because the p-glycoprotein (p-GP) on the cell membrane of stomach cells acts as a defense mechanism against harmful substances by pumping the irinotecan back into the intestinal lumen for excretion. With the discovery of the p-GP inhibitor encequidar …

A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this …