Pharmacy and Pharmaceutical Sciences Commons^™

Brief Overview Of Approaches And Challenges In New Antibiotic Development: A Focus On Drug Repurposing, Natalie K. Boyd, Chengwen Teng Pharm.D., Ph.D., Christopher R. Frei

Faculty Publications

Drug repurposing, or identifying new uses for existing drugs, has emerged as an alternative to traditional drug discovery processes involving de novo synthesis. Drugs that are currently approved or under development for non-antibiotic indications may possess antibiotic properties, and therefore may have repurposing potential, either alone or in combination with an antibiotic. They might also serve as “antibiotic adjuvants” to enhance the activity of certain antibiotics.

Multimodal Pain Control In Common Neonatal Surgeries: Post-Operative Pain Protocol Reduces Opiate Exposure And Side Effects, Jamesia Donato

Research Days

Background: Opioids are the primary post-operative (post-op) analgesic in neonates. Side effects include hypotension, apnea and ileus. Previous studies show IV acetaminophen decreases opiate need in specific populations including cleft palate repair, cardiac surgery. The effect of IV acetaminophen as part of a post-op pain algorithm is not known in common neonatal surgical procedures.

Objectives/Goal: To determine if (a) a post-op pain algorithm including IV acetaminophen and (b) IV acetaminophen exposure reduces cumulative opioid requirements in neonates undergoing common surgeries in the NICU.

Methods/Design: This is a retrospective cohort study comparing cumulative post-operative opiate exposure between infants with common surgeries …

Myeloid Arginase 1 Insufficiency Exacerbates Amyloid-Β Associated Neurodegenerative Pathways And Glial Signatures In A Mouse Model Of Alzheimer’S Disease: A Targeted Transcriptome Analysis, Chao Ma, Jerry B. Hunt, Andrii Kovalenko, Huimin Liang, Maj-Linda B. Selenica, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Brain myeloid cells, include infiltrating macrophages and resident microglia, play an essential role in responding to and inducing neurodegenerative diseases, such as Alzheimer’s disease (AD). Genome-wide association studies (GWAS) implicate many AD casual and risk genes enriched in brain myeloid cells. Coordinated arginine metabolism through arginase 1 (Arg1) is critical for brain myeloid cells to perform biological functions, whereas dysregulated arginine metabolism disrupts them. Altered arginine metabolism is proposed as a new biomarker pathway for AD. We previously reported Arg1 deficiency in myeloid biased cells using lysozyme M (LysM) promoter-driven deletion worsened amyloidosis-related neuropathology and behavioral impairment. However, …

Design, Synthesis And Antineoplastic Evaluation Of A Variety Of Small Molecule Scaffolds, Bader Huwaimel

Theses & Dissertations

Several appealing strategies emerged for selective anticancer therapy. Mitochondrial respiratory complex II (CII) is a potential target for many human diseases, including cancer. We have designed, synthesized, and characterized a library of potent CII inhibitors atpenin A5 and diazoxide analogs with enhanced ‘drug-likeness’ and evaluated their antineoplastic activity. Several of these derivatives showed greater activity and selectivity to inhibit the CII. Design aspects of lead derivatives (16c) include optimum ligand lipophilicity efficiency of >5, and half-life of >3 hours. This derivative displayed potent and selective inhibition of cell proliferation in both multiple human prostate cancer cell lines and …

Design, Synthesis And Evaluation Of Novel Inhibitors Of Type 5 And 10 17Β-Hydroxysteroid Dehydrogenases, Ahmed Morsy

Theses & Dissertations

17β-Hydroxysteroid dehydrogenases (17β-HSDs) are essential enzymes in steroid metabolism. More and more evidence points to the pivotal contributions of these enzymes in various other metabolic pathways. Therefore, the latest research results give new insights into the complex metabolic interconnectivity of the 17β-HSDs with human diseases. This dissertation focuses on the metabolic activities of type 5 and 10 17β-HSDs. More specifically, regarding 17β-HSD5 contributions to the progression of prostate cancer (PCa) and 17β-HSD10 aggravation of amyloid-beta (Aβ)-induced toxicity in Alzheimer's disease (AD).

The second leading cause of cancer-related death in males is PCa, with the highest incidence rate of all cancers …

Modification And Antichlamydial Activity Evaluation On Dysregulators Of Cylindrical Proteases, Jiachen Feng

Theses & Dissertations

Chlamydia trachomatis infection is the most commonly reported sexually transmitted disease in the United States and the world. This pathogen can cause long-term health problems including blindness, pelvic inflammatory disease (PID) and ectopic pregnancy, which can be life-threatening if left untreated. To this day, there is no chlamydia-specific drug on the market. The standard treatment uses broad-spectrum antibiotics, which may affect regular functions of the commensal microbiota and leads to the development of bacterial resistance. Recently, a series of compounds based on Activators of Self-Compartmentalizing Proteases (ACP) was reported to show antichlamydial activity. Based on that scaffold, we prepared 21 …

Characterization Of Di-Aryl Urea Compounds Against Acute And Chronic Toxoplasma Gondii, Austin Sanford

Theses & Dissertations

Toxoplasma gondii is an obligate intracellular parasite that has infected nearly 60 million individuals in the United States alone. Acute infection causes ill effects to the fetus in utero when mothers are primarily infected, and to immunocompromised individuals. Chronic infection consists of quiescent tissue cysts located primarily in brain tissue and is capable of reverting back to the acute stage causing severe toxoplasma encephalitis in immunocompromised individuals. Current treatments for acute infection are lacking while there are no approved treatments for the clearance of chronic infection. The aim of this research was to evaluate a family of di-aryl urea compounds …

Lipoxin A 4 (Lxa 4 ) Promotes Reduction And Antibiotic Efficacy Against Pseudomonas Aeruginosa Biofilm, Julianne M. Thornton, Jean Walker, Prem Yugandhar Kadiyam Sundarasivarao, Bernd Spur, Ana Rodriguez, Kingsley Yin

Rowan-Virtua Research Day

Pseudomonas aeruginosa (P aeruginosa) is an opportunistic bacterium commonly found in wound infections and airways of cystic fibrosis patients P aeruginosa readily forms biofilms which can reduce the efficacy of antibiotics used to eradicate the pathogen We have previously shown that a Specialized Pro resolving Mediator ( Lipoxin A 4 (LxA 4 is a quorum sensing inhibitor which can reduce P aeruginosa virulence In this study, we examined the direct actions of LxA 4 and RvD 2 on P aeruginosa biofilm formation and virulence gene expression The influence of LxA 4 on antibiotic efficacy and the combined effects on biofilm …

Evaluation Of A Keratin 1 Targeting Peptide-Doxorubicin Conjugate In A Mouse Model Of Triple-Negative Breast Cancer, Azam Saghaeidehkordi, Shiuan Chen, Sun Yang, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Chemotherapy is the main treatment for triple-negative breast cancer (TNBC), a subtype of breast cancer that is aggressive with a poor prognosis. While chemotherapeutics are potent, these agents lack specificity and are equally toxic to cancer and nonmalignant cells and tissues. Targeted therapies for TNBC treatment could lead to more safe and efficacious drugs. We previously engineered a breast cancer cell targeting peptide 18-4 that specifically binds cell surface receptor keratin 1 (K1) on breast cancer cells. A conjugate of peptide 18-4 and doxorubicin (Dox) containing an acid-sensitive hydrazone linker showed specific toxicity toward TNBC cells. Here, we report the …

Apigenin And Structurally Related Flavonoids Allosterically Potentiate The Function Of Human Α7-Nicotinic Acetylcholine Receptors Expressed In Sh-Ep1 Cells, Waheed Shabbir, Keun-Hang Susan Yang, Bassem Sadek, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Phytochemicals, such as monoterpenes, polyphenols, curcuminoids, and flavonoids, are known to have anti-inflammatory, antioxidant, neuroprotective, and procognitive effects. In this study, the effects of several polyhydroxy flavonoids, as derivatives of differently substituted 5,7-dihydroxy-4H-chromen-4-one including apigenin, genistein, luteolin, kaempferol, quercetin, gossypetin, and phloretin with different lipophilicities (cLogP), as well as topological polar surface area (TPSA), were tested for induction of Ca²⁺ transients by α7 human nicotinic acetylcholine (α7 nACh) receptors expressed in SH-EP1 cells. Apigenin (10 μM) caused a significant potentiation of ACh (30 μM)-induced Ca²⁺ transients, but did not affect Ca²⁺ transients induced by high K^{+ …}

Enantioselective Interactions Of Anti-Infective 8-Aminoquinoline Therapeutics With Human Monoamine Oxidases A And B, Narayan D. Chaurasiya, Haining Liu, Robert J. Doerksen, N. P. Dhammika Nanayakkara

Faculty and Student Publications

8-Aminoquinolines (8-AQs) are an important class of anti-infective therapeutics. The monoamine oxidases (MAOs) play a key role in metabolism of 8-AQs. A major role for MAO-A in metabolism of primaquine (PQ), the prototypical 8-AQ antimalarial, has been demonstrated. These investigations were further extended to characterize the enantioselective interactions of PQ and NPC1161 (8-[(4-amino-1-methylbutyl) amino]-5-[3, 4-dichlorophenoxy]-6-methoxy-4-methylquinoline) with human MAO-A and-B. NPC1161B, the (R)-(−) enantiomer with outstanding potential for malaria radical cure, treatment of visceral leishmaniasis and pneumocystis pneumonia infections is poised for clinical development. PQ showed moderate inhibition of human MAO-A and-B. Racemic PQ and (R)-(−)-PQ both showed marginally greater (1.2-and …

Hiv-1 Tat Protein Promotes Neuroendocrine Dysfunction Concurrent With The Potentiation Of Oxycodone’S Psychomotor Effects In Female Mice, Mohammed F. Salahuddin, Fakhri Mahdi, Suresh P. Sulochana, Jason J. Paris

Faculty and Student Publications

Human immunodeficiency virus (HIV) is associated with neuroendocrine dysfunction which may contribute to co-morbid stress-sensitive disorders. The hypothalamic-pituitary-adrenal (HPA) or-gonadal (HPG) axes are perturbed in up to 50% of HIV patients. The mechanisms are not known, but we have found the HIV-1 trans-activator of transcription (Tat) protein to recapitulate the clinical phenotype in male mice. We hypothesized that HPA and/or HPG dysregulation contrib-utes to Tat-mediated interactions with oxycodone, an opioid often prescribed to HIV patients, in females. Female mice that conditionally-expressed the Tat1–86 protein [Tat(+) mice] or their counter-parts that did not [Tat(−) control mice] were exposed to forced swim …

Optimizing The Role Of Clinical Pharmacy Services In Transitions Of Care, Dj Clark, Clara Mikhaeil, Karen White

Providence Pharmacy PGY2 Program at Providence Medical Group 2021

Purpose

Health & Services The purpose of this project is to improve clinical outcomes in patients transitioning from inpatient to outpatient care by optimizing the process that primary care pharmacists use to perform comprehensive medication reviews.

Background

• Transitions of care from the inpatient to outpatient setting is an area of great opportunity for improving patient outcomes. • One prospective cohort study found that 20% of patients discharged from the hospital to home experienced an adverse event within 3 weeks of discharge. Of these adverse events, 66% were medication related.1 • Another observational study found that 14% of patients had …

Detect Adverse Events And Medication Errors Using Technology, Kenneth Maxik, Craig Kimble, Alberto Coustasse

Pharmacy Practice & Administration

Technology has changed the practice of pharmacy. Many systems are now part of an ever increasingly interfaced or integrated health care system allowing the electronic exchange of prescriptions from electronic health records (EHRs) to the pharmacy information system and bidirectional data exchange for many items, such as lab results and test information. With meaningful use of automated distribution cabinet databases, EHR efforts, electronic data exchange, and smart pump technology, the availability of data to use for addressing and preventing adverse medication events has grown. Use of these systems has allowed a data-rich environment to store and retrieve reporting. Mining data …

Evaluation Of Clinical Pharmacist Management Trends For Depression, Adam Olesen, Kelsie Fiss, Judy Wong

Providence Pharmacy PGY2 Program at Providence Medical Group 2021

Background

• Depression affects almost 10 of Americans over 18 years old 1 • Per the Centers for Disease and Control Prevention, the 2020 COVID 19 pandemic has led to an increase in adults struggling with mental health 1 • There is currently a shortage of mental health prescribers, with over half of all counties within the United States not having a single psychiatrist 2 • Southern Oregon also has a shortage of mental health prescribers, resulting in longer wait times for care • Evidence demonstrates that depression managed by pharmacists in the primary care setting led to increased follow …

An Evaluation Of The Use Of Tranexamic Acid In The Treatment Of Bradykinin-Mediated Angioedema In The Emergency Department, Sarah Yb Kim, Carol Keller

Providence Pharmacy PGY1 Program at Providence Milwaukie and Providence Newberg Medical Centers 2021

Background

Bradykinin mediated angioedema is an overarching term that includes idiopathic angioedema, angiotensin converting enzyme inhibitor (ACEi) induced angioedema and hereditary angioedema (HAE). •This is an emergent condition that must be treated with the utmost urgency due to the fatal outcomes associated with the rapid constriction of the throat. •Bradykinin mediated angioedema is treated differently from histamine associated angioedema due to its resistance to corticosteroids and antihistamines. •HAE and ACEi induced angioedema are treated similarly but there is a lack of unanimity in the first line pharmacologic treatment. •Current treatment options include fresh frozen plasma, bradykinin-2 receptor antagonists, plasma-kallikrein inhibitors …

Medication And Pharmacy-Related Outcomes As Part Of The Seniors At Risk For Falls After Emergency Room Visit (Safer) Project, Hyesoo Chae, Sharon Leigh, Colleen M Casey

Providence Pharmacy PGY1 Program at Providence Portland and Providence St. Vincent Medical Centers 2021

Background

The United States is comprised of an aging population; adults over the age of 85 are the fastest-growing age group in the United States and will reach approximately 9 million in 2030.1 25% of patients ≥ 65 years old in the United States report falling each year.1 There are over 3 million emergency department visits related to falls in the United States, totaling approximately 50 billion dollars in total medical expenditures.2 Falls are a major threat for older adults as they can lead to increased risk of further injury, loss of independence, decreased mobility, and premature death.1,2 Despite numerous …

Review Of Prophylactic Anticoagulation Strategies And Outcomes For Covid-19 Patients (Research In Progress), Caleb Galindo, Pamela Levine, Melanie Geer

Providence Pharmacy PGY1 Program at Providence Portland and Providence St. Vincent Medical Centers 2021

Background

In March of 2020, the World Health Organization (WHO) declared the spread of COVID-19 a global pandemic. •Though largely considered a respiratory disease, research continues to demonstrate additional impacts of COVID-19 on other organ systems.2, 3 •A key characteristic of COVID-19 is marked inflammation leading to hypercoagulability.2, 3, 6 •Infected patients are at a higher risk of developing thromboembolic events (VTE and stroke) compared to healthy adults. 2, 3, 6 •Some clinicians have trialed varying anticoagulation strategies for patients with COVID-19 based on coagulation parameters such as D-dimer.4, 5, 6 •Multiple expert groups have released preliminary guidance on anticoagulation …

Evaluation Of Medication History Technician (Mht) Expansion At A Large Tertiary Medical Center, Sarah Auer, Rochelle Castrillo, Tony Lucchi

Providence Pharmacy PGY1 Program at Providence Milwaukie and Providence Newberg Medical Centers 2021

Background

• The yearly joint commission National Patient Safety Goals for 2020 and 2021 stress the importance of using medications safely which includes an emphasis on medication reconciliation and decreasing medication discrepancies. 1,2 o Pharmacy Medication History Technicians (MHTs) work as an integral part of the medication reconciliation process to gather complete medication histories o The goal of medication reconciliation is to decrease medication discrepancies  decreased medication related adverse events  improve patient outcomes • Pharmacist run medication reconciliation programs have shown decreased medication errors by over 80% when compared to standard medication reconciliation performed by nurses or other …

Assessing The Effect Of An Electronic Health Record Order Entry Guideline On Duration Of Outpatientantimicrobial Therapy Prescribed For Uncomplicated Urinary Tract Infections, Kasey Rubin, Chelsea Houshour, Christine Doran

Providence Pharmacy PGY2 Program at Providence Medical Group 2021

Background

• Fifty percent of antibiotics prescribed in the outpatient setting are unnecessary1. •Outside of unnecessary prescribing, the antibiotics chosen can be incorrect with an inappropriate duration of therapy1. •It has been estimated that resistant infections affect nearly 3 million Americans annually and are the cause of 35,000 deaths each year with added costs up to $33.2 billion dollars1. •The Centers for Disease Control (CDC) recommends that outpatient antimicrobial stewardship programs identify “high priority conditions.” •Examples of high priority conditions include acute respiratory infections, urinary tract infections (UTI)and skin and soft tissue infections (SSTI).2 •Antibiotics are not associated with a …