Pharmaceutics and Drug Design Commons^™

The Development Of Novel Apurinic/Aprymidinic Endonuclease/Redox-Factor 1 Inhibitors For The Treatment Of Human Melanoma, Bella Sharifi

Pharmaceutical Sciences (MS) Theses

Apurinic/apyrimidinic DNA repair endonuclease-1 (APE1), first recognized as an important DNA excision repair enzyme, is also known as Redox Factor-1 (Ref-1) involved in the activation of many nuclear transcription factors in both redox-dependent and independent manner. It has been well-documented that the overexpression of APE/Ref-1 contributes to the development of chemo-resistance and is associated with tumor progression in many human malignancies [1].

Our previous study in melanoma demonstrated that the development of novel inhibitors targeting the redox regulation domain of APE/Ref-1 is a promising strategy for melanoma treatment. To date, limited successes have been reported in developing novel …

Amphiphilic Cell-Penetrating Hybrid Cyclic-Linear Peptides As A Drug Delivery System, Saghar Mozaffari

Pharmaceutical Sciences (PhD) Dissertations

A number of cyclic peptides containing a positively charged ring composed of arginine residues attached to hydrophobic tail made of tryptophan residues through a lysine linker namely [R₅K]W₅, [R₆K]W₅, [R₅K]W₆, [R₇K]W₅, [R₅K]W₇, [R₆K]W₆, and [R₇K]W₇ were synthesized and evaluated as molecular transporters. The peptides were evaluated for their ability to deliver, fluorescence-labeled cell-impermeable negatively charged phosphopeptide (F′-GpYEEI), and fluorescent labeled anti-HIV drugs (F′-FTC and F′-d4T). The results indicated that the presence of positively …

After-Action Report: Tabletop Exercise On Opioid Crisis Response And Resilience, Alexander Siedschlag, Tiangeng Lu

Publications

AGENCY BRIEFINGS The opioid overdose epidemic has been characterized as the worst public health crisis in Pennsylvania, and the nation. Not only practitioners but also institutions of higher education with high research capacity, such as Penn State, are applying existing and developing new instruments to address opioid the crisis. Identifying best practices of preventing, protecting from, mitigating against, responding to, and recovering from opioid overdose outbreak is necessary for public health and safety and important for the overall homeland security enterprise, in consistency with the objectives of the Quadrennial Homeland Security Reviews (QHSR), the National Preparedness Goal (NPG), and the …

Ramucirumab: A New Agent For Advanced Or Metastatic Gastric Junction Adenocarcinoma, Adam Smith, Rebecca Worden, Jessica Hoffert, Brendon Rasor, Hannah Stewart, David Koh

Pharmacy and Wellness Review

Ramucirumab (Cyramza®), approved April 21, 2014, is a vascular endothelial growth factor receptor 2 (VEGFR2) antagonist with a U.S. Food and Drug Administration (FDA) indication for the treatment of advanced or metastatic gastric/gastroesophageal junction adenocarcinoma. Gastric cancer is a prevalent cancer in the United States with a poor prognosis. The phase 3 trial, REGARD, shows that ramucirumab, when used within four months after the last dose of first-line chemotherapy or six months after the last dose of adjuvant chemotherapy, increases overall survival. Also, ramucirumab has been included in combination therapy, such as in the RAINBOW trial, which demonstrated its effectiveness …

Memantine: Can It Be Used To Treat Children With Autism Spectrum Disorder?, Austin Brown, Katherine Liu, Pul Lee, Rachel Muhlenkamp, Manoranjan D'Souza

Pharmacy and Wellness Review

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social, behavior and communicative skills. The current therapy for ASD only targets the associated symptoms such as aggression, self-harming acts or temper tantrums but not the core symptoms of social dysfunction. The pathology of ASD is not fully understood. Interestingly, imaging studies in ASD patients have reported abnormal high levels of glutamate in certain brain regions that play an important role in social interaction and communication. Thus, it has been hypothesized that medications attenuating glutamate transmission may be used as treatment for some of the core symptoms of …

Outbreak Of Ebola Virus Disease, Alexandra Dimit, Tiffany Kneuss, Joelle Farano, Haley Armstrong, Jodi Otte, Andrew M. Roecker

Pharmacy and Wellness Review

Ebola virus disease (EVD) has existed as a major health concern with devastating and, many times, fatal symptoms. The recent outbreaks of EVD in West Africa and the Democratic Republic of the Congo (DRC) have incited international concern. In this article, the implications of EVD will be discussed including the etiology, transmission, signs and symptoms, diagnosis and treatment of the disease. In addition to this discussion, the manner in which major health care organizations, including the World Health Organization (WHO), are dealing with treating infected patients and containing spread of the disease will be covered.

Fda Approves New Inhaled Insulin: Afrezza® (Technosphere® Insulin), Benjamin Finley, Christina Ciccone, Kimberly Loughlin, Michelle Musser

Pharmacy and Wellness Review

Diabetes is an endocrine disease caused by deficiency or malfunction of insulin that results in high blood glucose levels and places patients at higher risk for a number of complications. This chronic disease is difficult to manage and affects millions of people in the United States, costing the health care system billions of dollars a year. Of a variety of antidiabetic agents used to control blood glucose, insulin is perhaps the most effective, but until recently it was only available in injectable form. As of June 27, 2014, a new inhaled insulin called Afrezza® (Technosphere® insulin) was approved by the …

Management Of Breakthrough Pain In Cancer Patients: Traditional And Novel Approaches, Courtney Porter, Nathaniel Hedrick, Katherine Salay, Lacey Shumate, Caitlin Swann, Kelly Reilly Kroustos

Pharmacy and Wellness Review

Approximately 80 percent of career patients experience breakthrough pain (BTP) characterized by acute onset, short duration, and moderate-to-severe intensity. Treatment of BTP using current available medications is often insufficient, leading to the development of various novel approaches that focus on rapid onset of action and short duration of action. Most of these products are still in clinical trials, and future studies are needed to compare the novel approaches to currently available treatments. Non-medication related issues, which arise from a lack of communication and understanding between the patient, physician and pharmacist, are also barriers to adequate BTP management. By educating patients …

Polycystic Ovarian Syndrome And Hyperinsulinemia: Overview And Treatment, Amanda M. Meyer, Lauren D. Bajbus, Sarah E. Drake, Kristen M. Quertinmont, Ashley Overy, Anne Gentry

Pharmacy and Wellness Review

Polycystic ovary syndrome is a prevalent issue in women's health that is associated with hyperinsulinemia and insulin resistance and can lead to long-term health problems. The most highly recommended treatments are diet and lifestyle changes. If these changes alone are not enough, pharmacologic treatments may be employed which include metformin, spironolactone or thiazolidinediones, although more research is needed to fully realize their role. The role of the pharmacist in this disease state includes counseling patients on healthy lifestyle changes, consulting with the physician about prescribing the best medication for each patient, and monitoring therapy adherence in the patient.

Management Of Hypertensive Emergencies In Pediatrics, Jennifer L. Bauer, Jamie L. Amero, Amanda C. Mcdavid, Ryan A. Fischer, Alison L. Huet, Karen L. Kier

Pharmacy and Wellness Review

As hypertension becomes more prevalent in the pediatric population, clinicians are more likely to encounter hypertensive emergencies in children, which require pharmacists and physicians to be educated on the therapeutic options for these emergencies. However, the strict governmental requirements on the testing of these drugs in pediatric patients have limited the amount of available evidence on which to base clinical decisions. This review will highlight the available evidence and preferred treatment options for the management of pediatric hypertensive emergencies.

Genetic Variations In A Cytochrome P450 Enzyme And The Effects On Clopidogrel Bioactivation And Metabolism, Maryanne Ventura, Lauren Desko, Kimberly Gathers, Ashley Overy, David Kisor

Pharmacy and Wellness Review

Clopidogrel, the top prescribed antiplatelet medication for individuals who have experienced a myocardial infarction or cerebral vascular accident or who have peripheral arterial disease, is administered orally as a prodrug. It relies on hepatic metabolism through cytochrome P450 enzymes for conversion to its active form. Current research shows that allelic variation m the gene coding for CYP2C19 is the main factor contributing to the variability of response associated with clopidogrel treatment. Through the promotion of genetic testing for variability in the CYP2C19 gene and competently interpreting test results, pharmacists have the opportunity to use these findings to significantly impact clopidogrel …

Recent Advances Spark Significant Guideline Change: Antiretroviral Therapy (Art) At High Cd4+ Counts In The Treatment Naïve Patient, Joshua Ilenin, Kelly Fargo, Lisa Berni, Kristen Thatcher, Caitlin Swann, Andrew Roecker

Pharmacy and Wellness Review

Human immunodeficiency virus (HIV) targets CD4+ lymphocytes, a critical component to proper functioning of the human immune system. HIV is a significant public health concern, having resulted in over 27 million deaths since its discovery. Currently, several different treatment options exist, with combination antiretroviral therapy (ART) at the forefront. Despite the success of ART therapy, there are number of problems, including poor patient compliance. Due to this, the appropriate time to initiate therapy in the treatment naïve patient is under continuous scrutiny. Recently, several trials have demonstrated evidence suggesting that initiating ART at high CD4+ counts in the treatment naïve …

The Use Of Propranolol In The Treatment Of Posttraumatic Stress Disorder, Tana M. Peterman, Alison L. Huet, Sarah E. Drake, Jamie L. Drees, Robert D. Raiff, B. Shane Martin

Pharmacy and Wellness Review

This article examines the rising issue of post-traumatic stress disorder (PTSD) and possible treatment options. PTSD is a behavioral disorder resulting from memory formation and association with a traumatic event. A search of the published literature reveals several positive studies and case reports suggesting that propranolol, a beta adrenergic receptor antagonist, may be useful for both treatment and prevention of PTSD. Additionally, current studies are being completed in different population groups to determine the overall effectiveness and mechanism by which propranolol is able to provide relief from certain symptoms common to the disorder. This article discusses the medical evidence and …

Options For Breast Cancer Prevention In High-Risk Patients, Ashley M. Overy, Lacey A. Shumate, Sarah M. Webb, Ashley E. Lehnert, Monica A. Weisenberger, Whitney N. Detillion, Andrew M. Roecker

Pharmacy and Wellness Review

Breast cancer is the most frequently diagnosed non-skin cancer in women, and one in eight women will develop breast cancer within their Iifetimes. Unfortunately, the strongest risk factors for breast cancer (i.e. age, family history, hormonal factors) are not easily modified. There is some evidence that chemopreventative drugs may be able to prevent breast cancer in high-risk patients. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer in high-risk women but may be associated with several serious adverse events. Clinical trials are currently in progress to determine if aromatase inhibitors are a viable alternative for breast …

A Review Of Dabigatran, An Oral Anticoagulant, Lindsey A. Hallman, Chad A. Rounds, Rebecca A. Carey, Nicole R. Hume, Karen L. Kier, James Spicer

Pharmacy and Wellness Review

Serious clinical complications associated with venous thrombotic embolism (VTE) necessitate prophylaxis in patient groups who are at high risk of VTE, specifically those recovering from orthopedic surgery with atrial fibrillation, with mechanical heart valves, at increased risk for stroke, or recovering post-MI. Currently, prophylaxis with warfarin, enoxaparin, or fondaparinux has been the standard of therapy, but these therapies each have their limitations. Dabigatran etexilate is an orally available pro-drug of dabigatran, a competitive, reversible, direct inhibitor thrombin (Factor lla). The agent is converted by esterases, and, thus, not associated with the complications of the CYP enzyme system. Dabigatran follows a …

Implementation Of Liberate Protocol With Focus On Delirium In An Acute Care Community Hospital’S Medical And Cardiovascular Intensive Care Units, Jasmine M. Hossler, Emily A. Sedio, Karen L. Kier

Pharmacy Faculty Scholarship

No abstract provided.

Evaluation Of A Perioperative Multi-Modal Analgesia Approach In Regards To Enhanced Recovery After Surgery, Seth Wollenhaupt, Jeremy Ebert, Karen Kier

Pharmacy Faculty Scholarship

No abstract provided.

A Recombinant Cholera Toxin B Subunit Variant (Ctb-Kdel) Exhibits Unique Colon Mucosal Healing Effects That Have Therapeutic Implications For Inflammatory Bowel Disease., Joshua Mark Royal

Electronic Theses and Dissertations

This dissertation uncovers the mechanism and explores the utility of a recombinant cholera toxin B subunit (CTB) variant containing a KDEL endoplasmic reticulum (ER) retention motif (CTB-KDEL) as a drug candidate for the treatment of inflammatory bowel disease (IBD). CTB is a mucosal immunomodulatory protein that induces robust mucosal and systemic antibody responses. This well-known biological activity has been exploited in cholera prevention (as a component of Dukoral® vaccine) and vaccine development for decades. On the other hand, several studies have investigated CTB’s immunotherapeutic potential in the treatment of inflammatory diseases such as Crohn’s disease and asthma. Here, we reveal …

Drug Interactions With Antimalarial Medications In Older Travelers: A Clinical Guide, Jelena Lewis, Tania Gregorian, Ivan Portillo, Jeff Goad

Pharmacy Faculty Articles and Research

Increasingly older adults are traveling to international destinations with malaria as a present risk. Surveillance systems indicate that older adults are more likely to suffer severe complications from malaria. The role of health care providers in selecting an appropriate medication for chemoprophylaxis or treatment of malaria in adults becomes more difficult as older adults undergo physiologic changes that alter the pharmacokinetic and pharmacodynamic nature of medications potentially causing increased drug interactions, adverse events, and altered drug action. A comprehensive literature search from 1970 to present, with a focus on the last 10 years, was conducted on drug interactions, pharmacokinetic and …

A Systematic Comparison Of Lipopolymers For Sirna Delivery To Multiple Breast Cancer Cell Lines: In Vitro Studies, Hamidreza Montazeri Aliabadi, Remant Bahadur Kc, Emira Bousoik, Ashley Barbarino, Bindu Thapa, Melissa Coyle, Parvin Mahdipoor, Hasan Uludağ

Pharmacy Faculty Articles and Research

Small interfering RNA (siRNA) therapy is a promising approach for treatment of a wide range of cancers, including breast cancers that display variable phenotypic features. To explore the general utility of siRNA therapy to control aberrant expression of genes in breast cancer, we conducted a detailed analysis of siRNA delivery and silencing response in vitro in 6 separate breast cancer cell models (MDA-MB-231, MDA-MB-231-KRas-CRM, MCF-7, AU565, MDA-MB-435 and MDA-MB-468 cells). Using lipopolymers for siRNA complexation and delivery, we found a large variation in siRNA delivery efficiency depending on the specific lipopolymer used for siRNA complexation and delivery. Some lipopolymers were …