Pharmacy and Pharmaceutical Sciences Commons^™

Novel Oral Anticoagulants: A Comparative Study Of The Clinical Potential For Dabigatran, Rivaroxaban, And Apixaban Versus Warfarin, Lindsay Mark, Joanne Tran, Zachary Jones, Jessica Beck, David Bright

Pharmacy and Wellness Review

Although Coumadin® (warfarin) has been the standard outpatient anticoagulant for long-term prevention of thrombosis for many decades, it presents with significant challenges for both patients and health care providers in optimizing standards of care including dietary and drug restrictions, regular monitoring of the patient's International Normalized Ratio (INR), and difficulty maintaining therapeutic levels. Despite its unmistakable effectiveness, there has been an interest from the medical community in developing potential alternative drug therapies. As a result, within the past three years the U.S. Food and Drug Administration (FDA) has approved the use of three new oral anticoagulant drugs (dabigatran, rivaroxaban, and …

Antidepressant Therapy: A Review Of Current Treatment Options And A Glance At The Future, Brittany Dye, Stacy Henthorne, Molly Kulp, Tristan Maiers, Zachary Crawford, Erin Petersen

Pharmacy and Wellness Review

Depression and anxiety disorders are two of the most common mental illnesses experienced by people within the United States, affecting 6.7 percent of the adult population per year. This article will focus on one specific type of depression, major depressive disorder (MDD), characterized by two or more weeks of depressed mood and/or decreased interest in normally enjoyed activities. Depression complicates treatment of other disease state(s), making successful treatment of depression essential in the management of a patient's overall health. This review will evaluate the pathophysiology, antidepressant treatment, and new approaches to treatment, specifically vortioxetine, for MDD.

Fda Approves New Tuberculosis Drug: Bedaquiline (Sirturo®), Megan Ruffner, Kent Wilin, Charles Hay, Zachary Crawford, Andrew Roecker

Pharmacy and Wellness Review

Tuberculosis (TB), caused by the acid-fast bacilli (AFB) Mycobacterium tuberculosis, is an infectious disease that continues to greatly impact morbidity and mortality worldwide; in 2011 it caused 1.4 million deaths. Some strains of the bacteria have become resistant to current treatment regimens, resulting in multidrug-resistant (MOR) and extensively drugresistant (XOR) TB. The emergence of these resistant strains of bacteria calls for new treatment regimens that can quickly and effectively eradicate the organism. The U.S. Food and Drug Administration (FDA) recently approved Sirturo® (bedaquiline) with the indication of MDR pulmonary TB. Bedaquiline introduces a novel mechanism of action via the inhibition …

Truvada® Recommended By Fda Committee For Pre-Exposure Prophylaxis In High-Risk Hiv-Negative Individuals, Justin Steele, Emily Blum, Alison Steinbrunner, Lara Long, Andrew M. Roecker

Pharmacy and Wellness Review

Once-daily combination tenofofovir disoproxil fumarate (TDF) and emtricitabine (FTC) has received Food and Drug Administration (FDA) approval for use in pre-exposure prophylaxis (PrEP) against Human Immunodeficiency Virus (HIV) infection in high-risk individuals. In clinical trials, FTC/TDF has been shown to reduce the risk of HIV acquisition by 62 percent in sexually active heterosexual men and women. Similarly, use of FTC/TDF demonstrated a 44 percent reduction in HIV infection within the men who have sex with men population.⁷ When used compliantly and in conjunction with safe sex practices, it appears that FTC/TDF can play an important role in reducing the …

Comparing The Glp-1 Receptor Agonists: Byetta®, Victoza® And Once-Weekly Bydureon™, Todd A. Tucker Jr., Sarah Turley, Kaila Bollinger, Jessica Beck, Sandra L. Hrometz

Pharmacy and Wellness Review

Type 2 diabetes mellitus (T2DM) has traditionally been managed with oral medications. However, in the last few years, subcutaneous glucagon-like peptide-1 (GLP-1) receptor agonists have risen to fame. These agents serve as a reliable addition to current monotherapy. GLP-1 receptor agonists offer a significant reduction in hemoglobin AlC (HbAlc), fasting plasma glucose, and have the added benefit of weight loss. They work primarily by enhancing glucose-dependent insulin secretion while inhibiting glucagon secretion. The available GLP-1 agonists are Byetta® (exenatide), Victoza® (liraglutide), and Bydureon™ (exenatide extended-release). Studies suggest that they are similar in safety and efficacy, with the longer acting GLP-1 …

Sildenafil As An Appropriate Monotherapy Option In The Treatment Of Pulmonary Arterial Hypertension (Pah), Kaitlin Horton, Kent Wilin, Sarah Ginty, Lara Long, David Bright

Pharmacy and Wellness Review

Pulmonary arterial hypertension (PAH) is a debilitating disease characterized by constriction in the diameter of the pulmonary arterial lumen.1,2 This leads to increased pressure and stress on the right ventricle of the heart, which may lead to heart failure and death.2,3 Currently there are only a few treatment options for patients with PAH. Sildenafil, a phosphodiesterase type 5 (PDE-5) inhibitor, can be used to treat PAH. Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP). Increased cGMP concentration results in pulmonary vasculature relaxation. Current clinical trials have indicated that sildenafil can significantly improve many of the symptoms of PAH. The …

Overview Of Stevens-Johnson Syndrome And Toxic Epidermal Necrolysis, Christina Spinaris, Sarah Kradel, Tara Tokar, Zachary Crawford, Michael M. Milks

Pharmacy and Wellness Review

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are immunologic reactions that typically present due to drug hypersensitivity. These reactions present with serious mucocutaneous manifestations that can lead to significant morbidity and mortality. The pathogeneses of SJS and TEN have yet to be clearly elucidated, but three potential immunologic mechanisms have been defined in literature: granulysin, Fas-FasL, and perforin and granzyme B. Medications have been immunologically linked as the primary causative agents of SJS/TEN. Corticosteroids, intravenous immunoglobulin administration (IVIG) and cyclosporine have been employed as treatments; however, none have resulted in consistent positive outcomes. Pharmacists have a significant role in …

The Impact Of Pharmacogenomics On Chemotherapeutic Drug Development And Use, Lara Long, Amy Pasternak, Ellen Hazelet, David Kisor

Pharmacy and Wellness Review

Cancer therapy is largely dependent on general treatment guidelines, and patients undergoing chemotherapy often experience treatment failure with standard drugs. The development of individualized drug therapy through pharmacogenomics has the potential to enhance chemotherapy regimen selection and improve patient outcomes. Antineoplastic agents such as cetuximab and trastuzumab are effective in treating cancers possessing specific genetic biomarker characteristics. Patients need to undergo genetic testing before these agents are administered to ensure appropriate use. Cetuximab has been shown to improve outcomes in metastatic colorectal cancers and head and neck squamous cell carcinomas positive for EGFR. Trastuzumab has shown benefit in human epidermal …

Improving Maternal And Fetal Health: A Look At Thyroid Function During Pregnancy, Sarah Ginty, Jessica Beck, Taylor Gauthier, Amanda Meyer, Michelle R. Musser

Pharmacy and Wellness Review

Maintenance of thyroid function during pregnancy is critical for both maternal and fetal health and development; therefore, knowledge regarding the relationship between thyroid hormones and pregnancy is essential. The American Thyroid Association task force has developed clinical guidelines on the diagnosis and treatment of thyroid disease during pregnancy. Gestational thyroid diseases are divided into two classifications, hypothyroidism and hyperthyroidism, which are further divided into more specific classifications based on clinical presentation. Differentiation, diagnosis, and monitoring of thyroid diseases throughout pregnancy require assessing symptoms, as well as obtaining levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) concentration by a simple …

Dronedarone: An Update To A Controversial Therapy For Atrial Fibrillation, Zachary Crawford, Sara Mcallister, Amanda Hoersten, Jennifer Bauer, Megan Keller, David Bright

Pharmacy and Wellness Review

As of 2004, it was estimated that 2.2 million Americans were diagnosed with paroxysmal or persistent atrial fibrillation (AF) resulting in one out of every six strokes in the United States. AF leads to a reduction in pumping efficiency of the heart increasing the risk of several serious sequelae such as thromboembolic stroke and congestive heart failure (CHF). It also results in a reduced quality of life for the patients suffering from the disease. Patients with AF require appropriate antiarrhythmic therapy to control symptoms and prevent adverse effects of the condition. Multaq® (dronedarone), an antiarrhythmic drug approved for AF in …

Lysteda® For Heavy Menstrual Bleeding, Erica B. Schoenberger, Todd A. Tucker Jr., Justin W. Steele, Amanda Meyer, Sandra L. Hrometz

Pharmacy and Wellness Review

Lysteda®, a novel formulation of tranexamic acid, is an antifibrinolytic medication recently approved by the Food and Drug Administration (FDA) for the treatment of heavy menstrual bleeding. Tranexamic acid has been shown to significantly reduce menstrual blood loss while simultaneously allowing a woman to safely become pregnant. The major advantage of Lysteda® (an oral modified-release formulation of tranexamic acid) compared to oral immediate-release tranexamic acid, is the decreased occurrence of gastrointestinal side effects. As there are no therapeutic equivalents to Lysteda® for heavy menstrual bleeding, it is important for pharmacists to be able to counsel patients appropriately on the specific …

Pharmacogenetic Implications Regarding Second Generation Antipsychotics Clozapine And Risperidone, Sarah E. Ginty, Amy Pasternak, Lauren Desko, Jamie Amero, David Kisor

Pharmacy and Wellness Review

Pharmacogenomics is a growing area of pharmacy that has the potential to improve individualization of medication choices, dosing and predictability of side effects. Clozapine and risperidone are atypical antipsychotics whose metabolism, efficacy and side effects are influenced by single nucleotide polymorphisms (SNPs) in a patient's genetic makeup. It has been shown that a polymorphism in the D3 dopamine receptor is associated with an increased risk in developing tardive dyskinesia as an adverse event while taking risperidone. Also, there is evidence that a patient with a homogenous C genotype in the gene coding for the 5-HTzc receptor has a higher risk …

Effects Of Hormone Therapy On Cognition In Post-Menopausal Women, Jessica Langhals, Megan Meyer, Erica Schoenberger, Amanda Meyer, Kristen Finley Sobota

Pharmacy and Wellness Review

Menopause occurs as a result of decreased natural estrogen production by the body. A variety of short-term and long-term symptoms can occur during menopause, which may significantly impact a woman's daily life. Hormone therapy (HT) is commonly employed to alleviate these unwanted symptoms and to regain balance of hormone levels. Options include estrogen-only or estrogen-progestin combination therapy. While HT may help relieve symptoms such as cognitive decline caused by menopause, it also carries potential side effects. Although HT has shown a potential benefit in women with Alzheimer's disease (AD), overall outcomes measuring cognitive function improvement are inconclusive. Therefore, HT should …

The Use Of Crizotinib In Late Stage Lung Cancer Patients With An Abnormal Alk Gene, Lara Long, Kelly Dye, Courtney Porter, Ellen Hazelet, Karen L. Kier

Pharmacy and Wellness Review

The relatively new anti-cancer drug, crizotinib (Xalkori®, Pfizer), has created excitement in the research community. This drug has exhibited dramatic clinical benefits for select non-small cell lung cancer patients showing evidence of a mutation in the EML4-ALK gene. This gene mutation is present in 4 to 5 percent of non-small cell lung cancer patients. Crizotinib acts through a tyrosine kinase inhibition pathway, targeting the ALK and MET tyrosine kinases, to inhibit phosphorylation of activated ALK, which halts the ALK gene mutation and impedes metastasis. In phase I clinical trials, a 57 percent overall response rate was shown, and researchers calculated …

Lithium Therapy In Alzheimer's Disease, Ross Robison, Sara Swick, Lauren Bajbus, Jennifer Bauer, B. Shane Martin

Pharmacy and Wellness Review

Alzheimer's disease (AD) is a neurodegenerative disorder with no known cure which has a strong impact on patients and their caregivers. Current treatments for AD can slow the disease progression, but cannot reverse the damage that has already been done, resulting in some level of lifelong disability for affected patients. The use of lithium has shown promising results in mice models of AD. While animal models have produced positive results, additional human trials need to be conducted in order to determine a place for lithium in Alzheimer's disease therapy. Pharmacists should be aware of this potential new use of lithium …

Fidaxomicin (Dificid®): New Antibiotic Approved For The Treatment Of Clostridium Difficile Infections, Sara M. Mcallister, Zachary Crawford, Joshua Ilenin, Ellen Hazelet, Andrew M. Roecker

Pharmacy and Wellness Review

Clostridium difficile is a gram-positive, spore forming bacteria normally transmitted by the fecal-oral route. Infection develops in patients with decreased normal gut flora and is typically associated with recent antibiotic use. Other risk factors include bowel surgery, compromised immune system function, extended hospital stays, and other underlying diseases. C. difficile bacteria produce two toxins, which cause increased intestinal fluid secretion and inflammation. Patients commonly present with diarrhea, abdominal discomfort, loss of appetite, and nausea. Current treatment guidelines are to discontinue antimicrobial agents and increase hydration. Less severe C. difficile associated diarrhea (CDAD) cases are treated with metronidazole 500 mg three …

The Emerging Role Of Ticagrelor In Acute Coronary Syndromes, Jennifer Bauer, Brittany Dye, Kimberly Baucher, Megan Keller, David Bright, Karen L. Kier

Pharmacy and Wellness Review

Antiplatelet therapy has become a mainstay in the treatment of acute coronary syndromes (ACS). Until recently, options were somewhat limited when it came to individualizing drug selection. Plavix® (clopidogrel) has been successfully used for many years but requires activation by CYP enzymes. Depending on an individual patient's genetic makeup, function of these CYP enzymes may be altered, which may increase the risk for clots. The recent approval of Effient® (prasugrel) and Brilinta® (ticagrelor) has provided physicians and pharmacists with more options and may hopefully lead to improved clinical outcomes. Ticagrelor specifically exhibits clinically different pharmacologic characteristics that require twice daily …

Synthesis Of Bis(Imino)Pyridine Iron(Ii) Complexes And Development Of Bis(Imino)Pyridine Iron(Ii) Catalyzed Carbene Transfer Reactions, Ban Wang

Masters Theses & Specialist Projects

Metal catalysis of symmetric and asymmetric carbene transfer reactions has been widely applied in natural product synthesis and material science over years. Metal carbene can be easily generated from the extrusion of nitrogen under the catalysis of metal complexes to further undergo various organic reactions, O/N/C-H insertions, cycloadditions, and ylide formations. Currently, the dominant effective catalysts for carbene reactions are built with expensive precious metal, for example, rhodium, ruthenium, palladium, gold. Notably, the effective reactivity and enantioselectivity of the dirhodium(II) catalysts are researched and established over the decades. However, the use of precious metal catalysts is the major source of …

Sipuleucel-T (Provenge®): Therapeutic Use And Financial Implications, Courtney Porter, Joshua Ilenin, Lisa Berni, Ashley Overy, Karen L. Kier

Pharmacy and Wellness Review

Although mortality rates have been declining, prostate cancer accounts for a large percentage of cancer diagnoses around the world. Sipuleucel-T (Provenge®), an autologous cellular immunotherapy targeted against the antigen expressed in most prostate cancers, has been shown to increase the median survival rate of castration-resistant prostate cancer. Even so, the therapeutic risks and benefits, as well as financial implications, all currently play a role in the governmental decision to reimburse for this new therapy.

The Pharmacogenetics Of Opioid Pain Management, Maryanne Ventura, Lauren Desko, Kimberly Gathers, Ashley Overy, David Kisor

Pharmacy and Wellness Review

High rates of interpatient variability in drug metabolism and drug response for nearly all medications lead to the hypothesis that assessment of an individual patient's genotype with respect to their ability metabolize certain drugs can be a useful tool in predicting a patient's responsiveness to certain medications. Evaluating patients using pharmacogenomics as a basis for assessment could allow pharmacists to decide which treatment options would be most efficacious in a given patient and, thereby, have significant impact in the clinical setting. This holds true especially in the case of prodrugs, which require in vivo activation to an active or more …

Prescription Drug Manufacturer Attempts To Prevent Abuse Of Controlled Substances, Amanda R. Hoersten, Nathaniel Hedrick, Lacey Shumate, H. Paige Stewart, Caitlin Swann, Michael Milks

Pharmacy and Wellness Review

In the United States, prescription drug abuse is on the rise. This trend has impacted the makers of OxyContin®, as well as the manufacturers of other controlled substances,to reevaluate how they formulate their products, resulting in medications, that are more difficult to abuse. These abuse-deterrent formulations utilize physical, chemical and aversion barriers, specific delivery systems, and prodrug technology to prevent abuse. Additionally, some manufacturers have implemented the use of risk-management campaigns and education programs, to reduce the misuse of their products. Working together with prescription drug manufacturers, pharmacists play an important role in preventing abuse and educating patients on the …

Chemical Epitope Targeting: Review Of A Novel Screening Technology, Qurrat Ul-Ain, Rene Kandler, Dylan Gillespie, Arundhati Nag

Scholarly Undergraduate Research Journal at Clark (SURJ)

Chemical Epitope Targeting is a novel technology developed for designing peptide ligands with high affinity and specificity against specific regions of a protein that may be inaccessible to small molecules or antibodies. In this review, we summarize the key steps and significant applications of this technology. Operating on the same principles as antibody-antigen interactions, this technique involves chemically synthesizing the region of interest on the protein, called the epitope, as a polypeptide with a biotin detection tag and a strategically placed alkyne or azide presenting amino acid. The constructed epitope is screened against a comprehensive linear or cyclic One Bead …

Exploration Of The Inhibitory Properties Of The Nucleoside Antibiotic Salicyl-Ams And Analogues Targeting Siderophore Biosynthesis In Mycobacterium Tuberculosis, Glennon Bythrow

Dissertations, Theses, and Capstone Projects

Mycobacterium tuberculosis (Mtb) is a resilient, obligate bacterial pathogen responsible for pulmonary tuberculosis disease (TB), that has upheld a significant impact on global public health throughout history. The World Health Organization (WHO) approximates nearly 10 million new TB cases arose in 2017 alone, accounting for 1.6 million deaths. There has been a notable rise in TB cases produced by multidrug‑resistant (MDR) and extensively drug-resistant (XDR) strains of Mtb. This, along with the intrinsic resistance of Mtb to many standard drugs and poor patient compliance, is deeply impacting global control of TB. Among the several strategies currently in …

Design And Synthesis Of Pyrimidine Based Heterocycles As Potential Anti-Cancer Agents With Combination Chemotherapeutic Potential Or Targeted One Carbon Metabolism Inhibition And Anti-Opportunistic Agents, Arpit Doshi

Electronic Theses and Dissertations

This dissertation describes the design, synthesis and biological evaluation of monocyclic, bicyclic and tricyclic pyrimidine-based heterocycles as a) single agents with combination chemotherapy potential having dual antiangiogenic effects and cytotoxic effects or b) one-carbon metabolism inhibitors for targeted tumor therapy; or c) selective Pneumocystis jirovecii (pj) dihydrofolate reductase (pjDHFR) inhibitors for pneumocystis pneumonia (PCP) infection.

The work in this dissertation is centered on identifying structural features that are necessary for inhibition of tubulin polymerization or thymidylate synthase as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), epidermal growth …

A Quantitative Study Of Drug Recrystallization In Drug-In-Adhesive Transdermal Patches Using Vibrational Spectroscopy, Yi Li

Electronic Theses and Dissertations

Drug-in-adhesive (DIA) transdermal patches are an important type of transdermal drug delivery system (TDDS). The drugs used in the DIA system are frequently present in metastable forms, such as amorphous solids or supercooled liquids. These drug states are thermodynamically unstable and tend to undergo recrystallization. Recrystallization of the active pharmaceutical ingredient can adversely affect the efficacy of transdermal products. This dissertation demonstrates a systematic approach to quantify the crystalline content of the API in DIA systems. This approach uses a novel method of preparing calibration standards and a spectroscopic method to reliably predict crystalline content in DIA patches. Spectroscopic tools, …

Synthesis And Characterization Of Long-Acting Rilpivirine Prodrugs, James R. Hilaire

Theses & Dissertations

Antiretroviral therapy (ART) requires lifelong daily dosing to suppress viral replication, restore or maintain immune function and improve quality of life. As an alternative, long-acting (LA) antiretrovirals (ARVs) aim to deliver therapeutic drug concentrations over an extended period, ultimately requiring monthly or even more extended dosing intervals. Specifically, the success of recent clinical trials examining LA cabotegravir and rilpivirine (CAB and RPV LA) highlight the advent of these novel HIV-1 therapeutics. Further optimization of LA dosage forms are required and rests upon improving dosing frequency, injection volumes and tissue distribution to viral compartments. To this end, we report the synthesis …

New Vaccines In The Pipeline 2019, Michael Phan, Luma Munjy, Nicole Benipayo, Jeff Goad, Sun Yang

Pharmacy Faculty Articles and Research

"Before clinicians can administer a vaccine in the United States, the FDA must approve and license it. Investigators conduct extensive research leading up to this process, typically testing a vaccine in thousands of patients over 6 to 7 years or longer. Even with large sample sizes and rigorous study designs, rare adverse effects may be missed. For example, RotaShield, the first vaccine for rotavirus, was withdrawn from the market in 1999, despite being tested in more than 10,000 patients. Postmarketing surveillance demonstrated that a rare, yet serious, risk of intussusception was linked to the vaccine, and the FDA determined that …

Helsinn Healthcare S.A. V. Teva Pharmaceuticals Usa, Inc.: “Sale” Keeps Its Old Meaning Under The Leahy–Smith America Invents Act, Sherrie Holdman

Minnesota Journal of Law, Science & Technology

No abstract provided.

Alzheimer's Disease Drug Development Pipeline: 2019, Jeffrey Cummings, Garam Lee, Aaron Ritter, Marwan Sabbagh, Kate Zhong

School of Medicine Faculty Research

Introduction Alzheimer's disease (AD) has few available treatments, and there is a high rate of failure in AD drug development programs. Study of the AD drug development pipeline can provide insight into the evolution of drug development and how best to optimize development practices. Methods We reviewed clinicaltrials.gov and identified all pharmacologic AD trials of all agents currently being developed for treatment of AD. Results There are 132 agents in clinical trials for the treatment of AD. Twenty-eight agents are in 42 phase 3 trials; 74 agents are in 83 phase 2 trials; and 30 agents are in 31 phase …

Identifying The Enzyme Involved In Vacuolar Atpase Acetylation During Doxorubicin-Induced Cardiotoxicity, Rebecca Dang, Tianqing Peng

Western Research Forum

Doxorubicin is an established anticancer medication infamous for its bright colouration and extremely toxic side effects. Emerging studies support that the imbalance between acetylation and deacetylation disrupts the autophagic flux leading to doxorubicin-induced cardiotoxicity. Vacuolar ATPases are a family of electrogenic proton pumps present on the lysosomal membrane that create an acidic environment for proteases to degrade proteins. Our preliminary study found that acetylated Vacuolar ATPase subunit V₀ D1 levels increased in doxorubicin-injected mouse hearts. However, it is unknown how acetylation of subunit V₀ D1 is modulated and whether this modification plays a role in doxorubicin-induced cardiotoxicity.

The …