Pharmaceutics and Drug Design Commons^™

Potential Use Of Dopamine And Dopamine Agonists As Angiogenesis Inhibitors In The Treatment Of Cancer, Benjamin Finley, Katherine Liu, Daniel Powell, Jamie Kellner, David H. Kinder

Pharmacy and Wellness Review

In recent years, there have been numerous developments in monoclonal antibodies used as anticancer drugs with a focus on reducing the ability of cancers to metastasize and produce new vasculature. These agents are called angiogenesis inhibitors and although these agents have been proven effective in treating certain types of cancers, production and administration of monoclonal antibodies comes at a steep cost with a severe side effect profile. Under normal physiologic conditions, angiogenesis is an important mechanism to create new blood vessels from preexisting vessels, usually occurring in adults. Tumor cells can hijack the angiogenesis pathway to produce new distant tumors …

New Cholesterol Guidelines: An Update For Pharmacists, Emily Limberg, Benjamin Finley, Stacy Henthorne, Sarah Kradel, David Bright

Pharmacy and Wellness Review

The American College of Cardiology and American Heart Association published new blood cholesterol guidelines in November 2013. The new guidelines place an emphasis on evidence-based treatment of dyslipidemias and primarily use randomized controlled trials to create recommendations for health care providers. Major changes from the previous guidelines include eliminating low-density lipoprotein goals, the classification of statins by lipid-lowering potential and the creation of four major statin benefit groups. The new guidelines also establish the role of non-statins in dyslipidemias and use the Pooled Cohort Risk Assessment Equations to calculate patients' risk for cardiovascular events and the need for cholesterol-lowering medications. …

Crohn's Disease: Management, Emerging Therapies And The Role Of The Pharmacist, Sarah Turley, Tiffany Kneuss, Lydia Suchecki, Alison Steinbrunner, Kristen Timperman

Pharmacy and Wellness Review

Crohn's disease is a relapsing-remitting disorder of the gastrointestinal tract caused by a mixture of genetic and environmental factors. Pharmacologic treatment of Crohn's disease is patient-specific, and regimens vary widely between individuals. Drug regimens are typically based on 5-aminosalicylate therapy and may include a combination of steroids, histamine 2 receptor antagonists, proton pump inhibitors, immunomodulators, antibiotics, biologic agents and other medications aimed at symptom relief. A new medication, vedolizumab, is currently in phase III clinical trials awaiting U.S. Food and Drug Administration (FDA) approval for use in Crohn's disease. Vedolizumab is an alpha-integrin inhibitor, which is anticipated to have a …

Advances In Treatment Of Chronic Hepatitis C Virus (Hcv) Infection, Halle Orlinski, Kimberly Loughlin, Haley Armstrong, Emily Blum, Andrew M. Roecker

Pharmacy and Wellness Review

Hepatitis C virus (HCV) infection is a prominent cause of chronic liver disease and may lead to serious complications such as liver failure and need for a transplant. The virus is transmitted via exposure to blood and is classified into various genotypes based on genetic mutations in the virus. Current treatment options for HCV infection are not effective in all patients, and there are limited options for patients infected with a genotype other than genotype 1. Two new medications have been approved recently for treatment of HCV infection. Simeprevir (Olysio®) gained U.S. Food and Drug Administration (FDA) approval in November …

Lbrutinib (Lmbruvica™) For Treatment Of Mantle Cell Lymphoma, Brittany Crowe, Joy Hoffman, Hannah Stewart, Alison Steinbrunner, Mark E. Olah

Pharmacy and Wellness Review

Mantle cell lymphoma (MCL) is a rare and moderately aggressive form of non-Hodgkin's lymphoma (NHL) that predominantly presents at an advanced stage in older males. Patients often present with multiple involvement in the lymph nodes, blood, spleen, bone marrow and gastrointestinal tract (GIT). Some patients may be asymptomatic in early stages or present with an incurable, indolent (slow progressing) form, while other patients display rapid growth of more aggressive lymphomas. Overall survival for patients diagnosed with MCL is four to five years and treatment should be initiated in those who are symptomatic. Mantle cell lymphoma responds well to first-line treatment, …

Dapagliflozin: A Newly Approved Sglt2 Inhibitor For The Treatment Of Type 2 Diabetes Mellitus, Ann Marie Ruhe, Rachel Muhlenkamp, Austin Brown, Emily Blum, Sandra L. Hrometz

Pharmacy and Wellness Review

Type 2 diabetes mellitus (T2DM) is a chronic disease in which a hyperglycemic state is induced by insulin resistance. While there are numerous treatment options available to manage T2DM, many patients require changes in therapy throughout treatment, as well as multiple medications. The sodium/glucose cotransporter 2 (SGLT2) inhibitors, canagliflozin and dapagliflozin, offer a therapeutic alternative in T2DM management through the utilization of a unique mechanism of action to provide intensified glycemic control. This article will evaluate the safety and efficacy of dapagliflozin in the management ofT2DM.

Trametinib And Dabrafenib: New Agents For Advanced Stage Melanoma, Kelsey Weisenburger, Kevin Krivanek, Armond Cosiano, Kasie Bellmann, Mark E. Olah

Pharmacy and Wellness Review

Melanoma, the deadliest form of skin cancer, is caused primarily by exposure to ultraviolet radiation. Tumor formation occurs early in disease progression and can easily metastasize. The development of the disease can be described by one of four stages, characterized by tumor size and risk of spreading. The B-rafprotein plays an important role in cell proliferation and has the ability to develop a mutation for continuous activation, resulting in uncontrolled cell growth. Sixty percent of melanomas possess a V600E mutation in the BRAF gene. Recently, drug developers have turned the focus of melanoma treatments toward preventing the activation of the …

The Safety Of Artificial Sweeteners And Their Use In Pharmaceuticals, Kaila Bollinger, Maureen Moynihan, Adam Smith, Alison Steinbrunner, Karen Kier

Pharmacy and Wellness Review

Artificial sweeteners are sugar substitutes that add sweetness to foods and beverages without the extra calories found in sugar. These additives are used to help patients with diabetes avoid hyperglycemia and assist people in losing weight or avoiding weight gain by providing a replacement to higher calorie sugar-sweetened foods. Artificial sweeteners can be found in many sugar-free beverages, candies and gum, as well as pharmaceutical products. Although artificial sweeteners are often recommended over the sugar-sweetened alternatives in weight loss and diabetes prevention, the use of such products are not without risk. Studies have been conducted to assess artificial sweeteners involvement …

Overview Of Kalydeco® (Ivacaftor) For Treatment Of Cystic Fibrosis, Andrew Skouby, Kayti Kintner, Kimberly Loughlin, Emily Blum, Michael Rush

Pharmacy and Wellness Review

Cystic fibrosis (CF) is a genetic disease associated with specific gene mutations that presents with pulmonary inflammation and frequent lung infections, exocrine pancreatic insufficiency, altered sweat composition and declining lung function. Ivacaftor (Kalydeco®) was approved for treatment of cystic fibrosis in patients 6 years of age and older with a G551D mutation on the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Ivacaftor is a CFTR potentiator and does not work in patients with a mutation of the F508del. Efficacy has been demonstrated in several trials with a primary outcome of improved FEV1, improvements in pulmonary exacerbations, patient-reported decrease in respiratory …

Celiac Disease: Current And Investigational Therapies And The Role Of The Pharmacist, Sarah Turley, Gabriella Gegenheimer, Emily Blum, Erin Petersen

Pharmacy and Wellness Review

Celiac disease is a genetically-linked autoimmune disease which affects the gastrointestinal tract. It is an inflammatory reaction to ingested gluten-containing substances that produces the most frequent symptoms of abdominal pain, bloating and intermittent or chronic diarrhea. Diagnosis can be made by blood testing for specific IgA autoantibodies and a confirmation duodenal biopsy to look for the characteristic scalloping and villous atrophy that occurs in response to the inflammation. A gluten-free diet, until recently, was the only treatment available and continues to be the mainstay of treatment. Newer adjunct therapies to dietary management include larazotide acetate, peptidases, the use of parasite …

A Comparison Of Mipomersen (Kynamro®) And Lomitapide (Juxtapid®): Medications For The Treatment Of Homozygous Familial Hypercholesterolemia, Ann Marie Ruhe, Austin Brown, Ginny Daniels, Kelsey Fink, David Bright

Pharmacy and Wellness Review

Homozygous familial hypercholesterolemia (HoFH) is a rare disease that involves mutations in the genes coding for low density lipoprotein (LDL) receptors, preventing the uptake of LDL cholesterol from the serum and resulting in extremely high cholesterol levels.1 Between December 2012, and January 2013, two orphan drugs were approved by the U.S. Food and Drug Administration (FDA) for the treatment of HoFH. Mipomersen (Kynamro®) is a subcutaneous injection that functions as an antisense oligonucleotide inhibitor and ultimately prevents the translation of mRNA coding for apolipoprotein B (apoB)-100 which binds to LDL and very low density lipoprotein (vLDL) cholesterol.7 Lomitapide (Juxtapid®) is …

Signifor® Receives Fda Approvalfor The Management Of Cushing's Disease, Justin Steele, Ann Marie Ruhe, Andrew Skouby, Eric Stack, Sandra L. Hrometz

Pharmacy and Wellness Review

Cushing's disease is a disorder characterized by supraphysiologic levels of circulating cortisol due to excessive adrenocorticotropic hormone (ACTH) secretion. Most often hypersecretion of ACTH is due to a pituitary adenoma, where surgical resection of the tumor is considered first-line treatment for the disease. Alternatively, the FDA has recently approved the somatostatin analogue, Signifor® (pasireotide), for the management of Cushing's disease in patients for whom surgery is not an option. In clinical trials, pasireotide has shown a statistically significant reduction in urinary free cortisol levels, as well as significant improvements in quality of life. Based on current data, pasireotide appears to …

Ado-Trastuzumab Emtansine For Her2 Positive Breast Cancer, Kimberly Baucher, Taylor Beale, Maria Laikos, Eric Stack, Mary Ellen Hethcox

Pharmacy and Wellness Review

No abstract provided.

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 …

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 …

Human Immunodeficiency Virus Theranostics, Christopher J. Woldstad

Theses & Dissertations

RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. However, maintenance of sustained plasma drug levels, for weeks or months, after a single high-level dosing, could improve regimen adherence but, at the same time, affect systemic toxicities. Of these, the most troubling are those that affect the central nervous system (CNS) In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal …

The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue

Senior Theses

Phenylketonuria, now known as phenylalanine hydroxylase (PAH) deficiency, is a genetic disorder of metabolism affecting approximately one in every 15,000 infants born in the United States. Patients have nonfunctional PAH enzyme secondary to one or more genetic mutations. The enzyme deficit results in destructive supraphysiologic blood phenylalanine levels upon consumption of the essential dietary amino acid phenylalanine. Current standards of care mitigate signs and symptoms of the disorder, but do not approach a cure. The methods for creating a prototype pharmabiotic as an innovative treatment strategy for PAH deficiency are described herein.

DNA molecular cloning techniques were utilized to engineer …

Systematic Literature Review Of Quetiapine For The Treatment Of Psychosis In Patients With Parkinsonism, Jack J. Chen, Henry Hua, Lilian Massihi, Ivan Portillo, Azita Alipour, William Ondo, Khashayar Dashtipour

Library Articles and Research

Objective:

The purpose of this article was to determine the efficacy and tolerability of quetiapine compared with placebo or other interventions for psychosis in parkinsonism.

Methods:

Participants with a diagnosis of parkinsonism participated in randomized controlled trials (RCTs) investigating the efficacy and tolerability of quetiapine for psychotic symptoms within a defined follow-up period. The authors conducted searches on PubMed, Cochrane Controlled Register of Trials, and EMBASE for articles published from January 1991 to October 2017. Study methodology and patient- and treatment-level data were independently extracted and summarized by using descriptive statistics. Studies underwent quality assessment for risk of bias.

Results: …

Inhibition Of Cancer Stem Cells By Glycosaminoglycan Mimetics, Connor P. O'Hara

Theses and Dissertations

Connor O’Hara July 29, 2019

Inhibition of Cancer Stem Cells by Glycosaminoglycan Mimetics

In the United States cancer is the second leading cause of death, with colorectal cancer (CRC) being the third deadliest cancer and expected to cause over 51,000 fatalities in 2019 alone.¹ The current standard of care for CRC depends largely on the staging, location, and presence of metastasis.² As the tumor grows and invades nearby lymph tissue and blood vessels, CRC has the opportunity to invade not only nearby tissue but also metastasize into the liver and lung (most commonly).³ The 5-year survival rate …

Synthesis And Antiproliferative Activities Of Doxorubicin Thiol Conjugates And Doxorubicin-Ss-Cyclic Peptide, Shaban Darwish, Neda Sadeghiani, Shirley Fong, Saghar Mozaffari, Parinaz Hamidi, Thimanthi Withana, Sun Yang, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Myocardial toxicity and drug resistance caused by drug efflux are major limitations of doxorubicin (Dox)-based chemotherapy. Dox structure modification could be used to develop conjugates with an improved biological profile, such as antiproliferative activity and higher cellular retention. Thus, Dox thiol conjugates, Dox thiol (Dox-SH), thiol-reactive Dox-SS-pyridine (SS = disulfide), and a Dox-SS-cell-penetrating cyclic peptide, Dox-SS-[C(WR)4K], were synthesized. Dox was reacted with Traut's reagent to generate Dox-SH. The thiol group was activated by the reaction with dithiodipyridine to afford the corresponding Dox-SS-Pyridine (Dox-SS-Pyr). A cyclic cell-penetrating peptide containing a cysteine residue [C(WR)4K] was prepared using Fmoc solid-phase strategy. Dox-SS-Py was …

Modulation Of Hypoxia-Induced Chemoresistance To Polymeric Micellar Cisplatin: The Effect Of Ligand Modification Of Micellar Carrier Versus Inhibition Of The Mediators Of Drug Resistance, Hoda Soleymani Abyaneh, Amir Hassan Soleimani, Mohammad Reza Vakili, Rania Soudy, Kamaljit Kaur, Francesco Cuda, Ali Tavassoli, Afsaneh Lavasanifar

Pharmacy Faculty Articles and Research

Hypoxia can induce chemoresistance, which is a significant clinical obstacle in cancer therapy. Here, we assessed development of hypoxia-induced chemoresistance (HICR) against free versus polymeric cisplatin micelles in a triple negative breast cancer cell line, MDA-MB-231. We then explored two strategies for the modulation of HICR against cisplatin micelles: a) the development of actively targeted micelles; and b) combination therapy with modulators of HICR in MDA-MB-231 cells. Actively targeted cisplatin micelles were prepared through surface modification of acetal-poly(ethylene oxide)-poly(-carboxyl-"-caprolactone) (acetal-PEO-PCCL) micelles with epidermal growth factor receptor (EGFR)-targeting peptide, GE11 (YHWYGYTPQNVI). Our results showed that hypoxia induced resistance against free and …

Astromimetics: The Dawn Of A New Era For (Bio)Materials Science?, Vuk Uskoković, Victoria M. Wu

Pharmacy Faculty Articles and Research

Composite, multifunctional fine particles are likely to be at the frontier of materials science in the foreseeable future. Here we present a submicron composite particle that mimics the stratified structure of the Earth by having a zero-valent iron core, a silicate/silicide mantle, and a thin carbonaceous crust resembling the biosphere and its biotic deposits. Particles were formulated in a stable colloidal form and made to interact with various types of healthy and cancer cells in vitro. A selective anticancer activity was observed, promising from the point of view of the intended use of the particles for tumor targeting across the …

Amine Containing Analogs Of Sulindac For Cancer Prevention, Bini Mathew, Judith V. Hobrath, Michele C. Connelly, R. Kiplin Guy, Robert C. Reynolds

Pharmaceutical Sciences Faculty Publications

Background:

Sulindac belongs to the chemically diverse family of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) that effectively prevent adenomatous colorectal polyps and colon cancer, especially in patients with familial adenomatous polyposis. Sulindac sulfide amide (SSA), an amide analog of sulindac sulfide, shows insignificant COX-related activity and toxicity while enhancing anticancer activity in vitro and demonstrating in vivo xenograft activity.

Objective:

Develop structure-activity relationships in the sulindac amine series and identify analogs with promising anticancer activities.

Method:

A series of sulindac amine analogs were designed and synthesized and then further modified in a “libraries from libraries” approach to produce amide, sulfonamide and N,N-disubstituted …

Current Approaches And New Developments In The Pharmacological Management Of Tourette Syndrome., Julio Quezada, Keith A. Coffman

Manuscripts, Articles, Book Chapters and Other Papers

Tourette syndrome (TS) is a neurodevelopmental disorder of unknown etiology characterized by spontaneous, involuntary movements and vocalizations called tics. Once thought to be rare, TS affects 0.3-1% of the population. Tics can cause physical discomfort, emotional distress, social difficulties, and can interfere with education and desired activities. The pharmacologic treatment of TS is particularly challenging, as currently the genetics, neurophysiology, and neuropathology of this disorder are still largely unknown. However, clinical experience gained from treating TS has helped us better understand its pathogenesis and, as a result, derive treatment options. The strongest data exist for the antipsychotic agents, both typical …

Evaluation Of A Drug Delivery System Based On Cyclodextrins For Cancer Therapy, Caroline Mendes

Doctoral

Due to the side-effects caused by regular chemotherapy, the development of drug delivery systems that can specifically target cancer cells and deliver the therapeutic dose is required. In this study, a folate-derivative of β-cyclodextrin has been studied as a vehicle for targeting folate receptors (FR) and delivering the chemotherapeutic drug methotrexate (MTX). FRs can be considered key cell membrane targets since they are commonly over-expressed in cancer cells and play an important role in cancer development and progression. Cyclodextrins (CDs) are cyclic oligosaccharides with a unique structure that allows them to form inclusion complexes with guest molecules, increasing their aqueous …