Pharmaceutics and Drug Design Commons^™

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, …