Pharmacy and Pharmaceutical Sciences Commons^™

A Proposed Mechanism For Drug-Induced Nightmares, Isaac Brezner

The Science Journal of the Lander College of Arts and Sciences

The following is the introduction of this article: The fields of neuropharmacology and psychopharmacology are known to be highly connected, despite our severe lack of knowledge in these fields. One of the many overlaps between the two fields is sleep, which itself entails many mechanisms and events which are, as of yet, unexplainable. From the perspective of either field, one of the most mysterious events occurring during sleep is dreaming. From the cause of dreams to their content, little is known about them or their more sinister subclassification: nightmares. In this field of disturbed dreaming, neuropharmacology makes a large intrusion …

Current Therapies For Chronic Hepatitis C, Mckenzie C. Ferguson

Pharmacy Faculty Research, Scholarship, and Creative Activity

Hepatitis C virus affects more than 180 million people worldwide and as many as 4 million people in the United States. Given that most patients are asymptomatic until late in the disease progression, diagnostic screening and evaluation should be performed in patients who display high-risk behaviors associated with acquisition of hepatitis C. Chronic hepatitis C is associated with cirrhosis, hepatic failure, and death; therefore, treatment is aimed at reducing these complications, as well as improving quality of life and minimizing adverse effects. The American Association for the Study of Liver Diseases Practice Guidelines on the Diagnosis, Management, and Treatment of …

Part A: Studies Towards Total Synthesis Of An Anticancer And Antifungal Natural Product, Pseudolaric Acid B; Part B: Synthesis And Biological Evaluation Of Berkeleyamide A And Its Derivatives, Swapnil Jayant Kulkarni

Electronic Theses and Dissertations

Part A: Studies towards total synthesis of an antifungal and anticancer agent, Pseudolaric acid B. Marked by the uncontrolled cell proliferation, cancer is one of the deadliest diseases, accounting for about 7.0 million deaths in 2007. Cancer is second leading cause of death worldwide, according to the American Cancer Society. Cancer chemotherapy has evolved through many years of painstaking research, and as a result, today we are able to cure at least some of cancers. One of the major impediments in the development of new drugs for treating cancer is that most of the approved drugs are themselves toxic and …

Synthesis Of 3-Phenylpyrazolopyrimidine-1,2,3-Triazole Conjugates And Evaluation Of Their Src Kinase Inhibitory And Anticancer Activities, Anil Kumar, Israr Ahmad, Bhupender S. Chhikara, Rakesh Tiwari, Deendayal Mandal, Keykavous Parang

Pharmacy Faculty Articles and Research

A series of two classes of 3-phenylpyrazolopyrimidine-1,2,3-triazole conjugates were synthesized using click chemistry approach. All compounds were evaluated for inhibition of Src kinase and human ovarian adenocarcinoma (SK-Ov-3), breast carcinoma (MDA-MB-361), and colon adenocarcinoma (HT-29). Hexyl triazolyl-substituted 3-phenylpyrazolopyrimidine exhibited inhibition of Src kinase with an IC50 value of 5.6 µM. 4-Methoxyphenyl triazolyl-substituted 3-phenylpyrazolopyrimidine inhibited the cell proliferation of HT-29 and SK-Ov-3 by 73% and 58%, respectively, at a concentration of 50 µM.

Mechanism And Kinetics Of Covalent Amide-Linked Adduct Formation In Solution And Solid Peptide Formulations, Michael Paul Dehart

Theses and Dissertations--Pharmacy

Peptides and proteins are prone to chemical and physical degradation in solutions and solids. One of the most common chemical degradation pathways involves deamidation of asparagine residues through a reactive succinimide intermediate resulting in the formation of aspartyl and isoaspartyl degradation products.

In this work, kinetic studies in aqueous solutions demonstrated that the succinimide intermediate is susceptible to attack by nucleophiles other than water. This may lead to a variety of alternative degradants. In solutions containing high concentrations of ammonia, the succinimide generated in the deamidation of the model peptides Phe-Asn-Gly and Phe-isoAsn-Gly underwent back-reaction with ammonia leading to peptide …

Target Validation Of Uk-101 And Functional Studies Of Β1i, Marie V. Wehenkel

Theses and Dissertations--Pharmacy

β1i is a major catalytic subunit of the immunoproteasome, an alternative form of the constitutive proteasome, and its upregulation has been demonstrated in a variety of disease states including cancer. Our lab has developed a small molecule inhibitor of β1i, dubbed UK-101. While UK-101 causes apoptosis in cancer cell lines, it was not clear whether this apoptotic effect was directly mediated by its irreversible inhibition of β1i. Since off-target effects are major roadblocks for the development of new and effective pharmaceuticals, target validation studies in this system would assist in the further progression of β1i inhibitors towards preclinical trials. Our …

Studies Of Solubilization Of Poorly Water-Soluble Drugs During In Vitro Lipolysis Of A Model Lipid-Based Drug Delivery System And In Mixed Micelles, Lin Song

Theses and Dissertations--Pharmacy

Lipid-based drug delivery systems (LBDDSs) are becoming an increasingly popular approach to improve the oral absorption of poorly-water soluble drugs. Several possible mechanisms have been proposed to explain the means by which LBDDSs act in vivo to enhance absorption. The goal of the current dissertation is to provide a better understanding of one proposed mechanism; the capability of lipoidal components in LBDDS formulations to create and maintain a drug in a supersaturated state under simulated GI conditions. Moreover, molecular details of equilibrium solubilization of a drug in a series of model lipid assemblies were examined. The results of these studies …

Preclinical Evaluation Of Lobeline For The Treatment Of Adhd: Comparison With Psychostimulant Therapies, Yolanda D. Williams

Theses and Dissertations--Pharmacy

This dissertation work investigated the effect of acute and repeated in vivo administration of lobeline on dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) function. The effects of lobeline were then compared to the effects of acute and repeated in vivo administration of methylphenidate and amphetamine to determine if lobeline produced similar effects compared to these Attention Deficit Hyperactivity Disorder (ADHD) medications. These medications are considered the first line of pharmacotherapy for ADHD, although there is a growing concern associated with their potential for abuse and other side effects. This merits the need for novel ADHD treatments that have a …

Student-Led Learning In The Pharmaceutical Sciences Curriculum, Melinda E. Lull, Jennifer L. Mathews, E. C. Jannetta, Christine R. Birnie

Pharmacy Faculty/Staff Publications

Objectives: A challenge of primarily didactic courses lies in keeping students engaged in a potentially monotonous learning environment. The objective of this study was to test the effectiveness of incorporating student-led activities into the pharmaceutical sciences curriculum. This alternative approach to traditional lecture-based learning allows for student engagement and ownership of materials. These activities were incorporated into P1 Pharmacology, Biosystems, and Calculations courses.

Methods: A variety of student-led learning activities were conducted in three courses (n=78 students). Following each activity, students were asked to participate in a survey rating the effectiveness, relevancy, productiveness, and overall impression of the activity using …

The Need For Transgender Health Content In The Pharmacy Curriculum, Jennifer Mathews, Amy L. Parkhill, Jeanne Gainsburg, Scott Fearing

Pharmacy Faculty/Staff Publications

The article, “The Need for Transgender Health Content in the Pharmacy Curriculum,” addresses transgender patients and how they often have complex medical, psychological, and social concerns. According to the article, these patients may not only need to learn to manage complicated medication regimens, which can have significant side effects, but may also face many barriers to treatment. Some of those barriers include difficulties with insurance, fear of discrimination, lack of support, and a mistrust of the healthcare system. Given the important role that medications play in maintaining their quality of life, the article suggests that pharmacists are in a unique …

Factors Controlling Hop Flowering And Their Potential For Use In The Brewing And Pharmaceutical Industries, Margaret Nicole Crain

Honors Program Theses

Hop (Humulus lupulus L.) is a dioecious, perennial vine grown in temperate regions across the world (Stevens et al., 1997). Today hop is being used for two purposes. The first and most prolific is its use in beer brewing. The other is a recent development, but ever growing interest in the use of hops for pharmaceuticals.

Cumulative Clinical Experience From Over A Decade Of Use Of Levofloxacin In Community Acquired Pneumonia; Critical Appraisal And Role In Therapy, Ayman M. Noreddin, Walid F. Elkhatib, Kenji M. Cunnion, George G. Zhanel

Pharmacy Faculty Articles and Research

Levofloxacin is the synthetic L-isomer of the racemic fluoroquinolone, ofloxacin. It interferes with critical processes in the bacterial cell such as DNA replication, transcription, repair, and recombination by inhibiting bacterial topoisomerases. Levofloxacin has broad spectrum activity against several causative bacterial pathogens of community-acquired pneumonia (CAP). Oral levofloxacin is rapidly absorbed and is bioequivalent to the intravenous formulation such that patients can be conveniently transitioned between these formulations when moving from the inpatient to the outpatient setting. Furthermore, levofloxacin demonstrates excellent safety, and has good tissue penetration maintaining adequate concentrations at the site of infection. The efficacy and tolerability of …

Efficacious And Safe Tissue-Selective Controlled Gene Therapy Approaches For The Cornea, Rajiv R. Mohan, Sunilima Sinha, Ashish Tandon, Rangan Gupta, Jonathan C. K. Tovey, Ajay Sharma

Pharmacy Faculty Articles and Research

Untargeted and uncontrolled gene delivery is a major cause of gene therapy failure. This study aimed to define efficient and safe tissue-selective targeted gene therapy approaches for delivering genes into keratocytes of the cornea in vivo using a normal or diseased rabbit model. New Zealand White rabbits, adeno-associated virus serotype 5 (AAV5), and a minimally invasive hair-dryer based vector-delivery technique were used. Fifty microliters of AAV5 titer (6.561012 vg/ml) expressing green fluorescent protein gene (GFP) was topically applied onto normal or diseased (fibrotic or neovascularized) rabbit corneas for 2-minutes with a custom vector-delivery technique. Corneal fibrosis and neovascularization in rabbit …

A Comparison Of Pharmacist Travel-Health Specialists' Versus Primary Care Providers' Recommendations For Travel-Related Medications, Vaccinations, And Patient Compliance In A College Health Setting, Melissa J. Durham, Jeffery A. Goad, Lawrence S. Neinstein, Mimi Lou

Pharmacy Faculty Articles and Research

Background. Pretravel medication and vaccination recommendations and receipt were compared between primary care providers (PCPs) without special training and clinical pharmacists specializing in pretravel health.

Methods. A retrospective chart review of patients seen for pretravel health services in a pharmacist-run travel clinic (PTC) compared to PCPs at a University Student Health Center. Vaccine/medication recommendations were assessed for consistency with national/international guidelines. Medical/pharmacy records were queried to determine the receipt of medications/vaccinations.

Results. The PTC recommended antibiotics for travelers' diarrhea were given more often when indicated (96% vs 50%, p < 0.0001), and patients seen in the PTC received their medications more often (75% vs 63%, p = 0.04). PCPs prescribed more antibiotics for travelers' diarrhea that were inconsistent with guidelines (not ordered when indicated 49% vs 6%, p < 0.0001 and ordered when not indicated 21% vs 3%, p < 0.0001). The PTC prescribed antimalarials more often when indicated (98% vs 81%, p < 0.0001), while PCPs prescribed more antimalarials that were inconsistent with guidelines (not ordered when indicated 15% vs 1%, p < 0.0001 and ordered when not indicated 19% vs 2%, p < 0.0001). The PTC ordered more vaccines per patient when indicated (mean = 2.77 vs 2.31, p = 0.0012). PTC patients were more likely to receive vaccines when ordered (mean = 2.38 vs 1.95, p = 0.0039). PCPs recommended more vaccines per patient that were inconsistent with guidelines (not ordered when indicated: mean = 0.78 vs 0.12, p < 0.0001, ordered when not indicated: mean 0.18 vs 0.025, p < 0.0001).

Conclusions. A pharmacist-run pretravel health clinic can …

Day Of Dialogue On Multipurpose Prevention Technologies: Toward Clarity In Nomenclature, Martha Brady, C. Elizabeth Mcgrory

Poverty, Gender, and Youth

The report summarizes a half-day meeting convened by the Population Council to clarify the wide variety of nomenclature and concepts associated with multipurpose prevention technologies (MPTs). The first section outlines where different types of products are reviewed within the FDA and existing processes that could be applied to MPTs. This is followed by a section that reviews what guidance exists and what else may be needed for review of products like MPTs that address two (or more) indications, including those with a single active, two actives, and multiple components. This meeting identified some of the specific opportunities and challenges for …

Synthesis, Screening And Cocrystallization Of Adenosine Based Inhibitors With Methyltransferases, Ermc' And Ksga, Matthew Baker

Theses and Dissertations

Antibiotic resistance threatens to throw mankind back into an era when infectious disease was the predominant cause of death. In an effort to mitigate this danger, we targeted ErmC’ and KsgA. Both methylate N6-adenosine of ribosomal RNA, though each serve different roles in their bacterial host. ErmC’ dimethylates A2058 on 23S rRNA, conferring resistance to MLSB antibiotics (macrolides, lincosamides, streptogramin B). KsgA aids in ribosome assembly, binding inactive 30S until dimethylating A1518/A1519 of 16S rRNA. Like most methyltransferases, ErmC’ and KsgA use cofactor S-adenosylmethionine (SAM) as their methyl source, which binds adjacent to their specific adenosine substrate. ErmC’ inhibitors could …

Combinatorial Biosynthetic Derivatization Of The Antitumoral Agent Gilvocarcin V, Micah Douglas Shepherd

University of Kentucky Doctoral Dissertations

Gilvocarcin V (GV), the principal product of Streptomyces griseoflavus Gö 3592 and other Streptomyces spp., is the most prominent member of a distinct class of antitumor antibiotics that share a polyketide derived coumarin-based aromatic core. GV and other members of this class including polycarcin V from Streptomyces polyformus, often referred to as gilvocarcin-like aryl C-glycosides, are particularly interesting because of their potent bactericidal, virucidal and antitumor activities at low concentrations while maintaining low in vivo toxicity. Although the precise molecular mechanism of GV bioactivity is unknown, gilvocarcin V has been shown to undergo a photoactivated [2+2] cycloaddition of …

Effect Of Azithromycin On Macrophage Phenotype During Pulmonary Infections And Cystic Fibrosis, Theodore James Cory

University of Kentucky Doctoral Dissertations

Azithromycin improves clinical outcomes in patients with cystic fibrosis (CF), specifically in patients infected with Pseudomonas aeruginosa. Azithromycin shifts macrophage programming away from a pro-inflammatory classical (M1) phenotype, and towards an anti-inflammatory alternative (M2) phenotype; however, little is known about this mechanism, nor of its impact upon immune response to pulmonary infection. We set out to determine the mechanism by which azithromycin is able to alter macrophage phenotype, and assess the effect of azithromycin induced macrophage polarization on inflammation during pulmonary infections.

Utilizing macrophage cell culture, we found that azithromycin increased IKKβ, a signaling molecule in the NFκB pathway, which …

Should Pseudoephedrine (Pse) Be Moved From Behind The Counter To Prescription-Only? An Analysis Of Pse As An Otc Medication And A Precursor For Methamphetamine Production, Jerry Dillon

MPA/MPP/MPFM Capstone Projects

Kentucky State Senator Tom Jensen recently sponsored Senate Bill 45, which would change pseudoephedrine (PSE) from an over-the-counter to a schedule V prescription-only drug. The bill failed, but the debate continues as to whether Kentucky should make PSE, a precursor required to manufacture illicit methamphetamine, a controlled drug that is available by prescription only.

Methamphetamine abuse has been increasing in Kentucky as well as in the rest of the country, despite efforts to control the sale of PSE through federal and state legislation. The Combat Methamphetamine Epidemic Act (CMEA) of 2006 and Kentucky’s initiative to electronically monitor the sales of …

The Incidence Of Hip Fracture Associated With Proton Pump Inhibitor (Ppi) And/Or H2 Receptor Antagonist (H2ra) Use In The Kentucky Medicaid Population, Timothy C. Umeh

MPA/MPP/MPFM Capstone Projects

No executive summary.

Use Of Structure-And Ligand-Based Drug Design Tools For The Discovery Of Small Molecule Inhibitors Of Cysteine Proteases For The Treatment Of Malaria And Sars Infection, Falgun Shah

Electronic Theses and Dissertations

A wide array of molecular modeling tools were utilized to design and develop inhibitors against cysteine protease of P. Falciparum Malaria and Severe Acute Respiratory Syndrome (SARS). A number of potent inhibitors were developed against cysteine protease and hemoglobinase of P. falciparum , referred as Falcipains (FPs), by the structure-based virtual screening of the focused libraries enriched in soft-electrophiles containing compounds. Twenty one diverse, non-peptidic, low micromolar hits were identified. A combined data mining and combinatorial library synthesis approach was performed to discover analogs of virtual screening hits and establish the structure-activity relationships (SAR). However, the resulting SAR of the …

New Synthetic Methodologies For The Construction And Optimization Of Natural Products, Amir E. Wahba

Electronic Theses and Dissertations

Toxicity associated with bioactive natural products is considered as a major obstacle in the process of drug discovery. Manzamine A (MA) is one such candidate that requires optimization to overcome the toxicity problem. The manzamine alkaloids represents a unique class of natural products that have shown a diverse range of bioactivities including antimicrobial, antiparasitic, cytotoxicity, anti-inflammatory, pesticidial, and was shown to possess activity against HIV-1 and AIDS opportunistic infections. The greatest potential for the manzamine alkaloids appears to be against malaria and neuroinflammation. Experimental and modeling studies suggested that the planer ?-carboline moiety can act as DNA intercalator and hence …

Do Statins Improve Outcomes In Patients With Asthma On Inhaled Corticosteroid Therapy? A Retrospective Analysis Of The Mississippi Medicaid Database 2002-2004., Tasneem Taher Lokhandwala

Electronic Theses and Dissertations

Animal model studies and clinical trials have looked at the potential benefits of the anti-inflammatory properties of statins in asthma management with contradictory results. Therefore, the objective of this study is to determine if asthma patients on concurrent statin therapy are less likely to have asthma-related hospitalizations and emergency room (ER) visits. We conducted a retrospective cohort study using Medicaid data for 2002–2004. Asthma patients ?18 years old were identified using the ICD9 code 493.xx, from Jul 1, 2002 through Dec 31, 2003. The index date for an exposed subject was any date within the identification period, 180 days prior …

Fairness-Trust-Loyalty Relationship Under Varying Conditions Of Supplier-Buyer Interdependence, Thani Jambulingam, Ravi Kathuria, John R. Nevin

Business Faculty Articles and Research

Relationship marketing plays a significant role in supply chain practice and academic studies. Using the resource advantage theory within the relationship marketing framework, we studied the mediating role of trust as a governance mechanism in the fairness-loyalty relationship under different types of interdependence structure between suppliers (wholesalers) and buyers (retailers). Our findings, based on data from retail pharmacies, demonstrate that only under conditions of symmetric independence, trust, as a governance mechanism, completely mediate the relationship between fairness and loyalty. Under conditions of both perceived independence (i.e., lack of interdependence) and asymmetric buyer dependence, however, trust does not mediate but fairness …

Adrenal Beta-Arrestin 1 Inhibition In Vivo Attenuates Post-Myocardial Infarction Progression To Heart Failure And Adverse Remodeling Via Reduction Of Circulating Aldosterone Levels, Anastasios Lymperopoulos, Phd, Giuseppe Rengo, Md, Carmela Zincarelli, Md, Jihee Kim, Phd, Walter J. Koch, Phd

Center for Translational Medicine Faculty Papers

ABSTRACT

OBJECTIVES: We investigated whether adrenal betaarrestin 1 (betaarr1)-mediated aldosterone production plays any role in post-MI HF progression.

BACKGROUND: Heart failure (HF) represents one of the most significant health problems worldwide and new and innovative treatments are needed. Aldosterone contributes significantly to HF progression after myocardial infarction (MI) by accelerating adverse cardiac remodeling and ventricular dysfunction. It is produced by the adrenal cortex after angiotensin II (AngII) activation of AngII type 1 receptors (AT1Rs), G protein-coupled receptors (GPCRs) that also signal independently of G proteins. G protein-independent signaling is mediated by betaarrestin (betaarr) -1 and -2. We recently reported that …

The Relationship Between Psychological Contract Breach, Professional Identity, And Organizational Citizenship Behaviors: An Equity Sensitivity Perspective, Leigh Ann Bynum

Electronic Theses and Dissertations

Objectives: The purpose of this research was twofold. First, it tested the effects of the type of perceived psychological contract breach, equity sensitivity, and identity salience on an important employee outcome, namely organizational citizenship behaviors. Second, the research explored the effects that discipline and pharmacist status have on organizational citizenship behaviors. More precisely, the effect of equity sensitivity on the relationships between identity salience (discipline or school), type of perceived contract breach (administrative or professional) and the performance of organizational citizenship behaviors toward the School of Pharmacy by pharmacy school faculty was examined. Methods: Existing organizational citizenship, identity salience and …

Biopharmaceutical Approaches For Improved Drug Delivery Across Ocular Barriers, Ketan Hippalgaonkar

Electronic Theses and Dissertations

The eye is protected from the external environment by various physiological and anatomical barriers. These barriers through there protective actions drastically diminish the ocular bioavailability of drugs. The corneal epithelium acts as a major barrier towards the permeation of hydrophilic agents, whereas poor aqueous solubility presents a formulation challenge for lipophilic compounds. Additionally, P-glycoprotein (P-gp) expressed on the retinal pigmented epithelium (RPE P-gp) limits the penetration of substrates, in therapeutically relevant concentrations, into the back-of-the-eye.

In the present research, use of penetration enhancers (chitosan, benzalkonium chloride (BAK) and ethylenediaminetetraacetic acid (EDTA)) and formulation approaches (cyclodextrins and solid lipid nanoparticles (SLNs)) …

Novel Approaches To The Control Of Infectious Diseases, Damaris Agathe Meujo Foping

Electronic Theses and Dissertations

As part of our ongoing efforts to find new drug leads against infectious diseases, several terrestrial and marine macro- and microorganisms were investigated. Several bioactive molecules, presented below, were isolated from these natural products. The mass-screening of dozens of marine Actinomycetes was completed and several Streptomyces with interesting biological activity profiles identified. A few examples are the Streptomyces code H747 and the Streptomyces code H668, a bacterium from which a new (5) and two known polyethers, the antimalarial agent K41-A (6) and its C-29 analog (7) were isolated. Five new six-membered ring cyclic peroxides: plakinastreloic acid A (8), methyl plakinastreloate …

Case-Mix Adjustment Of Adherence Based Pharmacy Quality Indicator Scores, Sai Hurrish Dharmarajan

Electronic Theses and Dissertations

Medication adherence has been shown to be influenced by demographics, health status and socio-economic status of the patient. Thus, adherence-based measures of pharmacy quality may be influenced by patient-related risk factors outside of the healthcare provider's control. This study examines the performance of a classical logistic regression model containing only patient characteristics and a random-effect model including patient characteristics and a pharmacy-specific effect in predicting medication adherence. These models were used to compute three different risk-adjusted scores on adherence-based pharmacy quality indicators: based on the classical logistic regression model (Method 1), the random effects model (Method 2) and the shrinkage …

Impairment Of Na/K-Atpase Signaling In Renal Proximal Tubule Contributes To Dahl Salt-Sensitive Hypertension, Jiang Liu, Yanling Yan, Lijun Liu, Zijian Xie, Deepak Malhotra, Bina Joe, Joseph I. Shapiro

Pharmaceutical Science and Research

We have observed that, in renal proximal tubular cells, cardiotonic steroids such as ouabain in vitro signal through Na/K-ATPase, which results in inhibition of transepithelial 22Na transport by redistributing Na/K-ATPase and NHE3. In the present study, we investigate the role of Na/K-ATPase signaling in renal sodium excretion and blood pressure regulation in vivo. In Sprague-Dawley rats, high salt diet activated c-Src and induced redistribution of Na/K-ATPase and NHE3 in renal proximal tubules. In Dahl salt sensitive (S) and resistant (R) rats given high dietary salt, we found different effects on blood pressure but, more interestingly, different effects on renal salt …