Medicine and Health Sciences Commons^™

Conflicts Of Interest In Clinical Practice Guidelines, Lisa Cosgrove, Allen F. Shaughnessy

Counseling, School Psychology & Sport Faculty Publication Series

Clinical practice guidelines are used increasingly across medical specialties and settings, making evaluation of their utility and validity a critical public health issue. In this paper, we describe some of the challenges that specialty organizations face as they try to ensure that their guidelines are trustworthy and useful. We examine the practice guidelines for Major Depressive Disorder recently published by the American Psychiatric Association (APA), identify five sources of potential bias that may affect the guideline development process and offer suggestions based on our review. For example, even for mild depression, this guideline privileges pharmacotherapy over other interventions, despite questions …

Natural Products Chemistry Of Leads Acting On Mrsa, Hcv, Malaria, And Depression Disorders, Mohamed Ali Mohamed Ali Ibrahim

Electronic Theses and Dissertations

Nature has proven to be an endless source of abundant diversity of chemical entities with varying biological activities. The World Health Organization (WHO) estimates that 80% of the world's population depends on traditional medicine for treating their everyday health problems. According to Gordon Cragg, former director of the natural products branch of the NCI, ″Nature has produced wonderfully complex molecules that no synthetic chemist could ever dream up.″ Moreover, he emphasized that over 60% of cancer therapeutics have been derived from nature whether directly through isolation or indirectly through semi-synthesis. Various examples have been reported such as extracts from Catharanthus …

Market Response To Food And Drug Administration's Safety Warnings: A Case Study Using An Interrupted Time Series Analysis Of The Medicare Database For 2006-2008, Hafiz Oko-Osi

Electronic Theses and Dissertations

Objectives: To evaluate the impact of a safety warning on the utilization rates of thiazolidinedione oral anti-diabetes medication using an interrupted time series analysis. Methods: We extracted data from a five percent national sample of Medicare Part D beneficiaries for the periods between January 2006 and December 2008. Beneficiaries with Part D claims for thiazolidinediones were classified into appropriate-use, at risk, and contraindicated groups based on certain comorbid conditions. We assessed the effects of the May 2007 FDA safety warning about an ongoing safety review of rosiglitazone's potential to increase cardiovascular risks on thiazolidinedione utilization rates using an interrupted time …

Factors That Physicians Find Encouraging And Discouraging About Electronic Prescribing: A Quantitative Study, Krutika Satish Jariwala

Electronic Theses and Dissertations

Research objective. While the adoption of e-prescribing is growing, the Institute of Medicine's recommendations that all prescriptions be routed electronically by 2010 certainly has not been met. Therefore, the objective of this study is to compare the factors that physicians find encouraging and discouraging about e-prescribing based on their e-prescribing adoption status. Study design. Cross-sectional, descriptive design. An Internet-based survey was sent to national convenience sample of physicians. Using e-prescribing literature, 44 items were developed concerning various factors related to the adoption of e-prescribing. Physicians rated how much the factors encouraged them or discouraged them about e-prescribing. Analysis procedures included …

Factors Affecting Community Pharmacy Owners' Attitudes Toward And Likelihood To Adopt Rxsync Service(Sm), Namita Joshi

Electronic Theses and Dissertations

Factors affecting community pharmacy owners' attitudes toward and likelihood to adopt RxSync ServiceSM. Objective. There is an increased recognition of the role of pharmacists in the provision of patient care services. Therefore, understanding factors that affect pharmacists' attitudes and likelihood to implement pharmacy services is warranted. The objective of this study is to examine how community pharmacy owners' entrepreneurial and demographic characteristics, perceptions of pharmacy service characteristics (perceived benefit, perceived compatibility, and perceived complexity), workload perceptions, and the number of pharmacy services they already offer, affect their attitude toward and likelihood to adopt RxSync ServiceSM, a newly developed prescription management …

Fatty Acyl Amide Dderivatives Of Doxorubicin: Synthesis And In Vitro Anticancer Activities, Bhupender S. Chhikara, Nicole St. Jean, Deendayal Mandal, Anil Kumar, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin is an anticancer drug extensively used in anticancer therapy. Doxorubicin is highly hydrophilic, has short half-life, and its use is associated with severe side effects at high doses. Fatty acyl amide derivatives of doxorubicin were synthesized with the expectation to improve the lipophilicity and anticancer activity of the drug. The lipophilicity was enhanced with the increase in chain length of fatty acyl moiety. Conjugation of 4-amino group with fatty acids through an amide bond reduced the anticancer activity in leukemia, breast, ovarian, and colon cancer cell lines, suggesting that the presence of free amino group is required for anticancer …

Should Benzodiazepines Be Prescribed To Treat Insomnia And Anxiety Related Disorders?, Judith Nicole Margareten

The Science Journal of the Lander College of Arts and Sciences

The following is an excerpt of the introduction of this article: Benzodiazepines are commonly prescribed drugs used to treat insomnia and anxiety. They are often found in forms such as Xanax (alprazolam) and Valium (diazepam). For many, these drugs have proven essential for ensuring a restful night’s sleep, but for others they are the cause of sleepless ones. Negative effects of benzodiazepines such as addiction, dependence, and impaired cognition plague many patients. While doctors are prone to prescribe these medications readily due to their high level of effectiveness, this practice can pose a great risk to certain populations.

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 …

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 …

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 …

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 …

Towards The Total Synthesis Of The Capuramycin Family Of Natural Products, Jesse M. Jacobsen

University of Kentucky Master's Theses

Despite over a century of advancement, tuberculosis remains a grave threat to world health. In particular, third world countries continue to struggle with the crushing weight of the disease. Furthermore, the emergence of drug resistance in TB strains poses a significant threat to the first world where incidence and mortality is low. The dwindling efficacy of current drug regimens necessitates research into new small molecules capable of arresting the growth and spread of TB. The capuramycin family of nucleoside antibiotics shows strong potential to become part of this new generation of anti-TB small molecules. Indeed, their ability to inhibit Translocase …

Isolation And Elucidation Of The Chrysomycin Biosynthetic Gene Cluster And Altering The Glycosylation Patterns Of Tetracenomycins And Mithramycin-Pathway Molecules, Stephen Eric Nybo

University of Kentucky Doctoral Dissertations

Natural products occupy a central role as the majority of currently used antibiotic and anticancer agents. Among these are type-II polyketide synthase (PKS)-derived molecules, or polyketides, which are produced by many representatives of the genus Streptomyces. Some type-II polyketides, such as the tetracyclines and the anthracycline doxorubicin, are currently employed as therapeutics. However, several polyketide molecules exhibit promising biological activity, but due to toxic side effects or solubility concerns, remain undeveloped as drugs.

Gilvocarcin V (GV) (topoisomerase II inhibitor) has a novel mechanism of action: [2+2] cycloaddition to thymine residues by the 8-vinyl side chain and cross-linking of histone …

The Influence Of Antidiabetic Medications On The Development And Progression Of Prostate Cancer, Anna Elizabeth Hitron

University of Kentucky Master's Theses

The development of prostate tumors has been linked to co-morbid diabetes mellitus (DM) in several studies, potentially through the stimulation of insulin-like growth factor receptor (IGFR). This study evaluates the effect of anti-diabetic medication use on the development of high grade tumors and time to tumor progression compared to non-diabetics. This retrospective, nested case control study identified patients with prostate cancer (PCa) from the Kentucky Medicaid Database. Cases were diagnosed with PCa and DM and using at least one of the following antidiabetic medications; sulfonylureas, insulin, metformin or TZDs. Cases were further stratified on their insulin exposure resulting from therapy. …

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 …