Pharmacy and Pharmaceutical Sciences Commons^™

Nucleoside Reverse Transcriptase Inhibitors Possess Intrinsic Anti-Inflammatory Activity, Benjamin J. Fowler, Bradley D. Gelfand, Younghee Kim, Nagaraj Kerur, Valeria Tarallo, Yoshio Hirano, Shoba Amarnath, Daniel H. Fowler, Marta Radwan, Mark T. Young, Keir Pittman, Paul Kubes, Hitesh Agarwal, Keykavous Parang, David R. Hinton, Ana Bastos-Carvalho, Shengjian Li, Testuhiro Yasuma, Takeshi Mizutani, Reo Yasuma, Charles Wright, Jayakrishna Ambati

Pharmacy Faculty Articles and Research

Nucleoside reverse transcriptase inhibitors (NRTIs) are mainstay therapeutics for HIV that block retrovirus replication. Alu (an endogenous retroelement that also requires reverse transcriptase for its life cycle)–derived RNAs activate P2X7 and the NLRP3 inflammasome to cause cell death of the retinal pigment epithelium in geographic atrophy, a type of age-related macular degeneration. We found that NRTIs inhibit P2X7-mediated NLRP3 inflammasome activation independent of reverse transcriptase inhibition. Multiple approved and clinically relevant NRTIs prevented caspase-1 activation, the effector of the NLRP3 inflammasome, induced by Alu RNA. NRTIs were efficacious in mouse models of geographic atrophy, choroidal neovascularization, graft-versus-host disease, and sterile …

Considerations For The Use Of Dietary Or Herbal Supplements, Samantha Morrison, Mary Menezes, Rodney Richmond

Faculty Research ​and Publications

No abstract provided.

Healthcare Provider Utilization And Patient Outcomes: The Call For Enhanced Coordinated Care For Medicare Beneficiaries, Yvonne Mai, Rajul A. Patel, Suzanne M. Galal, Sian M. Carr-Lopez, Joseph A. Woelfel

School of Pharmacy Faculty Presentations

Background: The use of complementary and alternative medicine (CAM) and other non-physician health care providers (dentists, optometrists, etc.) has steadily increased in the United States; however, the associated outcomes reported in the Medicare population is limited.

Objective: To evaluate the utilization of different healthcare providers by Medicare beneficiaries and assess resultant patient outcomes.

Methods: Fourteen outreach events targeting Medicare beneficiaries were conducted throughout Northern/Central California during the 2014 open enrollment period. Trained student pharmacists (working under licensed pharmacist supervision) provided beneficiaries with comprehensive medication therapy management (MTM) services. During each intervention, demographic, quality-of-life, health behavior, and health provider/service utilization data …

3,4,5-Trichloroaniline Nephrotoxicity In Vitro: Potential Role Of Free Radicals And Renal Biotransformation, Christopher Racine, Dakota Ward, Dianne K. Anestis, Travis Ferguson, Deborah Preston, Gary O. Rankin

Pharmaceutical Science and Research

Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determine if renal biotransformation and/or free radicals contributed to TCA cytotoxicity using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the animal model. IRCC (~4 million cells/mL; 3 mL) were incubated with TCA (0, 0.1, 0.25, 0.5 or 1.0 mM) for 60–120 min. In some experiments, IRCC were pretreated with an antioxidant or a …

Melampomagnolide B Derivatives As Antileukemic And Cytotoxic Agents, Peter A. Crooks, Craig T. Jordan, Shanshan Pei, Shama Nasim

Pharmaceutical Sciences Faculty Patents

Melampomagnolide B is disclosed as a new antileukemic sesquiterpene. A biotin-conjugated derivative of melampomagnolide B was prepared to elucidate its mechanism of action. Prodrugs of Melampomagnolide B are disclosed.

Crystal Structures Of 2-Meth­Oxy­Isoindoline-1,3-Dione, 1,3-Dioxoisoindolin-2-Yl Methyl Carbonate And 1,3-Dioxo-2,3-Di­Hydro-1h-Benzo[De]Isoquinolin-2-Yl Methyl Carbonate: Three Anti­Convulsant Compounds, Fortune Ezemobi, Henry North, Kenneth R. Scott, Anthohy K. Wutoh, Ray J. Butcher

Faculty Research ​and Publications

The title compounds, C9H7NO3, (1), C10H7NO5, (2), and C14H9NO5, (3), are three potentially anti­convulsant compounds. Compounds (1) and (2) are isoindoline derivatives and (3) is an iso­quinoline derivative. Compounds (2) and (3) crystallize with two independent mol­ecules (A and B) in their asymmetric units. In all three cases, the isoindoline and benzoiso­quinoline moieties are planar [r.m.s. deviations are 0.021 Å for (1), 0.04 and 0.018 Å for (2), and 0.033 and 0.041 Å for (3)]. The substituents attached to the N atom are almost perpendicular to the mean planes of the heterocycles, with dihedral angles of 89.7 (3)° …

New Oral Anticoagulants For The Treatment Of Venous Thromboembolism: Understanding Differences And Similarities., Paul P. Dobesh, John Fanikos

Journal Articles: Pharmacy Practice

Venous thromboembolism (VTE) is a major cause of morbidity, mortality, and healthcare expenditure. In the United States, approximately 0.1 % of the population experiences an initial VTE event each year. Anticoagulation therapy is the cornerstone of acute VTE treatment and for prevention of recurrent VTE events. Conventional anticoagulants, including heparin, low-molecular-weight heparins, fondaparinux, and vitamin K antagonists are widely used but have limitations. Newer oral anticoagulant agents, including direct thrombin inhibitors (e.g., dabigatran etexilate) and direct factor Xa inhibitors (e.g., rivaroxaban, apixaban, and edoxaban) have been developed to attempt to overcome some of the limitations of conventional anticoagulant therapy. These …

Availability And Perceived Value Of Bachelor Of Science Programs In Pharmaceutical Marketing And Management In The United States, Omar F. Attarabeen, Fadi M. Alkhateeb

Pharmacy Practice & Administration

Several academic institutions across the United States offer Bachelor of Science degree programs in Pharmaceutical Marketing and/or Management. In general, these programs are designed to provide students with stronger foundations and a broader understanding of the business side of pharmacy. The purpose of this study was to explore the availability of the Bachelor of Science programs in pharmaceutical marketing and management in the United States. Internet search was conducted in order to collect information about the programs of interest. Results showed that a total of 8 schools and colleges offer the Bachelor of Science degree programs. The total number of …

Pharmacy Law Brief: Alternative Dispute Resolution, Joseph L. Fink Iii

Pharmacy Practice and Science Faculty Publications

No abstract provided.

The Incentive Amplifying Effects Of Nicotine Are Reduced By Selective And Non-Selective Dopamine Antagonists In Rats, Matthew I. Palmatier, Marissa R. Kellicut, A. Brianna Sheppard, Russell W. Brown, Donita L. Robinson

ETSU Faculty Works

Nicotine is a psychomotor stimulant with ‘reinforcement enhancing’ effects — the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate …

Using Multi-Compartment Ensemble Modeling As An Investigative Tool Of Spatially Distributed Biophysical Balances: Application To Hippocampal Oriens-Lacunosum/Moleculare (O-Lm) Cellns, Vladislav Sekulic, J. Josh Lawrence, Frances K. Skinner

Biomedical and Pharmaceutical Sciences Faculty Publications

Multi-compartmental models of neurons provide insight into the complex, integrative properties of dendrites. Because it is not feasible to experimentally determine the exact density and kinetics of each channel type in every neuronal compartment, an essential goal in developing models is to help characterize these properties. To address biological variability inherent in a given neuronal type, there has been a shift away from using hand-tuned models towards using ensembles or populations of models. In collectively capturing a neuron’s output, ensemble modeling approaches uncover important conductance balances that control neuronal dynamics. However, conductances are never entirely known for a given neuron …

Overview And Impact Of Implementation Of A Pharmacy Concierge Service, William Balas, Phd, Christine H. Delash, Pharm.D, Brian G. Swift, Pharm.D., Mba, Lynda Thomson, Pharm D., Cacp

Pharmacy Presentations, Posters, and Grand Rounds

Problem / Issue:

Patients are at risk for adverse events and re-admissions due to outpatient medication errors and non-adherence to prescribed medication regimens. Patients are especially at risk for medication errors and misunderstanding of prescribed medication regimens during the transition of care process from the inpatient to outpatient setting.

Ph-Sensitive Mucoadhesive Film-Forming Gels And Wax-Film Composites Suitable For Topical And Mucosal Delivery Of Molecules, Russell J. Mumper, Michael Jay

Pharmaceutical Sciences Faculty Patents

The present invention relates to pH-sensitive mucoadhesive film-forming gels and wax-film composites suitable for topical and mucosal delivery of molecules of interest, namely active pharmaceuticals. The gels comprise a pharmaceutically acceptable pH-sensitive polymer that responds to a lowering of pH by precipitating into films when in contact with the skin or mucosal surface. The films also comprise an adhesive polymer that allows the film to remain in contact with the tissue for an extended period of time. The wax-film composites comprise a bi-layer film having both the said pH-sensitive mucoadhesive layer to promote strong adherence to the skin and mucosal …

Local Intra-Uterine Ang-(1-7) Infusion Attenuates Pge2 And 6-Keto Pgf1Α In Decidualized Uterus Of Pseudopregnant Rats, K. B. Brosnihan, V. M. Pulgar, M. S. Bharadwaj, L. A. Neves, L. M. Yamaleyeva

Pharmaceutical Sciences

Background: Cyclooxygenase (COX)-derived prostanoids (PGE2, PGI2) are important contributors to the process of decidualization. Previous studies showed the presence of Ang-(1-7) in the primary and secondary decidualized zones of the implantation site at early pregnancy. Decreased concentrations of Ang-(1-7) were found in the decidualized uterus compared to the non-decidualized uterus of pseudopregnant rats, suggesting that low levels of Ang-(1-7) are required for successful decidualization at early pregnancy.

Methods: To understand the role of Ang-(1-7) in prostaglandin production in a decidualized uterus, induced by a bolus injection of sesame oil, Ang-(1-7) (24 μg/kg/h) or vehicle was then infused directly into the …

Fda Approves A Wide Range Of New Drugs And Biologicals This Quarter, Rodney Richmond

Faculty Research ​and Publications

No abstract provided.

Sitagliptin Associated Pancreatic Carcinoma: A Review Of The Fda Aers Database, Angela Nagel, Gabriela Cipriano, Nabila Ahmed-Sarwar, Robbert Van Manen, Jack Brown

Pharmacy Faculty/Staff Publications

Purpose: Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor used in the treatment of type 2 diabetes mellitus in adults, as adjunct to diet and exercise to improve glycemic control. During phase III studies, sitagliptin was shown to cause toxicity to the pancreas, including pancreatitis. To date there is limited information available regarding its association with pancreatic carcinoma. Our goal was to qualitatively and quantitatively review available information in the AERS database in order to provide clinicians with a general understanding of the comparative occurrence of sitagliptin use and pancreatic carcinoma and any clinically relevant characteristics that may be useful in …

Methods To Impair Hematologic Cancer Progenitor Cells And Compounds Related Thereto, Craig T. Jordan

Pharmaceutical Sciences Faculty Patents

Primitive or progenitor hematologic cancer cells have been implicated in the early stages and development of leukemia and malignant lymphoproliferative disorders, including acute myelogenous leukemia (AML), chronic myelogenous leuke mia (CML) and chronic lymphoid leukemia (CLL). Interleu kin-3 receptor alpha chain (IL-3Ra or CD123) is strongly expressed on progenitor hematologic cancer cells, but is vir tually undetectable on normal bone marrow cells. The present invention provides methods of impairing progenitor hemato logic cancer (e.g., leukemia and lymphomic) cells by selec tively targeting cells expressing CD123. These methods are useful in the detection and treatment of leukemias and malig nant lymphoproliferative …

Hepatic Carboxylesterase 1 Is Induced By Glucose And Regulates Postprandial Glucose Levels, Jiesi Xu, Liya Yin, Yang Xu, Yuanyuan Li, Munaf Zalzala, Gang Cheng, Yanqiao Zhang

Chemical, Biomolecular, and Corrosion Engineering Faculty Research

Metabolic syndrome, characterized by obesity, hyperglycemia, dyslipidemia and hypertension, increases the risks for cardiovascular disease, diabetes and stroke. Carboxylesterase 1 (CES1) is an enzyme that hydrolyzes triglycerides and cholesterol esters, and is important for lipid metabolism. Our previous data show that over-expression of mouse hepatic CES1 lowers plasma glucose levels and improves insulin sensitivity in diabetic ob/ob mice. In the present study, we determined the physiological role of hepatic CES1 in glucose homeostasis. Hepatic CES1 expression was reduced by fasting but increased in diabetic mice. Treatment of mice with glucose induced hepatic CES1 expression. Consistent with the in vivo study, …

Acute Repeated Intracerebroventricular Injections Of Angiotensin Ii Reduce Agonist And Antagonist Radioligand Binding In The Paraventricular Nucleus Of The Hypothalamus And Median Preoptic Nucleus In The Rat Brain, Robert C. Speth, Peter J. Vento, Eduardo J. Carrera, Luz Gonzalez-Reily, Andrea Linares, Kira Santos, Jamala D. Swindle, Derek Daniels

HPD Articles

Angiotensin II (Ang II) stimulates water and saline intakes when injected into the brain of rats. This arises from activation of the AT1 Ang II receptor subtype. Acute repeated injections, however, decrease the water intake response to Ang II without affecting saline intake. Previous studies provide evidence that Ang II-induced water intake is mediated via the classical G protein coupling pathway, whereas the saline intake caused by Ang II is mediated by an ERK 1/2 MAP kinase signaling pathway. Accordingly, the different behavioral response to repeated injections of Ang II may reflect a selective effect on G protein coupling. To …

Ticagrelor: Pharmacokinetics, Pharmacodynamics, Clinical Efficacy, And Safety., Paul P. Dobesh, Julie H. Oestreich

Journal Articles: Pharmacy Practice

Dual antiplatelet therapy, composed of aspirin plus a P2Y12 -receptor antagonist, is the cornerstone of treatment for patients with acute coronary syndrome (ACS). A number of U.S. Food and Drug Administration-approved P2Y12 -receptor antagonists are available for treating patients with ACS, including the thienopyridine compounds clopidogrel and prasugrel. Ticagrelor, the first of a new class of antiplatelet agents, is a noncompetitive, direct-acting P2Y12 -receptor antagonist. Unlike the thienopyridine compounds, ticagrelor does not require metabolism for activity. Also, whereas clopidogrel and prasugrel are irreversible inhibitors of the P2Y12 receptor, ticagrelor binds reversibly to inhibit receptor signaling and subsequent platelet activation. In …

Increased Expression Of Angiotensin Ii Type 2 Receptors In The Solitary-Vagal Complex Blunts Renovascular Hypertension, Graziela Torres Blanch, André Henrique Freiria-Oliveira, Guilherme Fleury Speretta, Eduardo J. Carrera, Hongwei Li, Robert C. Speth, Eduardo Colombari, Colin Sumners, Débora S. Colombari

HPD Articles

Angiotensin II increases and decreases arterial pressure by acting at angiotensin type 1 and type 2 receptors, respectively. Renovascular hypertensive rats exhibit a high level of activity of the peripheral and central renin-angiotensin system. Therefore, in the present study, we evaluated the effect of increasing the expression of angiotensin type 2 receptors in the solitary-vagal complex (nucleus of the solitary tract/dorsal motor nucleus of the vagus), a key brain stem region for cardiovascular regulation, on the development of renovascular hypertension. Holtzman normotensive rats were implanted with a silver clip around the left renal artery to induce 2-kidney 1-clip renovascular hypertension. …

Risk Attitudes And Characteristics Of Student Pharmacists Across Cohorts, Kristin Rose Villa

Open Access Theses

In unstable environments, adaptation is a prerequisite for survival of organizations or groups. The Affordable Care Act has created a changing environment for health care providers. Unfortunately for Pharmacy, innovation within our profession has languished, leaving pharmacists in a precarious position. Many have noted the stagnation of the profession; in fact it has been a recurring theme in the commentary over the last five decades. The dialogue has focused on the externalities that represent barriers to the profession's evolution, including the direction change should take and the legal or organizational issues that inhibit change and innovation. Little attention has been …

Consumer-Oriented Drug Information Service Needs Assessment, Timothy K. Cheum, Kejal V. Patle, Rodney Richmond

Faculty Research ​and Publications

Federal legislation that has been introduced to amend the Social Security Act in order to provide for coverage of cognitive pharmacist services under the Medicare program in medically underserved communities. In the rural state of Arkansas this legislation would be well-received because a large portion of the state meets the criteria of a health professional shortage area. Considering the growing interest of using telecommunications as an alternative means of delivering healthcare services to medically underserved rural areas, a pharmacist-staffed consumer-oriented drug information service was explored. Over a 5-day period, 473 face-to-face consumer surveys were conducted in pharmacy and non-pharmacy settings …

Musculoskeletal Safety Outcomes Of Patients Receiving Daptomycin With Hmg-Coa Reductase Inhibitors, Christopher M. Bland, P Brandon Bookstaver, Z Kevin Lu, Brianne L. Dunn, Kathey Fulton Rumley

Faculty Publications

Daptomycin, a cyclic lipopeptide antibiotic, and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are commonly administered in the inpatient setting and are associated with creatine phosphokinase (CPK) elevations, myalgias, and muscle weakness. Safety data for coadministration of daptomycin with statins are limited. To determine the safety of coadministration of daptomycin with statin therapy, a multicenter, retrospective, observational study was performed at 13 institutions in the Southeastern United States. Forty-nine adult patients receiving statins concurrently with daptomycin were compared with 171 patients receiving daptomycin without statin therapy. Detailed information, including treatment indication and duration, infecting pathogen, baseline and subsequent CPK levels, and …

Extended-Release Hydrocodone: The Devil In Disguise Or Just Misunderstood?, Anne Schweighardt, Katherine Juba

Pharmacy Faculty/Staff Publications

Opioid abuse in the United States increased significantly over the past decade, leading to opioid-related deaths. Approval of Zohydro ER, a product that lacks an abuse-deterrent formulation, has provoked media controversy and aggressive legislative action from multiple stakeholders. Only the American Academy of Pain Management has released a position statement on this medication, and individual opinion varies. Additional single-entity extended-release hydrocodone formulations are in the pipeline, and Zohydro ER's limited clinical utility may make the controversy associated with its approval a moot point. As with other opioids, providers will need to assess individual patient risk versus benefit when prescribing Zohydro …

Effects Of Three Low-Doses Of D-Tagatose On Glycemic Control Over Six Months In Subjects With Mild Type 2 Diabetes Mellitus Under Control With Diet And Exercise, Mark Ensor, Jarrod Williams, Rebecca Smith, Amy Banfield, Robert A. Lodder

Pharmaceutical Sciences Faculty Publications

The primary objective of this study was to evaluate the safety and the effect of D-tagatose on the glycemic control of subjects with type 2 diabetes as determined by HbA_1c levels at the end of 6 months of therapy using the subject's own baseline HbA_1c level as a comparator. The determination of the minimal dose required to cause a statistically significant reduction in HbA_1c was of particular interest. Eight weeks after screening, the qualifying subjects were randomized to receive one of three doses of D-tagatose: 2.5 g TID, 5.0 g TID or 7.5 g TID. Blood levels …

The Yin: An Adverse Health Perspective Of Nanoceria: Uptake, Distribution, Accumulation, And Mechanisms Of Its Toxicity, Robert A. Yokel, Salik Hussain, Stavros Garantziotis, Philip Demokritou, Vincent Castranova, Flemming R. Cassee

Pharmaceutical Sciences Faculty Publications

This critical review evolved from a SNO Special Workshop on Nanoceria panel presentation addressing the toxicological risks of nanoceria: accumulation, target organs, and issues of clearance; how exposure dose/concentration, exposure route, and experimental preparation/model influence the different reported effects of nanoceria; and how can safer by design concepts be applied to nanoceria? It focuses on the most relevant routes of human nanoceria exposure and uptake, disposition, persistence, and resultant adverse effects. The pulmonary, oral, dermal, and topical ocular exposure routes are addressed as well as the intravenous route, as the latter provides a reference for the pharmacokinetic fate of nanoceria …

Systematic Review Of Potential Health Risks Posed By Pharmaceutical, Occupational And Consumer Exposures To Metallic And Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide And Its Soluble Salts, Calvin C. Willhite, Nataliya A. Karyakina, Robert A. Yokel, Nagarajkumar Yenugadhati, Thomas M. Wisniewski, Ian M. F. Arnold, Franco Momoli, Daniel Krewski

Pharmaceutical Sciences Faculty Publications

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007).

Challenges encountered in carrying out the present review reflected the experimental use of different physical …

The Impact Of An Omega-3 Enriched Diet On Hyperactivity And Biochemistry In An Animal Model For Attention-Deficit/Hyperactivity Disorder, Nadine M. Hammoud

Open Access Theses

Attention-deficit/hyperactivity disorder (ADHD) is the most diagnosed behavioral disorder in children. It affects around 5% of children worldwide and 11% of children in the United States, with rates increasing. Pharmaceutical treatments, such as amphetamines and methylphenidates, are not effective for everyone and are known to have unwanted side effects. While the etiology of the disorder is not yet fully understood, there are clear genetic and environmental components. Nutritional insufficiencies have recently become a popular environmental risk factor under investigation. Essential fatty acids (EFA), omega-3 polyunsaturated fatty acids (PUFA) in particular, are needed for proper brain development and function. Our lab …

Pharmacist Collaborative Drug Therapy Management In U.S. Hospitals, Pragya Mishra

Open Access Theses

The objectives for this study were to 1) assess the current extent, scope and perceptions of CDTM in U.S. hospitals, 2) determine the associations between hospital characteristics, pharmacy director characteristics, and perceptions of CDTM, 3) investigate hospitals' short-term and long-term plans regarding CDTM, and 4) identify pharmacy directors' views about the major facilitators and barriers for CDTM in hospitals.

A self-administered written survey was mailed to a national random sample of hospitals stratified by state. Pharmacy directors indicated whether any pharmacists were engaged in CDTM, what CDTM activities were permitted, and in what treatment categories CDTM was permitted. Demographic data …