Pharmacy and Pharmaceutical Sciences Commons^™

Pharmacy Newsletter : April 2009, Pharmacy Department

Department of Pharmacy Archives

Content:

• Pharmacy News
• FDA Alerts
• Interaction Update
• Establishment of a New Anti-H.pylori Regimen

Carbon Nanotube Membranes For Use In The Transdermal Treatment Of Nicotine Addiction And Opioid Withdrawal Symptoms, Caroline L. Strasinger, Nicole N. Scheff, Ji Wu, Bruce J. Hinds, Audra L. Stinchcomb

Pharmaceutical Sciences Faculty Publications

Transdermal systems are attractive methods of drug administration specifically when treating patients for drug addiction. Current systems however are deficient in therapies that allow variable flux values of drug, such as nicotine for smoking cessation or complex dosing regimens using clonidine when treating opioid withdrawal symptoms. Through the use of functionalized carbon nanotube (CNT) membranes, drug delivery to the skin can be controlled by applying a small electrical bias to create a programmable drug delivery system. Clearly, a transdermal patch system that can be tailored to an individual's needs will increase patient compliance as well as provide much more efficient …

Association Of Gucy2c Expression In Lymph Nodes With Time To Recurrence And Disease-Free Survival In Pn0 Colorectal Cancer., Scott A Waldman, Terry Hyslop, Stephanie Schulz, Alan Barkun, Karl Nielsen, Janis Haaf, Christine Bonaccorso, Yanyan Li, David S Weinberg

Department of Pharmacology and Experimental Therapeutics Faculty Papers

CONTEXT: The established relationship between lymph node metastasis and prognosis in colorectal cancer suggests that recurrence in 25% of patients with lymph nodes free of tumor cells by histopathology (pN0) reflects the presence of occult metastases. Guanylyl cyclase 2C (GUCY2C) is a marker expressed by colorectal tumors that could reveal occult metastases in lymph nodes and better estimate recurrence risk.

OBJECTIVE: To examine the association of occult lymph node metastases detected by quantifying GUCY2C messenger RNA, using the reverse transcriptase-polymerase chain reaction, with recurrence and survival in patients with colorectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 257 patients …

New Dosing Schedules Of Dasatinib For Cml And Adverse Event Management, Siu Fun Wong

Pharmacy Faculty Articles and Research

Resistance to imatinib in patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has emerged as a significant clinical issue. Dasatinib is a tyrosine kinase inhibitor that has 325-fold greater in vitro activity against native BCR-ABL (breakpoint cluster region-Abelson leukemia virus) compared with imatinib and can overcome primary (intrinsic) and secondary (acquired) imatinib resistance. Here, we review the clinical profile of dasatinib in imatinib-resistant and -intolerant patients and share clinical approaches for managing adverse events (AEs) to ensure maximum patient benefit. References were obtained through literature searches on PubMed as well as from the Proceedings …

Tablet Splitting: To Split Or Not To Split, J. Obenrader, Joseph A. Woelfel

School of Pharmacy Faculty Articles

No abstract provided.

Preparation Of Nanovehicles For Targeted Drug Delivery, Anagha Avinash Bhakay

Theses

Application of nanotechnology in pharmaceutical research has opened new frontiers for drug development and its efficient delivery. In recent years, the focus of the research has been on the engineering of nano/micro-particulate structures for efficient and targeted delivery of drugs for selective and enhanced absorption. This work throws light on the preparation of biodegradable and non-toxic nanoparticulate systems for targeted drug delivery. The drug vehicles were made by two different processes namely electrostatic interactions and desolvation process. The drug carriers made by these processes were found to be in the size range of 150-200nm which is necessary for cellular uptake …

Identification Of A Potent Herbal Molecule For The Treatment Of Breast Cancer, Srinivas Koduru, Srinivasan Sowmyalakshmi, Raj Kumar, Rohini Gomathinayagam, Jürgen Rohr, Chendil Damodaran

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Breast cancer (BCa)-related mortality still remains the second leading cause of cancer-related deaths worldwide. Patients with BCa have increasingly shown resistance and high toxicity to current chemotherapeutic drugs for which identification of novel targeted therapies are required.

METHODS: To determine the effect of PDBD on BCa cells, estrogen-receptor positive (ER+)-MCF-7 and estrogen-receptor negative (ER-)-MDA 231 cells were treated with PDBD and the cell viability, apoptotic, cell cycle, Western blot and Promoter assays were performed.

RESULTS: PDBD inhibits cell viability of ER+ and ER- BCa cells by inducing apoptosis without causing significant toxicity in normal breast epithelial cells. While dissecting …

A Structural Interpretation Of The Effect Of Gc-Content On Efficiency Of Rna Interference, Chi Yu Chan, C Steven Carmack, Dang D. Long, Anil Maliyekkel, Yu Shao, Igor Roninson, Ye Ding

Faculty Publications

BACKGROUND: RNA interference (RNAi) mediated by small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) has become a powerful technique for eukaryotic gene knockdown. siRNA GC-content negatively correlates with RNAi efficiency, and it is of interest to have a convincing mechanistic interpretation of this observation. We here examine this issue by considering the secondary structures for both the target messenger RNA (mRNA) and the siRNA guide strand. RESULTS: By analyzing a unique homogeneous data set of 101 shRNAs targeted to 100 endogenous human genes, we find that: 1) target site accessibility is more important than GC-content for efficient RNAi; 2) …

Effects Of Neurotensin 1 Receptor And D2 Dopamine Receptor Antagonist In Amygdaloid Learning Mechanisms, K. Laszlo, K. Toth, A. Molnar, E. Kertes, L. Peczely, L. Lenard

Pharmaceutical Sciences

No abstract provided.

In Silico Whole Genome Association Scan For Murine Prepulse Inhibition, Bradley Todd Webb, Joseph L. Mcclay, Cristina Vargas-Irwin, Timothy P. York, Edwin J. C. G. Van Den Oord

Biomarker Research and Personalized Medicine Publications

Background

The complex trait of prepulse inhibition (PPI) is a sensory gating measure related to schizophrenia and can be measured in mice. Large-scale public repositories of inbred mouse strain genotypes and phenotypes such as PPI can be used to detect Quantitative Trait Loci (QTLs) in silico. However, the method has been criticized for issues including insufficient number of strains, not controlling for false discoveries, the complex haplotype structure of inbred mice, and failing to account for genotypic and phenotypic subgroups.

Methodology/Principal Findings

We have implemented a method that addresses these issues by incorporating phylogenetic analyses, multilevel regression with mixed …

The Challenge Of Educating In A Highly-Connected And Multitasking World, Daniel A. Brazeau, Gayle A. Brazeau

Pharmaceutical Sciences Faculty Publications

Today’s students are more connected and more integrated with their world than any past generation and information is readily available today from a multitude of sources. To what extent have these advances improved our students’ ability to become learned pharmacy professionals who are informed not only of the current world and its events but the profession itself?

Interactions Of Alkali Cations With Glutamate Transporters, David C. Holley, Michael P. Kavanaugh

Biomedical and Pharmaceutical Sciences Faculty Publications

The transport of glutamate is coupled to the co-transport of three Na+ ions and the countertransport of one K+ ion. In addition to this carrier-type exchange behaviour, glutamate transporters also behave as chloride channels. The chloride channel activity is strongly influenced by the cations that are involved in coupled flux, making glutamate transporters representative of the ambiguous interface between carriers and channels. In this paper, we review the interaction of alkali cations with glutamate transporters in terms of these diverse functions. We also present a model derived from electrostatic mapping of the predicted cation-binding sites in the X-ray crystal structure …

Predicting The Drug Release Kinetics Of Matrix Tablets, Boris Baeumer, Lipika Chatterjee, Peter Hinow, Thomas Rades, Ami E. Radunskaya, Ian Tucker

Pomona Faculty Publications and Research

In this paper we develop two mathematical models to predict the release kinetics of a water soluble drug from a polymer/excipient matrix tablet. The first of our models consists of a random walk on a weighted graph, where the vertices of the graph represent particles of a drug, excipient and polymer, respectively. The graph itself is the contact graph of a multidisperse random sphere packing. The second model describes the dissolution and the subsequent diffusion of the active drug out of a porous matrix using a system of a partial differential equations. The predictions of both models show good qualitative …

Sildenafil For The Treatment Of Pulmonary Hypertension In Pediatric Patients, Alice J. Huddleston, Chad A. Knoderer, Jennifer L. Morris, Eric S. Ebenroth

Scholarship and Professional Work – COPHS

Sildenafil is a phosphodiesterase 5 inhibitor widely used for the treatment of pulmonary hypertension in children. Despite limited available safety and efficacy evidence, use of sildenafil continues to increase. To date, sildenafil use for pediatric pulmonary hypertension has been characterized for 193 children through 16 studies and 28 case series and reports. The primary efficacy data suggest that sildenafil is beneficial for facilitating the weaning of inhaled nitric oxide in children after cardiac surgery. Compiled safety data suggest that sildenafil is well tolerated among children with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease. This …

Administrators’ Perceptions Of Medication Management In Assisted Living Facilities: Results From Focus Groups, Priscilla T. Ryder, Melanie Joseph, Marnie Zuckermann, Ilene H. Zuckermann

Scholarship and Professional Work – COPHS

Objective: Assisted living (AL) residents are vulnerable to adverse events as a result of using numerous medications and frequently need assistance in administering medications. Very little is known, however, about the ways in which medications are managed within this level of care. Design: AL administrators from the metropolitan Baltimore, Maryland area were invited to participate in focus groups to explore issues involved in medication management.

Setting and Participants: Four administrators from smaller (15 beds or fewer) and six larger (more than 15 beds) certified AL facilities serving primarily older residents participated. Administrators must have served in their position at least …

Association Of Antipsychotic Use With Hospital Events And Mortality Among Medicare Beneficiaries Residing In Long-Term Care Facilities, Linda Simoni-Wastila, Priscilla T. Ryder, Jingjing Qian, Ilene H. Zuckermann, Thomas Shaffer, Lirong Zhao

Scholarship and Professional Work – COPHS

Objective—Antipsychotic (AP) utilization has grown significantly in long-term care (LTC) settings. Although a growing literature associates AP use with higher mortality in elderly with dementia, the association of APs with hospital events is unclear. The authors examine prevalence and trends in AP use by Medicare beneficiaries residing in LTC and the association of APs and other drug use variables with hospital events and mortality.

Design—Retrospective analysis using sequential multivariate Cox proportional hazards models.

Setting—Medicare Current Beneficiary Survey linked to Institutional Drug Administration and Minimum Data Set files.

Participants—A total of 2,363 LTC Medicare beneficiaries, 1999–2002. Measurements—Trends in LTC AP use …

Treatment Of Metastatic Renal Cell Carcinoma, David J. Reeves, Chin Y. Liu

Scholarship and Professional Work – COPHS

Purpose

To review the treatment of metastatic renal cell carcinoma (RCC), including the use of new targeted therapies.

Methods

A search of MEDLINE (1966 to August 2008) and American Society of Clinical Oncology Meeting abstracts (2005 to May 2008) was preformed using the search terms bevacizumab, everolimus, interferon-alfa (IFN-α), interleukin-2 (IL-2), sorafenib, sunitinib, temsirolimus, and RCC. Articles most pertinent to the treatment of metastatic RCC are reviewed.

Results

The treatment of metastatic RCC has undergone a paradigm shift over the past 5 years from biologic response modifiers to new targeted therapies. Historically, response rates for the biological response modifiers, aldesleukin …

Retrospective Evaluation Of Venous Thromboembolism Prophylaxis In The Adult Cancer Population, David J. Reeves, Chin Y. Liu

Scholarship and Professional Work – COPHS

Study objectives. Hospitalized cancer patients are at an increased risk for venous thromboembolism (VTE) and it is recommended they receive pharmacologic prophylaxis unless otherwise contraindicated. The majority of data supporting this recommendation comes from sub-group analyses and extrapolation of data gathered in general medical/surgical patients. This study seeks to assess the safety and efficacy of VTE prophylaxis in cancer patients admitted to our institution.

Methods. Charts of patients 18—89 years of age receiving VTE prophylaxis with unfractionated heparin, low molecular weigh heparin, or fondaparinux while admitted to Karmanos Cancer Center between September and October 2007 were retrospectively reviewed. Risk factors …

Urinary Levoglucosan As A Biomarker Of Wood Smoke Exposure: Observations In A Mouse Model And In Children, Christopher T. Migliaccio, M. A. Bergauff, Christopher P. Palmer, Forrest Jessop, Curtis W. Noonan, Tony Ward

Biomedical and Pharmaceutical Sciences Faculty Publications

BACKGROUND: Biomass smoke is an important source of particulate matter (PM), and much remains to be discovered with respect to the human health effects associated with this specific PM source. Exposure to biomass smoke can occur in one of two main categories: short-term exposures consist of periodic, seasonal exposures typified by communities near forest fires or intentional agricultural burning, and long-term exposures are chronic and typified by the use of biomass materials for cooking or heating. Levoglucosan (LG), a sugar anhydride released by combustion of cellulose-containing materials, is an attractive candidate as a biomarker of wood smoke exposure. OBJECTIVES: In …

Mass Stranding Of Marine Birds Caused By A Surfactant-Producing Red Tide., David A. Jessup, Melissa A. Miller, John P. Ryan, Hannah M. Nevins, Heather A. Kerkering, Abdou Mekebri, David B. Crane, Tyler A. Johnson, Raphael M. Kudela

Natural Sciences and Mathematics | Faculty Scholarship

In November-December 2007 a widespread seabird mortality event occurred in Monterey Bay, California, USA, coincident with a massive red tide caused by the dinoflagellate Akashiwo sanguinea. Affected birds had a slimy yellow-green material on their feathers, which were saturated with water, and they were severely hypothermic. We determined that foam containing surfactant-like proteins, derived from organic matter of the red tide, coated their feathers and neutralized natural water repellency and insulation. No evidence of exposure to petroleum or other oils or biotoxins were found. This is the first documented case of its kind, but previous similar events may have gone …

Trichostatin A Inhibits Corneal Haze In Vitro And In Vivo, Ajay Sharma, Maneesh M. Mehan, Sunilima Sinha, John W. Cowden, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. Trichostatin A (TSA), a histone deacetylase inhibitor, has been shown to suppress TGF- –induced fibrogenesis in many nonocular tissues. The authors evaluated TSA cytotoxicity and its antifibrogenic activity on TGF- –driven fibrosis in the cornea with the use of in vitro and in vivo models.

METHODS. Human corneal fibroblasts (HSFs) were used for in vitro studies, and New Zealand White rabbits were used for in vivo studies. Haze in the rabbit cornea was produced with photorefractive keratectomy (PRK) using excimer laser. Trypan blue exclusion and MTT assays evaluated TSA cytotoxicity to the cornea. Density of haze in the rabbit …

Human Cytomegalovirus Us28: A Functionally Selective Chemokine Binding Receptor, Jennifer Totonchy, Jay A. Nelson, Daniel N. Streblow

Pharmacy Faculty Articles and Research

The Human Cytomegalovirus (HCMV)-encoded chemokine receptor US28 is the most well-characterized of the four chemokine receptor-like molecules found in the HCMV genome. US28 been studied as an important virulence factor for HCMV-mediated vascular disease and, more recently, in models of HCMV-associated malignancy. US28 is a rare multi-chemokine family binding receptor with the ability to bind ligands from two distinct chemokine classes. Ligand binding to US28 activates cell-type and ligand-specific signaling pathways leading to cellular migration, an example receptor functional selectivity. Additionally, US28 has been demonstrated to constitutively activate PLC and NFkB. Understanding the structure/function relationships between US28, its ligands and …

Isoniazid Completion Rates For Latent Tuberculosis Infection Among College Students Managed By A Community Pharmacist, Karl M. Hess, Jeffery A. Goad, Joanne Wu, Kathleen Johnson

Pharmacy Faculty Articles and Research

Objective: The authors' objective was to document 9-month and previously recommended 6-month treatment completion rates for latent tuberculosis infection (LTBI) in a pharmacist-managed LTBI clinic in a community pharmacy oil a college Campus. and to describe patient characteristics. Participants: Participants were university Students diagnosed with LTBI. Methods: The authors conducted a retrospective review, of pharmacy records from 2000 to 2006. Main outcome measures included 6-month and 9-month LTBI treatment completion rates, total isoniazid (INH) tablets taken. characteristics of completers versus noncompleters. average time to treatment completion, and reported adverse drug events. Results: The 9-month completion rate was 59%, and the …

The Guinea Pig Ileum Lacks The Direct, High-Potency, M2-Muscarinic, Contractile Mechanism Of The Mouse Ileum, Michael T. Griffin, Minoru Matsui, Rennolds S. Ostrom, Frederick J. Ehlert

Pharmacy Faculty Articles and Research

We explored whether the M2 muscarinic receptor in the guinea pig ileum elicits a highly potent, direct-contractile response, like that from the M3 muscarinic receptor knockout mouse. First, we characterized the irreversible receptor-blocking activity of 4-DAMP mustard in ileum from muscarinic receptor knockout mice to verify its M3 selectivity. Then, we used 4-DAMP mustard to inactivate M3 responses in the guinea pig ileum to attempt to reveal direct, M2 receptor-mediated contractions. The muscarinic agonist, oxotremorine-M, elicited potent contractions in ileum from wild-type, M2 receptor knockout, and M3 receptor knockout mice characterized by negative log EC50 (pEC50) values ± SEM of …

Rat Cytomegalovirus Infection Depletes Mhc Ii In Bone Marrow Derived Dendritic Cells, Carmen C. Baca Jones, Craig N. Kreklywich, Ilhem Messaoudi, Jennifer Totonchy, Erin Mccartney, Susan L. Orloff, Jay A. Nelson, Daniel N. Streblow

Pharmacy Faculty Articles and Research

While cytomegalovirus (CMV) infects and replicates in a multitude of cell types, the ability of the virus to replicate in antigen presenting cells (APCs) is believed to play a critical role in the viral dissemination and latency. CMV infection of APCs and manipulation of their function is an important area of investigation. CMV down regulation of MHC II is reportedly mediated by the HCMV proteins US2, US3, UL83, UL111a (vIL10) or through the induction of cellular IL10. In this study, we demonstrate that rat CMV (RCMV) significantly reduces MHC II expression by mechanisms that do not involve orthologues of the …

Obesity And Contraception, Donald E. Greydanus, Hatim A. Omar, Artemis Tsitsika

Pediatrics Faculty Publications

All sexually active youth, whether obese or normal weight, should be offered counseling regarding contraception and appropriate contraceptive methods. However, obese youth who are sexually active may be less likely than their normal weight peers to use contraceptives correctly. Methods of contraception for obese adolescents are reviewed in this discussion. Combined oral contraceptives (COCs) and the contraceptive patch have higher failure rates in obese versus normal weight females, though failure rates are lower than noted with barrier contraceptives. The risk for venous thrombosis is higher in obese youth on COCs. Progestin-only pills and the levonorgestrel intrauterine system appear to be …

An Analysis Of Drug Dissolution Rates In The Usp 24 Type 2 Apparatus, David Mcdonnell, Brendan Redmond, Deirdre M. D'Arcy, Anne Marie Healy, Owen Corrigan

Articles

This paper applies boundary layer theory to the process of drug dissolution in the USP 24, Type 2 Apparatus. The mass transfer rate from the top flat surface of a compact in various positions within the device is evaluated by means of a Pohlhausen integral method.

Differential Ligand Binding To A Human Cytomegalovirus Chemokine Receptor Determines Cell Type-Specific Motility, Jennifer Totonchy, Ryan Melnychuk, Patricia P. Smith, Joshua Powell, Laurel Hall, Victor R. Defilippis, Klaus Fruh, Martine Smit, David D. Schlaepfer, Jay A. Nelson, Daniel N. Streblow

Pharmacy Faculty Articles and Research

While most chemokine receptors fail to cross the chemokine class boundary with respect to the ligands that they bind, the human cytomegalovirus (HCMV)-encoded chemokine receptor US28 binds multiple CC-chemokines and the CX3Cchemokine Fractalkine. US28 binding to CC-chemokines is both necessary and sufficient to induce vascular smooth muscle cell (SMC) migration in response to HCMV infection. However, the function of Fractalkine binding to US28 is unknown. In this report, we demonstrate that Fractalkine binding to US28 not only induces migration of macrophages but also acts to inhibit RANTES-mediated SMC migration. Similarly, RANTES inhibits Fractalkine-mediated US28 migration in macrophages. While US28 binding …

Compulsory Licensing Of Patented Pharmaceutical Inventions: Evaluating The Options, Jerome H. Reichman

Faculty Scholarship

In this Comment, the author traces the relevant legislative history pertaining to compulsory licensing of patented pharmaceuticals from the TRIPS Agreement of 1994 to the 2003 waiver to, and later proposed amendment of, article 31, which enables poor countries to obtain needed medicines from other countries that possess manufacturing capacity. The Comment then evaluates recent, controversial uses of the relevant legislative machinery as viewed from different critical perspectives. The Comment shows how developing countries seeking access to esential medicines can collaborate in ways that would avoid undermining incentives to innovation and other social costs attributed to compulsory licensing. It ends …

Rethinking The Role Of Clinical Trial Data In International Intellectual Property Law: The Case For A Public Goods Approach, Jerome H. Reichman

Faculty Scholarship

This article is a later version of the author's presentation at the Eleventh Annual Honorable Helen Wilson Nies Memorial Lecture March 26, 2008. Clinical trials are currently used to test drugs; however, the risk and cost of clinical trials are increasing so drastically that the clinical trials may become unsustainable. This article evaluates the legal and economic trends of intellectual property protection for pharmaceutical clinical trial data. The protection of clinical trials has become an alternative to patents as market exclusivity encourages the development and testing of unpatentable pharmaceuticals. This author argues that clinical trials should be treated as a …