Pharmacy and Pharmaceutical Sciences Commons^™

Antispasmodic And Ca++ Antagonist Potential Of Marrubiin, A Labdane Type Diterpene From Phlomis Bracteosa, Javid Hussain, Riaz Ullah, Arif-Ullah Khan, Fazal Mabood, Mohammad Raza Shah, Ahmed Al-Harrasi, Anwar Gilani

Department of Biological & Biomedical Sciences

A tricyclic labdane type diterpene was isolated for the first time from ethyl acetate soluble part of Phlomis bracteosa. Its structure was confirmed by x-ray which was found to be marrubiin. When studied in isolated rabbit jejunum, marrubiin caused concentration-dependent relaxation of spontaneous and high K+ (80 mM)-induced contractions, like that caused by verapamil, indicating that marrubiin exhibits spasmolytic activity, possibly mediated through Ca++ channel blocking action.

Constructing A Critical Path For Product Development, Commercialization, And Access, Martha Brady

HIV and AIDS

This brief discusses the Council's health technologies development and the product development path from conceptualization to market. It defines the steps in the Critical Path Framework, and examines activities at the preclinical and clinical stage.

Detecting Counterfeit Anti-Malarials Through Comparison Between High-Pressure Liquid Chromatography And Other Methods Of Analysis, Andrea Irby

Theses & Honors Papers

Counterfeit pharmaceuticals are an increasing trend in the world of criminal activity because the business of making fake pharmaceuticals is highly profitable. The scientific community needs to develop clear-cut methods of detection for counterfeit pharmaceuticals because this is an issue that affects human health and because the use of prescription drugs is so prevalent. This study used high-pressure liquid chromatography (HPLC) and fluorescence spectroscopy to produce qualitative and quantitative data about quinine, mefloquine and choloroquine. These were studied because they are common anti-malarial drugs used in developing nations and they are often counterfeited. Tablet mixtures meant to replicate pharmaceutical tablets …

3-Substitued Indoles: One Pot Synthesis And Evaluation Of Anticancer And Src Kinase Inhibitory Activities, V. Kameshwara Rao, Bhupender S. Chhikara, Amir Nasrolahi Shirazi, Rakesh Tiwari, Keykavous Parang, Anil Kumar

Pharmacy Faculty Articles and Research

An efficient and economical method was developed for the synthesis of 3-substituted indoles by one pot three-component coupling reaction of a substituted or unsubstituted benzaldehyde, N-methylaniline, and indole or N-methylindole using Yb(OTf)3-SiO2 as a catalyst. All the synthesized compounds were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), human ovarian adenocarcinoma (SK-OV-3), and c-Src kinase activity. The 4-methylphenyl (4o and 4p) and 4-methoxyphenyl (4q) indole derivatives inhibited the cell proliferation of SK-OV-3 and HT-29 cells by 7077% at a concentration of 50 μM. The unsubstituted phenyl (4d) and 3-nitrophenyl (4l) derivatives showed the inhibition of c-Src kinase …

Targeted Decorin Gene Therapy Delivered With Adeno-Associated Virus Effectively Retards Corneal Neovascularization In Vivo, Rajiv R. Mohan, Jonathan C. K. Tovey, Ajay Sharma, Gregory S. Schultz, John W. Cowden, Ashish Tandon

Pharmacy Faculty Articles and Research

Decorin, small leucine-rich proteoglycan, has been shown to modulate angiogenesis in nonocular tissues. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the rabbit stroma with adeno-associated virus serotype 5 (AAV5) impedes corneal neovascularization (CNV) in vivo without significant side effects. An established rabbit CNV model was used. Targeted decorin gene therapy in the rabbit stroma was delivered with a single topical AAV5 titer (100 μl; 5x10^12 vg/ml) application onto the stroma for two minutes after removing corneal epithelium. The levels of CNV were examined with stereomicroscopy, H&E staining, lectin, collagen type IV, CD31 immunocytochemistry and …

Click Chemistry Inspired One-Pot Synthesis Of 1, 4-Disubstituted 1, 2, 3-Triazoles And Their Src Kinase Inhibitory Activity, Dalip Kumar, V. Buchi Reddy, Anil Kumar, Deendayal Mandal, Rakesh Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Two classes of 1,4-disubstituted 1,2,3-triazoles were synthesized using one-pot reaction of α-tosyloxy ketones/α-halo ketones, sodium azide, and terminal alkynes in the presence of aq. PEG (1:1, v/v) using the click chemistry approach and evaluated for Src kinase inhibitory activity. Structure-activity relationship analysis demonstrated that insertion of C6H5- and 4-CH3C6H4- at position 4 for both classes and less bulkier aromatic group at position 1 in class 1 contribute critically to the modest Src inhibition activity (IC50 = 32-43 µM) of 1,4-disubstituted 1,2,3-triazoles.

Thiazolyl N-Benzyl-Substituted Acetamide Derivatives: Synthesis, Src Kinase Inhibitory And Anticancer Activities, Asal Fallah-Tafti, Alireza Foroumadi, Rakesh Tiwari, Amir Nasrolahi Shirazi, David G. Hangauer, Yahao Bu, Tahmineh Akbarzadeh, Keykavous Parang, Abbas Shafiee

Pharmacy Faculty Articles and Research

KX2-391 (KX-01/Kinex Pharmaceuticals), N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)acetamide, is a highly selective Src substrate binding site inhibitor. To understand better the role of pyridine ring and N-benzylsubstitution in KX2-391 and establish the structure-activity relationship, a number of N-benzyl substituted (2-morpholinoethoxy)phenyl)thiazol-4-yl)acetamide derivatives containing thiazole instead of pyridine were synthesized and evaluated for Src kinase inhibitory activities. The unsubstituted N-benzyl derivative (8a) showed the inhibition of c-Src kinase with GI50 values of 1.34 μM and 2.30 M in NIH3T3/c-Src527F and SYF/c-Src527F cells, respectively. All the synthesized compounds were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), breast carcinoma (BT-20), and leukemia (CCRF-CEM) cells. …

Comparative Pharmacodynamics Of Ceftobiprole, Daptomycin, Linezolid, Telavancin, Tigecycline, And Vancomycin In The Treatment Of Methicillin Resistant Staphylococcus Aureus: A Monte Carlo Simulation Analysis, Ahmed H. Salem, Ehab A. Noreddin, George G. Zhanel, Ayman M. Noreddin

Pharmacy Faculty Articles and Research

Background/Objectives: Appropriate initial treatment choices for methicillin resistant Staphylococcus aureus (MRSA) infections are very critical. The aim of this study was to compare the ability of Ceftobiprole, Daptomycin, Linezolid, Telavancin, Tigecycline, and Vancomycin to achieve their requisite pharmacokinetic/pharmacodynamic (PK/PD) target against clinical MRSA isolates.

Methods: Monte Carlo Simulations were performed to simulate the PK/PD indices of the investigated antimicrobials. Population Pharmacokinetic data and Pharmacodynamic indices were integrated into Monte Carlo Simulation routine with 10,000 iterations. Probability of target attainment (PTA) was estimated at MIC values ranging from 0.03-32 μg/ml to define the PK/PD susceptibility breakpoints. Cumulative fraction of …

Postgraduate Year One (Pgy1) Department Of Pharmacy Residency Program, Jessica Price Pharmd, Bcps

Department of Pharmacy

No abstract provided.

Polyethylenimine-Conjugated Gold Nanoparticles: Gene Transfer Potential And Low Toxicity In The Cornea, Ajay Sharma, Ashish Tandon, Jonathan C. K. Tovey, Rangan Gupta, J. David Robertson, Jennifer A. Fortune, Alexander M. Klibanov, John W. Cowden, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

This study examined the gene transfer efficiency and toxicity of 2-kDa polyethylenimine conjugated to gold nanoparticles (PEI2-GNP) in the human cornea in vitro and rabbit cornea in vivo. PEI2-GNP with nitrogen-to-phosphorus (N/P) ratios of up to 180 exhibited significant transgene delivery in the human cornea without altering the viability or phenotype of these cells. Similarly, PEI2-GNP applied to corneal tissues collected after 12 h, 72 h, or 7 days exhibited appreciable gold uptake throughout the rabbit stroma with gradual clearance of GNP over time. Transmission electron microscopy detected GNP in the keratocytes and the extracellular matrix of the rabbit corneas. …

Biophysical Techniques Of Transcutaneous Drug Sampling And Drug Delivery, Srinivasa Murthy Sammeta

Electronic Theses and Dissertations

Monitoring the time course of drug in the skin is critical for determining the frequency and dose of drug administration from safety and efficacy perspectives. Intermittent blood sampling is used as a surrogate for approximating concentration of drugs in the tissues, which leads to blood loss and discomfort to patients. A novel noninvasive technique called “Electroporation and transcutaneous sampling” (ETS) was developed for estimating the drug concentration in the skin extracellular fluid. The application of ETS technique in studying dermatokinetics of cephalexin, ciprofloxacin, and 8-methoxypsoralen was investigated. The results demonstrated the ability of ETS technique in dermatokinetic studies of drugs …

Topiramate: Safety And Efficacy Of Its Use In The Prevention And Treatment Of Migraine, Ginger C. Minton, April D. Miller, P Brandon Bookstaver, Bryan L. Love

Faculty Publications

Migraine headaches are typically episodic in nature and may affect nearly 10% of the population. In addition to treatment, prevention of subsequent episodes or progression to a chronic migraine state is an important therapeutic area. Topiramate is a centrally acting medication approved for both the prevention of seizures and migraine headache. At this time, the exact mechanism of how topiramate assists in migraine prevention is unknown. Several large randomized, controlled trials have aided in establishing topiramate's role in migraine prevention. Despite a favorable pharmacokinetic and adverse effect profile established in clinical trials, several additional studies, case reports and toxicology reports …

Diverse Inflammatory Responses In Transgenic Mouse Models Of Alzheimer's Disease And The Effect Of Immunotherapy On These Responses, Donna M. Wilcock, Qun Zhao, Dave Morgan, Marcia N. Gordon, Angela Everhart, Joan G. Wilson, Jennifer E. Lee, Carol A. Colton

Molecular Pharmacology & Physiology Faculty Publications

While the presence of an inflammatory response in AD (Alzheimer's disease) is well known, the data on inflammation are conflicting, suggesting that inflammation either attenuates pathology, exacerbates it or has no effect. Our goal was to more fully characterize the inflammatory response in APP (amyloid precursor protein) transgenic mice with and without disease progression. In addition, we have examined how anti-Aβ (amyloid β-peptide) immunotherapy alters this inflammatory response. We have used quantitative RT–PCR (reverse transcription–PCR) and protein analysis to measure inflammatory responses ranging from proinflammatory to anti-inflammatory and repair factors in transgenic mice that develop amyloid deposits only …

Design, Synthesis, Biological Evaluation And Metabolic Stability Studies Of Sigma Receptor Ligands, Rohit Bhat

Electronic Theses and Dissertations

Sigma receptors represent a unique family of proteins that includes two subtypes: sigma-1 and sigma-2. Sigma-1 receptors have been implicated in the behavioral and motivational effects of psychostimulants as well as in the pathophysiology of depression and Alzheimer's disease. Sigma-2 receptors are widely expressed on many tumor cells and they are believed to play an important role in tumor cell proliferation. Therefore, sigma receptors are attractive targets for developing pharmaceutical agents directed to the treatment of psychostimulant abuse, cancer, Alzheimer's disease as well as diagnostic agents for cancer and brain imaging. A derivatized 2(3H)-benzothiazolone, (3-(2-(azepan-1-yl)ethyl)-6-propylbenzo[ d]thiazol-2(3H)-one) was reported to have …

Lecture Podcasts--Supplement Or Replacement For In-Class Lectures In Traditional Classroom Courses?, Parag Budukh, Christine R. Birnie

Pharmacy Faculty/Staff Publications

No abstract provided.

The Design Of A Sterile Product Laboratory Module As Preparation For An Institutional Ippe Course, Fang Zhao, Christine R. Birnie, Anthony Corigliano, Susan Hughes, John Loughner, Stephen Valentine

Pharmacy Faculty/Staff Publications

Objectives: To develop a pharmaceutics laboratory module on compounded sterile products for the second year pharmacy students as preparation for an institutional pharmacy experiential course. Method: A 5-week lab module was designed and implemented as part of the Pharmaceutics Lab Course to provide training in the basic skills of sterile product compounding. The module included techniques in the handling of sterile products, aseptic techniques, medium risk products, and hazardous products. A practical exam was given at the end of this module to ensure student competency. Upon completion of the lab module, students enrolled in a required 4-week institutional pharmacy experiential …

Evaluation Of Student Performance Using Multiple Choice And Open-Ended Examination Questions In A Pharmacy Calculations Course., Christine R. Birnie, Parag Budukh

Pharmacy Faculty/Staff Publications

No abstract provided.

Anticoagulation Clinic Led By Experiential Education Team, Asim Abu-Baker

Pharmacy Faculty/Staff Publications

No abstract provided.

Increased Hypoglycemia Associated With Renal Failure During Continuous Intravenous Insulin Infusion And Specialized Nutritional Support, Roland N. Dickerson, Leslie A. Hamilton, Kathryn A. Connor, George O. Maish, Martin A. Croce, Gayle Minard, Rex O. Brown

Pharmacy Faculty/Staff Publications

Objective: To evaluate glycemic control for critically ill, hyperglycemic trauma patients with renal failure who received concurrent intensive insulin therapy and continuous enteral (EN) or parenteral nutrition (PN).

Methods: Adult trauma patients with renal failure, who were given EN or PN concurrently with continuous graduated intravenous regular human insulin (RHI) infusion for at least 3 days were evaluated. Our conventional RHI algorithm was modified for those with renal failure by allowing greater changes in blood glucose concentrations (BG) before the infusion rate was escalated. BG was determined every 1-2 hours while receiving the insulin infusion. BG control was evaluated on …

Significant Inhibition Of Corneal Scarring In Vivo With Tissue-Selective, Targeted Aav5 Decorin Gene Therapy, Rajiv R. Mohan, Ashish Tandon, Ajay Sharma, John W. Cowden, Jonathan C. K. Tovey

Pharmacy Faculty Articles and Research

PURPOSE. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the stroma with adeno-associated virus serotype 5 (AAV5) inhibits corneal fibrosis in vivo without significant side effects.

METHODS. An in vivo rabbit model of corneal fibrosis was used. Targeted decorin gene therapy was delivered to the rabbit cornea by a single topical application of AAV5 (100 L; 6.5 1012 g/mL) onto the bare stroma for 2 minutes. The levels of corneal fibrosis were determined with stereomicroscopy, slit lamp biomicroscopy, -smooth muscle actin ( SMA), fibronectin, and F-actin immunocytochemistry, and/or immunoblotting. CD11b, F4/80 immunocytochemistry, and TUNEL assay …

Pharmacy-Level Quality Measures And The Consumer: Preferences And Attitudes, Zainab S. Shahpurwala

Electronic Theses and Dissertations

Objectives. To determine the perceptions of consumers toward community pharmacy quality measures and compare their perceptions regarding their pharmacy's overall quality before and after exposure to these measures. To explore the use of evaluative criteria applied by consumers to determine their preference for information related to these measures. Methods. Focus groups were used to refine attributes and levels used in the quantitative phase of the study. An Internet-based survey was administered to a national, online, consumer panel of community pharmacy patrons using maintenance medications. Descriptive statistics, MANOVA and t-tests were used to determine and compare perceptions related to the community …

Pharmacokinetic Evaluation Of A Novel Compound, Sn79, A Putative Sigma-2 Receptor Antagonist, By Intravenous And Oral Administration In Rats, Harsha Vinnakota

Electronic Theses and Dissertations

Considering the alarming rates at which substance drug abuse, especially cocaine, is increasing in today's society, there is a lot of impetus on the development of medications that can effectively help alleviate its toxicity and addiction. The affinity of cocaine to sigma receptors (sigma-1 and sigma-2) rendered the hypothesis that blocking sigma receptors could be a possible mechanism to attenuate cocaine-induced toxicity and addiction. In this view, SN79, a synthetic compound with selectivity to both sigma-1 and sigma-2 receptors garnered our attraction for its use as an antagonist. This dissertation encompasses detailed investigation of SN79 from drug discovery and development …

The Strategic Value Driver Model: A Methodology For Examining Value Drivers For A New Pharmaceutical Product In Diabetes, Sumit Verma

Electronic Theses and Dissertations

Objective. Objective The primary objective of this study was to explore a new methodological framework—Strategic Value Driver Model (SVDM), for examining value drivers for new pharmaceutical inhaled insulin in diabetes. Methods. A cross-sectional, internet-based survey was used to collect a sample of 483 Type 2 diabetic patients via national panel of diabetic patients. The sample had two subgroups—insulin-naïve (52.9%, n=255) and insulin-user (47.1%, n=227) patients. The comparative performance of insulin syringes/vials, insulin pen and inhaled insulin was captured on four product attributes (i.e., safety, convenience, clinical efficacy and cost) after asking the patients to report the importance of these attributes. …

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.