Pharmaceutics and Drug Design Commons^™

Effects Of Three Dry Powder Inhalers On Deposition Of Aerosolized Medicine In The Human Oral-Pharyngeal-Laryngeal Regions, Mohammed Ali

Mohammed Ali

The dry powder inhaler (DPI) is a popular, effective and convenient drug delivery device for inhalation therapy to treat asthma. However, a large quantity (approximately 54%) of inhaled aerosols deposit in the oropharyngeal region. Deposition in this region is undesirable because it provides minimum therapeutic benefits and has adverse localized or systemic side effects. This study reports a method of examining electrostatic charge effects on deposition of three DPI aerosols (Spiriva^™ Handihaler, Advair Diskus^™, and Pulmicort^™ Turbohaler) in a cadaver-based cast of the human oral-pharyngeal-laryngeal (OPL) regions. Experimental aerosols were generated from the three commercially available …

A Standardized Patient Counseling Rubric For A Pharmaceutical Care And Communications Course, Niambi Horton Pharmd, Kenna D. Payne Pharmd, Michelle Jernigan Pharmd, Jill Frost Pharmd, Stephen Wise Pharmd, Mary Klein Pharmd, Joel Epps Mba, H. Glenn Anderson Pharmd

H. Glenn Anderson

Objective. To restructure a required pharmaceutical care and communications course to place greater emphasis on communication skills and include a high-stakes assessment. Design. A standardized counseling rubric was developed for use throughout the pharmacy curriculum and the counseling laboratory practicals were changed to high-stakes assessments. Assessment. An annual mid-semester and end-of-semester high-stakes patient-counseling objective structured clinical examination (OSCE) conducted prior to and after revision of the course and counseling rubric documented improvements in students’ scores. Performance on the post-course annual assessment patient counseling OSCE improved compared to that on the pre-course (p,0.001). Conclusion. The 2010 course revision improved students’ medication …

Reactive Oxygen Species Modulation Of Na/K-Atpase Regulates Fibrosis And Renal Proximal Tubular Sodium Handling, Jiang Liu, David J. Kennedy, Yanling Yan, Joseph I. Shapiro Md

Yanling Yan

The Na/K-ATPase is the primary force regulating renal sodium handling and plays a key role in both ion homeostasis and blood pressure regulation. Recently, cardiotonic steroids (CTS)-mediated Na/K-ATPase signaling has been shown to regulate fibrosis, renal proximal tubule (RPT) sodium reabsorption, and experimental Dahl salt-sensitive hypertension in response to a high-salt diet. Reactive oxygen species (ROS) are an important modulator of nephron ion transport. As there is limited knowledge regarding the role of ROS-mediated fibrosis and RPT sodium reabsorption through the Na/K-ATPase, the focus of this review is to examine the possible role of ROS in the regulation of Na/K-ATPase …

The Changing Landscape Of Biosimilars In Rheumatology, Thomas Dorner, Vibeke Strand, Paul Cornes, Joao Goncalves, Laszlo Gulacsi, Jonathan Kay, Tore K. Kvien, Josef S. Smolen, Yoshiya Tanaka, Gerd R. Burmester

Jonathan Kay

Biosimilars remain a hot topic in rheumatology, and some physicians are cautious about their application in the real world. With many products coming to market and a wealth of guidelines and recommendations concerning their use, there is a need to understand the changing landscape and the real clinical and health-economic potential offered by these agents. Notably, rheumatologists will be at the forefront of the use of biosimilar monoclonal antibodies/soluble receptors. Biosimilars offer cost savings and health gains for our patients and will play an important role in treating rheumatic diseases. We hope that these lower costs will compensate for inequities …

Which Drugs Cause Cancer?, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

Animal tests yield misleading results.

Effect Of Standard Treatment Guidelines With Or Without Prescription Audit On Prescribing For Acute Respiratory Tract Infection (Ari) And Diarrhoea In Some Thana Health Complexes (Thcs) Of Bangladesh, M. O. Faruk Khan, A.K. Azad Chowdhury, M. A. Matin, K. Begum, M. A. Galib

M. O. Faruk Khan

Inappropriate prescribing for ARI and diarrhoea is a serious health problem in many developing countries including Bangladesh. A baseline retrospective prescribing survey for ARI and diarrhoea have been conducted in randomly selected 60 thana health complexes (THCs) of Dhaka division of Bangladesh. In the 38 of 60 THCs, the prescribers did not comply with the standard treatment guidelines (STG) for ARI. They are marked as 'unsatisfactory performers'. In these THCs unnecessary antibiotics were prescribed in more than 50% of the encounters. The study further revealed that in 26 THCs, comprising 41.6% of the 38 THCs, the situation was even worse …

Why Patients Need Protection From The Sun, M. O. Faruk Khan, W. Steve Pray

M. O. Faruk Khan

Sunlight has been thought to be beneficial in recent decades, a time in which widespread tanning has become the norm. However, some patients’ quest for the perfect tan may lead them to permanent disfigurement and early death due to the damaging effects of ultraviolet (UV) radiation.

An Update On Braf Inhibitors And Other New Molecular Targets For The Treatment Of Malignant Melanoma Of The Skin, M. O. Faruk Khan, Carroll L. Ramos

M. O. Faruk Khan

Malignant melanoma of the skin originates from mutations in melanocytes and can be lethal if unrecognized or untreated in its earlier stages. Deaths from melanoma are increasing in the United States and around the world every year. The available treatments produce low rates of response with modest survival impact. Among potential molecular targets under investigation, which are mostly in the tyrosine kinase pathway, the BRAF (V-raf murine sarcoma viral oncogene homolog B1) gene is the best studied and most frequently reported mutation in melanoma. The molecular targets for melanoma treatment, promising drugs for future melanoma treatment as well as the …

In Vitro Metabolic Stability Study Of New Cyclen Based Antimalarial Drug Leads Using Rp-Hplc And Lc-Ms/Ms, Apoorva V. Rudraraju, Mohammad F. Hossain, Anjuli Shrestha, Prince N.A. Amoyaw, Babu L. Tekwani, M. O. Faruk Khan

M. O. Faruk Khan

Metabolic stability of the new antimalarial drug leads is determined using Human Liver Microsome (HLM) and specific cytochrome P450 enzyme (CYP2C8) taking the clinically used antimalarial drug chloroquine as a positive control. Experiment is done using standard methods. All the assays were conducted in 0.5 M phosphate buffer at pH 7.4. In general the metabolic reaction was initiated by adding 1 mM NADPH and 0.5 mg of enzyme. Incubations were done with time frequency of 0 hr, 1 hr, and 2 hrs at 37°C and the reactions were terminated by adding acetonitrile in the equal amounts of the assay mixture …

Biosimilars In Rheumatology: What The Clinician Should Know, Gilberto Castaneda-Hernandez, Rodrigo Gonzalez-Ramirez, Jonathan Kay, Morton A. Scheinberg

Jonathan Kay

Biosimilars are now a reality in rheumatology. Although analytical and non-clinical procedures to establish similarity have evolved significantly, clinical trials demonstrating equivalent efficacy and safety are absolutely required for all biosimilars. The design of such trials, including equivalence and non-inferiority statistical approaches, are discussed. Clinical evidence on biosimilars that have been approved recently or are presently being developed for use in rheumatology is also reviewed and contrasted with that available for biomimics (or intended copies), which are non-innovator biologics that are marketed in several countries but have not undergone review according to a regulatory pathway for biosimilars.

Which Drugs Cause Cancer?, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Andrew Knight, Ph.D.

Animal tests yield misleading results.

Drug Delivery To Posterior Intraocular Tissues: Third Annual Arvo/Pfizer Ophthalmics Research Institute Conference, Henry F. Edelhauser, Jeffrey H. Boatright, John M. Nickerson, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

The third Annual ARVO/Pfizer Ophthalmic Research Institute Conference was held Friday and Saturday, May 4 and 5, 2007 at the Fort Lauderdale Grande Hotel and Yacht Club, Fort Lauderdale, Florida. The conference, funded by the ARVO Foundation for Eye Research through a grant from Pfizer Ophthalmics, provided an opportunity to gather experts from within and outside ophthalmology to develop strategies to address drug delivery to posterior intraocular tissues—a topic of great interest, as the major route of drug delivery is via intravitreous injection.

Reactive Oxygen Species Modulation Of Na/K-Atpase Regulates Fibrosis And Renal Proximal Tubular Sodium Handling, Jiang Liu, David J. Kennedy, Yanling Yan, Joseph I. Shapiro Md

Jiang Liu

The Na/K-ATPase is the primary force regulating renal sodium handling and plays a key role in both ion homeostasis and blood pressure regulation. Recently, cardiotonic steroids (CTS)-mediated Na/K-ATPase signaling has been shown to regulate fibrosis, renal proximal tubule (RPT) sodium reabsorption, and experimental Dahl salt-sensitive hypertension in response to a high-salt diet. Reactive oxygen species (ROS) are an important modulator of nephron ion transport. As there is limited knowledge regarding the role of ROS-mediated fibrosis and RPT sodium reabsorption through the Na/K-ATPase, the focus of this review is to examine the possible role of ROS in the regulation of Na/K-ATPase …

Reactive Oxygen Species Modulation Of Na/K-Atpase Regulates Fibrosis And Renal Proximal Tubular Sodium Handling, Jiang Liu, David J. Kennedy, Yanling Yan, Joseph I. Shapiro Md

Joseph I Shapiro MD

The Na/K-ATPase is the primary force regulating renal sodium handling and plays a key role in both ion homeostasis and blood pressure regulation. Recently, cardiotonic steroids (CTS)-mediated Na/K-ATPase signaling has been shown to regulate fibrosis, renal proximal tubule (RPT) sodium reabsorption, and experimental Dahl salt-sensitive hypertension in response to a high-salt diet. Reactive oxygen species (ROS) are an important modulator of nephron ion transport. As there is limited knowledge regarding the role of ROS-mediated fibrosis and RPT sodium reabsorption through the Na/K-ATPase, the focus of this review is to examine the possible role of ROS in the regulation of Na/K-ATPase …

Canagliflozin, A New Sodium-Glucose Co-Transporter 2 Inhibitor, In The Treatment Of Diabetes, Sarah A. Nisly, Denise M. Kolanczyk, Alison M. Walton

Alison M. Walton

Purpose. The published evidence on the pharmacology, pharmacodynamics, pharmacokinetics, safety, and efficacy of a promising investigational agent for managing type 2 diabetes is evaluated. Summary. Canagliflozin belongs to a class of agents—the sodium–glucose cotransporter 2 (SGLT2) inhibitors—whose novel mechanism of action offers potential advantages over other antihyperglycemic agents, including a relatively low hypoglycemia risk and weight loss-promoting effects. Canagliflozin has dose-dependent pharmacokinetics, and research in laboratory animals demonstrated high oral bioavailability (85%) and rapid effects in lowering glycosylated hemoglobin (HbA1c) values. In four early-stage clinical trials involving a total of over 500 patients, the use of canagliflozin for varying periods …

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

Priscilla T. Ryder

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 …

Cinacalcet Administration By Gastrostomy Tube In A Child Receiving Peritoneal Dialysis, Kristen R. Nichols, Chad A. Knoderer, Bethanne Johnston, Amy C. Wilson

Chad A. Knoderer

A 2-year-old male with chronic kidney disease with secondary hyperparathyroidism developed hypercalcemia while receiving calcitriol, without achieving a serum parathyroid hormone concentration within the goal range. Cinacalcet 15 mg (1.2 mg/kg), crushed and administered via gastrostomy tube, was added to the patient’s therapy. This therapy was effective in achieving targeted laboratory parameters in our patient despite instructions in the prescribing information that cinacalcet should always be taken whole.

Are Elevated Vancomycin Serum Trough Concentrations Achieved Within The First 7 Days Of Therapy Associated With Acute Kidney Injury In Children?, Chad A. Knoderer, Kristen R. Nichols, Kelsey C. Lyon, Megan M. Veverka, Amy C. Wilson

Kristen R. Nichols

Background In 2008, the empiric vancomycin dosing recommendation in children at our institution was changed from 40 to 60 mg/kg per day. Subsequently, an increased incidence of acute kidney injury (AKI) in patients receiving vancomycin was suspected. The objective of this study was to evaluate AKI in children receiving vancomycin and to determine risk factors for AKI development. Methods Medical records of patients aged 30 days through 17 years who received vancomycin for at least 72 hours between January and December 2007 (40 mg/kg per day) and January and December 2010 (60 mg/kg per day) were reviewed. Patients with cystic …

Cinacalcet Administration By Gastrostomy Tube In A Child Receiving Peritoneal Dialysis, Kristen Nichols, Chad Knoderer, Bethanne Johnston, Amy Wilson

Kristen R. Nichols

A 2-year-old male with chronic kidney disease with secondary hyperparathyroidism developed hypercalcemia while receiving calcitriol, without achieving a serum parathyroid hormone concentration within the goal range. Cinacalcet 15 mg (1.2 mg/kg), crushed and administered via gastrostomy tube, was added to the patient’s therapy. This therapy was effective in achieving targeted laboratory parameters in our patient despite instructions in the prescribing information that cinacalcet should always be taken whole.

Cross-Sector Review Of Drivers And Available 3rs Approaches For Acute Systemic Toxicity Testing, Troy Seidle, Sally Robinson, Tom Holmes, Stuart Creton, Pilar Prieto, Julia Scheel, Magda Chlebus

Troy Seidle, PhD

Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or …

The Fit-Hansa Demonstrates Reliability And Convergent Validity Of Functional Performance In Patients With Shoulder Disorders, Prajyot Kumta, Joy Macdermid, Saurabh Mehta, Paul Stratford

Saurabh Mehta

Study

DesignPsychometric study design.

Objectives

To assess the test-retest reliability and convergent validity of the Functional Impairment Test-Hand and Neck/Shoulder/Arm (FIT-HaNSA) in patients with shoulder disorders.

Background

Performance tests that assess functional ability of patients with shoulder disorders can provide useful information for making clinical or return-to-activity decisions. No performance-based shoulder test has yet demonstrated sufficient relevance or clinical measurement properties. The FIT-HaNSA examines upper extremity performance during repetitive tasks that emphasize shoulder reaching and static postures and, therefore, has greater relevance for assessing performance.

Methods

Thirty-six patients with shoulder disorders and 65 healthy controls were recruited for the study. …

Considering A New Paradigm For Alzheimer’S Disease Research, Gillian R. Langley

Gill Langley, PhD

Using Alzheimer’s disease as a case study, this review argues that it might be time to consider a new paradigm in medical research and drug discovery. The existing framework is overly dependent on often unvalidated animal models, particularly transgenic mice. Translational success remains elusive and costly late-stage drug failure is common. The conventional paradigm tends to overlook species differences and assumes that animal-based findings are generally applicable to humans. Could pathways-based research using advanced human-specific models probed with new tools, including those of systems biology, take centre stage? The current transition in chemical toxicology to a 21st-century paradigm could be …

Are Elevated Vancomycin Serum Trough Concentrations Achieved Within The First 7 Days Of Therapy Associated With Acute Kidney Injury In Children?, Chad A. Knoderer, Kristen R. Nichols, Kelsey C. Lyon, Megan M. Veverka, Amy C. Wilson

Chad A. Knoderer

Background In 2008, the empiric vancomycin dosing recommendation in children at our institution was changed from 40 to 60 mg/kg per day. Subsequently, an increased incidence of acute kidney injury (AKI) in patients receiving vancomycin was suspected. The objective of this study was to evaluate AKI in children receiving vancomycin and to determine risk factors for AKI development. Methods Medical records of patients aged 30 days through 17 years who received vancomycin for at least 72 hours between January and December 2007 (40 mg/kg per day) and January and December 2010 (60 mg/kg per day) were reviewed. Patients with cystic …

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

Anwar Gilani

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.

Canagliflozin, A New Sodium-Glucose Co-Transporter 2 Inhibitor, In The Treatment Of Diabetes, Sarah A. Nisly, Denise M. Kolanczyk, Alison M. Walton

Sarah A. Nisly

Purpose. The published evidence on the pharmacology, pharmacodynamics, pharmacokinetics, safety, and efficacy of a promising investigational agent for managing type 2 diabetes is evaluated. Summary. Canagliflozin belongs to a class of agents—the sodium–glucose cotransporter 2 (SGLT2) inhibitors—whose novel mechanism of action offers potential advantages over other antihyperglycemic agents, including a relatively low hypoglycemia risk and weight loss-promoting effects. Canagliflozin has dose-dependent pharmacokinetics, and research in laboratory animals demonstrated high oral bioavailability (85%) and rapid effects in lowering glycosylated hemoglobin (HbA1c) values. In four early-stage clinical trials involving a total of over 500 patients, the use of canagliflozin for varying periods …

Use Of A Subcutaneous Insulin Computerized Glucostabilizer™ Program On Glycemic Control In The Intensive Care Setting: A Retrospective Data Analysis., Sarah A. Nisly, Serena Harris, Laura Aykroyd, Joni Carrol, Brian Ulmer, Michael Waddell, Samuel Flanders, Rattan Juneja

Sarah A. Nisly

Background: Despite guidelines that recommend strongly against Sliding Scale Insulin (SSI) it continues to be the most commonly insulin regimen used in hospitals to treat hyperglycemia. In addition to being reactionary to a glucose that has already increased, SSI offers practical challenges in the randomness of the doses of insulin prescribed and often a disconnect with glucose testing that should be occurring in congruence to the insulin dosing. While many clinical trials have shown improved glycemic control in critical care patients receiving intravenous insulin; few studies have demonstrated the efficacy of subcutaneous (SQ) insulin in this setting. In this study, …

Induction Of Apoptosis In Human Breast Cancer Cells Via Caspase Pathway By Vernodalin Isolated From Centratherum Anthelminticum(L.) Seeds, Kok Hoong Leong

Kok Hoong Leong

In this study, we showed that CACF inhibited growth of MCF-7 human breast cancer cells. CACF induced apoptosis in MCF-7 cells as marked by cell size shrinkage, deformed cytoskeletal structure and DNA fragmentation. To identify the cytotoxic compound, CACF was subjected to bioassay-guided fractionation which yielded 6 fractions. CACF fraction A and B (CACF-A, -B) demonstrated highest activity among all the fractions. Further HPLC isolation, NMR and LC-MS analysis of CACF-A led to identification of vernodalin as the cytotoxic agent in CACF-A, and -B. 12,13-dihydroxyoleic acid, another major compound in CACF-C fraction was isolated for the first time from Centratherum …

Anti-Cancer Drug Screening Of Dual Tubulin And Hsp27 Inhibitors With 2d And 3d Lung Cancer Cell Assays, Janine Maria Naim, Rati Lama

Rati Lama

Cancer is the leading cause of death worldwide. The current treatment options available for lung cancer are limited and have drawbacks such as poor bioavailability, numerous side effects, poor efficacy and drug resistance. 3D model serve as a novel approach for drug screening purposes and the evaluation of compounds in the platform can help identify potent compounds for further in vivo xenograft studies.

Acetaminophen: Beyond Pain And Fever-Relieving, Eric R. Blough, Miaozong Wu

Eric Blough

Acetaminophen, also known as APAP or paracetamol, is one of the most widely used analgesics (pain reliever) and antipyretics (fever reducer). According to the U.S. Food and Drug Administration, currently there are 235 approved prescription and over-the-counter drug products containing acetaminophen as an active ingredient. When used as directed, acetaminophen is very safe and effective; however when taken in excess or ingested with alcohol hepatotoxicity and irreversible liver damage can arise. In addition to well known use pain relief and fever reduction, recent laboratory and pre-clinical studies have demonstrated that acetaminophen may also have beneficial effects on blood glucose levels, …

Doxorubicin Loaded Polymeric Nanoparticulate Delivery System To Overcome Drug Resistance In Osteosarcoma, Michiro Susa, Arun K. Iyer, Keinosuke Ryu, Francis John Hornicek, Henry J. Mankin, Mansoor M. Amiji, Zhenfeng Duan

Arun Iyer

Background: Drug resistance is a primary hindrance for the efficiency of chemotherapy against osteosarcoma. Although chemotherapy has improved the prognosis of osteosarcoma patients dramatically after introduction of neo-adjuvant therapy in the early 1980's, the outcome has since reached plateau at approximately 70% for 5 year survival. The remaining 30% of the patients eventually develop resistance to multiple types of chemotherapy. In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure incurred from multidrug resistant (MDR) tumor cells, we explored the possibility of loading doxorubicin onto biocompatible, lipid-modified dextran-based polymeric nanoparticles and evaluated the …