Pharmacy and Pharmaceutical Sciences Commons^™

Development And Applications Of The Hint Forcefield In Prediction Of Antibiotic Efflux And Virtual Screening For Antivirals, Aurijit Sarkar

Theses and Dissertations

This work was aimed at developing novel tools that utilize HINT, an empirical forcefield capable of quantitating both hydrophobic and hydrophilic (hydropathic) interactions, for implementation in theoretical biology and drug discovery/design. The role of hydrophobicity in determination of macromolecular structure and formation of complexes in biological molecules is undeniable and has been the subject of research across several decades. Hydrophobicity is introduced, with a review of its history and contemporary theories. This is followed by a description of various methods that quantify this all-pervading phenomenon and their use in protein folding and contemporary drug design projects – including a detailed …

Investigation And Optimization Of A Solvent / Anti-Solvent Crystallization Process For The Production Of Inhalation Particles, Swati Agrawal

Theses and Dissertations

Dry powder inhalers (DPIs) are commonly used to deliver drugs to the lungs. The drug particles used in these DPIs should possess a number of key properties. These include an aerodynamic particle size < 5μm and particle crystallinity for long term formulation stability. The conventionally used micronization technique to produce inhalation particles offers limited opportunities to control and optimize the particle characteristics. It is also known to induce crystalline disorder in the particles leading to formulation instability. Hence, this research project investigates and optimizes a solvent/anti-solvent crystallization process capable of directly yielding inhalation particles using albuterol sulfate (AS) as a model drug. Further, the feasibility of the process to produce combination particles of AS and ipratropium bromide monohydrate (IB) in predictable proportions and in a size suitable for inhalation is also investigated. The solvent / anti-solvent systems employed were water / ethyl acetate (EA) and water / isopropanol (IPA). Investigation and optimization of the crystallization variables with the water / EA system revealed that particle crystallinity was significantly influenced by an interaction between the drug solution / anti-solvent ratio (Ra ratio), stirring speed and crystal maturation time. Inducing a temperature difference between the drug solution and anti-solvent (Tdrug solution > Tanti-solvent) resulted in smaller particles being formed at a positive temperature difference of 65°C. IPA was shown to be the optimum anti-solvent for producing AS particles (IPA-AS) in a size range suitable for inhalation. In vitro aerosol performance of these IPA-AS particles was found to be superior compared to the conventionally used micronized particles when aerosolized from the Novolizer®. The solvent / anti-solvent systems investigated and optimized …

Insights Into The Catalytic Mechanism Of Retro-Aldol Cleavage Of Β-Hydroxy Amino Acids By Escherichia Coli L-Threonine Aldolase, Remsh Soumya Govinda

Theses and Dissertations

With over 140 vitamin B6 (Pyridoxal 5’-phosphate, PLP) dependent enzymes, serving vital roles in various transamination, decarboxylation, retro-aldol cleavage and synthesis pathways these enzymes constitute the most versatile catalytic systems in nature. Enzymes of this group have an inherent reaction as well as substrate specificity. A single co-factor namely, PLP is used by specific enzymes of this group to serve distinct roles during the catalytic reaction. An ordered evolutionary adaptation in these enzymes has led to specialization achieved by each enzyme for catalyzing specific reactions. L-Threonine aldolase (L-TA) is one such PLP- dependent enzyme that catalyzes the retro-aldol cleavage of …

The Effect Of Anticholinergic Burden On Functional Outcomes In Patients With Moderate To Severe Alzheimer’S Disease, Sheetal Dharia

Theses and Dissertations

Background: Alzheimer’s disease (AD) is the most common form of dementia and is characterized by a progressive loss of memory, judgment, and thinking in older adults. The current treatment is cholinesterase inhibitors, which increase acetylcholine at the synapse. Medications with anticholinergic (AC) activity are given for a variety reasons including for the treatment of comorbid conditions or side effects of cholinesterase inhibitors (ChEIs). These drugs inhibit acetylcholine in the brain. Studies have shown the detrimental outcomes of using AC medications with ChEIs in older adults. Moreover, older patients take more medications and have an increased risk of developing AC toxicity …

Role Of Oxidative Reactive Species And Antioxidants In Metabolism And Transport Of Therapeutic Drugs, Svetlana Verenich

Theses and Dissertations

Oxidative stress (OS) is a frequent complication of various disease conditions such as Alzheimer’s and Parkinson’s disease, atherosclerosis, preeclampsia, rheumatoid arthritis, diabetes including gestational diabetes, etc. OS is defined as an imbalance between the production of reactive species and the ability of an organism to detoxify the reactive intermediates and repair the damage. As a result of OS, the excess of reactive species such as oxygen superoxide (O2-), hydroxyl radical (OH), peroxynitrite (ONOO−), 4-hydroxynonenal (4HNE), etc., have a tendency to react with nearby proteins/nucleic acids/lipids changing their functionality or inactivating them completely. The organism has many ways to protect itself …

Prediction Of Human Systemic, Biologically Relevant Pharmacokinetic (Pk) Properties Based On Quantitative Structure Pharmacokinetic Relationships (Qspkr) And Interspecies Pharmacokinetic Allometric Scaling (Pk-As), Prajakta Badri

Theses and Dissertations

This research developed validated QSPKR and PK-AS models for predicting human systemic PK properties of three, preselected, pharmacological classes of drugs, namely opioids, β-adrenergic receptor ligands (β-ARL) and β-lactam antibiotics (β-LAs) using pertinent human and animal systemic PK properties (fu,, CLtot, Vdss, fe) and their biologically relevant unbound counterparts from the published literature, followed by an assessment of the effect of different molecular descriptors on these PK properties and on the PK-AS slopes for CLtot and Vdss from two species (rat and dog). Lipophilicity (log (D)7.4) and molecular weight (MW) were found to be the most statistically significant and biologically …

In-Vitro Metabolism And Protein Binding Of 5-Hmf, A Potential Antisickling Agent, Taghrid Obied

Theses and Dissertations

Purpose. 5-HMF is a potential antisickling agent forming a Schiff-adduct with hemoglobin (Hb). In-vitro studies were designed to identify the metabolic pathways of 5-HMF in human hepatic cytosol, to assess inter-species differences in its hepatic metabolism, and to predict in-vivo PK properties. Moreover, metabolism of 5-HMF in human RBCs was investigated. Finally, in-vitro studies were done to characterize 5-HMF binding kinetics with human Hb and albumin (HSA). Methods. NAD+ reduction was monitored at 340 nm in human hepatic cytosol for 5-HMF (26 mM) and prototypical ADH and ALDH substrates in the presence or absence of their inhibitors. Furthermore, concentration-dependency studies …

Novel Cinnamic Acid-Based Dehydropolymers For Emphysema: In Vitro And In Vivo Assessment Of Their Activities, Bhawana Saluja

Theses and Dissertations

Pulmonary emphysema is a serious worldwide illness, causing progressive and irreversible alveolar wall loss and difficulty in breathing. It is caused mostly by cigarette smoking. However, its unresolved complex and multiple pathogenic mechanisms have left this disease without effective pharmacotherapy. This project hypothesized that cinnamic acid-based dehydropolymers (DHPs), originally discovered as novel anti-coagulants, protect against emphysema through their potent triple inhibitory actions against oxidative stress, inflammation and elastase, some of the pathogenic mechanisms associated with this disease. Three in vitro inhibitory activity assays for oxidative stress, lung inflammation and neutrophil elastase (NE) were developed and used to identify the most …

Quantitative Analysis Of Tobacco Specific Nitrosamine In Human Urine Using Molecularly Imprinted Polymers As A Potential Tool For Cancer Risk Assessment, Kumar Shah

Theses and Dissertations

Measuring urinary tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide conjugate may provide the best biomarker of tobacco smoke lung carcinogen metabolism. Existence of differences in the extent of NNAL metabolism rates may be potentially related to an individuals’ lung cancer susceptibility. Low concentrations of NNAL in smokers urine (<1 ng/mL) require sensitive and selective methods for analysis. Traditionally, this involves extensive, time-consuming sample preparation that limits throughput and adds to measurement variability. Molecularly imprinted polymers (MIPs) have been developed for the analysis of urinary NNAL by offline cartridge extraction combined with LC-MS/MS. This method when reproduced demonstrated problems with matrix effects. In the first part of this work, investigation of matrix effects and related problems with sensitivity for the published offline extraction method has been conducted. In order to address the need to improve throughput and other analytical figures of merit for the original method, the second part of this work deals with development of a high-throughput online microfluidic method using capillary-columns packed with MIP beads for the analysis of urinary NNAL. The method was validated as per the FDA guidance, and enabled low volume, rapid analysis of urinary NNAL by direct injection on a microfluidic column packed with NNAL specific MIP beads. The method was used for analysis of urinary NNAL and NNAL-Gluc in smokers. Chemometric methods were used with this data to develop a potential cancer-risk-assessment tool based on pattern recognition in the concentrations of these compounds in urine. In the last part, method comparison approaches for the online and the offline sample extraction techniques were investigated. A ‘fixed’ range acceptance criterion based on combined considerations of method precision and accuracy, and the FDA bioanalytical guidance limits on precision and accuracy was proposed. Data simulations studies to evaluate the probabilities of successful transfers using the proposed criteria were performed. Various experimental designs were evaluated and a design comprised of 3 runs with 3 replicates each with an acceptance range of ±20% was found appropriate. The off-line and the on-line sample extraction methods for NNAL analysis were found comparable using the proposed fixed range acceptance criteria.

Impact Of Statin Therapy On Outcomes In Aneurysmal Subarachnoid Hemorrhage Patients, Abdulkhaliq Alsalman

Theses and Dissertations

There is conflicting data on the effects of statins on cerebral vasospasm and clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH) patients. In this retrospective cohort study, patients were divided into those who received pravastatin (PRAV group) 40mg/d and those who did not (NP group). Data were analyzed using multivariate logistic regression. Eighty-one patients met inclusion criteria. There was a statistically significant decreased in the incidence of vasospasm in the PRAV group; however, this association did not retain significance after adjusting for WFNS, race, elevated WBC, and clipping (59% PRAV vs. 88% NP, p=0.08). There was no statistically significant difference in …

Effect Of Renin Angiotensin System Inhibition On Cardiovascular Sequelae In Elderly Hypertensive Patients With Insulin Resistance, Hala Zreikat

Theses and Dissertations

Background: Insulin resistance may play a pathogenic role in cardiovascular disease (CVD). Resistance to insulin has been associated with obesity, hypertension, and abnormal glucose and lipid metabolism. The constellation of these features among insulin resistant subjects has been called the metabolic syndrome. Prevalence of the metabolic syndrome increases with age and is most common in the elderly. Different criteria have been proposed to define the metabolic syndrome (ATP, WHO, AACE, EGIR). Current management of metabolic syndrome focuses on the specific risk factors that the patient may have without targeting the underlying insulin resistance. Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin …

Identification Of Clinical, Laboratory And Genetic Covariates For Pharmacokinetics, Efficacy And Toxicity Of Sorafenib In Patients With Solid Tumors, Lokesh Jain

Theses and Dissertations

The goal of this research work was to understand the clinical-pharmacology based treatment approaches for sorafenib. Treatment with sorafenib is associated with high inter-patient variability in pharmacokinetic exposures, efficacy and toxicity. We explored the demographic, laboratory, clinical and pharmacogenetic factors to elucidate the sources of variability. In addition, we examined the impact of pharmacogenetic variation in VEGFR2, an important mediator of the VEGF pathway, on risk of prostate cancer. To support these investigations, (mainly single-dose) pharmacokinetic, pharmacogenetic, efficacy and toxicity information were collected from patients with solid tumors, enrolled in five phase I / II clinical trials at National Cancer …

Age-Related Differences In In-Vitro Sensitivity To Inhibition Of Human Red Blood Cell Acetylcholinesterase And Plasma Butyrylcholinesterase By The Cholinesterase Inhibitors Physostigmine (Phys), Pyridostigmine (Pyr), Donepezil (Don) And Galantamine (Gal), David Lee

Theses and Dissertations

Alzheimer’s disease (AD) is a chronic, progressive neurodegenerative disorder, characterized clinically by a progressive loss of memory, cognitive function, ability to care for oneself and psychiatric symptoms. First-line agents for the treatment of AD are ChE inhibitors (DON, GAL), whose modest clinical efficacy and the high incidence of dose-limiting toxicities limit their clinical utility. In addition to AD, ChE inhibitors (PYR) are used for other medical conditions, such as myasthenia gravis (MG). Furthermore, ChE inhibitors (PYR) are used by military personnel prophylactically if impending exposure to chemical warfare agents, e.g., soman, is suspected. The purpose of this research project was …

To Evaluate The Level Of Agreement Between Two Self-Reported Medication Adherence Scales And Prescription Refill Records In Older Adults, Priyanka Kakad

Theses and Dissertations

Objective: To evaluate the level of agreement between two self-reported medication adherence scales and prescription refill records in older adults. Design: Cross-sectional study Setting: Imperial Plaza; a retirement community located in Richmond, Virginia. Participants: 32 independent-living older adults, taking anti-hypertensive medications and filling their prescriptions at on-site Plaza Professional Pharmacy were recruited in the study. Methods: Participants’ 6 months refill records were obtained and Medication Possession Ration (MPR) was calculated. Participants were interviewed using Morisky Medication Adherence Scale (MMAS) & Brief Medication Questionnaire (BMQ). Kappa statistics was used to evaluate the level of agreement. Results: Poor level of agreement was …

Factors Influencing Placental Transfer Of Lopinavir: Binding, Uptake And Efflux, Abhishek Gulati

Theses and Dissertations

HIV protease inhibitors are an important component of Highly Active Antiretroviral Therapy used to treat HIV infected pregnant women. They have a low placental transfer and are highly plasma protein bound. The purpose of this thesis was to characterize the factors limiting placental passage and fetal exposure to lopinavir. These factors include lopinavir plasma protein binding and uptake, cellular binding, and efflux of lopinavir in the placental trophoblast cells. First, we determined the unbound fraction of lopinavir in cord blood and characterized the binding of lopinavir to α1-acid glycoprotein (AAG) and human serum albumin (HSA), and displacement by ritonavir. Serum …

The Use Of Lactobacillus In The Treatment Of Clostridium Difficile Infection In Hospitalized Adult Patients, Ali Alhammad

Theses and Dissertations

Objective To describe the use of Lactobacillus by hospitalized patients and to examine its relationship with various Clostridium difficile infection (CDI) related outcomes. Methods The characteristics of Lactobacillus users and non-users and the initiation of Lactobacillus with respect to initiation of antibiotic therapy and CDI treatment were described using national hospital discharge database. The relationships between Lactobacillus use and post-CDI length of stay, mortality, switch of CDI therapy, and readmission were analyzed. Results Lactobacillus users and non-users were different in most characteristics. Metronidazole and fluoroquinolones were the most frequently used antibiotics by Lactobacillus users. They were mainly CDI cases, used …

The Economic Impact Of Antimicrobial Resistance In Patients With Nosocomial Staphylococcus Aureus Bacteremia, Suzanne Phillips

Theses and Dissertations

Background: The proportion of nosocomial Staphylococcus infections caused by methicillin-resistant Staphylococcus aureus (MRSA) has increased from 22% in 1995 to 63% in 2004. Blood stream infections, more commonly referred to as bacteremias, represented the majority (75.5%) of hospital-onset MRSA cases. The economic impact of Staphylococcus aureus bacteremia merits investigation. Methods: This was a retrospective cohort analysis within Cerner HealthFacts data warehouse. Eligible patients were those who had Staphylococcus aureus bacteremia and were discharged between January 1, 2000, and December 31, 2006. Inclusion criteria include age > 18 years old and onset of infection > 48 hours post admission. The crude association was …

Pulmonary Delivery Of Anorectic Gut Secreted Peptides For Appetite Suppression In Rats, Priya Nadkarni

Theses and Dissertations

This dissertation project aimed to demonstrate that pulmonary delivery of two anorectic gut secreted peptides, peptide YY (PYY) and oxyntomodulin (OXM) enabled food intake suppression and reduced body weight gain in rats via their systemic absorption from the lung and interaction with the brain. After PYY and OXM were administered to the lungs at varying doses, food intake and body weight gain were monitored in freely feeding rats. Significant 30-35 % food intake suppression was achieved for 4-6 h following pulmonary administration of endogenously active PYY3-36 and OXM1-37 at 0.80 and 0.50 mg/kg, respectively. Moreover, when administered daily for 7 …

In Vitro Models For Inhaled Corticosteroid (Ics) Aerosols: A Study Of Their Biopharmaceutics And Pharmacology, Deepika Arora

Theses and Dissertations

Lung cellular disposition and anti-inflammatory pharmacology of inhaled corticosteroids (ICSs) is complex, comprised of a cascade of aerosol deposition and dissolution, followed by cellular uptake for local pharmacological action. This project hypothesized that the kinetics of dissolution for certain ICS aerosols generated from inhaler products were kinetically rate-determined for their cellular uptake and local pharmacological action. A novel dissolution testing system was developed to determine the dissolution kinetics for the ICS aerosols. A total of 5 ICSs aerosols generated from 6 inhaler products were collected in 2.1-3.3 or 4.7-5.8 µm of aerodynamic diameters at 0.7-19.8 µg on filter membranes by …

Electrical Behavior Of Non-Aqueous Formulations: Role Of Electrostatic Interactions In Pressurized Metered Dose Inhalers (Pmdis), Reshma Kotian

Theses and Dissertations

Aerosol electrostatics is an important property of pharmaceutical aerosols. The electrostatic properties of pMDI aerosols have been shown to be a function of both formulation and packaging components. The modified ELPI enables measurement of aerosol charge as a function of particle size, and the simultaneous determination of the mass distribution using chemical analysis. However, in order to fully assess the cause and effects of aerosol electrostatics in terms of its biological and regulatory implications, it is necessary to understand the basic charging mechanisms inside the pMDI formulation.

Electrical resistivity and zeta potential measurements confirmed the presence of charged species within …

Effects Of Smoking And Gender On Tetrahydroisoquinolines And Beta-Carbolines In A Healthy Population And During Alcohol Detoxification, Satjit Singh Brar

Theses and Dissertations

The purpose of this investigation was to evaluate the effects of smoking and gender on 1) tetrahydroisoquinolines (TIQs) and beta-carbolines (BCs) in a population of healthy subjects and 2) TIQs in an alcohol-dependent population undergoing in-patient detoxification. Comparison in plasma TIQs between the populations was additionally conducted. To support the clinical investigations, a HPLC-FD method was developed and validated to assess plasma concentrations of BCs, harman and norharman, while a HPLC-ESI-MS/MS method was validated to quantify the TIQs, R/S-salsolinol along with dopamine. Forty-one young volunteers were recruited including 19 nonsmokers (NS), 11 light smokers (LS) and 11 heavy smokers (HS), …

Investigation Of Inosine And Hypoxanthine As Biomarkers Of Cardiac Ischemia In Plasma Of Non-Traumatic Chest Pain Patients And A Rapid Analytical System For Assessment, Don E. Farthing

Theses and Dissertations

Each year in the U.S., approximately 7-8 million patients with non-traumatic chest pain visit hospital emergency departments (ED) for medical evaluation. It is estimated that approximately 2-5% of these patients are experiencing acute cardiac ischemia, but due to the shortcomings of current test methods, they are incorrectly diagnosed and discharged without appropriate treatment provided, thus leading to poor patient outcome and potential medical malpractice litigation.The goals of this research were to evaluate plasma samples for potential biomarker(s) of acute cardiac ischemia prior to heart tissue necrosis, and to ultimately develop a rapid method for detection of the potential biomarker(s) in …

Physical And Computational Models Of Human Lung For Optimizing Respiratory Drug Delivery, Mohammed Ali

Theses and Dissertations

Respiratory drug particles aerosolized from the commercially available drug delivery devices may charge electrostatically. Investigations of the relevance of this charge on deposition in the human lung are just quite a few and they started early eighties though the aerosol science study is a decade old discipline. Additionally, the localized deposition of drug particles at desired sites such as inflamed tissue and appropriate receptors has been recognized by clinical investigators as being critical factors for the effective administration of respiratory drugs. To accomplish these tasks, it is imperative to undertake in vitro and in silico studies of medicinal drug aerosol …

A Capillary-Based Microfluidic System For Immunoaffinity Separations In Biological Matrices, Michael Peoples

Theses and Dissertations

The analysis of biological samples in clinical or research settings often requires measurement of analytes from complex and limited matrices. Immunoaffinity separations in miniaturized formats offer selective isolation of target analytes with minimal reagent consumption and reduced analysis times. A prototype capillary-based microfluidic system has been developed for immunoaffinity separations in biological matrices with laser-induced fluorescence detection of labeled antigens or antibodies. The laboratory-constructed device was assembled from two micro syringe pumps, a microchip mixer, a micro-injector, a diode laser with fused-silica capillary flow cell, and a separation capillary column. The columns were prepared from polymer tubing and packed under …

Prediction Of In-Vivo Antimuscarinic Activity (Ama) By In-Vitro Receptor Binding Assessment And Pk/Pd Modeling For Prototypical Drugs, Taghrid Y. Obied

Theses and Dissertations

Purpose: To establish a tool, termed as antimuscarinic activity (AMA), to predict the incidence of antimuscarinic adverse events (AMAEs).Methods: A literature review, focused on drugs having off-target interaction with muscarinic receptors, was performed. Prototypical drugs olanzapine, diphenhydramine, paroxetine were selected for the analysis. Scopolamine and darifenacin were included as positive and negative controls, respectively. Physiochemical properties, pharmacokinetic data, and clinical incidence of AMAEs for the selected drugs were collected from reported literature. Extrapolation of literature data was carried-out to obtain exposure data. To determine the drugs muscarinic affinity (Ki values), experiments were performed using 3H-QNB and membrane suspensions of M1, …

Interspecies Pharmacokinetic Scaling And Metabolism Of Alcohols And Glycols, Pankaj Gupta

Theses and Dissertations

Background: Despite the numerous pharmaceutical applications of alcohols andglycols, the interspecies differences with respect to their pharmacokinetics (PK) arepoorly understood. The aim of this research was to use in-vivo and in-vitro approaches to compare and model the PK characteristics across various species.Methods: Appropriate published in-vivo studies (in different species) foralcohols and glycols were carefully selected. PK analysis was performed using (a) noncompartmental analysis and (b) compartmental modeling to estimate relevant dose-independent PK parameters. Next, six alcohols (methanol, ethanol, 1 -propanol, 1 -butanol, 1-hexanol, and 1-octanol), two glycols (ethylene glycol and propylene glycol)and one secondary alcohol (2-propanol) were examined as in-vitro …

Characterization Of Perphenazine And Scopolamine Aerosols Generated Using The Capillary Aerosol Generator, Xihao Li

Theses and Dissertations

The characterization of perphenazine and scopolamine aerosols generated using the capillary aerosol generator (CAG) was reported. Variables including steady state power, the formulation vehicle, the drug concentration and the formulation flow rate were studied for their effects on the chemical stability and particle size of these drug aerosols.Stability-indicating HPLC and LC-MS assays were developed and validated for perphenazine and scopolamine, respectively. The chemical stability of each compound was investigated under a variety of stress conditions and the structure of degradation products was proposed.Perphenazine aerosols were generated from propylene glycol (PG) formulations with concentrations of 9, 48 and 90mM at formulation …

The Effect Of Variability In Substance Abuse And Dependence Terminology On Physicians' Prescribing Decisions, Lisa Rochelle Burroughs Phipps

Theses and Dissertations

Prescription drug abuse is a continuing problem in the United States. Educating physicians on issues related to prescription drug abuse is a key factor in preventing and treating this problem. High variability has been found in substance abuse terminology in the literature, textbooks, and FDA-approved product labeling. This dissertation describes a survey study designed to address how the variability in substance abuse terminology, specifically package inserts, affects the prescribing decisions made by physicians.A random sample of 1008 physicians currently licensed and residing in the Commonwealth of Virginia received a letter of explanation, a self-administered questionnaire, and a follow-up reminder and …

A 'Biorelevant' Approach For Accelerated In Vitro Release And In Vitro-In Vivo Relationship Of A Biodegradable, Naltrexone Implant, Sunil S. Iyer

Theses and Dissertations

Characterization of in vitro and in vivo drug release profiles constitutes an important step in developing and optimizing an effective, long acting delivery system for naltrexone. Accelerated in vitro methods are also important for quality assurance of manufactured dosage forms. For drug release testing of sustained release parenteral dosage forms, the modified USP Apparatus 4 (flow-through cell) has been recommended by the The Fédération Internationale Pharmaceutique/American Association of Pharmaceutical Scientists (FIP/AAPS) Guidelines. Details on such studies however, are generally not found in the literature. To incorporate 'biorelevance' to implant drug release studies, this research investigated an approach to apparatus design …

Length Of Hospital Stay, Delirium And Discharge Status Outcomes Associated With Anticholinergic Drug Use In Elderly Hospitalized Dementia Patients, Kelly J. Gauthier

Theses and Dissertations

Problem: There are a significant proportion of patients taking acetylcholinesterase inhibitors (ChEi) for cognitive dysfunction also taking medications with anticholinergic (ACh) properties that may counteract their effects. As the number of ACh medications, burden, increases so does the likelihood of an adverse outcome.Background: ACh medications are frequently used in the elderly population (Carnahan 2004) even those with dementia or AD (Roe et al., 2002; Giron et al., 2001; Altavela 2003; Gill et al., 2005; Kogut et al., 2005). Methods: Hospitalized patients > 65 years of age with dementia (AD, other dementias, or with inferred dementia based on ChEi or NMDA antagonist …