Faculty Books and Book Chapters
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Ligand-Mediated Toxicology: Characterization and Translational Prospects
Rais A. Ansari, Claude L. Hughes, and Kazim Husain
In biochemistry a ligand is a molecule that binds to a receptor or other biomolecule that forms a complex and produces a biological effect. We live in a world of exposure to exogenous ligands and there are three long-established strands of biological research that have investigated the actions of biologically active dietary or environmental compounds on animals, including humans.
First, in agricultural and animal husbandry research, there is extensive documentation of the many thousands of phytochemicals that mediate plant-animal interactions many of which produce toxic effects at certain levels of exposure in terms of dose, duration and window of sensitivity. In a broader biological context, many of these relationships have been formalized by concepts of co-evolution of plants and animals.
Second, there is a long history of toxicology research showing a wide range of adverse effects that often result from exposures to hormones and other modulators of endocrine function, especially during developmentally sensitive intervals. In recent decades much of this research has been encapsulated by a single term of “endocrine disruptors” even though many ligand-mediated actions are not endocrine per se or definitively adverse.
Third, nutritional and functional foods research have demonstrated a wide range of health benefits produced by consumption of many phytochemical ligands through mechanisms that are not truly distinct from those that seem to mediate the adverse effects noted in either the animal husbandry or developmental toxicology research arenas.
We are confident that environmental and public health can be enhanced by defining how such exposures to exogenous signaling molecules (ligands) pose both risks and benefits. Therefore, it is time to modify the scientific perspective and nomenclature to encompass these several streams of investigation such that both risks and benefits of exposure to dietary and environmental ligands may be characterized and translated into sound strategies to address environmental and public health concerns. Fetal alcohol spectrum disorder (FASD) is an illustrative case for translational toxicology-informed interventions where there is a viable prospect for a multi-component nutritional health benefit to reduce occurrence or severity of FASD. Health promoting interventional options must include reduction(s) in exposures to ligands that incur health risks but when exposures cannot be adequately reduced or preempted, we should also define and employ active mechanistically-based mitigative interventions.
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Pharmaceutical Polymers
Hamid Omidian, Kinam Park, and Patrick J. Sinko
Martin's Physical Pharmacy and Pharmaceutical Sciences is considered the most comprehensive text available on the application of the physical, chemical and biological principles in the pharmaceutical sciences. It helps students, teachers, researchers, and industrial pharmaceutical scientists use elements of biology, physics, and chemistry in their work and study. Since the first edition was published in 1960, the text has been and continues to be a required text for the core courses of Pharmaceutics, Drug Delivery, and Physical Pharmacy. The Sixth Edition features expanded content on drug delivery, solid oral dosage forms, pharmaceutical polymers and pharmaceutical biotechnology, and updated sections to cover advances in nanotechnology.
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Social Aspects of Drug Discovery, Development and Commercialization: From Laboratory to Clinic
Odilia Osakwe and Syed A. A. Rizvi
Social Aspects of Drug Discovery, Development and Commercialization provides an insightful analysis of the drug discovery and development landscape as it relates to society. This book examines the scientific, legal, philosophical, economic, political, ethical and cultural factors that contribute to drug development. The pharmaceutical industry is under scrutiny to develop safer and more effective drugs in a quicker and more affordable manner. Recent criticism and debates have emphasized varying opinions on the issues concerning the drug discovery and development process.
This book provides thoughtful and valuable discussions and analysis of the social challenges and potential opportunities through all stages of the pharmaceutical process, from inception through marketing. With a unique focus on the social factors that increasingly play a role in how drug development is planned, structured, and executed throughout the drug product lifecycle, this is an essential resource for students, professors, and researchers who seek a better understanding of the interface between the pharmaceutical industry, health care systems, and society.
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Neuronal Hormones and the Sympathetic/Parasympathetic Regulation of the Heart
A. Ranek, A. Vu, M. S. Willis, and Anastasios Lymperopoulos
The primary purpose of the heart is to contract and pump blood to the entire body and all peripheral organs. Heart rate and cardiac output are tightly regulated so the heart can adjust to meet the needs of the organism under any given circumstance. This regulation is provided by the autonomic nervous system, including hormones and other secreted factors. In this chapter, we discuss the physiological mechanisms by which cardiac function is controlled and modulated by the autonomic (sympathetic & parasympathetic) nervous system, by the endocrine organs (mainly pituitary and adrenal glands), and, finally, by its own intrinsic endocrine system (cardiac hormones). Particular emphasis is given to molecular receptor signaling mechanisms underlying these processes.
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Clinically Significant Interactions with Benzodiazepines and Other Sedative Hypnotics/Anxiolytics
Jose Valdes, Douglas L. Boggs, Angela A. Boggs, and Jose A. Rey
Benzodiazepines are a class of lipophilic compounds used for a variety of indications including anxiety disorders, insomnia, epilepsy, musculoskeletal disorders, and as sedatives during surgery. The chemical nucleus of each benzodiazepine as well as their pharmacodynamic activity is identical. However, alterations to this basic structure lead to numerous benzodiazepines with different pharmacokinetic properties and lipid solubility resulting in agents with differing rates of elimination, concentrations, volumes of distribution, and potencies. In this chapter we will review the varied kinetics of available benzodiazepines and discuss the metabolic pathways leading to excretion of these medications. This review includes the enzymes (Phase I and Phase II) responsible for metabolism of the parent compound and their intermediates. We also review the pharmacologic and pharmacokinetic activity of the intermediate metabolites. Furthermore we will identify pharmacokinetic interactions of benzodiazepines including: drug-drug interactions, P-gylcoprotein interactions, protein-binding interactions, and food/herbal interactions. Other factors that may require alterations in benzodiazepine dosing such as weight, sex, age, smoking status, genetic polymorphisms, and pharmacokinetic interactions will similarly be discussed. Finally we will identify the clinical monitoring that is required for individuals being prescribed benzodiazepines including respiratory depression, sedation, and withdrawal. The goal of this chapter is to give the reader a background of the factors that should be considered when choosing or monitoring the available benzodiazepines in clinical practice.
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Pathophysiology of Heart Failure
Leany Capote, Ruth Nyakundi, Brandon Martinez, and Anastasios Lymperopoulos
Cardiac dysfunction precipitates changes in vascular function, blood volume, and neurohormonal status. These changes serve as compensatory mechanisms to help maintain cardiac output and arterial blood pressure. However, these compensatory changes over months and years can worsen cardiac function. Overall, the changes in cardiac function associated with heart failure (HF) result in a decrease in cardiac output. This results from a decline in stroke volume that is due to systolic dysfunction, diastolic dysfunction, or a combination of the two. Systolic dysfunction results from a loss of intrinsic inotropy (contractility), most likely due to alterations in signal transduction mechanisms responsible for regulating inotropy. Systolic dysfunction can also result from the loss of viable, contracting muscle as occurs following acute myocardial infarction (MI). Diastolic dysfunction refers to the diastolic properties of the ventricle and occurs when the ventricle becomes less compliant (i.e., "stiffer"), which impairs ventricular filling. Both systolic and diastolic dysfunctions result in a higher ventricular end-diastolic pressure, which serves as a compensatory mechanism by utilizing the Frank-Starling mechanism to augment stroke volume. In this chapter, we discuss the various types of cardiac insults and morbidities/conditions that can cause myocardial damage (directly or indirectly) in humans, thereby precipitating chronic systolic HF. Particular focus is given to the pathophysiological mechanisms by which they initiate or aggravate the development of clinical HF.
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Introduction/General Considerations
Anastasios Lymperopoulos
The adrenergic nervous system (ANS) exerts numerous effects on the cardiovascular system, including increase in cardiac contractility (positive inotropy), heart rate acceleration (positive chronotropy), hastened cardiac relaxation (positive lusitropy), and accelerated atrioventricular conduction (positive dromotropy) Most of these effects are mediated by adrenergic receptors (also known as adrenoceptors, ARs), which belong to the guanine nucleotide-binding G-protein-coupled receptor (GPCR) superfamily [1]. GPCRs are heptahelical transmembrane sensors, accounting for approximately 4% of the entire protein-coding genome, widely considered the most important drug targets in physiology and medicine [2]. These receptors consist of seven membrane-spanning domains, three intra- and three extracellular loops, one extracellular N-terminal domain, and one intracellular C-terminal tail [3].
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The Cardiovascular Adrenergic System
Anastasios Lymperopoulos
An overview of all the available literature on the various aspects of the regulation of the cardiovascular system`s function and physiology by the adrenergic neurohormonal system, i.e. the catecholamines norepinephrine and epinephrine. Although there are several books describing the adrenergic system`s biology, physiology and pharmacology, and also several excellent books on cardiovascular physiology and pathology, this book focuses exclusively on the interface of these two areas: cardiovascular regulation by the adrenergic system and how it affects cardiovascular diseases and their treatments. Each chapter describe the roles of the adrenergic system first in each cardiovascular cell type (cell type-by-cell type) and then in specific areas of cardiovascular physiology, such as in exercise and in cardiovascular metabolism. Finally, the book concludes with a chapter on the adrenergic system`s role in the currently very “hot” (in terms of scientific investigations) area of cardiovascular stem cell biology. The book covers the adrenergic system—specifically and exclusively in the heart and vessels. It is formatted by cardiovascular cell type-by-cell type manner, rather than in an organ-by-organ or in a disease-by-disease manner, as usually discussed in standard, conventional biomedical textbooks. The book also discusses the adrenergic system in novel, cutting-edge cardiovascular research areas, in which it has not been covered well so far (e.g. stem cells, exercise). These three areas constitute the most important assets of the book, which sets it apart from others in the field.
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Regulation of Catecholamine Production from the Adrenal Medulla
Anastasios Lymperopoulos, Smit Chowdhary, Kamarena Sankar, and Isis Simon
The present book provides a state-of-the-art overview of the adrenal gland pathophysiology. It covers both up-to-date basic and clinical notions on adrenal glands. Amidst the molecular aspects, discussed by leading scientists in the field, there are ER stress, microRNA, hormone biosynthesis, and interactions with other organs. Clinical insights for students and physicians are also provided, from the imaging to the therapeutic management of common disorders of the gland, including adrenal failure, hyperaldosteronism, Cushing's syndrome, neurologic disease, and cancer both in adults and pediatric patients. As mentioned above, chapter contributions are made by worldwide renowned experts, scientists and physicians, working in prestigious hospitals and universities including Brown, Oxford, Case Western Reserve University, Cleveland Clinic, Chinese University of Honk Kong, University of Tennessee, Indiana University School of Medicine, Monash Health in Clayton, Australia, University of Calgary, Northern Ontario School of Medicine and Laurentian University, Medical University of Gdansk, Universite Pierre et Marie Curie in Paris, France, University of Minho, Braga, Portugal, St. Vincent's University Hospital in Dublin, Universities of Londrina, Alfenas, Sao Paulo, and Rio de Janeiro, Brazil. Throughout these chapters, the authors spotlight future avenues for research in basic pathophysiology and in therapy/prevention, in addition to thorough overviews of the current literature pertaining to the adrenal gland and its functional roles. The book also includes several color photographs, schemes and diagrams of molecular relationships, and tables that support and complement the text. The comprehensive and systematic overview provided within this book is expected to assist the reader in comprehending the importance of taking into account the functional roles of the adrenal gland and also to address questions and unresolved issues regarding the treatment of its disorders
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Tumor Angiogenesis and Novel Vascular Endothelial Receptor (VEGFR)-Specific Small Molecule Inhibitors
Appu Rathinavelu
The knowledge related to angiogenesis has grown exponentially over the past few decades with the recognition that angiogenesis is essential for numerous normal and pathological processes. Very importantly, angiogenesis is required for the growth and metastasis of solid tumors in human beyond the size of 1–2 mm³ (Arap et al. 1998; Folkman 1990, 1995). Angiogenesis is the process of developing buds and outgrowth of capillaries from existing blood vessels that are derived as extensions due to hypoxia or other forms of signaling that occurs in the microenvironment that surrounds a tissue or tumors. On the other hand neovascularization is defined as the formation of functional microvascular network with red blood cell perfusion. Angiogenesis is required for invasive tumor growth and metastasis and therefore constitutes an important step in the control of cancer progression. In general vascular tumors are severely restricted in their growth potential because of the lack of a blood supply. To achieve the new blood vessel formation, endothelial cells must first escape from their stable location by breaking through the basement membrane, and this degradation is associated with migration of endothelial cells out of the vascular channel toward the angiogenic stimulus. During this process, the subendothelial basement membrane, a dense meshwork of collagen, glycoproteins, and proteoglycans are proteolytically disrupted to allow formation of new capillaries. Though it is an integral component of normal processes such as reproduction and wound healing, angiogenesis is known to play an important role in other pathological processes ranging from tumor growth and metastasis to inflammation and ocular diseases. During angiogenesis tumor cells exploit their microenvironment by releasing cytokines and growth factors to activate normal, quiescent cells around them and initiate a cascade of events that quickly becomes dysregulated. For example, tumor cell-released vascular endothelial growth factor (VEGF) stimulates the sprouting and proliferation of endothelial cells and thereby play a crucial role in neovascularization of solid tumors (Leung et al. 1989). The expression of VEGF has been shown to correlate with the density of microvessels in various tumors and exhibit higher metastatic ability (Folkman 1995; Leung et al. 1989; Toi et al. 1994). Therefore, inhibition of angiogenesis triggered by VEGF or other factors is accepted as a valuable approach to cancer therapy.
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Building Capacity towards HIV Prevention in a Latino Migrant Worker Community in South Florida
Jesús Sánchez
The Patient Protection and Affordable Care Act (ACA) contains a provision that requires all nonprofit hospitals to conduct a Community Health Needs Assessment (CHNA) and an Implementation Plan every three years. The first chapter of this book provides a comprehensive analysis of the CHNA process, the priorities identified in the CHNA, and the implementation strategies produced by 31 small nonprofit rural hospitals in Nebraska. Chapter two discusses current capacity building mechanisms with community-based obesity programmes in the United Kingdom, revealing the importance of partnerships between multi-agencies involved in the process.
Chapter three offers reflections on a Community-based participatory research (CBPR) project in partnership with the Latino migrant worker community in South Florida. Chapter four examines “KEQ” (Kapazitätsentwicklung im Quartier [Capacity Building in Residential Are-as/Neighborhoods]), which is the name of a newly developed questionnaire for measuring community capacities considered relevant to health. Chapter five discusses research on disaster recovery in several countries and the lessons learned regarding how personal, family, community and societal factors interact to facilitate adaptation to the consequences of disaster.
The final chapter provides an overview of regional development planning, which is a conscious development strategy designed to bring about change and equity, and to improve the living standards of people by integrating economic, social and environmental policies and programmes in a spatial context.
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ASHP Guidelines on Pharmacist Involvement in HIV Care
Jason J. Schafer, Taylor K. Gill, Elizabeth M. Sherman, and Ian R. McNicholl
The epidemic of human immunodeficiency virus (HIV) infection in the United States has changed dramatically since its initial recognition in 1981.1 Early in the epidemic, the incidence of HIV reached over 130,000 new cases per year, and death as a result of acquired immunodeficiency syndrome (AIDS) was an almost certain prognosis for those infected.2 Significant advances in the strategies to prevent HIV transmission and in the medical care of patients with HIV infection led to significant reductions in both HIV transmission events and AIDS-related deaths over time. Among these advancements were an understanding of HIV infection pathophysiology, identification of HIV transmission modes, development of public health interventions targeting behavioral changes in high-risk populations, and identification of novel HIV medication targets leading to advances in HIV treatment and eventually combination antiretroviral therapy (ART).
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Autism Spectrum Disorder—Level 2
José Valdes and José A. Rey
Pediatric pharmacotherapy, a growing practice area, will become a board certified specialty in the USA 2015. Yet, with little clinical data on the efficacy of drugs used for children and their other special needs, these small patients can be your biggest challenge. Now there is a very effective way to assess and advance your pediatric pharmacotherapy skills, on your own time, at your own pace: ASHP's new Pediatric Pharmacotherapy Self Assessment. Sandra Benavides and Milap C. Nahata, co-lead editors of a major pediatric pharmacotherapy textbook, and Hanna Phan, Assistant Professor in Pharmacy and Pediatrics at the University Of Arizona College Of Medicine, have created this unique resource. A practical learning tool for all levels of proficiency, it allows students, residents, and practicing pharmacists alike to strengthen their knowledge and analytical skills through 32 cases involving varying degrees of diagnostic complexity. This book is based on real life situations, these cases present challenges in the use of supplements, OTC, drug formulations, and all other therapies for neonates, children, and adolescents for pediatric pharmacotherapy. This Self Assessment is a professional development tool for all areas of concern and levels of practice that can benefit you and your youngest patients for years to come.
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Seizure Disorders—Level 3
José Valdes and José A. Rey
Pediatric pharmacotherapy, a growing practice area, will become a board certified specialty in the USA 2015. Yet, with little clinical data on the efficacy of drugs used for children and their other special needs, these small patients can be your biggest challenge. Now there is a very effective way to assess and advance your pediatric pharmacotherapy skills, on your own time, at your own pace: ASHP's new Pediatric Pharmacotherapy Self Assessment. Sandra Benavides and Milap C. Nahata, co-lead editors of a major pediatric pharmacotherapy textbook, and Hanna Phan, Assistant Professor in Pharmacy and Pediatrics at the University Of Arizona College Of Medicine, have created this unique resource. A practical learning tool for all levels of proficiency, it allows students, residents, and practicing pharmacists alike to strengthen their knowledge and analytical skills through 32 cases involving varying degrees of diagnostic complexity. This book is based on real life situations, these cases present challenges in the use of supplements, OTC, drug formulations, and all other therapies for neonates, children, and adolescents for pediatric pharmacotherapy. This Self Assessment is a professional development tool for all areas of concern and levels of practice that can benefit you and your youngest patients for years to come.
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Metabolism (Biotransformation)
Shakil Ahmed Saghir and Rais Ahmad Ansari
Metabolism is the sum of all chemical reactions occurring in organisms at the cellular level to sustain life. The main purpose of metabolism is to convert food to energy to run cellular processes, build macromolecule building blocks, i.e., proteins, lipids, nucleic acids and carbohydrates and eliminate nitrogenous wastes. Metabolism is catalyzed by enzymes, which are protein in nature. There are thousands of enzymes in an organism catalyzing a great variety of metabolic pathways (e.g., glycolysis, Krebs cycle), the sum of which is called metabolism, and the molecules that are produced during the process (intermediates or final products) are called metabolites. Metabolism allows organisms to grow, maintain their structures, respond to their environment, and reproduce. Metabolism is usually divided into two categories: catabolism or the breaking down of organic matter by cellular respiration, and anabolism or the building up of cellular components like proteins and nucleic acids. Usually, catabolism releases energy and anabolism consumes energy. These two processes are linked through cofactors, especially through widely distributed pyridine nucleotides in the form of NAD, NADP and adenine nucleotides in the form of ATP, ADP, and AMP. A primary catabolic process is cellular respiration where starting molecules such as glucose are oxidized in a stepwise fashion to pyruvate and the released energy is captured in the form of ATP and water and carbon dioxide are released as waste products of oxidation. The ATP is in turn used to drive anabolic processes such as amino acid and lipid biosynthesis.
In addition to converting food to energy, biosynthesizing cellular components, and eliminating nitrogenous waste, metabolism also covers biotransformation of foreign chemicals (xenobiotics) through a series of enzyme-catalyzed processes. Biotransformation alters the physicochemical properties of xenobiotics making them from accessible into cells, by enhancing their absorption across biological membranes, to eliminate into urine or bile, by enhancing hydrophilicity. The enzymes responsible for the xenobiotic biotransformation are often called drug-metabolizing enzymes. In the absence of biotransformation, xenobiotics we routinely exposed to, unintentionally or intentionally, for example, pharmaceuticals, industrial chemicals, pesticides, pollutants, cooked food containing pyrolysis products, alkaloids, plant metabolites of pesticides/chemicals, and toxins produced by plants, fungi and microbes will accumulate and eventually reach to toxic levels.
This article is part of the absorption, distribution, metabolism, and excretion or ADME series; the four main processes governing chemical (including drug) disposition in biological systems. Therefore, this article will summarize some fundamental principles of xenobiotic biotransformation (or metabolism) in mammals and major enzymes involved in this process.
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Pharmacokinetics
Shakil Ahmed Saghir and Rais Ahmad Ansari
Pharmacokinetics may be defined as the study of the dynamic movements of foreign chemicals (xenobiotics) during their passage through the body and as such encompass the kinetics of absorption, distribution, biotransformation/metabolism and excretion (ADME). It can simply be described as how the body handles xenobiotics. Pharmacokinetics uses mathematical equations (models) to describe the time course of ADME of xenobiotics in the body enabling us to better understand, interpret and even predict the nature and the extent of the biological effects (therapeutic or toxic) of xenobiotics. Several approaches are used in pharmacokinetic to describe the fate of xenobiotics in the body, including considering the body as one or more homogenous compartments based either on mathematical fitting or physiological properties. Description of the rates of the movement of xenobiotics into tissue(s) allows better interpretation and prediction of the fate of xenobiotics inside the body. This article will introduce the reader to basic concepts and principles of pharmacokinetic analysis using both compartmental and physiologically based models.
