This volume describes methods and protocols for a number of drugs and toxins in a stepwise manner. Chapters in the book cover a wide array of topics such as: quantitation of Flecainide, Mexiletine, Propafenone, and Amiodarone in Serum or Plasma; quantitation of total Buprenorphine and Norbuprenorphine in Meconium; quantitation or Carisoprodol and Meprobamate in Urine; and quantitation of Tricyclic Antidepressants in Serum. Each chapter contains a brief introduction to the topic, clinical utility of the analyte(s), and useful notes to help laboratorians easily reproduce the protocols discussed. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and thorough, Clinical Applications of Mass Spectrometry in Drug Analysis: Methods and Protocols, is a great resource for laboratorians who are already using mass spectrometry or thinking of introducing this technology to their laboratories.

Contents

E.I. Christensen and R. Nielsen: Role of Megalin and Cubilin in Renal Physiology and Pathophysiology

G. Zifarelli and M. Pusch: CLC Chloride Channels and Transporters: A Biophysical and Physiological Perspective

S.F.J. van de Graaf, R.J.M. Bindels and J.G.J. Hoenderop: Physiology of Epithelial Ca2 and Mg2+ Transport

Currently, there are tremendous advances being made in understanding the basic science of both the structure and function of botulinum neurotoxins. This knowledge is opening up opportunities in regard to both therapeutic uses and treatment and protection options for civil and bio-defense applications. This volume fully evaluates the status of neurotoxin research and exploitation. The book is a multi-authored collection of chapters written by the leading authorities responsible for the current scientific and clinical research that is advancing the understanding and exploitation of the neurotoxins and is both up to date and authoritative.

Although the importance of calcium (Ca2+) in the maintenance of cardiac contractility was recognized as early as 1880, the critical role of the ion in the contractile process in skeletal, cardiac, and smooth muscle has only been established within the last three decades. As the complexity of the pharmacological actions of the Ca2+ channel inhibitors grows, there is a continued need to further clarify the inhibitors, both chemically and functionally. This volume provides an update of the field based on the work presented at the 5th International Symposium on Calcium Antagonists: Pharmacology and Clinical Research. It reviews the current state of the growing area of molecular biology of Ca2+ channels in the cardiovascular area, in addition to the well-established clinical uses of Ca2+ channel inhibitors, recent work pointing to an application in atherosclerosis is described. The text also includes important uses of Ca2+ antagonists in novel areas of interest such as the gastrointestinal tract, renal protection and multi-drug resistance.

Comprehensive and authoritative, Opioid Receptors and Antagonists: From Bench to Clinic offers neuroscientists, pharmacologists and interested clinicians a unique survey of the extensive and diverse research efforts currently employed with opioid antagonists to develop novel innovative drug therapies. Summarizes the present understanding of the chemistry, pharmacology and molecular biology of opioid receptors and their subtypes Highlights differences and similarities between the opioid pharmacology of animals and human Describes current and potential therapeutic areas for opioid antagonists, including substance abuse, alcohol and ingestive behaviors, behavioral disorders and other medical indications, supported by nonclinical and clinical evidence Focuses on the development of exciting and innovative drug delivery approaches that are being used with opioid antagonists for the above medical indications

The intent of this volume of Current Topics in Microbiology and Immunology was to bring together a collection of in-depth and cutting edge reviews that highlight our current understanding of the biology of ricin and Shiga toxin (Stx), with the long term goal of advancing the development of countermeasures against these toxic agents. In May of 2011, Western Europe experienced a severe outbreak of Stx-producing E. coli (STEC) that culminated in more than 3200 cases and 39 deaths. While Stx is not the only virulence factor associated with STEC, it is certainly the primary determinant associated with the onset of hemolytic uremic syndrome (HUS). At the present time, there are no clinically approved measures to neutralize Stx in individuals suffering from STEC infection. Nor are there any preventatives or therapeutics for ricin toxin. Although incidents of ricin exposure are largely unheard of, federal agencies and public health officials consider it a significant threat. It is well documented that domestic and international terrorist groups have stockpiled, and in some cases weaponized ricin with the intent of releasing it into the public sphere and causing panic, illness and/or death on a local, regional, or possibly national scale. As the title of this volume indicates, the chapters, written by leading experts in the field, are organized so as to cover all aspects of ricin and Stx, including pathogenesis, immunity, vaccines and therapeutics. This outstanding collection of reviews will serve as an important and readily accessible resource for the research community in the coming years.

Mitochondria are far more than the "powerhouse" of the cell as they have classically been described. In fact, mitochondria biological activities have progressively expanded to include not only various bioenergetic processes but also important biosynthetic pathways, calcium homeostasis and thermogenesis, cell death by apoptosis, several different signal transduction pathways mainly related to redox control of gene expression and so on. This functional and structural complexity may undergo important derangements so to justify the definition of 'mitochondrial medicine', which should include all the clinical consequences of congenital or acquired mitochondrial dysfunctions. There are actually a growing number of studies which assign a significant pathogenic role to damaged mitochondria in different diseases: ischemia/reperfusion injury, neurodegenerative diseases, cancer with its dramatic sequelae (i.e, metastasis), metabolic syndrome, hyperlipidemias, just to mention a few of the most important pathologies. In this context, a further aspect that should not be disregarded is the interaction of pharmacological agents with mitochondria, not only in regard of the toxicological aspects but, above all, of the potential therapeutic applications. In fact, it is interesting to note that, while the properties of different so-called "mitoxicants" are well-known, the subtle linkages between drugs and mitochondria is still in need of a real pharmacological and therapeutic control at the clinical level. This lack of consideration can often lead to an underestimation of unwanted toxic effects but also of desirable therapeutic activities. A reevaluation of the potential clinical role of mitochondria could give a new light on some yet obscure aspects of human pathophysiology.

Although more than 10 new antiepileptic drugs have been developed in the past decade, epilepsy remains resistant to drug therapy in about one third of patients, many of whom struggle with the disease their entire lives. Managing these patients is a challenge and requires a structured multidisciplinary approach. The book includes chapters on all issues related to pharmacoresistance in epilepsy and describes recent developments in the pathogenesis and treatment of this disorder. It addresses abnormalities in inhibitory mechanisms, epilepsy-related changes to the immune system, development of pharmacoresistance caused by chronic exposure to antiepileptic drugs, and novel therapeutic strategies for preventing or slowing down the progression of the disease. Clinicians and basic scientists alike will find up-to-date information on the development of pharmacoesistance, as well as reviews of mechanisms associated with epilepsy that may help them consider novel strategies for preventing the development of pharmacoresistance in the first place. The book also features information on new therapeutic strategies for control of epilepsy, such as transcutaneous electrical stimulation and virtual screening of new antiepileptic drugs. "Pharmacoresistance in Epilepsy" " From Genes and Molecules to Promising Therapies" is useful to anyone working in the field, whether they re studying epilepsy in the lab or treating it in a doctor s office. "

The treatment of attention deficit/hyperactivity disorder (ADHD) is a complex challenge. This book provides comprehensive, scientific coverage of the numerous different types of drugs that are used to treat ADHD, and it examines the historical, sociological, and policy-related factors involved in the use of ADHD medications. A national study indicated that 11 percent of U.S. children and teens were diagnosed with attention deficit/hyperactivity disorder (ADHD) in 2011-a figure 43 percent higher than in 2003. The incidence of ADHD diagnoses among females has also increased significantly. For the millions of Americans of all ages who are diagnosed with ADHD, the proper treatment of this disorder is critically important. ADHD Medications: History, Science, and Issues provides readers with the complete story of ADHD drugs. The book discusses the pharmacological basis of the effects of these powerful drugs; examines the myriad social dimensions of the use, misuse, and abuse of these substances; and identifies the range of issues that affect the recognition, diagnosis, and treatment of ADHD. After an introductory case study of an individual with ADHD and this individual's problems and successes with ADHD medicines, this new book in the Story of a Drug series provides an overview of ADHD and its various symptoms, as well as the causes, prevalence, and diagnosis of ADHD. Various treatment approaches-including information about the many medications used-are discussed in detail, as well as other substances and alternative ways used to treat individuals with ADHD. Readers will also gain an understanding of neurotransmission and the specific mechanism of action of ADHD medications; the effects and applications of these drugs, plus their associated risks, misuse, and abuse; as well as related policy issues, with special focus on the controversial issues regarding ADHD drug scheduling (categorization). Provides broad background coverage of ADHD and of various types of drugs that can be used to treat symptoms of ADHD Explains how different types of ADHD medications work in the body Delves into issues and controversies related to ADHD medications, including their prescription to young children and recreational use by individuals without ADHD

PEGylation technology and key applications are introduced by this topical volume. Basic physical and chemical properties of PEG as basis for altering/improving in vivo behaviour of PEG-conjugates such as increased stability, improved PK/PD, and decreased immunogenicity, are discussed. Furthermore, chemical and enzymatic strategies for the coupling and the conjugate characterization are reported. Following chapters describe approved and marketed PEG-proteins and PEG-oligonucleotides as well as conjugates in various stages of clinical development. The volume closes with chapters on FDA regulations and EMEA guidelines for these drugs and general perspectives for future developments.

In the view of most experts pharmacology is on drugs, targets, and actions. In the context the drug as a rule is seen as an active pharmaceutical ingredient and not as a complex mixture of chemical entities of a well defined structure. Today, we are becoming more and more aware of the fact that delivery of the active compound to the target site is a key. The present volume gives a topical overview on various modern approaches to drug targeting covering today s options for specific carrier systems allowing successful drug treatment at various sites of the body difficult to address and allowing to increase the benefit-risk-ratio to the optimum possible."

Driving further the research on mammalian alkaline phosphatase structure and function, Phosphatase Modulators collects expert contributions into one "how to" manual for basic scientists interested in initiating a drug discovery effort. While this book contains the traditional method chapters and some typical reviews on the structure and known functions of phosphatases, other contributions are meant to discuss approaches and alternatives useful in making "go/no-go" decisions in high throughput screening (HTS) and lead optimization campaigns. Many chapters focus on tissue-nonspecific alkaline phosphatase (TNAP) as well as protein phosphatases. Written for the highly successful Methods in Molecular Biology series, chapters in this volume include the kind of detail and key implementation advice that promotes reproducible results. Step-by-step and practical, Phosphatase Modulators offers a path to understanding many of the facets and complexities associated with undertaking a drug discovery effort and will serve as a roadmap to initiating those efforts.

Germination of the thought of "Enzymatic- and Transporter-Based Drug-Drug Interactions: Progress and Future Challenges" Proceedings came about as part of the annual meeting of The American Association of Pharmaceutical Scientists (AAPS) that was held in San Diego in November of 2007. The attendance of workshop by more than 250 pharmaceutical scientists reflected the increased interest in the area of drug-drug interactions (DDIs), the greater focus of PhRMA, academia, and regulatory agencies, and the rapid pace of growth in knowledge. One of the aims of the workshop was to address the progress made in quantitatively predicting enzyme- and transporter-based DDIs as well as highlighted areas where such predictions are poor or areas that remain challenging for the future. Because of the serious clinical implications, initiatives have arisen from the FDA (http://www.fda.gov/cber/gdlns/interactstud.htm) to highlight the importance of enzyme- and transporter-based DDIs. During the past ten to fifteen years, we have come to realize that transporters, in addition to enzymes, play a vital role in drug elimination. Such insight has been possible because of the continued growth in PK-ADME (pharmacokinetics-absorption-distribution-metabolism-excretion) knowledge, fueled by further advances in molecular biology, greater availability of human tissues, and the development of additional and sophisticated model systems and sensitive assay methods for studying drug metabolism and transport in vitro and in vivo. This has sparked an in-depth probing into mechanisms surrounding DDIs, resulting from ligand-induced changes in nuclear receptors, as well as alterations in transporter and enzyme expression and function. Despite such advances, the in vitro and in vivo study of drug interactions and the integration of various data sets remain challenging. Therefore, it has become apparent that a proceeding that serves to encapsulate current strategies, approaches, methods and applications is necessary. As Editors, we have assembled a number of opinion leaders and asked them to contribute chapters surrounding these issues. Many of these are the original Workshop speakers whereas others had been selected specially to contribute on topics related to basic and applied information that had not been covered in other reference texts on DDI. The resulting tome, entitled Enzyme- and Transporter-Based Drug Interactions: Progress and Future Challenges, comprises of four sections. Twenty-eight chapters covering various topics and perspectives related to the subject of metabolic and transporter-based drug-drug interactions are presented.

This book discusses the emergence of a new class of genes with a specific anticancer activity. These genes, recently defined as "Anticancer Genes", are reviewed in individual chapters on their mode of action, the specific cell death signals they induce, and the status of attempts to translate them into clinical application. Anticancer Genes provides an overview of this nascent field, its genesis, current state, and prospect. It discusses how Anticancer Genes might lead to the identification of a repertoire of signaling pathways directed against cellular alterations that are specific for tumor cells. With contributions from experts worldwide, Anticancer Genes is an essential guide to this dynamic topic for researchers and students in cancer research, molecular medicine, pharmacology and toxicology and genetics as well as clinicians and clinical researchers interested in the therapeutic potential of this exciting new field.

Deciphers amylin's physiology and reveals previously unrecognized mechanisms fundamental to control body weight and fuel homeostasis. Also discusses therapeutic utility of amylin as the first new medicine to treat diabetes since insulin.
*Provides a current comprehensive treatment of amylin the hormone
*Identifies the majority of amylin's physiologic functions

This book offers pertinent basic science information on strategies used for the rational design and discovery of novel anticancer agents, and, in addition, translational studies involving clinical trial design and execution with these novel, mostly cytostatic agents. This book covers basic science strategies that are being used in drug discovery and preclinical evaluation focused on novel molecular targets, as well as clinical trial methodology including clinical pharmacokinetics and imaging to address issues of efficacy evaluation of the new, relatively non-cytotoxic anticancer agents.
At present, there is no book that provides such an integration of basic and clinical studies of novel anticancer agents, covering both drug discovery and translational research extensively.
* Addresses the critical issues involved in the development of novel agents for cancer therapy by experts in the field
* Presents drug discovery strategies
* Discusses regulatory issues surrounding drug development
*

In this book, a worldwide panel of leading experts discuss the role of inflammation in the pathogenesis of major chronic diseases and the current controversy regarding risk versus benefit of selective cyclooxygenase-2 (COX-2) inhibitors. The authors provide exciting and enlightening perspectives on COX-2 and related molecular targets in the future of medicine, including historical perspectives.

Food Toxicants Analysis covers different aspects from the field of analytical food toxicology including emerging analytical techniques and applications to detect food allergens, genetically modified organisms, and novel ingredients (including those of functional foods). Focus will be on natural toxins in food plants and animals, cancer modulating substances, microbial toxins in foods (algal, fungal, and bacterial) and all groups of contaminants (i.e., pesticides), persistent organic pollutants, metals, packaging materials, hormones and animal drug residues. The first section describes the current status of the regulatory framework, including the key principles of the EU food law, food safety, and the main mechanisms of enforcement. The second section addresses validation and quality assurance in food toxicants analysis and comprises a general discussion on the use of risk analysis in establishing priorities, the selection and quality control of available analytical techniques. The third section addresses new issues in food toxicant analysis including food allergens and genetically modified organisms (GMOs). The fourth section covers the analysis of organic food toxicants.
* step-by-step guide to the use of food analysis techniques
* eighteen chapters covering emerging fields in food toxicants analysis
* assesses the latest techniques in the field of inorganic analysis

Ocular toxicity is routinely assessed in toxicology studies conducted for regulatory purposes. Ocular anatomy and physiology and the assessment of ocular toxicity itself can be challenging to scientists involved in the safety assessment of pharmaceuticals, pesticides and other agents. Anatomical and physiological differences between species can impact the nature of ocular effects observed following intended or unintended exposure of ocular tissues to xenobiotics. "Ocular Toxicity in Laboratory Animals" provides a concise reference addressing ocular anatomy and physiology across species that will enhance the design and interpretation of toxicology studies conducted for regulatory purposes.

The book provides an overview of routine and advanced techniques that are used to assess ocular toxicity including slit lamp biomicroscopy, indirect ophthalmoscopy, electrophysiology and imaging methods for the anterior and posterior segments of the eye. Additionally, the book defines the regulatory expectations for pharmaceuticals intended to treat ocular diseases and for other non-pharmaceutical regulated chemicals. With contributions from experts in the field, "Ocular Toxicity in Laboratory Animals" is an authoritative, accessible guide for toxicologists and other scientists involved in conducting toxicology studies for regulatory purposes and/or reviewing data from such studies."

A revision book to help pharmacist students prepare for the pre-registration exam of the Royal Pharmaceutical Society of Great Britain (RPSGB) and other similar exams. It consists of over 400 multiple choice questions (MCQs), with explanatory answers, as well as an introductory chapter on exam preparation and four useful appendixes of abbreviations and symbols used in pharmacy. All the MCQs are written in the same style as the RPSGB pre-registration exam. The topics covered are core aspects of any pharmacy curriculum, making the book suitable for pharmacy students preparing for undergraduate exam and similar pre-registration exams in all parts of the world. Over 400 multiple-choice questions cover all the topics in the pre-registration exam of the RPSGB. All questions are written in the style of the RPSGB exam. Four types of multiple-choice questions are given, covering all three parts of the pre-registration RPSGB - all in the same style as the exam. Questions are grouped according to core pharmacy topics. Explanations are thorough and helpful. Four appendices provide helpful summaries of abbreviations and symbols used in pharmacy.

The discipline of developmental toxicology is an integration of concepts, models, and methodologies based heavily on the superimposition of toxicology principles upon the science of developmental biology. The science of developmental toxicology also borrows from other research areas that are concerned with regulation of cell growth, migration, differentiation and cell death, as such are central to the study of stem cells, cancer, and chronic diseases. In Developmental Toxicology: Methods and Protocols expert researchers in the field detail many of the methods which are now commonly used to study developmental toxicology highlighting the evolution of methods from classical teratology approaches to the dynamic, state-of-the-art molecular methods, systems biology, and next generation models and procedures. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Developmental Toxicology: Methods and Protocols is a valuable resource to those planning experiments to investigate consequences of environmental, nutritional, or chemical effects caused during development.