Bøger i Milestones in Drug Therapy serien

During the past decade research into the pharmacology of cognition, particularly regarding learning and memory, has supported the concept that many potential neural targets exist for the development of cognitive-enhancing drugs.

Although surprising, it seems fitting that a drug developed at the dawn of the era of rational drug design and therapeutics, methotrexate, should remain in common use for the therapy of so many different kinds of illnesses.

The main effect of calcium channel blockers is the blockade of calcium entry into cells through voltage operated calcium channels. This volume gives a comprehensive overview of the different classes of CCBs and their various effects. It covers historical development, pharmacology, clinical aspects, and perspectives.

Chronic viral hepatitis has emerged as one of the most common causes of disease and death worldwide. Because of their unique modes of replication and intimate association with the host immune system, hepatitis B virus (HBV) and hepatitis C virus (HCV) pose challenging problems to scientists in basic and applied research as well as to clinicians engaged in disease management. Although approved antiviral therapy is available for chronic HBV, the emergence of viral resistance provides a rationale for the development of novel chemotherapeutic agents. The lack of a robust cell culture system for HCV replication and a readily accessible small-animal model of HCV infection have hampered the development of antiviral agents for HCV. Neverthe-less, new antiviral agents targeting HCV are now in preclinical and clinical development.This monograph, providing an up-to-date overview of the field of Hepatitis Prevention and Treatment, includes contributions from internationally recognized experts in the field of viral hepatitis, and covers the current state of knowledge and practice regarding the molecular biology, immunology, biochemistry, pharmacology and clinical aspects of chronic HBV and HCV infection. The volume includes salient topics such as: the history and epidemiology of HBV and HCV; recent insights into the molecular mechanisms of viral replication; the host immune response to infection and a discussion of the use (HBV) or potential development (HCV) of vaccines; the current standard of care for chronically-infected patients; and emerging therapies and issues associated with current antiviral treatments. The latest information to researchers and clinicians actively engaged in viral hepatitis research is provided, but also sufficient background and discussion of the literature to benefit the newcomer to the field.

Recombinant protein drugs are intimately associated with the impressive success story of the Biotech Industry during the past thirty years, some of them belonging to the most successful pharmaceutical products.

An extensive assessment of combination therapy of AIDS. Main focus is put on the Highly Active Antiretroviral Therapy (HAART) but other therapies like salvage therapy are also discussed. The chapters cover efficacy, treatment, causes of treatment failure, clinical care, guidelines, pharmacology.

In addition anxiety is no longer considered to be a unique entity but rather an umbrella term for a series of specific anxiety disorders such as panic disorder without or with agoraphobia, generalised anxiety disorder (GAD), specific phobias, social phobias and post-traumatic stress disorder (PTSD).

First, the antipsychotics had very little effect on the so-called negative or defect symptoms, like social isolation, apathy and anhedonia, and secondly virtually all antipsychotics produced a number of side-effects, of which the neurological (often called extra pyramidal) side-effects were the most troublesome.

The text is ideal for researchers and clinical investigators in academia, biotechnology, and pharmaceutical companies, as well as clinical research associates, clinical monitors, and physician investigators.

Recombinant protein drugs are intimately associated with the impressive success story of the Biotech Industry during the past thirty years, some of them belonging to the most successful pharmaceutical products.

The following group of chapters cover the complex chemistry of the macro lactone structures, giving historic background, basic structure-activity relation ships of various derivatization strategies, and perspectives for future discovery of new semisynthetic macrolide antibiotics.

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.

Since the introduction of ciprofloxacin in 1987, fluoroquinolones have expanded far beyond their early role in the treatment of urinary tract infections. Clinical applications beyond genitourinary tract infections include upper and lower respiratory infections, gastrointestinal infections, gynecologic infec­ tions, sexually transmitted diseases, and some skin and soft tissue infections. Their ease of administration, favorable pharmacokinetic properties, excellent tolerability, and efficacy give them enormous potential for use and misuse alike. Quinolones have few common adverse effects, most notably nausea, headache and dizziness. Less frequent but more serious adverse events include prolongation of the corrected QT interval, phototoxicity, liver enzyme abnor­ malities, arthropathy, and cartilage and tendon abnormalities. While possess­ ing many of the favorable properties of intravenous agents, most fluoro­ quinolones offer the convenience of oral administration, thus contributing to decreased health-care costs through increased outpatient therapy and short­ ened hospital stays. With the recent introduction of agents such as gatifloxacin and moxifloxacin, the traditional Gram-negative coverage of fluoroquinolones has been expanded to include Gram-positive organisms, most importantly Streptococcus pneumoniae.

In this monograph about gene therapy of autoimmune and inflammatory d- orders we have gathered international experts and leaders from different fields to review the state of the art advances on topics ranging from disease entities to vectors and engineered cells.

COX-2 inhibitors are important drugs with analgesic and anti-inflammatory effects. This book presents both pre-clinical and clinical information and is important for clinicians interested in the latest information about this class of drugs, for researchers and for students in the field.

Since the introduction of ciprofloxacin in 1987, fluoroquinolones have expanded far beyond their early role in the treatment of urinary tract infections. Clinical applications beyond genitourinary tract infections include upper and lower respiratory infections, gastrointestinal infections, gynecologic infec­ tions, sexually transmitted diseases, and some skin and soft tissue infections. Their ease of administration, favorable pharmacokinetic properties, excellent tolerability, and efficacy give them enormous potential for use and misuse alike. Quinolones have few common adverse effects, most notably nausea, headache and dizziness. Less frequent but more serious adverse events include prolongation of the corrected QT interval, phototoxicity, liver enzyme abnor­ malities, arthropathy, and cartilage and tendon abnormalities. While possess­ ing many of the favorable properties of intravenous agents, most fluoro­ quinolones offer the convenience of oral administration, thus contributing to decreased health-care costs through increased outpatient therapy and short­ ened hospital stays. With the recent introduction of agents such as gatifloxacin and moxifloxacin, the traditional Gram-negative coverage of fluoroquinolones has been expanded to include Gram-positive organisms, most importantly Streptococcus pneumoniae.

The main effect of calcium channel blockers is the blockade of calcium entry into cells through voltage operated calcium channels. This volume gives a comprehensive overview of the different classes of CCBs and their various effects. It covers historical development, pharmacology, clinical aspects, and perspectives.

Angiotensin converting enzyme inhibitors (ACEI) represent the first class of antihypertensive agents that was designed and developed on the basis of a well-defined physiopathological axis of arterial hypertension, a vascular dis­ order that is now becoming one of the major causes of morbidity/mortality, not only in developed societies but also in the highly populated developing coun­ tries [1]. CAPTOPRIL, the prototype of the "PRIL" family, which now comprises more than 40 molecule-species, was quite hazardous and the clinical develop­ ment almost failed when serious side-effects were reported in an alarmist fash­ ion in reputable scientific journals, such as the New England Journal of Medicine and Lancet. Squibb & Sons came very close to withdrawing CAPTOPRIL from clinical investigation [2]. However, after re-examination of the data obtained from different categories of patients and appropriate dose-adjustments, the clinical use of CAPTOPRIL turned out to be revolutionary. The prototype, as well as other members of the "PRIL" family became the starting point for numerous basic and clinical research programs, focusing on the interactions of ACEI with the kinin, endothelin, and nitric oxide systems, and the contribution of the receptors for AT I, AT 2, bradykinin Bland B , ETA and ET B to the pharmacological actions 2 of the respective peptides. This research activity led to the development of new pharmacological agents, such as the angiotensin receptor antagonists and, more recently, the neutral endopeptidase inhibitors. In the near future, bradykinin receptor antagonists also will be available to modulate ACEI phar­ macological actions.

This book deals with statins which have substantially altered the approach to therapy of atherosclerosis and its sequelae. This book not only provides the reader with valuable information but also stimulates further research into the pathogenesis of atherosclerosis and the mechanisms behind the action of effective statins.

Important clinical issues as the outcome of long term treatment with antidepressants, the time of onset of the antidepressant response and the limitations of the antidepressants currently available are covered in this monograph.

First, the antipsychotics had very little effect on the so-called negative or defect symptoms, like social isolation, apathy and anhedonia, and secondly virtually all antipsychotics produced a number of side-effects, of which the neurological (often called extra pyramidal) side-effects were the most troublesome.

In addition anxiety is no longer considered to be a unique entity but rather an umbrella term for a series of specific anxiety disorders such as panic disorder without or with agoraphobia, generalised anxiety disorder (GAD), specific phobias, social phobias and post-traumatic stress disorder (PTSD).

This drug is a landmark discovery, which consequently has become the definitive therapy for the treatment of erectile dysfunction (ED). Following the major breakthrough in the field of nitric oxide (NO)-physiology and pharmacology leading to sildenafil being marketed, the most current information is presented in this reference book, including ongoing research from several disparate groups about NO as endothelium-derived relaxing factor (EDRF) and also as a neurotransmitter for nerves innervating erectile tissue in mammals.The development of sildenafil as an oral phosphodiesterase-5 (PDE5) inhibitor drug for the treatment of ED resulted in one of the first products, which made its way successfully from basic NO research to routine clinical therapy.This volume addresses all fields of sildenafil application in both men and women. In a highly competitive research environment with a critical medical need for drug improvements the reader will learn more about clinical resistance to sildenafil treatment and the modalities to overcome the failure rates. The individual chapters cover clinical use, pharmacokinetics, pharmacodynamics, biochemistry, and cultural aspects. They are written by leading experts in their respective fields. Therefore, readers ¿ whether professionals in the pharmaceutical industry, physicians treating ED, biochemists, chemists or pharmacologists ¿ will find a detailed and up-to-date knowledge base about current research activities and an excellent overview for further research on this compound class and its cultural impact.

In this volume on valproate emphasis is placed on the scientific back ground leading to the discovery of val pro ate, its subsequent pharmacologi cal and toxicological characterization, and its clinical development into one of the most widely and successfully used anti epileptic drugs, a real mile stone in drug therapy.

The following group of chapters cover the complex chemistry of the macro lactone structures, giving historic background, basic structure-activity relation ships of various derivatization strategies, and perspectives for future discovery of new semisynthetic macrolide antibiotics.

Following 50 years of glucocorticoid use in a clinical setting, an international body of expert scientists and physicians presents the most expansive survey of glucocorticoid pharmacology to date.

During the past decade research into the pharmacology of cognition, particularly regarding learning and memory, has supported the concept that many potential neural targets exist for the development of cognitive-enhancing drugs.

Inhibition of the proton pump in the parietal cells has been established as the main therapeutic principle in the treatment of acid-related diseases, such as peptic ulcer and gastro-oesophageal reflux.

Expanding from the classic use of immunosuppressants in transplantation and rejection, this current overview highlights their new roles in clinical medicine.