Novel Antimicrobial Agents and Strategies

The science and applied approaches of enzyme inhibition in drug discovery and development Offering a unique approach that includes both the pharmacologic and pharmaco-kinetic aspects of enzyme inhibition, Enzyme Inhibition in Drug Discovery and Development examines the scientific concepts and experimental approaches related to enzyme inhibition as applied in drug discovery and drug development. With chapters written by over fifty leading experts in their fields, Enzyme Inhibition in Drug Discovery and Development fosters a cross-fertilization of pharmacology, drug metabolism, pharmacokinetics, and toxicology by understanding the «good» inhibitions—desirable pharmacological effects—and «bad» inhibitions—drug–drug interactions and toxicity. The book discusses: The drug discovery process, including drug discovery strategy, medicinal chemistry, analytical chemistry, drug metabolism, pharmacokinetics, and safety biomarker assessment The manipulations of drug metabolizing enzymes and transporters as well as the negative consequences, such as drug–drug interactions The inhibition of several major drug target pathways, such as the GPCR pathway, the NFkB pathway, and the ion channel pathway Through this focused, single-source reference on the fundamentals of drug discovery and development, researchers in drug metabolism and pharmacokinetics (DMPK) will learn and appreciate target biology in drug discovery; discovery biologists and medicinal chemists will also broaden their understanding of DMPK.

Filling an obvious gap in the scientific literature, this practice-oriented reference is the first to tie together the working knowledge of large screening centers in the pharmaceutical and biotechnological field. It spans the entire fi eld of this emerging discipline, from compound acquisition to collection optimization for specific purposes, to technology and quality control. In so doing, it applies two decades of expertise gathered by several large pharmaceutical companies to current and future challenges in high-throughput screening. With its treatment of libraries of small molecules as well as biobanks containing biomolecules, microorganisms and tissue samples, this reference is universally applicable for any molecular scientist involved in a large screening program.

Dr. Paris has written an honest, balanced presentation of the ways in which psychiatric drugs are evaluated and prescribed. He highlights the complexity of the task, the limits of what is known and the mixed picture that research often produces. His conclusions are refreshing because they are built from an even-handed, pragmatic assessment of the empirical evidence. The result is a stimulating look at the world of treatments for emotional disorders that acknowledges the usefulness of both biological and psychosocial explanations where appropriate. His recommendations provide helpful roadmaps for patients, practitioners and researchers alike. The book is sure to serve as a welcome catalyst for the continuing debates about which treatments are likely to produce the best outcomes. —Roger P. Greenberg, Ph.D. Distinguished Professor and Head, Psychology Division Dept. of Psychiatry & Behavioral Science SUNY Upstate Medical University, NY, USA The message of this book is that psychiatrists have some very good drugs, but can expect bad results when they are over-used, prescribed outside of evidence-based indications, or given to the wrong patients. While acknowledging that many current agents are highly effective and have revolutionized the treatment of certain disorders, Joel Paris criticizes their use outside of an evidence base. Too many patients are either over-medicated or are misdiagnosed to justify aggressive treatment. Dr. Paris calls for more government funding of clinical trials to establish, without bias, the effectiveness of these agents. He has written this book for practitioners and trainees to show that scientific evidence supports a more cautious and conservative approach to drug therapy. After describing the history of psychopharmacology, including its early successes, Dr. Paris reviews the relationship between psychiatry and the pharmaceutical industry. This problem has received considerable popular attention in recent years and Dr. Paris documents initiatives to increase transparency and decrease the influence of pharmaceutical marketing on diagnosis and prescribing habits. Dr Paris then examines some major controversies. One is the fact that newer drugs have not been shown to be superior to older agents. Another is that while the number of prescriptions for antidepressants has increased dramatically, meta-analyses show that their value is more limited than previously believed. Still another is the widespread prescription of mood stabilizers and antipsychotic drugs for patients, including children and adolescents, who do not have bipolar illness. Polypharmacy is an especially contentious area: very few drug combinations have been tested in clinical trials, yet many patients end up on a cocktail of powerful drugs, each with its own side effects. Dr Paris briefly considers alternatives to pharmacology and again calls for more clinical trials of these approaches. He also discusses the current trend to medicalizing what many would describe as normal distress and states succinctly: Some things in life are worth being upset about.

This book answers the questions about the process and costs of pharmaceutical R & D in a compelling narrative focused on the discovery and development of important new medicines. It gives an insider's account of the pharmaceutical industry drug discovery process, the very real costs of misperceptions about the industry, the high stakes–both economic and scientific–of developing drugs, the triumphs that come when new compounds reach the market and save lives, and the despair that follows when new compounds fail. In the book, John LaMattina, former president of Pfizer Global Research and Development, weaves themes critical to a vital drug discovery environment in the context. This is a story that Dr. LaMattina is uniquely qualified to tell.

This book bridges the gap between practitioners of supply-chain management and pharmaceutical industry experts. It aims to help both these groups understand the different worlds they live in and how to jointly contribute to meaningful improvements in supply-chains within the globally important pharmaceutical sector. Scientific and technical staff must work closely with supply-chain practitioners and other relevant parties to help secure responsive, cost effective and risk mitigated supply chains to compete on a world stage. This should not wait until a drug has been registered, but should start as early as possible in the development process and before registration or clinical trials. The author suggests that CMC (chemistry manufacturing controls) drug development must reset the line of sight – from supply of drug to the clinic and gaining a registration, to the building of a patient value stream. Capable processes and suppliers, streamlined logistics, flexible plant and equipment, shorter cycle times, effective flow of information and reduced waste. All these factors can and should be addressed at the CMC development stage.