Handbook of Experimental Pharmacology

This is the very first book to deal with sex and gender differences in drug therapy - an increasingly recognized medical need. It starts with an overview on S/G in clinical syndromes and a documentation of the medical and socioeconomic damage caused by gender specific adverse drug effects. Part I covers S/G differences in pharmacokinetics. Researchers will be satisfied by the detailed discussion of the mechanisms of S/G differences in drug effects that represents cutting edge science and includes interaction of drugs with sex hormones, genomic and epigenetic mechanisms. It also covers S/G in drug development, in animal models and clinical development and S/G in drug prescriptions. Part II targets S/G differences in drug effects in cardiovascular, pulmonary, CNS, neuromuscular, neuropsychiatric and metabolic diseases, in cancer, inflammation, and rheumatic diseases, in bacterial and retroviral infections, thrombosis, embolism. New drugs will be discussed.

Fungal diseases have been with us from antiquity; interest in the chemo therapy of fungal disease has exploded in the past decade. To plan and pro duce a book on the topic of antifungal chemotherapy has come as a personal challenge - and something of an eye-opener - towards the end of my re search career. A landmark publication which still merits reading is Antifungal Chemotherapy (John Wiley & Sons, Chichester, UK), edited by David Speller, which appeared in 1980. However, the fact that ketoconazole, the first of the modern, orally active, wide-spectrum antifungals, attracted no more than two sentences in it indicates just how far we have come in the 1980s. A steady stream of original papers and a number of conference proceedings have chronicled this progress in drug research; outstanding among the latter are the proceedings of an international telesymposium, entitled Recent Trends in the Discovery, Development and Evaluation of Antifungal Agents, edited by Robert Fromtling (J.R. Prous, Barcelona, 1987) and volume 544 of the Annals of the New York Academy of Sciences, entitled Antifungal Drugs, edited by Vassil St. Georgiev, and containing papers and posters presented at a most enjoyable 3-day conference held at Garden City, New York, in the autumn of 1987.

In recent years alcohol abuse has received increased international attention. Such attention is justified by the enormous negative impact that this disorder has on health, as well as on economic and social well-being. Governmental and other sources of research support have promoted substantial investigation into the negative consequences of alcohol, examining both animal models and human subjects. Consequently, there has been a virtual explosion of preclinical and clinical data, much of it focused on alcohol's pharmacologic effects. However, there have been few efforts to integrate this wealth of new information into a single, manageable volume. This volume provides an up-to-date, in-depth treatment of the phar macology of alcohol, particularly as it relates to alcohol abuse. The over riding theme of the book is the interplay between the preclinical and clinical domains. Increasingly, these areas of investigation have served to inform one another, a trend that can be expected to grow with time. The topics covered include the effects of alcohol on biological systems and the impact of medications on those effects. In addition, recent insights obtained from molecular biological investigations are discussed in terms of their relevance for understanding the effects of alcohol at the cellular level and the implica tions of these for the development of medications. Consideration is also given to important methodological issues that influence the evaluation of medications in the context of clinical trials.

The toxicology of metals has been concerned in the past with effects that produced clinical signs and symptoms. However, this view of metal toxicology has expanded in recent years due principally to two advances. There has been a considerable increase in our knowledge of the biochemical effects of metals. In addition, biomarkers of toxicity can now be recognized that identify toxicity at levels of exposure that do not produce overt clinical effects. Thus, the toxicology of metals is now focused on nonclinical events that reflect adverse health effects. This new awareness has produced the challenge of determining the lowest adverse level of exposure. With increasing analytical sensitivity and methodologies to detect small changes at the molecular level, the lowest level of exposure of some toxic metals, like lead, is very small. Indeed, for metals in which there is no biologic requirement, it may be questioned whether there is a level of exposure that does not produce some degree of toxicity. For essential metals, the question is being asked as to the levels at which exposure exceeds biologic require ments and excess exposure becomes toxic. The appropriateness of health decisions and the formation of public policy are dependent on the availability of current scientific information that addresses these questions. The information in this volume is intended to be a resource for this purpose as well as a reference for students of toxicology and other health professionals.