Drugs may cause disease, or they may aggravate the morbidity of the condition for which they are prescribed, and certain patients may for one or other reason be particularly liable to drug injury. The inextricable relationships between the toxic profiles of drugs, the natural history of the diseases for which they are given, and the adverse drug effects that may develop in the course of such diseases are of considerable interest. It is the study of these rather neglected aspects of pharmacology and therapeutics which has formed the basis of this book. An explanation is required of the approach and the style which have been followed. The monograph does not purport to be comprehensive. Only important drug groups which are commonly used in practice are considered. Emphasis has been placed on achieving maximum benefit and safety of the appropriate drugs in the management of common illnesses. When treatment fails, either ab initio or subsequent to an initial response, the risk-benefit relationship of drugs inevitably alters. For this reason the main factors responsible for treatment failure have been considered, with special attention to the possible contribution of or implications for drug therapy in such a situation. Finally, proposals have been put forward for improving the diagnosis and reporting of adverse drug effects. In order to be practical and, as far as possible, constructive it has been necessary for me to "take a position" on numerous issues.

Many chemotherapeutic agents introduced for use in humans are carcinogenic in laboratory animals (Conklin et al. 1965; Shimkin et al. 1966; Griswold et al. 1968; Harris 1976). However, initially their beneficial effect in disseminated cancer was of such short duration that the inevitable death of the patient from his primary disease precluded any clinical manifestation of the carcinogenic potential. During the last decade, chemotherapy has radically changed the outlook for many patients with cancer. Combinations of drugs, administered as the primary treatment, have resulted in high rates of cure in patients with disseminated malignancies, such as stage IV Hodgkin's disease or childhood acute lymphocytic leukemia. In other disseminated forms of neoplasia, induction of a remission, a substantial palliation and a prolongation of survival have been achieved. In many instances of localised disease, where surgery with or without radiotherapy are the primary form of treatment, anticancer drugs have been used with success as adjuvant therapy for distant microscopic disease. With these spectacular achievements, secondary malignancies, in particular acute non-lymphocytic leukemia (ANLL), has become of major concern. Incidence Acute leukemia is the most frequent form of secondary neoplasia in patients treated for cancer (Penn 1981). In one large series, 5. 9% of all ANLL could be attributed to previous chemotherapy (Kapadia et al. 1980).

Nervous system is in the most cases a likely target for the untoward effects of chemicals. The harmful consequences affect primarily the individual but may also considerably strain the whole society. The consumption of ethanol is a glaring example (National Institute on Alcohol Abuse and Alcoholism 1978). As ethanol, many organic liquids have similar immediate effects on the nervous system. The rapidity of the response suggests the involvement of the neuronal communication. The nervous system is also vulnerable to the depletion of oxygen, another common cause for the rapid deterioration of the brain function. It is quite impossible to list all the effects produced by the very large number of the individual chemicals. It would be more fruitful to try to understand the characteristics of the nervous system and the biochemical toxic mechanisms in the evaluation of the neurotoxicity of chemicals. Transfer of Xenobiotics in the Brain The adult central nervous system displays a functional barrier toward the blood-borne chemicals so that water-soluble compounds with an approximate molecular weight above 100 are largely prevented from directly entering the brain (Bradbury 1979). The functional barrier has morphological features typical to it and has a very close association of adjacent capillary cells separated by clefts of 12 A wide (Jacobs 1978). The nervous system capillaries are enveloped by glial cell tongues, and these pericytes contain contractile elements (Le Beux and Willemot 1978a, b) so that the capillaries can be constricted.

Venomous Animals have been a threat to man at all times, in the warm and wilder regions more than in the temperate areas. People in especially dangerous regions know about these risks and live accordingly. However, with modern tourism and nearly unlimited travel oppor tunities more and more people without experience and knowledge about venomous animals come into contact with them; this book is intended to provide these people with an introduction to the subject. Venomous animals, their habits, their whole ecology and their venoms have been the object or research since the beginning of this century; truly intensive work, how ever, first started about thirty years ago. Medical treat ment therefore has been changed by new insights in the mechanism of action and the constituents of the various venoms. In this regard this book is also directed to physi cians, biologists and chemists to give them an introduc tion in this important and interesting field. New aspects of treatment of envenomations are reported. This book cannot replace bigger textbooks and monographs - they are cited in the references - but it gives an overview and an entry into this field. The original German edition was written at the request of colleagues and students of medicine, biology and chemistry as well as frequent travellers in tropical countries. It was sold out within eight months, thus showing that it really filled a gap."

In der heutigen Zeit nimmt die Brisanz von Viruserkrankungen in der Human- und VeterinArmedizin immer mehr zu. Dazu gehAren nicht nur AIDS und Hepatitis. Leider sind trotz der rasanten Entwicklung in allen Bereichen der Medizin die MAglichkeiten zur BekAmpfung von Virusinfektionen noch begrenzt. Um so wichtiger sind prophylaktische MaAnahmen, wie z. B. Desinfektionsverfahren zur Inaktivierung von Viren. Das vorliegende Buch ist ein praxisorientiertes Nachschlagewerk und faAt den aktuellen Kenntnisstand zur Desinfektion in einem Konzept zusammen. Es enthAlt zum einen Grundlagen A1/4ber Aufbau und Eigenschaften von Viren und zum anderen genaue Handlungsanweisungen zur Virusdesinfektion in der Human- und VeterinArmedizin, im Lebensmittelbereich und bei der Wasseraufbereitung. Unverzichtbar fA1/4r Mediziner, HygienefachkrAfte, Pflegepersonal, GesundheitsbehArden und alle Berufsgruppen, die an der PrAvention von Virusinfektionen interessiert sind.

The last thirty years have seen an unprecedented increase in the discovery of new drugs, and moreover, these drugs, unlike many of the nostra of former times, have varied and powerful pharmacological actions. The occurrence of one or two "drug disasters," together with a change in public attitudes, has made it necessary for governments to introduce legislation to control the intro duction and release of new therapeutic agents, and most countries in the Western World have some form of drug licensing agency. Whole series of regulations have appeared which aim at discovering and defining the toxicity of new drugs. Many of these regulations rely heavily on testing drugs in animals before they are used in man, and at present very extensive and prolonged animal studies are required by most licensing authorities. It is most opportune that Professor Folb has decided to review the present position in this monograph. It is not only inhumane but also wasteful of time and money if extensive animal experiments which have little or no relevance to the human situation are carried out; furthermore, such results may even be dangerously misleading. There is little doubt that some preliminary animal investigations are necessary, but it is essential to keep their relevance under continuous review and to adopt a critical and flexible approach rather than heap regulation upon regulation."

"We pharmacologists must acquire a knowledge of the tools we use . . . Fortunately a surgeon who uses the wrong side of a scalpel cuts his own fingers and not the patient; if the same applied to drugs they would have been investigated very carefully a long time ago . . . More ceterum censeo is perhaps necessary in order to rouse pharmacology from its sleep. The sleep is not a natural one since pharma- cology, as judged by its past accomplishments, has no reason for being tired. " From R. Buchheim Beitrage zur Arzneimittel/ehre, Voss, Leipzig, 1849. Chapter 1 Preface and introduction Methods, clinical pharrnacology and the clinical pharmacologist In this book are brought together the proceedings from lecures and poster-demonstrations at the International Symposium on Methods in Clinical Pharmacology held in Frankfurt, May 6th-8th 1979. The symposium provided a forum for a group of invited clinical pharmacologist to speak on a topic of their own selection. They were asked to place special emphasis on the methodological aspects of their work they considered to be important. Seventeen of the speakers came from overseas. The sym- posium was thus an attempt to establish a methodological basis for further advancements in clinical pharmacology. This book, we hope, will be recognised as documentary evidence that this has been done. Owing to the considerable advancements that have been achieved, it may be forgotten or not realised that clinical pharmacology is a relativelyyoung discipline (7 to 10 years at the most).

This is a little book with no great pretensions. The authors do not claim it to be world-startling nor Nobel- or Pulitzer-prize-winning. It is a valuable primer for pharmacokinetics for those desiring a proper initiation into previously assumed mysteries. It is fully intended as an introduction to the basic concept of pharmacokinetics and will be welcomed by all who wish to apply its principles to their own disciplines, whether in life sciences or medicine, without being confused by excess mathematics. It is edited by two well-known German scientists who are primarily practicing pediatricians and who use pharmacokinetics in their daily work, in a field of medicine where the proper adjustment of doses for infants and children is a delicate and life-preserving art. They were trained as pediatricians and as pharmacokinetists by the world-renowned Profes sor F. HARTMUT DOST, who uniquely synthesized these two disciplines and who, as a pioneer in this field, published the first book on pharmacokine tics in 1953. In their own right, the editors have conducted excellent and unique research on the effect and fate of drugs and have followed up the unexpected changes in drug action accompanying the rapid developments encountered in the initial hours, days, and weeks after birth. You will find some interesting Germanisms in this book a la Professor DOST. I personally feel that these will give some spice to their renditions.

This book is based on Hans Zahner's Biologie der Antibiotica, published in 1965. There is a vast literature on antibiotics, covering chemical, phar macological, and clinical aspects. We have made no attempt to cover this literature comprehensively. Our effort is directed toward discuss ing antibiotics as biological agents. They are substances produced by living cells, yet they are able to inhibit the growth of living cells - in many cases even the cells that produce them. We have taken this apparent biological paradox as our point of departure and have tried to look in this light at the production of antibiotics and at their mode of action. In a sense antibiotics are comparable to mutations. They are useful as tools in the study of metabolism by blocking specific reactions. At the same time their mode of origin and their effects on the organisms that produce them are interesting problems in their own right. We have tried to incorporate both aspects into our consider ations. This little book, designed for biology students and medical stu dents, provides them with a framework into which to fit more specialized and detailed information on antibiotics."

Nachdem die BAnde 1 ("Die wissenschaftlichen Grundlagen") und 2 ("Trockner und Trocknungsverfahren") in dritter bzw. zweiter Auflage schon seit lAngerem verfA1/4gbar sind, schlieAt dieser dritte Band die Neubearbeitung dieses Standardwerkes ab. Damit konnte der besonders von Praktikern geAuAerte Wunsch erfA1/4llt werden, auch auf deren Probleme bezA1/4glich der TrocknungsgA1/4ter einzugehen. In diesem Band 3 werden die produktspezifischen Fragen der Trocknung behandelt. FA1/4r die 10 wichtigsten Produktgruppen - beginnend bei der Landwirtschaft und endend bei der Lackverarbeitung - werden die verschiedenartigsten TrocknungsablAufe und die hierzu gehArenden speziellen Trockner eingehend erlAutert. Besondere Aufmerksamkeit wird den Produkteigenschaften, den TrocknungsablAufen, den mAglichen VerAnderungen beim Trocknen, der Beeinflussung der Gutseigenschaften, der GerAte- und Verfahrenstechnik sowie der Lagerung und Verpackung gewidmet. Die einzelnen BeitrAge stammen aus der Feder von 31 namhaften Fachleuten aus Industrie oder Forschung und ergeben einen zuverlAssigen und praxisnahen Ratgeber fA1/4r die angesprochenen Industriezweige.

A symposium on molecular orbital studies in chemical pharmacology was held at the Battelle Seattle Research Center of Batteile Memorial Institute in Seattle, Washington, U.S.A, on October 20-22, 1969. This volume is a col lection of the lectures presented at that symposium. The use of quantum mechanics to study the actions of molecules of biological importance is being developed by a number of scientists concerned with these phenomena. The advent of high speed computers has made possible the appl i cation of this technique to large molecules, of the kind important in living systems. One result of this expanded computational abi I ity has been the uti I i zation of molecular orbital theory by a group of scientists of diverse backgrounds. The lecturers at this symposium, all interested in molecular orbital theory, have backgrounds in pharmacology, physical chemistry, theoretical chemistry, bio chemistry and medicinal chemistry. The common denominator among these scientists has been the realization that they must search at the primary level of chemical events for explanations of biological phenomena. Since these events are governed to a large extent by the properties of the valence electrons of molecules, molecular orbital theory offers great promise in explaining and predicting biological phenomena. October, 1969 Lemont B. Kier Table of Contents v Preface BERNARD PULLMAN - Electrons in Nucleic Acids and their Cons- tu ent s JAMES R. HOYLAND - Semiempirical MO Theories: A Critique and 31 a Rev i ew of Progress ***** . ***.

Numerous phenomenal advances have been made towards understanding the role of neurotransmitters in the pathophysiology of neurological disorders, and these have resulted in a large number of novel molecules with the potential to revolutionize the treatment and prevention of such disorders. This book provides a comprehensive and detailed explanation of brain neurotransmitters and their receptors and associated channels. It includes a basic introduction, and also discusses the functions and recent advances and their pharmacology, highlighting the role of various computer aided drug design (CADD) strategies for the development of therapeutic ligands to modulate these receptors/ion channels. Written in an easy-to-read style, it is intended for neuroscience and pharmaceutical students and researchers working in the area of brain neurotransmitters.

According to Roth (1964), the term "psychopharmakon" was used for the first time by Reinhardus Lorichius of Hadamar who, in 1548, edited a collection of prayers of comfort and in preparation for death under the title "Psychopharmakon, hoc est: medicina animae." With the introduction of chlorpromazine in 1952, the era of psychopharma cology began. The "psychopharmakon" of the Renaissance and the twentieth century differ from each other in concept and meaning; the spiritual support in times of increased anxiety and fear has been replaced by drugs which "tranquilize" the agitated and brighten the mood of the depressed. Thus, the pioneering discovery by Delay et al. (1952) of the usefulness of phenothiazines in schizophrenics, followed by the report of Loomer et al. (1957) on the antidepressant effect of iproniazid and Kuhn's (1957) observation of the thymoleptic property of imipramine triggered a revolution in psychiatry. Subsequently, numerous new psychopharmaka have been introduced. Parallel with this development, the interest in experimental behavioral research which began to utilize the newly discovered drugs as tools grew rapidly. The experience gained from studies of human and animal behavior found expression in the attempt to introduce a nomenclature and classify psychopharmaka on a purely psychological basis."

Everything students and pharmacy technicians need to master pharmacology and become experienced and proficient practitioners. The second edition includes the latest material on the principles of pharmacology, biopharmaceutics, pharmacokinetics, and pharmacodynamics. Throughout the book, anatomy and physiology are discussed in relation to various disorders and associated pharmacotherapies to give context for how drugs work. Key Features: Extensively updated content, including a new chapter on Pharmacogenomics. Updated commonly used and comprehensive drug tables. Cases to open each chapter, along with questions for discussion. Pronunciations for difficult terms or words such as disease names. Figures and illustrations of essential concepts. Alerts that point out areas of potential dangers or errors, including look-alike/sound-alike drugs. Practice points, including mention of any FDA-required patient medication guides, and any "special" drug storage and dispensing considerations, including beyond-use dating of open multi-use products. The book's content is written to meet ASHP accreditation standards and therefore is one of the most comprehensive books on the market related to pharmacology for technicians.