Posts Tagged ‘Pharmacology’

Neurochemical Pharmacology

Neurochemical Pharmacology — A Tribute to B.B. Brodie. Fidia Research Foundation Symposium Series. Volume 2

Edited by E. Costa

New York, Raven Press, 1989. 369 pp.

This book represents the proceedings of a Symposium held in April 1988 to honor Dr. Bernard Brodie, who died in February 1989 while the book was in press. The book consists of a series of articles in neuropharmacology by many of the world’s leading experts in the field and is a fitting tribute to Dr. Brodie and his remarkable career.

Dr. Brodie was for many years director of the Laboratory of Chemical Pharmacology at the National Heart Institute. Under his direction, the laboratory played an important role in establishing a new approach to pharmacology, termed by the editor of this book “Neurochemical Pharmacology.” This approach, elaborated in the 1950—60s, was based on the view that it would ultimately be possible to understand all of the brain’s functions, including mental functions, on the basis of the underlying biochemistry of the brain. The approach had an enormous influence on the biomedical sciences and provided the basis for a generation or two of research in biological psychiatry. An impressive number of investigators trained in the Brodie laboratory during this time, among whom were Julius Axelfrod, Jack Cooper, Erminio Costa, and Solomon Snyder. In fact, the extraordinary productivity of Dr. Brodie’s laboratory and its disciples was the subject of a recent book, Apprentice to Genius by Robert Kanigel.

The current volume is divided into four sections entitled: “Transmitters,” “Transmitter Function,” “Receptor Modulation,” and “Signal Transduction.” The following articles are particularly noteworthy: Arvid Carlsson presents a challenging overview of the role played by brain dopamine systems in motor and mental functions. Tomas Hokfelt and others offer a comprehensive and helpful review of the localization of peptide neurotransmitters in monoaminergic and cholinergic neurons. Of note in the second section are reviews of the role of monoaminergic systems in satiety (by S. Garattini and others) and stress (by Roger Maickel). An article by S. Roy and others in the third section describes attempts partially to purify opiate receptors and prepare monoclonal antibodies to the receptor. K. Fuxe and colleagues describe “receptor/ receptor interactions,” the critical idea that neurotransmitter systems interact with one another, making it likely that psychotropic drugs influence brain function through effects on multiple types of neurotransmitter and receptor systems. Goran Sedvall and others describe their experience in the use of positron emission tomography to image neurotransmitter receptors in living human subjects. In the fourth section. Fridolin Sulser and Elaine Sanders-Bush offer a very thoughtful and up-to-date analysis of the probable mechanisms involved in the clinical actions of antidepressant treatments and experimental approaches. Erminio Costa presents some of the data obtained over the years, much from his own laboratory, underscoring the importance of the role played by the regulation of gene expression in adaptive changes in brain function.

As would be expected, the quality and focus of the articles in this book are variable. Despite the considerable delay in publication of this volume, most of the articles remain up to date. The book would be useful to individuals in the field for its reviews and to individuals only peripherally associated with the field as a more general overview of current research in neuropharmacology.

Managing Side Effects of Psychotropic Drugs

Managing Side Effects of Psychotropic Drugs: A Clinical Handbook for Health Care Professionals

Oyewumi LK, de Wit R

London (ON): Zxmaxx Communications; 1998. 263 pp. with index

ISBN 0-9684372-0-6 (paper)

As the authors note in their Introduction, the plethora of new psychopharmacological agents introduced in the last decade has led to an extensive literature on the use and proposed mechanisms of action of these drugs. However, the literature on the side effects of these medications is limited at best. Rare is the patient who does not have at least some side effects from our treatments, yet far too often the patient’s only source of information on the drug and its side effects is the Compendium of Pharmaceutical and Specialties (CPS).1 Unfortunately, more often than it should be, the CPS is also the physician’s side effect “handbook”!

The authors have attempted to bridge this gap in our psychopharmacological knowledge base with a user-friendly, spiral-bound “handbook” on managing side effects of psychotropic drugs. They have done a good job.

The 8 chapters begin with an overview of the different classes of psychoactive agents, which includes an excellent table listing all antipsychotic and antidepressant agents (generic and trade names) and the average daily dose ranges. Unfortunately, hypnotics, anxiolytics, mood stabilizers and stimulants are omitted from the tables without explanation.

Chapter 2 reviews predisposing risk factors, epidemiology and classification (e.g., predictable v. idiosyncratic, initial v. tardive) of side effects, while the bulk of the handbook — Chapter 3 — is a detailed overview of these side effects. The format of Chapter 3 is unique, with “generic” headings such “dermatological” followed by subheadings (e.g., acne, allergic rash, alopecia, etc.). Under the subheadings, prevalence, occurrence, presentation, mechanism of action, and commonly associated drugs with this specific side effect are outlined. This is a very useful presentation for mental health professionals (physicians, nurses and students), but I suspect that drug “consumers” would have difficulty navigating this section. (Would they know to look under dermatological and alopecia for “hair loss”?)

Chapter 4 is a more academic chapter on evaluating side effects, and provides a listing of the various rating scales available to measure and monitor side effects.

Chapter 5, “Management of Psycho-tropic Drug Side Effects/’ offers very practical, clinically relevant treatment guidelines. These “bedside tips” in the management of dry mouth, pruritis, incontinence, etc., is clearly lacking in most pharmacology and clinical psychiatry textbooks.

The last 3 chapters review the consequences of drug side effects (compliance, economic effects); administrative aspects (the lack of postmarketing data on side effects); and psychodynamic/psychological aspects of side effects, such as placebo effect, “catching” side effects, drug side effects, and the transference/counter-transference in the doctor-patient relationship. All good stuff! The bibliography and references are detailed and up to date.

This is a very good start as a handbook that will be of value to psychiatrists, residents, nurses and consumers. It should find its way to psychiatric inpatient units, mental health centres and mental health support organizations as an excellent reference book. I do hope the authors are working on their second edition, as new drugs such as citalopram, reboxitine, and mirtazapine are already here, and additional new drugs could soon make this useful book outdated.

Some minor editing (e.g., in one section, it should have read “pharmacodynamic” not “psychodynamic” parameters) and combining the chapters on identifying and managing side effects would be helpful in the next edition. Further, more detail on the specifics of managing side effects (the book is entitled Managing Side Effects), such as specific dosages of drugs used to treat specific side effects, would enhance this work.

Pharmacology of Anxiolytic Drugs

Pharmacology of Anxiolytic Drugs. WHO Expert Series on Neuroscience, vol. 3

Racagni G, Masotto C, Steardo L

Seattle (WA): Hogrefe and Huber; 1997. 132 pp. with index

ISBN 0-88937-088-5 (cloth)

This monograph forms part of the World Health Organization’s expert series in neuroscience, which is intended to help prevent or control mental neurological disorders and psychosocial problems, as well as to ensure broad use of mental health knowledge in general health care within WHO member states. It is indeed a textbook of pharmacology and should be viewed as such.

The authors must be world renowned in the field of pharmacology and its clinical application, although I could find only one citation by one of the authors (a publication in Nature in 1979) through MEDLINE. As well, the authors do not cite themselves in the book, indicating either that they are modest or that their publications are now aged. The University of Milan, however, has a reputation for expertise in pharmacology.

The book begins with a succinct history of the search for anxiolytics. The comprehensive contents of the book are then divided into 4 groups. Group 1, on benzodiazepines, is the most comprehensive of the chapters and includes a detailed description of each of the benzodiazepines, including their 2-dimensional chemical formulae. There is an extensive discussion of action, side effects, dependance and interactions. Group 2 discusses compounds with benzodiazepine-like activity, and details agonists, partial-agonists and antagonists. Group 3 reviews compounds that act on nonbenzodiazepine receptors and includes a large discussion of the role of serotonin in anxiety. Group 4 considers the role of antidepressants as anxiolytics and includes tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, α2-adrenergic blockers and β-blockers.

Only generic drug names are used throughout the book.

This book is a very comprehensive, well-organized and crisp discussion of anxiolytic drugs, and includes scientifically backed clinical use. Remember, the title is Pharmacology of Anxiolytic Drugs, and so the rather dry chemical formulae, pharmacokinetics and pharmacodynamics seem clinically sterile. The authors include substances that we prescribe routinely as well as medications that are not very commonly used in this country but may be in other parts of the world.

There are other texts, such as those by Goodman and Gilman or by Schatzberg and Nemeroff, that are more enjoyable to read, but they are not as complete as this book, and they cannot be held in one hand. This book is not a light read, but is a good, comprehensive reference.

My main criticism is that there is a lack of reference to the clinical situation, but then, this is a textbook of pharmacology.

The readership is meant to include nurse practitioners, social workers, family physicians, and others, but I believe they would use this book only as a reference text. Psychiatrists, residents in psychiatry and anesthetists would find this book quite valuable.

Handbook of Essential Psychopharmacology

Handbook of Essential Psychopharmacology

Pies RW

Washington: American Psychiatric Press; 1998. 416 pp. with index

ISBN 0-88048-765-8

This concise, slim, well-edited paperback review of essential psychopharmacology is divided into 4 chapters, on antidepressants, anti-psychotics, anxiolytics and sedative-hypnotics, and mood stabilizers, including novel anticonvulsants. Each chapter begins with an overview that includes drug class indications, mechanism of action, pharmacokinetics, common side effects, drug interactions, augmentation strategies, and use in special populations, such as pregnant women, the elderly, and develop-mentally disabled patients. Each chapter ends with a series of well-selected, clinically relevant questions, along with answers and a case discussion that illustrate and clarify various teaching points.

The chapter on antidepressants is a general review of the literature in that area. I often hear residents expressing their concern about the inability to keep up with the number of new antidepressants being introduced into our pharmacopoeia. It is also not uncommon to meet residents who, in their final years of training, have yet to prescribe or be familiar with the frequent clinical challenges in using tricyclic antidepressants or monoamine oxidase inhibitors. This chapter provides a user-friendly review of the newer agents and also the “older” classes of antidepressants. The author succeeds in assembling the information in a way that is not information overload and yet is academically and clinically useful, particularly for residents. This is made possible in part by the author’s careful use of various tables, which compare clinical issues such as off-label indication, neurotransmitter effects, side effects and their basic management, drug-drug interactions, and therapeutic drug monitoring.

The chapter on antipsychotics provides the reader with a concise, comparative review of conventional and atypical antipsychotics. Tables illustrate comparative mechanisms of action and side effects, along with strategies for antipsychotic potentiation. This latter issue is something clinicians are often faced with, particularly in patients who cannot tolerate or respond poorly to antipsychotics, including the newer atypicals. The question section deals with disparate clinical areas, and has a very good review of neuroleptic malignant syndrome.

The chapter on sedative-hypnotics and anxiolytics has several useful charts, such as a diazepam equivalency chart, a chart of clinical indications, and a table on the off-label uses for clonidine and β-blockers.

The final chapter, on mood stabilizers, has a clinically relevant review of lithium, valproate and carbamazepine. The author has included an up-to-date review of gabapentin and lamotrigine and their potential interactions with other commonly used psychiatric medicines.

As a psychiatric educator, I was very pleased with the question-and-answer section in this book. In fact, I have yet to come across a similar psychiatric textbook that effectively asks well-selected clinically relevant questions and provides the reader with practical answers. I do like how the author began by providing the basic informational background to these various compounds, followed by questions forcing the reader to “work” the information, and rounding up with a practical case to apply this new-found knowledge.

I found the graphs, diagrams and tables very useful, and very good complements to the written material, often clarifying the concepts presented. The large print of the text is very easy to read. The information is presented in a systematic way and includes extensive references to the literature for those interested in pursuing more knowledge on the topics.

Dr. Pies’ book is intended to be a “micropedia” for residents and busy clinicians. I see it as a very useful, helpful teaching textbook and resource for its intended audience. Psychiatric psychopharmacology has had a history of being somewhat limited by the absence of clearly established evidence-based algorhythmic approaches to treatment. That being said, there have recently been useful treatment guidelines for the diagnosis and treatment of major depressive disorder, bipolar disorder, and schizophrenia, among others. The author may wish to incorporate some of these reviews in future work. Overall, I congratulate the author and recommend this text.

Psychiatric Comorbidity in Epilepsy

Psychiatric Comorbidity in Epilepsy: Basic Mechanisms, Diagnosis, and Treatment

H. Mc-Connell, Peter J. Snyder, editors

Washington (DC): American Psychiatric Press; 1998

ISBN 0-88048-853-0 (hardcover)

There is a fascinating and complex interrelation between psychiatric pathology and epilepsy. Historically, epilepsy was known as the “sacred” disease because of its alleged association with astrology, with the divine, and with demoniacal possession. Despite Hippocrates’ assertion that epilepsy “is no more divine nor more sacred than other diseases, but has a natural cause like other diseases,” these misconceptions continued until well into the 19th century, when the neuropathologic origins of epilepsy were identified.

However, the association between epilepsy and psychiatric illness did not cease when it was identified as a neurologic condition. People with epilepsy have an increased prevalence of both affective and schizophreniform disorders. Personality and adjustment disorders are common and seizures may be simulated by conversion states. Epilepsy also has profound socioeconomic implications for the sufferer. It is perhaps therefore the “psychosomatic” illness par excellence.

This book is a compendium of the psychiatric conditions associated with epilepsy. Its 12 chapters cover the historic, physiologic, pathologic, clinical and social aspects of epilepsy. There is an excellent chapter on the changing systems of classification of the epilepsies; the current international classification bears little resemblance to the systems used even 50 years ago. The advent of sophisticated investigative techniques for studying neuronal activity, such as EEG recordings and neuroimaging, has given this system a firm neuroanatomical basis, and has helped to integrate the neuroanatomical changes with the clinical seizure pattern.

There are excellent chapters on the neuropsychological assessment of patients with seizures, and on the mood disorders and psychoses associated with epilepsy. The latter chapter is of particular interest because recent developments have shown that there are lesions in the medial temporal structures of the brain in both epilepsy and schizophrenia. This etiologic overlap may explain not only the increased prevalence of schizophreniform psychoses in patients with epilepsy, but also suggests that there may be a neurophysiologic overlap at the neurotransmitter level between these seemingly disparate conditions.

Perhaps the 2 most useful chapters in the book are those on pharmacology. One reviews the behavioural effects of antiepileptic drugs, the other discusses the treatment of psychiatric disorders in patients with epilepsy. They provide an excellent state-of-the-art summary of the pharmacology of epilepsy and give many practical suggestions about the use of psychotropic agents and their effects on seizure threshold.

The book ends with 2 chapters on the “social” part of biopsychosocial aspect of epilepsy: one on family systems theory and the other, written by a man with epilepsy, entitled “Living with Epilepsy.” The latter is of special interest because the experiences he describes and the problems he raises are not dealt with elsewhere in the book. For example, he describes memory dysfunction, post ictal pain, social rejection and communication difficulties with his neurologists — experiences that are surely not unique to people with epilepsy. It would have rounded out the book if these consumer-driven issues had been dealt with in the clinical sections.

There are weaknesses in the book. The history of epilepsy is long and colourful and it is unfortunate that it is described here in a trite and cliche-ridden way. The chapter on diagnosis and treatment of nonepileptic seizures was superficial and unhelpful. It is puzzling why such seizures should be described in negative language when acceptable terms such as “conversion” or even “hysterical” seizures are available.

On the whole, however, this is a comprehensive, well structured and well referenced book. Each chapter ends with a conclusion that summarizes the main points in that chapter. I was very glad also to see

a uniform and consistent use of the term “people with epilepsy” rather than “epileptic” throughout the book. The word “epileptic” brands the sufferer in a pejorative manner and reinforces the very stigma we try to avoid. If only psychiatrists would similarly use the term “people with schizophrenia” rather than “schizophrenics”!

This book is highly recommended to psychiatrists, neurologists, neuropsychologists and others who see people with epilepsy in their practice.

Biology of Schizophrenia and Affective Disease

Biology of Schizophrenia and Affective Disease

SJ Watson, editor

Washington (DC): American Psychiatric Press; 1996. 540 p

Over the past 30 y and particularly over this last decade — the decade of the brain — there has been marked acceleration of research efforts in the fields of neuroscience, molecular genetics, and biochemistry of mental disorders. Coupled with increasing sophistication in clinical observations, there has been an explosion of information about mechanisms of normal and pathological brain function. Although we are still far away from a clear understanding of the psychopathology behind 2 of the major psychiatric disorders, schizophrenia and affective disorders, substantial information already exists linking subcellular biological activities and the functioning of the neurons. The integration of information from molecular genetics, biochemistry, pharmacology, brain anatomy, and neuroimaging has advanced our knowledge about the impact of mental illness on specific brain neural circuits and their response to treatment. The recent and evolving knowledge about such specific brain circuits has inspired a new strategy of pharmacological targeting in the treatment of mental disorders. In this context, this book has its major strength focusing on the interface between several mental disorders and the genetics, pharmacology, neurochemistry, brain imaging, and postmortem studies reported by the researchers themselves, who are active in these fields.

The book emanates from contributions by a number of well-known and accomplished researchers in neuroscience to the 73rd meeting of the Association for Research in Nervous and Mental Disease, which took place in New York in 1993. One major feature of that meeting was that speakers were asked not only to present an overview of their field and their own work but also to provide their views on future developments. The book includes 17 chapters that deal with topics related to schizophrenia, affective disorders, infantile autism, an introductory chapter by the editor himself, and an overview chapter with discussions at the end. The introductory chapter by Watson presents an overview of mood disorders, autism, and schizophrenia from a clinical perspective and sets the stage for the basic science chapters that follow. The chapter written by Akil, “Biology of Stress from Periphery to the Brain,” explores the concept of “stress” as a trigger for psychiatric illnesses. The contributor documents her extensive work on the regulation of the limbic-hypothalamic pituitary-adrenal access and makes clear the well-known point that “the stressful nature of any given stimulus resides less in its objective characteristics and more in the organism’s ability to cope with it” (p 15).

The 5 chapters that relate to affective disorders include a contribution by Blakely about norepinephrine and serotonin transporters that highlights the progress on the molecular targeting of antidepressant effects. Another chapter, by Owens and others, deals with peptides and affective disorders and concludes with an account of future directions in the area based on the development of such new approaches as the application of ribonuclease (RNASE) protection assay, the expanding knowledge of the peptidergic brain circuits, and the ability to image central nervous system tissue with magnetic resonance imaging and positron emission tomography technology. The chapter about the mechanism of action of antidepressants by Berman and others elegantly reviews information, both basic and clinical, about well-known monoamines that have been explored in terms of their mechanism of action: serotonin, norepinephrine, dopamine, and neuropeptides. The chapter delves beyond the monoamines theory, however, by exploring postreceptors signal transduc-tion and neuroanatomy of antidepressant action and their relevance for the development of novel treatment approaches to depressive disorders. The chapter by Raichle and Drevets maps brain circuits relative to brain function and explores its implication for psychiatric illnesses. Another excellent chapter, by Mann and others, presents an up-to-date review of available information spanning more than 2 decades about postmortem studies of suicide victims.

The book includes 8 chapters related to schizophrenia. The chapter by Benes entitled “Excitotoxicity in the Development of Cortico Limbic Alterations in Schizophrenia” examines both the proposition that schizophrenia is a neurodegenerative disorder and the evidence for glutamatergeric dysfunction in schizophrenia. Goldman-Rakic, in her chapter, “Dissolution of Cerebral Cortical Mechanisms in Schizophrenia,” advances the argument from a neurocognitive perspective about the importance of frontal cortex and the role of working memory in the disordered thinking of patients with schizophrenia. Using postmortem studies, Kleinman and Nawroz provide evidence for the involvement of dorsal lateral prefrontal cortex, the hippocampus, and the entrorhinal cortex in the pathology of schizophrenia. An up-to-date review of the “Epidemiology and Behavioral Genetics of Schizophrenia” is provided by Tsuang and Faraone. Khan and her colleagues, in their excellent chapter, “Revisiting the Dopamine Hypothesis in Schizophrenia,” advance the argument for schizophrenia as both a hyper- and hypodopamine state, thus linking such diverse elements of the broad spectrum of symptomatology as positive and negative symptoms as well as neurocognitive deficits. The contributions of neuroimaging to the understanding of the psychopathology of schizophrenia is well presented in a chapter by Van Horn and colleagues. “Abnormal Frontotemporal Interactions in Patients with Schizophrenia,” by Friston and others, provides results of their extensive work using neuroimaging in examining functional connectivity by studying corticocortical interactions in patients with schizophrenia. The last contribution related to schizophrenia is the excellent chapter by Meltzer and others, “Exploring the Mechanism of Atypical Anti-psychotic Medications,” which provides evidence for Meltzer’s recent argument for a major role for serotonergic mechanics in the improved therapeutic effects of atypical antipsychotics, particularly their tendency to produce significantly fewer extrapyramidal side effects.

The chapter devoted to “Linkage and Molecular Genetics of Infantile Autism” by Ciaranello reports the results of extensive linkage studies of 1 of the least understood disorders: infantile autism. This chapter, coming after the recent sudden and untimely death of its author, serves as a memorial to a distinguished scientist.

Overall, the book is a significant contribution, providing valuable information for understanding the mechanisms of normal and pathological brain function and its relevance to schizophrenia and affective disorders. The book makes a good attempt to integrate information at the level of functional neurocircuits. It should be of interest not only to neuroscientists but also to psychiatrists, neurologists, and psychologists. Although the book is about basic neuroscience, its relevance to clinicians is obvious because it explores the basic biological brain functions in relation to mental

illness. The book reads well, which reflects the skills of its editor, Stanley Watson. The only regret I have is that it took 3 y to publish the proceedings of that 73rd meeting of the Association for Research in Nervous and Mental Disease, which is rather a relatively long time in terms of the rapidly evolving neuroscience research. Nevertheless, the book is a valuable contribution and continues to be equally relevant today.

Essential Psychopharmacology: Neuroscientific Basis and Practical Applications

Essential Psychopharmacology: Neuroscientific Basis and Practical Applications

SM Stahl

New York: Cambridge University Press; 1996. 379 p

If you, like many others, admired Stephen Stahl’s beautiful slides on neuropharmacology during one of his many lectures at psychiatric meetings, you can now have his graphics in 1 book, all 300 of them. His charming drawings intelligently reduce very technical neuroscience concepts to very comprehensible illustrations.

The book will appeal to a wide readership. It provides an easily readable introduction to neurobiological concepts for the novice, and for the practicing psychiatrist, it offers a quick review of the principles. Never before have I had such an enjoyable refresher course on neuropsychopharmacology. The book will also appeal to educators, whether they are teaching nurses, medical students, residents, or physicians taking continuing medical education.

The text is remarkably lucid, instructive, and entertaining, and yet it remains an authoritative representation of the field. In the rapidly expanding arena of neurosciences, where it is so difficult to keep up with the explosion of knowledge, the book is commanding yet easy to assimilate. The text will certainly prepare the reader well for dealing with more complex professional literature. The reader can sense that the material has been tested in many lectures and polished for clarity.

One particularly delightful aspect of the book is its attempt to apply the principles of programmed learning. Thus it is possible to acquire a good overview of the material by 1 st going through the book from beginning to end and reviewing only the color graphics and the corresponding legends. In the 2nd reading, the graphics may be reviewed while the text is read in detail. Finally, a rapid review of the graphics can serve ‘ as a solid refresher.

The text is accompanied by a wealth of high-quality color graphics, simplified diagrams, and funny cartoons. This whimsical approach serves the author very well when dealing 1 with the neuroscience issues, although some of his clinical points come across as less happy that way. In the clinical parts, there are a few inaccuracies, and some oversimplifications went, in my opinion, a bit too far (for example, “virtually every known antidepressant has the same response rate namely . . . 67%”; or suggestions of the genetic basis of posttraumatic stress disorder). If you are a visual learner and are looking for an excellent book on the basic neuropharmacology of psychotropic drugs, I suggest you buy this one.