Half Title Page Pharmacokinetics and Pharmacodynamics of Abused Drugs

Transcription

1 Half Title Page Pharmacokinetics and Pharmacodynamics of Abused Drugs

2 Title Page Pharmacokinetics and Pharmacodynamics of Abused Drugs Edited by Steven B. Karch, MD, FFFLM Consultant Pathologist and Toxicologist Berkeley, California Boca Raton London New York CRC Press is an imprint of the Taylor & Francis Group, an informa business

3 CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed in the United States of America on acid-free paper International Standard Book Number-13: (Hardcover) This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access ( or contact the Copyright Clearance Center, Inc. (CCC) 222 Rosewood Drive, Danvers, MA 01923, CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at and the CRC Press Web site at

4 Contents Chapter 1 Pharmacokinetics: Basic Concepts and Models...1 Chapter 2 Pharmacokinetic Modeling and Pharmacokinetic Pharmacodynamic Correlations...15 Chapter 3 Toxicokinetics and Factors Affecting Pharmacokinetic Parameters...21 Chapter 4 Pharmacokinetics of Specific Drugs...25 Chapter 5 Pharmacodynamics: Effects of Abused Drugs on Human Performance: Laboratory Assessment...65 Stephen J. Heishman, Ph.D. and Carol S. Myers, Ph.D. Chapter 6 Performance-Based Assessment of Behavioral Impairment in Occupational Settings...97 Thomas H. Kelly, Ph.D., Richard C. Taylor, M.A., Stephen J. Heishman, Ph.D., and Jonathan Howland, Ph.D. Chapter 7 Pupillometry and Eye Tracking as Predictive Measures of Drug Abuse Wallace B. Pickworth, Ph.D. and Rudy Murillo, B.A. Chapter 8 Abuse of Marketed Medications Kenzie L. Preston, Ph.D., David H. Epstein, Ph.D., John P. Schmittner, M.D., and Sharon L. Walsh, Ph.D.

5 Preface This volume discusses pharmacokinetics and pharmacodynamics. Chapters 1 through 4 discuss aspects of pharmacokinetics. Chapters 5 through 8 discuss aspects of pharmacodynamics. Pharmacokinetics is defined as the study of the quantitative relationship between administered doses of a drug and the observed plasma/blood or tissue concentrations. The field of pharmacokinetics is concerned with drug absorption, distribution, biotransformation, and excretion or elimination. These processes, in addition to the dose, determine the concentration of drug at the effector or active site and, therefore, the intensity and duration of drug effect. The practice of pharmacokinetics has been used in clinical medicine for many years in order to optimize the efficacy of medications administered to treat disease. Through a consideration of pharmacokinetics, physicians are able to determine the drug of choice, dose, route, frequency of administration, and duration of therapy in order to achieve a specific therapeutic objective. In the same manner, study of the pharmacokinetics of abused drugs aids investigators in addiction medicine, forensic toxicology, and clinical pharmacology in understanding why particular drugs are abused, factors that affect their potential for abuse, how their use can be detected and monitored over time, and also provides a rational, scientific basis for treatment therapies. Pharmacodynamics is the study of the physiological and behavioral mechanisms by which a drug exerts its effects in living organisms. An effect is initiated by the drug binding to receptor sites in a cell s membrane, setting in motion a series of molecular and cellular reactions culminating in some physiological (e.g., opioid-induced analgesia) or behavioral (e.g., alcohol-induced impairment) effect. Drugs typically have multiple effects. For example, a benzodiazepine will produce its primary anxiolytic effect, but may also cause side effects of sedation and impaired performance. The question of the behavioral effects of abused drugs has been the focus of research by behavioral pharmacologists for many decades. Because of the widespread use of psychoactive drugs throughout society, employers have become increasingly concerned about drugs in the workplace and the potential for impaired job performance and onsite drug-related accidents. There are now computerized tests that employers can use to aid in the detection of impaired employees. Some drugs of abuse also produce characteristic effects on the visual system, and for this reason, devices that detect eye movement and function are also being tested for their ability to predict drug ingestion and potential impairment in the workplace. Knowledge of both pharmacokinetics and pharmacodynamics is central to an understanding of drug abuse and its treatment.

6 The Editor Steven B. Karch, M.D., FFFLM, received his undergraduate degree from Brown University. He attended graduate school in anatomy and cell biology at Stanford University. He received his medical degree from Tulane University School of Medicine. Dr. Karch did postgraduate training in neuropathology at the Royal London Hospital and in cardiac pathology at Stanford University. For many years he was a consultant cardiac pathologist to San Francisco s Chief Medical Examiner. In the U.K., Dr. Karch served as a consultant to the Crown and helped prepare the cases against serial murderer Dr. Harold Shipman, who was subsequently convicted of murdering 248 of his patients. He has testified on drug abuse related matters in courts around the world. He has a special interest in cases of alleged euthanasia, and in episodes where mothers are accused of murdering their children by the transference of drugs, either in utero or by breast feeding. Dr. Karch is the author of nearly 100 papers and book chapters, most of which are concerned with the effects of drug abuse on the heart. He has published seven books. He is currently completing the fourth edition of Pathology of Drug Abuse, a widely used textbook. He is also working on a popular history of Napoleon and his doctors. Dr. Karch is forensic science editor for Humana Press, and he serves on the editorial boards of the Journal of Cardiovascular Toxicology, the Journal of Clinical Forensic Medicine (London), Forensic Science, Medicine and Pathology, and Clarke s Analysis of Drugs and Poisons. Dr. Karch was elected a fellow of the Faculty of Legal and Forensic Medicine, Royal College of Physicians (London) in He is also a fellow of the American Academy of Forensic Sciences, the Society of Forensic Toxicologists (SOFT), the National Association of Medical Examiners (NAME), the Royal Society of Medicine in London, and the Forensic Science Society of the U.K. He is a member of The International Association of Forensic Toxicologists (TIAFT).

7 Contributors David H. Epstein, Ph.D. Stephen J. Heishman, Ph.D. Jonathan Howland, Ph.D. Social and Behavioral Sciences Department Boston University School of Public Health Boston, Massachusetts The Office of the Cuyahoga County Coroner Cleveland, Ohio Thomas H. Kelly, Ph.D. Department of Behavioral Science University of Kentucky College of Medicine Lexington, Kentucky Rudy Murillo, B.A. Carol S. Myers, Ph.D. National Institute of Health Wallace B. Pickworth, Ph.D. Battelle Centers for Public Health Research and Evaluation Kenzie L. Preston, Ph.D. John P. Schmittner, M.D. Richard C. Taylor, M.A. Sharon L. Walsh, Ph.D. Department of Behavioral Science Center on Drug and Alcohol Research University of Kentucky College of Medicine Lexington, Kentucky