Pharmacokinetics and Pharmacodynamics of Abused Drugs

204 Pages·2016·3.81 MB·English

by  Steven Karch MD FFFLM (Author)

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Half Title Page
Pharmacokinetics
and
Pharmacodynamics
of
Abused Drugs
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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
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Contents
Chapter 1 Pharmacokinetics: Basic Concepts and Models........................................................1
Amanda J. Jenkins, Ph.D.
Chapter 2 Pharmacokinetic Modeling and Pharmacokinetic–Pharmacodynamic
Correlations..............................................................................................................15
Amanda J. Jenkins, Ph.D.
Chapter 3 Toxicokinetics and Factors Affecting Pharmacokinetic Parameters.......................21
Amanda J. Jenkins, Ph.D.
Chapter 4 Pharmacokinetics of Specific Drugs........................................................................25
Amanda J. Jenkins, Ph.D.
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.............127
Wallace B. Pickworth, Ph.D. and Rudy Murillo, B.A.
Chapter 8 Abuse of Marketed Medications............................................................................143
Kenzie L. Preston, Ph.D., David H. Epstein, Ph.D., John P. Schmittner, M.D.,
and Sharon L. Walsh, Ph.D.
Index..............................................................................................................................................175
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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 pharmaco-
kinetics is concerned with drug absorption, distribution, biotransformation, and excretion or elim-
ination. 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 med-
icine, 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 impair-
ment) 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.
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The Editor
Steven B. Karch, M.D., FFFLM, received his under-
graduate degree from Brown University. He attended grad-
uate school in anatomy and cell biology at Stanford Univer-
sity. 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 Med-
ical 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 trans-
ference 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 2006. 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).