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Clinical Toxicology and Clinical Analytical Toxicology
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20 Clinical Toxicology and Clinical Analytical Toxicology Priya Tailor and Shayne Gad
Introduction
part of either animal toxicity studies or the investigation of poisoning in a wide variety of other species. As such, one could consider clinical analytic toxicology to have at least three separate (but not independent) areas of investigation – clinical chemistry, tissue evaluations (histopathology, covered in another entry in this book), and forensic toxicology. To a degree, each of these is a part of a clinical analytic toxicology evaluation. Clinical chemistry evaluations are commonly recommended in animal toxicology studies. Regulatory agencies such as the U.S. Food and Drug Administration and the U.S. Environmental Protection Agency have set guidelines for clinical pathology testing in nonclinical toxicity and safety studies. Measurement of chemical components of biological fluids allows the toxicologist to do serial sampling, detect metabolic injury or organ-specific effects, and perhaps gain additional information helpful in establishing the no-effect level and determining the mechanism of toxicity. When using serum enzymes as markers of tissue or organ damage, the enzyme of interest must reasonably reflect pathological change in a specific tissue, organ, or group of organs and must be easily measured. The tests that are routinely performed provide information concerning hepatocellular and biliary integrity and function, renal function, carbohydrate, protein and lipid metabolism, and mineral and electrolyte balance. Modern analytical techniques require only small sample volumes to make accurate determinations, allowing in-life evaluations of effects in mice and larger species at multiple times during the course of a study without compromising animal health. Forensic toxicology evaluates exogenously sourced materials in the body, with the information generated
Clinical toxicology includes physicians and scientists involved with the understanding of the diagnosis and treatment of poisoning. Some clinical toxicologists work with poisoned patients through poison control (and poison information and treatment) centers (see Poison Centers chapter), while others are in a university, hospital, government agency, or in industry. A related discipline is veterinary toxicology, dealing with the diagnosis and treatment of poisoning in animals (see Veterinary Toxicology chapter). The function of clinical analytic toxicology (also called clinical chemistry in toxicology) is to provide, via laboratory analysis of tissues and fluids, evaluations of the qualitative and quantitative characteristics of (1) specific endogenous and potentially adverse exogenous chemical components present in samples of blood, urine, feces, spinal fluid, and tissues, (2) changes in the formed elements of the blood and their function, and (3) histological changes in tissues and the components of the blood. The purpose is to help identify abnormal or pathological changes or their causes in organ system functions. The most common biological specimens used in such analyses are blood, urine, and selected postmortem tissue samples. Many different tests exist to test for almost any type of chemical or cellular component in blood or urine; for example, blood glucose, electrolytes, enzymes, hormones, lipids (fats), other metabolic substances, proteins, red blood cells, white blood cells, and platelets. The tests used here were all initially developed for human clinical medicine, and may not possess the same utility when performed as
INFORMATION RESOURCES IN TOXICOLOGY, FOURTH EDITION
183
Copyright © 2009 by Academic Press. All rights of reproduction in any form reserved.
184
Resources
having potential legal uses from the determination of whether harm was done by the intentional or accidental exposure to toxic materials (see Forensic Toxicology chapter). The techniques employed are those of analytical toxicology (see Analytical Toxicology chapter).
Related chapters Analytical toxicology Forensic toxicology Poison control centers Veterinary toxicology
intoxication, incidence and frequency of poisoning, mechanisms of action, clinical signs and symptoms of poisoning and management guidance. Haddad LM, Shannon MW, Winchester JF (1998) Clinical Management of Poisoning and Drug Overdose, 3rd edition Philadelphia, PA: WB Saunders Company. Hoffman R S, Nelson L S, Howland MA, Lewin NA 2006 Goldfrank’s Toxicologic Emergencies New York: McGraw-Hill Professional
Resources Books Barile FA (2004) Clinical Toxicology: Principles and Mechanisms Boca Raton, FL: CRC Press LLC. This book focuses on the current and contemporary principles and mechanisms of clinical toxicology. It examines the complex interactions associated with clinical toxicological events and chemical exposure. It also addresses the signs and symptoms of diseases and pathology caused by toxins and drug administration. Topics such as biological and chemical toxins, changes in protocols for managing toxic ingestions, new antidotes, and changes in particular treatments are also covered. Dart RC (2004) Medical Toxicology, 3rd edition Philadelphia, PA: Lippincott Williams & Wilkins. Ford M (ed.) Delaney K, Ling L, Erickson T (2000) Clinical Toxicology Los Angeles, CA: W.B. Saunders. This book provides a detailed outline needed to assess, diagnose, and manage poisoned and overdosed patients. Clinically oriented and practical, this complete, yet concise, resource is organized to give clinicians quick access to fundamental toxicological information. Gossel TA, Bricker JD (1994) Principles Of Clinical Toxicology 3rd edition New York: Raven Press Ltd. In this third edition, the editors have made numerous changes for managing poison ingestion and treatment selection. It focuses primarily on the classes of toxic agents, their common sources and usual methods of
Katzung BG (2006) Basic & Clinical Pharmacology (Basic and Clinical Pharmacology) 10th edition New York: McGraw-Hill Medical. The 10th edition of this book has up-to-date information on integration of basic with clinical science as well as in-depth coverage of key pharmacology topics. For example it covers basic principles to pharmacologic considerations for autonomic, cardiovascular–renal, smooth muscle, CNS, endocrine, antimicrobial, and chemotherapeutic and immunotherapeutic drugs. It is also updated with dozens of new, recently approved drugs, including monoclonal antibodies. Ling L, Clark RF, Erickson T, Trestrail JH (2001) Toxicology Secrets, 1st edition Philadelphia, PA: Hanley & Belfus. This text contains 64 chapters covering topics such as general toxicology principles, over-the-counter drugs, prescription medications, antibiotics, cardiac drugs, psychopharmacologic medications, drugs of abuse, metals, chemicals, pesticides, gases, food poisoning, botanicals, envenomations, and toxic terrorist threats. Lyle DP (2004) Forensics for Dummies Hoboken, NJ: Wiley Publishing, Inc. Wecht C, Saitz G, Curriden M (2003) Mortal Evidence: The Forensics behind Nine Shocking Cases Amherst, New York: Prometheus Books.
Review articles Bateman D (2005) Clinical toxicology: Clinical science to public health. Clin. Exp. Pharmacol. Physiol. 32(11): 995–998. Breckenridge A (1996) A clinical pharmacologist’s view of drug toxicity. Br. J. Clin. Pharmacol. 42(1): 53–58.
20. Clinical Toxicology and Clinical Analytical Toxicology
Wiener SW, Hoffman RS (2005) Trends in clinical toxicology: Advances that may change your practice. Basic Clin. Pharmacol. Toxicol. 97(1): 1–7.
Journals Basic & Clinical Pharmacology & Toxicology British Journal of Clinical Pharmacology Clinical and Experimental Pharmacology and Physiology Clinical Toxicology (formerly the Journal of Toxicology: Clinical Toxicology) Forensic Toxicology Journal of Forensic Medicine and Toxicology Journal of Medical Toxicology General interest works Howdunit Book of Poisons: A Guide for Writers Stevens S, Bannon A (2007) Writers Digest Books. Poisons: From Hemlock to Botox to the Killer Bean of Calabar Macinnis P (2005) Arcade Publishing.
185
Databases (U.S.) National Library of Medicine. Drug Information Portal. http://druginfo.nlm.nih.gov The Drug Information Portal provides a gateway to current and accurate drug information. Information for more than 15 000 drugs is available for searching. Poisindex®, Thompson Healthcare Web: www.micromedex.com/products/poisindex/
Organizations American Academy of Clinical Toxicology Web: www.clintox.org American Association of Poison Control Centers Web: www.aapcc.org American Board of Forensic Toxicology Web: www.abft.org American College of Medical Toxicology Web: www.acmt.net European Association of Poisons Centres and Clinical Toxicologists Web: http://www.eapcct.org Society of Forensic Toxicology Web: www.soft-tox.org
20 Clinical Toxicology and Clinical Analytical Toxicology Priya Tailor and Shayne Gad
Introduction
part of either animal toxicity studies or the investigation of poisoning in a wide variety of other species. As such, one could consider clinical analytic toxicology to have at least three separate (but not independent) areas of investigation – clinical chemistry, tissue evaluations (histopathology, covered in another entry in this book), and forensic toxicology. To a degree, each of these is a part of a clinical analytic toxicology evaluation. Clinical chemistry evaluations are commonly recommended in animal toxicology studies. Regulatory agencies such as the U.S. Food and Drug Administration and the U.S. Environmental Protection Agency have set guidelines for clinical pathology testing in nonclinical toxicity and safety studies. Measurement of chemical components of biological fluids allows the toxicologist to do serial sampling, detect metabolic injury or organ-specific effects, and perhaps gain additional information helpful in establishing the no-effect level and determining the mechanism of toxicity. When using serum enzymes as markers of tissue or organ damage, the enzyme of interest must reasonably reflect pathological change in a specific tissue, organ, or group of organs and must be easily measured. The tests that are routinely performed provide information concerning hepatocellular and biliary integrity and function, renal function, carbohydrate, protein and lipid metabolism, and mineral and electrolyte balance. Modern analytical techniques require only small sample volumes to make accurate determinations, allowing in-life evaluations of effects in mice and larger species at multiple times during the course of a study without compromising animal health. Forensic toxicology evaluates exogenously sourced materials in the body, with the information generated
Clinical toxicology includes physicians and scientists involved with the understanding of the diagnosis and treatment of poisoning. Some clinical toxicologists work with poisoned patients through poison control (and poison information and treatment) centers (see Poison Centers chapter), while others are in a university, hospital, government agency, or in industry. A related discipline is veterinary toxicology, dealing with the diagnosis and treatment of poisoning in animals (see Veterinary Toxicology chapter). The function of clinical analytic toxicology (also called clinical chemistry in toxicology) is to provide, via laboratory analysis of tissues and fluids, evaluations of the qualitative and quantitative characteristics of (1) specific endogenous and potentially adverse exogenous chemical components present in samples of blood, urine, feces, spinal fluid, and tissues, (2) changes in the formed elements of the blood and their function, and (3) histological changes in tissues and the components of the blood. The purpose is to help identify abnormal or pathological changes or their causes in organ system functions. The most common biological specimens used in such analyses are blood, urine, and selected postmortem tissue samples. Many different tests exist to test for almost any type of chemical or cellular component in blood or urine; for example, blood glucose, electrolytes, enzymes, hormones, lipids (fats), other metabolic substances, proteins, red blood cells, white blood cells, and platelets. The tests used here were all initially developed for human clinical medicine, and may not possess the same utility when performed as
INFORMATION RESOURCES IN TOXICOLOGY, FOURTH EDITION
183
Copyright © 2009 by Academic Press. All rights of reproduction in any form reserved.
184
Resources
having potential legal uses from the determination of whether harm was done by the intentional or accidental exposure to toxic materials (see Forensic Toxicology chapter). The techniques employed are those of analytical toxicology (see Analytical Toxicology chapter).
Related chapters Analytical toxicology Forensic toxicology Poison control centers Veterinary toxicology
intoxication, incidence and frequency of poisoning, mechanisms of action, clinical signs and symptoms of poisoning and management guidance. Haddad LM, Shannon MW, Winchester JF (1998) Clinical Management of Poisoning and Drug Overdose, 3rd edition Philadelphia, PA: WB Saunders Company. Hoffman R S, Nelson L S, Howland MA, Lewin NA 2006 Goldfrank’s Toxicologic Emergencies New York: McGraw-Hill Professional
Resources Books Barile FA (2004) Clinical Toxicology: Principles and Mechanisms Boca Raton, FL: CRC Press LLC. This book focuses on the current and contemporary principles and mechanisms of clinical toxicology. It examines the complex interactions associated with clinical toxicological events and chemical exposure. It also addresses the signs and symptoms of diseases and pathology caused by toxins and drug administration. Topics such as biological and chemical toxins, changes in protocols for managing toxic ingestions, new antidotes, and changes in particular treatments are also covered. Dart RC (2004) Medical Toxicology, 3rd edition Philadelphia, PA: Lippincott Williams & Wilkins. Ford M (ed.) Delaney K, Ling L, Erickson T (2000) Clinical Toxicology Los Angeles, CA: W.B. Saunders. This book provides a detailed outline needed to assess, diagnose, and manage poisoned and overdosed patients. Clinically oriented and practical, this complete, yet concise, resource is organized to give clinicians quick access to fundamental toxicological information. Gossel TA, Bricker JD (1994) Principles Of Clinical Toxicology 3rd edition New York: Raven Press Ltd. In this third edition, the editors have made numerous changes for managing poison ingestion and treatment selection. It focuses primarily on the classes of toxic agents, their common sources and usual methods of
Katzung BG (2006) Basic & Clinical Pharmacology (Basic and Clinical Pharmacology) 10th edition New York: McGraw-Hill Medical. The 10th edition of this book has up-to-date information on integration of basic with clinical science as well as in-depth coverage of key pharmacology topics. For example it covers basic principles to pharmacologic considerations for autonomic, cardiovascular–renal, smooth muscle, CNS, endocrine, antimicrobial, and chemotherapeutic and immunotherapeutic drugs. It is also updated with dozens of new, recently approved drugs, including monoclonal antibodies. Ling L, Clark RF, Erickson T, Trestrail JH (2001) Toxicology Secrets, 1st edition Philadelphia, PA: Hanley & Belfus. This text contains 64 chapters covering topics such as general toxicology principles, over-the-counter drugs, prescription medications, antibiotics, cardiac drugs, psychopharmacologic medications, drugs of abuse, metals, chemicals, pesticides, gases, food poisoning, botanicals, envenomations, and toxic terrorist threats. Lyle DP (2004) Forensics for Dummies Hoboken, NJ: Wiley Publishing, Inc. Wecht C, Saitz G, Curriden M (2003) Mortal Evidence: The Forensics behind Nine Shocking Cases Amherst, New York: Prometheus Books.
Review articles Bateman D (2005) Clinical toxicology: Clinical science to public health. Clin. Exp. Pharmacol. Physiol. 32(11): 995–998. Breckenridge A (1996) A clinical pharmacologist’s view of drug toxicity. Br. J. Clin. Pharmacol. 42(1): 53–58.
20. Clinical Toxicology and Clinical Analytical Toxicology
Wiener SW, Hoffman RS (2005) Trends in clinical toxicology: Advances that may change your practice. Basic Clin. Pharmacol. Toxicol. 97(1): 1–7.
Journals Basic & Clinical Pharmacology & Toxicology British Journal of Clinical Pharmacology Clinical and Experimental Pharmacology and Physiology Clinical Toxicology (formerly the Journal of Toxicology: Clinical Toxicology) Forensic Toxicology Journal of Forensic Medicine and Toxicology Journal of Medical Toxicology General interest works Howdunit Book of Poisons: A Guide for Writers Stevens S, Bannon A (2007) Writers Digest Books. Poisons: From Hemlock to Botox to the Killer Bean of Calabar Macinnis P (2005) Arcade Publishing.
185
Databases (U.S.) National Library of Medicine. Drug Information Portal. http://druginfo.nlm.nih.gov The Drug Information Portal provides a gateway to current and accurate drug information. Information for more than 15 000 drugs is available for searching. Poisindex®, Thompson Healthcare Web: www.micromedex.com/products/poisindex/
Organizations American Academy of Clinical Toxicology Web: www.clintox.org American Association of Poison Control Centers Web: www.aapcc.org American Board of Forensic Toxicology Web: www.abft.org American College of Medical Toxicology Web: www.acmt.net European Association of Poisons Centres and Clinical Toxicologists Web: http://www.eapcct.org Society of Forensic Toxicology Web: www.soft-tox.org