Toxicology Testing In The Hospital Setting – Sample

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ContentsPreface . xviiContributing Authors . xviiiSection I. Toxicology Testing in the Hospital SettingBarbarajean Magnani, EditorChapter 1. Introduction and Organizational Aspects of a Hospital Toxicology Laboratory . 3Tai C. Kwong and Barbarajean MagnaniIntroduction, 3Emergency Toxicology, 3Toxicology Testing Supporting Other Clinical Services, 3On-Site Testing, 4Confirmation Testing and Adulterant Testing, 4Confirmation Testing, 4Urine Adulterant Testing, 5Medical-Legal Testing, 5Clinical Testing with Legal Implications, 5Legal Testing, 5Summary, 6Chapter 2. Supporting the Emergency Department. 7Barbarajean Magnani and Tai C. KwongIntroduction, 7Tier 1 Tests, 7Quantitative Serum Tests, 8Urine Qualitative Tests, 9Tier 2 Tests, 9Unique Challenges Associated with Testing in the ED, 10Toxidromes, 12Chapter 3. Supporting the Pain Service. 15Catherine A. Hammett-Stabler and Barbarajean MagnaniIntroduction, 15Role of the Clinical Laboratory in Pain Management, 16Samples, Analytes, and Methods, 17Clinical Pathology Consultations, 21Alternate Specimens and Issues, 24Summary and Conclusions, 24

Chapter 4. Biomonitoring of Medical Professional Substance Abuse: Practical and Analytical Issues. 27Robert A. MiddlebergIntroduction, 27Treatment and Monitoring of Impaired Medical Professionals, 27Oversight, 27Treatment Monitoring, 28Substances Commonly Abused by Medical Professionals, 28Analytical Considerations of Medical Professional Testing, 28General, 28Preanalytical Considerations, 29Analyses, 30Scope of Testing, 30Screening, 30Confirmation Testing, 31Interpretive Issues, 31Summary, 32Chapter 5. Workplace Drug Testing and the Role of the Medical Review Officer. 33Michael G. BissellIntroduction, 33Workplace Drug Testing, 33The Medical Review Officer, 34Positivity Criteria and Sources of Legitimate Medical Explanations for HHS 5 Urine Tests, 35Amphetamines, 35Amphetamine, 35Methamphetamine, 35Cocaine, 36Marijuana, 36Opiates, 36Heroin, 37Morphine, 37Codeine, 37Opiate Identification, 37Phencyclidine, 37Medical Review Officer Review of Specimen Validity Testing, 38Definitions of Specimen Validity Testing Results and Associated Medical Review Officer Actions, 38Negative or Positive Specimen, 38Negative Dilute Specimen, 38Positive Dilute Specimen, 38Substituted Specimen, 38Adulterated Specimen, 38Invalid Drug Test, 39Summary, 39Chapter 6. The Hospital Autopsy and Toxicology Testing. 41D. Kimberley Molina and Barbarajean MagnaniIntroduction, 41The Autopsy, 41Specimen Collection, 42Specimen Selection, 44Ordering Toxicology Testing, 44Interpretation of Toxicology Results, 45Medicolegal Issues, 46Summary, 47iv

Chapter 7. Regulatory Issues of Toxicology Laboratory Operations. 49Wayne R. MarkusIntroduction, 49CLIA Certification, 49CLIA Certificates, 49CLIA-Exempt Laboratories, 50State Exemption from CLIA, 50Forensic Testing Accreditation, 50The CAP FDT Accreditation Program, 50Forensic Testing in the Clinical Laboratory, 51Medical Testing with Legal Implications, 51Waived Tests, 51Nonprofit Agencies with Deemed Status to Accredit Laboratories, 51Five Condition Level Requirements for Accreditation, 52First Condition Level Requirement: Proficiency Testing, 52Second Condition Level Requirement: Facility Administration, 52Third Condition Level Requirement: Quality Systems, 53Quality Assurance (Assessment)/Quality Management, 53Proficiency Testing and Alternative Performance Assessment, 54Evaluation of Proficiency Testing and Alternative Performance Assessment, 54Method Validation, 54Fourth Condition Level Requirement: Personnel, 56Competency Evaluation of Technical Staff, 57Fifth Condition Level Requirement: Inspection, 57ISO 15189, 57Alcohol and Volatiles Proficiency Testing, 57Immunoassay Urine Drug Screen Proficiency Testing, 57Broad-Spectrum Urine Drug Screen Proficiency Testing, 58Whole Blood, Serum, and Plasma Drug Screen Proficiency Testing, 59Urine Adulteration Proficiency Testing, 59Summary, 59Chapter 8. Adverse Drug Events, Poisonings, and Abuse. 61Daniel J. CobaughIntroduction, 61Experience Across the Continuum of Care, 62Identifying the Point of Occurrence of Adverse Drug Events, 64Medications Frequently Implicated in Adverse Drug Events, 64System Failures Versus “Bad Apples,” 65Poisonings, 66Drug Abuse and Misuse, 66Conclusions, 67Section II. Methodologies for the Toxicology LaboratoryTai C. Kwong, EditorChapter 9. Alternate Specimens for Drugs-of-Abuse Testing:Preanalytical and Interpretative Considerations. 71Uttam Garg and Angela M. FegusonIntroduction, 71Hair, 71Preanalytical and Interpretive Considerations in Drug Testing of Hair Samples, 73Environmental or External Contamination, 73Hair Color and Drug Incorporation, 74Adulteration Issues, 75v

Oral Fluid, 75Preanalytical and Interpretative Considerations in Drug Testing of Oral Fluid Samples, 76Sample Collection, 76Correlation of Drug Concentrations and Positivity Rate Between Saliva and Urine or Blood, 77Sample Adulteration Issues, 77Sweat, 77Preanalytical and Interpretative Considerations in Drug Testing of Sweat Samples, 78Sample Collection, 78Drug Detection in Sweat and Its Relationship to Urine Testing, 78Sample Adulteration and Contamination Issues, 78Meconium, 79Other Alternative Samples for Drug Testing, 79Summary, 79Chapter 10. Analytical Methodologies for the Toxicology Laboratory. 83Petrie M. Rainey and Geoffrey S. BairdIntroduction, 83Spot Tests, 83Spectrometry, 83Direct Spectrometry, 83Atomic Absorption Spectrometry, 84Spectrochemistry, 84Immunoassays, 84Chromatography, 87Thin Layer Chromatography, 88High Performance Liquid Chromatography, 88Gas Chromatography, 89Mass Spectrometry, 90Ionization Techniques, 90Separation of Ions, 91Ion Detection, 93Section III A. The Toxicology Laboratory’s Test Menu: Abused SubstancesMichael G. Bissell, EditorChapter 11. Ethanol. 97Graham R. JonesDescriptive Chemistry, 97Pharmacology, 97Type of Agent, 97Context of Human Use, 97Abuse Potential and Characteristics, 97Adverse Effects, 97Overdose and Toxicity, 98Toxic Dose, 98Pharmacokinetics, Metabolism, and Excretion, 98Pharmacokinetics, 98Metabolism and Excretion, 98Analysis, 98Analytical Parameters, 98Specimen Types, Requirements, and Characteristics, 99Plasma/Serum Versus Blood, 99Urine, 99Postmortem Considerations, 99Analysis of Vitreous Fluid, 99Other Specimens, 99vi

Modes of Analysis, 100Colorimetric, 100Enzymatic, 100Gas Chromatography, 100Known Analytical Issues and Problems, 100Clinical Issues, 101Clinical Interpretation of Analytical Findings, 101Back-Extrapolation of Blood Alcohol Concentration, 101Estimation of Dose, 101Other Sources of Alcohol, 102Treatment and Rehabilitation for Overdose and Toxicity, 102Chapter 12. Cannabis. 104Michael G. BissellDescriptive Chemistry, 104D9-tetrahydrocannabinol, 104D8-tetrahydrocannabinol, 104Cannabinol, 104Cannabidiol, 105D9-tetrahydrocannabinolic acid, 105Origin, 105Pharmacology, 105Type of Agent, 105Context of Human Use, 105Abuse Potential and Characteristics, 106Overdose and Toxicity, 106Adverse Effects and Complications, 107Central Nervous System, 107Cardiovascular, 107Respiratory, 107Reproductive, 107Toxic Dose, 108Pharmacokinetics, Metabolism, and Excretion, 108Pharmacokinetics, 108Metabolism, 108Excretion, 109Volume of Distribution, 109Half-Life, 109Analysis, 109Analytical Parameters, 109Specimen Types, Requirements, and Characteristics, 109Modes of Analysis, 110Known Analytical Issues and Problems, 110Clinical Issues, 110Clinical Interpretation of Analytical Findings, 110Treatment and Rehabilitation for Overdose and Toxicity, 110Chapter 13. Cocaine. 112Michael G. BissellDescriptive Chemistry, 112Cocaine, 112Cocaine Hydrochloride, 112Origin, 112Pharmacology, 112Type of Agent, 112Context of Human Use, 112vii

Intoxication and Abuse, 113Overdose and Toxicity, 114Adverse Effects and Complications, 114Central Nervous System, 114Cardiovascular, 114Respiratory, 115Musculoskeletal and Renal, 115Sexual, 115Pregnancy, 115Breast-feeding, 115Toxic Dose, 115Pharmacokinetics, Metabolism, and Excretion, 116Pharmacokinetics, 116Metabolism, 116Excretion, 117Analysis, 117Analytical Parameters, 117Specimen Types, Requirements, and Characteristics, 117Modes of Analysis, 117Known Analytical Issues and Problems, 117Clinical Issues, 118Clinical Interpretation of Analytical Findings, 118Treatment of Acute Overdose, 118Chapter 14. Amphetamines. 119Marion L. Snyder and Stacy Eugenie MelansonDescriptive Chemistry, 119Amphetamine, 119Methamphetamine, 119Origin, 119Pharmacology, 120Type of Agent, 120Context of Human Use, 120Abuse Potential and Characteristics, 120Overdose and Toxicity, 120Complications, 120Toxic Dose, 120Pharmacokinetics, Metabolism, and Excretion, 120Pharmacokinetics, 120Metabolism and Excretion, 121Analysis, 121Clinical Issues, 123Clinical Interpretation of Analytical Findings, 123Treatment of Overdose and Toxicity, 124Chapter 15. Barbiturates. 126Marion L. Snyder and Stacy Eugenie MelansonDescriptive Chemistry, 126Amobarbital, 126Butalbital, 126Butabarbital, 126Mephobarbital, 127Pentobarbital, 127Phenobarbital, 127Secobarbital, 127Thiopental, 127viii

Origin, 127Pharmacology, 127Type of Agent, 127Context of Human Use, 128Abuse Potential and Characteristics, 128Overdose and Toxicity, 128Complications, 128Toxic Dose, 128Pharmacokinetics, Metabolism, and Excretion, 128Pharmacokinetics, 128Metabolism and Excretion, 130Analysis, 130Clinical Issues, 131Clinical Interpretation of Analytical Findings, 131Treatment of Overdose and Toxicity, 131Chapter 16. Benzodiazepines. 132Marion L. Snyder and Stacy Eugenie MelansonDescriptive Chemistry, 132Alprazolam, 132Diazepam, 132Nordiazepam, 132Lorazepam, 133Oxazepam, 133Chlordiazepoxide, 133Triazolam, 133Flurazepam, 133Flunitrazepam, 134Clonazepam, 134Origin, 134Pharmacology, 134Type of Agent, 134Context of Human Use, 134Abuse Potential and Characteristics, 134Overdose and Toxicity, 135Toxic Dose, 135Pharmacokinetics, Metabolism, and Excretion, 135Pharmacokinetics, 135Metabolism and Excretion, 135Analysis, 135Clinical Issues, 138Clinical Interpretation of Analytical Findings, 138Treatment of Overdose and Toxicity, 138Chapter 17. Opioids 1: Opiates. 140Michael G. Bissell and Michael A. PeatDescriptive Chemistry, 140Morphine, 140Codeine, 140Thebaine, 141Heroin, 141Hydromorphone, 141Hydrocodone, 141Oxymorphone, 141Oxycodone, 142Origin, 142ix

Pharmacology, 142Type of Agent, 142Context of Human Use, 143Abuse Potential and Characteristics, 143Overdose and Toxicity, 143Adverse Effects and Complications, 144Cardiovascular, 144Respiratory, 144Renal, 144Metabolic, 144Immune, 144Reproductive, 144Toxic Dose, 144Pharmacokinetics, Metabolism, and Excretion, 144Pharmacokinetics, 144Metabolism, 145Excretion, 145Analysis, 146Specimen Types, Requirements, and Characteristics, 146Modes of Analysis, 146Known Analytical Issues and Problems, 147Clinical Issues, 147Clinical Interpretation of Analytical Findings, 147Treatment and Rehabilitation, 147Chapter 18. Opioids 2: Synthetic Opioids. 149Hoi-Ying Elsie YuDescriptive Chemistry, 149Fentanyl, 149Meperidine, 149Propoxyphene, 149Tramadol, 150Origin, 150Pharmacology, 150Type of Agent, 150Context of Human Use, 150Abuse Potential and Characteristics, 151Overdose and Toxicity, 151Drug and Disease Interactions, 152Toxic Dose, 152Pharmacokinetics, Metabolism, and Excretion, 152Pharmacokinetics, 152Metabolism and Excretion, 153Analysis, 153Specimen Types, Requirements, and Characteristics, 153Modes of Analysis, 153Known Analytical Issues and Problems, 154Clinical Issues, 154Clinical Interpretation of Analytical Findings, 154Treatment and Rehabilitation, 154Chapter 19. Opioids 3: Synthetic Opioids Continued (Methadone and Buprenorphine). 157Glynnis B. Ingall and Bharathi VennapusaDescriptive Chemistry, 157Methadone, 157Buprenorphine, 157Origin, 157x

Pharmacology, 158Type of Agent, 158Context of Human Use, 158Abuse Potential and Characteristics, 158Overdose and Toxicity, 159Toxic Dose, 160Pharmacokinetics, Metabolism, and Excretion, 160Pharmacokinetics, 160Metabolism, 160Excretion, 161Analysis, 161Specimen Types, Requirements, and Characteristics, 161Modes of Analysis, 161Known Analytical Issues and Problems, 161Clinical Issues, 162Clinical Interpretation of Analytical Findings, 162Treatment and Rehabilitation, 162Chapter 20. Phencyclidine. 164Donald L. FrederickDescriptive Chemistry, 164Origin, 164Pharmacology, 164Type of Agent, 164Context of Human Use, 164Abuse Potential and Characteristics, 165Overdose and Toxicity, 165Toxic Dose, 165Pharmacokinetics, Metabolism, and Excretion, 165Pharmacokinetics, 165Metabolism, 165Excretion, 166Analysis, 166Specimen Types, Requirements, and Characteristics, 166Modes of Analysis, 166Known Analytical Issues and Problems, 166Clinical Issues, 166Clinical Interpretation of Analytical Findings, 166Treatment and Rehabilitation, 166Chapter 21. Club Drugs (GHB, DXM, MDMA). 168Donald L. FrederickDescriptive Chemistry, 168Gamma-Hydroxybutyric Acid (GHB), 168Dextromethorphan (DXM), 168Methylenedioxymethamphetamine (MDMA), 168Origin, 169Pharmacology, 169Type of Agent, 169Context of Human Use, 169Abuse Potential and Characteristics, 170Overdose and Toxicity, 170Toxic Dose, 171Pharmacokinetics, Metabolism, and Excretion, 171Pharmacokinetics, 171Metabolism, 171Excretion, 172xi

Analysis, 172Specimen Types, Requirements, and Characteristics, 172Modes of Analysis, 172Clinical Issues, 173Clinical Interpretation of Analytical Findings, 173Treatment and Rehabilitation, 173Section III B. The Toxicology Laboratory’s Test Menu: Toxic Substances and OverdosesMichael G. Bissell, EditorChapter 22. Over-the-Counter Analgesics. 179Hoi-Ying Elsie Yu and Barbarajean MagnaniIntroduction, 179Descriptive Chemistry, 179Salicylate, 179Acetaminophen, 179Origin, 179Salicylate, 179Acetaminophen, 179Pharmacology, 180Type of Agent, 180Context of Human Use, 180Overdose and Toxicity, 180Salicylate, 180Acetaminophen, 181Pharmacokinetics, Metabolism, and Excretion, 182Pharmacokinetics, 182Metabolism and Excretion, 182Analysis, 183Specimen Types, Requirements, and Characteristics, 183Modes of Analysis, 183Salicylate, 183Acetaminophen, 183Known Analytical Issues and Problems, 184Salicylate, 184Acetaminophen, 184Clinical Issues, 184Clinical Interpretation of Analytical Findings, 184Salicylate, 184Acetaminophen, 184Treatment and Rehabilitation, 185Salicylate, 185Acetaminophen, 185General Considerations for Patients with Potential Analgesic Toxicity, 185Chapter 23. Non-Ethanol Volatiles and Ethylene Glycol. 188Michael G. BissellDescriptive Chemistry, 188Acetone, 188Methanol, 188Isopropanol, 188Ethylene Glycol, 188Pharmacology, 188Context of Human Use, 189Exposure, 189Airborne and Workplace Exposure: Hazardous Material (Hazmat) Considerations, 189Exposure by Ingestion: Epidemiology, 189xii

Pharmacokinetics, Metabolism, and Excretion, 190Pharmacokinetics, 190Metabolism and Excretion, 190Toxicity, 191Acetone, 191Methanol, 191Isopropanol, 192Ethylene Glycol, 192Analysis, 192Specimen Types, Requirements, and Characteristics, 192Modes of Analysis, 192Known Analytical Issues and Problems, 193Clinical Issues, 193Clinical Interpretation of Analytical Findings, 193Acetone and Isopropanol, 193Methanol and Ethylene Glycol, 193Treatment and Management, 194Acetone, 194Isopropanol, 194Methanol, 194Ethylene Glycol, 195Chapter 24. Lead and Other Toxic Metals. 196Robert A. MiddlebergIntroduction, 196Descriptive Chemistry, 196Lead, 196Arsenic, 196Cadmium, 196Mercury, 196Thallium, 196Pharmacology, 196History and Context of Human Use, 196Lead, 196Arsenic, 197Cadmium, 197Mercury, 197Thallium, 197Exposure, 197Lead, 197Arsenic, 198Cadmium, 198Mercury, 198Thallium, 198Toxicokinetics, Metabolism, and Excretion, 199Lead, 199Arsenic, 199Cadmium, 199Mercury, 200Thallium, 200Toxicity, 200Lead, 200Arsenic, 202Cadmium, 202Mercury, 203Thallium, 203xiii

Analysis, 203Specimen Types, Requirements, and Characteristics, 203Lead, 203Arsenic, 204Cadmium, 204Mercury, 204Thallium, 204Modes of Analysis, 204Lead, 204Arsenic, 204Cadmium, 204Mercury, 204Thallium, 204Known Analytical Issues and Problems, 204Lead, 204Cadmium, 204Mercury, 204Clinical Issues, 205Clinical Interpretation of Analytical Findings, 205Treatment and Management, 205Lead, 205Arsenic, 205Cadmium, 206Mercury, 206Thallium, 206Chapter 25. Common Household and Environmental Toxins(Carbon Monoxide, Cyanide, Organophosphates, Warfarins). 208Leland B. BaskinIntroduction, 208Descriptive Chemistry, 208Carbon Monoxide, 208Hydrogen Cyanide, 208Organophosphates, 208Parathion, 208Warfarins, 209Warfarin, 209Dicoumarol, 209Pharmacology, 209History and Context of Human Exposure, 209Carbon Monoxide, 209Cyanide, 209Organophosphates, 209Warfarins, 210Toxicokinetics, Metabolism, and Excretion, 210Carbon Monoxide, 210Cyanide, 210Organophosphates, 210Warfarins, 210Toxicity, 211Carbon Monoxide, 211Cyanide, 212Organophosphates, 212Warfarins, 213Toxic Dose, 213Carbon Monoxide, 213xiv

Cyanide, 213Organophosphates, 213Analysis, 213Specimen Types and Requirements, 213Carbon Monoxide, 213Cyanide, 213Organophosphates, 213Modes of Analysis, 213Carbon Monoxide, 213Cyanide, 214Organophosphates, 214Warfarins, 214Known Analytical Problems, 214Carbon Monoxide, 214Organophosphates, 214Clinica

Modes of Analysis, 172 Clinical Issues, 173 Clinical Interpretation of Analytical Findings, 173 Treatment and Rehabilitation, 173 Section III B . The Toxicology Laboratory’s Test Menu: Toxic Substances and Overdoses Michael G. Bissell, Editor Chapter 22.

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