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TABLEOFCONTENTS

Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxvii

Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .xxviii

1 HistoricalPrincipIesand Perspectives 1PaulM. Wax

2 Toxicologic Plagues and Disasters in History . . . .. 18PaulM. Wax

PARTA

THEGENERALAPPROACHTO MEDICALTOXICOLOGY 31

3 Initial Evaluation of the Patient: Vital Signs andToxic Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

LewisS.Nelson, Neal A. Lewin, Mary Ann Howland, Robert S.Hoffman, LewisR. Goldfrank, and Neal E. Flomenbaum

4 PrincipIesof Managingthe AcutelyPoisoned orOverdosedPatient . . . . . . . . . . . . . . . . . . . . . 37

Lewis S. Nelson, Neal A. Lewin, Mary Ann Howland, Robert S.

Hoffman, Lewis R. Goldfrank, and Neal E. Plomenbaum

5 Diagnostic Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

David T. Schwartz

6 Laboratory PrincipIes. . . . . . . . . . . . . . . . . . . . . . . . . . 70

PetrieM. Rainey

7 Techniques Used to Prevent GastrointestinalAbsorption. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

Anne-Bolette Gude and Lotte C. G. Hoegberg

A 1 Syrup of Ipecac . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 104

Mary Ann Howland

A2 ActivatedCharcoal. . . . . . . . . . . . . . . . . . . . . . . . . . . 108

Mary Ann Howland

A3 Whole-Bowel Irrigation and Other IntestinalEvacuants. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114

Mary Ann Howland

8 Pharmacokinetic and Toxicokinetic PrincipIes .119MaryAnn Howland

9 PrincipIes and Techniques Applied to EnhanceElimination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135

David S. Goldfarb

10 Use ofThe Intensive Care Unit 148Mark A. Kirk

PARTB

THEFUNDAMENTALPRINClPLESOFMEDICALTOXICOLOGY. . . .. . . . .. . . . . . . . .. . .. .. 155

BiochemicalandMolecularBasis. . . . . . . . ... . . .. . . .. .157

11 ChemicalPrincipIes. . . . . . . . . . . . . . . . . . . . . . . . .. 157

Stephen ,. Traub and Lewis S. Nelson

12 BiochemicaI and Metabolic PrincipIes . . . . . . . . .. 170Kurt C.KleinschmidtandKathleenA. Delaney

13 Neurotransmitters and Neuromodulators . 189

Steven C. Curry, Kirk Charles Milis, Anne-Michelle Ruha,

and Ayrn D. Q'Connor

14 WithdrawaI PrincipIes. . . . . . . . . . . . . . . . . . . . . . . . 221

Richard ,. Hamilton

PathophysiologicBasis:Organ Systems. . . . . . . . . . . . . . . 228

15 Thermoregulatory PrincipIes . . . . . . . . . . . . . . . . . . 228

Susi U. Vassalloand Kathleen A. Delaney

16 Fluid, Electrolyte, and Acid-Base PrincipIes. . . . . 249

Alan N. Charney and Robert S. Hoffman

17 Psychiatric PrincipIes. . . . . . . . . . . . . . . . . . . . . . . . . 265

Kishor Malavade and Mark R. Serper

18 Neurologic PrincipIes. . . . . . . . . . . . . . . . . . . . . . . . . 275Rama B. Rao

19 Ophthalmic PrincipIes. . . . . . . . . . . . . . . . . . . . . . . . 285

Adhi Sharma

20 Otolaryngologic PrincipIes. . . . . . . . . . . . . . . . . . . . 292WilIiam K. Chiang

21 Respiratory PrincipIes . . . . . . . . . . . . . . . . . . . . . . . . 303

Andrew Stolbach and Robert S. Hoffman

22 Electrophysiologic and ElectrocardiographicPrincipIes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314

Cathleen Clancy

23 Hemodynamic PrincipIes . . . . . . . . . . . . . . . . . . . . . 330Robert A. Hessler

24 Hematologic PrincipIes. . . . . . . . . . . . . . . . . . . . . . . 340Marco 1. A. Sivilotti

ix

Contents

- -- -

25 GastrointestinaI PrincipIes . . . . . . . . . . . . . . . . . . . . 359

Richard G. Church and Kavita M. Babu

26 Hepatic PrincipIes. . . . . . . . . . . . . . . . . . . . . . . . . . . . 367

Kathleen A. Delaney

27 RenalPrincipIes 381Donald A. Feinfeldand Nikolas B. Harbord

28 Genitourinary PrincipIes. . . . . . . . . . . . . . . . . . . . . . 396

JasonChu

29 DermatologicPrincipIes . . . . . . .. . 410Neal A. Lewin and Lewis S. Nelson

SpecialPopulations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423

30 Reproductive and PerinataI PrincipIes . . . . . . . . . . 423JeffreyS. Fine

31 Pediatric PrincipIes. . . . . . . . . . . . . . . . . . . . . . . . . . . 447

JeffreyS. Fine

32 Geriatric PrincipIes. . . . . . . . . . . . . . . . . . . . . . . . . . . 461

Judith C. Ahronheim and Mary Ann Howland

33 Postmortem Toxicology . .. .. .. .. . .. . . . . . . . . . . 471Rama B. Rao and Mark A. F/omenbaum

se1 Organ Procurement from Poisoned Patients 479Rama B. Rao

PARTe

THECLlNICALBASISOF MEDICALTOXICOLOGY.. . . . . .481

A. AnalgesicsandAntiinflammatoryMedications.. . .483

34 Acetaminophen 483Robert G. Hendrickson

A4 N-Acetylcysteine 500Mary Ann Howland and Robert G. Hendrickson

35 Salicylates 508Neal E. Flomenbaum

AS Sodium Bicarbonate. . . . . . . . . . . . . . . . . . . . . . . . . . 520

Paul M. Wax

36 NonsteroidaI Antiinflammatory Drugs 528

William J. Holubek

--

J

37 Colchicine, PodophyIlin, and the Vinca Alkaloids... 537Joshua G. Schier

Se2 IntrathecaI Administration of Xenobiotics. . . . . . . 548Rama B. Rao

38 Opioids 559Lewis S. Nelson and Dean Olsen

A6 Opioid Antagonists 579Mary Ann Howland and Lewis S. Nelson

B. Foods,DietaryandNutritionalXenobiotics.. . . . . . 586

39 Dieting Agents and Regimens . . . . . . . . . . . . . . . . . 586Jeanna M. Marraffa

40 Iron 596Jeanmarie Perrone

A7 Deferoxamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 604

Mary Ann Howland

41 Vitamins 609

Beth Y. Ginsburg

42 EssentiaI Oils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 624

Sarah Eliza Halcomb

43 HerbaI Preparations . . . . . . . . . . . . . . . . . . . . . . . . . . 631

Oliver L. Hung

44 Athletic Performance Enhancers . . . . . . . . . . . . . . . 654

Susi U. Vassallo

45 Food Poisoning. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 668

Michael G. Tunik

46 Botulism 682

Howard L. Geyer

A8 Botulinum Antitoxin . . . . . . . . . . . . . . . . . . . . . . . . . 695

Lewis R. Goldfrank and Howard L. Geyer

C. Pharmaceuticals . . . . . . . . . . . . . . . . . . . . . . . . 698

47 AnticonvuIsants . . . . . . . . . .. 698

Suzanne Doyon

A9 L-Carnitine 711

MaryAnn Howland

48 Antidiabetics and Hypoglycemics . . . . . . . . . . 714George M. Bosse

A 1O Dextrose 728

Larissa 1. Velez and Kathleen A. Delaney

A11 Octreotide 734

Mary Ann Howland

49 Thyroid and Antithyroid Medications . . . . . . . . . . 738Nicole C. Bouchard

50 Antihistaminesand Decongestants. . 748Anthony J. Tomassoni and Richard S. Weisman

A 12 Physostigmine Salicylate . . . . . . . . . . . . . . . . . . . . . . 759

Mary Ann Howland

51 Antimigraine Medications 763Jason Chu

52 Antineoplastics Overview . . . . . . . . . . . . . . . . . . . . . 770

RichardY. Wang

53 Antineoplastics: Methotrexate . . . . . . . . . . . . . . . . . 778

RichardY. Wang

A 13 Leucovorin (Folinic Acid) and Folic Acid . . . . . . . 783

Mary Ann Howland

A 14 Glucarpidase (Carboxypeptidase GJ . . . . . . . . . . . 787Si/as W. Smith

SC3 Extravasation of Xenobiotics . . . . . . . . . . . 793

Richard Y. Wang

54 Miscellaneous Antineoplastics . . . . . . . . . . . . . . . . . 796

Richard Y. Wang

55 Pharmaceutical Additives . . . . . . . . . . . . . . . . . . . . . 803

Sean P. Nordt and Lisa E. Vivero

D. Antimicrobials 817

56 Antibacterials,Antifungals,and Antivirals 817Christine M. Stork

57 Antituberculous Medications . . . . . . . . . . . . . . . . . . 834

Christina H. Hernon and Edward W. Boyer

A15 Pyridoxine 845Mary Ann Howland

58 Antimalarials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 849

/. Dave Barry

E. Cardiopulmonary Medieations . . . . . . . . . ..861

59 Anticoagulants ... . . . . . . . . . . . . . . . . . . . . . . . . . . . 861

MarkSu

A 16 Vitamin K. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 876

Mary Ann Howland

A17 Protamine 880

Mary Ann Howland

60 Calcium Channel Blockers . . . . . . . . . . . . . . . . . . . . 884

PrancisJeromeDeRoos

Contents

A 18 Insulin-EuglycemiaTherapy 893William Kerns

61 ~-Adrenergic Antagonists. . . . . . . . . . . . . . . . . . . . . 896JeffreyR. Brubacher

A 19 Glucagon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 910

Mary Ann Howland

62 Other Antihypertensives 914Prancis Jerome DeRoos

63 Antidysrhythmics 925Lewis S. Nelson and Neal A. Lewin

64 Cardioactive Steroids . . . . . . . . . . . . . . . . . . . . . . . . . 936

Jason B. Hack

A20 Digoxin-SpecificAntibody Fragments . . . . . . . . . . 946Mary Ann Howland

65 Methylxanthines and Selective ~2AdrenergicAgonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 952

Robert J. Hoffman

F. Anestheties and Related Medieations. . . . . . . . . . . . 965

66 Local Anesthetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . 965

David R. Schwartz and Brian Kaufman

A21 Intravenous Fat Emulsions . . . . . . . . . . . . . . . . . . . . 976

Theodore C. Bania

67 Inhalational Anesthetics . . . . . . . . . . . . . . . . . . . . . . 982

Brian Kaufman and Martin Griffel

68 Neuromuscular Blockers . . . . . . . . . . . . . . . . . . . . . . 989

Kenneth M. Sutin

A22 Dantrolene Sodium . . . . . . . . . . . . . . . . . . . . . . . . . 1001

Kenneth M. Sutin

G. PsyehotropieMedieations... . . . . 1003

69 Antipsychotics 1003David N. Juurlink

70 Lithium 1016Howard A. Greller

71 Monoamine Oxidase Inhibitors. .. .. 1027Alex P. Manini

72 Serotonin Reuptake Inhibitors and AtypicalAntidepressants. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1037

Christine M. Stork

73 Cyclic Antidepressants. . . . . . . . . . . . . . . . . . . . . . . 1049Erica 1. Liebelt

74 Sedative-Hypnotics 1060David C. Lee and Kathy Lynn Ferguson

A23 Flumazenil 1072

Mary Ann How/and

H. Substances of Abuse. . . . . . . . . . . . . . . . . . . . . . . . 1078

75 Amphetamines . . . . . . . . . . . . . . . .. . . . . . . .. .. . . 1078

William K. Chiang

76 Cocaine 1091

Jane M. Prosser and Robert S. Hoffman

SC4 Internal Concealment ofXenobiotics 1103

Jane M. Prosser

A24 Benzodiazepines 1109Robert S. Hoffman, Lewis S. Ne/son, and Mary Ann How/and

77 Ethanol 1115

LukeYip

A25 Thiamine Hydrochloride 1129Robert S. Hoffman

78 EthanolWithdrawal. . . . . . . . . . . . . . . . . . . . . . . . . 1134

Jeffrey A. Go/d and Lewis S. Ne/son

79 Disulfiramand Disulfiram-LikeReactions.. . . . . 1143

Edwin K. Kuffner

80 y-HydroxybutyricAcid .. .. .. .. .. .. .. .. .. .. .. 1151Brenna M. Farmer

81 Inhalants 1157

Heather Long

82 Hallucinogens 1166Kavita M. Babu

83 Cannabinoids 1177

Michae/ A. McGuigan

84 Nicotine ... . . 1185

Sari Soghoian

85 Phencyclidine and Ketamine .. . . 1191Ruben E. O/medo

1. Metals 1202

86 Aluminum 1202Brenna M. Farmer

87 Antimony 1207Asim F. Tarabar

88 Arsenic 1214

Stephen W. Munday and Marsha D. Ford

A26 Dimercaprol (British Anti-Lewisite or BAL) 1229

Mary Ann How/and

89 Bismuth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1233

Rama B. Rao

90 Cadmium 1237

Stephen J. Traub and Robert S. Hoffman

91 Chromium 1243Steven B. Bird

92 Cobalt 1248

Gar Ming Chan, MD

93 Copper . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1256

Lewis S. Ne/son

94 Lead 1266

Fred M. Henretig

A27 Succimer (2,3-Dimercaptosuccinic Acid) 1284MaryAnn How/and

A28 Edetate Calcium Disodium (CaNazEDTA) 1290MaryAnn How/and

95 Manganese 1294Sari Soghoian

96 Mercury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1299

Young-Jin Sue

97 Nickel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1308

John A. Curtis and David A. Haggerty

98 Selenium 1316Diane P. Ca/ello

99 Silver 1321Melisa W. Lai Becker and Miche/e Burns Ewa/d

100 Thallium 1326

Maria Mercurio-Zappa/a and Robert S. Hoffman

A29 Prussian Blue . ... . . ... .. 1334

Robert S. Hoffman

1O1 Zinc 1339

Nima Maj/esi

J. HouseholdProducts. . . . . . . . . . . . . . . . . . . . . . . . 1345

102 Antiseptics, Disinfectants, and Sterilants . . . . . . . 1345Pau/M. Wax

103 Camphor and Moth Repellents . . . . . . . . . . . . . . . 1358Edwin K. Kuffner

104 Caustics . . . . . . . . . . . . . 1364Jessica A. Fu/ton

105 Hydrofluoric Acid and Fluorides 1374Mark Su

A30 Calcium .. . . . . . . . . . . . . . . .. .. .. .. . .. .. .. .. .. 1381

Mary Ann Howland

106 Hydrocarbons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1386

David D. Gummin

107 ToxicAlcohols..... .. . . . . . . . . . . . . ... 1400

Sage W. Wiener

SC5 Diethylene Glycol. . . . . . . . . . . . . . . . . . . . . . . . . . . 1411foshua G. Schier

A31 Fomepizole 1414Mary Ann Howland

A32 Ethanol 1419

Mary Ann Howland

K. Pesticides 1423

108 Pesticides: An Overview of Rodenticides

and a Focus on Principies. . . . . . . . . . . . . . . . . . . . 1423Neal E. Flomenbaum

109 Barium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1434

Andrew Dawson

110 Sodium Monofluoroacetate andFluoroacetamide. . . . . . . . . . . . . . . . . . . . . . . . . . . . 1437

Fermin Barrueto, fr.

111 Phosphorus 1440Michael C. Beuhler

112 Strychnine . . . . . . . . . . . .. .. .. .. .. .. .. .. . . . . . . 1445Yiu-cheung Chan

113 Insecticides: Organic PhosphorusCompounds and Carbamates . .. . . . 1450Michael Eddleston and Richard Franklin Clark

A33 Pralidoxime 1467

MaryAnn Howland

A34 Atropine 1473MaryAnn Howland

114 Insecticides: Organic Chlorines,Pyrethrins/Pyrethroids, and Insect Repellents. . . 1477Michael G. Holland

115 Herbicides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1494

DarrenM. Roberts

116 MethylBromideand Other Fumigants .. 1516Keith K. Burkhart

Contents xiii

L. NaturalToxinsandEnvenomations.. . . . . . . . . . . 1522

117 Mushrooms 1522

Lewis R. Goldfrank

118 Plants . . . . . . . . . . . . . . . . . . . . . 1537

Mary Emery Palmer and foseph M. Betz

119 Arthropods 1561In-Hei Hahn

A35 Antivenom (Scorpionand Spider). . 1582Richard Franklin Clark

120 Marine Envenomations . . . . . . . . . . . . . . . . . . . . .. 1587D. Eric Brush

121 Snakes and Other Reptiles. . . . . . . . . . . . . . . . . . . . 1601

Bradley D. Ri/ey,Anthony F. Pizon, andAnne-Michelle Ruha

A36 Antivenom (Crotaline) 1611

AnthonyF.Pizon,BradleyD.Ri/ey,andAnne-MichelleRuha

M. OccupationalandEnvironmentalToxins.. . . . . . . 1615

122 Industrial Poisoning:Information andControl. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1615

Peter H. Wald

123 Nanotoxicology 1625Si/asW.Smith

124 Simple Asphyxiants and Pulmonary Irritants . . . 1643Lewis S. Nelson and Oladapo A. Odujebe

125 Carbon Monoxide. . . . . . . . . . . . . . . . . . . . . . . . . . . 1658Christian Tomaszewski

A37 HyperbaricOxygen .. .. .. . 1671Stephen R. Thom

126 Cyanideand Hydrogen Sulfide.. . . . . . . . . . . . . . . 1678

ChristopherP. Holstege,Gary E. 150m,and Mark A. Kirk

A38 Sodium and Amyl Nitrite . . . . . . . . . . . . . . . . . . . . 1689Mary Ann Howland

A39 SodiumThiosulfate ... 1692

Mary Ann Howland

A40 Hydroxocobalamin 1695MaryAnn Howland

127 Methemoglobin Inducers . . . . . . .. . . . . . . . . . . . . 1698Dennis P. Price

XIV Contents

------- --- -----

A41 Methylene Blue . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 1708

Mary Ann Howland

128 Smoke Inhalation . . . . . . . . . . . . . . . . . . . . . . . . . . . 1711

Nathan Phillip Charlton and Mark A. Kirk

N. Disaster Preparedness . . .. .. . . . .. . . . . . .. .. .. 1721

129 Risk Assessment and Risk Communication. . . . . 1721

Charles A. McKay

130 Hazmat Incident Response . . . . . . . . . . . . . . . . . . . 1727

Bradley J. Kaufman

131 Chemical Weapons 1735Jeffrey R. Suchard

132 BiologicaI Weapons . . . . . . . . . . . . . . . . . . . . . . . . . 1750

Jeffrey R. Suchard

133 Radiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1759

Joseph G. Rella

A42 Potassium lodide ... . .. . . . . . . . . . . . . . . . . . . . . . 1775

Joseph G. Rella

A43 DTP A [Pentetic Acid or Pentetate(Zinc or Calcium) Trisodium] . . . . . . . . . . . . . . . . 1779

JosephG. Rella

n

PoisonCentersand Epidemiology. . . . . . . . . . . . . . . . . . 1782

134 Poison Prevention and Education . . . . . . . . . . . . . 1782

Lauren Schwartz

135 Poison Centers and Poison Epidemiology . . . . . . 1789

Robert S. Hoffman

136 International Perspectiveson MedicalToxicology . . . . . . ... .. 1796Michael Eddleston

137 PrincipIesof EpidemiologyandResearch Design . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1803

Kevin C. Osterhoudt

138 Adverse Drug Events and PostmarketingSurveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1811

Louis R. Cantilena

139 Medication Safety and Adverse Drug Events. . . . 1820Brenna M. Farmer

140 RiskManagement and LegalPrincipIes. . . . 1831Barbara M. Kirrane and Dainius A. Drukteinis

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1839