Critical care toxicology : diagnosis and management of the critically poisoned patient

Foreword Preface to the Second Edition Preface to the First Edition Contents About the Editors Contributors Part I: General Management of the Critically Poisoned Patient 1: The Critically Poisoned Patient Epidemiology Incidence Hospital Visits Toxins Fatalities by Toxin Medical Toxicology Training Medical Students Residency Training Fellowship Training Medical Toxicologists Other Health Care Professionals Medical Toxicology Practice Standards Toxicology Resources Sites of Care Recommended Equipment and Resources Poison Centers Poison Information Centers Poison Treatment Centers References 2: The Diagnostic Process in Medical Toxicology History Physical Examination Vital Signs Clinical Signs Toxidromes Opioid Toxidrome Sedative-Hypnotic Antimuscarinic Toxidrome Cholinergic Syndrome Sympathomimetic Toxidrome Serotonin Syndrome Neuroleptic Malignant Syndrome Diagnostic Testing EKG Arterial Blood Gases Biochemical Analysis Toxicology Testing Osmolal Gap Imaging References 3: Therapeutic Approach to the Critically Poisoned Patient General Approach to Patient Data for the Poisoned Patient Patients with Toxicologic Exposures Admitted to an Intensive Care Unit Initial Assessment Supportive Care Decisions Airway Maintenance Respiratory Function Circulation and Hemodynamics Hypertension Hypotension and Shock Cardiac Dysrhythmias and Conduction Abnormalities Fluid Resuscitation Vasoactive Agents Lipid Emulsion Therapy Extracorporeal Membrane Oxygenation Overdose and Cardiac Arrest Invasive and Noninvasive Measurements of Hemodynamic Function Sedation and Paralysis Ventilator Liberation Ancillary Issues in the Intensive Care Unit Management of Poisoned Patients Gastrointestinal Decontamination Antidotes Subspecialty Care References 4: Extracorporeal Membrane Oxygenation and Cardiopulmonary Bypass in the Poisoned Patient ECMO Principles Veno-Venous ECMO (VV ECMO) Veno-Arterial ECMO (VA ECMO) ECMO in Xenobiotic-Induced Cardiopulmonary Failure Experimental Evidence Clinical Reports Direct-Acting Cardioactive Agents Direct Pulmonary Toxins Anti-inflammatory Drugs Antimalarials Chemotherapeutic Agents Newer Antidepressants Opioid Analgesics Pesticides Plants Miscellaneous Xenobiotics Bridge to Organ Donation Complications Compatibility Pharmacokinetic Considerations Concomitant Use of Other Technological Treatments Complication and Compatibility Summary Suggested Use of ECMO for Xenobiotic Toxicity Conclusions References 5: Post-Resuscitation Management of the Poisoned Patient Initial Post-cardiac Arrest Clinical Assessment Post-cardiac Arrest Management Ventilator Management Hemodynamic Management Vasopressors Poison-Based Interventions Hyperinsulinemia-Euglycemia Intravenous Lipid Emulsion Extracorporeal Membrane Oxygenation Hypothermia Seizures Drug Metabolism During Induced Hypothermia Other Considerations in Hypothermic Patients Rewarming Therapeutic Hypothermia in the Poisoned Patient Neuroprognostication References 6: Psychiatric Issues in the Critically Poisoned Patient Epidemiology Roles for Consultation-Liaison Psychiatry Psychobehavioral Problems Impact of the Hospital Environment Delirium Nonpharmacologic Management of Psychobehavioral Disturbance Pharmacologic Management of Psychobehavioral Disturbance Acute Treatment Ongoing Treatment Legal and Ethical Issues Vulnerable Populations Adolescents and Children Elderly Patients Psychosomatic Interventions and Outcomes Psychiatric Treatment Repeat Episodes of Poisoning Suicide Collaborative Research Areas Future Interdisciplinary Developments References 7: Poisoning in Pregnancy Epidemiology Teratology Physiology of Pregnancy Maternal Physiologic Changes Placental Factors Fetal Factors Treatment of Poisonings in Pregnancy Decontamination Antidotes Enhanced Elimination Specific Agents Abortifacients Acetaminophen Salicylates Iron Carbon Monoxide Cyanide Cocaine Opioids Other Intoxications Toxicity of Pregnancy-Related Medications Magnesium Sulfate Methotrexate Vagotonics/Tocolytics References 8: Geriatric Poisoning Pharmacology and Pathophysiology Pharmacokinetic Considerations Pharmacodynamic Factors Drug-Drug, Drug-Food, and Drug-Lifestyle Interactions Social and Behavioral Factors Clinical Presentation Diagnosis Treatment and Prevention References 9: Intensive Care of Pediatric Poisoning Cases Epidemiology Admission to the PICU General Pediatric Intensive Care Unit Treatment Neurologic Toxicity Seizures Cardiovascular Toxicity Dysrhythmias Respiratory Support Mechanical Ventilation High-Frequency Ventilation Noninvasive Ventilation Mechanical Circulatory Support/ECMO Circulatory Assist Devices Renal Toxicity Organ Donation References 10: The Critically Poisoned Worker Occupational Pulmonary Toxicology Occupational Asthma Toxic Inhalant Injury Simple Asphyxiants Chemical Asphyxiants Irritant Gases Reactive Airways Dysfunction Syndrome Inhalational Fevers and Hypersensitivity Syndromes Occupational Cardiac Toxicology Myocardial Infarction Cardiac Dysrhythmia Occupational Hepatic Toxicology Halogenated Hydrocarbons Solvents Miscellaneous Compounds Occupational Renal Toxicology Acute Renal Failure Occupational Neurotoxicology Central Nervous System Peripheral Neuropathy Occupational Hematopoietic Toxicology MethemoglobinemiaHemolysis Aplastic Anemia References 11: Complications of Chronic Alcoholism That Affect Critical Illness Pathophysiology and Clinical Features of Liver Injury Low Platelet Count and Coagulopathy Hemodynamic Effects Infection Gastrointestinal Bleeding Ascites Renal Failure and Hepatorenal Syndrome Pulmonary Abnormalities Spontaneous Bacterial Peritonitis Encephalopathy Abnormal Glucose Metabolism Muscle Wasting and Nutritional Deficiencies Alcoholic Ketoacidosis Altered Drug Metabolism Alcohol Withdrawal Prognostic and Ethical Considerations for Acute Deterioration of Patients with Alcoholic Liver Disease and the ICU References 12: Extracorporeal Substance Removal Principles and Factors Influencing Poison Removal During Extracorporeal Treatments Poison-Related Factors Molecular Size Protein Binding Volume of Distribution Endogenous Clearance ECTR-Related Factors Available Extracorporeal Treatments to Enhance Elimination of Poisons Processes of Poison Removal Diffusion (Hemodialysis) Convection (Hemofiltration) Adsorption (Hemoperfusion) Specific Extracorporeal Treatments Hemodialysis, Hemoperfusion, and Hemofiltration Continuous Renal Replacement Therapy Peritoneal Dialysis Therapeutic Plasma Exchange and Plasmapheresis Exchange Transfusion Extracorporeal Liver Assist Devices (Albumin Dialysis) General Indications for Extracorporeal Removal of Poisons Practical Considerations Patient disposition Poisons Amenable to Extracorporeal Elimination References 13: Poisoning Fatalities Epidemiology of Toxic Deaths Mechanisms of Death Diagnosis of Brain Death in Poisoned Patients Organ Donation from Poisoned Donors Heart Donation Lung Donation Liver Donation Kidney Donation Pancreas Donation Organ Donation from Non-Heart-Beating Poisoned Donors Conclusion References Part II: Toxic Syndromes 14: The Assessment and Management of Hypotension and Shock in the Poisoned Patient Epidemiology Definition of Hypotension and Shock Pathophysiology Diagnostic Approach Hemodynamic Variables Assessing Severity of Hypotension and Shock Management Antidotal Therapy Fluid Resuscitation Should a Target MAP >65 mmHg Generally Be Maintained? Vasopressors and Classical Inotropes Other Inotropes and Phosphodiesterase-III Inhibitors Levosimendan Vasopressin Analogues Intravenous Lipid Emulsion Therapy High-Dose Insulin in Toxic Hypotension or Shock Methylene Blue Prolonged External Chest Compression Using Mechanical Resuscitation Devices Extracorporeal Life Support (ECLS) Conclusion References 15: Acid-Base Balance in the Poisoned Patient Rapid Review of Key Factors in Acid-Base Equilibrium Toxicant-Induced Respiratory Alkalosis and Acidosis Toxicant-Induced Metabolic Alkalosis Toxicant-Induced Metabolic Acidosis Clinical Suspicion of Acid-Base Disorders Laboratory Diagnostic Tools in Acid-Base Balance Gaps in Our Knowledge of Acid-Base Disturbances Anion Gap Analytic Limitations and Errors Physiologic Limitations Delta Gap Base Excess Quantitative Acid-Base Analysis: The Strong Ion Gap Applying Strong Ion Theory to the Base Excess Osmol Gap Arterial Blood Gases Treatment of Acid-Base Disorders Summary References 16: Treatment of Acute Respiratory Distress Syndrome in the Poisoned Patient Lung-Damaging Toxicants Three Types of Acute Inhalation Exposures Type I Inhalation Injury Type II Inhalation Injury Type III Inhalation Exposure Non-pulmonary Absorption of Lung-Damaging Toxicants Pathophysiology of ARDS Clinical Definition(s) of ARDS Mortality of ARDS Treatment of ARDS Lung-Protective Ventilation Oxygen and Fractional Inspired Oxygen Rationale for Lung-Protective Ventilation Prone Positioning of the Patient Corticosteroids Sedation and Paralysis to Improve Ventilation Antibiotic Prophylaxis in Toxic ARDS Extracorporeal Membrane Oxygenation (ECMO) ECMO Techniques Cost Effectiveness Long-Term Outcome Conclusions and Recommendations to Overcome Areas of Uncertainty Acknowledgments References 17: Toxicant-Induced Hepatic Injury Definitions Pathogenesis Etiology and Differential Diagnosis Frequency of Causes Toxic Causes Pharmaceuticals Herbal Medications Drugs of Abuse Chemicals Biologic Agents Nontoxic Causes Infections Vascular Events Metabolic and Other Causes Diagnosis and Complications Coagulopathy Encephalopathy Cerebral Edema Cardiovascular Derangements Renal Failure Pulmonary and Ventilatory Derangements Infection Gastrointestinal Bleeding Metabolic Derangements Diagnostic Studies Treatment Coagulopathy Encephalopathy Cerebral Edema Renal Failure Infection Gastrointestinal Bleeding Metabolic Derangements Nutrition Specific Antidotes Prognosis Future Trends References 18: Toxicant-Induced Renal Injury Review of Renal Anatomy and Physiology AKI: Definitions and Clinical Importance Prerenal Acute Kidney Injury Intrinsic Acute Kidney Injury Postrenal Failure Diagnostic Evaluation of Acute Kidney Injury Complications of AKI Management of Acute Kidney Injury References 19: Toxicant-Induced Alterations in Consciousness Pathophysiology Clinical Characteristics Laboratory Studies Treatment of Patients with Altered Mentation Opioid Antagonists Flumazenil Physostigmine Lipid Emulsion Therapy Management of the Agitated Patient Prognosis References 20: Toxicant-Induced Seizures Epidemiology Pathophysiology Gamma-Aminobutyric Acid (GABA) Antagonism Glycine Antagonism Glutamate Agonism Acetylcholine (Muscarinic) Agonism Adenosine Antagonism Other Mechanisms Pathophysiology of Neurologic Sequelae and Systemic Complications Clinical Features Diagnosis Patient History Bedside Evaluation Laboratory Evaluation Electroencephalogram Electrocardiogram Differential Diagnosis Treatment Initial Anticonvulsant Therapy First-Line Therapy Second-Line Therapy Special Conditions Treatment of Refractory Status Epilepticus Special Populations References 21: Cardiac Conduction and Rate Disturbances Cardiac Physiology Myocardial Cell Physiology Role of Calcium Ions in Myocardial Cells Regulation of Cardiac Function Sympathetic Nervous System Parasympathetic Nervous System Pathophysiology Abnormal Impulse Initiation Triggered Rhythms Abnormal Impulse Conduction Toxic Mechanisms of Arrhythmogenesis Membrane Depression Sodium Channel Blockade Slow Calcium Channel Blockade Outward Potassium Channel Blockade Sodium-Potassium ATPase Blockade Adrenergic Receptors β-Receptors α-Adrenoceptor Cholinergic Receptors Nicotinic Cholinergic Receptors Muscarinic Cholinergic Receptors Altered Central Autonomic Nervous System Activity Systemic Influences Clinical Manifestations of Toxic Effects: Cardiac Arrhythmias and Conduction Abnormalities Bradycardia Bradycardia with Conduction Abnormality or Hypoperfusion Bradycardia Without Conduction Abnormalities or Hypoperfusion Treatment Tachycardia Wide-Complex Tachycardia Narrow-Complex Tachycardia Specific Toxins Drugs Causing Bradyarrhythmias β-Adrenergic Receptor Blockers Calcium Channel Blockers Severe Cocaine and Tricyclic Antidepressant Poisoning Drugs Causing Tachyarrhythmias Amphetamines and Cocaine Anticholinergics Antihistamines Tricyclic Antidepressants Caffeine and Theophylline Drugs Causing Either Tachyarrhythmias Or Bradyarrhythmias Cardiac Glycosides Type I Antiarrhythmics Antipsychotic Drugs Summary References 22: Toxicant-Induced Torsade de Pointes Background Pathophysiology Risk Drugs for Torsade de Pointes Risk Factors for Torsade de Pointes in Poisoned Patients Methods for Measurement of the QT Interval How to Best Measure the QT Interval Management of QTc Prolongation in Poisoned Patients Management of Toxicant-Induced Torsade de Pointes References 23: Anticholinergic Syndrome Overview and Incidence History Pathophysiology Toxic Mechanism Clinical Presentations and Life-Threatening Complications Routes of Exposure Intention or Cause of Exposures Adverse Drug Reactions Unintentional Overdose Intentional or Suicidal Overdose Recreational Abuse Malicious Use Toxic Causes or Sources Range of Toxicity Organ System Effects Seizures Cardiovascular Effects Gastrointestinal Effects Skeletal Muscle Effects Temperature Effects Urinary Tract Effects Diagnosis Laboratory Tests Differential Diagnosis Diagnostic Studies Toxicologic Analyses Abnormal Routine Laboratory Test Findings Differential Features Treatment Specific Treatment References 24: Serotonin Syndrome Biochemistry and Clinical Pharmacology Clinical Presentation and Life-Threatening Complications Diagnosis Laboratory Testing Differential Diagnosis Treatment References 25: Sympathomimetic Syndrome Sympathomimetic Toxidrome Pathophysiology Adrenergic Receptors Clinical Presentation Central Nervous System (CNS) Cardiovascular System Renal System Diagnostic Studies Differential Diagnosis Diagnostic Studies Treatment Special Populations References 26: Toxicant-Induced Immunological Reactions History Pathophysiology Drug Reactions Anaphylaxis IgE-Dependent Anaphylaxis IgE-Independent Anaphylaxis Serum Sickness Drug Fever Reactions with a Predominant Organ Involvement Urticaria and Angioedema Severe Cutaneous Adverse Reactions (SCAR) Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) Drug Reaction with Eosinophilia and Systemic Symptoms Vasculitis Hepatitis Renal Failure Hematologic Disorders Hypersensitivity Pneumonitis Immunologic Reactions Due To Specific Agents Antibiotics Penicillins and Other β-Lactams Cross-Reactivity of β-Lactams Other Antibiotics Antiepileptics Local Anesthetics General Anesthesia Latex Nonsteroidal Anti-Inflammatory Drugs Radiographic Contrast Material Biologics Differential Diagnosis Testing In Vitro Tests In Vivo Tests Treatment Anaphylaxis Angioedema Severe Cutaneous Adverse Reactions Readministration of the Drug via Desensitization References 27: Withdrawal Syndromes History Pathophysiology Toxic Effects: Withdrawal Syndrome Alcohol Withdrawal Alcohol Withdrawal Seizures Alcoholic Hallucinosis Delirium Tremens Sedative-Hypnotic Withdrawal Opioid Withdrawal Cocaine Withdrawal Neonatal Withdrawal Differential Diagnosis Diagnostic Studies Treatment Ethanol Withdrawal Sedative-Hypnotic (and γ-Hydroxybutyrate) Withdrawal Opioid Withdrawal Summary References 28: Acute Radiation Injuries Background/Introduction and Possible Scenarios of Acute Radiation Injuries Definition and Types of Ionizing Radiation Biological Effects of Ionizing Radiation Routes of Exposure to Ionizing Radiation Radiation Units of Measurements Personal Protection Principles of Health-Care Providers at the Hospital Acute Radiation Syndrome Management of the Acute Radiation Syndrome Delayed Effects of Acute Radiation Exposure Internal Contamination References 29: Malignant Hyperthermia History Incidence Pathophysiology Diagnostic Testing Clinical Presentation Time of Onset Malignant Hyperthermia-Like Conditions Sudden Cardiac Arrest and Myopathies Awake Malignant Hyperthermia Non-anesthetic Drugs and Circumstances Infection Exercise and Heat Stress Differential Diagnosis Management of Patients with Known Malignant Hyperthermia Susceptibility Treatment Sources of Information Concerning Malignant Hyperthermia References 30: Toxicant-Induced Hematologic Syndromes Hemolysis Pathophysiology and Etiology Clinical Presentation and Diagnosis Treatment Methemoglobinemia Pathophysiology Etiology Congenital Causes Acquired Causes Diagnosis Differential Diagnosis Treatment Asymptomatic Patients Symptomatic Patients Failure to Respond to Methylene Blue Sulfhemoglobin Background and Characteristics Formation and Etiology Diagnosis Clinical Presentation Treatment References 31: Neuroleptic Malignant Syndrome Epidemiology Incidence Demographics Risk Factors Pathophysiology Clinical Features Clinical Course Laboratory Findings Complications and Mortality Diagnosis Differential Diagnosis Evaluation Treatment References 32: Toxicant-Induced Rhabdomyolysis Pathophysiology Drug-Induced Rhabdomyolysis Statins Doxylamine Tricholoma (equestre/flavovirens) Water Hemlock Cocaine Propofol Clinical and Laboratory Manifestations Complications Acute Kidney Injury Treatment Prognosis References Part III: Medication Safety in the Intensive Care Unit 33: Adverse Drug Reactions in the Intensive Care Unit Background Organ System ADRs Allergic/Hypersensitivity ADRs Infusion Reactions Drug-Induced Angioedema Drug-Induced Bronchospasm Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Dermatologic ADRs Steven-Johnson Syndrome and Toxic Epidermal Necrolysis Cardiovascular ADRs Drug-Induced Arrhythmias and Conduction Disturbances Drug-Induced QT Prolongation Drug-Induced Hypotension Drug-Induced Cardiogenic Shock Drug-Induced Distributive Shock Opioids Propofol Treatment Inotropic Agents Vasopressors Hematologic ADRs Drug-Induced Thrombocytopenia Drug-Induced Methemoglobinemia Pulmonary ADRs Drug-Induced Respiratory Disease Drug-Induced Airway Dysfunction Drug-Induced Parenchymal and Interstitial Lung Disease (ILD) Drug-Induced Pulmonary Edema and Vasculopathy Pulmonary Arterial Hypertension Drug-Induced Neuromuscular Respiratory Disease Gastrointestinal ADRs Drug-Induced Constipation/Ileus Delayed Absorption Diarrhea Drug-Induced Hepatotoxicity Drug-Induced Pancreatitis Renal ADRs Drug-Induced Acute Renal Failure Prerenal Nephrotoxicity Intrarenal Nephrotoxicity Postrenal Nephrotoxicity and Nephrotic Syndrome Treatment Neurologic ADRs Drug-Induced Delirium Analgesics Antibiotics Antipsychotics Benzodiazepines Steroids Disturbances in Circadian Rhythm Treatment Drug-Induced Seizures Strategies to Decrease ICU ADRs References 34: Medication Errors and Drug-Drug Interactions in the Intensive Care Unit The ICU Setting Epidemiology Medication Use Process Prevention Strategies Drug-Drug Interactions References Part IV: Medications: Cardiovascular 35: Alpha-2 Adrenergic and Imidazoline Receptor Agonists: Clonidine, Dexmedetomidine, and Related Antihypertensives, Decongestants, and Sedatives Biochemistry and Clinical Pharmacology Clonidine and Related Agents Dexmedetomidine and Etomidate Clinical Pharmacology Pathophysiology of Toxic Effects Clinical Toxicology of Dexmedetomidine Drug Interactions Clinical Presentation and Life-Threatening Complications Diagnosis Treatment Disposition Special Populations Pregnant Patients Pediatric Patients Geriatric Patients Other Special Populations Exposures and Poison Prevention References 36: Beta-Receptor Antagonists Introduction Biochemistry and Clinical Pharmacology Pharmacokinetics Pathophysiology Beta Receptors Effects of β-Receptor Blockade Airways Cardiac Membrane Stabilizing Activity Blood Vessels Metabolic Effects Clinical Presentation Cardiac Bradydysrhythmias Cardiac Conduction Defects Pump Failure Hypotension Pulmonary Respiratory Depression Neurologic Miscellaneous Diagnosis Treatment Decontamination Cardiovascular Effects Bradydysrhythmias Cardiac Conduction Defects Pump Failure Noncardiovascular Effects Special Population Pediatric Patients Elderly Patients Pregnant Patients Breast-Feeding Patients References 37: Calcium Channel-Blocking Agents Biochemistry and Clinical Pharmacology Pathophysiology of Toxic Effects Cardiac Effects Arterial Vasculature Pancreatic Effects Metabolic Effects Clinical Presentation and Life-Threatening Complications Hypotension Cardiac Conduction Deficits Cardiac Dysrhythmias Noncardiogenic Pulmonary Edema Diagnosis Treatment Asymptomatic Patients Symptomatic Patients: First-Line Treatments Calcium (Level II-3 Evidence) High-Dose Insulin (Level II-2 Evidence) Norepinephrine or Epinephrine (Level II-3 Evidence) Other Vasopressors and Inotropes Symptomatic Patients: Refractory to First-Line Treatments Cardiac Pacing (Level II-3 Evidence) Lipid Emulsion (Level II-3 Evidence) Symptomatic Patients: Refractory Shock or Peri-arrest Extracorporeal Life Support (Level II-3 Evidence) Patients in Cardiac Arrest Other Treatments Glucagon Methylene Blue Other Therapies Special Populations Pediatric Patients References 38: Digitalis Glycosides Biochemistry of Digitalis Glycosides Pharmacology and Mechanisms of Toxicity Clinical Presentation and Life-Threatening Complications Clinical and ECG Features Fatality and Prognosticators Diagnosis Management Gastrointestinal Decontamination Extracorporeal Removal Techniques Indications for ICU Admission Electrolyte Disorders Non-antidotal Therapies Anti-digoxin-Specific Fab Fragments Special Populations Pediatric Patients Known Digoxin Intoxication Signs and Symptoms of Digitalis Toxicity Pregnant Patients Elderly Patients Renal Dysfunction Patients References 39: Sodium Channel-Blocking Antidysrhythmics Clinical Pharmacology Pathophysiology of Cardiac Action Potentials and Myocardial Toxicity Resulting from Sodium Channel-Blocking Antidysrhythmic Poisoning Clinical Presentation and Life-Threatening Complications Diagnosis Treatment Decontamination Hypertonic Sodium Bicarbonate Respiratory Alkalosis to Induce Serum Alkalization Hypertonic Saline Intraventricular Conduction Delays Dysrhythmia Hypotension High-dose Insulin Euglycemia (HIE) Therapy Intravenous Lipid Emulsion Seizures Hypoglycemia Disposition References 40: Sodium Nitroprusside Cyanide Toxicity from Sodium Nitroprusside Chemistry and Pathophysiology Pharmacokinetics Clinical Findings and Toxic Doses Diagnosis Prevention Treatment Thiocyanate Toxicity from Sodium Nitroprusside Clinical Findings and Toxic Doses Diagnosis Prevention of and Monitoring for Toxicity Treatment Special Populations Pregnant Patients References 41: Sympathomimetic Agents Chemistry and Biochemistry of Sympathomimetic Agents Pathophysiology Adrenergic Receptors Agents with Combined α-Adrenergic and β-Adrenergic Activity Epinephrine, Norepinephrine, and Dopamine Ephedrine and Pseudoephedrine Metaraminol, Mephentermine, Methoxamine, and Midodrine β-Adrenergic Agonists Nonselective β-Adrenergic Agonists Selective β2-Agonists Selective β3-Agonists α-Adrenergic Agonists Clinical Presentation Epinephrine, Norepinephrine, and Dopamine Ephedrine and Pseudoephedrine β-Adrenergic Agonists Nonselective β-Adrenergic Agonists Selective β2-Agonists Adverse Effects of β-Adrenergic Agonists Adverse Effects of β2-Adrenergic Agonists Adverse Effects of β3-Adrenergic Agonists Adverse Effects of α1-Adrenergic Agonists Phenylephrine and Synephrine Methoxamine, Metaraminol, and Mitodrine Diagnosis Treatment Treatment of Toxicity from Combined α-Adrenergic and β-Adrenergic Agents Treatment of β-Adrenergic Agonist Poisoning Treatment of α-Adrenergic Agonist Toxicity Special Situations References Part V: Medications: Decongestant/Antihistaminergic/Bronchodilatory 42: Antihistamines Biochemistry and Clinical Pharmacology Kinetics for Oral Exposure in Healthy Adults Pathophysiology of Toxic Effects Clinical Presentation and Life-Threatening Effects Neurologic Effects Cardiac Effects Other Effects Diagnosis Treatment Special Populations Pediatric Patients Female Patients Elderly Patients Patients Taking Other Medications Pregnant Patients Key Points References 43: Theophylline and Other Methylxanthines Biochemistry and Pharmacology Pathophysiology of Toxic Effects Clinical Presentation and Life-Threatening Complications Organ System Effects Gastrointestinal Manifestations Cardiovascular Manifestations Central Nervous System Manifestations Metabolic Manifestations Drug Concentrations: Therapeutic and Toxic Drug Monitoring Treatment Supportive Care Gastrointestinal Decontamination Pharmacologic Management Vasopressors Electrolytes Arrhythmias Hypotension Seizures Emesis Enhancement of Elimination Other Methylxanthines: Caffeine and Pentoxifylline Special Populations References Part VI: Medications: Psychotropic 44: Antipsychotics Classification Clinical Pharmacology Pathophysiology of Therapeutic and Toxic Effects Pharmacokinetics Drug Interactions Clinical Presentation Overdose Cardiovascular Toxicity Seizures Hepatotoxicity Blood Dyscrasias Extrapyramidal Syndromes Diagnosis Differential Diagnosis Treatment Overdose Acute Dystonic Reactions Akathisia Parkinsonism Tardive Dyskinesia Disposition Special Populations Patients with Renal Impairment Patients with Hepatic Impairment Infants, Children, and Elderly Patients Patients of Different Races and Ethnic Groups Pregnant and Breast-Feeding Patients References 45: Anxiolytics, Sedatives, and Hypnotics Biochemistry and Clinical Pharmacology of Benzodiazepines Pathophysiology of Toxic Effects Clinical Presentation and Life-Threatening Complications Anxiolytic/Sedative-Hypnotic Drug Withdrawal Special Agents Dexmedetomidine Propofol Ramelteon Suvorexant Chloral Hydrate Older, Less Used Sedative-Hypnotics Glutethimide Ethchlorvynol Meprobamate Methaqualone Diagnosis Treatment Treatment: Chloral Hydrate Treatement: Acute Sedative-Hypnotic Withdrawal Special Populations Pediatric Patients Pregnant and Breast-Feeding Patients Elderly Patients Special Populations: Chloral Hydrate References 46: Barbiturates Biochemical and Pharmacokinetic Properties Pathophysiology of Therapeutic and Toxic Effects Clinical Presentation and Life-Threatening Complications Diagnosis Treatment Barbiturate Withdrawal Special Populations Pediatric Patients Pregnant and Breastfeeding Patients Elderly Patients Veterinary Medicine Professionals References 47: Bupropion Biochemistry and Clinical Pharmacology Clinical Presentation Therapeutic Dose Overdose Neurologic Toxicity Cardiovascular Toxicity Brain Death mimic Death Recreational Abuse and Misuse Diagnosis Treatment Supportive Care Decontamination Seizure Management Cardiovascular Support Conduction Abnormalities Cardiovascular Instability References 48: Cyclic Antidepressants Biochemistry and Clinical Pharmacology Pharmacokinetics Pathophysiology Antihistaminic Effects Anticholinergic (Antimuscarinic) Effects Antagonism of α-Adrenergic Receptors Inhibition of Amine Reuptake Sodium Channel Blockade Potassium Channel Antagonism γ-Aminobutyric Acid A Receptor Antagonism Clinical Presentation Clinical Manifestations of Acute Overdose Diagnosis Treatment Altered Level of Consciousness Seizures Hypotension Dysrhythmias Disposition References 49: Lithium Biochemistry and Clinical Pharmacology Chemistry Pharmacokinetics Pathophysiology Central Nervous System Effects Cardiac Effects Thyroid Effects Renal Effects Clinical Presentation Neurologic Effects Renal Effects Thyroid Effects Cardiac Effects Diagnosis Acute Toxicity Chronic Toxicity Treatment Gastrointestinal Decontamination Activated Charcoal Gastric Lavage/Whole-Bowel Irrigation Sodium Polystyrene Sulfonate Enhancement of Elimination Extracorporeal Techniques Hemodialysis Continuous Hemodialysis, Hemofiltration, Hemodiafiltration, and Related Techniques Peritoneal Dialysis Indications for Extracorporeal Removal Other Therapies Treatment of Nephrogenic Diabetes Insipidus Special Populations Pregnant Patients Other Patients References 50: Monoamine Oxidase Inhibitors Biochemistry, Pathophysiology, and Clinical Pharmacology Pharmacokinetics Clinical Presentation of Acute Overdose Tyramine Reaction Diagnosis Treatment Hypertension Hypotension Dysrhythmias Seizures Hyperthermia Admission Criteria Extracorporeal Removal Techniques Tyramine Reaction Drug Interactions References 51: Serotonergic Antidepressants SSRIs Biochemistry and Clinical Pharmacology Pathophysiology of Toxic Effects Clinical Presentation and Life-Threatening Complications Serotonin Syndrome Cardiovascular Diagnosis Treatment Serotonin Syndrome Decontamination QT Prolongation NSRIs (SNaRIs) Biochemistry and Clinical Pharmacology Pathophysiology of Toxic Effects Clinical Presentation and Life-Threatening Complications Serotonin Syndrome Central Nervous System Effects Cardiovascular Diagnosis Treatment Tetracyclic Antidepressants Biochemistry and Clinical Pharmacology Pathophysiology of Toxic Effects Clinical Presentation and Life-Threatening Complications Mirtazapine Mianserin Diagnosis Treatment Triazolopyridines (Phenylpiperazines) Biochemistry and Clinical Pharmacology Pathophysiology of Toxic Effects Clinical Presentation and Life-Threatening Complications Diagnosis Treatment References Part VII: Medications: Anticonvulsant 52: Hydantoin Anticonvulsants: Phenytoin and Fosphenytoin Biochemistry and Clinical Pharmacology Pharmacokinetics Pathophysiology Diluent Effects Clinical Presentation Relationship Between Plasma Concentration and Toxicity Central Nervous System Toxicity Cardiovascular Toxicity Vascular and Soft Tissue Injury Non-Dose-Related Adverse Effects Diagnosis Treatment Fosphenytoin References 53: Iminostilbene Anticonvulsants: Carbamazepine and Oxcarbazine Biochemistry and Clinical Pharmacology Pharmacodynamics Pharmacokinetics Toxicokinetics Toxicodynamics Clinical Presentation of Carbamazepine Overdose and Life-Threatening Complications Corre