Toxicology of Organophosphate Poisoning : New Insights

the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Preface 5 About the Book 7 Contents 9 About the Author 12 Chapter 1: Overview of Organophosphate Compounds 14 1.1 Introduction 14 1.2 Classification, Properties, and Synthesis of Organophosphates 15 1.2.1 Classification 15 1.2.2 General Properties 16 1.2.3 Physicochemical Properties and Structure-Activity Relationships 17 1.2.4 Synthesis 18 1.3 Applications 18 1.3.1 Agriculture 19 1.3.2 Industry 19 1.3.3 Nerve Agent or Warfare Agent 20 1.4 OP Poisoning in Biotic and Abiotic Components 22 1.4.1 Biotic Component 23 1.4.1.1 Human 23 1.4.2 Aquatic and Marine Life 24 1.4.3 Soil Biota 27 1.5 Abiotic Component 28 1.5.1 Water 28 1.5.2 Soil 29 1.5.3 Air 31 1.6 The Major Concern and Future Prospects 31 References 32 Chapter 2: Toxicology of Organophosphate Poisoning in Human 39 2.1 Introduction 39 2.2 Pathophysiology and Clinical Manifestation 41 2.2.1 Receptor-Specific Manifestations 41 2.2.2 Duration-Based Manifestations 43 2.2.3 Organs-Specific Manifestations 44 2.2.3.1 Neurological Manifestations 44 2.2.3.2 Cardiovascular Manifestations 44 2.2.3.3 Respiratory Manifestations 45 2.2.3.4 Hepatological Disorders 45 2.3 Toxicokinetics of OP 46 2.4 Assessment of Organophosphate Exposure 47 2.4.1 Through Metabolites of OP Present in the Urine 47 2.4.2 Blood Cholinesterase Activities 48 2.4.3 Other Methods of Detection 49 2.5 Future Prospect and Concern 49 References 50 Chapter 3: Enzymatic Targets of Organophosphates 56 3.1 Cholinergic Enzymes as Primary Targets of Organophosphate 56 3.2 Insights of Functional Aspect of Acetylcholinesterase 57 3.3 The Binding Pocket Is Lined with Conserved Aromatic Amino Acids 59 3.4 Mechanistic of Acetylcholinesterase Inhibition 60 3.4.1 Kinetic Behavior of Acetylcholinesterase Inhibition 63 3.4.2 Acetylcholinesterase: Reactivation Versus Aging 65 3.4.2.1 Aging of Acetylcholinesterase 65 3.4.3 Reactivation of Human Acetylcholinesterase 67 3.4.4 Feasibility of Reactivation of Aged Cholinesterase 69 3.5 Other Targets of Organophosphate 70 3.5.1 Butyrylcholinesterase (BuChE) 70 3.5.2 Arylformidase or Kynurenine Formidase 70 3.5.3 Neuropathy Target Esterase (NTE) 71 3.5.4 Acylpeptide Hydrolase (APH) 71 3.5.5 Monoacylglycerol Lipase (MAGL) and Fatty Acid Amide Hydrolase (FAAH) 72 3.6 Future Prospect and Major Concern 72 References 72 Chapter 4: Management and Modulation of Cholinesterase 78 4.1 Introduction 78 4.2 Resurrection of Acetylcholinesterase 79 4.2.1 Use of Oximes as Potential Reactivators of AChE 79 4.2.2 Bioscavenging the Organophosphates 81 4.2.2.1 Stoichiometric Bioscavengers 81 4.2.3 Catalytic Bioscavengers 82 4.2.4 Nanotechnology Approach 83 4.2.5 Realkylation of Aged AChE 84 4.3 Major Concern and Future Prospect 85 References 85 Chapter 5: Pharmacological Interventions for OP Poisoning 89 5.1 Introduction 89 5.2 The Antidotes for the Management of OP Poisoning 91 5.2.1 Atropinization: Controlling the Muscarinic Symptoms 91 5.2.1.1 Oximes: Rescuing the Phosphorylated Cholinesterases 91 5.2.2 Benzodiazepines: Seizure Management 92 5.3 Other Pharmacological Interventions 93 5.3.1 Magnesium Sulfate 93 5.3.2 Clonidine 94 5.3.3 Sodium Bicarbonate (NaHCO3) 95 5.3.4 Bioscavenging 95 5.4 Future Prospect and Major Concern 96 References 96 Chapter 6: Management of Human Organophosphate Poisoning 100 6.1 Introduction 100 6.2 Clinical Management 101 6.2.1 Initial Assessment of Poisoning 101 6.2.2 Identification of Causative Agent 101 6.2.3 Atropinization and Administration of Fluids 102 6.2.4 Use of Oximes 102 6.2.5 Procedures for Life Support 102 6.2.5.1 Resuscitation of Patients and Managing the Airway 102 6.2.5.2 Decontamination 103 6.2.5.3 Hemodialysis 103 6.3 Role of Community Health Management System 104 6.4 Policy Framework 105 6.4.1 Community Intervention and Training 105 6.4.2 Future Prospect and Major Concern 106 References 106 Index 109 This book addresses the consequences of high agricultural pesticide use over the last few decades in the form of organophosphate poisoning. The authors provide a background overview of organophosphate compounds, their environmental toxicity, non-target exposures and cases of human poisoning. The authors also compile and analyze data from the last two decades to demonstrate the toxicological aspects of organophosphates, and how they can pose a threat to human health. Readers will learn about the clinical manifestation of organophosphate exposure in humans, as well as the enzymatic pathways and mechanisms by which organophosphates are processed in the body and cause harm. The book concludes by providing techniques, practices and recommendations for how to manage organophosphate exposure and poisoning. It will be useful for clinicians and public health professionals, scientists, medical practitioners, researchers and environmental toxicologists.