Public Health and Toxicology Issues in Drug Research, Volume 2

Public Health and Toxicology Issues in Drug Research: Toxicity and Toxicodynamics, Volume Two examines implications on public health and the impact of pharmaceuticals, chemical and food toxicants, dietary phytochemicals, and medical treatments. The book cover topics on pharmacokinetics and toxicokinetics, such as population pharmacokinetics/toxicokinetics, the design of toxicokinetic studies, and the use of toxicokinetic data in preclinical safety assessments. In addition, it investigates the health effect caused by the bioaccumulation of pharmaceutical and personal care products and the impact of drug-induced toxicity on different systems of the body.

Final sections discuss the mechanistic pathways of food toxicants and illustrate the molecular mechanisms of the chemopreventive role of dietary phytochemicals. Ethical, legal, societal, and professional issues in toxicology round off coverage, making this a valuable resource for anyone interested in learning more about the health impact and public health issues related to the toxicity of pharmaceuticals, dietary supplements, personal care products, and medical treatments.

Cover image
Title page
Table of Contents
Copyright
Contributors
Chapter 1. Biomarkers: Revolutionizing disease monitoring and therapeutic strategies
1.1. Introduction to biomarkers
1.2. Biomarker types
1.3. Positive and negative influences of biomarkers
1.4. Role of biomarkers in disease prevention, diagnosis and treatment
1.5. Future perspective and challenges of biomarkers
1.6. Conclusion
Chapter 2. Connecting biotransformation with toxicity
2.1. Introduction
2.2. Role of hepatic enzymes in phase I of biotransformation
2.3. Role of hepatic enzymes in phase II of biotransformation
2.4. Significance of CYP 450 in biotransformation of xenobiotics other than hepatic cells
2.5. Case studies highlighting biotransformation-induced toxicity
2.6. Role of nanoparticles in biotransformation-induced toxicity
2.7. Conclusion
Chapter 3. Idiosyncratic drug reactions and toxicities
3.1. Introduction
3.2. Clinical characteristics of idiosyncratic drug reactions
3.3. Mechanistic hypotheses on IDRs
3.4. Role of drug metabolism in toxicity
3.5. Drug-induced idiosyncratic reaction
3.6. Genetic basis of idiosyncratic toxicity
3.7. Screening tools for idiosyncratic toxicity
3.8. Prevention of IDRs in IDILI
3.9. Conclusions
Abbreviations
Chapter 4. Importance of dose selection in toxicity studies
4.1. Introduction
4.2. Toxicity testing: An overview
4.3. Factors essential for dose selection
4.4. Selection of dose level
4.5. Dose selection method for toxicity studies
4.6. Case studies
4.7. Conclusion
Abbreviations
Chapter 5. Implication of sex differences in toxicology
5.1. Introduction
5.2. Gender-based medicine and its importance
5.3. Gender differences influencing toxicology
5.4. Sex differences influencing variations in toxicological parameters
5.5. Conclusion
Abbreviations
Chapter 6. Toxicological risk assessment and risk management
6.1. Introduction
6.2. Importance of toxicological risk assessment and risk management
6.3. Basic steps involved in toxicological risk assessment
6.4. Uncertainty factors in toxicological risk assessment
6.5. Various strategies and techniques for risk assessment
6.6. Epidemiological methods usage in risk assessment
6.7. Emerging problems and challenges in risk assessment
6.8. Conclusion
Abbreviations
Chapter 7. Adverse outcome pathway: A paradigm shift in chemical toxicological analysis
7.1. Introduction
7.2. Adverse outcome pathway
7.3. Applications of AOP
7.4. Strategies for AOP development
7.5. Review and assessment process for AOP
7.6. AOP Knowledge Base
7.7. AOPs for nanomaterials
7.8. AOPs for drug-induced diseases
7.9. Epigenetic modification and AOP
7.10. Advantages and limitations of AOP
7.11. In vitro data and in silico models for predictive toxicology
7.12. Conclusion and future perspective
Abbreviations
Chapter 8. Design of toxicokinetic studies
8.1. Introduction
8.2. Biopharmaceutical assessment before toxicology
8.3. Dose–response relationship with toxicokinetics
8.4. Sampling schedules in toxicokinetics
8.5. Importance of toxicokinetics studies
8.6. Types of toxicokinetic models
8.7. Parameters measured in toxicokinetic studies
8.8. Role of toxicokinetics in clinical studies
8.9. Role of toxicokinetics in risk assessment
8.10. Conclusion
Abbreviations
Chapter 9. Use of toxicokinetic data in preclinical safety assessment
9.1. Introduction
9.2. Role of toxicokinetics in preclinical studies
9.3. Toxicokinetic data in selection of route of administration
9.4. Toxicokinetic data in dose selection
9.5. Conclusion and future aspects
Abbreviations
Chapter 10. Drug-induced cardiotoxicity
10.1. Introduction
10.2. Mechanisms of cardiac toxicity
10.3. Diagnosis and monitoring of drug-induced cardiotoxicity
10.4. Classes of drugs that induced cardiac toxicity
10.5. Antineoplastic agents
10.6. Herb's role in blocking anticancer drug-induced cardiac toxicity
10.7. Prevention and management of cardiac toxicity
10.8. Conclusion
Abbreviations
Chapter 11. Drug-induced immunotoxicity
11.1. Introduction
11.2. Clinical features of drug-induced immunotoxicity
11.3. Different types of immunotoxic effects and associated adverse clinical consequences
11.4. Immunotoxicity assessment guidelines
11.5. Evaluation of immunotoxicity
11.6. Correlation between in vitro and in vivo immunotoxicity test for nanomedicines
11.7. Conclusion
Abbreviations
Chapter 12. Drug-induced photosensitivity
12.1. Introduction
12.2. Phototoxic versus photoallergy reaction
12.3. Biological aspects of drug-induced photosensitivity
12.4. Mechanism of drug-induced photosensitivity
12.5. Common phototoxic and photoallergic drugs
12.6. Screening tools and guidelines for photosensitizing agents
12.7. Management of photosensitivity
12.8. Diagnostic challenge in drug-induced photosensitivity
12.9. Conclusion
Abbreviations
Chapter 13. Toxic effects of cancer therapies
13.1. Introduction
13.2. Toxicities caused by anticancer chemotherapeutics and their interventions
13.3. Financial toxicity of anticancer therapies
13.4. Conclusion
Abbreviations
Chapter 14. High content screening in toxicology
14.1. Introduction
14.2. High content screening in drug discovery
14.3. Imaging-based HCS
14.4. Mechanistic investigation of toxicity with HCS
14.5. HCS in toxicology
14.6. In vitro neuronal models for analysis of proliferation using HCS
14.7. In vivo HCS in toxicology
14.8. Developmental toxicity assay using HCS of zebrafish embryos
14.9. Applications of HCS-based assay in toxicity assessment
14.10. Success of HCS with high throughput screening in toxicology
14.11. Automation in HCS
14.12. Conclusion
Abbreviations
Chapter 15. High-throughput screening in toxicity assessment
15.1. Introduction
15.2. HTS in toxicology
15.3. HTS for analysis of in vitro toxicity
15.4. In vivo methods for high throughput toxicity screening
15.5. HTS to identify chemical cardiotoxic potential
15.6. HTS techniques for investigating drug metabolism and PK
15.7. HTS in drug discovery
15.8. Computer-aided prediction of drug toxicity in HTS
15.9. Conclusion
Abbreviations
Chapter 16. Population pharmacokinetics/toxicokinetics
16.1. Introduction
16.2. Population models
16.3. Methods to estimate population PK parameters
16.4. Applications of population approaches in toxicology
16.5. Challenges and opportunities associated with population variability
16.6. Statistical issues in TK modeling with a Bayesian perspective
16.7. Case studies
16.8. Conclusion
Abbreviations
Chapter 17. Quantitative extrapolation interspecies scaling/low-dose extrapolation
17.1. Introduction
17.2. Biological basis for extrapolation across mammalian species
17.3. Tools to assist in the analysis of data
17.4. Interspecies extrapolation methods
17.5. Low-dose-rate extrapolation using the multistage model
17.6. Low-dose extrapolations in toxicology
17.7. In vitro–in vivo extrapolation and allometric scaling
17.8. Interspecies extrapolations in risk analysis
17.9. Limitations and applications of interspecies scaling and in vitro extrapolation in pharmacokinetics
17.10. Extrapolation of animal toxicity to humans for interspecies comparisons in drug development
17.11. Quantitative analysis of interspecies extrapolation of historical toxicity data
17.12. Conclusion
Abbreviations
Chapter 18. Toxicity and toxicodynamics of cryoprotectant used in pharmaceutical products
18.1. Introduction
18.2. Types of cryoprotective agents
18.3. Mechanism of cryoprotectant toxicity
18.4. Cryopreservation of cells
18.5. Challenges during cryopreservation
18.6. Dimethyl sulfoxide—A key component of cryobiology
18.7. Quantification methods for cryoprotectant toxicity
18.8. Methods for prevention of cryoprotectant toxicity
18.9. Conclusion
Chapter 19. Insect repellents as an environmental chemical toxicant to human health
19.1. Introduction
19.2. Types of insect repellants
19.3. Safety evaluation or toxicity testing of insect repellants
19.4. Impact of insect repellents on human health and environment
19.5. Conclusion
Abbreviations
Chapter 20. Clinical toxicity of antibody–drug conjugates
20.1. Introduction
20.2. Role of antibody–drug conjugate
20.3. Mechanism of action of ADC
20.4. Toxicity of ADC and its pharmacology
20.5. Pharmacokinetic considerations for ADC
20.6. Challenges and advances in the assessment of the disposition of ADC
20.7. Analytical techniques for ADCs physicochemical characterization
20.8. ADCs as targeted cancer therapies
20.9. Conclusion
Abbreviations
Chapter 21. Cumulative toxicity of herbal drugs
21.1. Introduction
21.2. Need for herbal toxicity testing
21.3. Toxic contaminants in herbal medicines
21.4. Toxicity from different systems of medicines
21.5. Toxicity from herbal substitute/adulteration
21.6. Drug–herb interaction
21.7. Current “omics” methods for assessing the toxicity of herbal medicines
21.8. Zebrafish embryo for herbal medicine toxicity assessment
21.9. Strategies to eliminate toxicity
21.10. Toxicological challenges related to herbal medicinal products use
21.11. Quality and regulatory challenges
21.12. Conclusion
Abbreviations
Chapter 22. Radiotherapy toxicity
22.1. Introduction
22.2. Mechanism/pathophysiology of radiotherapy toxicity
22.3. Different organ toxicity caused by radiotherapy
22.4. Types of toxicity: Acute and chronic
22.5. Immunomodulatory effect of radiation
22.6. Diagnosis of radiotherapy toxicity
22.7. Prevention and management of radiotherapy toxicity
22.8. Radiotherapy toxicity measurement assay
22.9. Different prediction models of radiotherapy toxicity
22.10. Genetics and genomics of radiotherapy toxicity
22.11. Molecular biomarkers for predicting radiotherapy toxicity
22.12. Conclusion and future prospects
Abbreviations
Chapter 23. Toxicities and toxicodynamic of anesthetics
23.1. Introduction
23.2. Types of anesthetic toxicities
23.3. Consequences of LAs in infants and children
23.4. Toxicodynamics of anesthetics acting alone or in combination with other drugs
23.5. Conclusion
Abbreviations
Chapter 24. Toxicity of nanomaterials
24.1. Introduction
24.2. Characterization of nanomaterials
24.3. Effect of various nanomaterial properties on the toxicity of nanomaterials
24.4. Epidemiological findings
24.5. Impact on nanomaterial exposure
24.6. Possible human exposure to nanomaterials
24.7. Assays for toxicity
24.8. Need for toxicity evaluation of nanomaterial
24.9. Metabolism of nanomaterials
24.10. Toxicity of nanomaterials
24.11. Recent advances in toxicological assessment of nanomaterials
24.12. Safety guidelines for handling nanomaterials
24.13. Applications and toxic influence of recent nanomaterials
24.14. Emerging challenges
24.15. Conclusion
Abbreviations
Chapter 25. Principles of management of acute poisoning
25.1. Introduction
25.2. Acute poisoning: Some myths and misconceptions
25.3. Accuracy of diagnosis
25.4. Common complications associated with acute poisoning
25.5. Toxicological analysis
25.6. Approach to the individual patient
25.7. Activated charcoal as a universal antidote
25.8. Drug pharmacokinetics in overdoses
25.9. Conclusion
Abbreviations
Chapter 26. Connecting link between pesticides and Parkinson's disease
26.1. Introduction
26.2. Epidemiological evidence
26.3. Mechanisms involved in the PD progression by pesticide exposure
26.4. Pesticides associated with Parkinson's disease
26.5. Conclusions
Abbreviations
Chapter 27. Psychopharmacology in late life: Key challenges and opportunities
27.1. Introduction
27.2. Geriatric psychopharmacology
27.3. Psychotropic drugs in late life
27.4. Opportunities for psychopharmacology in late life
27.5. Challenges of psychopharmacology in the elder patients
27.6. Conclusion
Abbreviations
Chapter 28. Ethical, legal, societal, and professional issues in toxicology
28.1. Introduction
28.2. Toxicology studies of drugs
28.3. Ethical issues in toxicology
28.4. Legal aspects of toxicology
28.5. Societal issues
28.6. Professional issues
28.7. Conclusion
Abbreviations
Index

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Public Health and Toxicology Issues in Drug Research, Volume 2

Toxicity and Toxicodynamics

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Rakesh Kumar Tekade