Abstract
Low molecular weight organic chemicals can be transformed by normal drug-metabolising systems into shortlived metabolites that are inherently reactive towards cellular macromolecules. There is direct evidence that the formation of such chemically reactive metabolites may lead to mutagenesis, carcinogenicity, apoptosis and necrosis in both cell and animal models. A number of drugs associated with non-pharmacological drug toxicities in man have been shown to undergo bioactivation either in vivo or in vitro. We have therefore examined the evidence for the role of reactive metabolites in the three most common drug-induced toxicities: hepatotoxicity, skin reactions and blood dyscrasias.
Keywords: hepatotoxicity, skin reaction, blood dyscrasias, reactive metabolites
Current Drug Metabolism
Title: Are Chemically Reactive Metabolites Responsible for Adverse Reactions to Drugs?
Volume: 3 Issue: 4
Author(s): D. P. Williams, N. R. Kitteringham, D. J. Naisbitt, M. Pirmohamed, D. A. Smith and B. K. Park
Affiliation:
Keywords: hepatotoxicity, skin reaction, blood dyscrasias, reactive metabolites
Abstract: Low molecular weight organic chemicals can be transformed by normal drug-metabolising systems into shortlived metabolites that are inherently reactive towards cellular macromolecules. There is direct evidence that the formation of such chemically reactive metabolites may lead to mutagenesis, carcinogenicity, apoptosis and necrosis in both cell and animal models. A number of drugs associated with non-pharmacological drug toxicities in man have been shown to undergo bioactivation either in vivo or in vitro. We have therefore examined the evidence for the role of reactive metabolites in the three most common drug-induced toxicities: hepatotoxicity, skin reactions and blood dyscrasias.
Export Options
About this article
Cite this article as:
Williams P. D., Kitteringham R. N., Naisbitt J. D., Pirmohamed M., Smith A. D. and Park K. B., Are Chemically Reactive Metabolites Responsible for Adverse Reactions to Drugs?, Current Drug Metabolism 2002; 3 (4) . https://dx.doi.org/10.2174/1389200023337423
DOI https://dx.doi.org/10.2174/1389200023337423 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
Call for Papers in Thematic Issues
Exploring oxidative stress and the anti-oxidant defense system in chronic diseases: therapeutic strategies and future perspective
Ageing is facilitated by oxidative stress (OS), which happens spontaneously. Several studies have demonstrated that OS over an extended period of time has a role in the emergence of several chronic illnesses. Diabetes, cancer, and heart disease are a few examples of these ailments. An imbalance between the body's antioxidants ...read more
Impact of brain tissue binding and plasma protein binding of drugs in DMPK
The impression of brain tissue binding (BTB) or plasma protein binding (PPB) in Drug Metabolism and Pharmacokinetics is critical to understanding the distribution, efficacy, and potential toxicity of drugs that target the central nervous system (CNS). BTB and high PPB influence the distribution of drugs in the body and their ...read more
Interaction between drugs and endocrine diseases
The introduction of highly active antiretroviral therapy accelerated studies and our understanding on the interaction between pharmacological therapies and endocrine diseases. Drugs can precipitate endocrine via different mechanisms, including direct alteration of hormone production and secretion, dysregulation of hormonal axis, effects on hormonal transport, receptor-binding, and cellular signalling. Common drug-induced ...read more
Safety evaluation of vaccine combination
Vaccine combination safety evaluation is a critical field within immunology and public health that focuses on assessing the safety and efficacy of combining different vaccines to maximize protection against various diseases while minimizing potential adverse effects. This process is significant because it ensures that vaccines can be administered together without ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
HtrA Protease Family as Therapeutic Targets
Current Pharmaceutical Design Cross Talk Among Leukocytes, Platelets, and Endothelial Cells and its Relevance to Atherosclerosis and Coronary Heart Disease
Current Nutrition & Food Science Antioxidant Therapy and Drugs Interfering with Lipid Metabolism: Could They Be Effective in NAFLD Patients?
Current Pharmaceutical Design Nitric Oxide and Protection against Cardiac Ischemia
Current Pharmaceutical Design Pathogenesis of Alzheimer Disease: Role of Oxidative Stress, Amyloid-β Peptides, Systemic Ammonia and Erythrocyte Energy Metabolism
CNS & Neurological Disorders - Drug Targets Anti-inflammatory Sulfur-Containing Agents with Additional Modes of Action
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Myocardial Infarction with and without ST-segment Elevation: a Contemporary Reappraisal of Similarities and Differences
Current Cardiology Reviews Cellular Mechanisms of the Protective Effect of Polyphenols on the Neurovascular Unit in Strokes
Cardiovascular & Hematological Agents in Medicinal Chemistry The Urocortins: Mechanisms of Cardioprotection and Therapeutic Potential
Mini-Reviews in Medicinal Chemistry Proteinase-Activated Receptor 2 (PAR2): A Challenging New Target for Treatment of Vascular Diseases
Current Pharmaceutical Design Controlled Release of Growth Factors for Regenerative Medicine
Current Pharmaceutical Design Ecto-Nucleotidase Inhibitors: Recent Developments in Drug Discovery
Mini-Reviews in Medicinal Chemistry A Review on Clinical Management and Pharmacological Therapy on Hereditary Haemorrhagic Telangiectasia (HHT)
Current Vascular Pharmacology Drugs of Abuse: Epigenetic Mechanisms in Toxicity and Addiction
Current Medicinal Chemistry Significant Overlapping Modules and Biological Processes Between Stroke and Coronary Heart Disease
CNS & Neurological Disorders - Drug Targets FTY720: A Most Promising Immunosuppressant Modulating Immune Cell Functions
Mini-Reviews in Medicinal Chemistry Gut Microbiota and Cardiovascular Disease: Symbiosis Versus Dysbiosis
Current Medicinal Chemistry Fish Oil Fatty Acids as Cardiovascular Drugs
Current Vascular Pharmacology Hydrogen Sulfide and Inflammatory Joint Diseases
Current Drug Targets Treatment of Foot Disease in Patients with Type 2 Diabetes Mellitus using Human Umbilical Cord Blood Mesenchymal Stem Cells: Response and Correction of Immunological Anomalies
Current Pharmaceutical Design