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
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
Tissue Distribution and Metabolism of Micro- and Nanoparticles and Medical Implants
With the continuous advancement of modern science and engineering, numerous functional materials and active molecules have been developed and utilized in various industrial, medical, and food applications. Many of these can enter the body, either actively or passively, and have significant and intricate impacts on human health. For example, biomaterials ...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
-
Research Progress of the UPR Mechanism and its Effect on Improving Foreign Protein Expression
Protein & Peptide Letters Chemokines as Therapeutic Targets for Renal Diseases
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Inhibitors of c-jun-N-Terminal Kinase (JNK)
Mini-Reviews in Medicinal Chemistry Clinical Applications of Creatine Supplementation on Paediatrics
Current Pharmaceutical Biotechnology The Possible Involvement of Glycogen Synthase Kinase-3 (GSK-3) in Diabetes, Cancer and Central Nervous System Diseases
Current Pharmaceutical Design Hydroxysafflor Yellow A Attenuates Renal Ischemia- Reperfusion Injury in a Rat Model
Letters in Drug Design & Discovery Potential Role of ADAMTS13 in the Progression of Alcoholic Hepatitis
Current Drug Abuse Reviews On the Cellular and Molecular Regulatory Transcriptional Mechanisms and Responsive Putative Pathways to Inflammatory Oxidative Stress Revisited: Current Immunological Breakthroughs and Views at a Glance
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Structure-Function Relationships of PEDF
Current Molecular Medicine Vasorelaxation Caused by Cannabinoids: Mechanisms in Different Vascular Beds
Current Vascular Pharmacology Pulmonary Hypertension: Current Therapy and Future Prospects
Cardiovascular & Hematological Agents in Medicinal Chemistry Editorial (Thematic Issue: Linkage of Neurodegenerative Disorders with Other Health Issues – Volume II)
CNS & Neurological Disorders - Drug Targets Bridging Innate Immunity and Myocardial Ischemia/Reperfusion Injury: The Search for Therapeutic Targets
Current Pharmaceutical Design Mitochondrial Dysfunction and Oxidative Stress in Insulin Resistance
Current Pharmaceutical Design Multiplex Analysis of Cardiac Hypertrophic Signaling: Reduced in vivo Phosphorylation of Glycogen Synthase Kinase-3β and Proline-Rich Akt Substrate (PRAS40)
Current Signal Transduction Therapy HIF Prolyl 4-Hydroxylases and their Potential as Drug Targets
Current Pharmaceutical Design Use of Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging in Drug Development for Ischemic Stroke
Current Drug Targets - CNS & Neurological Disorders Membrane Ion Channels and Diabetes
Current Pharmaceutical Design The Etiology of Hypertension in the Metabolic Syndrome Part Three: The Regulation and Dysregulation of Blood Pressure
Current Vascular Pharmacology Small Heat Shock Proteins (sHSPs) As Potential Drug Targets
Current Pharmaceutical Biotechnology