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 |
- 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
-
HDL Therapy for the Treatment of Cardiovascular Diseases
Current Vascular Pharmacology Melatonin, A Natural Programmed Cell Death Inducer in Cancer
Current Medicinal Chemistry Synergistic Effect of Inhibitors of MMPs and ROS-dependent Modifications of Contractile Proteins on Protection Hearts Subjected to Oxidative Stress
Current Pharmaceutical Design Design, Synthesis and Biological Evaluation of Ligands Selective for the Melanocortin-3 Receptor
Current Topics in Medicinal Chemistry Techniques to Investigate Neuronal Mitochondrial Function and its Pharmacological Modulation
Current Drug Targets Erythropoietin Signaling and Neuroprotection
Current Signal Transduction Therapy Statins and Solid Organ Transplantation
Current Pharmaceutical Design Differential Regulation of microRNAs in Patients with Ischemic Stroke
Current Neurovascular Research Inflammatory Modulation of Hepatocyte Apoptosis by Nitric Oxide: In Vivo, In Vitro, and In Silico Studies
Current Molecular Medicine Vascular Endothelial Growth Factor and Angiopoietins in Neurovascular Regeneration and Protection Following Stroke
Current Neurovascular Research Mesenchymal Stem Cells in Renal Ischemia-Reperfusion Injury: Biological and Therapeutic Perspectives
Current Stem Cell Research & Therapy Intravenous Antihypertensives within Cardiovascular-Based Continuity of Care
Current Vascular Pharmacology Regulatory Role of Chinese Herbal Medicine in Regulated Neuronal Death
CNS & Neurological Disorders - Drug Targets Therapeutic Potential of Endothelial Progenitor Cells for Cardiovascular Diseases
Current Vascular Pharmacology Raxofelast, (±)5-(Acetyloxy)-2,3-dihydro-4,6,7-trimethyl-2-benzofuranacetic Acid: A New Antioxidant to Modulate the Inflammatory Response During Ischemia-Reperfusion Injury and Impaired Wound Healing
Mini-Reviews in Medicinal Chemistry The Na+/Ca2+ Exchanger Mediates the Effects of Oxidative Stress in Hypertension
Current Hypertension Reviews Chemical Advances in Therapeutic Application of Exosomes and Liposomes
Current Medicinal Chemistry Cardiac Protection by Volatile Anaesthetics: A Review
Current Vascular Pharmacology In Search for the Troponin of the Kidney
Current Medicinal Chemistry Rational Design and Development of RDP58
Current Pharmaceutical Design