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Forensic Science, Medicine and Pathology
Published in: Forensic Science, Medicine and Pathology 2/2011

01-06-2011 | Review

Review: Pharmacogenetic aspects of the effect of cytochrome P450 polymorphisms on serotonergic drug metabolism, response, interactions, and adverse effects

Authors: J. L. Pilgrim, D. Gerostamoulos, Olaf H. Drummer

Published in: Forensic Science, Medicine and Pathology | Issue 2/2011

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Abstract

The field of pharmacogenetics contains a wealth of potential for the enhancement of clinical practice by providing a more effective match between patient and drug, consequently reducing the probability of an adverse drug reaction. Although a relatively novel concept in the forensic context, pharmacogenetics has the capability to assist in the interpretation of drug related deaths, particularly in unintentional drug poisonings where the cause of death remains unclear. However, the complex pharmacology of the drugs when subjected to genetic variations in metabolism makes interpretation of the expected response and adverse events difficult. Many possess multiple metabolic pathways, narrow therapeutic indices and active metabolites or enantiomers which may be eliminated via different pathways to the parent drug. A number of these drugs, which are metabolised primarily by the CYP450 system, are also associated with serotonin syndrome, or serotonin toxicity, especially when used concomitantly with other serotonin active drugs which rely on the same metabolic pathways for drug elimination. A comprehensive understanding of polymorphic drug metabolism and its expected outcomes is therefore essential when interpreting the involvement of drugs in adverse reactions. This review examines the genetically variable CYP450-mediated metabolism of a number of serotonin-active drugs that are often implicated in cases of serotonin toxicity, to assess the impact of pharmacogenetics on drug metabolism, response, interactions and adverse effects.
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Metadata
Title
Review: Pharmacogenetic aspects of the effect of cytochrome P450 polymorphisms on serotonergic drug metabolism, response, interactions, and adverse effects
Authors
J. L. Pilgrim
D. Gerostamoulos
Olaf H. Drummer
Publication date
01-06-2011
Publisher
Springer US
Published in
Forensic Science, Medicine and Pathology / Issue 2/2011
Print ISSN: 1547-769X
Electronic ISSN: 1556-2891
DOI
https://doi.org/10.1007/s12024-010-9188-3

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