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Cytochrome P450 Genes: Their Role in Drug Metabolism and Violence

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Handbook of Anger, Aggression, and Violence

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Abstract

Cytochrome P450 (CYP450) enzymes are well-known for their ability to metabolize endogenous and xenobiotic substrates. Fifty-seven functional P450 genes have been identified in humans. This chapter focuses on P450 gene families 1, 2, and 3, as about a dozen enzymes in these families are responsible for the metabolism of the majority of prescription drugs. Genetic polymorphism for these CYP450s can have severe metabolic consequences, since toxicity can be caused by reduced or loss-of-function variant alleles. In addition, drug-drug (DDI), drug-gene (DGI), and drug-drug-gene (DDGI) interactions can significantly impact the ability of individuals to properly metabolize prescriptive medications and may result in adverse drug events (ADEs) or adverse drug reactions (ADRs), which are a major medical concern. Pharmacogenetic testing is a powerful tool in predicting these effects, but there are complicating issues, e.g., substrate specificity, enzyme promiscuity, phenoconversion, epigenetics, heterogeneity of CYP450 enzyme activity in different organs, altered sensitivity to inhibition, and interindividual or interethnic variations in metabolic ability. The best way to estimate metabolic rates is by combining genotyping, phenotyping, and therapeutic drug monitoring, in addition to carefully observing and listening to the patient.

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Abbreviations

ADE:

Adverse Drug Event

ADR:

Adverse Drug Reaction

CYP450:

Cytochrome P450

DDGI:

Drug-Drug-Gene Interaction

DDI:

Drug-Drug Interaction

DGI:

Drug-Gene Interaction

EM:

Extensive Metabolizer

EPS:

Extrapyramidal Symptoms

IM:

Intermediate Metabolizer

PharmVar:

Pharmacogene Variation Consortium

SNP:

Single Nucleotide Polymorphism

SSRI:

Selective Serotonin Re-uptake Inhibitor

UM:

Ultrarapid Metabolizer

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Authors and Affiliations

  1. Independent Forensic Services, Santa Fe, NM, USA

    Selma J. M. Eikelenboom-Schieveld

  2. Department of Biological Sciences, University of Denver, Denver, CO, USA

    James C. Fogleman

Authors
  1. Selma J. M. Eikelenboom-Schieveld
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  2. James C. Fogleman
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Corresponding author

Correspondence to James C. Fogleman .

Editor information

Editors and Affiliations

  1. Institute for Clinical and Applied Health Research, University of Hull, Hull, UK

    Colin Martin

  2. King's College London, London, UK

    Victor R. Preedy

  3. University of Westminster, London, UK

    Vinood B. Patel

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Eikelenboom-Schieveld, S.J.M., Fogleman, J.C. (2022). Cytochrome P450 Genes: Their Role in Drug Metabolism and Violence. In: Martin, C., Preedy, V.R., Patel, V.B. (eds) Handbook of Anger, Aggression, and Violence. Springer, Cham. https://doi.org/10.1007/978-3-030-98711-4_84-1

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  • DOI: https://doi.org/10.1007/978-3-030-98711-4_84-1

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