Elsevier

The Lancet

Volume 356, Issue 9242, 11 November 2000, Pages 1667-1671
The Lancet

Adverse Drug Reactions
Pharmacogenetics and adverse drug reactions

https://doi.org/10.1016/S0140-6736(00)03167-6Get rights and content

Summary

Polymorphisms in the genes that code for drug-metabolising enzymes, drug transporters, drug receptors, and ion channels can affect an individual's risk of having an adverse drug reaction, or can alter the efficacy of drug treatment in that individual. Mutant alleles at a single gene locus are the best studied individual risk factors for adverse drug reactions, and include many genes coding for drug-metabolising enzymes. These genetic polymorphisms of drug metabolism produce the phenotypes of “poor metabolisers” or “ultrarapid metabolisers” of numerous drugs. Together, such phenotypes make up a substantial proportion of the population. Pharmacogenomic techniques allow efficient analysis of these risk factors, and genotyping tests have the potential to optimise drug therapy in the future.

Section snippets

History of pharmacogenetics

Pharmacogenetics had its beginning in the 1950s when researchers realised that some adverse drug reactions could be caused by genetically determined variations in enzyme activity. For example, prolonged muscle relaxation after suxamethonium was explained by an inherited deficiency of a plasma cholinesterase, and haemolysis caused by antimalarials was recognised as being caused by inherited variants of glucose-6-phosphate dehydrogenase. Similarly, inherited changes in a patient's ability to

References (29)

  • UA Meyer et al.

    Molecular mechanisms of genetic polymorphisms of drug metabolism

    Annu Rev Pharmacol Toxicol

    (1997)
  • JP Miners et al.

    Cytochrome P4502C9; an enzyme of major importance in human drug metabolism

    Br J Clin Pharmacol

    (1998)
  • RS Kidd et al.

    Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele

    Pharmacogenetics

    (1999)
  • T Furuta et al.

    Effects of clarithromycin on the metabolism of omeprazole in relation to CYP2C19 genotype status in humans

    Clin Pharmacol Ther

    (1999)
  • Cited by (533)

    • The effect of alpha-2A adrenergic receptor (ADRA2A) genetic polymorphisms on the depth of sedation of dexmedetomidine: a genetic observational pilot study

      2022, Brazilian Journal of Anesthesiology (English Edition)
      Citation Excerpt :

      According to recent studies, the individual variability of the effectiveness of a drug can often be associated with genetically determined variations. Especially, the polymorphisms of drug metabolizing targets, carriers, and enzymes can have a significant impact on individual dose-response relationships.14 Likewise, the genomic polymorphisms of ADRA2A can contribute to individual responses to dexmedetomidine.

    • Polymorphisms in drug-metabolizing enzymes: Challenges and strategies

      2022, Biochemistry of Drug Metabolizing Enzymes: Trends and Challenges
    • Bioenergetics theory and components: Cytochrome P450

      2021, Encyclopedia of Biological Chemistry: Third Edition
    View all citing articles on Scopus
    View full text