DOING IT BETTER: Tailoring drug therapy with pharmacogenetics

April 2005 
Volume 35  Number 4
Pages 22 - 23
  PDF Version Available!


  • How enzyme variability affects response

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  • Your role

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    THREE PATIENTS received identical doses of codeine for postprocedural pain 2 hours ago. Dora Ames has good pain relief and is now smiling and joking with her husband, but Tony Silva is still complaining of pain, grimacing, and moaning. Patricia Stevens isn't complaining about anything, but she seems groggy.

    Why have these three patients responded so differently to the same dose of the same drug? Each patient's genetic makeup plays a part. In this article, I'll introduce you to pharmacogenetics , the study of how genetic variations influence a patient's response to drugs. A working understanding of pharmacogenetics will help you individualize your interventions so each patient gets the maximum benefit from his medications with minimal adverse reactions.

    To find out why these three patients responded so differently to codeine, let's look into drug-metabolizing enzymes.

    How enzyme variability affects response

    Enzymes in the cytochrome P-450 (CYP 450) system help metabolize from 25% to 30% of currently available drugs. Approximately 40 CYP 450 genes have been identified. A genetic variation in any of these genes can affect how a person metabolizes certain drugs.

    In the case of codeine, for example, the enzyme CYP 2D6 metabolizes the drug to morphine. A variation in the gene producing this enzyme, found primarily in the liver, affects how much of the enzyme is available to metabolize codeine. More than 100 alternative forms (alleles) of CYP 2D have been identified.

    In some people, genetic variations have no effect on normal enzyme activity. In others, variations produce increased, decreased, or absent enzyme activity, altering the clinical response to medication.

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