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    Pharmacogenetics

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    Pardeep Sony
    Pharmacogenetics is concerned with genetic variability in drug effects. Polymorphisms can influence pharmacokinetics, like how the body absorbs, distributes, metabolizes, and eliminates drugs. For example, 10% of patients have a genetic polymorphism causing reduced activity of the enzyme thiopurine methyltransferase, leading to higher drug levels and risk of toxic effects from drugs like azathioprine. Genetic variants can also influence pharmacodynamics, changing a drug's biological effects rather than plasma levels, like variants in beta-adrenoceptors affecting blood pressure response to drugs like metoprolol. Future research may identify more genetic polymorphisms important for determining safe and effective drug treatment based on a

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    Pharmacogenetics

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    Pardeep Sony
    127 views3 pages
    Pharmacogenetics is concerned with genetic variability in drug effects. Polymorphisms can influence pharmacokinetics, like how the body absorbs, distributes, metabolizes, and eliminates drugs. For example, 10% of patients have a genetic polymorphism causing reduced activity of the enzyme thiopurine methyltransferase, leading to higher drug levels and risk of toxic effects from drugs like azathioprine. Genetic variants can also influence pharmacodynamics, changing a drug's biological effects rather than plasma levels, like variants in beta-adrenoceptors affecting blood pressure response to drugs like metoprolol. Future research may identify more genetic polymorphisms important for determining safe and effective drug treatment based on a

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    Pharmacogenetics

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    Pharmacogenetics is concerned with genetic variability in drug effects. Polymorphisms can influence pharmacokinetics, like how the body absorbs, distributes, metabolizes, and eliminates drugs. For example, 10% of patients have a genetic polymorphism causing reduced activity of the enzyme thiopurine methyltransferase, leading to higher drug levels and risk of toxic effects from drugs like azathioprine. Genetic variants can also influence pharmacodynamics, changing a drug's biological effects rather than plasma levels, like variants in beta-adrenoceptors affecting blood pressure response to drugs like metoprolol. Future research may identify more genetic polymorphisms important for determining safe and effective drug treatment based on a

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    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    127 views3 pages

    Pharmacogenetics

    Uploaded by

    Pardeep Sony
    Pharmacogenetics is concerned with genetic variability in drug effects. Polymorphisms can influence pharmacokinetics, like how the body absorbs, distributes, metabolizes, and eliminates drugs. For example, 10% of patients have a genetic polymorphism causing reduced activity of the enzyme thiopurine methyltransferase, leading to higher drug levels and risk of toxic effects from drugs like azathioprine. Genetic variants can also influence pharmacodynamics, changing a drug's biological effects rather than plasma levels, like variants in beta-adrenoceptors affecting blood pressure response to drugs like metoprolol. Future research may identify more genetic polymorphisms important for determining safe and effective drug treatment based on a

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    Pharmacology Tutor – Learn Pharmacy in easy steps

    Pharmacogenetics

    Pharmacogenetics is concerned with the genetic variability of drug effects. Differences

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    in genetic sequences that occur at a frequency of at least 1% are designated as


    polymorphisms. Rare variants are observed in less than 1% of a population.
    Polymorphisms may either influence the pharmacokinetics of a drug (A) or occur in the
    target genes that mediate the therapeutic effect of drugs (B).

    Genetic variants of pharmacokinetics.

    Polymorphisms can occur in all genes that participate in the absorption, distribution,
    biotransformation, and elimination of drugs. Subjects who break down a drug more
    slowly owing to a genetic defect are classified as “slow metabolizers” or poor
    metabolizers” in contrast to “normal metabolizers.” When delayed biotransformation
    causes an excessive rise in plasma levels, the incidence of toxic effects increases, as
    evidencedby the example of the immunosuppressants azathioprine and mercaptopurine.
    Both substances are converted to inactive methylthiopurines by the enzyme thiopurine
    methyltransferase (TMPT). About 10% of patients carry a genetic polymorphism that
    leads to reduced TMPT activity and in < 1% enzyme activity is undetectable. As a result
    of the diminished purine methylation, the plasma level of active drug rises and, hence, the
    risk of toxic bone marrow damage rises. To avoid unwanted toxic effects, TMPT activity
    can be determined in erythrocytes before therapy with mercaptopurine is started. In fact,
    TMPT polymorphism is the first pharmacogenetic test to be introduced into clinical
    practice. In patientswith complete TMPT deficiency, the dose of azathioprine should be
    reduced by 90%.

    Other genetic variants of drug metabolism may have a similar impact: a defect of
    Nacetyltransferase 2 impedes the N-acetylation of diverse drugs, including isoniazid,
    hydralazine, sulfonamides, clonazapam, and nitrazepam. “Slow acetylators” (50–60%
    of the population) are more likely than “fast acetylators” to develop toxic reactions and
    neuropathy. A genetic defect of the cytochrome P450 isozyme CYP2D6 (originally
    described as debrisoquine–sparteine polymorphism) occurs in ~8% of Europeans and
    results in delayed elimination of a various drugs, including metoprolol, flecainide,
    nortriptyline, desipramine, and amitriptyline.

    Genetic variants of pharmacodynamics.

    Genetic polymorphisms can also involve genes that directly or indirectly mediate the
    effects of drugs and, hence, alter pharmacodynamics (B). In these cases, the biological
    effects of a drug are changed, rather than its plasma levels. The genetic variants of β-
    adrenoceptors provide an example. For instance, hypertensive patients carrying an
    arginine at amino acid position 389 of the β1-receptor respond to metoprolol with a
    more marked fall in blood pressure than do patients carrying a glycine residue at this
    position. Since β1-blockers have a relatively large margin of safety and, as a rule, dosage
    is determined by the observed effect, genotyping of patients prior to administration of β-
    blockers would appear unnecessary.

    Future research may be expected to identify numerous genetic polymorphisms in the


    target molecules of drugs. A genetic examination before the start of drug therapy will be

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    a sensible precaution, particularly when drugs with a narrow margin of safety or a long
    half-life are to be used on a fixed dosage regimen.

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