Metabolism of xenobiotics

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Metabolism of Xenobiotics
R. C. Gupta Professor and Head Department of
Biochemistry National Institute of Medical
Sciences Jaipur, India
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Phase 1 reactions
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Hydroxylation
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XH O2 NADPH H ? XOH H2O NADP
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Cytochrome P-450
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Overlapping specificities are particularly
important in the metabolism of drugs
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One drug can increase or decrease the metabolism
of some other drug
Hence, alertness is required when prescribing a
combination of drugs
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Example 1 Phenobarbital and warfarin
CYP2C9 metabolizes phenobarbital as well as
warfarin
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Phenobarbital induces CYP2C9
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If phenobarbital is subsequently withdrawn,
concentration of CYP2C9 decreases
This necessitates a decrease in the dose of
warfarin
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Example 2 Rifampicin and contraceptive steroids
CYP3A4 metabolizes rifampicin as well as
contraceptive steroids
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CYP3A4 is induced by rifampicin
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If rifampicin and contraceptive steroids are
taken together -
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Oxidation
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Reduction
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Phase 2 reactions
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Methylation
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Conjugation
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Conjugation with glucuronic acid
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Conjugation with sulphate
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Conjugation with acetate
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Conjugation with glycine
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Conjugation with glutathione
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Environmental health hazards
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Thank you