PGx Drug Receptors - Study Guide

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10 Terms

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  • Direct protein drug target: receptors, enzymes

  • Pharmacologic response proteins: signal transduction proteins, downstream proteins

  • Disease/risk pathogenesis proteins

Polymorphisms can affect drug response by targeting different drug targets. What are they?

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GPCR’s and Nuclear receptors

What subunits are disproportionally targeted ?

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ADRB1 transduction pathway - encodes for beta-adrenergic receptor

What transduction pathway is antagonized/targeted by beta blockers?

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Ser49Gly - Gly49 causes agonist-induced receptor down regulation - body becomes less sensitive to beta-agonists // Ser49 is less so (think less receptors)

Gly389Arg - causes the receptor to not bend and become STIFF - The variant Arg389 is more active than Gly389 (causes stronger response to beta-blockers)

SNPs can affect Beta-1 adrenergic receptors/ADRB1 receptor - How?

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Alzheimers; lipids are processed in the brain

The APOE4 gene is associated with higher risk of ______, and variants in the gene changes how ______ 

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Amyloid Targeting drugs

  • Leqembi

  • Kisunia

How do you treat Alzheimers?

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Leqembi

  • BBW for risk of ARIA

    • ESPECIALLY with APOE4 homozygote alleles (*X/*X)

    • Patients with 2 copies of APOE4 hid higher rates of severe brain swelling and bleeding!!!

Kisunia

  •  BBW for risk of ARIA

    • ESPECIALLY with APOE4 homozygote alleles (*X/*X)

What are the black box warnings for the Alzhemier treating drugs, and how do they relate to APOE4 receptor polymorphisms? 

8
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patients with KRAS/NRAS mutations experience same toxicities of Erbitux without the benefit that wild type genotypes get

  • Essentially getting the side effect without the cancer killing benefit! 

Why should patients with KRAS/NRAS mutations not use Erbitux?

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Gene associated with severe skin sensitivity reaction to Abacavir

  • Recommended to test before using drug

HLA-B*5701 polymorphism:

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Associated with hypersensitivity reactions (urticaria aka hives, SJS, TEN) to carbamazepine, primarily in those from Han Chinese ancestry

  • Testing of this gene recommended in patients with asian ancestry

HLA-B*1502 polymorphism: