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20 Cards in this Set
- Front
- Back
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Personalized medicine purpose
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Tailor dosages, prescriptions to individual patient's geno/phenotype to be max. efficient
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HER2
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Human growth factor, produced in many breast cancers
- Presence means harder to treat - won't respond to hormone therapies - Also easier to treat - Herceptin = specific antibody to HER2 producing cells |
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Gene amplification
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1) Double minutes - small accessory chromosomes
2) Homogenously staining regions - same sequences amplified, same color |
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Drug response
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Typically 25-75% effective
- Depends on enzyme activity of patient |
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Pharmacogenetics
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Impact of genetic variation on drug response/metabolism
- Which drugs are individually most/least effective, give most/least side effects |
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Pharmacokinetics
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What the body does to a drug
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Pharmacodynamics
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What a drug does to the body
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Drug responsiveness factors
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- Pharmacokinetics/dynamics
- Genomic factors - Pathological factors - Age, race, sex, health |
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Variable drug reactivity affects:
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- Distribution
- Biotransformation (converting drug) - Metabolism - Excretion |
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Biotransformation
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Converting drugs to active form (also more H20 solvent for excretion)
- Active drugs - don't need converting, already active - Prodrugs - not active til converted |
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CYP450 26D (CYP26D)
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Liver enzyme, 25% of drugs
- Codeine prodrug -> morphine - More/less = faster/slower prodrug conversion |
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Extensive metabolizers
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Normal response to standard dose
- Pain relief effective - Small chance of toxicity |
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Poor metabolizers
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Inadequate expression of enzyme - some caucasians
- Small morphine production - Poor pain relief - Side effects (nausea) of high codeine remnant |
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Ultrametabolizers
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Overexpression of enzyme - some E. Africans
- Increased morphine production - Overdose side effects (low resp, heart rate) - Toxicity |
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Thiopurine methyltransferase (TPMT)
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Breaks down chemo drug Thiopurines
- If TPMT is too slow, thiopurine levels -> toxic! |
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Thiopurine dosage
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Depends on TPMT levels in patient
- Poor metabolizers = better outcomes (low toxicity) @ lower doses |
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Warfarin
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Common oral anticoagulant
- Inhibits Vitamin K epoxide reductase complex 1 (VKORC1) - Metabolized by CYP2C9 |
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CYP2C9 variants
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In the coding region - affect actual enzyme activity
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VKORC1 variants
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Non-coding region - affect expression (amount) of enzyme present
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Warfarin-related haplotypes
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A - Asian americans - more sensitive, smaller doses
B - African-americans - less sensitve, larger doses |
