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20 Cards in this Set
- Front
- Back
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CYP2D6 (antipsychotics)
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- antipsychotics
- chromosome 22 - 4 metabolic types (PM, IM, EM, UR) i. UM: will need increased doses of meds for effect (may result in tx failures) ii. PM: may develop side effects or ADE with low doses (may need med that uses different enzymes for therapeutic effect) - Ex Meds: haloperidol, chlorpromazine |
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CYP1A2
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- antipsychotics
- chromosome 15 - susceptible to induction by external factors (>30% of populations w/ European ancestry) i. Tobacco SMOKE: most common inducer of 1A2 a) unrelated to nicotine intake or replacement b) smokers who take these meds metabolized 1A2 may need dose decrease if they quit c) smokers started on these meds may need higher doses - Example Meds: clozapine, olanazapine (Zyprexa) - Hospital admission i. smoke-free (pt needs nicotine patches, NO SMOKE) ii. admission: increase dose, discharge: decrease - if med levels get too high --> sedation, orthostasis, seizures at doses >600 |
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HTR2C
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- serotonin 2C receptor gene
- chromosome 13 - variants (rs3813929) cytosine or thymine allele i. cytosine causes weight gain in patients ii. thymine showed less weight gain; considered "protective" from weight gain |
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Clozapine
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- risk of agranulocytosis = 1%
- use requires regular blood draws - if ANC (absolute neutrophil count) <500, it can NEVER be given again |
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Future Targets for Metabolic Syndrome (Weight Gain) Effects
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- 5-HT2C
- Alpha-2a receptor genes - leptin (neuro hormone that makes you feel full) - current practice i. treat them like diabetics: fasting lipids, glucose, A1c, BMI, waist circumference at baseline & q6months (change therapy if weight gain >/= 5% starting weight) |
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Major Depression
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- environmental factors must be present as well as genetics to display symptoms
- current practice: SSRIs 1st line then SNRIs |
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CYP2D6 (major depression)
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- PM more likely to experience severe GI effects from venlafaxine
- fluoxetine (case with death of child) |
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SLC6A4
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- serotonin transporter gene
- chromosome 17 - important for serotonin reuptake - variant 5-HTTLPR i. 43-44 base pairs in length ii. found in both adults and children w/ depression iii. long allele: AA>Jap iv. SS (short) genotype: decreased response to SSRIs; may also be predictor of suicidality |
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Serotonin 2A Receptor Gene
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- chromosome 13
- variant rs7997012 i. if adenine allele, may have better response to citalopram - variant rs6313 i. associated w/ intolerance to paroxetine |
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Vilazodone (Viibryd)
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- antidepressant w/ SSRI & 5-HT1A agonist properties
- metabolized by CYP3A4 - phase III trials found no promising results |
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Future Targets (MD)
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- tryptophan hydroxylase gene
i. rate-limiting enzyme in serotonin synthesis - genetic testing at time of treatment initiation i. New testing to specifically identify genes and enzymes that play a role in psychiatric care; some covered by insurance companies |
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GeneSightRx
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- assesses key genes & enzymes to determine "best" med options
- tests available: 1. psychotropic 2. ADHD 3. analgesic |
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2B6 Gene
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- chromosome 19
- primary enzyme for metabolism of bupropion i. bupropion used to decrease nicotine cravings ii. patients w/ T allele are less likely to respond to bupropion |
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2A6
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- chromosome 19
- responsible for metabolism of nicotine - slow metabolizers may achieve higher levels of plasma nicotine when using replacement therapy |
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Alcohol Dehydrogenase (ADH)
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- ADH1B*2
i. preventative effect against alcoholism ii. regardless of gender or race - ADH1C*2 i. codes for less active subunit ii. associated w/ higher risk of alcohol dependence |
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Aldehyde Dehydrogenase (ALDH)
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- inactive mitochondrial ALDH2 leads to higher acetaldehyde [ ]s causing more AE
- ALDH*2 i. flushing, nausea, tachycardia, HA w/ alcohol use |
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Mu-Opioid Receptor Gene (OPRM1)
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- chromosome 6
- key receptor in alleviation of pain, also target of anticraving meds - pts w/ alcohol dependence and 1-2 copies of G allele may be more likely to benefit from naltrexone |
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Period Homolog 2 Clock Gene (PER2)
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- chromosome 2
- variation in PER2 may lead to diff response to acamprosate (Campral 333 mg) |
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Dopamine 4 Receptor Gene (DRD4)
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- chromosome 11
- pts w/ 1-2 copies of 7 repeat allele of DRD4 have positive reaction to alcohol (REALLY like it) i. pts w/ this allele have larger decrease in consumption of alcohol when treated w/ olanazepine |
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ADHD
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- atomoxetine
i. non-stimulant used for ADHD ii. MOA: inhibits reuptake of NE iii. metabolized through CYP2D6 iv. PM = 10 X AUC, 5 X peak [ ] a) increased insomnia, appetite suppression, BP, HR, efficacy, and symptom improvement |
