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34 Cards in this Set
- Front
- Back
definition of pharmacogenetics/pharmacogenomics?
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investigation of variations in DNA sequence and RNA sequences/characteristics as related to drug response and toxicity
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consequences of genetic polymorphisms?
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increased risk of adverse effects, lack of efficacy, enhanced efficacy, increase or decreased susceptibility to pathological agents
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difficulty of prescribing meds for children?
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genes may not express the same as if they were an adult
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4 drugs that have explicit recommendations for using pharmacogenetic info to improve efficacy and safety?
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6-mercaptopurine, irinotecan, tamoxifen, abacavir
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phenotype or genotype determinations easier and more valuable?
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genotype: amplify gene of interest without need of specific probe, invasiveness, or confounding by diet, disease, etc
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genetic basis of slow acetylators?
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SNP in one or both of alleles for NAT2 (N-acetyltransferase) gene
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acetylation polymorphism is often seen with?
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ethnicity differences
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slow acetylators treated with isoniazid and hydralazine?
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peripheral neuropathy more common
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slow acetylators treated with procainamide and hydralazine?
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drug-induced lupus and ANA development more common
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slow acetylators treated with sulfonamides?
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hypersensitivity reactions more common
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rapid acetylators treated with amonafide?
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myelosuppression more common
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slow acetylators and smoking?
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urinary bladder cancer more common
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thiopurine-s-methyltransferase?
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cytosolic enzyme that catalyzes s-methylation (deactivation) of anticancer and antiinflammatory drugs such as mercaptopurine and azathioprine
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thiopurine-s-methyltrasferase genetic polymorphisms?
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deficient as AR, variant alleles with reduced stability/catalytic activity
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thiopurine-s-methyltransferase deficient patients treated with thiopurines?
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AR: severe hematopoietic toxicity;
heterozygous: increased risk of toxicity |
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UGTs (uridine diphosphate glucuronyltransferase)?
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glucuronidation of bilirubin as well as vrious drugs and xenobiotics
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lower than normal UGT activity?
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gilbert's syndrome
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genetic polymorphism in UGT?
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TA repeats in proximal promoter vary from 5-8 in length; lower the number of repeats, the more efficient the trxnal activity of the gene
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allele associated with gilbert's syndrome?
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UGT1A1*28
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UGT1A1 polymorphism treated with irinotecan?
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increased toxicity (myelosuppression and diarrhea)
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FDA-required package insert for irinotecan?
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homozygous for UGT1A1*28 alleles are at increased risk for neutropenia
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which drug does FDA have required package insert and pharmacogenetic test to identify these individuals?
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irinotecan
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consequences of CYP2D6 poor metabolizer phenotype?
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accumulation of parent drug for a number of beta-blockers, antiarrhythmics, tricyclic and atypical antidepressants, and neuroleptics
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CYP2D6 poor metabolizer treated with tamoxifen?
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decreased metabolism to active drug; independent predictor of breast cancer outcome in post-menopausal women receiving tamoxifen for early breast cancer
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CYP2D6 poor metabolizer treated with codeine?
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less metabolism to morphine leading to therapeutic failure
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CYP2D6 poor metabolizer treated with phenacetin?
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shift of metabolism to alternate and more toxic pathways
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CYP2C9?
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oxidation of S-warfarin, sulfonylureas, phenytoin
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variant CYP2C9 treated with warfarin?
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reduced oxidation of warfarin leading to higher blood concentration and risk of bleeding complications
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2 important drug oxidation polymorphisms?
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CYP2D6, CYP2C9
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variant allele for serum cholinesterase?
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change in critical aa in substrate binding site causing reduced affinity for succinylcholine
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serum ChE polymorphism treated with succinylcholine?
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reduced hydrolyzation leading to succinylcholine apnea
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variant associated with abacavir hypersensitivity?
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HLA-B variants
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clinical consequence of β2 agonists on β2 receptor polymorphism?
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bronchodilation, susceptibility to agonist induced desensitization, cardiovascular effects
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P-glycoprotein variant effect?
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altered drug disposition and response of anticancer drugs and cardiac glycosides
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