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25 Cards in this Set
- Front
- Back
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These are groups of SNPs often inherited togather, forming common sets of inherited variant genes among large number of possible combinations of SNPs?
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Haplotypes
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What would you use to isolate and characterize inter-individual variation in drug metabolism?
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Pharmacogenetic probes
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Debrisoquin, an anti-hypertensive is now used as a probe to look for genetic polymorphism at this CYP450?
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CYPD26 (sparteine also used)
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CYP2D6 polymorphisms cause slow metabolism in 7% of caucasian populations for which drugs?
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Codeine, B-blockers, tricyclic antidepressants, dextromethorphan (cough supresant and dissociative hallucigen found in robitussen).
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What inhibits CYP2D6?
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fluoxetine, haloperidol, paroxetine, quinidine (further inhibit metabolism in slow metabolizers)
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T/F CYP2D6 polymorphisms only cause slow metabolism of substrate drugs?
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FALSE; also have fast metabolism
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(slow or fast) metabolsim in CYP2D6 mutants are found in 30% of East Africans?
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Fast
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What population has the highest percent of slow metabolizers of CYP2C19 (drugs like omeprazole and phenytoin)?
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China and Japan
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CYP2C19 slow metabolizers will have (decreased or increased) efficacy when prescribed omeprazole?
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Increased (get better)
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What are the clinically relevant substrates for CYP2C9 polymorphism?
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S-warfarin, phenytoin, losartan
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People with CYP2C9 polymorphism given warfarin will experience (thombosis or bleeding)?
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Bleeding (slow metabolism, less breakdown)
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A person ingesting large amounts of coffee has a non-fatal myocardial infarction. Which polymorphism is he most likely to have?
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CYP1A2*1F (F= Fucked)
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What enzyme metabolizes 5-fluorouracil?
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dihydropyrimidine dehydrogenase
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During a treatment of electroconvulsive therapy, a patient given a depolarizing neuromuscular blocker experiences prolonged paralysis unexpectedly. A polymorphism in an enzyme that breaks down this blocker is suspected. The polymorphism affects what enzyme?
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pseudocholinesterase (succinylcholine)
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What are the two drug metabolizing N-acetyltransferases?
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NAT1 and NAT2 (most SNPs occur in NAT2)
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What are some compunds acetylated by NAT-2?
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Isoniazid, procainimide, sulfonamide (NATS sometimes play inside)
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What cancer are slow acetylators (NAT2 polymorphism) at risk for?
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Bladder cancer
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What cancer are fast-acetylators (NAT2 polymorphism( at risk for?
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colon cancer
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A child with leukemia is given chemotherapuetic drugs and experience myeolosuppresion (reduced activity of bone marrow). A polymorphism in an enzyme is suspected. What enzyme is affected, and what drugs could he have been given?
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TPMT3 (thiopurine methyl transferase), 6-mercaptopurine and azathioprine (imuran)
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A patient is being treated for colon cancer and develops severe neutropenia. The doses are double checked and appear to be properly derived for the patient's age and weight. A polymorphism in Glucuronyl Transferase is suspected, what drug could he been given?
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Irinotecan
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Reduced metabolism of levodopa are seen in patients with a polymorphism in what enzyme?
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COMT (enhanced drug effect and possible toxicity)
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The 3435T/T polymorphism in MDR-1 is associated with lower plasma levels of which drugs?
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anti-retroviral (nelfinavir)
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The 2677 T MDR-1 genotype is associated with lower plasma levels of this drug ?
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fexofenadine (antihistamine drug to treat hayfever)
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Arg/Arg polymorphism at codon 16 causes what during infusion of isoproterenol?
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decreased venodilation response, increased bronchodilation response
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Polymorphism in VKORC1 may cause what?
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insensitivity to warfarin (need higher doses)
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