Term
| People who ahve a high degree of response to a drug are termed ______, while people who have a poor response are termed ______. |
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Definition
| mean good responders; mean poor responders |
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Term
| What types of hereditary variations cause the different responses to drugs? |
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Definition
| variations in drug metabolism, drug inactivation/elimination, and target receptors |
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Term
| Psuedocholinesterase deficiency causes what drug reaction? |
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Definition
| causes abnormally slow degredation of succinylcholine (general anesthetic); deficiency results in prolonged action of succinylcholine, procaine and cocaine |
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Term
| A patient presenting with paralysis of respiratory muscles after a standard dose of anesthesia, might have... |
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Definition
| pseudocholinesterase deficiency |
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Term
| What is teh physiologic function of psuedocholinesterase? |
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Definition
| there is no known function |
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Term
| What percent of the population is heterozygous for pseudocholinesterase deficiency? homozygous? |
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Definition
| 4% are heterozygous; 1:3,200 are homozygous |
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Term
| What is the name of the rare varient of the pseudocholinesterase gene that actually has a higher than normal enzyme activity and is resistant to the paralytic effects of succinylcholine? |
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Definition
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Term
| What is the incidence of thiopurine methyltransferase "null variants"? |
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Definition
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Term
| What drug interactions occur with thiopurine methyltransferase "null variants"? |
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Definition
| pts cannot metabolize chemo drugs used to treat leukemia (6-mercaptopurine, 6-thioguanine and azathioprine) into their inactive methylated forms |
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Term
| Can you give patients with thiopurine methyltransferase null variant drugs like azathioprine? |
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Definition
| yes but you have to treat them with 10-15x less chemo than commonly prescribed |
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Term
| Should you test every patient you treat with mercatopurines for TPMT metabolism before giving them the drug? |
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Definition
| genotyping or functional assay is now standard practice in cancer centers |
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Term
| How many patients on warfarin experience a major bleeding episode? |
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Definition
| 1.2 to 7 patients out of 100 |
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Term
| Warfarin is responsible for what percent of hospital admissions? |
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Definition
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Term
| What is the relative risk of fatal extracranial bleeds in patients on warfarin? |
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Definition
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Term
| Why is the dosing of warfarin so complex? |
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Definition
| narrow therapeutic index, nonlinear dose-response, wide range of doses to achieve target INR |
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Term
| What genetic variants affect warfarin sensitivity? |
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Definition
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Term
| T/F Patients with CYP2C9 or VKORC1 may need higher doses of warfarin. |
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Definition
| false; they may need lower doses of warfarin |
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Term
| How can you look at someone and gauge their liklihood of having the CYP2C9 and VKORC1 variants for warfarin metabolism? |
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Definition
| allelic frequencies of these two genes are usually associated with ethnicity |
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Term
| _______ may explain up to 25% of the patient variability in response to warfarin. |
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Definition
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Term
| What must be taken into account with CYP2C9 variants being dosed for warfarin? |
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Definition
| these variants take more time to achieve stable dosinga nd are associated with increased risk of bleeding events |
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Term
| Patients with VKORC1 on warfarin are at risk for.. |
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Definition
| exaggerated anticoagulant reponse; therefore they need a lower dose |
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Term
| Clopidogrel is a prodrug that is activated by _______. |
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Definition
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Term
| What drug interaction occurs with CYP2C19 loss of function alleles? |
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Definition
| diminished response to Clopidogrel and higher rates of recurrent cardiovascular events |
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Term
| Which genetic variation affect a patient's response to clopidogrel? |
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Definition
| CYP2C19 loss of function alleles and mutant alleles that are involved in modulating clopidogrel's absorption |
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Term
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Definition
| single nucleotide polymorphisms that occur throughout the genome about every 1,000 bases. These may be linked to differences in drug response and are under intense study by pharmaceutical companies |
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Term
| Pharmacogenomics will most likely use _____ to calculate the relative risk-benefit ratio of a particular therapeutic course for an individual patient. |
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Definition
| "panels" of polymorphisms |
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