Term
sotalol; most patients it is a good beta blocker |
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Definition
others it can cause arrhithmias |
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Term
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Definition
death via hepatic failure, but not class effect |
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Term
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Definition
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Term
steven johnson's syndrome |
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Definition
allergic reaction that can cause death |
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Term
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Definition
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Term
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Definition
coding region variants, DNA variants in non-coding regions and variable drug transport |
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Term
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Definition
genes encoding drug targets (receptors) and controlling the biological context in which drugs act |
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Term
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Definition
can effect regulation of gene |
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Term
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Definition
changes in DNA sequence that occur in regions that encode protein may lead to changes in primary AA sequence and protein function |
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Term
types of coding region variants of interest |
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Definition
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Term
CYP coding region variants |
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Definition
frequency vary by ethnicity |
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Term
CYP2D6--poor metabolizers |
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Definition
10% Caucasian and African Americans are homozygous for loss of activity; can be good, can be bad |
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Term
poor metabolizers may have accumulation and |
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Definition
increased side effects with some anti-depressants |
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Term
poor metabolizers do not metabolize codeine to it's active metabolite morphine |
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Definition
therefore have reduced analgesia |
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Term
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Definition
Asian-Americans mostly have higher cure rates of H.pylori with omeprazole therapy |
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Term
CYP2C19 poor metabolizer and clopidogrel |
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Definition
increased risk of CV death, MI or stroke compared to other better able to convert prodrug to active metabolite |
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Term
non-coding region variants |
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Definition
small fraction of genome; regulation of amount of mRNA, amount of proteins generated and differences in response to drugs |
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Term
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Definition
encodes glucuronosyltransferase which is important in the metab of bilirubin and some drugs |
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Term
two extra base-pairs in the regulatory region (non-coding/promoter region) of UGT1A1 |
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Definition
results in reduced protein expression of gene |
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Term
Gilbert's syndrome and UGT1A1 mutation with extra base pairs |
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Definition
jaundice because inability to produce functioning enzyme that normally should break down conjugated bilirubin |
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Term
UGT1A1 mutation and camptosar (irinotecan) |
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Definition
more diarrhea and neutropenia--immunocompromised |
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Term
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Definition
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Term
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Definition
drug entry into and removal from cells are dependent on specific drug transport molecules--can lead to variable drug response |
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Term
p-glycoprotein and organic ion transporters (OAT's) |
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Definition
important eflux transporters; protective mechanism to shunt things in and out of cells |
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Term
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Definition
transport drugs into the GI tract (part of 1st pass or gatekeeprs for CYP), out of brain and into renal tubules |
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Term
drugs mediated by p-glycoproteins |
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Definition
colchicine, immunosuppressive agents, glycosides, steroids, and antiretroviral agent |
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Term
OAT's (uptake transporters) |
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Definition
directional movement of drugs across organs, substrates of this secretory pathway are strikingly diverse |
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Term
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Definition
lactam antibiotics, probenacid, loop and thiazide diuretcs, ACE inhibitors and statins |
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Term
genetically determined PD |
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Definition
variability in the genes encoding drug targets, variability in biological context in which drugs act |
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Term
drugs can produce highly variable effects |
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Definition
even in the absence of change in drug concentrations at the site of action |
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Term
PD variability tends to be more |
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Definition
drug or disease specific, compared with PK |
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Term
beta2 receptor polymorphism and response to agonist therapy |
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Definition
differences in genotype can result down regulation of receptors |
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Term
genetic surveys of patients with drug-induced torsades |
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Definition
have identified pre-disposing mutations not only to the drug target (KCNH2) but also to other genes that control the QT interval |
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Term
variability in the physiologic control of the QT interval |
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Definition
can contribute to the variable effects of KCNH2 blockers |
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Term
genetically determined PD |
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Definition
variability in the genes encoding drug targets, variability in biological context in which drugs act |
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Term
drugs can produce highly variable effects |
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Definition
even in the absence of change in drug concentrations at the site of action |
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Term
PD variability tends to be more |
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Definition
drug or disease specific, compared with PK |
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Term
beta2 receptor polymorphism and response to agonist therapy |
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Definition
differences in genotype can result down regulation of receptors |
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Term
genetic surveys of patients with drug-induced torsades |
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Definition
have identified pre-disposing mutations not only to the drug target (KCNH2) but also to other genes that control the QT interval |
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Term
variability in the physiologic control of the QT interval |
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Definition
can contribute to the variable effects of KCNH2 blockers |
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Term
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Definition
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Term
mutation in one gene had been selected for and had spread through the population of rats over time |
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Definition
CYP2C9--lead to studies in resistant humans |
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Term
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Definition
warfarin resistance that necessitates daily doses in excess of 15 mg/day |
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Term
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Definition
especially homozygosity for the *3 allele can result in sensitivity to the drug such that doses less than 1mg/day are sufficient |
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Term
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Definition
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Term
about 6-10% of the variability |
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Definition
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Term
TPMT homozygous wild type |
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Definition
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Term
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Definition
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Term
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Definition
negligible activity; 0.3% |
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Term
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Definition
converts 6MP to active and inactive metabolites |
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Term
TPMT inactivity results in |
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Definition
toxicity of 6MP due to a dramatic decrease in degradation of drug into inactive form |
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Term
ultra-rapid CYP2D6 metabolism |
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Definition
dramatic increase of conversion of codeine to morphine may result in overdose and serious respiratory depression |
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