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