Pharmacogenomics Flashcards
1842 First human drug metabolism experiment by Keller showed ________ acid converted in urine to hippuric acid
benzoic acid
______________ : study of the relationship between variations in a single gene (or small collection of genes) and variability in drug disposition, response, and toxicity.
pharmacogenetics (PGx)
_______________ : study of the relationship between variations in a large collection of genes (up to the whole genome) and variability in drug disposition, response, and toxicity.
pharmacogenomics
The liver’s primary mechanism for metabolizing drugs is via a group of cytochrome____________ enzymes
P-450
___________: mathematics of the time course of Absorption, Distribution, Metabolism, and Excretion of drugs
pharmacokinetics
Drug metabolism is usually monogenic/multigenic?
monogenic
Polymorphisms can affect protein function and can make ____________ bimodal or even trimodal
distribution
Variable ______________ phenotypes may influence drug dosing, efficacy, and/or toxicity
pharmacokinetic
Genetic variants in a metabolizing enzyme can alter enzyme _________, enzyme _________ or inactivate the enzyme
activity, affinity
Genetic variants in a metabolizing enzyme can ___________ clearance, ___________ the AUC and ______________half-life
decrease clearance
increase AUC
increase t1/2
Duplications/multiplications in a metabolizing enzyme are more rare but can ___________ clearance, ___________ the AUC and ______________half-life
increase clearance
decrease AUC
decrease t1/2
The impact of drug metabolizing enzyme gene variants on the pharmacologic effect and toxicity profile of a drug depends, in part, on whether the drug is active in its parent form or is a ___________
prodrug
Star nomenclature is typically numbered in order of _____________
discovery
1 / (1A/B/C) are typically ____________ allele
reference/normal
Some * alleles are defined by the presence of more than 1 variant in _____
Phasing is required
cis
Interpretation of phenotype requires knowledge of ____________, not just genotype
diplotype
Break down CYP-2-C-19-*17
Superfamily - CYP
Family - 2
Subfamily - C
Gene - 19
Allelic variant *17
FDA box warning discusses testing of _______________ for Plavix
CYP2C19
___________ collects, curates and disseminates knowledge about the impact of human genetic variation on drug responses.”
PharmGKB
PharmGKB Clinical Annotation Levels of Evidence
1A/B high, 2A/B moderate, 3 low, 4 preliminary
PharmGKB may state that genetic testing for a drug is ____________ or ____________ and that it is _____________ or __________________
required or recommended
actionable or informative
CPIC (2009 PGKC and PGRN) stands for ______________ ________________ _______________ _______________
Clinical Pharmacogenetics Implementation Consortium
CPIC currently has ______________ guidelines
33
_______________ is linked to statin-induced myopathy
SLC01B1
SLCO1B1 : Gene expressed at the hepatic ____________ membrane that reabsorbs a variety of chemicals from plasma into the liver
sinusoidal
*____ allele of SLC01B1 rs4149056 / p.Val174Ala results in lower transport into liver and decreases clearance of simvastatin = lower dose means that patient has greater exposure to active drug
5
SLCO1B15
Number needed to __________________ is the number of tests that must be performed to affect healthcare
genotype (like number needed to treat)
SLC01B1*5 rs4149056 involves a ______ to ________ mutation at 174
Val174Ala
