central dogma
DNA-transcription-RNA-mRNA-translation-protein
pharmacodynamics
what the drug does to the body
pharmacokinetics
what the body does to the drug
therapeutic window
concentration between the effective dose and adverse effects
duration of action
length of time the drug is effective; altered by metabolic breakdown/activation
drug metabolism
drug - intermediate - elimination
phase 1
phase of drug metabolism involving the functionalization of a drug; ex. CYP P450 enzymes
phase 2
phase of drug metabolism where the parent drug participates in conjugation reactions that form an easily-excreted and inactive conjugate; ex. addition of UGT
phase 3
phase of drug metabolism where transport occurs; ex. abc or sclo families of transporters
CYP P450
liver enzyme that detoxifies substances, produces cholesterol/steroids, metabolizes drugs
superfamily
CYP2D6*4
CYP
family
CYP2D6*4
2
subfamily
CYP2D6*4 - D
isoform
CYP2D6*4 - 6
allele
CYP2D6*4 - *4
*1
in most cases if a genetic test is not able either due to failure or by design make a call of the proper allele, a _____ is assigned
1, 2, 3
CYP _, _, and ___ are involved in drug and steroid metabolsm
inhibitor
CYP P450 drug interaction that slows down the normal metabolism of the drug causing the level of the drug to rise and potentially increase the risk of adverse effects
inducer
CYP P450 drug interaction that increases the rate of another drug's metabolism, causing a need for dose adjustment or therapeutic failure
polymorphism
the coexistence of two or more distinct forms in the same population.
allele
alternative form of a gene (member of a pair) that is located at a specific position on a specific chromosome
haplotype
combination of alleles along a chromosome that tend to be linked genetically and are usually inherited together; this info saves the cost of sequencing every gene
genotype
genetic makeup of an organism
phenotype
physical characteristics of an organism
genome
the complete instructions for making an organism, consisting of all the genetic material in that organism's chromosomes
exome
all exons in a genome
open reading frame
AUG followed by a number of codons and a stop codon in the same reading frame
promoter, enhancer
change in gene structure can alter expression level by affecting the proteins on the ___________ and ____________
1%
polymorphisms should be found at a frequency greater than ___ in the population
snp
polymorphism caused by a change in a single nucleotide
indel
polymorphism cause by the presence or absence of a nucleotide(s)
vntr
polymorphism caused by consecutive base pair groups that are differently repetitive
cnv
polymorphism caused by variation in the number of copies in a gene
CYP2C19
clopidogrel
loss of function
CYP2C19 - *2-*8
gain of function
CYP2C19 - *17
SCLO1B1
statins (except fluvastatin)
normal
SLCO1B1 - TT
intermediate
SCLO1B1 - TC
low function
SCLO1B1 - CC
TPMT
mercaptopurine and azathioprine
gain of function
TPMT - VNTR
CYP2D6
codeine, tramadol, morphine, psych drugs
normal function
CYP2D6 - *1, *2, *35
reduced function
CYP2D6 - *9, *10, *17
non-functional
CYP2D6 - *3, *4
deletion
CYP2D6 - *5
DUP
duplication of part of a chromosome; does not say which allele is duplicated
CYP2C9
rifampicin; amiodaron, fluconazole, sulfaphenazole
CYP2C9, VKORC
warfarin (2)