pharmacogenetics conceptual

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)