Test 3 Flashcards
clearance
volume of blood that has drug completely removed from it
ROE units
mass/time
concentration units
mass/volume
clearance units
volume/time
Q
blood flow same on both sides
extractor
organ removing drug / liver kidney etc
E
extraction ratio
whats coming in / whats coming out
.1 = 10% each time = 1st order removal always
ROP
Cin x Q
ROE
Q x (Cin - Cout)
E
ROE/ROP
(Cin - Cout)/ Cin
ways you could impact the ability of the extractor to remove drug
blood flow heart failure = lower Q liver failure - any change in Q or E enzyme inhibitors
ROE is concentration independent or dependent
dependent / 1st order
clearance is a constant or variable
constant
CL =
vol/time
Q x E
flow rate x extraction ratio
ROE =
Cin x Q x E
k =
CL/VD
volume/time
——————- = time^-1
volume
inactive metabolite
devoid of pharmacological activity; results in termination of a drug, chemical properties are changed affecting how a drug interacts with target or changes in distribution
active metabolite
has pharmacological activity; similar to the desired activity, new activity not observed with the parent drug
drug bioactivation
parent has no activity; must be activated
phase 1 reactions
add or reveal polar functional group, generally increase H2O solubility and facilitate excretion; does not always terminate; may undergo phase 1
phase 2 reactions
conjugation; add biomolecule to a functional group or phase 1 metabolite; increase water solubility; increase molecular weight; high energy cofactors; usually terminate
5 types of reactions catalyzed by CYP
N/S oxidation alkene oxidation O/N dealkylation aromatic, acyclic, aliphatic hydroxylation deamination
other phase 1 reactions
epoxide hydrolase ADH/ALDH esterase nitro reduction keto reduction azo reduction
most common phase 2
glucronidation
high capacity system
glucuronidation
low capacity system
sulfation
protects from electrophiles, conc. usually is high but can be depleted rapidly
glutathione
phase 2 reaction co substrates are rate limiting meaning
if one pathway becomes saturated alternative metabolic pathways can be used
object drug
drug being effected; E
precipitant drug
drug doing the inhibition or induction; Q
inhibition
reduces activity
major issue with CYPs
rapid onset
decreases CL, increase pharm affect, decreases metabolite toxicity
induction
induces activity
slow onset
less common
increases CL, decrease pharm affect, increases metabolite toxicity, increases pharm affect if prodrug
strong inhibitors
greater than 80% reduction in clearance, 5 fold increase in AUC
weak inhibitors
greater than 50-80% reduction in clearance, 3-5 fold increase in AUC
cigs & charcoal broiled food
induces CYP1A2
cruciferous veggies
induces CYP1A2
ethanol consuption
induces CYP2E1; reduces GSH
piperine
inhibits CYP3A4
herbal products
induce / inhibit various transporters
fruit juices
inhibit CYP3A4 transporters
gene
the basic physical and functional unit of heredity transferred from parent to offspring that codes for a specific characteristic; it is a distinct sequence of nucleotides forming part of a chromosome, the order which determines the order of monomers in a polypeptide or nucleic acid molecule which a cell or virus may synthesize
allele
a particular form or variant of a gene that can affect phenotypic expression of traits
homozygous
describes an organism that possesses two identical alleles for a particular trait
heterozygous
describes an organism that possess two different alleles for a particular trait
wild type
a characteristic that prevails among individuals in natural conditions; the product of the normal allele
mutation
a change in the nucleotide sequence of the genome of an organism that is either a result of mistakes made when DNA is copied or due to exposure to environmental factors that cause irreparable damage
polymorphism
the presence of genetic variation within a population due to multiple alleles that occupy the same locus on a chromosome
promotor
a region of DNA that initiates the transcription of a particular gene; a promotor is located upstream on the same strand near the transcription start site of a gene
untranscribed regions
genomic sequences that are not transcribed to the primary transcript; untranscribed regions may contain important regulatory elements such as promotors
3’
refers to the carbon number in DNA backbone that has a hydroxyl group attached to it
5’
refers to the carbon number that has a phosphate group attached to it
intron
any nucleotide sequence within a gene that is removed by RNA splicing during maturation of the final RNA product
exon
any part of a gene that will encode a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing
stop codon
nucleotide triplet within messenger RNA that signals a termination of translation into proteins; 3 stop codons are UGA, UAA, UAG
transcript
a single stranded RNA product synthesized by transcription of DNA and processed to yield various mature RNA products such as mRNAs, tRNAs, rRNAs
gene product
the biochemical material, either RNA or protein, resulting rom expression of a gene
single nucleotide polymorphism
SNPs; most common genetic variation among people, each SNP represents a difference in a single nucleotide; SNPs do not always cause a change in gene products activity or expression
synonymous SNP
results in no change to the AA sequence
nonsynonymous SNP
results in a different AA put into the gene product
TA repreats
TATA box is a DNA sequence consisting of repeating thymine and adenine that indicates where a genetic sequence can be read and decoded; if TA are inserted or deleted, phenotypic changes can occur in the gene product that the TATA box precedes
insertion
occurs when one or more nucleotides are added to an AA sequence
deletion
occurs when one or more nucleotides are removed from an AA sequence
nonsense mutation
occurs when a SNP results in a premature stop codon in protein translation, truncating the protein and most likely rendering it nonfunctional; stop codon is TAG
