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Pharm Exam 5 > Pharmacogenomics + Pharmacogenetics > Flashcards

Pharmacogenomics + Pharmacogenetics Flashcards

1
Q

CYP2D6

A

Pharmacogenetic phenotype- PHARMACOKINETIC

-enzyme that metabolizes about 25% of all meds

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2
Q

CYP2C9

A

Pharmacogenetic phenotype- PHARMACOKINETIC
-metabolism of many drugs - ESP KNOWN FOR METABOLISM OF WARFARIN

-some people are poor metabolizers=hgih warfarin levels = bleeding complications

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3
Q

CYP2C19

A

Pharmacogenetic phenotype- PHARMACOKINETIC

  • chinese and japanese have this = greater cure rate bc more activity of the drugs
  • proton pump inh inactivators (omeprazole and iansoproazole)
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4
Q

TYMS

A
  • pharmacogenetic phenotype - RECEPTOR/TARGET:
  • thymidylate synthetase
  • methotrexate - anticancer or immunosuppressive inh methionine and DNA synthesis
  • indel occurs where promoter enhanced for TYMS = inc breakdown of methotrexate = dec efficacy and poorer prognosis
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5
Q

ERalpha

A
  • pharmacogenetic phenotype - RECEPTOR/TARGET: ESTROGEN RECEPTOR alpha
  • polymorphism in the intron between the 1st and 2nd exon of the ERalpha gene
  • homozygotes for the less common (c/c) allele had a greater inc in HDL levels following HRT
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6
Q

APOE

A
  • pharmacogenetic phenotype- INDIRECT: Apolipoprotein E
  • lipoprotein found in chylomicrons VLDL, IDL, and HDL
  • absence of certain allelesin the APOE gene corelate with better than therapeutic success for alzheimers disease therapy with tacrine
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7
Q

KCNE2

A
  • pharmacogenetic phenotype- INDIRECT: Potassium channel sub-unit
  • 1.6% of population are variants
  • antibiotic therapy (clarythromycin) can induce prolonged QT interval
  • result in a deadly cardiac arrhythmia
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8
Q

OCT1

A

-hepatic transporter that mediates the uptake of organic cations

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9
Q

pharmacogenetics definition:

A

study of the genetic basis for variations in drug response

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10
Q

pharmacogenomics definition:

A

uses tools for surveying the entire genome to assess multigenetic determinants of a drug response

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11
Q

gene by environment phenotype definition:

A

complex interplay between environmental and genetic factors

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12
Q

monogenic response v multigenic response:

A

expression of a single gene yields single phenotype

vs

networks of genes acting together to create a single phenotype

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13
Q

recessive trait

A

phenotype exhibited when a non-functional allele occurs on both the maternal and paternal chromosome

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14
Q

dominant trait

A

phenotype exhibited when a non-functional allele occurs on either the maternal or paternal chromosome

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15
Q

co-dominant trait

A

heterozygotes display an intermediate phenotype as compared to wild type and homozygotes

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16
Q

polymorphism definition

A

variation in the genetic code present at an allele frequency of >=1%

-ex = SNPs

17
Q

single nucleotide polymorphism (SNP)

-genetic consequence:

A

1) if in coding region:
a) nonsynonymous/missense
- BP change–> single amino acid change (different amino acid!)
- change in protein structure, stability, substrate affinity, intro of stop codon
b) synonymous/sense
- BP change= NO amino acid substitution (still get same amino acid)
- result in dec transcript stability or alter splicing
2) non-coding region:
- promoter
- intron
- reg region
- Results:
- -> transcription factor binding change
- -> enhancer change
- -> splicing change
- -> transcript stability change

18
Q

Indels:

A
  • insteritions = frameshift (change is structure, alter promoter =inc transcript quality, gene dup/mult, stop codon)
  • deletions =loss of genetic material (loss of gene; premature stop codon)
19
Q

cosmopolitan polymorphisms:

A

polymorph common across all ethnic groups

20
Q

population polymorphism:

A

polymorph that differ between groups (ethnic or race)

21
Q

phenotype to genotype measuring:

A

drug response outliers are compared to normal responders to identify altered responses to drugs

OUTCOME (PHENOTYPE) AND THEN YOU GO LOOKING FOR WHATS DIFFERENT (GENOTYPE)

22
Q

measure a pharmacogenetic trait:

A

TRAIT IS NOT THE GENETIC SEQUENCE - ITS THE MEASURABLE RESPONSE TO THE DRUG!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!*** IT IS SOMETHING THAT CAN CHANGE!!!! CANT CHANGE THE GENETIC SEQUENCE SO IT IS NOT A TRAIT!

CAN I CHANGE IT WITH DRUG??=

  • enzyme activity
  • drug levels in bodily fluids
  • drug metabolite in bodily fluids
  • physiological response (BP)
  • gene expression patterns
23
Q

Adv/Disadv of pharmacogenetic traits:

A
  • adv=sum of all genes giving rise to an effect (LOOKING AT FINAL ENDPOINT)
  • disadv=non-genetic influences giving rise to and unstable result (CANT FACTOR DIET OR OTHER DISEASE)
24
Q

Genotype to phenotype definition:

A

genome is surveyed to determine if genomic variability results in phenotypic variability

25
Q

genotyping:

A
  • testing that reveals the specific genetic sequence of an allele
  • requires extraction of the DNA from somatic cells (blood or buccal)
26
Q

adv/disadv of genotyping:

A

1) adv=
- DNA is stable
- testing needs to be done only once
2) disadv=
- dependent upon annealing (TAGGING) of an oligonucleotide sequence to DNA
- false pos/neg

27
Q

candidate gene approach:

A

candiadte gene:

  • known or partially known cellular pathway involved in a drug response
  • identify polymorphisms which result in a response (patient screening, data base)
  • test the polymorphism in a function assay
28
Q

Disadv to candidate gene approarch?

A

-wrong gene may be studied

29
Q

genome wide approach:

A
  • unbiased survery of the genome

- compare DNA, RNA, or protein of identically treated patients (those with adverse drug reaction vs normal responders)

30
Q

disadv to genome wide approach:

A

-id of a variation that does not matter

31
Q

Pharmacogenetic phenotype- PHARMACOKINETIC:

A
  • polymorphism in a gene or genes that regulate pharmacokinetics
  • enzymes or transporters
  • alter drug concentrations resulting in changes in therapeutic and adverse events

P450s, OCT1, CYP2D6, CYP2C9 … other metabolism enzymes

32
Q

pharmacogenetic phenotype - RECEPTOR/TARGET:

A
  • polymorphism in a gene that codes for drug target
  • alters drug response (impaired drug binding for example)

CHANGE IN DRUG BINDING AFFINITY TO TARGET

ex- TYMS, ERalpha

33
Q

pharmacogenetic phenotype- INDIRECT:

A

-polymorphism in a gene that does not interact with the drug, is not a direct target of the drug, or is not involved with the drugs disposition

Ex: APOE, KCNE2

34
Q

Major types of evidence?

A
  • screens of tissue from mult patients linking a polymorphism to a trait
  • preclinical functional studies
  • clinical phenotype/genotype studies
35
Q

Results of pharmacogenomic data can lead to:

A
  • id of new drug targets
  • genomic-specific development of new drugs
  • genotype-specific dosing regimens

Pharm Exam 5 (10 decks)

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