Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Advanced Pharm- Test 1 > Pharmacogenomics > Flashcards

Pharmacogenomics Flashcards

1
Q

What are introns?

A
  • Regulatory piece of DNA/RNA
  • Transcription factors bind here
  • non coding
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are exons?

A
  • coding region
  • Map for proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is splicing?

A

where introns are removed and exons put together

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is alternative splicing?

A

initial RNA can be modified to make slightly different proteins (different mRNA, depending on how splicing occured)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Order of events for protein transcription?

A

Gene (DNA)–> Transcription –> primary transcript (RNA)–> splicing–> mature transcript (mRNA)–> translation–> protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What 4 bases make up DNA?

A
  • Adenine- Thymine
  • Guanine- Cytosine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the sugar backbone of DNA?

A

Deoxyribose sugar phosphate backbone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What nucleotide bases make up RNA?

A
  • Adenin- uracil
  • Guanine- cytosine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What backbone does RNA consist of?

A

Ribose sugar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What makes an amino acid?

A

3 nucleotides= 1 codon–> 1 amino acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What does an amino acid sequence start with? End with?

A

Start= methionine

end- stop codon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is a SNP?

A
  • Single nucleotide polymorphism is a DNA sequence variation that occurs when a single nucleotide in the genome is altered
  • Frequency: mutation found in at least 1 % of the population
  • accounts for 90% of human genetic variation
  • can occur in coding or non-coding regions
  • generally not a huge deal UNLESS the SNP inserts an extra nucleotide or removes nucleotid.
    • if it does this, it causes a frameshift and can be a huge deal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is G6PD?

A
  • part of pentose phosphate pathway
  • provides reducing energy (NADPH) to cells to protect them from ROS
  • makes glutathione (rely on it for detoxifying acetaminophen)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is G6PD deficiency?

A
  • Subject to oxidative stress, causing hemolysis, RBC breakdown–> hemolytic anemia
    • RBC borken down faster than body can produce them
    • generally goes unnoticed until oxidative stress
  • Men more likely to suffer from G6PD def. because it resides on the X chromosome
    • X-linked ressessive pattern
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the survival advantage to G6PD deficiency?

A

Provides protection against malaria

Heavily found genetically from countries where malaria is a higher risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What does a BChE deficiency cause?

A
  • prolonged apnea after succinylcholine administration
  • BChE= butycholinesterase aka pseudocholinesterase aka plasma cholinesterase
17
Q

What are some drugs metabolized by plasma cholinesterase?

A
  • succinylcholine
  • mivacurium
  • chloroprocaine
  • tetracaine
  • procaine
18
Q

What type of variant is BChe deficiency?

A
  • autosomal recessive
  • not an all-or-nothing variant. varying degree of butylcholinesterase activity
19
Q

What is porphyria?

A
  • one of several mutation in the biosynthetic pathway of heme
  • clinical symptoms result from buildup of pre-cursors
    • precursors can be very dangerous and can be fatal in buildup
  • exacerbation can be spontaneous or result from exposure to drugs, hormones and other compounds
20
Q

What is the main porphryia type we encounter? Symptoms?

A
  • Acute Intermittent Porphyria
  • Symptoms:
    • pain in abdomen, back
    • nausea
    • tachycardia without fever
    • seizures
    • urine normal to dark amber
21
Q

What is NAT2? What happens when deficient in NAT2 or increased NAT2?

A
  • Found that with isoniazid (1st effective drug for TB) that the concentration of isoniazid in urine depended on individual’s ability to convert isoniazid to acetylisoniazid (by NAT2= n- ACETYLTRANSFERASE)
    • Slow acetylators- (Low NAT2) prone to isoniazid toxicity (peripheral neuropathy)
    • fast acetylators- (High NAT2) more prone to hepatotoxicity
  • acetyltransferase also important in metabolism of hydralazine, procainamide, dapson and sulfonamides
    • deficiency can lead to lupus type syndrome
22
Q

What is heredity of NAT2 deficiency mutation?

A

single recessive gene

  • 2 most common alleles (NAT2*5 AND 2*6)
    • acocund for 90% of slow acetylators
  • 27 known variables, so variation is hard to determine
  • most variant alleles involve 2-3 point mutations
23
Q

What is phase I drug metabolism?

A
  • Functionalization reaction
  • 80% of drugs metabolized this way
  • exposes a functional group
  • small increase in polarity
  • ex- oxidation, reduction, hydrolysis
24
Q

What is phase II drug metabolism?

A
  • Conjugation reaction- more invovled
  • large polar compound attached to functional group (covalent bond)
  • large icnrease in polarity
  • ex- acetylation, glucoronidation
25
Q

What are some main enzymes involved in phase I metabolism?

A
  • CYP 3A,4,5,7
  • CYP2D6
26
Q

What are some pharmacogenmoic implications with wafarin?

A
  • Wafarin is a racemic mixture
    • R-warfarin- metabolized by CYP3A4, 1A2, 1A1
    • S-warfarin- metabolized by CYP 2C9
      • 5 x more potent than R warfarin
  • Warfarin inhibits vitamin K epoxide reductase
    • reduced vitamin K is a cofactor for GGCX, which catalyzes the formation of functional clotting factors
    • decreased clotting factors–> decreased coags
27
Q

What are some main enzymes involved in phase II metabolism?

A

UGT

NAT1/2

(also COMT is phase II, side note)

28
Q

What were some goals of the human genome project?

A
  • Coordinated by US dept of energy and NIH
  • Goals
    • id all gnees
    • determine sequences of base paird that make up human DNA
    • store this info
    • improve data analysis toolds
    • transfer technologies to private sector
    • address ethical, legal and social issues that may arise form project
29
Q

What are factors contributing to warfarin metabolism?

A

unknown> VKORC1> sex/BMI/age/diet/drugs >cyp2C9

  • the contribution of warfarin metabolism by CYP2C9 is rather small, esimated to be approximately 10% warfarin dose variations
  • contribution of VKORC1 is 25%
  • clinical factors such as age, sex, diet, drgus, BMI contribute 20%
  • thus, the identified factors that contribute to variable warfarin responses account for approx. 50%, the other, as yet unidentified factors reach almost 50%
30
Q

What is GINA?

A
  • Genetic information nondiscrimination act (2008)
  • protects americans from discrimination based on genetic information in health insurance and employment
31
Q

What is the role of CYP2C9 SNP in drug metabolism?

A
  • This enzyme metabolizes S- warfarin ( 5 x more potent than R)
  • Wild-type variant *1- metabolizes warfarin normally
  • Two polymorphic variants *2 and *3
    • *2 reduces warfarin metabolism by 30%
    • *3 reduces warfarin metabolism by 90%
      *
32
Q

What is VKORC1?

A
  • Vitamin K expoxide reductase
  • reduces vit K in order to make coagulation factors
  • common polymorphism is G1639A
    • This variant has lower level of VKOR enzyme
    • more sensitive to Coumadin
  • If you have more robust VKORC1- you would need more drug to have an effect
33
Q

What is clopidogrel MOA?

A
  • Binds to ADP receptors on plt and prevent aggregation and thrombosis
  • However, clopidogrel is a prodrug and it is the active metabolite that actually binds to the P2RY12 receptor
  • Prodrug mdae active by CYP2C19
    • this enzyme has many different variants
    • 2,3,4,5 have NO activity and drug is ineffective
    • 17 has increased actiivty and exaggerated response
34
Q

What are some CYP2C19 variants and what is a drug is impacts?

A
  • CYP2C19 impacts clopidogrel metabolism
  • *2 and *17 are most common
  • *2- this variant causes CYP2C19 activity to be decreased- clopidogrel to not work because it can’t be transformed into its active form
    • why clopidogrel has black box warning for recommendaiton of genetic testing
  • *17 causes CYP2C19 activity to be increased
35
Q

What enzyme is involved in codeine metabolism? Implications?

A

CYP2D6

  • Low affinity for opioid receptors. considered a prodrug
  • 10% of codeine is converted to morphine, partially by CYP 2D6
  • Poor metabolizers- can’t convert codeine–> morphine and do not feel pain relief (placebo, no CYP2D6)
  • Ultra rapid metabolizers: metabolize codeine too efficiently, which can cuase morphine intoxication (robust cyp2d6)
    • Usually noted ethnic difference, with ethiopian being the highest percentage of ultrarapid metabolizers
36
Q

What enzyme is tamoxifen metabolizes by?

A

CYP2D6

  • Prodrug, metabolized by CYP2D6
    • CYP2D6 is rate limiting enzyme in caralysis of tamoxifen to metabolites with greater affinicty for estrogen receptor
    • if have low activity of CYP2D6, likely giving placebo
      • do enzyme acitivty test before admin
37
Q

What can vemurafenib be used for? What is the mutation involved?

A
  • Melanoma drug for BRAF V600E mutations only
  • B-raf mutated in 80% melanomas (commonly BRAF V6003, >60% of melanomas–> constitutive activaiton of Braf
    • braf important in signaling bathway
    • drug stops clelular proliferation
  • shows lots of drug resistance
38
Q

What are some reasons pharmacogenomics hasn’t really taken off as much as expected?

A
  • gap in translation between research and putting results into clinical practice
  • associations between genotype and phenotype not always reproducible
  • hard to get companies to invest
  • many mutations are rare and the tests would only benefit some people
  • takes time

Advanced Pharm- Test 1 (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions