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Pharmacology FINAL > Pharmacogenomics part 1 > Flashcards

Pharmacogenomics part 1 Flashcards

1
Q

define pharmacogenomics

A

the study of genetic factors that underline variation in drug responses

basically the study of how genes affect a person’s response to drugs

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2
Q

____ + _____ = pharmacogenomics

A

pharmacology + genomics

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3
Q

true or false

both endogenous and exogenous factors cause variations in drug response

A

true

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4
Q

name 3 ways in which there have been advances in pharmacogenomics

A

human genome project
advances in sequencing
GWAS (large genome wide associated studies)

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5
Q

what is an allele

A

one of 2 or more alternate forms of a gene.

arise by mutation. found at the same genetic locus

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6
Q

give an example of an allele

A

CYP2D6*3 is a important variant allele for the drug metabolizing enzyme CYP2D6

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7
Q

what is allele frequency

A

the fraction or percentage of times a specific allele is observed in proportion to the TOTAL OF ALL POSSIBLE ALLELES that could occur at a specific location on a chromosome

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8
Q

what is another name for polymorphism

A

variant

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9
Q

define polymorphism

A

any genetic variation in the DNA sequence

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10
Q

what is SNP

A

single nucleotide polymorphisms

base pair substitutions that occur in the genome

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11
Q

what is cSNP

A

coding single nucleotide polymorphism

base pair substitutions that occur in the CODING REGION

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12
Q

what are insertions/deletions

A

insertions or deletions of base pairs

may occur in coding or noncoding regions

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13
Q

true or false

insertions or deletions of base pairs always occur in the coding region

A

false - may be coding or non coding region

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14
Q

what are copy number variations

A

a segment of DNA in which a variable number of that segment has been found

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15
Q

what are PM, IM, EM, UM

A

they are different phenotypes that exist due to polymorphism

PM = poor metabolizer
IM = intermediate metabolizer
EM = extensive metabolizer
UM = ultra rapid metabolizer

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16
Q

what is haplotype

A

a series of alleles found in a linked locus on a chromosome

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17
Q

explain the relationship between glucose transporters and polymorphism

A

a mutation in glucose transporters that causes them not to work properly will cause glucose to not be transported into the cell and remain in the blood, causing HYPERGLYCEMIA

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18
Q

polymorphism is defined as variations with a prevalence of the minor allele of at least ___% in at least ____ population(s)

A

at least 1-2% in at least 1 population

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19
Q

name the 4 classes of DNA polymorphisms

which is most common?

A

RFLP - restriction fragment length polymorphisms

VNTR - variable number tandem repeats

STR - short tandem repeats (1-8 base pairs)

SNP - single nucleotide polymorphism (*** most common)

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20
Q

what are the benefits of pharmacogenomics?

A

there will be improved drug choices because you can predict who is likely to have a therapeutic response or experience an adverse effect based on genetics.

-appropriate dosing options
-improvement for drug development
-health care costs and harm to pts decrease

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21
Q

rank the following according to the relative dose of drug they will receive:

-extensive metabolizers
-intermediate metabolizers
-poor metaboliers
-ultrarapid metabolizers

A

will receive the most dose: ultrarapid metabolizers
extensive metabolizers
intermediate metabolizers
will receive least dose - POOR METABOLIZERS

22
Q

Which type of metabolizer is the most common?

A

extensive metabolizer (then intermediate)

23
Q

how many whole gene deletions exist for all the types of metabolizers

A

PM = ~0
IM = ~0.5
EM = 1-2
UM = greater than or equal to 2

24
Q

phase 1 enzymes are involved in the biotransformation of over what % of prescription drugs?

A

over 75%

25
Q

what may significantly affect drug levels in the blood?

A

polymorphisms in the phase 1 enzymes that metabolize over 75% of prescription drugs, like…

CYP2C19
CYP2D6

26
Q

CYP2D6 metabolizes roughly _____% of all drugs

A

25%

27
Q

name 4 classes of drugs that are metabolized by CYP2D6

A

beta blockers
antidepressants
antipsychotics
opioids

28
Q

the gene for what enzyme is highly polymorphic, with about 100 alleles?
how many of these alleles are important?

A

gene for CYP2D6

9 are important

29
Q

which CYP2D6 alleles are nonfunctional?

A

*3, *4, *5, *6

30
Q

which CYP2D6 alleles have REDUCED function?

A

*10, *17, *41

31
Q

which CYP2D6 alleles are fully functional?

A

*1, *2

32
Q

which CYP2D6 allele is found in europeans at 20% frequency, but almost absent in asians at less than 1% frequency?

A

*4

33
Q

which enzyme isoform is responsible for the metabolism of codeine/morphine

A

CYP2D6

34
Q

Explain the phase 1 metabolism of codeine

A

metabolized by CYP2D6 via O-Demethylation into MORPHINE, which is 200x more potent than codeine.

this morphine binds to the micro Opioid receptor to produce analgesic activity

35
Q

what is the significance of the fact that codeine is metabolized by CYP2D6 and some people may be ultra rapid/intermediate/extensive/poor metabolizers via this enzyme due to polymorphism?

A

poor and intermediate metabolizers will not get sufficient pain relief bc codeine is not being metabolized into the 200x more potent analgesic: morphine

poor metabolizers should receive an alternative agent like morphine or a non-opioid

intermediate metabolizers should receive the standard dosing but be closely monitored, and alternatives may be used

extensive metabolizers will receive the standard dosing

ultra metabolizers have an increases rink of side effects like drowsiness and respiratory depression. alternate agents should be used

36
Q

which CYP isoform metabolizes acidic drugs?
name 4 classes of acidic drugs

A

CYP2C19

proton pump inhibitors
antidepressants
anti-epileptics
anti-platelet agents

37
Q

how many major alleles of CYP2C19 are there?
name them

A

4
*2 and *3 are non function
*1 is fully functional
*17 has increased function

38
Q

what class is fluoxetine

A

SSRI antidepressant

selective serotonin reuptake inhibitor

39
Q

what is the name of the device that can check for 31 variations in 2 genes?
what 2 genes are they?

A

CYP2D6 and CYP2C19

AMPLICHIP - drop of blood obtained from inside the patient’s cheek

40
Q

polymorphic phase 2 enzymes may cause what?

A

may diminish drug elimination and increase the risk for toxicities

41
Q

phase 2 enzymes biotransformation reactions typically do what?

A

CONJUGATE endogenous molecules like sulfuric acid, glucuronic acid, and acetic acid onto a wide variety of substrates

so they can be eliminated

42
Q

phase 2 reactions are primarily which enzymes

A

TRANSFERASES

43
Q

a deficiency in glucose-6-phosphate dehydrogenase will cause what?
(G6PDH)

A

hemolytic anemia

44
Q

what enzyme is part of the first and rate limiting step in the pentose phosphate pathway?

A

G6PDH

45
Q

explain what G6PDH is important for

A

GSH and NADPH generation (imp for metabolism)

imp in RBC detoxification of ROS

protects hemoglobin oxidation

46
Q

the gene for G6PDh is located on what chromosome

A

X chromosome (female)

47
Q

the G6PDH gene is highly polymorphic with over ____ variants

A

180

48
Q

___ females and ______ males show reduced G6PDH activity

A

homozygous deficient females and hemizygous (gene where one of its pairs is deleted) deficient males

49
Q

how many WHO classes of G6PDH deficiency are there?

A

5

1 and 2 are severe deficiency

3 is moderate deficiency

4 is no deficiency (normal)

V has ENHANCED G6PDH activity, which is also bad

50
Q
A

Pharmacology FINAL (11 decks)

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