Brainscape's Knowledge GenomeTM

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


See full index

Personalized Theraputics > Lassila > Flashcards

Lassila Flashcards

1
Q

What is CPIC?

A

Clinical Pharmacogenetics Implementation Consortium- guidelines designed to help clinicians understand how available genetic test results should be used to optimize drug therapy

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

What is PharmGKB?

A

Pharmacogenomics knowledgebase- collects, curates, and disseminates knowledge about PGx

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

What kind of data does PharmGKB publish?

A
  1. annotate genetic variants and gene-drug-disease relationships via lit review
  2. curate FDA labels containing PGx Information
  3. create clinical annotations for drug-gene pairs based on curated lit
  4. assign levels of evidence based on criteria such as replication, stat significance, and study size
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is pharmacogenetics?

A

study of the relationship between variations in a single gene and variability in drug disposition, response, and toxicity

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

What is pharmacogenomics?

A

study of the relationship between variations in a large collection of genes (up to the whole genome) and variability in drug disposition, response, and toxicity

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

What is a genome?

A

organism’s complete set of DNA including all its genes regulatory elements, and other nucleotide sequences

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is genomic organization?

A

Genome
Chromosome
Gene
Nucleotide

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

What is a genetic variant?

A

difference in DNA sequence compared with a reference sequence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is a polymorphism?

A

common genetic variant, occurring 1% or more of the population

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

What is a mutation?

A

genetic variant, occurring in less than 1% of the population

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

What are single nucleotide variants?

A

the difference in 1 nucleotide of DNA account for most variations the human genome

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

What are insertion/ deletion variants?

A

insertion or deletion of one or more consecutive nucleotides from DNA sequence
Ex. insertion/ deletion of 287 consecutive bps in the ACE enzyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are variable number of tandem repeats?

A

Sequences of nucleotides repeated a variable number of times
Ex. Gilberrt’s Syndrome is caused by a variable number of TA repeats in the UGT1A1 gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is copy number variation?

A

gain (duplication) or loss (deletion) of a large region, usually >1000 bps
Ex. CYP2D6 drug metabolizing gene has CNVs, including deletions, duplications, and multiplications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is an allele?

A

1 of 2 or more forms of DNA sequence that is located at a specific position on a specific chromosome

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

what is a genotype?

A

combination of alleles a person carries at a particular location in DNA (1 from other and 1 from father)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is a phenotype?

A

measurable characteristic of an organism
(environmant and genetics)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are pharmacologic phenotypes?

A
  1. ultrarapid, extensive, intermediate, poor metabolizers
  2. Pk- plasma drug concentration, AUC, clearance, Cmax
  3. Pd- responder, non-responder
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is a haplotype?

A

set of closely linked alleles that are located on one chromosome and inherited together as a unit or block

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is a diplotype?

A

combination of two haplotypes (1 haplotype from mom and 1 haplotype from dad) 2/3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the result of genetic variants in drug-metabolizing enzyme function?

A

Would affect:
1. clearance
2. AUC
3. half life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What does it mean if someone has decreased metabolism of an active parent drug?

A

increased plasma exposure of the active parent drug and decreased metabolism to inactive metabolites lead to increased risk of toxicity/ effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What does it mean if someone has increased metabolism of an active parent drug?

A

decreased plasma exposure and decreased effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What does it mean if someone has decreased metabolism of a prodrug?

A

decreased plasma exposure and effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What does it mean if someone has increased metabolism of a prodrug?

A

increased plasma exposure of the active parent drug and decreased metabolism to inactive metabolites lead to increased risk of toxicity/ effect

26
Q

What is a HLA?

A

Human Leukocyte Antigens- present intracellular antigens (drugs) to the immune system to determine if they are self or non-self; highly polymorphic

27
Q

What HLA variation is associated with Abacavir-gene-related immune response?

A

HLA-B *57:01

28
Q

What HLA variation is associated with Allopurinol-gene-related immune response?

A

HLA-B *58:01

29
Q

What HLA variation is associated with aromatic anticonvulsants (carbamazepine) -gene-related immune response?

A

HLA-B *15:02
HLA-A *31:01

30
Q

When do patients experience an Abacavir HSR?

A

within the first 6 weeks (median onset, 10 days)

31
Q

What are the symptoms of Abacavir HSR?

A
  1. fever
  2. rash
  3. GI symptoms
  4. fatigue
  5. cough
  6. dyspnea
32
Q

What should be done if Abacavir HSR occurs? When can the med be restarted?

A
  1. immediate discontinuation and supportive care
  2. re-challenge is CI
33
Q

What did the PREDICT-1 study find?

A

Presence of HLA-B *57:01 is predictive of clinically- diagnosed and immunologically confirmed Abacavir HSR

34
Q

What is analytical validity?

A

ability of a genetic test to measure accurately and reliably the genotype of interest

35
Q

What is clinical validity?

A

accuracy with which a test can predict the presence or absence of the clinical outcome (phenotype) or disease of interest

36
Q

What is clinical utility?

A

likelihood that the test will lead to an improved outcome

37
Q

What are the types of Carbamazepine cutaneous HSRs?

A
  1. Mild maculopapular eruptions (MPE)
  2. drug reaction with eosinophilia and systemic symptoms (DRESS)
  3. SJS
  4. TENs
38
Q

What is MPE?

A

Mild Maculopapular Eruptions- mild skin rash

39
Q

What is DRESS?

A

Drug reaction with eosinophilia and systemic symptoms- skin rash plus fever, angioedema, lymphadenopathy, hepatitis

40
Q

What gene is associated with an increased risk of Carbamazepine- induced SJS and TENs?

A

HLA-B *15:02

41
Q

What gene is associated with MPE, DRESS, SJS, TENS, and is a driver of Carbamazepine HSRs in populations where HLA-B*15:02 is lower (Europeans, Africans, Japanese)?

A

HLA-A *31:01

42
Q

What BBW does Carbamazepine have?

A

patients with ancestry in genetically at-risk populations should be tested for the presence of HLAB*15:02

43
Q

What populations are at-risk for the presence of HLAB*15:02?

A
  1. Chineese (han, hong kong)
  2. Malaysia
  3. Thailand
  4. Philippines
  5. India
  6. Vietnam
  7. Cambodia
44
Q

If someone is HLA-B*15:02 positive what other anticonvulsants be avoided?

A
  1. Oxcarbazepine
  2. Phenytoin
  3. Fosphenytoin
45
Q

If someone is HLA-B*15:02 positive what other anticonvulsants be used with caution?

A
  1. Lamotrigine
  2. Eslicarbazepine
  3. Phenobarbital
46
Q

What other HLA-B alleles are associated with Carbamazepine SJS/TEN in Southeast Asians?

A
  1. HLA-B *15:08
  2. HLA-B *15:11
  3. HLA-B *15:21
47
Q

What gene is associated with allopurinol-induced HSR, SJS, and TEN?

A

HLA-B58:01

48
Q

When should genetic testing for allopurinol be done?

A

testing for HLA-B*58:01 is conditionally recommended for patients of Southeast Asian descent

49
Q

What gene is associated with Phenytoin SJS/ TEN?

A

HLA-B*15:02

50
Q

What should be done if someone already taking Phenytoin test positive for the HLA-B*15:02 gene?

A

if used continuously for longer than 3 months without incidence of HSR, cautiously consider use in the future

51
Q

What enzyme is responsible for the conversion of Amitryptiline to Nortriptyline?

A

CYP2C19

52
Q

What enzyme is responsible for converting Amitryptiline and Nortriptyline to their active metabolites?

A

CYP2D6

53
Q

How are CYP2D6 poor metabolizers affected by Amitryptiline and Nortriptyline?

A

increased plasma concentration and higher risk of adverse effects

54
Q

How are CYP2C19 poor metabolizers affected by Amitryptiline and Nortriptyline?

A

increased plasma concentration and higher risk of adverse effects

55
Q

When is CYP2D6 active and fully mature?

A

early childhood

56
Q

When is CYP2C19 active and fully mature?

A

increased activity in children; activity decreased with age

57
Q

What are common SEs with CYP2D6 and CYP2C19 metabolites of Amitryptiline and Nortriptyline?

A
  1. arrhythmias
  2. heart block
  3. tachycardia
58
Q

What SSRIs are metabolized by CYP2D6?

A
  1. Paroxetine
  2. Fluvoxamine
59
Q

What SSRIs are metabolized by CYP2C19?

A
  1. Citalorpam
  2. Escitalopram
  3. Sertraline
60
Q
A

Personalized Theraputics (6 decks)

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