Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Spring 2024 (All Classes Except Therapeutics+ Lab) > Pharmacogenomics Final > Flashcards

Pharmacogenomics Final Flashcards

1
Q

What are the indications for clopidogrel?

A

STEMI
Unstable Angina
PCI

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

What is the MOA of Clopidogrel?

A

Prodrug

-Active metabolite: R-130964

-Irreversible binds to the P2Y12 receptor on platelets

-Inhibits ADP-mediated platelet aggregation

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

After giving clopidogrel, what % is hydrolyzed to inactive metabolites?

A

85%

(only 15% is active)

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

Which enzyme is important in clopidogrel metabolism?

A

CYP2C19

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

What are the barriers to implementing CYP2C19 genetic testing prior to a PCI?

A

Turn-around-time of test
Strength of association has been questioned

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

What is warfarin used for?

A

Afib
Prevention and treatment of thromboembolic disease (DVT), (PE)

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

What is the MOA of warfarin?

A

Inhibits vitamin K epoxide reductase 1 (VKORC1)

-decreases formation of vitamin K dependent clotting factors

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

CYP2C9 eliminates which enantiomer of warfarin?

A

S-enantiomer

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

What is the surrogate marker used in clinical practice to decide if warfarin treatment is working?

A

INR

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

What are the 2 most studied alleles of CYP2C9?

A

*2 and *3

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

By how much does the loss of function CYP2C9*2 reduce warfarin clearance?

A

30-40%

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

What dose reduction is needed with CYP2C9*2 and warfarin?

A

19% dose reduction per allele

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

The loss of function CYP2C983 reduces warfarin clearance by what?

A

75-90%

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

What dose reduction is needed with CYP2C9*3?

A

33% dose reduction per allele

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

What are the two SNP locations in VKORC1 with warfarin?

A

1639G>A

1173C>T

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

Which VKORC1 SNP has the greatest sensitivity?

A

AA/TT

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

Which VKORC1 SNP has the greatest tolerance?

A

GG/CC

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

What is the function of CYP4F2?

A

Metabolizes vitamin K to hydroxyl metabolite

-results in less vitamin K for clotting factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the CYP4F2 SNP?

A

rs2108622

1297G>A
*reduced function allele
*greater vitamin K availability

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

How much variability is contributed to warfarin dosing by CYP4F2?

A

1-3%

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

What is the MOA of statins?

A

Inhibit rate-limiting step in cholesterol biosynthesis

-Up-regulate LDL receptors
-Decrease serum LDL concentrations

HMG Co-A Reductase Inhibitors

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

Which statin is not affected by the SLCO1B1 genotype?

A

Fluvastatin

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

What drugs are affected by the Human Leukocyte Antigen Complex (HLA)?

A

Carbamazepine
Abacavir
Allopurinol

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

What role does HLA play?

A

Critical in the immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Carbamazepine HLA-B*1502 and SJS-TEN is associated with what adverse reaction?
Steven's Johnson Syndrome
26
Why is the association between HLA-B*1502 and Steven's Johnson Syndrome weaker in other Asian populations and not established in Caucasians?
These populations have less of the variant present
27
Who has the highest risk of Steven's Johnson Syndrome as a result of having HLA-B*1502 and taking carbamazepine?
Chinese
28
Which drug has a non-linear pharmacokinetic disposition?
Phenytoin (when you double the drug, the exposure will more than double)
29
For which group of drugs does hereditary involvement suggest a role in pharmacogenomics?
Psychosis and Depression
30
what are the goals of pharmacogenomics in psychiatry?
Focus on drug-metabolizing enzymes Minimize side effects Identify patients unlikely to respond
31
What are the future goals of pharmacogenomics in psychiatry?
Predict positive drug response
32
Which enzyme is upregulated by smoking?
CYP1A2
33
Which enzyme may be active in the brain and metabolize serotonin?
CYP2D6
34
What is personalized medicine?
*Does not just apply to genetics -It is how every pharmacist and clinician practices: right dose, right drug, to right patient Revisited definition: A form of medicine that uses information about a person's genes, lifestyle, and environment to prevent, diagnose, and treat disease
35
How many drugs have pharmacogenomic information in their labeling?
>300
36
When is pharmacogenomics most informative?
When we are considering drug and event characteristics Event characteristics: Serious (fatal, irreversible) Difficult to predict Alternative therapy available
37
What is the goal for pharmacogenomics in the future?
Take a patient's full genetic profile and apply the best therapy to that patient (overall goal is to know more than just SNPs)
38
Where are we currently in clinical pharmacogenomic practice?
Identify a known SNP with a large clinical effect and adjust drug therapy or dosage accordingly (Identify SNPs that change clinical outcome)
39
Where are we going in clinical pharmacogenomics practice?
Genome wide screening (including variants of unknown significance) with bioinformatic prediction to adjust drug therapy or dosage (sequencing the entire human genome and using it to adjust drug therapy or dosage)
40
What is the difference between pharmacogenetics and pharmacogenomics?
NONE -used synonymously Pharmacogenetics=Pharmacogenomics=PGx
41
What type of drug is voriconazole?
Triazole antifungal -used for invasive fungal infections including aspergillosis and candidiasis
42
What is the greatest risk with voriconazole dosing?
Therapeutic failure
43
What are 2 important things to remember about Voriconazole's pharmacokinetics?
Narrow therapeutic index Nonlinear pharmacokinetics
44
Management of cancer genetics has shifted from what to what?
From cytotoxic agents (chemotherapy, kills all quick growing cells) **typical gold standard To chemical and biological agents (target critical genes or pathways, not as narrow of a therapeutic index, gene expression determines proper agent) **less adverse effects, where treatment is heading
45
What are somatic mutations in the context of oncology?
Variations found within the tumor (non-inheritable) -Include oncogenes that drive the cancer and can be targeted
46
What are germline mutations?
Heritable variations found within the individual
47
What are predictive markers in oncology used for?
Used to identify subpopulations of patients most likely to respond to a therapy
48
What is Acute Lymphoblastic Leukemia (ALL)?
-Cancer of the blood and bone marrow *Most common childhood malignancy -90% survival rate
49
What is the treatment for Acute Lymphoblastic Leukemia (ALL)?
Maintenance chemotherapy (up to 2y) Oral 6-mercaptopurine 50mg***
50
When there is a mutation in a cancer-associated gene what normally happens to its function?
Typically leads to overactivity of the receptor -bad, enhances cancer's survival ability -can increase angiogenesis (increased blood vessels help the tumor grow)
51
What are the 2 types of lung cancer?
Non-Small Cell Lung Cancer (NSCLC) Small Cell Lung Cancer (SCLC)
52
What is the most common type of lung cancer?
Non-Small Cell Lung Cancer (NSCLC)
53
What is the first-line drug treatment for lung cancer (NSCLC)?
Chemotherapy *targeted therapy linked to biomarkers may help overcome drug resistance
54
Which receptor do Tyrosine Kinase Inhibitors target (TKIs)?
EGFR -because it has a tyrosine kinase domain in it
55
How does the EGFR protein tyrosine kinase family contribute to cancer formation?
-Overexpression implicated in numerous cancers -Dysregulated and active
56
What drug might we use to treat Non-small cell lung cancer (NSCLC) instead of chemotherapy?
TKI inhibitors
57
When would we choose to use TKI inhibitors to treat NSCLC rather than chemotherapy?
If mutations in EGFR (HER1/ErbB1) are present: Use TKI inhibitors If mutations are not present: Chemotherapy may be more effective
58
When would we use erlotinib and afatinib?
In treatment of patients with NSCLC who have: Exon 19 deletions Exon 21 (L858R) substitution mutations -in EGFR
59
What is a clinical barrier to genotype guided dosing with the use of such drugs as erlotinib and afatinib?
In many cases, it is desired to begin therapy before the genotype results are available
60
What is the function of Cetuximab/Panitumumab?
MABs that inhibit the growth and survival of tumor ells with overexpressed EGFR
61
What cancer types are Cetuximab/Panitumumab indicated in?
Colon Head and Neck NSCLC
62
Resistance to cetuximab and panitumumab has an association with mutations in what?
KRAS
63
What kind of receptor is ALK?
Tyrosine Kinase receptor
64
Phase II reactions are primarily what?
Conjugation Reactions -add a conjugate to deactivate drug/metabolite

Spring 2024 (All Classes Except Therapeutics+ Lab) (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions