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Pharm > Lecture 32: Pharmacogenomics > Flashcards

Lecture 32: Pharmacogenomics Flashcards

1
Q

What number cause of death are ADRs?

A

The 4th leading cause of death

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2
Q

What 5 things contribute to different response to medications?

A
  • Pharmacogenetics
  • Demographic factors
  • Clinical factors
  • Dosing factors
  • Other factors
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3
Q

How can ethnicity and drugs affect African Americans?

A

African-Americans increased risk of heart failure from hydralazine

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4
Q

How can ethnicity and drugs affect Asian Americans?

A

East Asian descent people have issues with alcohol metabolism

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5
Q

How do Sex and Variation affect drug response?

A

Women tend to be underrepresented in drug trials and have more adverse events

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6
Q

How does age affect variation in drug response?

A
  • Drug metabolism is less efficient in newborns and the elderly
  • More side effects in vulnerable groups
  • Body fat composition changes
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7
Q

How does age affect Renal Excretion?

A
  • GFR rates is lower in neonates
  • GFR decline from 20 years
  • Takes longer to excrete drugs
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8
Q

How does age affect Drug Metabolism?

A
  • Changes in enzyme expression levels
  • CYPs and Phase II conjugating enzymes
  • Disease of metabolic organs (kidney/liver)
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9
Q

What three ways can genetic variation in a gene cause altered enzyme activity?

A
  • Regulatory variation
  • Coding variation
  • Splice-slice variation
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10
Q

How can Regulatory variation affect gene expression?

A
  • Increased expression of the regulatory element

* Decreased expression

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11
Q

How can Coding variation affect gene expression?

A
  • Missense
  • Start/stop lost
  • Inframe insertion/deletion
  • Stop gained
  • Frameshift
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12
Q

How can Splice-site variation affect gene expression?

A
  • Create/abolish the acceptor site

* Create/abolish donor site

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13
Q

What parts of DNA are spliced out?

A

Introns

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14
Q

What occurs in a single nucleotide polymorphism?

A

One nucleotide is replaced with another nucleotide

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15
Q

What is the start codon?

A

AUG

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16
Q

What is a splicing defect?

A

When introns aren’t spliced out properly

17
Q

What is expression quantitative trait loci (eQTL)?

A

A variant in a sequence is changing the expression level of another gene

18
Q

What is the difference between cis and trans eQTL?

A

Trans - affecting a gene somewhere else

Cis - affecting a drug downstream

19
Q

What does Precision health do?

A

Takes both genetic and non-genetic factors into account

20
Q

What enzyme is important in metabolizing drugs?

A

CYP2D6

21
Q

Why is CYP2D6 important?

A

There are so many genetic variants changing the function of CYP2D6

22
Q

How is drug metabolism affected by increased or decreased CYP2D6?

A

Increased CYP2D6 will increase drug metabolism

Decreased CYP2D6 will decrease drug metabolism

23
Q

What are the pharmacokinetics of Codeine?

A

It is converted to morphine by CYP2D6

24
Q

Why should some people not be prescribed codeine?

A

Because ultrarapid metabolizers should not be prescribed codeine due to toxicity risks it will be converted into morphine at increased rates

25
Q

What are important clinical considerations for pharmacogenomic biomarkers and clinical implementation?

A
  • Association between genetic variants and adverse drug reactions should be reliably replicated
  • Robust ADR phenotyping is essential
  • Risk conferred by variants should be clinically relevant
  • Implementation is assisted by clinical practice guidelines
26
Q

What is CPIC?

A

An organization that helps drug therapy through phenotype

27
Q

What is the issue with cancer treatments?

A

They are effective but not safe for children and associated with many health conditions

28
Q

What is Cisplatin?

A

A cancer drug that causes hearing loss

29
Q

What causes CIO susceptibility in people taking Cisplatin?

A

A variant in TCERG1L that changes levels of cytokines

30
Q

What is Mercaptopurine (6-MP)?

A

A purine analog that is a treatment for cancer and autoimmune diseases

31
Q

How does Mercaptopurine (6-MP) work?

A

It is a purine antagonist and inhibits DNA synthesis/replication

32
Q

How does Mercaptopurine (6-MP) work?

A

It is a purine antagonist and inhibits DNA synthesis/replication

33
Q

What are the side effects of Mercaptopurine (6-MP)?

A

It causes Myelosuppression (hematological toxicity)

34
Q

What is Mercaptopurine metabolized by?

A

Thiopurine Methyltransferase (TPMT) gene

35
Q

What do variants in TPMT and NUDT15 cause?

A

It can cause it to be inactive in some patients so Mercaptopurine cannot be cleared and it builds up even when dosed properly and cause cytotoxicity

Pharm (31 decks)

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