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Pharmacology > Pharmacogenomics > Flashcards

Pharmacogenomics Flashcards

1
Q
  1. What is pharmacogenetics❓

2. What is pharmagenomics❓

A
  1. Study of individual gene-drug interactions
  2. Study of genomic influence on drug response
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2
Q

The human genome project was a research program for mapping and understanding of all the genes in human beings.

When did it begin❓

When was it completed❓

How many genes were discovered❓

A

1984
2003

20,500 genes

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3
Q

If humans are 99.9% identical at the DNA level, what influences the differences in appearance/behavior/response to medications❓

A

The 0.1% difference is responsible about 3,000,000 specific DNA differences btwn pple

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4
Q

What are mutations❓

What is the normal codon for:

  1. Methionine
  2. Valine
  3. Leucine
  4. Serine
  5. Proline
  6. Tyrosine
A

Changes in DNA

  1. ATG
  2. GTG
  3. CTG
  4. TCT
  5. CCT
  6. ACT
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5
Q

What would you observe with administration of suxamethonium to a patient deficient in serum pseudocholinesterase❓

What is the rate of prevalence of this deficiency❓

A

Prolonged respiratory paralysis

1 in 2000 caucasians

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6
Q

What would you observe with administration of an anti-malaria to a patient deficient in G6PD❓

What is the rate of prevalence of this deficiency❓

A

Hemolysis of RBC (anemia)

1 in 100 African American

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7
Q

What enzyme is probably deficient in a pt that presents with bone marrow toxicity from administration of thiopurine/mercaptopurine❓

A

Thiopurine methyl transferase (TPMT)

  • 70% -High expression
  • 20% -Medium
  • 2% -Low
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8
Q
  1. A deficiency in N-acetylase (NAT2) transferase will lead to a slow inactivation of which drugs❓
  2. What is the rate of prevalence of this deficiency….
    a) Caucasians
    b) Africans
A
  1. Isoniazid
    Dapsone

2.

a. 45-65%
b. 10-15%

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9
Q

ADRs rank as the fourth leading cause of death (40,000-100,000 per year)

True or false

A

True

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10
Q

Drugs have a patent life of about 20 years

True or false❓

A

True

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11
Q

Cytochrome P450 is a family of isozymes that bio transform several drugs.

How many genes code for it❓

Divided among how families❓

Which are responsible for metabolizing most clinically important drugs❓

A

57 genes

18 families

CYP 2A6
CYP 2B6

CYP 2C9
CYP 2C19

CYP 2D6

CYP 2E1

CYP 3A4

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12
Q

What is the function of CYP1❓

How many subfamilies does it have❓

How many genes does it have❓

A

Drugs metab
Steroid (esp. estrogen) metab

2 subfamilies

3 genes

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13
Q

What is the function of CYP2❓

How many subfamilies does it have❓

How many genes does it have❓

A

Drug and steroid metab

13 subfamilies

16 genes

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14
Q

What is the function of CYP3❓

How many subfamilies does it have❓

How many genes does it have❓

A

Drug and steroid (+testosterone) metab

1 subfamily

4 genes

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15
Q

The CYP enzyme, 1A1, is responsible for the metabolism of which drugs❓

A

Caffeine
Testosterone
R-Warfarin

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16
Q

The CYP enzyme, 1A2, is responsible for the metabolism of which drugs❓

A

Acetaminophen
Caffeine
R-Warfarin

Phenacetin

17
Q

The CYP enzyme, 2A6, is responsible for the metabolism of which drugs❓

A

Testosterone

17beta-Estradiol

18
Q

The CYP enzyme, 2B6, is responsible for the metabolism of which drugs❓

A

Cyclophosphamide

Erythromycin
Testosterone

19
Q

The CYP enzyme, 2C-family, is responsible for the metabolism of which drugs❓

A

Acetaminophen
Testosterone
R-Warfarin

Phenytoin 
Zidovudine 
S-Warfarin 
Hexobarbital
Tolbutamide
20
Q

The CYP enzyme, 2E1, is responsible for the metabolism of which drugs❓

A

Acetaminophen

Caffeine

21
Q

The CYP enzyme, 2D6, is responsible for the metabolism of which drugs❓

A

Acetaminophen

Codeine

22
Q

The CYP enzyme, 3A4, is responsible for the metabolism of which drugs❓

A 
Acetaminophen 
Caffeine 
Cyclophosphamide 
Testosterone 
S and R-Warfarin 
Erythromycin 
Phenytoin 
Carbamazepine 
Cortisol 
Zidovudine
23
Q
  1. What substance can induce the action of CYP 3A4,5,7 on Felodipine❓
  2. a. What substance can inhibit it❓
    b. Will its concentration ⬆️/⬇️❓
A
  1. Glucocorticoid

2a. Grapefruit juice
b. It will increase if 3A4,5,7 is inhibited

24
Q
  1. What substance can induce the action of CYP 1A2 on Clozapine/Haloperidol❓
  2. a. What substance can inhibit it❓
    b. Will its concentration ⬆️/⬇️❓
A
  1. Tobacco smoke

2a. Cimetidine
b. It will increase if 1A2 is inhibited

25
Q

What is the risk associated with CYP enzyme inhibition❓

A 
Inhibition of enzyme
⬇️
Decreased degradation of drug
⬇️
Increased drug plasma conc.
⬇️
Risk of adverse effect
26
Q

What is the risk associated with CYP enzyme induction❓

A 
Increased degradation 
⬇️
Decreased drug plasma conc. 
⬇️
🚫pharmacological effect
⬇️
Risk of therapeutic failure
27
Q

What do tricyclic antidepressants do❓

A

⬇️serotonin reuptake

⬆️serotonin levels in cleft

28
Q

Response rates of antidepressants are low (1/3 +)

  1. True or false
  2. Why❓
  3. Give examples of TCA
  4. Give examples of SSRI
A
  1. True
  2. Biomarkers that can predict clinical efficacy or safety responses are not utilized
  3. Nortriptyline
    Imipramine
  4. Fluoxetine
    Paroxetine
29
Q

Which CYP enzyme is the most investigated with regard to antidepressant pharmacogenomics❓

30
Q

Hanson’s

31
Q
  1. Which drug group does codeine belong❓
  2. Is codeine a pro-drug❓
  3. What is it’s metabolizing enzyme❓
  4. What is the rate of deficiency of this enzyme❓
A
  1. Opioid
  2. Yes, it must be metabolized into morphine for activity
  3. CYT P450
    Allele CYP 2D6

7% of Caucasians are deficient

32
Q
  1. Which drug group does tamoxifen belong❓
  2. What is it’s metabolizing enzyme❓
  3. What is it metabolized to for its activity❓
  4. What is the rate of deficiency of this enzyme❓
A
  1. Antineoplastic (breast ca)
  2. CYP 2DE
  3. Endoxifen

6-10% European population

33
Q

What are the benefits of pharmacogenomics❓

What are it’s limitations❓

A 
1.
Max. drug efficacy 
Min. drug toxicity 
Predict pt that respond to interventions 
Aid in new drug development

2.
Costs and access to technology
Confidentiality of information

Pharmacology (10 decks)

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