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Pharmacology > Pharmacogenomics > Flashcards

Pharmacogenomics Flashcards

1
Q

What are the black box drugs:

A

black box warnings highlight serious and sometimes life-threatening adverse drug reactions within the labeling of prescription drug products

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2
Q

What are the common black box drugs (5)

A

Abacavir

Carbamazepine

Clopidigrel

Codeine

Rasburicase

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3
Q

Why do different people respond differently to the same dose of the same drug?

A

Genetic polymorphism

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4
Q

Describe the first pharmacodynamic study.

What was the conclusion?

A

Taste blindness

3/4 of the population. Can taste PTC
1/4 cannot

Autosomal recessive
Receptor- Ligand interactions differ on a hereditary basis

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5
Q

What are the 5 basic categories of genetic variation?

A
  1. variations that affect pharmacokinetics,
    Enzymes that metabolize drugs
    Transporters the move drugs (rare)
  2. receptor variations CYP450
  3. Variability that leads to adverse reactions G6PD
  4. Variation in pathogenesis/ progression
  5. cancer pharmacogenetics
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6
Q

What are the most common bio markers that appear on drugs?

A

CYPs

G6PD

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7
Q

CYP2D6

A

Metabolizes 25% of drugs

Highly polymorphic

Can reduce or boost metabolism

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8
Q

What phenotypes does CYP2D6 give rise to?

A

Poor
Intermediate
Extensive
Ultra rapid

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9
Q

What is the relationship between CYP2D6 and Codeine?

A

Codeine is a prodrug converted into morphine by CYP2D6

Poor metabolizers get no effect.

Rapid metabolizers can activate codeine quickly risking morphine intoxication coma and death.

Black box

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10
Q

CYP2C19

A

Metabolized 10% of drugs

Highly polymorphic

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11
Q

What metabolic phenotypes does CYP2C19 give rise to?

A

Poor
Intermediate
Extensive
Ultra-Rapid

Poor (Asians)

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12
Q

What is the relationship between Clopidogrel and CYP2C19?

A

Clopidogrel is a prodrug activated by CYP2C19.

Clopidogrel is an anti platelet drug.

Poor metabolizers don’t activate Clopidogrel

CYP2C19 oxidizes Clopidogrel thenits hydrolyzed

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13
Q

What is the alternative to Clopidogrel?

A

Prasugrel also a prodrug does not rely on CYP2C19

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14
Q

What is the significance of UGT1A1?

A

It’s a phase 2 enzyme that glucaronizes billirubin.

Glucaronization increases solubility for excretion.

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15
Q

What does the homozygous polymorphism in UGT1A1 lead to?

A

Mild jaundice in 25% of Europeans.

Gilbert’s syndrome.

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16
Q

How does Irinotecan demonstrate variation in phase 2 enzymes?

A

Irinotecan is a prodrug And topoisomerase inhibitor for colon cancer.
Actively it’s SN38
SN38 suppresses bonemarrow and damages GI.
It’s inactivated by UGT1A1 glucoronidation

17
Q

What is the relationship between Irinotecan and UGT1A1?

A

Individuals with reduced function of UGT1A1 cannot deactivate the SN38. And have toxicity.

18
Q

What is G6DP

A

Glucose 6 Phosphate Dehydrogenase

It produces NADPH in red blood cells

Gene for G6PD on the X Chromosome

19
Q

What is the result of G6PD deficiency

A

The most common enzyme deficiency world wide and cells cannot handle oxidative stress.
And they lose

20
Q

What are causes of G6PD activity?

A

Infection food drugs primaquine

Blacks and Mediterranean males most susceptible

21
Q

What is Rasburicase:

A

A drug used to treat high levels of Uric acid in chemotherapy recipients.

Converts Uric acid to allantoin.
Creating Hydrogen Peroxide

22
Q

How is Rasburicase related to G6PD?

A

Rasburicase is contraindicated in People with G6PD deficiency because it can cause hemolytic lysis.

23
Q

How does Human Leukkocyte antigen variations cause skin hypersensitivities?

A

BecAuse the immune systems responds like a burn.

24
Q

What drugs display HLA variation sensitivity?

A

carbamazepine ( mood stabilizer) Asian black box

Abacavir( antiretroviral )

25
Q

What is the significance of Warfarin?

A

It prevents thrombosis

Top 10 reported drugs for adverse effects

Narrow Therapeutic index

4 genetic variables address in labeling

26
Q

What does warfarin inhibit?

A

Vitamin K Epoxide reductase VKORC1

Vitamin K helps with clotting factors

27
Q

How many dosing sensitivity phenotypes are there for warfarin for VKORC1 and what are they.

A

Low dose AA 27mg / Day Asians

Intermediate dose AB 4.9mg Per day European

Hi Dose BB 6.2 mg per day

25% of dosing variability

28
Q

What is Hepatic CYP2C9 in relationship to Warfarin?

A

CYP2C9 metabolizes warfarin into hydroxy- warfarin the inactive version.

CYP2C9 deficiency causes high plasma concentrations of warfarin and heavy bleeding

5-10%

29
Q

Why does Warfarin have to be given with Heparin at times?

A

Because warfarin inhibits both procoagulants and anticoagulants.

Mutated protein C is inhibited before Vitamin K can be inhibited.

This puts patients at risk of clot formation.

30
Q

Where do most pharmacogenetc problems arise from?

A

CYP2D6
CYP2C19
CYP2C9
G6PD

Pharmacology (4 decks)

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