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Flashcards in Pharmacogenetics Deck (100)
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1

NAT Gene effects which drug?

Isoniazid for TB

2

NAT Gene effects the pharmacology of Isoniazid for tuberculosis
How so?

Rate of acetylation is determined by genetic polymorphisms

3

What is NAT gene for?

N-Acteyltransferase enzyme

4

N-Acetyltransferase enzyme is important in which pathway?

Phase II Pathway

5

What is phase II pathway again?

Drug metabolism - attachment of a sugar/acetyl group to detoxify drug and make easier to excrete

6

What variation is seen for NAT polymorphisms?

Fast vs Slow acetylators of the drug Isoniazid
Asian - fast metabolizers
White - slower

7

What is Isoniazid used to treat?

TB

8

Fast isoniazid are at lower risk for

Toxic effects of liver but lower effectiveness for TB

9

Low isoniazid are at higher risk for

Toxic effects of liver but higher potency for TB

10

Isoniazid metabolism is associated with which gene?

NAT

11

Drugs influenced by CYP3A

Cyclosporine

12

What is cyclosporine

immunosuppressant

13

CYP3A and Mechanism of Mutation?

Genetically is less important than other drug metabolism genes because the population distribution is continuous and unimodal

14

CYP3A Inhibitor

Ketoconazole
Grapefruit juice

15

CYP3A inducers

Rifampin

16

So using logic, if CYP3A is a gene that is responsible for drug metabolism, and one of the drugs it targets is cyclosporine,
What should we think about when perscribing cyclosporine to patients on Ketoconazole or Grapefruit juice?

These inhibit CYP3A which metabolizes Cyclosporine (clears) thus, we may have a buildup of immunosuppressant and oversuppress our immune system?

17

What should we think about when perscribing Rifampin and Cyclosporine simultaneously?

Rifampin is a CYP3A inducer, so we may be excreting cyclospobyrine more rapidly than normal, thus reducing is immunosuppressive activity? may need to perscribe more?

18

Ketocanazole - a drug to treat fungal infection (topical) - let's say you want to perscribe it to your patient and your patient is also taking cyclosporine, what would be your concern?

Well, cycosporine is an immunosuppressant that is detoxified/cleared from the body in part by CYP3A - However, ketoconazole is an inhibitor of CY3PA thus, it would seem that if my patient was goint to also start taking ketoconazole, we would need to lower her dose of cyclosporine because she would not be clearing it as fast?

19

What three specific factors should we be thinking about when we perscribe cyclosporine for immunosuppressant agent?

Ketoconazole
Grapefruit juice and
Rifampin

Ketoconazole inhibits CYP3A
Graprefuit juice inhibitbs CYP3A
and Rifampin induces CYP3A

20

Your patient loves Grapefruit juice and you perscribe her cyclosporine, what should you consider in terms of dosing?

Maybe a wee bit less because Grapefruit juice is an inhibitor or the enzyme (CYP3A) that clears the cyclosporine from the body?

21

Your patient is taking Rifampin for a fungal infection... You also want to perscribe Cyclosporine for an immunosuppressant drug... what should you consider?

Rifampin is an inducer of CYP3A - the eznyme that clears cyclosporine - thus you might want to consider a little bit more cyclosporine in this patient

22

What specific substrates of CYP2D6 should we be aware of?

Tricyclic antidepressants
Codeine

23

What makes CYP2D6 unique?

It is an activator - unlike most of the enzymes that we are looking at - CYP2D6 is not so much required to clear drugs as it is to activate them?

24

Let's say you had a patient that was on a tricyclic antidepressant and you wanted to perscribe them quinidine (antiarrhythmic) what should you take under consideration?

quinidine is an inhibitor of CYP2D6

CYP2D6 is an metabolizer of tricyclic antidepressants

May need to perscribe lower dose Tricyclic antidepressant to account for quinidine inhibition of CYP2D6 clearance

25

Let's say you had a patient who was taking fluoxtine (for depression/ocd) and you needed to perscribe them codeine, what should you consider?

Well, Codeine is activated by CYP2D6

CYP2D6 is inhibited by Fluoixitine

Thus, activation of codeine by CYP2D6 may be diminished due to CYP2D6 inhibition, so perscribe a little more codeine?

26

What are the substrates of CYP2D6 that we should know? (2)

Tricyclic antidepressant - metabolism

Codeine - acitvation

27

What are the inhibitors of CYP2D6 that we should know? (3)

Quinidine
Fluoxetine
Paroxetine (depression/ocd)

28

CYP2C9 - which drug is associated with this gene?

Warfarin

29

Warfarin is a substrate of an enzyme encoded by which gene?

CYP2C9 and VKORC1

30

Mutations in CYP2C9 may effect the metabolism of which drug?

Warfarin