Gurley Feb 5 pt. 2 (CYP1A2 & CYP2D6) Flashcards Preview

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Flashcards in Gurley Feb 5 pt. 2 (CYP1A2 & CYP2D6) Deck (30)
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1
Q

where is CYP1A2 expressed

A

primarily in the liver

2
Q

what gender tends to express more CYP1A2

A

males more than females

3
Q

CYP1A2 is very sensitive to what?

A

inhibition and induction

4
Q

what is the classic CYP1A2 substrate

A

caffeine

5
Q

list some inducers of CYP1A2

A
cigarette smoke
charbroiled meat
cruciferous vegetables
Primidone
Rifampin
Omeprazole
Phenobarbital
6
Q

list the CYP1A2 substrates (major pathway)

A
Caffeine
Clozapine
R-Warfarin
Riluzole
Ropivicane
Tacrine 
Theophylline
Phenacetin
Olanzipine
7
Q

what is the most potent inhibitor of CYP1A2

A

fluvoxamine

8
Q

what SSRI has the least amount of drug-drug interactions

A

citalopram

9
Q

Fluvoxamine/Theophylline combinations result in how much of an increase in theophylline concentrations

A

3 fold increase

10
Q

Fluvoxamine/Clozapine combinations can lead to how much of an increase in clozapine

A

5 fold increase

11
Q

what class of drugs is known to inhibit theophylline increase via CYP1A2

A

fluoroquinolones

12
Q

arrange these in most inhibitory to least inhibitory of theophylline clearance via CYP1A2 inhibition:
ofloxacin, enoxacin, ciprofloxacin, norfloxacin, perfloxacin

A

Enoxacin>ciprofloxqacin>perfloxacin>norfloxacin= ofloxacin

just remember enoxacin is most then huge drop

13
Q

what nuclear receptor causes induction of CYP1A2?

A

AhR (arylhydrocarbon nuclear receptor)

14
Q

list the important types of drugs substrates of CYP2D6

A
Antiarrhythmics
Beta blockers
Antipsychotics
Opioid analgesics
Tricyclic antidepressants
SSRIs
(note that not all of these types are substrates just some of them)
15
Q

what are the inducers of 2D6

definite test Q

A

no inducers (don’t have to worry about drug drug interactions for 2d6 induction; can be inhibited)

16
Q

what are the important inhibitors of CYP2D6

A

Fluoxetine
Paroxitine
Quinidine

17
Q

what is interesting about quinidines CYP interactions

A

It most potent inhibitor of 2D6, but not a substrate (so not metabolized by it); primarily a 3A4 substrate

18
Q

list the SSRIs that are the most problematic 2D6 inhibitors

list the SSRI’s that have little effect on 2D6

A

problematic = fluoxetine and paroxetine

little effect = citalopram and fluvoxamine

19
Q

what is 2D6’s effect on codeine

A

metabolizes it to morphine (otherwise it doesn’t work)

20
Q

extensive metabolizers of 2D6 have what genotype

A

heterozygous

or homozygous dominant

21
Q

poor metabolizers via 2D6 have what genotype

A

homozygous for mutated alleles

22
Q

what should you immediately think of if you see CYP2D6*2

Test q according to Gurley

A

potential ultra rapid metabolizer

means multiple wildtype copies of the gene

23
Q

what CYP2D6 polymorphism designations indicate normal

A

CYP2D61
CYP2D6
2 (with exception of multiple wildtype copies)
CYP2D6*35

24
Q

of P450’s what enzyme do polymorphisms effect the most

A

2D6

25
Q

what is the “bottom line” of what the AmpliChip CYP450 is?

A

A microarray chip that with a blood sample parts become fluorescent showing which alleles someone has

26
Q

what CYPs are “AmpliChip CYP450” used for

A

CYP2D6 and CYP2C19

27
Q

what is the halflife of dsipramine in extensive metabolizers of 2D6?
poor metabolizers?

A

extensive = 17 hours

poor - 100 hours

28
Q

what can occur with propefenone being taken by poor metabolizers?

A

can become arrhythmogenic

29
Q

what occurs with poor metabolizers of CYP2D6 taking codeine; more analgesia or less analgesia

A

less analgesia (prodrug that must be metabolized to active form)

30
Q

what is the max number of 2D6 gene copies can an individual have

A

up to 13 copies