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

he said to be sure and understand chart on p. 11 and 22-24

1
Q

where is CYP1A2 expressed

A

primarily in the liver

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2
Q

what gender tends to express more CYP1A2

A

males more than females

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3
Q

CYP1A2 is very sensitive to what?

A

inhibition and induction

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4
Q

what is the classic CYP1A2 substrate

A

caffeine

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5
Q

list some inducers of CYP1A2

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

list the CYP1A2 substrates (major pathway)

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

what is the most potent inhibitor of CYP1A2

A

fluvoxamine

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8
Q

what SSRI has the least amount of drug-drug interactions

A

citalopram

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9
Q

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

A

3 fold increase

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10
Q

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

A

5 fold increase

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11
Q

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

A

fluoroquinolones

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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

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13
Q

what nuclear receptor causes induction of CYP1A2?

A

AhR (arylhydrocarbon nuclear receptor)

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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)
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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)

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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

25
what is the "bottom line" of what the AmpliChip CYP450 is?
A microarray chip that with a blood sample parts become fluorescent showing which alleles someone has
26
what CYPs are "AmpliChip CYP450" used for
CYP2D6 and CYP2C19
27
what is the halflife of dsipramine in extensive metabolizers of 2D6? poor metabolizers?
extensive = 17 hours | poor - 100 hours
28
what can occur with propefenone being taken by poor metabolizers?
can become arrhythmogenic
29
what occurs with poor metabolizers of CYP2D6 taking codeine; more analgesia or less analgesia
less analgesia (prodrug that must be metabolized to active form)
30
what is the max number of 2D6 gene copies can an individual have
up to 13 copies