Gurley Feb 5 pt. 2 (CYP1A2 & CYP2D6)

Question 1

where is CYP1A2 expressed

Answer 1

primarily in the liver

Question 2

what gender tends to express more CYP1A2

Answer 2

males more than females

Question 3

CYP1A2 is very sensitive to what?

Answer 3

inhibition and induction

Question 4

what is the classic CYP1A2 substrate

Answer 4

caffeine

Question 5

list some inducers of CYP1A2

Answer 5

cigarette smoke
charbroiled meat
cruciferous vegetables
Primidone
Rifampin
Omeprazole
Phenobarbital

Question 6

list the CYP1A2 substrates (major pathway)

Answer 6

Caffeine
Clozapine
R-Warfarin
Riluzole
Ropivicane
Tacrine 
Theophylline
Phenacetin
Olanzipine

Question 7

what is the most potent inhibitor of CYP1A2

Answer 7

fluvoxamine

Question 8

what SSRI has the least amount of drug-drug interactions

Answer 8

citalopram

Question 9

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

Answer 9

3 fold increase

Question 10

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

Answer 10

5 fold increase

Question 11

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

Answer 11

fluoroquinolones

Question 12

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

Answer 12

Enoxacin>ciprofloxqacin>perfloxacin>norfloxacin= ofloxacin

just remember enoxacin is most then huge drop

Question 13

what nuclear receptor causes induction of CYP1A2?

Answer 13

AhR (arylhydrocarbon nuclear receptor)

Question 14

list the important types of drugs substrates of CYP2D6

Answer 14

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

Question 15

what are the inducers of 2D6

definite test Q

Answer 15

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

Question 16

what are the important inhibitors of CYP2D6

Answer 16

Fluoxetine
Paroxitine
Quinidine

Question 17

what is interesting about quinidines CYP interactions

Answer 17

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

Question 18

list the SSRIs that are the most problematic 2D6 inhibitors

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

Answer 18

problematic = fluoxetine and paroxetine

little effect = citalopram and fluvoxamine

Question 19

what is 2D6’s effect on codeine

Answer 19

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

Question 20

extensive metabolizers of 2D6 have what genotype

Answer 20

heterozygous

or homozygous dominant

Question 21

poor metabolizers via 2D6 have what genotype

Answer 21

homozygous for mutated alleles

Question 22

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

Test q according to Gurley

Answer 22

potential ultra rapid metabolizer

means multiple wildtype copies of the gene

Question 23

what CYP2D6 polymorphism designations indicate normal

Answer 23

CYP2D61
CYP2D62 (with exception of multiple wildtype copies)
CYP2D6*35

Question 24

of P450’s what enzyme do polymorphisms effect the most

Answer 24

2D6

Question 25

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

Answer 25

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

Question 26

what CYPs are “AmpliChip CYP450” used for

Answer 26

CYP2D6 and CYP2C19

Question 27

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

Answer 27

extensive = 17 hours

poor - 100 hours

Question 28

what can occur with propefenone being taken by poor metabolizers?

Answer 28

can become arrhythmogenic

Question 29

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

Answer 29

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

Question 30

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

Answer 30

up to 13 copies