Gurley Feb 5 pt.1 (CYP3A4)

Question 1

what is the most abundant Cytochrome in humans?

Answer 1

CYP3A4

Question 2

where is CYP3A4 in highest concentrations?

what is the efflux pump co-expressed with it in these locations?

Answer 2

liver and small intestines

P-glycoprotein (a.k.a. ABCB1)

Question 3

about what percent of prescription drugs are metabolized by CYP3A4

Answer 3

50%

Question 4

what are two features noted with genetic polymorphisms in CYP3A4

Answer 4

1. large intersubject variability

2. don’t have a major effect on its metabolism

Question 5

what has the least allelic varience 3A4 or 3A5

Answer 5

3A4 (least amount of allelic varience out of all CYPs)

Question 6

what type of drugs are effected the most by changes in CYP3A4?

Answer 6

drugs with a narrow therapeutic window

Question 7

true/ false:

A drug can be both a substrate and an inhibitor?

Answer 7

true

Question 8

what two benzodiazipines are not 3A4 substrates

TEST Q according to gurley

Answer 8

oxazepam and lorazepam

Question 9

what are the general drug ‘categories’ of CYP3A4 substrates (6 total; exceptions not included)?

Answer 9

1. azole antifungals
2. benzodiazepines
3. Ca channel blockers
4. HMG-co reductase inhibitors
5. macrolide antibiotics
6. steroids

Question 10

what HMG-co reductase inhibitor is not a CYP3A4 substrate?

Answer 10

pravastatin

Question 11

what macrolide antibiotic is not a CYP3A4 substrate

Answer 11

azithromycin

Question 12

list the CYP3A4 inhibitors noted in class

Answer 12

1. troleandomycin
2. ritonavir
3. itraconazole
4. clarithromycin
5. ketoconazole
6. erythromycin

Question 13

what is probably the most potent CYP3A4 inducer

Answer 13

St. John’s wart

Question 14

what are the CYP3A4 inducers (10 total)

Answer 14

1. carbamazepine
2. dexamethasone
3. efavirenz
4. nevirapine
5. phenobarbital
6. phenytoin
7. primidone
8. rifampin
9. rifabutin
   10 st. johns wort

Question 15

what is probably the most potent CYP3A4 inhibitor

Answer 15

ritonavir

Question 16

1. what immunosuppressant given for transplants taken in conjunction with Azole antifungals inhibits CYP3A4?
2. what does this often lead to?
3. why do some doctors do this intentionally?

Answer 16

1. cyclosporine
2. nephrotoxicity (from cyclosporine toxicity)
3. reduce cyclosporine dose needed (very expensive drug)

Question 17

Erythromycin, a potent CYP3A4 inhibitor taken in conjunction with what antihistamine can lead to Torsades?

Answer 17

terfenadine

Question 18

what orphan nuclear receptor is most commonly activated by induction of CYP3A4?

Answer 18

SXR (steroid-xenobiotic receptor)

Question 19

activation of SXR does what

Answer 19

induces overexpression of CYP3A4

Question 20

the activation of transcription factors such as CAR, SXR and PXR requires what 3 things

Answer 20

1. binding of ligands
2. formation of heterodimers
3. heterodimer binding to XRE (xenobiotic response elements)

Question 21

what is considered ‘the quintessential substrate’ for 3A4?

Answer 21

midazolam

Question 22

what is the overall average increase in CYP3A4 if a patient is given St. Johns Wort? (seen in studies with midazolam plasma ratios )

Answer 22

98%

Question 23

what is shown to be the most potent ligand for PXR?

Answer 23

hyperphin (sp?)

Question 24

St. John’s wort and rifampin induce CYP3A4 and what else?

where

Answer 24

p-glycoprotein (P-gp)

in the small intestine