ILA: Drug Metabolism CYTP450

Question 1

2 ways a drug can be inactivated

Answer 1

1. metabolism
2. excretion

Question 2

primary site for metabolism of drugs

Answer 2

hepatocyte

Question 3

T or F: Drugs are toxins

Answer 3

True

Question 4

what induces metabolism that handles drug elimination

Answer 4

enzymes

Question 5

Phase 1 of detoxification in hepatocyte

Answer 5

oxidation/reduction, hydrolysis

Question 6

goal of phase I of detoxification:

Answer 6

water solubility!!!! (always) + drug activation (sometimes)

Question 7

Phase 2 of detoxification in hepatocytes

Answer 7

conjugation

Question 8

goal of phase 2 of detoxification:

Answer 8

drug inactivation!!!! + water solubility

Question 9

Phase 3 of detoxification in hepatocytes

Answer 9

excretion (into bile)

Question 10

in phase 1, what does making drugs water soluble mean

Answer 10

drugs will stay longer in the bloodstream; increase effectiveness and minimize SE

Question 11

in phase 1, bile acid oxidation happens by what

Answer 11

CYPs (cytochrome P450) enzymes

Question 12

one CYP often can metabolize______ drugs

Answer 12

many

Question 13

one drug can be metabolized by _______ CYPs

Answer 13

several

Question 14

CYP2C9
CYP2C19
CYP2D6
CYP34A

Answer 14

CYPs in Phase 1

Question 15

substrate for CYP2C9 enzyme

Answer 15

warfarin (anti-coagulant)

Question 16

substrate for CYP2C19

Answer 16

omeprazole (PPI)

Question 17

substrate for CYP2D6

Answer 17

codeine

Question 18

substrate for CYP34A

Answer 18

amiodarone (slows HR)

Question 19

location of CYP450s in phase 1

Answer 19

smooth ER

Question 20

in phase 1, activation of codeine to morphine is done by what enzyme

Answer 20

CYP2D6

Question 21

in phase 1, activation of clopidogrel is done by what enzyme

Answer 21

CYP2C19

Question 22

simvastatin is a substrate of what CYP enzyme

Answer 22

CYP3A4

Question 23

this enzyme is responsible for simvastatin’s elimination

Answer 23

CYP3A4

Question 24

what juice inhibits CYP3A4

Answer 24

grapefruit juice

Question 25

if someone drinks grapefruit juice while taking a simvastatin, what happens

Answer 25

simvastatin elimination will be lower, and its plasma concentration will exceed MTC-----causing toxicity

Question 26

inducer of CYP3A4

Answer 26

St. John's Wort

Question 27

what happens when someone take St. John's Wort (antidepressant) while on simvastatin

Answer 27

simvastatin elimination will be higher, and its plasma concentration will not even reach MEC, meaning the drug will not work

Question 28

St. John's Wort Rifampin Griseofulvin Phenobarbital Phenytoin Carbamazepine

Answer 28

CYP3A4 inducers (decrease effectiveness of drug)

Question 29

grapefruit juice cimetidine ciprofloxacin erythromycin ketoconazole

Answer 29

CYP3A4 inhibitors (increase toxicity)

Question 30

Warfarin metabolized by

Answer 30

CYP2C9

Question 31

what inactivates CYP2C9

Answer 31

Cimetidine

Question 32

Warfarin + Cimeditine=

Answer 32

bleeding

Question 33

erythromycin inhibits what

Answer 33

CYP3A4

Question 34

erythromycin + warfarin=

Answer 34

bleeding

Question 35

basically, if warfarin (anticoagulant) is unable to be eliminated, it reaches MTC and has what toxic effect

Answer 35

bleeding

Question 36

what two drugs raise each other's levels (they do the same thing)

Answer 36

erythromycin and ketoconazole

Question 37

erythromycin and ketoconazole together increase the risk of long what

Answer 37

long QT (ventricular depolarization)

Question 38

long QT + long QT=

Answer 38

Torsades de Pointes (ventricular tachycardia)

Question 39

what happens before heart goes into V-fib

Answer 39

Torsades de Pointes (ventricular tachycardia)

Question 40

clopidogrel is bioactivated by what

Answer 40

CYP2C19

Question 41

CYP2C19 is inactivated by its substrate

Answer 41

omeprazole

Question 42

omeprazole + clopidogrel=

Answer 42

platelet aggregation (no active form of clopidogrel---blood thinner)

Question 43

grapefruit juice + statins=

Answer 43

myopathy, including rhabdomyolysis (muscle breakdown)

Question 44

rifampin induces what

Answer 44

CYP3A4

Question 45

hormones in birth control pills are degraded by what

Answer 45

CYP3A4

Question 46

rifampin + oral contraceptive=

Answer 46

baby

Question 47

phase 2 deals with conjugation by what enzyme

Answer 47

transferases

Question 48

major transferase in phase 2 that is located in ER

Answer 48

glucuronidation

Question 49

what is (UDP-glucuronosyltransferases, UGTs)

Answer 49

another name for glucuronidation that is used to inactivate drugs in phase 2

Question 50

how does glucuronidation make drug inactivated

Answer 50

basically makes the drug extremely water soluble, so it can be excreted

Question 51

Gemfibrozil inhibits uptake of ______ into hepatocytes in phase 2

Answer 51

statins

Question 52

when statin levels rise in plasma, it leads to ______

Answer 52

rhabdomyolysis

Question 53

gemfribrozil + simvastatin=

Answer 53

myoglobinuria