Al-Mehdi: Drug Metabolism

Question 1

goal of phase 1 of liver detoxification

Answer 1

water solubility
drug activation

Question 2

goal of phase 2 of liver detoxification

Answer 2

water solubility
drug inactivation

Question 3

goal of phase 3 of liver detoxification

Answer 3

excretion into bile

Question 4

therapeutic window of a drug is between what two thresholds

Answer 4

minimal effective concentration (MEC)
minimal toxic concentration (MTC)

Question 5

grapefruit juice + simvastatin =

Answer 5

myopathy (toxicity)

Question 6

St. John’s Wort + simvastatin =

Answer 6

drug ineffective (never reaches MEC)

Question 7

CYP450s located where

Answer 7

smooth ER

Question 8

what induces enzyme production

Answer 8

phenobarbitol

Question 9

receptor for Rifampin that dimerizes and goes into nucleus and leads to CYP3A4 being produced and rifampin’s degradation

Answer 9

PXR

Question 10

____ activated by CYP2C19

Answer 10

Clopidogrel

Question 11

inhibits CYP2C19

Answer 11

Omeprazole

Question 12

omeprazole + clopidogrel=

Answer 12

platelet aggregation

Question 13

cimetidine + omeprazole =

Answer 13

bleeding

Question 14

_____inactivates CYP2C9

Answer 14

Cimetidine

Question 15

warfarin + cimetidine =

Answer 15

bleeding

Question 16

____ inhibits CYP3A4

Answer 16

Erythromycin (macrolide)

Question 17

Erythromycin + Warfarin =

Answer 17

bleeding

Question 18

Erythromycin + Ketoconazole

Answer 18

long QT + long QT = Torsades de Pointes

Question 19

Rifampin + oral contraceptives =

Answer 19

baby

Question 20

main reaction used in phase 2 of liver detoxification

Answer 20

Glucuronidation (UDP, UGT1A1) for drug inactivation (and drug conjugation)

Question 21

what happens when glucuronidation happens w/ phenytoin +/or bilirubin

Answer 21

conjugation (water solubility)

Question 22

active form of IRINOTECAN

Answer 22

SN-38

Question 23

inactive form of IRINOTECAN

Answer 23

SN-38 + glucuronic acid (inactivated by UGT1A1)

Question 24

mutation in OATP1B1/P1B3

Answer 24

Rotor syndrome
no reuptake of conjugated bilirubin

Question 25

blocks urate reabsorption in kidneys blocks MRP2 (drugs not going into biliary space)

Answer 25

PROBENECID

Question 26

used to treat irinotecan induced diarrhea

Answer 26

PROBENECID

Question 27

transporter on apical side of hepatocyte that is found on many cells and cancer cells

Answer 27

MDR1

Question 28

MRP2 mutation

Answer 28

Dubin-Johnson syndrome

Question 29

transporter on apical side for Cu1+ (copper)

Answer 29

ATP7B

Question 30

conjugated bilirubin exported through basolateral side through back through blood by _____

Answer 30

MRP3

Question 31

____mutation leads to IRINOTECAN toxicity

Answer 31

UGT1A1

Question 32

patient with Gilbert syndrome should not take _____ due to toxicity

Answer 32

IRINOTECAN

Question 33

GEMFIBROZIL + SIMVASTATIN =

Answer 33

myoglobinuria

Question 34

glucuronidation of bilirubin

Answer 34

double

Question 35

UGT1A1 mutation (absence) infants and children kernicterus seen

Answer 35

type I Crigler-Najjar

Question 36

UGT1A1 mutation (1-10% UGT1A1 activity) infants and children

Answer 36

type II Crigler-Najjar

Question 37

10-30% UGT1A1 activity teens-30s

Answer 37

Gilbert syndrome

Question 38

zone 3 necrosis seen with this drug induced toxicity

Answer 38

Acetaminophen

Question 39

Rx acetaminophen toxicity

Answer 39

NAC

Question 40

autoantibody causing fulminant hepatic necrosis w/ what drug induced toxicity

Answer 40

Halothane

Question 41

mitochondrial injury from what drug induced toxicity

Answer 41

Valproic acid

Question 42

drug induced toxicity leading to hepatic venous thrombosis

Answer 42

oral contraceptives

Question 43

liver and brain injury due to previous virus and aspirin use

Answer 43

Reye syndrome

Question 44

triad of fatty liver degeneration, elevated ALT/AST, and encephalopathy

Answer 44

Reye syndrome

Question 45

hepatocyte mitochondrial dysfunction elevated NH3 encephalopathy

Answer 45

Reye syndrome