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DIG Biweekly 2 > Al-Mehdi: Drug Metabolism > Flashcards

Al-Mehdi: Drug Metabolism Flashcards

1
Q

goal of phase 1 of liver detoxification

A

water solubility
drug activation

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2
Q

goal of phase 2 of liver detoxification

A

water solubility
drug inactivation

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3
Q

goal of phase 3 of liver detoxification

A

excretion into bile

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4
Q

therapeutic window of a drug is between what two thresholds

A

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

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5
Q

grapefruit juice + simvastatin =

A

myopathy (toxicity)

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6
Q

St. John’s Wort + simvastatin =

A

drug ineffective (never reaches MEC)

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7
Q

CYP450s located where

A

smooth ER

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8
Q

what induces enzyme production

A

phenobarbitol

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9
Q

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

A

PXR

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10
Q

____ activated by CYP2C19

A

Clopidogrel

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11
Q

inhibits CYP2C19

A

Omeprazole

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12
Q

omeprazole + clopidogrel=

A

platelet aggregation

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13
Q

cimetidine + omeprazole =

A

bleeding

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14
Q

_____inactivates CYP2C9

A

Cimetidine

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15
Q

warfarin + cimetidine =

A

bleeding

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16
Q

____ inhibits CYP3A4

A

Erythromycin (macrolide)

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17
Q

Erythromycin + Warfarin =

A

bleeding

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18
Q

Erythromycin + Ketoconazole

A

long QT + long QT = Torsades de Pointes

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19
Q

Rifampin + oral contraceptives =

A

baby

20
Q

main reaction used in phase 2 of liver detoxification

A

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

21
Q

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

A

conjugation (water solubility)

22
Q

active form of IRINOTECAN

A

SN-38

23
Q

inactive form of IRINOTECAN

A

SN-38 + glucuronic acid (inactivated by UGT1A1)

24
Q

mutation in OATP1B1/P1B3

A

Rotor syndrome
no reuptake of conjugated bilirubin

25
Q

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

A

PROBENECID

26
Q

used to treat irinotecan induced diarrhea

A

PROBENECID

27
Q

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

A

MDR1

28
Q

MRP2 mutation

A

Dubin-Johnson syndrome

29
Q

transporter on apical side for Cu1+ (copper)

A

ATP7B

30
Q

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

A

MRP3

31
Q

____mutation leads to IRINOTECAN toxicity

A

UGT1A1

32
Q

patient with Gilbert syndrome should not take _____ due to toxicity

A

IRINOTECAN

33
Q

GEMFIBROZIL + SIMVASTATIN =

A

myoglobinuria

34
Q

glucuronidation of bilirubin

A

double

35
Q

UGT1A1 mutation (absence)
infants and children
kernicterus seen

A

type I Crigler-Najjar

36
Q

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

A

type II Crigler-Najjar

37
Q

10-30% UGT1A1 activity
teens-30s

A

Gilbert syndrome

38
Q

zone 3 necrosis seen with this drug induced toxicity

A

Acetaminophen

39
Q

Rx acetaminophen toxicity

A

NAC

40
Q

autoantibody causing fulminant hepatic necrosis w/ what drug induced toxicity

A

Halothane

41
Q

mitochondrial injury from what drug induced toxicity

A

Valproic acid

42
Q

drug induced toxicity leading to hepatic venous thrombosis

A

oral contraceptives

43
Q

liver and brain injury due to previous virus and aspirin use

A

Reye syndrome

44
Q

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

A

Reye syndrome

45
Q

hepatocyte mitochondrial dysfunction
elevated NH3
encephalopathy

A

Reye syndrome

DIG Biweekly 2 (11 decks)

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