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 =

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

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
blocks urate reabsorption in kidneys blocks MRP2 (drugs not going into biliary space)
PROBENECID
26
used to treat irinotecan induced diarrhea
PROBENECID
27
transporter on apical side of hepatocyte that is found on many cells and cancer cells
MDR1
28
MRP2 mutation
Dubin-Johnson syndrome
29
transporter on apical side for Cu1+ (copper)
ATP7B
30
conjugated bilirubin exported through basolateral side through back through blood by _____
MRP3
31
____mutation leads to IRINOTECAN toxicity
UGT1A1
32
patient with Gilbert syndrome should not take _____ due to toxicity
IRINOTECAN
33
GEMFIBROZIL + SIMVASTATIN =
myoglobinuria
34
glucuronidation of bilirubin
double
35
UGT1A1 mutation (absence) infants and children kernicterus seen
type I Crigler-Najjar
36
UGT1A1 mutation (1-10% UGT1A1 activity) infants and children
type II Crigler-Najjar
37
10-30% UGT1A1 activity teens-30s
Gilbert syndrome
38
zone 3 necrosis seen with this drug induced toxicity
Acetaminophen
39
Rx acetaminophen toxicity
NAC
40
autoantibody causing fulminant hepatic necrosis w/ what drug induced toxicity
Halothane
41
mitochondrial injury from what drug induced toxicity
Valproic acid
42
drug induced toxicity leading to hepatic venous thrombosis
oral contraceptives
43
liver and brain injury due to previous virus and aspirin use
Reye syndrome
44
triad of fatty liver degeneration, elevated ALT/AST, and encephalopathy
Reye syndrome
45
hepatocyte mitochondrial dysfunction elevated NH3 encephalopathy
Reye syndrome