Exam 3: Lecture 13, Drug-Induced Liver Injury Flashcards

1
Q

DILI accounts for nearly….

A

50% of cases of acute liver failure in USA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Most common drug associated with hepatotoxicity in USA?

A

Acetaminophen

Amox Clav = world wide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How many drugs have some degree of DILI risk?

A

750 per FDA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

DILI categorized as…

A

Acute or Chronic

Hepatitis, Cholestatic, or mixed pattern injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Hepatitis

A

Hepatocyte necrosis and associated with poor prognosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Is DILI major cause of drug attrition?

A

Yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Cholestatic Drug-induced injury

A

has to do with issues in bile secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

2 mechanisms for chronic cholestasis

A

Obliteration of bile ducts

Extrahepatic biliary obstruction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Drugs causing Cholestatic hepatitis

A

amoxicillin clav, sulfonylureas, vitamin A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Drugs causing Hepatocellular necrosis

A

Acetaminophen, isoniazid, niacin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Drugs causing Microvesicular Steatosis/lactic acidosis

A

Antiretrovirals, Aspirin, valproic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Drugs causing Fatty liver

A

Amiodarone, corticosteroids, ethanol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Factors of DILI

A

PK of the drug
patient age/sex/comorbidities

Hard to predict

positive correlation between age/risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Men or women more prone to developing hepatitis and progress to acute liver failure?

A

women

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which oral meds have higher chance to result in DILI?

A

drugs with significant hepatic metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Mechanisms of DILI

A

direct toxicity from admin of drug and their metabolites

result from immune-mediated mechanisms

can be distinct or interconnected

17
Q

One of earliest events of DILI is…

A

inhibition of mitochondrial respiratory chain

increased ROS
depletion of ATP

18
Q

Immune-mediated injury

A

characterized by prolonged interval between admin of drug and recognized liver toxicity

19
Q

6 Mechanisms for DILI

A
Mitochondrial impairment
Inhibition of Biliary efflux
Lysosomal impairment
Reactive metabolites
ER stress
Immune system
20
Q

Symptoms of DILI

A
fever
jaundace
tired
itching
unusual weight gain
swelling of feet/legs
nausea/vomiting/pain in abdomen
21
Q

How to diagnose DILI?

A

Blood test

Biochemical test for liver enzymes AST/ALT elevation

22
Q

Management of DILI

A

based on proper diagnosis and recognition of what caused it/withdrawal

23
Q

When should drug admin be stopped DILI?

A

ALT> 8 x upper limit of normal
ALT > 5 x ULN for 3 weeks
ALT > 3 x ULN + Bilirubin > 2 X ULN
Prothrombin time/international normalized ratio > 1.5 ULN
Presence of symptoms suggesting liver injury

24
Q

antidote for DILI?

A

Nothing

reception is N-acetylcysteine for acetaminophen

25
How to consider patients for liver transplant?
Kings College has some chart
26
Acetaminophen DILI
fraction of drug metabolized by CYP to toxic intermediate metabolite that can interact with intracellular proteins and induce hepatocyte death
27
toxic intermediate metabolite from Acetaminophen?
NAPQI
28
Hepatotoxicity occurs when GST is...
depleted or NAPQI generation exceeds GST binding capacity *both Get depletion/increased NAPQI seen in alcoholics, can develop severe liver injury with low doses of acetaminophen*
29
How to prevent acetaminophen toxic metabolite toxicity?
GSH binds and prevents it from occurring otherwise intermediate goes and binds protein
30
By what mechanism does INH cause DILI?
direct hepatotoxic effects of INH metabolites accumulation of acetylhydrazine/hydrazine accumulation dependent on acetylator phenotype of patient