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Gastrointestinal System > EXAM #3: DRUG-INDUCED LIVER INJURY > Flashcards

EXAM #3: DRUG-INDUCED LIVER INJURY Flashcards

1
Q

What is the value of a RUQ US in the setting of suspected drug induced liver disease?

A

Rule out organic process

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2
Q

On liver biopsy, what are the characteristics of drug-induced liver injury (DILI)?

A

1) Portal inflammation including
- Eosinophils
- Cholestasis
2) Mild steatohepatitis

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3
Q

What is the number one antibiotic to cause DILI?

A

Augmentin i.e. Amoxacillin + Clavulanic acid

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4
Q

What type of drug cause the most cases of DILI?

A

Antibiotics

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5
Q

When does the onset of DILI start after Augmentin?

A

2-6 weeks post therapy

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6
Q

What is DILI?

A

Hepatotoxicity resulting from ANY drug (legal, illegal, herbal, OTC…etc)

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7
Q

What labs assist in the diagnosis of DILI?

A

Bilirubin
ALP
Transaminases (AST/ALT)
GGT*

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8
Q

What most oftenly causes an increase in GGT?

A

Alcohol and drugs

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9
Q

What is intrinsic DILI? Give an example.

A

Predictable DILI that occurs in a short time frame

E.g. Acetominophen

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10
Q

What is an idiosyncratic DILI?

A

Unpredictable and variable DILI

*Note that the majority of DILI are idiosyncratic. Also, do NOT rechallenge when a patient has had this kind of reaction

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11
Q

What it Hy’s Law?

A

Rule that outlines the circumstances that lead to a 10% mortality rate from DILI

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12
Q

What are the three major criteria for Hy’s Law?

A

1) Serum ALT or AST 3x normal
2) Serum Bilirubin 2x normal
3) No other reason explains the elevation of liver enzymes

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13
Q

What three major drug categories commonly cause DILI?

A

1) Antibiotics*
2) NSAIDs
3) Anti-convulsants

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14
Q

In western countries, what is the most common cause of acute liver failure and transplantation?

A

DILI

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15
Q

What are the risk factors of DILI?

A

1) Extremes of age
- Reye
- Polypharmacy
2) Gender
3) Obesity
4) Drug abuse/ alcoholism
5) Hx of previous other drug reactions

Note that for men and women, there is different susceptibility for different drugs/ drug classes

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16
Q

What is the leading cause of acute liver failure in the US?

A

Acetaminophen

17
Q

How has the FDA limited Acetaminophen exposure?

A

Reducing the dose allowed in opioids

500mg–>325mg

18
Q

What is the max dose of Acetaminophen in a 24 hour period safely?

A

4g

19
Q

What are the three major metabolites of Acetaminophen?

A

1) Glucuronide
2) Sulfate
3) N-ACETYL-P BENZOQUINONE IMINE I.E. NAPQI *

This is the toxic metabolite

20
Q

What happens to NAPQI in Acetaminophen metabolism?

A

Most is convertied into Mercapturic acid (non-toxic)

21
Q

How does NAPQI induce liver damage?

A

Covalently binding to the liver

22
Q

What is the antidote for Acetaminophen overdose?

A

NAC, N-Acetylcysteine

23
Q

In an admitted hospital patient with a fever, what are the concerning historical factors DILI?

A

1) Active alcoholism
2) Malnutrition
3) Starvation

These factors would lead you to giving Motrin

24
Q

What is the definition of acute DILI?

A

Manifestation lasts less than 3 months

25
Q

What is acute drug induced cholestatic injury?

A

Drug induced liver injury mimicing extrahepatic obstructive jaundice

26
Q

What is the mixed pattern of acute liver injury?

A

Combination of acute hepatocellular and cholestatic injury

27
Q

What is chronic DILI?

A

Manifestations that last for longer than 3 months

28
Q

How can you differentiate between mononucleosis and pseudomononucelosis?

A

Monospot test

Will be negative in a patient with DILI

29
Q

What are the extrahepatic manifestations of DILI?

A
  • Fever
  • Rash
  • Eosinophilia

Note that this is most commonly seen with a hypersensitivity pattern of injury

30
Q

How does Ketoralac compare the the risk of DILI with Diclofenac?

A

Diclofenac is 100x more likely to cause DILI

31
Q

What do you do if you give a patient a drug and their liver enzymes are 5x normal?

A

Stop the drug

32
Q

What do you do if a patient has signs/sx of poor liver function but not enzyme elevation after starting a new drug?

A

Stop the drug

33
Q

What do you do if you give a drug and a patient has liver enzymes 3x normal?

A

Continue drug and repeat in 3 months

34
Q

What do you do if you give a drug and a patient’s enzymes increase 3-5 times normal?

A

Continue drug and repeat in 1 months

35
Q

Is re-challenge encouraged?

A

NO

Gastrointestinal System (42 decks)

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