EXAM #3: DRUG-INDUCED LIVER INJURY Flashcards
What is the value of a RUQ US in the setting of suspected drug induced liver disease?
Rule out organic process
On liver biopsy, what are the characteristics of drug-induced liver injury (DILI)?
1) Portal inflammation including
- Eosinophils
- Cholestasis
2) Mild steatohepatitis
What is the number one antibiotic to cause DILI?
Augmentin i.e. Amoxacillin + Clavulanic acid
What type of drug cause the most cases of DILI?
Antibiotics
When does the onset of DILI start after Augmentin?
2-6 weeks post therapy
What is DILI?
Hepatotoxicity resulting from ANY drug (legal, illegal, herbal, OTC…etc)
What labs assist in the diagnosis of DILI?
Bilirubin
ALP
Transaminases (AST/ALT)
GGT*
What most oftenly causes an increase in GGT?
Alcohol and drugs
What is intrinsic DILI? Give an example.
Predictable DILI that occurs in a short time frame
E.g. Acetominophen
What is an idiosyncratic DILI?
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
What it Hy’s Law?
Rule that outlines the circumstances that lead to a 10% mortality rate from DILI
What are the three major criteria for Hy’s Law?
1) Serum ALT or AST 3x normal
2) Serum Bilirubin 2x normal
3) No other reason explains the elevation of liver enzymes
What three major drug categories commonly cause DILI?
1) Antibiotics*
2) NSAIDs
3) Anti-convulsants
In western countries, what is the most common cause of acute liver failure and transplantation?
DILI
What are the risk factors of DILI?
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
What is the leading cause of acute liver failure in the US?
Acetaminophen
How has the FDA limited Acetaminophen exposure?
Reducing the dose allowed in opioids
500mg–>325mg
What is the max dose of Acetaminophen in a 24 hour period safely?
4g
What are the three major metabolites of Acetaminophen?
1) Glucuronide
2) Sulfate
3) N-ACETYL-P BENZOQUINONE IMINE I.E. NAPQI *
This is the toxic metabolite
What happens to NAPQI in Acetaminophen metabolism?
Most is convertied into Mercapturic acid (non-toxic)
How does NAPQI induce liver damage?
Covalently binding to the liver
What is the antidote for Acetaminophen overdose?
NAC, N-Acetylcysteine
In an admitted hospital patient with a fever, what are the concerning historical factors DILI?
1) Active alcoholism
2) Malnutrition
3) Starvation
These factors would lead you to giving Motrin
What is the definition of acute DILI?
Manifestation lasts less than 3 months
What is acute drug induced cholestatic injury?
Drug induced liver injury mimicing extrahepatic obstructive jaundice
What is the mixed pattern of acute liver injury?
Combination of acute hepatocellular and cholestatic injury
What is chronic DILI?
Manifestations that last for longer than 3 months
How can you differentiate between mononucleosis and pseudomononucelosis?
Monospot test
Will be negative in a patient with DILI
What are the extrahepatic manifestations of DILI?
- Fever
- Rash
- Eosinophilia
Note that this is most commonly seen with a hypersensitivity pattern of injury
How does Ketoralac compare the the risk of DILI with Diclofenac?
Diclofenac is 100x more likely to cause DILI
What do you do if you give a patient a drug and their liver enzymes are 5x normal?
Stop the drug
What do you do if a patient has signs/sx of poor liver function but not enzyme elevation after starting a new drug?
Stop the drug
What do you do if you give a drug and a patient has liver enzymes 3x normal?
Continue drug and repeat in 3 months
What do you do if you give a drug and a patient’s enzymes increase 3-5 times normal?
Continue drug and repeat in 1 months
Is re-challenge encouraged?
NO
