What is the most common reason for drug recall?
Drug-induced hepatotoxicity
T or F: drug induced hepatotoxicity can be acute or chronic
True
Examples of hepatotoxins
Arsenic
Carbon tetrachloride
Copper
Dimethylformamide
Fluorine
Toluene
Vinyl chloride
How is DILI classified?
Can be difficult because:
- drugs may cause >1 pattern of damage
- cause not always possible to determine
- in some cases, different types may occur at once
- mechanisms are not fully understood
How is DILI diagnosed?
Temporal relationship to drug use
Exclusion of other causes of liver damage
What drug can cause hepatocellular injury?
Allopurinol
What drugs can cause steatonecrosis?
Tetracycline
Valporic acid
Alcohol
What drug can cause fibrosis?
Methotrexate
What drugs can cause cholestatic injury?
Carbemazapine
Arithromycin
What is the definition of hepatotoxicity?
ALT>3x the upper limit of normal AND
Total bilirubin >2x the upper limit of normal
*indicators of injury and functional changes
What is the R value and what is it used for?
(Measured ALT/upper normal limit of ALT) / (measured ALP/upper normal limit of ALP)
- used to determine cause of liver injury
What does an R value >/= 5 determine?
Hepatocellular injury
What does an R value between 2-5 determine?
Mixed injury
What does an R value </= 2 determine?
Cholestatic injury
What are the general mechanisms of DILI?
Intrinsic: predictable
Idiosyncratic: unpredictable
What is the most common cause of acute liver failure?
Acetaminophen - intrinsic DILI
Extremely high AST/ALT levels (>3500)
What causes acetaminophen toxicity?
CYP becomes primary pathway which produces NAPQI (toxic), this covalently binds to and modifies critical hepatic cell proteins?
T or F: acetaminophen toxicity leads to survivors having chronic hepatic dysfunction.
False. It is an acute event
What are the toxic doses of acet?
Adults: >7.5g
Kids: >150mg/kg
When can we use the Rumack-Matthew nomogram?
When <24hours
Not reliable for extended release products
- predicts only the likelihood of AST/ALT >1000
- does not predict survival or death
What is the antidote of choice for acet toxicity?
Acetylcysteine (Mucomyst)
What Child Pugh?
Scoring system to evaluate survival rate
Higher score = worse survival rate
A = 5-6 points
B = 7-9 points
C = 10-15 points
