Drugs of drug induced liver injury Flashcards
Acetaminophen: classical presentation for liver toxicity
nausea, vomiting, and malaise in first 24 hrs.
No symptoms next 24-72 hrs
Anorexia, nausea, vomiting, abdominal pain with hepatitis.
often accidental overdose: pts don’t realize that many drugs contain acetaminophen.
How does acetaminophen toxicity work?
acetaminophen is metabolized to NAPQI, wich is toxic. Normally the liver can quickly metabolize NAPQI, but if the concentration of NAPQI gets too high (if you overwhelm the next steps), or if there aren’t enough intrinsic antioxidants around, you can see liver damage. People with a PMH of EtOH abuse are more susceptible.
Agumentin
most common cause of DILI when you’ve ruled out acetaminophen, maybe because of clavulanic acid.
presentation: cholestasis with reversible jaundice. often show show fever, rash, and eosinophilia.
Risk factors for augmentin liver toxicities
male, over 60, prolonged course,
Amiodarone toxicity
usually mixed micro and macro vesicular steatohepatitis
occasionally shows micronodular cirrhosis
can also cause granlomas, phosophlipidosis, cholangitis, acute liver failure.
Amiodarone liver toxicity: timing issues
onset is delayed and insidious
drug half life is long: persists for a long time even after the pt discontinues the medication.
mortality may be high in advanced cases.
Methotrexate
may cause overt fibrosis w/o elevation of liver numbers in a relatively dose-dependent fashion. duration of tx and cumulative dose are the most important factors
Risk factors for methotrexate toxicity
advanced age, dose, EtOH, obestiy, DM, metabolic syndrome, pre-existing liver disease, lack of folate supplementation, systemic disease, impaired renal function.
Valproate
esp. dangerous in kids under 3
microvesicular steatosis in a DOSE-DEPENDENT fashion. can cause massive hepatic necrosis in up to 2/3 of DILI cases
valproate in kids: clinical presentation
non-specific: lethargy, malaise, poor feeding, somnolence, worsening seizures, muscle weakness, facial swelling; then, jaundice, hypoglycemia, ascities, coagulopathy, and encephalopathy (with coma and death).
Management of valproate toxicity and monitoring
treat with L-carnitine
LFT monitering isn’t helpful: high freq of non-specific liver test abnormalities. monitor kids for signs of toxicity
Risk factors for valproate toxicity
family hx of mitochondrial enzyme deficiency, freidrich’s ataxia, Reye’s syndrome, sibling affected by VAP toxicity, multi-drug therapy
HAART: nucleoside/tide reverse transcriptase inhibitors
present with microvesciuclar steatosis, esp in older agends like zidovudine and didanosine
Oral contraceptives
promote enlargement of hemangiomas
incr. risk of hepatic adenomas
increased risk of HCC
bland cholestasis
