hepatotoxicity Flashcards
what are the risk factors for hepatotoxicity
- age (old/young)
- F>M
- alcohol
- pre existing liver disease
- genetics
- co-morbidities
- drug formulations
what are some mechanisms of hepatotoxicity
- hepatocyte destruction
- transport protein disruption
- cytolytic T cell activation
- hepatocyte apoptosis
- mitochondrial disruption
- bile duct injury
what are the two types of adverse drug reactions
A and B
what is an ADR A
- intrinsic or predictable
- reproducible in animals
- injury is dose related
what is an ADR B
- idiosyncratic or unpredictable
- hypersensitivity or immunoallergenic
- metabolite-idiosyncratic - indirect metabolite of offending drug
what are the signs of hepatotoxicity
- LFTs raised 2x upper
- ALT >2x upper
- conj. bilirubin >2x upper
- combined ALP and total bilirubin with one >2x upper PLUS symptoms
how is hepatotoxicity managed
- drug withdrawal
- antidote if appropriate
- corticosteroids - evidence?
- supportive therapy
- yellow card report
how can hepatotoxicity be prevented
LFT monitoring
patient education on symptoms and OTC causes
how does paracetamol cause hepatotoxicity
in overdose - 4 stages
how is paracetamol induced hepatotoxicity diagnosed
serum paracetamol concentration
what are the 4 phases of paracetamol induced hepatotoxicity
- up to 24hrs - asymptomatic
- 18-72 hrs - N&V, RUQ pain, anorexia, oliguria
- hepatic phase 72-96hrs - jaundice, hypoglycaemia, coagulopathy, acute renal failure
- recovery - if complete resolution and survival of phase 3
how is paracetamol metabolised
mostly conjugated with glucuronide and excreted via urine, 5% metabolised to toxic NABQI
why is paracetamol only dangerous at high doses
at therapeutic doses any NABQI can be conjugated with glutathione and excreted in urine
how does NABQI cause hepatic damage
binds directly to hepatocytes and causes cell damage
how is paracetamol induced hepatotoxicity treated
N-acetyl cysteine within first 8 hrs
dosed based on plasma conc
- methionine 2nd line
