Paracetamol and liver toxicity Flashcards
At what dose could paracetamol cause hepatotoxity?
10g
How many paracetamol can be bought GSL compared to P
16 and 32
How much paracetamol suspension can be bought GSL and P
100ml (GSL) and 200ml (P)
how many paracetamol can pharmacists sell?
up to 100 in justifiable circumstances
what is the legal limit of “effervescent” tablets, powders or liquid paracetamol
no limit (not all soluble/dispersible formulations comply with medicines legislation)
what is the licence for IV paracetamol?
- short term treatment of moderate pain or fever
- IV clinically justified, other routes not possible
what are advantages of IV paracetamol
- rapidly achieves therapeutic concentrations and pain relief
- removes variability in absorption after surgery
- reduces morphine/opioid dose requirements and side effects
what are disadvantages of IV paracetamol
- dose based on body weight
- dose reduced: hepatocellular insufficiency, chronic alcoholism, malnutrition, dehydration
what is the dose of paracetamol for people under 50kg
3g
what is the IV dosage of paracetamol for adults and children >50kg
0.5g to 1g every 4-6 hours maximum of 4g daily
what is the dosage for IV paracetamol for adults and children under 50kg
15mg/kg every 4-6hrs to a max of 60mg/kg daily
what is the different metabolic pathways of paracetamol
60% glucuronide conjugation
35% sulphate conjugation
5% oxidised to NAPQI (toxic metabolite)
what happens to the metabolic pathway if you take paracetamol and already have liver problems/malnourised?
increased this toxic pathway by inducing liver enzymes
what does NAPQI do to liver cells?
binds to hepatocytes and damages them
what causes an increased rate of NAPQI formation?
- induction of CYP2E1 and CYP3A4 isoenzymes
- chronic high ethanol intake
- enzyme inducers: carbamazepine, phenobarbital, phenytoin, st john’s wart
•identified by abnormal liver function tests: INR increased and G-GT
what is the toxicity levels and worsening levels for AST or ALT?
> 1000IU/L
3000IU/L
what causes glutathione depletion?
- malnourised, eating disorders
•identified by low body mass index, ketonuria, low serum urea
what are the initial symptoms of paracetamol toxicity?
nausea and vomiting
when is liver damage likely to be detected?
after 24hrs (first 24hrs are usually symptomless)
what are symptoms of liver failure?
- jaundice, liver pain or tenderness, impaired consciousness, sweet faecal smell in breath, heamorrage, elevated LFTs)
how long does complete liver failure take?
2-3 days
when would you consider activated charcoal in paracetamol toxicity?
<2 hrs after ingestion or <4 for massive overdose
what is the paracetamol nomogram?
the time against plasma paracetamol conc with a treatment line
if it’s a value above the line then treat the patient with acetyl cysteine
when else would you give N-acetylcysteine?
when the timing of the paracetamol ingestion is unclear eg. unconscious
