Paracetamol Overdose Flashcards
What are the unique features of Paracetamol compared to NSAIDs?
- non anti-inflammatory
- non opiate
- analgesic
- antipyretic
Briefly describe what happens during trauma/injury which leads to pain
- Trauma > damaged cells release phospholipase
- Phospholipase breaks down phospholipids in cell membrane into arachidonic acid
- Arachidonic acid converted to prostaglandins by COX
- Prostaglandins elicit fever, dilation, pain
How does Paracetamol work?
- Inh. COX 2 in CNS
- decrease prostaglandin production
- lesser pain and fever
Why is Paracetamol better than NSAIDS?
- well tolerated
- fever ADRs (Renal ADRs like low renal blood flow and Gastro ADRs like dyspepsia, nausea, peptic ulcer, bleeding, perforation)
- no effect on platelets
- limited effect on GI
How is paracetamol metabolised?
- Metabolised by the liver into (all inactive)
- paracetamol glucuronide -55%
- paracetamol sulfate - 30%
- paracetamol glutathione - 15%
What is paracetamol’s intermediate product before reaching paracetamol glutathione?
Why is it harmful?
- NAPQI
- Highly nucleophilic
- oxidise metabolic enzymes > necrosis
What is the Px of paracetamol overdose?
- Normal therapeutic dose - paracetamol conjugated to glucoronide and sulphate (both biologically inactive)
- In paracetamol overdose, paracetamol converted to NAPQI but inactivated by glutathione
- Once glutathione stores depleted, NAPQI reacts with neuclophilic aspect of cells
- Necrosis of liver and kidney tubules
What dose is required to cause irreversible damage?
- 150mg/kg
What are the Sx of paracetamol overdose?
- First 24 hrs > asymptomatic / N&V
- >24hrs, hepatic necrosis occurs
- Acute liver failure pic
- High transaminase
- RUQ pain
- Jaundice
- Acute liver failure pic
- Encephalopathy - confusion
- Scars
- Asterixis
- jaundice
- oliguria
- tachycardia / hypotension
- coma
- lactic acidosis
What Ix would you order for PO?
- Bloods
- Paracetamol level
- Salicylate level
- U&E
- LFT - normal if present early
- Glucose
- Clotting screen- Prothrombin time
- ABG
How would you mx PO?
- `Activated charcoal 50g
- N-acetylcysteine
- 1st infusion: loading dose 150mg/kg in 1 hr
- 2nd infusion: 50mg/kg in 4 hrs
- 3rd infusion: 100mg/kg in 16 hrs
- Take blood test after to look for signs of hepatic impairment
- Gastric lavage (last resort)
Deescribe the King’s College Hospital criteria used for liver transplantation in paracetmaol-induced acute liver failure?
- Arterial pH < 7.3, 24 hours after ingestion
- or all of the following:
- prothrombin time > 100 seconds
- creatinine > 300 µmol/l
- grade III or IV encephalopathy
What are the criterias for safely discharging paracetamol overdose pt?
- Paracetamol con. below tx line
- INR and ALT normal
- Pt asymptomatic
- Normal serum Cr
- Advice to return to hospital if abdo pain occurs
What is the most common overdose in the UK?
- Paracetamol toxicity
What is most common cause of acute liver failure?
- Paracetamol overdose
What risk assessment should Paracetamol overdose pt have?
- Date of ingestion: is there a delay in presentation?
- Timing of ingestion: single overdose or staggered
- Time since last ingestion (even staggered)
- Weight: if >110 kg, used 110 kg as the maximum weight for calculations.
- Pregnancy: use pre-pregnancy weight to determine toxicity and current weight for treatment
- Total amount ingested (mg/kg)
- Current suicidal risk: consider a registered mental health nurse (RMN) to stay with the patient
What are the different types of Paracetamol ingestion?
*4 types
-
Acute ingestion
- ingested > 75 mg/kg within 1hr or less
-
Staggered ingetsion
- ingested > 150 mg/kg in any 24 hour
- Unknown time of ingestion
- Delayed presentation
- unintentional
What is the nomogram?
- paracetamol ingestion graph
- used to determine if tx with NAC is needed
- Paracetamol peak at 4hrs after last ingestion
