Paracetamol Overdose

Question 1

What are the unique features of Paracetamol compared to NSAIDs?

Answer 1

• non anti-inflammatory
• non opiate
• analgesic
• antipyretic

Question 2

Briefly describe what happens during trauma/injury which leads to pain

Answer 2

1. Trauma > damaged cells release phospholipase
2. Phospholipase breaks down phospholipids in cell membrane into arachidonic acid
3. Arachidonic acid converted to prostaglandins by COX
4. Prostaglandins elicit fever, dilation, pain

Question 3

How does Paracetamol work?

Answer 3

1. Inh. COX 2 in CNS
2. decrease prostaglandin production
3. lesser pain and fever

Question 4

Why is Paracetamol better than NSAIDS?

Answer 4

• 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

Question 5

How is paracetamol metabolised?

Answer 5

• Metabolised by the liver into (all inactive)
  
  • paracetamol glucuronide -55%
  • paracetamol sulfate - 30%
  • paracetamol glutathione - 15%

Question 6

What is paracetamol’s intermediate product before reaching paracetamol glutathione?

Why is it harmful?

Answer 6

• NAPQI
• Highly nucleophilic
  
  • oxidise metabolic enzymes > necrosis

Question 7

What is the Px of paracetamol overdose?

Answer 7

1. Normal therapeutic dose - paracetamol conjugated to glucoronide and sulphate (both biologically inactive)
2. In paracetamol overdose, paracetamol converted to NAPQI but inactivated by glutathione
3. Once glutathione stores depleted, NAPQI reacts with neuclophilic aspect of cells
4. Necrosis of liver and kidney tubules

Question 8

What dose is required to cause irreversible damage?

Answer 8

• 150mg/kg

Question 9

What are the Sx of paracetamol overdose?

Answer 9

• First 24 hrs > asymptomatic / N&V
• >24hrs, hepatic necrosis occurs
  
  • Acute liver failure pic
    
    • High transaminase
    • RUQ pain
    • Jaundice
• Encephalopathy - confusion
• Scars
• Asterixis
• jaundice
• oliguria
• tachycardia / hypotension
• coma
• lactic acidosis

Question 10

What Ix would you order for PO?

Answer 10

• Bloods
  
  • Paracetamol level
  • Salicylate level
  • U&E
  • LFT - normal if present early
  • Glucose
  • Clotting screen- Prothrombin time
  • ABG

Question 11

How would you mx PO?

Answer 11

• `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)

Question 13

Deescribe the King’s College Hospital criteria used for liver transplantation in paracetmaol-induced acute liver failure?

Answer 13

1. Arterial pH < 7.3, 24 hours after ingestion
2. or all of the following:

• prothrombin time > 100 seconds
• creatinine > 300 µmol/l
• grade III or IV encephalopathy

Question 14

What are the criterias for safely discharging paracetamol overdose pt?

Answer 14

• Paracetamol con. below tx line
• INR and ALT normal
• Pt asymptomatic
• Normal serum Cr
• Advice to return to hospital if abdo pain occurs

Question 15

What is the most common overdose in the UK?

Answer 15

• Paracetamol toxicity

Question 16

What is most common cause of acute liver failure?

Answer 16

• Paracetamol overdose

Question 17

What risk assessment should Paracetamol overdose pt have?

Answer 17

• 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

Question 18

What are the different types of Paracetamol ingestion?

*4 types

Answer 18

• 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

Question 20

What is the nomogram?

Answer 20

• paracetamol ingestion graph
• used to determine if tx with NAC is needed
• Paracetamol peak at 4hrs after last ingestion