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TAS Accidents and Poisoning ✅ > Paracetamol Poisoning ✅ > Flashcards

Paracetamol Poisoning ✅ Flashcards

1
Q

What is the most common medication taken in overdose by children in developed countries?

A

Paracetamol

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2
Q

Why is paracetamol the most common drug taken in overdose?

A

Due to its wide over-the-counter availability

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3
Q

Why is it hard to determine the toxic dose of paracetamol?

A

It can be very variable

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4
Q

What are higher doses of paracetamol associated with?

A

Greater risk of adverse effects

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5
Q

What single dose of paracetamol is considered to have a reasonable likelihood of causing toxicity?

A

200mg/kg

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6
Q

Can doses lower than 200mg/kg of paracetamol cause problems?

A

Yes, lower single doses can result in significant problems, as can multiple smaller doses which cumulatively exceed this threshold taken within a 24 hour period

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7
Q

What phases is paracetamol toxicity divided into?

A
  • 0-24 hours
  • 24-72 hours
  • 72-120 hours
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8
Q

What features may be present 0-24 hours after a paracetamol overdose?

A
  • Nausea
  • Vomiting
  • Excessive sweating
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9
Q

What features may be present 24-72 hours after paracetamol overdose?

A
  • Right upper quadrant pain
  • Liver dysfunction
  • Possible renal impairment
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10
Q

What features may be present 72-120 hours after paracetamol overdose?

A
  • Hepatic necrosis leading to liver failure
  • Renal failure
  • Cerebral oedema
  • Death
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11
Q

What is the biochemical evidence of paracetamol-induced liver damage?

A
  • Elevated blood concentrations of AST and ALT

- Prolonged prothrombin time

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12
Q

What evidence of a paracetamol overdose might be found on blood gas?

A

Metabolic acidosis in severe cases

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13
Q

What causes AKI in paracetamol overdose?

A
  • May be primary manifestation of paracetamol toxicity

- Can occur as result of hepatorenal syndrome or multi-organ failure

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14
Q

By what processes is paracetamol metabolised?

A
  • Sulfation
  • Glucuronidation
  • Hydroxylation by CYP450
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15
Q

What is formed from sulfation of paracetamol?

A

Sulfate moiety

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16
Q

Is the sulfate moiety formed from paracetamol sulfation toxic?

A

No

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17
Q

What is formed from the glucuronidation of paracetamol?

A

Glucuronide moiety

18
Q

Is the glucuronide moiety formed from paracetamol glucuronidation toxic?

A

No

19
Q

What is formed from the hydroxylation by paracetamol by CYP450?

A

NAPQI (N-acetyl-p-benzo-quinone imine)

20
Q

Is the NAPQI formed by the hydroxylation of paracetamol toxic?

A

Yes

21
Q

What happens to the NAPQI formed in paracetamol metabolism?

A

It is conjugated to glutathione

22
Q

What is produced from the conjugation of NAPQI to glutathione?

A

Cysteine and mercapturic acid conjugates

23
Q

Are cysteine and mercapturic acid conjugates toxic?

A

No

24
Q

What % of metabolism of therapeutic doses of paracetamol is done by sulfation and glucuronidation?

A

Over 90%

25
Q

Where does glucuronidation and sulfation of paracetamol take place?

A

In the liver

26
Q

What % of paracetamol undergoes metabolism to NAPQI at therapeutic doses?

A

Approx 5%

27
Q

Why does NAPQI not have toxic effects at therapeutic doses?

A

Because the small amount produces is easily detoxified by conjugation with glutathione

28
Q

What happens to the metabolism pathways of paracetamol in overdose?

A

The glucuronidation and sulfation pathways become saturated and a much higher proportion of paracetamol is converted to NAPQI

29
Q

What happens with the excessive amounts of NAPQI in paracetamol overdose?

A

Hepatic stores of glutathione are depleted rapidly, and NAPQI remains in its active toxic form causing acute hepatic necrosis

30
Q

What is the treatment for paracetamol overdose?

A

Administration of N-acetylcysteine (NAC)

31
Q

In what timeframe should NAC be given in paracetamol overdose?

A

Within 8 hours of ingestion

32
Q

What is the purpose of NAC in paracetamol overdose?

A

Helps limit hepatotoxicity and prevents death

33
Q

What happens to the effectiveness of NAC the longer that administration is delayed after this time?

A

It is progressively less effecrtive

34
Q

How does NAC work in paracetamol overdose?

A

Primarily by augmenting glutathione reserves, which enhances the ability to detoxify NAPQI

35
Q

How is the need for administration of NAC guided in paracetamol overdose?

A

Measurement of plasma paracetamol levels at least 4 hours after overdose, and the use of a monogram to assess risk of toxicity

36
Q

What factors put individuals at greater risk of paracetamol toxicity?

A
  • Starvation/malnutrition
  • CYP450-inducing drugs
  • Neonates
37
Q

Why does starvation/malnutrition put individuals at a greater risk of paracetamol toxicity?

A

Probably as a result of depleted hepatic glutathione stores

38
Q

Give 2 examples of CYP450-inducing drugs?

A
  • Carbamazepine

- Phenytoin

39
Q

How is paracetamol metabolism different in a neonate?

A
  • The sulfation pathway is the primary metabolic pathway for paracetamol in the neonate because of low glucuronidation activity
  • The CYP450 pathway displays significantly lower activity than in later life
40
Q

What is the result of the CYP450 pathway of paracetamol metabolism showing significantly lower activity in the neonatal period than in later life?

A

May be protective

41
Q

What is used to identify patients in which liver transplantation should be considered?

A

King’s College criteria

42
Q

What are the King’s College criteria indicating a referral for consideration of transplant should be considered?

A
  • Arterial pH <7.3
  • All 3 of;
    • INR >6.5
    • Serum creatinine >300
    • Grade III/IV hepatic encephalopathy

TAS Accidents and Poisoning ✅ (12 decks)

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