Overdose

Question 1

Which organ is the principal site of paracetamol toxicity?

How does it cause damage?

Answer 1

Liver conjugation becomes inundated with all the paracetamol, so the liver starts metabolising it via a different pathway

This pathway produces a toxic metabolite (NAPQI) which is inactivated by glutathione.

When glutathione stores are depleted to less than 30%, NAPQI reacts with liver and renal tubule cells causing necrosis.

Question 2

What is the toxin that damages the liver and kidneys in paracetamol OD?

Answer 2

NAPQI

N-acetyl-p-benzoquinone

Question 3

How much paracetamol is likely to cause liver damage?

How much is likely to be fatal?

Answer 3

Varies between people but generally

More than 250mg/kg - damage

More than 12g - fatal

Question 4

When does paracetamol reach peak plasma concentration?

When do patients become symptomatic?

When does hepatic necrosis start to occur?

Answer 4

Peak plasma concentration after 1 hour

Patients are often asymptomatic for the first 24 hours, or they just have N+V

Necrosis starts after 24 hours

Question 5

The liver is the principal site of damage from paracetamol OD. What other organs can be affected?

Answer 5

Kidneys: NAPQI causes necrosis of renal tubule cells

Brain: hepatic encephalopathy

If severe can get multiple organ failure

Question 6

Clinical presentation of paracetamol OD?

Answer 6

Initially asymptomatic
N+V
RUQ pain
Jaundice
Encephalopathy (confusion, reduced consciousness)
AKI (low UO, oedema)

Question 7

In what cases would you treat with NAC?

Answer 7

Use a graph (plasma paracetamol conc vs time since OD) to see whether treatment is needed.

If they fall above the treatment line give: N-acetyl cysteine (Parvolex)

Start straight away if:

• they took a staggered OD over 1 hour or more
• there’s any doubt about the timing of the OD or if suspected large OD

Question 8

Investigations of paracetamol OD?

Answer 8

Bloods:

• glucose
• U+E
• LFT
• INR
• serum paracetamol (at 4hr post ingestion)

ABG

Question 9

Management of paracetamol OD?

Answer 9

N-acetyl cysteine (only if meet criteria)

Sometimes: activated charcoal, or gastric lavage

Continued bloods monitoring

Refer to liver team if continued deterioration

Question 10

How is NAC given?

Answer 10

IV

In 5% dextrose over 15 min - 1 hour

Question 11

Clinical features of salicylate OD?

Answer 11

Unlike paracetamol OD, there are early features…

N+V
Dehydration
Vertigo, tinnitus
Hyperventilation
Seizures
Reduced GCS

Question 12

In salicylate OD, what would you see on ABGs over time and why?

Answer 12

Initially respiratory alkalosis b/c due to direct stimulation of respiratory centre causing hyperventilation

Then metabolic acidosis due to the salicylic acid

Question 13

What drugs contain salicylate and how do they work?

Answer 13

Aspirin: analgesic and anti-inflammatory, suppress the production of prostaglandins and thromboxanes due to its irreversible inactivation of the COX enzyme.

Skin: keratolytic, comedolytic and bacteriostatic, remove the outer layer of the skin, psoriasis, acne, ringworm

Question 14

Investigations of salicylate OD?

Answer 14

Bloods: salicylate level, glucose, U&E, LFTs, INR

ABG

Urine: check pH and output

Question 15

Management of salicylate OD?

Answer 15

Activated charcoal if over 125 mg/kg salicylate, less than one hour previously.

Gastric lavage if over 500mg/kg

Rehydration

Replacement of glucose and pottasium

Haemodialysis

Question 16

When can you give activated charcoal to treat poisoning?

Which types of poisoning does it treat?

Answer 16

Within an hour of ingestion, unless its a drug that delays gastric emptying

Weakly ionic, hydrophobic substances are generally well adsorbed to activated charcoal

These include aspirin, benzos, methotrexate