Paracetamol OD

Question 1

What happens when normal paracetamol metabolic pathways become saturated?

Answer 1

Normal pathways (safe pathways): 1) glucuronyl transferase 2) phenolsulphotranseferase

When normal pathways get saturated (overwhelmed by OD)-> 3rd pathway activated (it is called N-acetyl-p-benzoquinoneimine) -> NAPQI produced -> it destroys hepatocytes in the liver

Question 2

How does the body get rid of NAPQI?

Answer 2

It combines with Glutathione -> that conjugates NAPQI and gets rid of it (by removing it from the body)

Question 3

What do we give in paracetamol OD/ what’s the physiological princple?

Answer 3

We want to increase Glutathione dose -> so we can conjugate NAPQI (harmful metabolites of paracetamol in OD)

For that purpose we give N-acetylcysteine

Question 4

What is the timeframe to give N-acetylcysteine after paracetamol OD?

Answer 4

within 4 hours from OD

Question 5

What is the connection between the inducer of cytP450 and paracetamol OD?

Answer 5

As more liver CytP450 activity -> more activation of pathway that produce NAPQI = more dangerous

Question 6

Treatment protocol for paracetamol

to treat or not to treat

Answer 6

Drug paracetamol level is taken 4 hours after the OD -> to check what blood Paracetamol level is

If it is above the line -> treat with NAC (N-acetylcysteine)

If the blood level of Paracetamol is below -> then do not treat *at that point perhaps enough glutathione to metabolise paracetamol + side effects of having NAC

Question 7

Side effects of NAC treatment

Answer 7

NAC = N-acetylcysteine

• nausea/ vomiting
• bronchospasm
• anaphylactoid reation* - rash (in about 20% of people)
• anaphylactoid reaction is anaphylaxis - like picture but not mediated by IgE but by direct release of inflammatory mediators from mast cells

Question 8

Best investigations for a person coming with Paracetamol OD

Answer 8

• Paracetamol level
• LFT -> to check liver function and bilirubin
• INR -> to make sure clotting is not affected (synthetic function)
• U&Es -> to ensure that there is no multi-organ failure
• glucose -> if pt has low GCS/mental state - to role out that cause of pt state
• ABG -> always to do with a patient with low GCS
• metabolic flap test -> to check if encephalopathy has happened

Question 9

Paracetamol OD management

if taken <1 hour ago

Answer 9

Activated Charcoal

MoA: it is going to the stomach and absorbs paracetamol particles

*but effective only if a drug is in the stomach

Question 10

Main treatment for Paracetamol OD

Answer 10

NAC (N-acetylcysteine)

Question 11

What criteria are used to determine who should be referred for an immediate liver transplant?

Answer 11

King’s criteria

to determine who should receive a liver transplant after acute or chronic paracetamol induced severe liver injury