Drug overdose: Paracetamol (Complete)

Question 1

List common types of overdose

Answer 1

Paracetemol

Opioids

Salicyclates (e.g. Ibuprofen)

Benzodiazepines

TCAs

Lithium

Warfarin

Heparin

Beta-blockers

Question 2

What is the most common agent used in overdose for self harm?

Answer 2

Paracetemol

Question 3

What are the main signs/sypmtoms of paracetemol overdose?

Answer 3

No symptoms

Nausea and vomiting

Loin pain

Haematuria and proteinuria

Jaundice

Abdominal pain

Coma

Severe metabolic acidosis

Question 4

Briefly describe the pathophysiology of paracetemol overdose

Answer 4

Paracetemol overdose results in buildup of toxic metabolite NAPQI

NAPQI is inactivated by glutathione however in overdose, glutathione levels are greatly depleted.

Buildup of NAPQI causes liver and kidney damage

Question 5

What is management for suspected drug overdose?

Answer 5

Pharmacological:

Activated charcoal: If ingestion less <1 hour and >150mg/kg ingested

N-acetylcysteine:
If ingested >15 hours ago or staggered dose: Immediate administration
If ingested < 4 hours: Wait until 4 hour mark, measure levels and then treat with dose depending on levels.
If ingestion 4-15 hours: Take immediate level measures and treat with dose depending on level.

Take bloods:
FBC
Urea and Electrolytes
INR
Venous gas

Surgical:

Liver transplant in severe cases

Question 6

When would you give N-acetylcysteine immediately in management of paracetemol overdose?

Answer 6

If ingestion occured >15 hours

If patient took staggered overdose (all tablets were not taken within 1 hour)

Question 7

What is management for patient who has overdosed on paracetomol between 4-15 hours?

Answer 7

Take immediate measure of plasma paracetemol levels.

Administer N-acetylcysteine with dose dependin on levels

Question 8

What is management for patient who has overdosed on paracetomol <4 hours ago?

Answer 8

Wait until 4 hours have elapsed

Measure plasma paracetemol levels

Administer N-acetylcysteine based on levels

Question 9

What criteria is used to determine whether patient with paracetemol overdose is in need of a liver transplant?

Answer 9

King’s college hospital criteria for liver transplantation

Question 10

What criteria must be met to meet King’s college criteria for liver transplant?

Answer 10

1) pH <7.3 24 hours after ingestion

2) OR all of the following:

PT > 100
Creatinine >300
Grade III or IV encephalopathy

Question 11

Which patients are at increased risk of developing hepatotoxicity in paracetomol overdose?

Answer 11

Patients taking liver-eznyme inducing drugs (e.g. St John’s Wort, Rifampicin)

Malnourished patients (e.g. anorexia nervosa or patients who havent eaten in couple of days)

Chronic alcohol excess (Acute has been shown to actually have protective effects)

Question 12

List examples of liver enzyme inducing drugs which can increase risk of hepatotoxigenicity in paracetamol overdose.

Answer 12

St John’s Wort (Common over the counter)

Rifampicin

Phenytoin (Epilepsy)

Carbamazepine (Epilepsy)

Chronic alcohol excess

Question 13

Why is paracetomol measures only given after 4 hours of ingestion?

Answer 13

Paracetemol would still be in stomach and not in circulatory system so would show normal levels which is falsely reassuring

Question 14

Why should N-acetylcysteine be given immediately after 15 hours?

Answer 14

Effects of N-acetylcysteine greatly lower post 8 hours of ingestion