Substance abuse

Question 1

In addition to paracetamol, what are the other drugs regularly taken as overdoses?

Answer 1

1. Ibuprofen
2. Codeine
3. Sertraline
4. Diazepam
5. Citalopram
6. Mirtazapine
7. Zopiclone
8. Tramadol

Question 2

What are the variables that change how each person will react to paracetamol poisoning and the amount taken?

Answer 2

1. Age
2. Health status
3. Substances taken with the paracetamol

Question 3

What are the ranges for paracetamol intake and likely poisoning on the body?

Answer 3

<150mg/kg = unlikely
>250mg/kg = likely
More than 12 grams total = potentially fatal

Question 4

After taken orally, after how long do paracetamol plasma levels peak?

Answer 4

After 1 hour

Question 5

How is paracetamol normally metabolised?

Answer 5

By the liver - using to metabolites - glucuroinde or sulphate. It is then excreted really.

Question 6

What happens when paracetamol is taken in excess?

Answer 6

The liver conjugation becomes inundated, causing paracetamol to be metabolised by an alternative pathway. It results in a toxic metabolite - N-acetyl-p-benzoquinone imine (NAPQI) which is itself inactivated by glutathione, rapidly preventing harm. When the glutathione stores are depleted to less than 30%, the NAPQI reacts with nucleophilic aspects of the cell, leading to necrosis.

Question 7

Where does necrosis occur in paracetamol poisoning?

Answer 7

1. Liver

2. Kidney tubules

Question 8

What can increase paracetamol toxicity due to induction of the P450 system?

Answer 8

Drugs such as rifampicin, phenobarbitals, phenytoin, carbamazepine and alcohol.

Question 9

What are the causes of low glutathione reserves? (4)

Answer 9

1. Genetic variation
2. HIV positive status
3. Malnutrition
4. Alcohol-related or other, liver disease

Question 10

Why do paediatric patients under 5 seem to fare better after paracetamol poisoning?

Answer 10

They have a greater capacity to conjugate with sulphate and possibly greater glutathione reserves

Question 11

How may people present with paracetamol poisoning/overdose - clinical features?

Answer 11

In the first 24 hours they are commonly asymptomatic, or have non-specific abdominal symptoms such as nausea and vomiting.
After 24 hours hepatic necrosis begins to develop presenting with RUQ pain and jaundice

Question 12

What signs/complications may patients develop with paracetamol poisoning alongside RUQ pain and jaundice? (5)

Answer 12

1. Encephalopathy
2. Oliguria
3. Hypoglycaemia
4. Renal failure
5. Lactic acidosis

Question 13

What questions are important to ask as part of a history for paracetamol poisoning?

Answer 13

1. Number of tablets taken
2. Concomitant tablets
3. Time of overdose
4. Suicide risk - was a note left, what lengths did they go to not to be detected etc.
5. Alcohol?

Question 14

What investigations need to be carried out in someone presenting with paracetamol poisoning? (6)

Answer 14

1. Paracetamol levels
2. U&Es, creatinine
3. LFTs
4. Glucose - hypoglycaemia is common in hepatic necrosis
5. Clotting screen
6. ABG - acidosis can occur at an early stage, even when the patient is asymptomatic

Question 15

What is the antidote for paracetamol poisoning?

Answer 15

N-Acetylcysteine (NAC)