paracetamol overdosing

Question 1

what is the recommended maximum dose of paracetamol for adults in 24 hours ?

Answer 1

4g

ie. 2x500mg 4 times a day, 6 hours between each dose.

Question 2

what are the 3 types of paracetamol overdose

Answer 2

acute

staggered

therapeutic excess

Question 3

what is the difference between acute and staggered oversdose of paracetamol

Answer 3

acute = excessive amounts of paracetamol ingested over a period of less than 1 hour;

staggered = ingested over longer than 1 hour

both are usually in the context of self harm

Question 4

describe paracetamol overdose by therapeutic excess

Answer 4

• excessive paracetamol taken with the intent to treat NOT self harm
• its ingested at a dose greater then licensed dose and over 75mg/kg/24 hours
• can involve taking more then one paracetamol containing product at one time

Question 5

what dose of paracetamol is considered an overdose

Answer 5

over 150mg/kg in 24 hours

Question 6

what factors change the threshold of toxicity of a paracetamol dose within a patient?

Answer 6

pregnancy

BMI

Question 7

risk factors for paracetamol overdose

Answer 7

history of self-harm

history of frequent or repeated use of medications for pain relief

alcohol abuse

anorexia nervosa

malnourished

HIV (more susceptible to toxins)

drugs that induce liver enzymes (cytochrome P450 inducers)

Question 8

signs/symptoms of paracetamol overdose in the first 24 hours

Answer 8

mild nausea and vomiting

lethargy

malaise

can be asymptoamtic

Question 9

signs/symptoms of paracetamol OD 24-72hrs

Answer 9

can still be asymptomatic

mild nausea

vomiting

liver enlargement an tenderness

Question 10

signs/symptoms of paracetamol OD after 72hrs

Answer 10

increasing confusion

jaundice

coagulopathy (blood not clotting normally)

hypoglycaemia

renal angle pain

Question 11

what are the 1st line of investigations to order if suspected paracetamol overdose

Answer 11

test the serum paracetamol concentration

LFTs

blood glucose

prothrombin time and INR (how long it takes from clot to form in a blood sample)

Question 12

what can untreated paracetamol over dose lead to

Answer 12

varying degrees of liver injury over the 2 to 4 days following ingestion,

fulminant (rapid) hepatic failure.

Question 13

what are the rare/extreme presentations of a paracemtol overdose

Answer 13

coma and metabolic acidosis

Question 14

what is the treatment for paracetamol overdose ?

Answer 14

IV N-Acetylcysteine

within 8 hours over overdose

Question 15

epidemiology of paracetamol OD

• is it common?
• in which gender is it more common?

Answer 15

common

more in women

Question 16

how is 95% of paracetamol normally metabolised and excreted?

what are the 2 metabolic processes called

Answer 16

phase 2 hepatic metabolism !

by the addition of glucuroinide ( process is glucuronidation)

or by the addition of sulfate ( process of sulfation)

and then they are excreted harmlessly by the kidneys

Question 17

how is the other 5% of paracetamol normally metabolised?

Answer 17

phase 1 hepatic metabolism

oxidation reactions

byt cytochrome P450

Question 18

how it paracetamol metabolised in the event of an OD ?

(When glucuroinide and sulfate run out because too much needs to be metabolised)

Answer 18

oxidation by the cytochrome P450 system

Question 19

what highly reactive species is formed by the oxidation of paracetamol but the P45 system ?

Answer 19

NAPQI

Question 20

what happens to the NAPQI formed by the metabolisation of excess paracetamol

Answer 20

if only a little bit, it can be metabolised by glutathione in the liver cells into a harmless substance

if in excess (like during an OD), glutathione runs out and so the NAPQI cannot be broken down and it remains in the liver cells

Question 21

what does a build up of NAPQI in the liver cells lead to

Answer 21

hepatotoxic environment

kills liver cells, leads to hepatic necrosis