Simple analgesia: aspirin and paracetamol

Question 1

What is the onset of action time for IV paracetamol?

Answer 1

5 minutes

Question 2

How long after administration is peak effect of IV paracetamol, and how long can the effects last for?

Answer 2

40-60 minutes is peak, and can last up to 6 hours.

Question 3

Where in the gut is oral paracetamol absorbed?

Answer 3

Well absorbed from the small intestine

Question 4

What is the bioavailability of oral paracetamol?

Answer 4

63-89% - it is subject to first pass metabolism. Undergoes hepatic metabolism and renal excretion.

Question 5

What is the volume of distribution of oral paracetamol?

Answer 5

0.9 L/kg

Question 6

Following a severe paracetamol overdose (true or false):

Paracetamol metabolites are scavenged by glutamine

Answer 6

False. The metabolites are usually scavenged by glutathione (not glutamine), but in a severe overdose this scavenging mechanism is rapidly overwhelmed.

Question 7

Following a severe paracetamol overdose (true or false):

The initial clinical features provide a reliable guide to the severity of the poisoning

Answer 7

False. The initial clinical features of the overdose do not provide a reliable guide to the severity of poisoning, with more serious complications developing after 36 hours.

Question 8

Following a severe paracetamol overdose (true or false):

Hypothermia can occur

Answer 8

Severe complications of paracetamol overdose include:
-Acute haemolytic anaemia
-Hypothermia
-Hypoglycaemia
-Metabolic acidosis
-Delerium
-Acute hepatic failure (AHF).

Question 9

Following a severe paracetamol overdose (true or false):

Acute haemolytic anaemia is a recognised complication

Answer 9

Severe complications of paracetamol overdose include:
-Acute haemolytic anaemia
-Hypothermia
-Hypoglycaemia
-Metabolic acidosis
-Delerium
-Acute hepatic failure (AHF).

Question 10

Which of the following can aspirin be used for?

A. Mild to moderate pain
B. Anti-inflammatory in rheumatoid arthritis
C. Anti-inflammatory in osteo-arthritis
D. Secondary prevention in myocardial ischaemia
E. Prevention of all strokes
F. Deep vein thrombosis prophylaxis
G. Pre-eclampsia

Answer 10

All apart from E. Only prevents TIA/ischaemic stroke.

Aspirin is licensed for patients over 16 years of age. It should not be prescribed to patients below the age of 16 years due to the risk of Reye’s syndrome.

Question 11

What is the oral bioavailability of aspirin?

Answer 11

70%. It is rapidly hydrolysed by hepatic and intestinal esterases to form salicylate.

Question 12

Which of the following may be caused by normal doses of aspirin?

A. Myocardial infarction
B. Hyperventilation
C. Reduced clotting time
D. Gastric ulceration and bleeding
E. Reduced blood sugar

Answer 12

D & E. Aspirin causes reduced blood sugar at low doses, but some confusion at high doses. E-lfh says increases blood sugar at high doses, but also says that hypoglycaemia is a potential complication of salicylate toxicity.

Question 13

In context of aspirin overdose, what salicylate levels are considered mild, moderate and severe toxicity?

Answer 13

Mild: <500 mg/L (3.6 mmol/L)
Moderate: 500-750 mg/L
Severe: >750 mg/L

Question 14

True or false: aspirin overdose causes thrombocytopenia

Answer 14

False. Associated with hypothrombinaemia and inhibition of platelet aggregation.

Question 15

True or false: aspirin overdose causes coma

Answer 15

True

Question 16

True or false: aspirin overdose causes metabolic acidosis

Answer 16

True. Aspirin uncouples oxidative phosphorylation

Question 17

True or false: aspirin overdose causes jaundice

Answer 17

False

Question 18

True or false: aspirin overdose causes pulmonary oedema

Answer 18

True. Rare but non-cardiac pulmonary oedema can occur due to increased capillary permeability.

Question 19

Which of the following aids in the excretion of paracetamol:

A. Raising urinary pH
B. Activated charcoal
C. NAC
D. Repeated IV fluid boluses

Answer 19

None of them.

A. Useful in salicylate excretion, not for paracetamol.

B. Activated charcoal binds to paracetamol to reduce absorption, not excretion. It is most effective if taken within 1 hour of paracetamol ingestion.

C. NAC increases glutathione synthesis, binds to NAPQI, reduces NAPQI back to paracetamol and provides inorganic sulphates for paracetamol conjugation. But does not increase excretion.

E. Supportive treatment, does not affect excretion.

Question 20

An 80-year-old female is brought into the ED after her carers found her drowsy in her armchair with empty packets of paracetamol next to her which she takes for chronic osteoarthritic pain.

Which of the following factors does not increase her risk of hepatotoxicity?

A. Cigarette smoke
B. Malnutrition
C. Old age
D. Chronic alcoholism
E. Hypertension

Answer 20

A. Incorrect. Smoking is a risk factor for hepatotoxicity in paracetamol overdose.

B. Incorrect. Reduced glutathione stores due to malnutrition lead to build up of NAPQI.

C. Incorrect. Reduced liver function could result in result in quicker saturation of paracetamol metabolism pathways and increased NAPQI concentrations.

D. Incorrect. CYP450 system is induced and could increase the production of NAPQI.

E. Correct. Does not cause increase the risk of hepatotoxity in paracetamol overdose and is the correct response.

Question 21

One of the mechanisms of actions of paracetamol is:

A. Inhibiting descending serotonergic pathways
B. Activating dopaminergic pathways
C. Inhibiting prostaglandin synthesis
D. Inhibiting MOP and KOP receptors
E. Inhibiting cannabinoid receptors

Answer 21

C. Correct. Irreversible COX enzyme inhibitor.

A. Incorrect. Paracetamol activates descending serotonergic pathways.

B. Incorrect. Not known to target it.

D. Incorrect. These are opioid receptors.

E. Incorrect. Paracetamol activates cannabinoid receptors.