What is paracetamol’s mechanism of action?  How does it differ from that of aspirin?

Peripherally: Paracetamol is a weak COX1 & COX2 inhibitor. It has analgesic & antipyretic effects and weak to no anti-inflammatory action. There is also no effect on platelet aggregation, which is the opposite in Aspirin. Aspirin decreases platelet aggregation and inhibits COX1&2 irreversibly.

CNS: COX 3 inhibition, modulate body's endogenous cannabinoid (cannabis) system & 5-HT descending pain pathways AND inhibits NMDA receptors, reducing nociception (blocks the receptors thus neurotransmitters cannot bind thus perception of pain is blocked).

Name the indications for paracetamol.  Under which circumstances is it a drug of choice for the treatment of mild pain and fever?

It is used in the treatment of light to moderate pain of somatic origin, when an anti-inflammatory effect not needed.  Acute pain, chronic pain and fevers. Paracetamol is used when anti-inflammatory effects are not needed and it is used in patients where NSAIDs are contraindicated. It is also the choice of means in children.

Name side-effects that can occur with paracetamol use.  Concentrate only on general side effects and not on acute paracetamol overdose

Skin rash and urticuria.

Due to the ready availability of paracetamol and the general perception by the public that paracetamol is a very safe drug, paracetamol poisoning (by accident/intentional) is fairly common.  Compile a report in which you discuss acute paracetamol toxicity, stressing the dose, signs and symptoms and treatment.  In your textbook, as well as in the SAMF, there is valuable information that you can use

Signs and symptoms:

Within 1-2 days: Nausea, vomiting, abdominal pain, fatigue and weakness in the beginning.

After 1-2 days: Renal impairment & hepatotoxicity occurs 24-48h after overdose with light subcostal pain, tar liver, jaundice, renal insufficiency, liver necrosis and death.

A dose of 10-15g can be fatal.

Chronic use of 2g / day can also lead to paracetamol poisoning.

Treatment:

• Within 1h of overdose: Induce vomiting, gastric lavage, activated charcoal.
• Liver damage can be prevented with large dosage of NAC if given before 12hrs after ingestion. Given iv (150mg/kg) / orally (140 mg/kg). NAC less useful after 12hrs.
• Immediate supplementation of –SH groups to supplement glutathione in liver and prevent liver cell necrosis.
• N-acetylcysteine ​​(Parvolex®) administered within 8-12 hours IV.
• Initial dose : 150mg/kg in 200ml 5% glucose over 15 minutes, thereafter 50 mg/kg in 500 ml 5% glucose over 4 hours, thereafter 100 mg/kg in 1 000 ml 5% glucose over 16 hours.
• Oral Treatment: acetylcysteine ​​(Solmucol®, ACC®), 140mg / kg or carboscistein (Mucosirop®, Flemex®) 150mg / kg

NB: treatment only effective within 10hrs of poisoning