Paracetamol And Aspirin

Question 1

What are the two modes of action of paracetamol?

Answer 1

*NAPQI binds to TRPA-1 calcium channel receptors- stops influx of Ca- no action potential- anti-nociception
*cannabinoid receptors- increases cannabinoid activation- inhibits nociception- pain relief

Question 2

How does paracetamol overdose occur ?

Answer 2

*NAPQI toxic metabolite
*usually detoxified by glutathione
*too much- detoxification pathway saturated- glutathione stores diminish
*NAPQI builds up in liver- binds to hepatocytes- necrosis and cell death
*liver toxicity

Question 3

How is paracetamol metabolised?

Answer 3

By cytochrome p450 to NAPQI

Question 4

What are the effects of paracetamol on the body?

Answer 4

Anti pyretic
Analgesic

Question 5

What are the first signs of paracetamol OD?

Answer 5

*nausea and vomiting- settled within 24 hours

Question 6

What are the next signs of paracetamol OD?

Answer 6

*nausea and vomit returns within 2-3 days with tenderness on right side- hepatic necrosis
*liver damage peaks 3-4 days post OD

Question 7

What can be administered to reverse paracetamol OD?

Answer 7

IV N-acetylcysteine (NAC)
- effective if given in first 8 hours of ingestion
-NAC replenishes liver glutathione levels- allows NAPQI detoxification

Question 8

What is the chemical name of aspirin?

Answer 8

Acetylsalicylic acid

Question 9

What effects does aspirin have on the body?

Answer 9

*analgesic- inhibits PGE2
*anti pyretic- inhibits PGE2- thermoregulation of hypothalamus
*anti inflammatory- inhibits PGE2/D2
*ANTI THROMBOTIC- reduced TXA2 production in platelets

Question 10

What type of inhibitor is aspirin?

Answer 10

Irreversible

Question 11

Why does aspirin act as an anti thrombotic but other NSAIDs do not?

Answer 11

Because it binds IRREVERSIBLY to COX1- platelets cannot re synthesise after inhibition- have no nucleus
/DNA
COX inhibited entire lifespan of platelet (10 days)

Question 12

What is the dose for aspirin (for pain not CV)?

Answer 12

300-900mg every 4-6 hours

Question 13

What is the main metabolite of aspirin?

Answer 13

Salicylic acid

Question 14

Where and how is aspirin metabolised?

Answer 14

In the liver by hydrolysis

Question 15

What are the SE’s of aspirin?

Answer 15

*GI disturbances- inhibition of PG synthesis in stomach- reduced mucus secretion, increased acid production
- peptic ulcers, bleeding

Question 16

What drug does aspirin interact with?

Answer 16

WARFARIN- both have anti coagulant properties

Question 17

What can be given for aspirin OD?

Answer 17

Activated charcoal- given within 1hr of ingesting 125 mg/kg

Question 18

How does activated charcoal work?

Answer 18

*absorbs ingested toxins
*prevents systemic absorption of salicylic acid/salicylate
*initial 50g