Clinical Use of Analgesics: Paracetamol & NSAIDs

Question 1

What is the mechanism of action of paracetamol?

Answer 1

• Probably inhibits PG centrally (COX-3?)
• Enhances 5-HT (serotonin)
• TRPA1 agonist

Question 2

What preceded paracetamol infusions?

Answer 2

Suppositories in surgery

Question 3

What are the adverse effects of paracetamol?

Answer 3

• Rash, blood disorders, acute pancreatitis

- Liver and renal damage following OD

Question 4

What interacts with paracetamol?

Answer 4

Warfarin; increased INR in some patients (not an issue in short term)

Question 5

How many tablets of paracetamol induce overdose?

Answer 5

14 tablets in any 24 hour period; treatment with N-acetylcysteine

Question 6

What GI tract-related side effects occur with NSAIDs?

Answer 6

• GIT erosion + ulceration

Question 7

What adverse effects are seen with NSAIDs and the kidney?

Answer 7

• Reduce renal blood flow
• Na+/K+/water retention
• Acute renal failure

Question 8

What haematological side effects can occur with NSAIDs?

Answer 8

• Reduced platelet aggregation
  Aspirin = irreversible
  NSAIDs = reversible

Question 9

When would you stop NSAIDs/aspirin respectively before a surgical procedure?

Answer 9

NSAIDs; 2-3 days prior

Aspirin; 7-10 days prior (body has to regenerate)

Question 10

What respiratory-related adverse effects are NSAIDs associated with?

Answer 10

Bronchospasm; PGs involved w/patency (keeping airways open); blocking PGs = more leukotrienes and greater bronchial sensitivity

Question 11

What are the options for gastroprotection with NSAID use? (list in order)

Answer 11

PPIs (proton pump inhibitors):
- inhibit acid secretion by binding irreversibly to proton pumps

Misoprostol:
- synthetic PGE1 analogue

H2 receptor antagonists:
- e.g. ranitidine, competitively inhibit histamine @ H2 receptor sites on gastric parietal cells modulating gastric pH

Question 12

What cautions are associated for COXIBs?

Answer 12

Patients with SIGNIFICANT risk factors for CVD (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) or peripheral vascular disease

Question 13

What are COXIB’s contraindications?

Answer 13

• Congestive heart failure

- Established ischaemic heart disease and or cerebrovascular disease

Question 14

What is the recommendation of NSAID prescribing?

Answer 14

• Low-dose ibuprofen (

Question 15

Which NSAIDs are most appropriate for those with CV risk factors?

Answer 15

• Low dose ibuprofen or naproxen 1000mg

Question 16

When would a PPI be co-prescribed with an NSAID?

Answer 16

Those at high GI risk (partic. elderly) and long-term NSAID users