PHAR: Non-opioid analgesics

Question 1

What are different non-opioid analgaesics?

Answer 1

• Paracetamol
• NSAIDs
• Others (e.g. nefopam, dipyrone)

Question 2

What is paracetamol recommended first-line analgesic for? (Probably don’t need to know this lol)

Answer 2

• Osteoarthritis (since 2000)
• MSK pain in elderly (since 2002)
• Patients with renal disease (since 1996)
• Treatment of cancer pain (since 1984)

Question 3

What is the mechanism of paracetamol toxicity during overdose?

Answer 3

Excess of reactive intermediate (N-acetyl-p-benzoquinone imine - NAPQI) that kills liver cells

Question 4

What is the mechanism of action of NSAIDS?

Answer 4

Inhibition of cyclooxygenase (COX) to prevent prostaglandin production (which in turn is responsible for inflammation and pain)

Question 5

What are the functions of prostaglandins?

Answer 5

• Support renal and platelet function
• Protect gastric mucosa
• Inflammation and pain

Question 6

Are there many NSAIDS on the market?

Answer 6

YES - between 50 and 60 molecules which are all anti-inflammatory drugs. They all have similar efficacy.

Question 7

What are some of the adverse effects of NSAIDS?

Answer 7

• GI:
  
  • GI bleeding
  • Ulcers - bleeds/perforations (can be fatal)
• Renal:
  
  • Oedema, hypertension
  • Renal dysfunction
  • Heart failure
• Anti-platelet effects:
  
  • Contributes to blood loss
• Hypersensitivity:
  
  • Angiodema, bronchospam (bcus body makes more leukotrienes to make up for no prostaglandins)

Question 8

Explain the dual cyclooxygenase pathways

Answer 8

COX-1 and COX-2: able to use medication to just target COX-2 which is responsible for inflammation, pain and fever.

Question 9

Explain the selectivity of drugs like ibuprofen (NSAID), naproxen (NSAID) and celecoxib (Coxib)

Answer 9

• Non-selective linear shape:
  
  • Ibuprofen
  • Naproxen
• COX-2 selective bulky shape:
  
  • Celecoxib

Question 10

Explain the inhibition of Cox-2 by celecoxib

Answer 10

Celecoxib can’t fit into COX-1, so Arachadonic acid can be converted into prostaglanding. COX-2 it gets in the way.

Question 11

Do COX-2 selective inhibitors cause bronchospasm in patients with aspirin/conventional NSAID-sensitive asthma?

Answer 11

Celecoxib and rofecoxib given orally do not cause bronchospasm

Question 12

When should a non-selective COX inhibitor be given over a COX-2 inhibitor?

Answer 12

Kidney (renal) failure - although a non-RCT trial found risk of acute kidney injury was less with celecoxib than with other non-selective NSAIDS

Question 13

Is there an increased cardiovascular risk for coxibs?

Answer 13

No

Question 14

What patients are at risk from NSAID and Coxib usage?

Answer 14

• elderly
• history GI ulcers
• CV risk factors
• renal risk factors
• long periods of time

(Most adverse events occur in first 3-4 weeks)

Question 15

In what situations is COX-2 selective advantageous to non-selective NSAIDs?

Answer 15

• acute pain
  
  • rate of ulcers comparable to placebo
  • less blood loss
  • less effect on bone healing
• patients increased GI ulcer risk
• patients history of aspirin-induce asthma

Question 16

Explain considerations for aspirin medication

Answer 16

• Unique mechanism of action on COX
  
  • unique activity on platelets (irreversible blockade):
    
    • platelets contain COX1 only.
    • All non-selective NSAIDs block COX1 for 4-8 hours.
    • Aspirin goes onto COX1 and doesn’t go off.
• Note: when adding low-dose aspirin (BP) and ibuprofen (Inflam.) - need to separate intake by few hours otherwise by time ibuprofen comes off platelets, aspirin already been metabolised