Wk10 NSAIDs

Question 1

What is the mechanism of action of NSAIDs?

Answer 1

NSAIDs - inhibits cyclooxygenase (COX) enzyme to block the generation of prostaglandins

Note:
> common inflammatory mediators: prostaglandins, leukotrienes, substance P, bradykinin
> traditional NSAIDs: aspirin, ibuprofen, diclofenac, naproxen
> COX 2 inhibitors: celecoxib, meloxicam

Question 2

What are the pharmacological effects of NSAIDs and what are their therapeutic uses?

Answer 2

Pharmacological effects:

• analgesic
• anti-inflammatory
• antipyretic
• anti-platelet

Therapeutic uses:

• headache, backache
• muscle pains
• osteoarthritis, rheumatoid arthritis
• GOUT, some cancer
• thrombotic events (low dose aspirin)

Question 3

What are the differences and similarities between COX-1 and COX-2 inhibitors?

Answer 3

Cyclooxygenase exists in two forms:
Cyclooxygenase 1 (COX 1):
- exists in most cells
- produce “good” prostaglandins
> involves in homeostasis, especially in maintaining mucosal gastric protection and gastric acid secretion (protect stomach and duodenum walls)
> regulates platelet functions through Thromboxane A2 (↑platelet aggregation) and Prostacyclin (↓platelet aggregation) - low dose Aspirin ↓ TXA2
Cyclooxygenase 2 (COX 2):
- exists in kidney and vascular tissues
- produce “bad” prostaglandins, which are involved in pain and inflammation
> produce vasodilation
> sensitize nerve terminals to pain signals

Similarities: both COX 1 and COX 2 promotes inflammation, pain, and fever.

Differences:

• COX 1 protects stomach and intestine linings, while COX 2 produce vasodilation effects
• COX-1 is involved in normal physiological functions, while COX 2 is triggered by inflammation

Question 4

What are the side effects which may be produced by NSAIDs?

Answer 4

Traditional NSAIDs: blocking COX 1

• gastrointestinal ulcers
• increased tendency to bleed
• reduced renal function & Na+/water retention (prostaglandin is a vasodilator, and its reduce may cause vasoconstriction and acute kidney injury)
• prolongation of labour
• acute asthma attack (aspirin-sensitive asthma)

COX 2 inhibitors: fewer GI ulcers
- reduced renal function & Na+/water retention
- Interaction with some important drugs:
ACE inhibitors, A2RA, diuretics, lithium

> Both types of NSAIDs are associated with ↑ adverse cardiovascular effects.
CON for NSAIDs: peptic ulcers, HF, HTN, renal impairment, asthma, elderly (bad for osteoarthritis as it stops the body’s inflammatory repair mechanism)

Question 5

What are the differences in the pharmacological and therapeutic effects of NSAIDs and paracetamol?

Answer 5

Paracetamol:

• have analgesic and antipyretic effects
• does not have anti-inflammatory effects
• does not block COX 1/2

As to the side effects, paracetamol does not cause:

• gastrointestinal ulcers
• ↑ bleeding tendencies
• ↓ renal function, Na+/H2O retention
• prolongation of labour

Question 6

What are the treatments for paracetamol overdose?

Answer 6

Paracetamol overdose S/S:

• N/O
• liver toxicity, ie jaundice, metabolic disturbance

Antidote is acetylcysteine, which restores glutathione levels and/or inactivates NABQI