NSAIDs

Question 0

COX-2 and peripheral sensitisation

Answer 0

1. Tissue injury causes COX-2 to be expressed
2. Which stimulates PGE2 by the EP receptor. Prostaglandins produce increase Nonciceptive sensitivity to pain.
3. This activates a process in a positive charge inside the nerve cell
4. Increased neurone membrane excitability
5. Neurone firing threshold decreases which makes it easier to perceive pain

Question 1

What is the mechanism of action of NSAIDs?

Answer 1

Non-selective inhibitor of the enzyme cyclooxygenase, inhibiting both COX-1 and COX-2. COX catalyses the formation of prostaglandins and thromboxane form arachidonic acid.
Anti-inflammatory
Analgesic
Antipyretic

Question 2

COX-2 and central sensitisation

Answer 2

Peripheral inflammation leads to induction of COX-2 in the CNS
Prostaglandins produced by COX-2 in the CNS cause further sensitisation to pain.
Results in hyperalgesia (feel more pain) and allodynia (pain to a stimulus that normally does not provoke pain)

Question 3

What are some adverse effects of NSAIDs?

Answer 3

Upper GI effects - indigestion, bleeding, ulcers
Renal effects - fluid retention, renal dysfunction/failure, heart failure
Anti-platelet effects - blood loss
Hypersensitivity effects - angioedema, bronchospasm

Question 4

Which COX-2 selective NSAID is used to treat asthma?

Answer 4

Celecoxib

Refecoxib

Question 5

Examples non-selective NSAID drugs?

Answer 5

Salicylates - aspirin
Arylpropionic - ibuprofen, naproxen
Phenylacetic acid - diclofenac
Oxicam - piroxicam

Question 6

Example of COX-2 selective NSAID drugs?

Answer 6

Celecoxib, parecoxib, etoricoxib

Rofecoxib - increases blood pressure - stroke

Question 7

Benefits of COX-2 selective over non-steroidal NSAIDs?

Answer 7

COX-2 selective is advantageous in acute pain.
Less ulcers and blood loss.
Can be used in patients with:
- increased risk of GI ulcers
- past history of aspirin induced asthma
- cardiovascular risk factors
No difference between both groups in renal adverse effects

Question 8

What are the effects of aspirin?

Answer 8

Irreversible blockade on platelets.
Some renal elimination.
Unique toxicity in therapeutic doses:
- Reye's syndrome 
- particular risk of bronchospasm
Unique toxicity in overdose
- acidosis - respiratory suppression
- fever
- renal failure
- high mortality rate