NSAIDs

Question 1

What are the functions of prostaglandin, thromboxane and prostacyclin?

Answer 1

Prostaglandin (PGE2):

1. Vascular permeability
2. Pain
3. Increases body temperature (thermal regulation)
4. Inhibits Na+ reabsorption at TAL where 25% of Na+ is reabsorbed

Prostacyclin (PGI2):

1. Vasodilation
2. Inhibits platelet aggregation
3. Promotes mucous secretion
4. Decreases gastric acid secretion
5. Promotes bicarbonate secretion
6. Stimulates renin production and thus aldosterone, which promotes Na+/H2O reabsorption and K+/H+ excretion

Thromboxane:

1. Vasoconstriction
2. Promotes platelet aggregation

Question 2

What are the properties of Aspirin?

Answer 2

1. Anti-inflammatory
   Aspirin inhibits PGI2 and PGE2 production, thus blocking pain perception (stimulated by PGE2) and reducing swelling and inflammation from decreased vascular permeability (PGE2) and vasodilation (PGI2)
2. Antipyretic
   PGE2 plays a role in thermal regulation by increasing body temperature. By inhibiting PGE2 production during fever, body temperature decreases back to normal.
3. Analgesic
   PGE2 is responsible for stimulation of pain. Blocking the production of PGE2 produces the analgesic effect.
4. Antiplatelet
   Aspirin has long term platelet affects as the replenishment of PGI2 is faster than TXA2 and thus exerts anti-platelet effects.

Question 3

What are the AEs of Aspirin?

Answer 3

Dose dependent AEs:

1. Headache
2. Nausea
3. Gastric intolerance
4. Bleeding
5. Tinnitus (1st sign of OD)
6. Reye’s Syndrome (increased risk when used in children with viral infections)

Question 4

AEs of COX inhibition?

Answer 4

GI effects:

1. GI bleeding
2. Peptic ulcer
3. Dyspepsia
4. Nausea and vomiting

Renal effects:

1. Hyperkalemia
2. Acute renal failure

Other:

1. Pseudoallergic reactions
2. Asthma - Aspirin-sensitive asthma (excess leukotrienes can lead to bronchospasm in asthmatics)
3. Bleeding (due to failure of hemostasis)

Question 5

AEs of COX-2 inhibition?

Answer 5

1. Renal toxicity due to alteration of renal blood flow
2. Effects on ovulation and delayed follicular rupture
3. Premature closing of ductus arteriosus (makes it a strong contraindication for 3rd trimester)
4. Impair wound healing due to failure of hemostasis
5. Increased risk of peptic ulcer formation
6. Increased risk of thrombosis

Question 6

What are the various COX inhibitors arranged in increasing selectivity for COX-2 inhibition?

Answer 6

1. Ketoprofen
2. Piroxicam
3. Indomethacin
4. Aspirin
5. Naproxen
6. Ibuprofen
7. Diclofenac
8. Mefenamic acid
9. Meloxicam
10. Celecoxib
11. Parecoxib
12. Etoricoxib

Question 7

What are the advantages and disadvantages of Paracetamol?

How is it metabolised?

Answer 7

Advantages:

1. Relatively safe for use in children
2. Good analgesic
3. Potent antipyretic
4. Spares the GIT

Disadvantages:

1. Weak anti-inflammatory
2. Toxic doses can lead to liver damage

Metabolism:
CYP2e1 metabolises paracetamol to toxic NAPQI, which is then metabolised by glutathione and into non-toxic metabolite