NSAIDs and SAIDs

Question 1

What target do selective NSAIDs inhibit?

Answer 1

COX-2

Question 2

What targets to non-selective NSAIDs inhibit?

Answer 2

COX-1 and COX-2

Question 3

Explain the renal effects associated with NSAID use.

Answer 3

COX-1 promotes the conversion of arachadonic acid to prostaglandins which converts to PGE2 which vasodilates the afferent arteriole of the kidney.
By blocking COX-1 this is causing vasoconstriction of the afferent arteriole of the kidney.

Question 4

Explain the cardiovascular effects associated with COX-2 selective NSAIDs.

Answer 4

By inhibiting COX-2 this decreases concentrations of PG12 which is responsible for decreases in platelet aggregation and vasodilation. COX-1 not being inhibited causes an increase in TBXA2 which promotes platelet aggregation. Blocking COX-2 disrupts this balance and TBXA2 is more predominant causing a significant increase in platelet aggregation which increases the likelihood of blockages.

Question 5

Explain the D-D interaction Triple Whammy.

Answer 5

1. NSAIDs cause vasoconstriction of the afferent arteriole.
2. ACEi cause efferent arteriole vasodilation.
3. Diuretics cause an initial increase in GFR but then later on GFR decreases due to reduced blood flow to the kidney caused by points 1 and 2.
   Collectively this can cause kidney damage and drying out of the nephron.

Question 6

Explain why osteoporosis occurs with SAIDs.

Answer 6

1. Decrease absorption of Ca2+ in GIT.
2. Leaching of Ca2+ from bones.
3. Increased cell death of osteoblasts.
4. Osteoclasts stay alive for longer causing a build up of old bone.
5. Increased cell death of osteocytes= not replacing main structure of bone.
   This all causes brittle bones= Osteoporosis.