NSAIDs

Question 1

Arachidonic Acid pathways

Answer 1

3 pathways:

1. cyclo oxygenase pathway
2. lipoxygenase pathway
3. liver microsomal family CYP 450 enzymes

Question 2

AA

Answer 2

is a 20 polyunsaturated fatty acid and is normally found esterified to phospholipids in the cell membrane.

inflammatory stimulus will activate phospholipase A2 causing the release of AA from esterified position.

Question 3

products of AA pathways = eicosanoids

Answer 3

1. prostanoids
2. leukotrienes
3. EETs = epoxyeicosatrienoic acids

Question 4

prostanoids

Answer 4

3 to remember:

1. prostaglandins
2. TxA2 = thromboxane (causes platelet aggregation)
3. PGI2 = prostacyclin (prevents platelet aggregation)

Question 5

COX isoforms

Answer 5

COX 1 = good isoform (released for homeostasis regulation and housekeeping)
COX 2 = bad isoform (inducible during inflammation)

Question 6

COX - 2

Answer 6

is the drug target for new NSAIDs that are specific for COX 2 = coxibs

Question 7

COX enzyme catalytic functions

Answer 7

2 functions:
1. cyclo oxygenase function: the addition of molecular oxygen to AA to produce = prostaglandin G2

2. peroxidase function: where electrons are added i.e. reduction step to reduce prostaglandin G2 to —>
   parent prostaglandin H2

Question 8

COX isomerases acting on prostaglandin H2

Answer 8

TXA2 = thromboxane promotes platelet aggregation
PGI2 = prostacyclin prevents platelet aggregation
PGE2 + PGD2 = potent vasodilators
PGF2 = brings about uterine contraction in labour

Question 9

NSAID MOA

Answer 9

block prostanoid formation

DO NOT BLOCK prostanoid receptors directly but can bind to them acting as agonists of PPARs

many different types of prostanoid receptors but PPAR are an example of anti inflammatory receptors.

Question 10

PPAR

Answer 10

peroxisome proliferator activated receptors

Question 11

not true NSAIDs

Answer 11

aspirin and paracetamol