NSAIDs Flashcards
Where is Arachidonic acid primarily derived from?
Dietary linoleic acid (vegetable oils converted hepatically to Arachidonic acid and incorporated into phospholipid membrane)
Arachidonic acid is found throughout the body, but in what in what 4 tissues/ organs mainly?
- Brain
- Muscle
- Liver
- Kidney
List 3 types of Prostanoids
- Prostaglandins
- Prostacyclins (E.g PGI2)
- Thromboxanes
Describe the production of Prostanoids
- Produced from Arachidonic acid via Cyclooxygenase pathways
- Produced locally on demand via different enzymes
What feature of Prostanoids allows their concentration to be finely controlled?
Short half lives
How do TXA2 and PGI2’s effects differ?
PGI2- Protective for CVS
TXA2- Bad for CVS (causes platelet aggregation and vasodilation)
Fine balance needed between them
Which Prostanoids are good for the stomach and how?
PGE2: Regulates acid secretion from Parietal cells
PGI2: Maintains blood flow and mucosal repair
Do Prostanoids act through GPCRs?
Yes
A diet rich in what can lead to conversion of TXA3 and PGI3 (healthier prostanoids) reducing CVD incidence?
Fish oils/ Omega fatty acids
Compare 2 functional isomers of COX enzymes
COX-1;
- Always active in most tissues
COX-2;
- Inducible (mostly) in chronic inflammation
- Always active in Brain + Kidney + Bone
(Possibly COX-3)
How do NSAIDs work?
Inhibition of COX by competing with Arachidonic acid
Thus reducing synthesis of Prostanoids
How do NSAIDs act as analgesics?
Inhibition of Prostaglandin synthesis reduced pain fibre sensitivity
How do NSAIDs act as anti-inflammatory agents
Reduces prostaglandin production-> Reduced vasodilation and oedema
List 4 ADRS of NSAIDs
- GI irritation & bleeding (peptic ulcers, perforation)
- Exacerbation of IBD
- Reversible drop in GFR and Renal Blood Flow
- Increased Na absorption-> Raised BP
List some DDIs of NSAIDs
Can all increase GI irritation, so may have to give a PPI;
- Aspirin
- Glucocorticoid steroids
- Anticoagulants
- ACEi, ARB, Diuretics