Summary Pharmacokinetics explained

NSAIDS inhibit COX, thereby inhibiting prostaglandin synthesis

SALICYLIC ACID PROPIONIC ACID OTHERS SELECTIVE COX-2 ANALGESIC
DERIVATIVES DERIVATIVES INHIBITORS ONLY

 Aspirin  Ibuprofen  Diclofenac  Etoricoxib
 Naproxen  Indomethacin  Celecoxib  Paracetamo
 Nabumetone  Lumiracoxib l




Mechanism of action:



ANALGESIC action

 Peripheral actions predominate
 Associated with anti-inflammatory action
 Results from inhibition of prostaglandin synthesis in inflamed tissues
 Prostaglandins potentiate the pain caused by inflammatory mediators

Anti-inflammatory action:

 Attenuates inflammation (NOT abolish)
 Rheumatoid arthritis
 Not alter the course of the disease

Anti-pyretic action:

 Aspirin prevents temperature-raising effects of IL-1
 Prevent ↑ in brain prostaglandins levels

On COX:

 Enzymes with a long channel (wider in COX2)
 Block the channel by binding to arginine halfway down (hydrogen bonds)
 Reversibly inhibits enzyme by preventing access of arachidonic acid
 Aspirin acetylates enzyme at serine 530 (irreversible)



PARACETAMOL:

 ↓ Cytoplasmic peroxide tone
 Peroxide: activate haem enzyme  ferryl form