NSAIDS Flashcards
Arachidonic acid
essential fatty acids
most abundant and important precursor of eicosanoids
released from the membrane phospholipids by PLA2
corticosteroids suppresses the productions PLA2
Oxygenation of arachidonic acid
COX: prostaglandins and thromboxanes
Lipoxygenase: Leukotrienes
Epoxygenase: epoxides
Free radicals: isoprostanes
PGH synthase
both cyclooxygenase and hyper peroxidase activities
COX reactions requires a free radical
Hydroperoxidase reaction converts OOH to OH
COX 1 vs. COX 2
COX 1 is expressed in various tissues
Housekeeping function
COX 2 is expressed upon stimulus in inflammatory and immune cells
stimulated by GF, tumor promoters, and cytokines
Inhibited by NSAIDS
Prostaglandins vs. Thromboxanes
PGI2: vascular epithelia, vasodilator, blocks platelet aggregation
TXA2: platelets, vasoconstrictor, induce platelet aggregation
Mechanism of action of NSAIDs
inhibitor of PGHs or COX which catalyzes the production of prostaglandins
Salicylates
aspirin
Arylacetic acids
indomethacin
Arylproprionic acids
ibuprofen
Non-carboxylate NSAIDs
meloxicam
COX-2 selective NSAIDs
celecoxib
Side effects of NSAIDs
dyspepsia, nausea, vomiting
blood loss, ulcer, GI hemorrhage
Blood coagulation
renal
hypersensitivity
Reye’s syndrome: specific to aspirin
CNS
Aspirin
only NSAID that irreversibly inhibits COX 1 by acetylating a serine residue in the active site
Blocks TXA2; increases the risk of bleeding but also reduces the risk of MI
Selective COX 2 inhibitors
valine binding site of COX2 is sunsituted for isoleucine in that of COX1
