L11 - NSAIDs Flashcards
Eicosanoids
Prostanoids
Lipoxygenase
Prostanoids
Produced locally on demand with a short half life for fine control
PGE2
Secreted for gastrointestinal mucosal protection
PGI2 - prostacyclin
Inhibits platelet aggregation
Vasodilator
TXA2 - thromboxane A2
Platelet aggregation
Vasoconstrictor
Arachidonic acid
Derived primarily from dietary linoleic acid in vegetable oils and supplements
- converted hepatically into arachidonic acid and incorporated into phospholipids
- found through out the body - muscle, brain and liver
COX -1 homeostatic function
- active across most tissues
- platelets only contain COX 1 therefore platelet aggregation via TXA2
- gastrointestinal mucosal protection - PGE2
- vascular resistance - vasoconstriction- TXA2
COX 1 pathological function
Chronic inflammation
Chronic pain
Raised blood pressure - vasoconstriction THXA2
COX 2 homeostatic function
Inducibke mostly in the brain, kidney and bone
Renal homeostasis
Tissue repair and healing
Reproduction - uterine contractions
Inhibition of platelet aggregation - PGI2 (prostacyclin)
COX 2 pathological functions
Chronic inflammation Chronic pain Fever Blood vessel permeability Tumour cell growth
How do prostanoids exert their effects?
Action is local at GPCRs
Specific action dependent on receptor subtype and location
Imbalance between TXA2 and PGI2
TXA2 and PGI2 antagonise each other Imbalance can cause: - hypertension - MI - Stroke
Diet rich in fish oils (omega FAs)
Omega fatty acids are converted to TXA3 and PGI3
Better prostanoids with lower incidence of CVD
Effects of NSAIDs
Analgesic
Anti- inflammatory
Anti - pyretic
By inhibiting prostaglandins
NSAID mechanism of action
Inhibition of COX - competes with arachidonic acid for the hydrophobic site of COX
Decrease in prostanoids - prostaglandin, prostacyclin and thromboxane synthesis