NSAIDs Flashcards
What compounds do NSAIDs work on?
COX-1
COX-2
What is the action of the COX enzymes?
Convert arachidonic acid to proteinoids
Where is COX-1 found?
Most tissues
Where is COX-2 found?
Active tissues
Inflamed tissues
What are the homeostatic functions of COX-1?
GI protection (acid + mucus)
Platelet aggregation
Vascular resistance
Renal blood flow
What are the homeostatic functions of COX-2?
Renal homeostasis
Tissue repair + healing
Reproduction (uterine contractions)
Inhibition of platelet aggregation
What are the pathological functions of COX-1?
Chronic inflammation
Chronic pain
Raised blood pressure
What are the pathological functions of COX-2?
Chronic inflammation
Chronic pain
Fever
Blood vessel permeability
What are the prostanoids?
PGE2 PGE2α PGD2 PGI2 TXA2
What is PGI2 also known as?
Prostacyclin
What is TXA2 also known as?
Thromboxane
What is the action of NSAIDs?
Competitive inhibition of COX enzymes -> reduction of prostanoid synthesis
What are the analgesic effects of NSAIDs?
Reduced PGE2 synthesis in dorsal horn
Reduced neurotransmitter release
Reduced excitability of neurones in pain relay
What are the anti-inflammatory effects of NSAIDs?
Reduction in prostaglandin synthesis
Decreased vasodilation
Decreased swelling
What are the antipyretic effects of NSAIDs?
Inhibition of hypothalamic COX-2
What is the order of selectivity? (COX-1 -> COX-2)
Aspirin Ibuprofen Naproxen Diclofenac Celecoxib Parecoxib Etoricoxib
What are the GI side effects of NSAIDs?
Decrease mucuc + HCO3
Increase acid secretion
Decrease mucosal blood flow
Nausea
Peptic ulceration
Exacerbate IBD
What are the renal side effects of NSAIDs?
Reduce GFR Increase creatinine Reduce renal medullary blood flow Increase salt + water retention Decrease renin secretion
Oedema
Hypertension
Hyperkalaemia
What are the CVS side effects of NSAIDs?
Increase salt + water retention
Vasoconstriction
Exacerbate HF
When are NSAIDs contraindicated?
Drugs
- sulphonylurea
- methotrexate
- warfarin
RA
Children <12 = Reye’s syndrome
What is paracetamol?
Non-NSAID, non opiate analgesic
What is the indication for paracetamol?
Mild to moderate pain
Fever
What is the mechanism of paracetamol?
COX-2 selective inhibition in spinal cord
What is NAPQI?
N-acetyl-p-benzoquinone imine
Minor oxidation product of paracetamol
