W1 6 NSAIDs Flashcards
(33 cards)
Give examples of NSAIDs
Ibuprofen, diclofenac, naproxen, piroxicam, aspirin, celecoxib
What is the general mechanism of NSAIDs?
NSAIDs inhibit production of certain eicosanoids = lipid derivatives
What are the 3 main categories of eicosanoids?
Prostaglandins (PGs) (prostanoids)
Thromboxanes (TX) (prostanoids)
Leukotrienes (LT)
(NSAIDs mainly affect PGs in their anti-inflammatory effect)
Describe the biosynthesis of prostanoids (PG52)
Enzyme PLA2 releases arachidonic acid from the cell membrane
COX converts arachidonic acid into intermediates = cyclic endoperoxides
Depending on the cell and enzymes present, you get a specific end-cell product:
- prostacyclin synthase is present in endothelial cells making prostacyclin
- thromboxane synthase is present in platelets producing TXA2
Do NSAIDs affect lipoxygenase or cyclooxygenase?
NSAIDs don’t directly affect lipoxygenase. Only affected if COX is inhibited and there is more arachidonic acid and thus potentially more production of leukotrienes from the lipoxygenase pathway.
(how do steroids affect the prostanoids pathway)
Increase expression of annexin1 which inhibits release of PLA2 so decreases free arachidonic acid
Decrease COX2 expression
What’s the difference between COX1 and COX2?
COX1 - constructive (most cells), produces prostanoids almost all the time
COX2 - inducible (inflammatory cells), produces prostanoids more when stimulated under inflammation
Where are the different end-products produced from?
PGI2 from endothelium
TXA2 from platelets
What are the primary actions of prostaglandins?
(All linked to inflammation)
Cause vasodilatation
Pyrexia - increased body temperature via action in hypothalamus
Pain
What are the non-inflammation related actions of PGs?
Prevent platelet aggregation, contraction of uterine smooth muscle, protects lining of stomach
What are the actions of thromboxanes?
Platelet aggregation, vasoconstriction
Which NSAIDs irreversibly inhibits COX1+2?
Aspirin
Which NSAID reversibly inhibits COX1+2?
Ibuprofen, diclofenac
Which NSAID is selective and inhibits COX2?
Celecoxib
What does paracetamol do?
Weakly inhibits COX in the presence of peroxides
(Peroxide levels high in inflammation and low in CNS)
Can have effect on canaboid receptors involved in pain pathways so beneficial for analgesia
What are the general effects of NSAIDs linked to the blockage of prostanoids?
Analgesia (esp musculoskeletal pain)
Reduced inflammation via less vasodilation
Reduced fever via reset of hypothalamus thermostat
When are NSAIDs used in dentistry?
Temperorary releif of mild/moderate dental pain/inflammation, I.e. 1-7 days until cause controlled
Ibuprofen, diclofenac, aspirin are effective
Is paracetamol an NSAID?
It is an analgesic and antipyretic, but has poor anti-inflammatory effect
What are the general side effects of NSAIDs?
- gastric irritation due to loss of protective PG in stomach lining (PGs decrease acid secretion and increase mucous)
- increased risk of cardiac arrest with ibuprofen and diclofenac
- hypersensitivity (asthma, rhinitis, urticaria, angioedema)
- decreased renal function
- renal necrosis following prolonged use
- prolonged gestation (due to loss of PG activity for labour - PG cause contraction)
When are NSAIDs contraindicated?
If hypersensitivity occurs, NSAIDs are contraindicated in future
(maybe more production of leukotrienes can cause constriction of airways)
Should you use NSAIDs in children and elderly?
OK in children (but not aspirin)
Caution in elderly (due to renal effects)
What does aspirin do?
Irreversibly inhibits COX1+2
What are the actions of aspirin?
Analgesic, antipyretic
Antiplatelet - important for ‘blood thinning’ to prevent clots
How does aspirin have an antiplatelet effect?
Platelets: produce TXA2 which aggregates platelets and causes vasoconstriction
Endothelium: produce PGI2 which inhibits aggregation of platelets and causes vasodilation
