NSAIDs Flashcards
This enzyme is responsible for the production of arachidonic acid (precursor to prostaglandins)
phospholipase A2
COX2 is generally inducible, but constitutively active in the following tissues:
kidney, female reproductive tract, and CNS
What enzymes convert PGH2 into biologically active prostanoids?
tissue-specific isomerases
effects of PGI2 (aka prostacyclin)
Inhibition of platelet aggregation, vasodilation, renin release (autoregulatory), natriuresis
effects of TXA2 (thromboxane)
vasoconstriction and promotion of platelet aggregation
Effects of PGE2 (‘classical’ prostaglandin’)
causes pain (via sensitisation of nociception neurons) and fever (through the hypothalamus), increases vascular permeability, + gastric effects (inhibits stomach acid secretion and promotes gastric cytoprotection, which is why NSAIDs that inhibit PGE2 can cause upset stomach)
Effects of PGF2alpha
uterine contraction, vaso- and bronchoconstriction
Effects of PGD2
same as PGI2 (vasodilation, bronchoconstriction, inhibition of platelet aggregation), except without the increased renin production
This NSAID irreversibly acetylates COX at Ser529, inhibiting prostanoid production
aspirin. All other NSAIDs function reversibly.
Why does aspirin function as an anti-platelet blood-thinning drug?
Its effect on platelets persists throughout their life, while endothelial cells which produce PGI2 can regenerate COX
Which drug causes Reye’s syndrome following viral infection in pediatrics?
aspirin
What is the treatment for hepatotoxicity caused by paracetamol + alcohol abuse?
N-acetyl cysteine (NAC) to replenish glutathione
Adverse effects of NSAIDs
-gastric upset due to lowered PGE2 levels
-Idiosyncratic pseudoallergic response (MRGPRX2-mediated)
-bleeding on aspirin
-aspirin-induced asthma (arachidonic acid is redirected to LOX –> leukotriene production)
-chronic (type C ADR) kidney defects
This is a COX2-selective inhibitor
celecoxib
These are NSAIDs apart from aspirin
paracetamol, ibuprofen, naproxen