NSAIDS Flashcards
why are they used
analgesics
reduces fever in flu (anti-PYRETIC)
anti-inflammatory eg in inflammatory conditions
mechanism of NSAID’s
inhibit COX 1 and 2, thus arachidonic acid from phospholipid membranes can’t be converted into prostaglandin H2, so can’t be converted into prostacyclin/thromboxane A2/PGE2
unwanted effect of PGE2
increased pain perception, body temp, inflammation, tumorigenesis
main reason why NSAIDS used
PGE2 analogues
lower pain threshold
how PGE2 works
PGE2 is a prostanoid that acts on E1-4 receptors= increased cAMP= increased PKA= more activation of nociceptors
during inflammation, these nociceptors are recruited more
effect of PGE2 on body temp
pyrogenic- stimulates hypothalamic neurones to cause body temp rise, thus NSAIDS reduce temp
good effects of PGE2
bronchodilation
protects GI tract
renal water/salt homeostasis by increasing renal blood flow
vasoregulation ie constriction/dilation
respiratory effect of NSAIDS
should NOT be used by asthmatics, as COX inhibition= more leukotrienes= bronchoconstriction
gastric effect of NSAIDS and danger
increases ulceration risk, as COX 1 mediated PGE2 downregulates HCL, and upregulates HCO3-
thus half of deaths from NSAIDS due to GI ulcers
different forms of COX and importance
COX 1 selective, so bad at causing ulcers
CO2-selective NSAIDS like the COXIB family cause less ulcers
effect of NSAIDs on kidney
NSAIDS lower renal blood flow and GFR= increased salt/water retention
effects of NSAIDS on CVS
vasoconstriction, water retention and less effect of antihypetensives= half of death from NSAIDS due to CVD eg hypertension, Mi
problem with COX 2 inhibitors and mechanism
cause less ulcers, but increase CVS
due to more platelet activation/aggregation
overall issue with NSAIDS, with difference
all NSAIDS increase risk of GI bleeding/CVS events, but drugs inhibiting COX2 ie coxib family more CVS related, and vice versa for GI risk
risk vs benefit of NSAID use
occasional analgesic use ok, but for elderly patients using it for inflammatory conditions, risk of side effects greater due to chronic usage
how to stop GI side effects without COX 2 selective inhibitors
topical application, give NSAID with omeprazole (proton pump inhibitor stops HCL production), don’t give to patients with history of GI issues
effect of aspirin on COX
binds IRREVERSIBLY
effect of LOW DOSE aspirin on platelet aggregation
TXA2 made by COX1 by PLATELETS, prostacyclin made by both by ENDOTHELIAL CELLS
aspirin inhibits both, but because platelet has no nucleus, so TXA2 can’t be made, but prostacyclin can be made= less platelet aggregation
side effects of aspirin
worse than others due to its irreversible effect
reyes syndrome
younger ppl take aspirin and have a viral infection together, which can permanently damage mitochondria and lead to oedema
why is paracetamol NOT an NSAID
has all actions of NSAID, but NOT anti-inflammatory
effect of paracetamol overdose
leads to too much NAPQI, as glutathione enzyme depleted= NAPQI binds to SH groups= destruction of hepatic enzymes
how to treat paracetamol poisoning
intravenous acetylcesteine, which produces lots of SH groups for NAPQI to bind to
