NSAIDS

Question 1

why are they used

Answer 1

analgesics

reduces fever in flu (anti-PYRETIC)

anti-inflammatory eg in inflammatory conditions

Question 2

mechanism of NSAID’s

Answer 2

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

Question 3

unwanted effect of PGE2

Answer 3

increased pain perception, body temp, inflammation, tumorigenesis

main reason why NSAIDS used

Question 4

PGE2 analogues

Answer 4

lower pain threshold

Question 5

how PGE2 works

Answer 5

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

Question 6

effect of PGE2 on body temp

Answer 6

pyrogenic- stimulates hypothalamic neurones to cause body temp rise, thus NSAIDS reduce temp

Question 7

good effects of PGE2

Answer 7

bronchodilation

protects GI tract

renal water/salt homeostasis by increasing renal blood flow

vasoregulation ie constriction/dilation

Question 8

respiratory effect of NSAIDS

Answer 8

should NOT be used by asthmatics, as COX inhibition= more leukotrienes= bronchoconstriction

Question 9

gastric effect of NSAIDS and danger

Answer 9

increases ulceration risk, as COX 1 mediated PGE2 downregulates HCL, and upregulates HCO3-

thus half of deaths from NSAIDS due to GI ulcers

Question 10

different forms of COX and importance

Answer 10

COX 1 selective, so bad at causing ulcers

CO2-selective NSAIDS like the COXIB family cause less ulcers

Question 11

effect of NSAIDs on kidney

Answer 11

NSAIDS lower renal blood flow and GFR= increased salt/water retention

Question 12

effects of NSAIDS on CVS

Answer 12

vasoconstriction, water retention and less effect of antihypetensives= half of death from NSAIDS due to CVD eg hypertension, Mi

Question 13

problem with COX 2 inhibitors and mechanism

Answer 13

cause less ulcers, but increase CVS

due to more platelet activation/aggregation

Question 14

overall issue with NSAIDS, with difference

Answer 14

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

Question 15

risk vs benefit of NSAID use

Answer 15

occasional analgesic use ok, but for elderly patients using it for inflammatory conditions, risk of side effects greater due to chronic usage

Question 16

how to stop GI side effects without COX 2 selective inhibitors

Answer 16

topical application, give NSAID with omeprazole (proton pump inhibitor stops HCL production), don’t give to patients with history of GI issues

Question 17

effect of aspirin on COX

Answer 17

binds IRREVERSIBLY

Question 18

effect of LOW DOSE aspirin on platelet aggregation

Answer 18

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

Question 19

side effects of aspirin

Answer 19

worse than others due to its irreversible effect

Question 20

reyes syndrome

Answer 20

younger ppl take aspirin and have a viral infection together, which can permanently damage mitochondria and lead to oedema

Question 21

why is paracetamol NOT an NSAID

Answer 21

has all actions of NSAID, but NOT anti-inflammatory

Question 22

effect of paracetamol overdose

Answer 22

leads to too much NAPQI, as glutathione enzyme depleted= NAPQI binds to SH groups= destruction of hepatic enzymes

Question 23

how to treat paracetamol poisoning

Answer 23

intravenous acetylcesteine, which produces lots of SH groups for NAPQI to bind to