Aspirin/NSAIDS Flashcards
What are the general indications for NSAIDS?
Pain Relief
Reduce Inflammation
Fever REduction
What are Aspiring specific indications?
Stroke/MI prevention
How do NSAIDs work?
Block COX enzymes -> prevent prostaglandin production -> dec inflammation, pain, fever
How do NSAIDs block COX enzymes?
All NSAIDS except Aspirin act as competitive inhibitors for the COX enzyme
Aspirin blocks as an irreversible non-competitive COX enzyme inhibitor via covalent modification of the active site
Where are COX1 enzymes found and what do they do?
Constitutively expressed in most tissues
General housekeeping role
Where are COX2 enzymes found and what do they do?
Induced in macrophages, monocyte
Constitutive in kidney and endothelium at low levels
Pro inflammatory responses
What are the housekeeping functions of COX1 in the GI tract?
PG production provides cytoprotective functions to stomach Dec acid secretion Inc gastric bicarb production Inc gastric mucous production Vasodilate-> gastric blood flow inc
How do NSAIDS reduce fever?
Blocking PG production and thus no action on CNS at the thermoregulatory center of the hypothalamus for fever
What are the housekeeping functions of COX1 i the CV system?
Platelets expresss only COX-1 => produce TXA2 (thromboxane) => vasoconstriction + platelet aggregation
Endothelial cells => COX1 and COX2 => no TXA2 synthase => produce PGI2 (prostacyclin) => vasodilation and inhibit platelet aggregation
Balance between the two can have differing results
What are hte functions of COX enzymes in the kidney?
Both COX1 and COX2 => PGs promote vasodilation to prevent renal ischemia
*Important in diseased state to counter vasoconstrictors
How can NSAIDs be used during labor?
It would delay it as PG production stimulates uterine contraction and NSAIDs would block this
What can happen if a women is treated with NSAID during pregnancy?
Premature closure of hte ductus arteriousus -> deleterious to fetal circulation
What can be done with patent ductus?
Treat with NSAID to inhibit fetal PGs that are keeping hte ductus open
How are Coxibs differnt from Aspirin/NSAIDs?
Coxib only inhibits COX-2
Why does aspirin block COX1 better than COX2?
COX2 has a larger binding site so it can partially bind arachidonic acid
How does aspirin block the COX enzymes?
Irreversibly acetylates a serine residue in the actie site
What is the unique indication for aspirin?
prophylactc prevention of CV events via low dose (81mg) aspirin
Why should you not give more aspirin for the protective CV effects?
At high doses the anti platelet effect of inhibiting TXA2 in platelets is offset by increased inhibition of PGI2 from the endothelium
Why don’t other NSAIDs show the same protective effects of low dose aspirin?
They are reversible inhibitors while aspirin is irreversible
How does low dose aspirin help treat CVD?
Aspirin acetylates COX1 in platelets permanently -> dec TXA2 (Platelets have no nucleus so more permanent)
Endothelial cells have nucleus -> COX1 inhibition is minimal -> produce PGI2
Result: More Anti thrombotic environment with PGI2>TXA2
What are some other salicylates and their unique properties?
Diflusinal: does not cross BBB -> no anti fever properties
Methyl Salicylate: bengay/icy hot
What kind of inhibitors are hte salicylates (except for aspirin)
Competitive inhibtor
When should salicylates be used over aspirin?
Pts at inc risk for GI problems or bleeding
Why do we see aspirin/salicylate toxicities?
At low dose its fine with 1st order kinetics
High dose -> metabolic enzymes in liver are overwhelmeed -> get 0 order kinetics
