Where are COX-1 found in? under what conditiona are they important? How about COX-2?
- many tissues, normal conditions
- inflammatory itissue, during inflammation
What is PGH-synthase 1? how is it expressed? What is PGH-synthase-2?
- COX-1, expressed constitutively
- cox2
What does PGH-synthase-2 depend on? Is it readily inducible?
readily inducible and depends on stimulus
Which channel is bigger, COX 1 or 2? What drug doesn’t act by entering the channel?
COX-2
aspirin
How do NSAIDs block COX 1,2 channels?
forming H-bonds w/ arg
What does aspirin do to COX1,2?
acetylates enzyme at Ser
Name a cox-1 inhibitor, name one for cox 2 inhibitor
- flurbiprofen
- celecoxib
What is an important target for anti-inflammatory agents?
A-A pathway
Are NSAIDs a chemically diverse group? Do NSAIDs work directly or indirectly on PGs?
yes
indirect
What is the timeline of the evoltion of the creation of aspirin?
Is aspirin antipyretic or pyretic?
Common uses for it?
salicin - salicylic acid - acetysalicyclic acid - aspirin
antipyretic
pain & fever
dosing of aspirin for adults (mg & hrs)
How much mg is low dose aspirin & what’s it used to help with?
- 325 to 650 mg every 4-6 hrs
- 81 mg for cardiovascular protection
Who’s aspirin SPECIFICALLY contradincicated for? why?
kids/teens with viral illness/infection - reyes syndrome - 20-40% mortality
give APAP instead, dialysis used to remove salicylates
Where does aspirin centrally effect? Does it inhibit or induce platelet aggregarion/clotting?
Why is it bad to take it with warfarin
antipyretic region of hypothalamus
inhibit - causes more bleeding
warfarin prevents platelet aggregation, increased risk of bleeding
In what patients is apirin very effective in? Are fevers pyretic or antipyretic? Through what are antipyretic effects of aspirin mediated through?
febrile patients
antipyretic
hypothalamus
What does aspirin help to treat?
headache, gout, rheumatic fever, and rheumatoid arhtritis
Once aspirin acts on the hypothalamus, what happens?
temp decreases (fever down), decreases pain
(inhibits PGE2 and PGF2a)
What happens to the respiratory cente when aspirin is administered at low or moderate doses?
increases ventilation (hyperventilation)
pH increases → respiratory alkalosis
What happens to the respiratory cente when aspirin is administered at high doses?
aspirin depresses the respiratory center.
decreases ventilation
decreases pH
acidosis
What happens to the cardiovascular system when aspirin is administered at a normal dose?
no effect
What happens to the cardiovascular system when aspirin is administered at a high dose?
blood vessel relax - vasodilation
What happens to the tissue when aspirin is administered?
decline in PGs - decreased inflammation
What happens to the blood when aspirin is administered?
decreased TXa2 - decreased platelet aggregation
What happens to the GI when aspirin is administered?
Decereased PGE2, 2a - decreased mucous - increased ulcer formation
What happens to the kidney when aspirin is administered?
decreased PGI2, blood flow, filtration, increased Na+/H20, increased swelling
