The acute phase (vasodilation, edema and pain). Corticosteroids affect all stages of inflammation.
In order to achieve an anti-inflammatory effect from an NSAID, how much of a greater dose do you need to give compared with just getting its anti-pyretic/analgesic effect?
~2x as much. These drugs are more effective at fever reduction and pain relief.
Under a low pH situation, will an acidic drug be charged or neutral?
It will be neutral -- it gets protonated aka loses its negative charge.
How do NSAIDs act as analgesics?
The inhibition of COX2 prevents the sensitization of nociceptors to pain. Unlike opioids, these do not alter sensory perception and are ineffective against certain types of pain.
How do NSAIDs get their anti-pyretic effect?
IL-1 will stimulate prostaglandin production which will raise temperature in the hypothalamus. NSAIDs inhibit this through COX-2.
What are NSAID's effects on platelets?
If you block COX-1, you block thromboxane which inhibits platelet aggregation.
Why would Cox-2 inhibitors increase aggregation via thromboxane?
COX-2 derived PGI2 inhibits platelet aggregation; if you block this, then you have increased aggregation from the COX-1 pathway.
Why are proteins esepcially sensitive to irreversible inhibition of COX by aspirin?
Platelets don't make new COX enzymes.
What is a biological antagonist to Ang II's vasoconstrictive effects?
Cox-2 derived PGI2; So if you inhibit COX-2, then you lose the vasodilatory effect of PGI2 and you get a slight raise in blood pressure from Ang II acting unopposed.
What are the effects of COX-2 derived PGs on atherosclerotic plaques?
On the 1 hand, inhibition of Cox-2 can slow development of atherosclerosis. On the other hand, COX-2 derived PGE2 can promote stabilization of plauqes; therefore inhibition by NSAIDs will elad to destabilization of plaques.
What are the important effects of COX-1 and 2 derived PGS on the kidneys?
PGE2 will decrease sodium resorption
PGI2 will increase potassium secretion, increase renal blood flow and GFR (elderly and volume depleted). Will lead to kidney ischemia in some cases
So - NSAIDs tend to promote sodium retention, peripheral edema and can therefore increase BP; counteracts the effects of many anti-hypertensives.