3 & 4 - NSAIDs Flashcards
What are the side effects of NSAIDs?
- GI irritation and bleeding
- Platelet dysfunction
- Kidney damage
- Bronchospasm
What are the therapeutic actions of NSAIDs?
1) Inhibit COX-1
2) Inhibit COX-2
When does COX-1 function?
On an “as-needed” basis
When is COX-2 over-expressed?
During injury, inflammation, and infection
What is cyclooxygenase the rate limiting enzyme for?
Biosynthesis of pro-inflammatory prostaglandins
What are the functions of various prostaglandins?
- PGD2, PGE2, PGI2, and PGF2a = pain transmission, inflammation, and fever
- TXA2 and PGI2 = modulation of platelet activity
- PGE2 and PGI2 = gastric acid secretion/cytoprotection
- PGE2 = renal blood flow
Prostaglandins are ____-like molecules
Lipid
In what part of the process do NSAIDs inhibit cyclooxygenase?
During the rate-limiting oxidative cyclization of arachidonic acid into hydroperoxy-endoperoxide PGG2, which is reduced to PGH2
What is the key intermediate needed for all prostaglandin biosynthesis?
PGH2
What are the key steps of biosynthesis of prostaglandins?
Phospholipids -> arachidonic acid -> PGG2 -> PGH2 -> PGD2/ PGE3/ PGF2a/ PGI2/ thromboxanes
What would blockade of PGH2 production cause?
Prevention of the down-stream production of resulting prostaglandin analogues
What does the 2 mean in prostaglandin E2?
of double bonds in the chain
What family do prostanoids and thromboxanes belong to?
Eicosanoids
How is arachidonic acid produced?
From linoleic and linolenic acid from plants through the human diet
What is important about the structure of prostaglandins?
Contain a bicyclic endoperoxide ring system
What do alpha and beta mean w/ respect to stereochemistry of functional groups?
- Alpha = down (into page)
- Beta = up (out of page)
Which prostaglandins are used in glaucoma?
Latanoprost and fluprostenol (23 and 49)