Park lecture 6 Flashcards
How is arachidonic acid released from the membranes
released from membrane phospholipids by phospholipase A (PLA)`
How do corticosteroids suppress arachidonic acid
Corticosteroids inhibit PLA.
What is the most abundant precursor of eicosanoids
Arachidonic acid
2 end product of COX pathway
Thromboxanes
prostaglandins
2 endproducts of lipoxygenase pathway
leukotrienes
other names for PGH synthase 1 and 2
COX 1 and 2
Difference between cox-1 and cox-1
cox 1 in constitutively expressed in the body, where as cox 2 is expressed upon stimulus in inflammatory and immune cells
COX-1 action in stomach
COX 1 releases prostaglandins in stomach for acid protetction
how does TXA affect blood vessels
Vasoconstrictor
How does PGI affect the blood vessel
Potent vasodilator
Difference between prostaglandins and thromboxanes
prostaglandins facilitate vasodilation, while thromboxanes are potent vasoconstrictors
Name two prostaglandins
Alprostadil
Misoprostol (have (pro) in their name)
What are the pharmacologic activities of NSAIDs
Anti-inflammatory
analgesic
anti-pyretic
mechanism of action of NSAIDS
inhibit production of COX, which catalyze formation of prostaglandins, inhibits both COX-1 and2
mechanism of gastric bleeding caused by NSAIDs
Two insults, primary and secondary.
primary- acidity of NSAIDs
Secondary insult- NSAIDs inhibit production of cytoprotective prostaglandins (PGEs) in gastric mucosa,
NSAIDs alsoinhibit platelet aggregation, increasing bleeding
Naproxen, Aspirin, indomethacin, suldinac rank in terms of how bad they are for GI
Aspirin-indomethacin, Naproxen, suldinac
Why does a low dose of Aspirin reduce blood coagulation
Because aspirin can inhibit COX enzyme irreversibly
Why is aspirin contraindicated before a surgery
Due to the the ability of aspirin to reduce blood coagulation
Where do NSAIDs bind 90% of the time?
Serum albumin
Why do NSAIDs have drug drug interactions
They comptete with other drugs for serum albumin
What is reyes syndrome caused by and what are its symptoms
Reyes syndrome is caused when salicylates are given to a child below 12 with a fever (chicken pox, flu). It could cause brain damage
Distinguish between Salicylates, arylacetic acids and arylpropinoic acid
arylpropinoic acids always have COOH
arylacetic acids always have CH2COOH
What is the role of a-methyl group in structure activity
addition of a-methyl group enhances its activity and reduces many side effects
difference in mechanism of action between acetaminophen and NSAIDs
Acetaminophen scavenges peroxynitrate that is required for PGH synthase activity
NSAIDs inhibit arachidonic acid from binding to PGHS
What is the major oxidant for PGH synthase activity in CNS
peroxynitrite
structural difference between COX-1 and COX-2
COX-1 has iso-leucine
COX-2 has valine
Structural reason for selectivity of COX-2 inhibitors
COX-2 drugs exploit the larger binding area of COX-2.
Why do COX-2 selective drugs increase the risk of heart attack
COX-2 is needed for PGI production. COX-1 is needed for TXA production, causing more blood clots
