Park lecture 6

Question 1

How is arachidonic acid released from the membranes

Answer 1

released from membrane phospholipids by phospholipase A (PLA)`

Question 2

How do corticosteroids suppress arachidonic acid

Answer 2

Corticosteroids inhibit PLA.

Question 3

What is the most abundant precursor of eicosanoids

Answer 3

Arachidonic acid

Question 4

2 end product of COX pathway

Answer 4

Thromboxanes
prostaglandins

Question 5

2 endproducts of lipoxygenase pathway

Answer 5

leukotrienes

Question 6

other names for PGH synthase 1 and 2

Answer 6

COX 1 and 2

Question 7

Difference between cox-1 and cox-1

Answer 7

cox 1 in constitutively expressed in the body, where as cox 2 is expressed upon stimulus in inflammatory and immune cells

Question 8

COX-1 action in stomach

Answer 8

COX 1 releases prostaglandins in stomach for acid protetction

Question 9

how does TXA affect blood vessels

Answer 9

Vasoconstrictor

Question 10

How does PGI affect the blood vessel

Answer 10

Potent vasodilator

Question 11

Difference between prostaglandins and thromboxanes

Answer 11

prostaglandins facilitate vasodilation, while thromboxanes are potent vasoconstrictors

Question 12

Name two prostaglandins

Answer 12

Alprostadil
Misoprostol (have (pro) in their name)

Question 13

What are the pharmacologic activities of NSAIDs

Answer 13

Anti-inflammatory
analgesic
anti-pyretic

Question 14

mechanism of action of NSAIDS

Answer 14

inhibit production of COX, which catalyze formation of prostaglandins, inhibits both COX-1 and2

Question 15

mechanism of gastric bleeding caused by NSAIDs

Answer 15

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

Question 16

Naproxen, Aspirin, indomethacin, suldinac rank in terms of how bad they are for GI

Answer 16

Aspirin-indomethacin, Naproxen, suldinac

Question 17

Why does a low dose of Aspirin reduce blood coagulation

Answer 17

Because aspirin can inhibit COX enzyme irreversibly

Question 18

Why is aspirin contraindicated before a surgery

Answer 18

Due to the the ability of aspirin to reduce blood coagulation

Question 19

Where do NSAIDs bind 90% of the time?

Answer 19

Serum albumin

Question 20

Why do NSAIDs have drug drug interactions

Answer 20

They comptete with other drugs for serum albumin

Question 21

What is reyes syndrome caused by and what are its symptoms

Answer 21

Reyes syndrome is caused when salicylates are given to a child below 12 with a fever (chicken pox, flu). It could cause brain damage

Question 22

Distinguish between Salicylates, arylacetic acids and arylpropinoic acid

Answer 22

arylpropinoic acids always have COOH
arylacetic acids always have CH2COOH

Question 23

What is the role of a-methyl group in structure activity

Answer 23

addition of a-methyl group enhances its activity and reduces many side effects

Question 24

difference in mechanism of action between acetaminophen and NSAIDs

Answer 24

Acetaminophen scavenges peroxynitrate that is required for PGH synthase activity
NSAIDs inhibit arachidonic acid from binding to PGHS

Question 25

What is the major oxidant for PGH synthase activity in CNS

Answer 25

peroxynitrite

Question 26

structural difference between COX-1 and COX-2

Answer 26

COX-1 has iso-leucine
COX-2 has valine

Question 27

Structural reason for selectivity of COX-2 inhibitors

Answer 27

COX-2 drugs exploit the larger binding area of COX-2.

Question 28

Why do COX-2 selective drugs increase the risk of heart attack

Answer 28

COX-2 is needed for PGI production. COX-1 is needed for TXA production, causing more blood clots