Eisosanoids

Question 1

Main eicosanoids

Answer 1

1. Prostaglandins (PGs)
2. Thromboxanes (TX)
3. Leukotrienes (LT)

Question 2

Functions of eicosanoids

General

Answer 2

Most potent regulators of cell function in nature and are produced by almost every cell in the body

Short lived local signaling hormones

Very restricted in the location in which they exert their effect…therefore

Affect the cell that produced it and/or nearby cells

Question 3

More specific functions of eicosanoids

Answer 3

1. Mediate inflammatory response
2. Blood coagulation
3. Elicit responses to inflammatory response…like pain, swelling, and fever
   —> if severe…allergic or hypersensitivity reaction
4. Regulate SmM contraction in intestine and uterus
5. Increase water and sodium excretion by the kidney…effecting the EC volume
6. Blood pressure (vasoconstrictors and dilators)
7. Bronchoconstriction and dilators

Question 4

What poly-unsat FA are eicosanoids derived from?

Answer 4

ARA (omega-6)

Which is found in the cell membrane esterified in membrane phospholipids at C2 of glycerol

It is derived from our diet or made from the essential FA linoleate

Question 5

Phospholipase A2

Answer 5

Activated when signal promotes eicosanoid production

Liberates ARA from membrane PLs

Question 6

What do glucocorticoids inhibit?

Answer 6

Phospholipase A2

Anti-inflammatory response…stops eicosanoid production

Question 7

3 major pathways ARA can be used for?

Answer 7

1/2. Prostaglandin or thromboxane
production

—> both via prostaglandin H2

3. Leukotriene production

Question 8

COX1 and COX2

Answer 8

Enzyme involved in Prostaglandin and TX production

ARA —> PGH2

Possesses cyclo-oxygenase and perodiase activities

Question 9

COX1

Answer 9

Expressed in almost all tissues and has normal physiologic functions

Question 10

COX2

Answer 10

Inducible in response to cytokines and GFs from activated immune and inflammatory cells

Therefore has activity due to more abnomral or pathologic functions

Question 11

Aspirin

Answer 11

Irreversibly acetylates and inhibits COX1/2

Minimizes PG symptoms

Side effects = upset stomach or ulcer formation

Question 12

Ibuprofen

Answer 12

Reversibly acetylate COX1/2

Reduces fever, body aches, swelling, redness and pain caused by PGs

Question 13

Acetaminophen

Answer 13

Reduce fever, aches and pain…but doesn not reduce inflammation

Milder in GI tract than IBF

Can be toxic to liver though

Question 14

Vioxx, bextra, and Celebrex

Answer 14

specific COX2 inhibitors produced without GI and antiplatelet side effects

And maintain COX1 function

Not safe anymore

Question 15

Thromboxane

Answer 15

Most common = TXA2

Potent promoter of vasoconstriction and platelet aggregation

Pathologic functions invulding thrombus formation and myocardial infacrction

Aspirin and COX inhibitors could block these pathologic functions…basis for lose does aspirin for people with history of heart disease

Question 16

Leukotriene production

Answer 16

Directly from ARA by

Lipoxygenases

Primarily mediate allergic response, vasoconstriction, bronchoconstriction and chemotaxis

NSAIDs can induce an asthmatic response in response to blocking PG and TX…thus making a overproduction of LTs