Unit 2 - F. Eicosanoids

Question 1

Eicosanoids

Answer 1

- majority are synthesized from arachidonic acid and are mediators that can cause inappropriate/exaggerated inflammatory process
3 subfamilies:
1. Prostaglandins (PG) = COX synthesis
2. Thromboxanes (TX) = COX synthesis
3. Leukotrienes (LT) = LOX synthesis

Question 2

Prostaglandins

Answer 2

• short lived, produced in small amounts, not really stored

- act like hormones but are limited to near by cells

Question 3

Functions of Prostaglandins

Answer 3

1. protective effects on GI by decreasing secretion of hydrochloric acid and increasing secretion of mucous from parietal cells
2. potent vasodilator in blood vessels and inhibitor of platelet aggregation = myocardial protection
3. regulates kidney function by maintaining blood flow and increasing sodium ion re-absorption

Question 4

Leukotrienes

Answer 4

• synthesized in white blood cells and other body tissue

- cysteinyl leukotrienes = LTC4, LTD4, LTE4

Question 5

Functions of Leukotrienes

Answer 5

• cause contraction of smooth muscle, vasoconstriction, bronchoconstriction, and increase in vascular permeability
• SRS-A = slow reacting substance - anaphylaxis = severe allergic reaction, inflammation, and asthmatic episodes

Question 6

Thromboxanes

Answer 6

TXA2 = synthesized in platelets. Promote platelet aggregation and induce smooth muscle contraction (vascular and respiratory) - powerful vasoconstrictor

TXB2 = biologically inactive; results from hydrolysis of TXA2

TXA3 = weak vasoconstrictor

Question 7

Drugs affecting eicosanoid biosynthesis

Answer 7

• glucocorticoids / corticosteroids
• NSAIDS
• Leutriene drugs
• classic COX inhibitors
• COX-2 inhibitors

Question 8

glucocorticoids / corticosteroids

Answer 8

• decreases production of phospholipase A2 which reduces release of Arachidonic acid

Question 9

NSAIDS

Answer 9

• inhibit cycloxygenase (COX) enzymes which inhibits prostaglandin and thromboxane synthesis

Question 10

Leukotriene drugs

Answer 10

• inhibit lipoxygenase which inhibits leukotriene synthesis or acts as receptor antagonist

Question 11

Classic COX inhibitors

Answer 11

• inhibits COX-1 and COX-2
• COX-1 (good) inhibition can lead to altered environment in stomach = upset stomach, heartburn, and GI bleeding (ex. asprin and Ibuprofen)

Question 12

COX-2 inhibitors

Answer 12

• inhibits only COX-2 (bad) but if taken over 18 months can lead to increase risk of MI (ex. Celebrex, Vioxx, Bextra)