Lec 10 Pharm Arachidonic

Question 1

Eicosanoids are products of what process?

Answer 1

oxygenation of polyunsaturated long chain fatty acids

Question 2

What is the most abundant eicosanoid precursor?

Answer 2

arachidonic acid

Question 3

What is path of eicosanoid synthesis?

Answer 3

• arachidonic acid is released from membrane phospholipids by phospholipase A2 [PLA2]
• arachidonic acid oxygenated to eicosanoid

Question 4

What is action of phospholipase A2?

Answer 4

releases arachidonic acid from membrane phospholipids

Question 5

What are the 4 paths arachidonic acid can take to become eicosanoid?

Answer 5

• Cyclooxygenase [COX]
• Lipoxygenase
• P450 epoxygenase
• isoeicosanoid

Question 6

Do eicosanoids act as autocrine, paracrine, and/or hormone?

Answer 6

autocrine and paracrine; not hormone b/c short half life

Question 7

Which prostaglandins/ thromboxanes are vasoconstrictors?

Answer 7

• TXA2

- PGF2

Question 8

Contraction of smooth muscle is mediated by what molec?

Answer 8

mediated by Ca

Question 9

Relaxation of smooth muscle is mediated by what molec?

Answer 9

mediated by cAMP

Question 10

Which prostaglandins/ thromboxanes are vasodilators?

Answer 10

• PGI2

- PGE2

Question 11

What is mech by which PGI2/PGE2 are vasodilators?

Answer 11

• increase cAMP and decrease intracellular Ca in smooth muscle –> relaxation of smooth muscle

Question 12

Where is PGI2 synthesized?

Answer 12

smooth muscle and endothelial cells

Question 13

What type of drug inhibits phospholipase from releasing arachidonic acid?

Answer 13

steroids

Question 14

What type of drug [s] inhibit cyclooxygenase path?

Answer 14

• aspirin
• indomethacin
• Cox1/Cox2 inhibitors

Question 15

What is another name for prostacyclin?

Answer 15

prostaglandin I2

Question 16

What is general action of Cox1 path on GI?

Answer 16

more productive for GI
- increase mucous; decrease acid
regulate body temp

Question 17

Which Cox path is inducible?

Answer 17

Cox2 is inducible –> from pro inflammatory mediators

Question 18

Which PG causes contraction of longitudinal and circular GI muscles?

Answer 18

PGF2

Question 19

Which PG causes relaxation of circular muscle?

Answer 19

PGE2

Question 20

What happens to GI if you administer PGE2/PGF2?

Answer 20

get colicky cramps

Question 21

Which PGs/TXs cause contraction of respiratory smooth muscle?

Answer 21

PGD2
TXA2
PGF2

Question 22

Which PGs/TXs cause relaxation of respiratory smooth muscle?

Answer 22

PGE2

PGI2

Question 23

What is effect of prostaglandins on platelet aggregation?

Answer 23

inhibit platelet aggregation

particularly PGE2, PGD2, PGI2

Question 24

What is the only COX isoform expressed in mature platelets? action?

Answer 24

thromboxane A2

directly enhances platelet aggregation

Question 25

What is effect of PGI2/PGE2 on kidneys/GFR?

Answer 25

- vasodilate [mostly afferent arteriole] --> increase hydrostatic P in glomerulus --> increase GFR - stimulate renin release

Question 26

What is effect of TXA2 on kidneys/GFR?

Answer 26

- vasoconstricts [mostly afferent arteriole] --> decrease GFR

Question 27

What is net effect of eicosanoids [PGs + TXs] on GFR?

Answer 27

net effect is increase GFR - increase by PGI2/PGE2 way bigger than the decrease by TXA2

Question 28

What is PGE2/PGI2 effect on Na/water regulation? Effect on BP overall?

Answer 28

- decrease Na reabsorption from tubules --> increase Na excretion - attenuates ADH - overall decrease BP

Question 29

What is role of PGEs and neurotransmission?

Answer 29

PGEs inhibit release of NE from sympathetic postganglionic nerve endings

Question 30

What causes vasoconstriction see with COX inhibitors?

Answer 30

- disinhibition of NE release | - inhibition of PGE2/PGI2 vasodilators normally synthesized in endothelium

Question 31

What is role of prostaglandins in pain?

Answer 31

- spinal cord COX1/COX2 release prostaglandins when stimulated with pain - central pain sensitization by PGE2 - peripheral nerve sensitization by PGE2/PGI2

Question 32

Which PGs/TXs cause inflammation?

Answer 32

PGE2 and PGI2

Question 33

What is effect of PGE2 on lymphocyte function?

Answer 33

PGE2 inhibits - humoral antibody response - cytotoxic T cell response

Question 34

What is effect of prostaglandins on the eye?

Answer 34

lower intraocular pressure

Question 35

What is effect of prostaglandins on cancer?

Answer 35

PGE2 aids initiation, progression, metastasis of tumors

Question 36

What are two main products of lipoxygenase path?

Answer 36

- leukotrienes | - lipoxins

Question 37

Why could you get bronchospasm from NSAIDS?

Answer 37

NSAIDS block cox path --> get more of lypoxygenase path leukotrienes cause bronchoconstriction

Question 38

What is main action of leukotriene C4?

Answer 38

bronchial constriction

Question 39

What is main action of leukotriene E4?

Answer 39

vasodilates

Question 40

What are main actions of TXA2?

Answer 40

- platelet aggregation | - vasoconstriction

Question 41

What are main actions of PGE2?

Answer 41

- vasodilator - smooth muscle relaxer - renal homeostasis: increase Na/H2O excretion, increase GFR, decrease BP - increase mucous/decrease acid in stomach

Question 42

What are main actions of PGI2?

Answer 42

- vasodilator - inhibits platelet aggregation - renal homeostasis: increase Na/H2O excretion, increase GFR, decrease BP

Question 43

What is main action of PGD2?

Answer 43

sleep wake cycle

Question 44

What are main actions of PGF2?

Answer 44

- constriction | - labour