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GI/Liver > Lec 10 Pharm Arachidonic > Flashcards

Lec 10 Pharm Arachidonic Flashcards

1
Q

Eicosanoids are products of what process?

A

oxygenation of polyunsaturated long chain fatty acids

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2
Q

What is the most abundant eicosanoid precursor?

A

arachidonic acid

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3
Q

What is path of eicosanoid synthesis?

A
  • arachidonic acid is released from membrane phospholipids by phospholipase A2 [PLA2]
  • arachidonic acid oxygenated to eicosanoid
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4
Q

What is action of phospholipase A2?

A

releases arachidonic acid from membrane phospholipids

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5
Q

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

A
  • Cyclooxygenase [COX]
  • Lipoxygenase
  • P450 epoxygenase
  • isoeicosanoid
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6
Q

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

A

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

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7
Q

Which prostaglandins/ thromboxanes are vasoconstrictors?

A
  • TXA2

- PGF2

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8
Q

Contraction of smooth muscle is mediated by what molec?

A

mediated by Ca

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9
Q

Relaxation of smooth muscle is mediated by what molec?

A

mediated by cAMP

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10
Q

Which prostaglandins/ thromboxanes are vasodilators?

A
  • PGI2

- PGE2

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11
Q

What is mech by which PGI2/PGE2 are vasodilators?

A
  • increase cAMP and decrease intracellular Ca in smooth muscle –> relaxation of smooth muscle
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12
Q

Where is PGI2 synthesized?

A

smooth muscle and endothelial cells

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13
Q

What type of drug inhibits phospholipase from releasing arachidonic acid?

A

steroids

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14
Q

What type of drug [s] inhibit cyclooxygenase path?

A
  • aspirin
  • indomethacin
  • Cox1/Cox2 inhibitors
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15
Q

What is another name for prostacyclin?

A

prostaglandin I2

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16
Q

What is general action of Cox1 path on GI?

A

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

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17
Q

Which Cox path is inducible?

A

Cox2 is inducible –> from pro inflammatory mediators

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18
Q

Which PG causes contraction of longitudinal and circular GI muscles?

A

PGF2

19
Q

Which PG causes relaxation of circular muscle?

A

PGE2

20
Q

What happens to GI if you administer PGE2/PGF2?

A

get colicky cramps

21
Q

Which PGs/TXs cause contraction of respiratory smooth muscle?

A

PGD2
TXA2
PGF2

22
Q

Which PGs/TXs cause relaxation of respiratory smooth muscle?

A

PGE2

PGI2

23
Q

What is effect of prostaglandins on platelet aggregation?

A

inhibit platelet aggregation

particularly PGE2, PGD2, PGI2

24
Q

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

A

thromboxane A2

directly enhances platelet aggregation

25
Q

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

A
  • vasodilate [mostly afferent arteriole] –> increase hydrostatic P in glomerulus –> increase GFR
  • stimulate renin release
26
Q

What is effect of TXA2 on kidneys/GFR?

A
  • vasoconstricts [mostly afferent arteriole] –> decrease GFR
27
Q

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

A

net effect is increase GFR

  • increase by PGI2/PGE2 way bigger than the decrease by TXA2
28
Q

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

A
  • decrease Na reabsorption from tubules –> increase Na excretion
  • attenuates ADH
  • overall decrease BP
29
Q

What is role of PGEs and neurotransmission?

A

PGEs inhibit release of NE from sympathetic postganglionic nerve endings

30
Q

What causes vasoconstriction see with COX inhibitors?

A
  • disinhibition of NE release

- inhibition of PGE2/PGI2 vasodilators normally synthesized in endothelium

31
Q

What is role of prostaglandins in pain?

A
  • spinal cord COX1/COX2 release prostaglandins when stimulated with pain
  • central pain sensitization by PGE2
  • peripheral nerve sensitization by PGE2/PGI2
32
Q

Which PGs/TXs cause inflammation?

A

PGE2 and PGI2

33
Q

What is effect of PGE2 on lymphocyte function?

A

PGE2 inhibits

  • humoral antibody response
  • cytotoxic T cell response
34
Q

What is effect of prostaglandins on the eye?

A

lower intraocular pressure

35
Q

What is effect of prostaglandins on cancer?

A

PGE2 aids initiation, progression, metastasis of tumors

36
Q

What are two main products of lipoxygenase path?

A
  • leukotrienes

- lipoxins

37
Q

Why could you get bronchospasm from NSAIDS?

A

NSAIDS block cox path –> get more of lypoxygenase path

leukotrienes cause bronchoconstriction

38
Q

What is main action of leukotriene C4?

A

bronchial constriction

39
Q

What is main action of leukotriene E4?

A

vasodilates

40
Q

What are main actions of TXA2?

A
  • platelet aggregation

- vasoconstriction

41
Q

What are main actions of PGE2?

A
  • vasodilator
  • smooth muscle relaxer
  • renal homeostasis: increase Na/H2O excretion, increase GFR, decrease BP
  • increase mucous/decrease acid in stomach
42
Q

What are main actions of PGI2?

A
  • vasodilator
  • inhibits platelet aggregation
  • renal homeostasis: increase Na/H2O excretion, increase GFR, decrease BP
43
Q

What is main action of PGD2?

A

sleep wake cycle

44
Q

What are main actions of PGF2?

A
  • constriction

- labour

GI/Liver (36 decks)

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