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Flashcards in Santanam Deck (47):
1

Arachidonic acid is cleaved from membrane phospholipid by what

PLA2

PLC - specifically cleaves phosphatidylinositides, also requires Diglyceride lipase to get to AA

2

what are eicosanoids

oxygenated products of polyUNsaturated FAs

3

What affects the function of eicosanoids

nature of the precursor fatty acids

4

TXA2 vs TXA3

TXA2 - vasoconstrictor
TXA3 - inactive

5

What is prostaglandin synthetase

Enzyme complex of:

- COX
- Peroxidase

6

Which COX is constitutive? Inducible?

COX-1 : Constitutive
COX-2 : Inducible

7

Where do you find COX-1

BV, stomach, kidney

8

What is COX-2 involved with?

Inflammation

9

What causes elevation of COX-2

Inflammation and cytokines

10

What is the effect of glucocorticoids on COX-2?

Decreased COX-2 activity

11

Mechanism of Action: Prostaglandins

1. Acts locally: paracrine, autocrine - short half life
2. Interacting with a receptor (GPCRs) ***

12

What happens after Prostaglandins bind receptor?

Inc or dec of adenylate cyclase

stimulation of phosphatidylinositol

13

Where is the major effect of prostaglandins seen? name the four types/areas

Smooth muscle: vascular, GI, airway, and reproductive

14

Which enzyme is involved with the linear pathway

Lipoxygenase

15

Which enzyme is involved with the cyclic pathway

PGH synthetase

16

In the COX pathway, what is the resulting product of action of COX on AA?

Unstable endoperoxide (PGG2)

17

What is the action of peroxidase in COX pathway?

C15 hydroperoxide (PGG2) --> C15 hydroxyl group (PGH2)

18

What are the four products of COX pathway? what is the intermediate for all four?

- TXA2
- PGI2
- PGE2
- PGF2a

Intermediate: PGH2 with hydroxyl group

19

Where is COX-2 constitutively expressed?

Brain and kidney

20

What does COX-1 protect against? how?

HCl via increase in stomach mucus

21

What is a common side effect of COX-1 inhibition?

GI ulcers

(dec stomach mucus, more susceptible to damage due to HCl in stomach)

22

Effect of prostacyclin on:

Vascular:
Airway:
GI:
Reproductive:
Pain:

- Vasodilator and Inhibit platelet aggregation
- Bronchodilator
- Inhibit gastric acid secretion, increased mucus secretion
- Relaxes uterine muscle
- Induces pain

23

Effect of Prostaglandin on:

Vascular:
Airway:
GI:
Reproductive:
Pain:

Vascular, Airway, GI, pain: same as prostacyclin

CONTRACTS uterine smooth muscle - low conc
relaxes in high conc

24

What is the effect of prostaglandins on fever?

Direct pyrogen in hypothalamus

25

What cytokine stimulates PGE2?

IL-1

26

Effect of Thromboxane on:

Vascular:
Airway:
Reproductive:

- Vasoconstrictor and stimulates Platelet aggregation
- Bronchoconstrictor
- Uterine contraction

27

What is major product of platelet COX-1? COX-2?

Thromboxane

Prostacyclin

28

Effect of Prostaglandin F2a on:

Vascular:
Airway:
Reproductive:

- Vasoconstrictor
- Bronchoconstrictor
- Contracts uterine muscle

29

What effect does PGF2a have on the eye?

Decreases intraocular pressure

30

What is PGF2a used to treat? What is defective in this disease?

Glaucoma
loss of COX-2

31

What keeps DA open in fetus?

PGE2/1 and PGI2

32

What happens to DA after birth?

Closes because of decreased PGE2/1, PGI2

33

What is used to keep DA open in cyanotic heart disease?

Alprostadil via IV infusion

34

What is used to close DA?

Indomethacin

35

What specific enzyme is used in the lipoxygenase pathway?

5-lipoxygenase

36

What is the intermediate in LOX pathway?

5-HETE

37

Name two chemotactic agents for PMN, Eosinophils, monocytes formed in the linear pathway

- 5-HETE
- LTB4

38

What does LTE4 (LTC4, LTD4) do?

Potent bronchoconstrictor
Inc vascular permeability
Components of slow reacting substance of anaphylaxis

39

What are LTE4, LTC4, LTD4 known as

Cysteinyl leukotrienes

40

What is the side group on 5-HETE and what is it converted to by ______ to LTA4?

5-hydroperoxide to 5,6-epoxide by Dehydrase

41

What enzyme converts LTA4 to Cysteinyl leukotrienes

Glutathione-S-transferase

42

What enzyme converts LTA4 to LTB4?

Hydrolase

43

What is the LOX pathway associated with?

Asthma, anaphylactic shock, CVD

44

Which leukotriene produces hyperalgesia

LTB4

45

Which leukotrienes are chemoattractants for eosinophils?

Cysteinyl leukotrienes

46

What is FLAP?

5-LOX activated protein

47

Which receptor does Zafirlukast, Montelukast antagonize?

Cys-LT1 (LTD4)