Regal- Prostaglandins, Thromboxane and NSAIDS Flashcards Preview

IHO Week 6 > Regal- Prostaglandins, Thromboxane and NSAIDS > Flashcards

Flashcards in Regal- Prostaglandins, Thromboxane and NSAIDS Deck (64)
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1

How are leukotrienes synthesized?

Phospholipase A2 cleaves membrane phospholipids into AA

5 LPO converts AA to 5HPETE then LTA4

2

What do LTC4 synthase or glutathione S transferase do to LTA4? What converts LTE4 to LTB4?

LTA4>
LTC4
LTD4
LTE4-->LTA hydrolase
LTB4

3

Where does LT synthesis occur?

Many cells and tissues

Predominately synthesized in leukocytes

4

What enzyme is associated w/ mast cells and basophils and what to they primarily make?

LTC4 synthase

peptido LTs

5

What enzyme is associated with endothelial cells and smooth muscle cells?

Glutathione S transferase

6

What are the 2 (4) types of leukotrienes?

LTB4

Peptidoleukotrienes
LTC4, LTD4, LTE4

7

How is LTB4 degraded?

Oxidized to inactive compound by enzymes in PMNs and others

8

What are the biological effects of LTB4?

Chemotactic for neutrophils
enhanced leukocyte adhesion

Decreased pain threshold--> hyperalgesia

9

What receptors does LTB4 target?

Non mentioned specifically but they're distinct from peptide LTs

10

How is LTE4 degraded?

It is excreted in urine or acetylated and excreted in bile

11

LTC4, LTD4, LTE4 act on what receptor?

Cys LTR1

Cyst LTCR2

12

Interaction of peptido leukotriens w/ LTR1 leads to...

increased vascular permeability-> swelling
chemotactic for eosinophils and cytokine secretion
bronchoconstriction
increased mucous production
DC maturation and migration
smooth muscle proliferation

13

Interaction of peptido leukotrienes w/ LTR2 leads to...

endothelial cell and macrophage activation

fibrosis

14

What two peptido leukotrienes are important in asthma?

LTC4
LTD4

15

What drugs are leukotriene modifiers?

Zileuton
Zafirlukast
Montelukast

16

What is the therapeutic use of leukotriene modifiers?

bronchial asthma

CHRONIC not acute

17

What is the MOA of zileuton?

Inhibits 5-LPO
prevents synthesis of LTB4 and peptido LT

18

How is zileuton eliminated?

M: cyp450

19

What are the toxicities associated with zileuton?

drug interactions
hepatic toxicity (req monitoring)

20

What is a unique property of zileuton related to asthma?

It can decrease the need for beta agonists in asthma

21

What is the MOA of zafirlukast and montelukast?

LTR antagonists (cys LTR1)

22

What is a toxicity associated w/ zafirlukast?

inhibits cyp450--> drug interactions

23

What is a unique property of montelukast?

it can be administered once daily w/out regard to meals

24

What are prostanoids?

PGD2
PGE2
PGF2
PGI2- prostacylcin
TXA2

25

How are prostanoids synthesized?

Phospholipase A2 cleave membrane bound phospholipids into AA>
Cox acts on platelets to form products

26

What cells produce cos?

numerous cells in response to different stimuli

27

Where is COX1 found?

platelets
constitutively expressed in most cells and is thought to protect mucosa

28

Where is cox 2 found? What products is it more involved inmaking?

not in platelets
inducible
more involved in production of PG and TXA in inflammation

29

How does enzyme expression of PG synthases influence the type of PG produced?

Platelets--> thromboxane (vasoconstrictor)

Endothelium--> prostacylcin (vasodilator)

Mast cells--> PGD2 (bronchoconstrictor)

30

How are prostanoids degraded?

spontaneous chemical hydrolysis or rapid enzyme degradation