Lipid Mediators Of Inflammation

Question 1

What does eicosanoids branch into?

Answer 1

Cyclooxygenases and lipoxyoxygenase.

Cyclooxygenase are prostaglandins and thromboxanes

Lypooxygenases are leukotrines and Lipoxanes

Question 2

Why is eicosanoids important?

Answer 2

Eicosanoids are molecules with powerful inflammatory actions. They are also targets for major anti inflammatory drugs.

Question 3

What are major anti inflammatory drugs?

Answer 3

NSAIDS
Glucocorticoids
Lip oxygenate inhibitors
Leukotriene inhibitors

Question 4

What is he rate limiting step of prostanoids?

How is it made?

Answer 4

The production of archidonic acids.

AA are made from phospholipids via a 1 step or the two step pathways.

Question 5

What is the one step pathway the produce AA?

Answer 5

Phospholipids are made in AA via pospholipase A2

Question 6

What is the two step method of making AA?

Answer 6

First of phospholipids can undergo two pathways, either via phospholipids C or phospholipids D. Which converts it into diaclglycerol or phosphatidic acid then uses DAG lipase or phospholipids A2 to convert into AA

Question 7

What are the initiators of the AA cascade?

Answer 7

Bradykinin and adrenaline are, they are known to initiate the action of phospholipse at the cell membrane.

Question 8

How to make cyclooxygenase /prostanoids?

Answer 8

Conversion of AA to prostanoids require enzyme cyclooxygenase aka cox. There are two types of cox protein cox 1 and cox 2

Question 9

What is cox made out of

Answer 9

Cox are fatty acids that are attached to endoplasmix membranes

Question 10

What is cox one and what does it do?

Answer 10

Cox one is always active and is responsible for the physiological effects of prostaglandins and thromboxanes such as the regulation of peripheral vascular resistance, renal blood flow, platelet aggregation and gastric protection.

Question 11

What is cox 2 and what does it do?

Answer 11

Cox 2 needs to be stimulated be things such as inflammatory cytokines for example interleukine 1 and tumour necrosis factor alpha. Cox 2 is also responsible for the inflammatory effects of prostaglandins and thromboxanes such as fever and pain.

Question 12

What is cox 3?

Answer 12

Cox 3 is a variant of cox 1 which is involved with pin perception of CNS

Question 13

What happens when cyclooxygenase acts on archidonic acids?

Answer 13

It produces prostaglandin endopeoxides such as PGG2 and PGH2.

PGH2 have a short half life of 30 minutes, after which it turns into PGI2 aka prostacyclin.

Question 14

What is prostacyclin?

Answer 14

Prostacyclin are anti-coagulating prostaglandins. It is made via prostacyclin synthase

Question 15

Which prostanoids are known bronchoconstrictors?

Answer 15

PGF2-alpha is a know bronchoconstrictor and uterine contractor

PGD2 is another.

Question 16

What are classical prostaglandins?

Answer 16

PGD2
PGF2-alpha
PGE2

Question 17

What is thromboxane A2

Answer 17

It is a important platelet aggregator

It is used against PGI2 to form an balance and control platelet aggregation.

Question 18

How does the lipooxygenase pathways start from AA and end at LTB5

Answer 18

AA is Forst converted into 5HPETE. Enzyme involved in this reaction is 5-lipooxygenase

The same enzyme then converts 5HPETE into leukotrine A4

Leukotrine A4 is then converted into LTB4 which is a potent chemoattractant and is used to pull molecules to the site of injury.

Question 19

What does LTA4 gets made into sulphidopeptides? And what is it?

Answer 19

Sulphidopeptide leukotrine are made via glutathione via LTA4.
Examples are LTC4, LTD4 and LTE4, these are slow reacting substances of anaphylaxis (SRSA), they are very potent mediators of inflammation that causes thick mucus secretion.

Question 20

What are anti-inflammatory lipid mediators?

Answer 20

They are Lipoxanes and CyPG (cyclopenteone prostaglandins)

There is a switch for PG synthase from pro-inflammatory at onset of inflammation to anti-inflammatory Lipoxins and CyPGs during resolution.

Question 21

What does Lipoxins don?

Answer 21

They recruit monocytes to clear inflamed site of necrotic apoptotic neutrophils

They regulate the activation levels of neutrophils and dampens their damaging effects … E.g. Increase phagocytosis of neutrophils.

Question 22

How does CyPGs work?

Answer 22

They inhibit macrophage activation which lead to a decrease in uncontrolled tissue damage.

Question 23

Which cells specialise in making particular eicosanoids?

Answer 23

Mast cells make PGD2
Platelets make TXA2
Endothelial cells make PGI2 and PGE2

Question 24

What are prostaglandin subs type receptors?

Answer 24

They act at DP, FP, IP and EPC1-3

Txt and at TP receptors

Question 25

What are leukotriene receptors?

Answer 25

LTB4 acts at BLT receptors; LTC/D/E4 act at cys Lt receptors these are chemotactic and bronchoconstrictors as well as increase vascular permeability. They cause oedema and increase in secretion of thick viscous mucus.

Question 26

What does DP receptor do?

Answer 26

DP cause vasodilation, decrease in platelet aggregation and bronchoconstriction.

Question 27

What does FP receptor do?

Answer 27

They cause myomere oak contraction in uterus aka bronchoconstriction

Question 28

What does IP receptors do?

Answer 28

IP receptor cause vasodilation, decrease in platelet aggregation and renin release.

Question 29

What does EP1 receptor do?

Answer 29

It cause contraction of bronchioles and GIT sloth muscles

Question 30

What does EP2 receptor do?

Answer 30

It cause bronchodilator, vasodilation, relaxation of GIT smooth muscle and increase in intestinal fluid secretion

Question 31

What does EP3 receptors do?

Answer 31

Induce contraction of intestinal smooth muscle and increase gastric mucus secretion. They can also reduce gastric acid secretion and pyrexia.

Question 32

What does thromboxanes do?

Answer 32

They mainly have vascular effects, TP receptors cause vasoconstriction and increased platelet aggregation.

Question 33

What does leukotrienes do in acute allergy response?

Answer 33

They cause enteral inflammation and lung vascular response BLT1 and 2 receptor cause chemotactic and proliferation of immune cells and increased adhesion. Cys LT1 and 2 receptors cause bronchoconstriction, vasodilation and increase vascular permeability

Question 34

What are leukotrienes receptor antagonists?

Answer 34

``` Zafirlukast Montelukast Pranlukast Zileuton They block receptors for cysLT so LTC-E ``` these leukotrienes cause airway oedema, secretion of thick mucus and smooth muscle contraction

Question 35

What are pranlukast useful for?

Answer 35

Is useful in prevention of mild to moderate asthma, it is also useful to treat early to late bronchoconstriction effects of allergens It is also useful in treating exercise induced asthma and asthma provoked NSAIDS

Question 36

What are side effects of monteleukast

Answer 36

GI upset, dry mouth, thirst, rashes and oedema

Question 37

Is histamine more potent as bronchospasm than LTE4, LTC4 and LTD4?

Answer 37

No the order of power of in reverse

Question 38

How does PGI2 and TXA2 counter each other

Answer 38

PGI2 act on IP receptor to increase cAMP within vascular smooth muscle cells to produce an relaxation effect. TXA2 act on TP receptor to increase calcium release to produce contraction.

Question 39

How does PGE2 regulate gastric secretion?

Answer 39

EP3 receptors can switch off acid secretion by binding to PGE2, to ensure acid doesn't damage the gut mucus is secreted blood flow is increased.

Question 40

Why are fish oils good?

Answer 40

When fish oil are made into leukotrienes their products are less chemotactic to neutrophils so less tissue damage. They also produce shorter half life of prostaglandins and thromboxanes Polyunstaturated fatty acids also inhibit the AA metabolism pathway producing an antiinflammatory response