Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

SBT > Lipid mediators of inflammation > Flashcards

Lipid mediators of inflammation Flashcards

1
Q

What are eicosanoids?

A
  • PGs, Thtomboxanes and leukotrienes are collectively known as eicosanoids
  • There are two pathways:
  • cyclic (cycloxygenase) pathway -> Prostanoids (PGs and TXs)
  • Lipoxygenase pathway -> LTs and lipoxins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Why are eicosanoids important?

A
  • They have powerful inflammatory actions

- targets of major anti-inflammatory drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Give 4 examples of anti-inflammatory drug types

A
  • NSAIDs (aspirin)
  • Glucocorticoids (methotrexate)
  • Lipoxygenase inhibitors
  • Leukotriene antagonists - expensive but very good for aspirin-induced asthma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the process of prostanoid formation?

A
  • Prostanoids are not ‘ready-to-go’ (unlike histamine)
  • Prostanoids are generated from arachidonic acid (AA, poly-unsaturated fatty acid). This is rate-limiting step
  • AAs are produced from phospholipids (PLs) via 1-step/2-step pathways
  • These steps are triggered by many agents, e.g. thrombin on platelets and antigen-antibody reactions on mast cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How is AA made?

A

1 step
- PLs (via Phospholipase A2) –> AA

2 step

  • PLs (Via PLC) –> DAG (via DAG lipase) –> AA
  • PLs (Via PLD) –> phosphatidic acid (via PLA2) –> AA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What sort of stimulus causes AA to come out of esterification with the membrane phospholipid?

A
  • Inflammatory stimuli such as Bradykinin and adrenaline
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are cyclooxygensases?

A
  • Enzyme that converts AA to prostanoids

- Two main isoforms (COX-1/2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

COX-1 vs COX-2 vs COX-3

A

COX-1

  • Constitutively active
  • Responsible for physiological roles of PGs/TXs such as regulation of TPR, renal blood flow, platelet aggregation, gastric cytoprotection

COX-2

  • Needs to be stimulated (by inflammatory cytokines such as IL-1b or TNFa)
  • Responsible for roles of PGs/TXs in inflammatory responses (pain and fever)

COX-3

  • Variant of COX-1
  • Pain perception of CNS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the cyclooxygenase pathway?

DRAW IT

A
  • AA (via COX) –> PGG2
  • PGG2 is very unstable and so is quickly converted to PGH2
  • PGH2 -> Thrombxane synthase -> TXA2
  • PGH2 -> tissue-specific isomerases (mPGES-1) -> PGD2/PGE2/PGf2a
  • PGH2 -> prostacyclin synthase -> PGI2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What do the specific prostanoids do?

A
  • TXA2 = platelet aggregator
  • PGD2 = allergic responses, bronchoconstrictor, inhibits platelet aggregation
  • PGE2 = myometrium contraction in labour
  • PGF2a = bronchoconstrictor and uterine contraction
  • PGI2 = inhibits platelet activation and vasodilator
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is homeostatic balance?

A
  • TXA2 is a platelet aggregator
  • PGD2 and PGI2 inhibit platelet aggregation and activation
  • The balance between them means that your blood isnt always clotted
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Give 2 drugs that inhibit thromboxane synthase

A
  • Aspirin
  • picotamide
  • Ifetroban
  • Terutroban
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Give 2 drugs that inhibit prostacyclin synthase

A
  • Epoprostenol
  • Iloprost
  • Treprostinil
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the lipoxygenase pathway?

DRAW IT

A
  • FLAP (5-lipoxygenase activator protein) acts on AA
  • 5-lipoxygenase then acts on it to produce 5-HPETE
  • 5-lipoxygenase then acts again to produce LTA4
  • In turn, glutathiones transpeptidases and various AAs (e.g. glycine and cysteine) are all added to produce sulphidopeptide LTs (LTC4, LTD4, LTE4)
  • If LTA4 hydrolase acts on LTA4 instead, then it produces LTB4
  • other lipoxygenases can act on AA/LTA4 to make lipoxins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are some anti-inflammatory lipid mediators?

A
  • Lipoxins

- Cyclopentenone PGs (CyPGs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How do Lipoxins and CyPGs carry out the anti-inflammatory actions?

A
  • Lipoxins recruit monocytes to clear the inflamed site of necrotic/apoptotic neutrophils - regulate the activation of neutrophils and increase their phagocytosis
  • Acting with CyPG, they promote phagocytic clearance of apoptotic cells by macrophages
  • CyPGs inhibit macrophage activation, which decreases uncontrolled tissue damage, and decreases NF-kB activation
  • This helps to decrease activation of inflammatory genes and dampen down inflammation
17
Q

What cells make the particular eicosanoids?

A
  • Mast cells = PGD2, LTs
  • Platelets = TXA2
  • Endothelial cells = PGI2, PGE2
  • Neutrophils/ Basophils/ Eosinophils = LTs
18
Q

What receptors do the eicosanoids act on?

A
  • PGs (lungs, vascular, gut, CNS, kidney, uterus) = DP, FP, IP, EP1,2,3
  • TXs (vascular/platelets) = TP
  • LTs (general inflammation, lungs/vascular in acute allergy) = BLT (1&2) and CysLT (1&2)
19
Q

What do DP receptors do?

A

Vasodilation, decreased platelet aggregation, bronchoconstriction

20
Q

What do FP receptors do?

A

Contraction of myometrial smooth muscle, bronchoconstriction

21
Q

What do EP receptors do?

A 
EP1 = bronchioconstriction, GIT smooth muscle constriction
EP2 = Bronchodilation, vasodilation, relaxation of GITSM and increase intestinal fluid
EP3 = Contraction of GITSM, increase gastric mucus secretion, decrease gastric acid, pyrexia
22
Q

What do TP receptors do?

A
  • Vasoconstriciton and platelet aggregation
23
Q

What do BLT receptors do?

A

Chemotaxis and proliferation of immune cells, increased adhesion
- LTB4 is a very potent chemotactic for neutrophils

24
Q

What do CysLT receptors do?

A

Bronchoconstriction, vasodilation, increased vascular permeability

25
Q

Give 4 examples of LT receptor antagonists

A

Zafirlukast
Montelukast
Pranlukast
Zileuton

Block receptor for Cysteinyl LTs (C,D,E)

26
Q

What do CysLTs do in general?

A

Cause airway oedema, secretion of thick mucus and smooth muscle contraction

27
Q

Why are LT antagonists useful?

A
  • Prevent mild to moderate asthma
  • Early to late bronchoconstrictor effects of allergens
  • Exercise induced asthma and NSAID induced astham
28
Q

How can NSAIDs lead to asthma?

A
  • Aspirin blocks COX, however the lipoxygenase pathway is still active
  • Therefore we still produce LTs
  • This give thick sticky mucus, bronchoconstriction, cellular infiltration of eosinophils + neutrophils
29
Q

What are some side effects of LT antagonists?

A

GI upset
Irritability
Dry mouth, thirst
Rashes, oedema

30
Q

Give the order of potency of bronchoconstriction (least to highest)

A

Histamine
LTE4
LTC4
LTD4

31
Q

What type of receptors are EP receptors?

A

GPCRs

  • EP1 = Gq
  • EP2 = Gs
  • EP3 = Gi
32
Q

How does PGI2 carry out its actions?

A
  • Inhibits platelet aggregation

- Also acts on IP receptors on SM in response to shear stress -> Increase cAMP -> relaxation

33
Q

How does PGE2 protect our stomach?

A
  • Acts on EP3 receptors on parietal cells to reduce gastric acid secretion
  • EP3 receptors on mucus secreting cells to increase the mucus secretion along with bicarbonate
34
Q

Why are fish oils beneficial for our health?

A
  • Provide substrates for the generation of alternative eicosanoids
  • Increasing PUFA uptake means that more ecosapentoic acid (EPA) and docosahexaenoic acid (DHA) is produced, essentially replacing AA
  • Less AA available to less PGE2,TXB2, LTB4, 5-HETE, LTE4 produced
  • EPA and DHA are used as substrates for alternative eicosanoids
  • Increases production of LTB5, LTE4, 5-HPETE (with different strcture to ones produced from AA)
  • LTB5 is 10-100x less chemotactic to neutrophils
35
Q

What anti-inflammatory metabolites can be made by COX activity EPA and DPA?

A
  • E-series resolvins (resolvin D1-4, EPA-derived mediators) have anti-inflammatory actions
  • Docosatrienes and neuroprotectins (D series resolvins, DHA-derived mediators) also have anti-inflammatory effects

SBT (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions