L18: Eicosanoids Flashcards
What are the 3 main categories of eicosanoids
Prostaglandins
Thromboxanes
Leukotrienes
What are eicosanoids
Lipid derivatives that are locally synthesised and acting in the body
What are the major function of eicosanoids
Inflammation
Are eicosanoids stored in the body
No they are made as required
What is eicosanoids made from
Arachidonic acid
How is prostanoids synthesised from arachidonic acid
1) arachidonic acid is liberated from the membrane by phospholipase A2 enzyme
2) cox-1 or cox-2 act on the arachidonic acid to generate free intermediates of cyclo endoperoxides
3) if cox-2 acts then prostacyclin synthase acts on cyclic endoperoxides it gives prostacyclin
4) if cox-1 acts then thromboxane synthase acts on cyclic endoperoxides it gives TXA2
What are prostanoids
Groups of eicosanoids of:
Prostaglandins
Thromboxanes
When does cox-2 act on free arachadonic acid
During inflammation
Which cell makes prostacyclin
Endothelium
What makes. TXA2
Platelets
How is leukotrienes synthesised by free arachidonic acid
1) arachidonic acid is liberated from membranes by phospholipase A2
2) lipoxygenase enzyme acts on the free arachidonic acid to give HPETE (intermediate compound)
3) HPETE gives leukotrienes of LTB4 and/or LTD4
Which drugs inhibit cox-1 and cox-2 enzyme
NSAIDS
Which drugs inhibits cox-2 only
Selective NSAIDS
Which drugs reduced the expression of cox-2
Glucocorticoid
What is the other role of glucocorticoid on the production of prostanoids and leukotrienes
Glucocorticoid increase the expression of annexin-1 which inhibit phospolipase A2
There is less arachidonic acid liberated therefore less prostanoids and leukotrienes made
What is the role of prostaglandins
Inflammatory response
Vasodilation to allow movement of prostaglandins
Raise temperature
Increase peripheral sensory nerves for pain
Muscle contraction
Gastric mucous secretion
Inhibition of platelets aggregation
Name a prostaglandin
Prostacyclin (PGI2)
What is the role of thromboxanes
Vasoconstriction
Bronchoconstriction
Platelet aggregation
Name an example of thromboxanes
TXA2
What do eicosanoids bind to once produced to bring about their effects
G-protein coupled receptors
Which drugs inhibits 5-lipoxgenase to reduce leukotrienes
Zileuton
In which clinical condition is zileuton used in
Asthma
What other drugs act to alter leukotriene production
Glucocorticoid by inducing annexin-1 which inhibits phosholipaseA2 to reduce overall eicosanoids production
What is the role of leukotriene
Attract neutrophil and macrophages to site of inflammation
Simulate proliferation of immune cells
Involved in rhematoid arthritis, ulcerative colitis
Bronchoconstriction
Mucus secretion
Vasodilation and vasoconstriction
What is the name of the receptor that prostacyclin binds to
IP
What happens when prostacyclin binds to it’s receptor
Activates CAMP and protein kinase A
What is the name of the receptor that TXA2 binds to
TP
What happens when TXA2 binds to its receptor
Activates phospholipase C and protein kinase C
What is the pathway for leukotrienes when it binds to leukotrienes receptor
Phospholipase c
Protein kinase c
Name an leukotrienes receptor antagonist
Montelukast
When is montelukast used
In asthma
Name an IP receptor agonist
Epoprostenol
When is epoprostenol used
In pulmonary hypertension
Name an EP receptor agonist
Misoprostol
When is misoprostol used
In gastric ulcer to reduce hydrochloric acid
Does cox-1 result in vasodilation or vasoconstriction
Vasoconstriction
Does cox-2 result in vasodilation or vasoconstriction
Vasodilation
What is thrombosis
Blood clotting
Why is the balance of cox-1 and cox-2 important
To stop thrombosis from occuring
What are the 2 ways preventing thrombosis
Fish oil
Aspirin
Does leukotrienes result in bronchoconstriction or bronchodilation
Bronchoconstriction
Does prostanoids give bronchoconstriction or bronchodilation
Both
Name 3 drugs used to treat allergic asthma
Glucocorticoids
Zileuton
Montelukast
