18 Eicosanoids

Question 1

What are the 2 main pathways of the reactions from arachidonic acid, and what products do they form?

Answer 1

Cyclo-oxygenase COX
(thromoxane and prostoglandins)
Lipoxygenase LOX
(leukotrienes)

Question 2

What is the fish equivalent of arachidonic acid, and what is the difference?

Answer 2

eicosapentanoic acid (5 double bonds)
arachidonic acid (4 double bonds)

Question 3

What kinds of prostanoids do endothelial cells, platelets, and immune cells produce?

Answer 3

endo - PGI(2)
platelets - TXA(2)
immune - mixture really

Question 4

What is the rough function of thromboxane and how does it achieve this?

Answer 4

increases BP
vasoconstriction
platelet activation

Question 5

What is the rough function of prostoglandins and how do they achieve this?

Answer 5

decrease BP
vasodilation
inhibits platelet activation

Question 6

What do NSAID’s do?
what problem do they present?
Give 2 examples

Answer 6

non-selective anti-inflammatory drugs (inhibit COX-1 and COX-2)
PG synthesis recovers faster than TXA so overall anti-inflammatory

we may see unwanted side-effects

ibuprofen and aspirin

Question 7

What do SAID’s do?

name one example

Answer 7

inhibit COX-2

celecoxib

Question 8

What effects do glucocorticoids have on these pathways?

Answer 8

increase expression of annexin-1, which will inhibit both the COX and LOX pathways, increasing the amount of free arachidonic acid

Question 9

name 2 glucocorticoids used to treat asthma

Answer 9

beclamethasone

fluticasone

Question 10

What is the rough function of leukotrienes, and by what 3 methods do they achieve this?

Answer 10

stimulate inflammation

chemotaxis
proliferation of immune cells
release of cytokines

Question 11

What drugs might we use for asthma which interacts with the LOX pathway?

Answer 11

Zileuton - inhibits 5-lipox

GLucocorticoids (induce annex-1)

Question 12

What are the different prostanoid receptors, and what are their agonists?
What is special about one of them?

Answer 12

IP (PG)
DP (PG)
EP (PG)
FP (PG)
TP (TXA) - works through Gq, stimulating calcium release and hence smooth muscle contraction for vasocontriction

Question 13

What are the 3 leukotriene receptors?

Answer 13

P2Y
GPR
CysLT

Question 14

What drug would we use as an antagonist of CystLT’s?

Who would use them?

Answer 14

Monteleukast

Asthmatics

Question 15

Name 2 agonists of prostanoid receptor agonist drugs, and their uses

Answer 15

epoprostenol (IP agonist), used for pulmonary hypertension

misoprostol (EP agonist), used for treating gastric ulcer and inducing labour

Question 16

What is CVST, and what effects do platelets and endothelial cells have on it?

Answer 16

cerebral venous sinus thrombosis
platelets - TXA2 (aggregatory agent and vasoconstrictor)
endothelial cells - PGI
(anti-aggregatory agen and vasodilator)

Question 17

Why might some COX-2 inhibitors cause heart attacks?

Answer 17

vasodilation and antri-aggregatory agents

Question 18

What are the products of using fish oil, and why is this significant?

Answer 18

eicosapentanoic acid
TXA3 (not TXA2), acting as a weaker aggregator
PGI3 (not PGI2), acting as a more potent inhibitor
therefore we’re more likely to decrease blood pressure

Question 19

name one side effect of an overdose of aspirin

Answer 19

GI haemorrhage

Question 20

What effects do PG’s, TX’s, and LT’s have on bronchoconstrictino / dilation?

Answer 20

PG’s -dilation
TX’s - constriction
Lt’s constriction

Question 21

what are the different phases of allergic asthma?

Answer 21

allergen binds to IgE on mast cells
intermmediate - more LT’s, histamine, and interleukins
Late phase - recruitment of esosinophils and T lymphocytes

Question 22

Why do NSAID’s offer no benefit for asthamtics?

Answer 22

excess Leukotrienes, diverted from prostanoid synthesis