COX Pathways

Question 1

What are eicosanoids?

Answer 1

Signalling molecules made in the arachidonic acid pathway

Question 2

What do leukotrienes do?

Answer 2

They sustain inflammatory processes and are released by mast cells during asthma attack’s

They are the primarily responsible for bromchoconstriction

Question 3

How is arachidonic acid formed?

Answer 3

It is cleaved from phospholipids by the enzyme PLA2

Question 4

What are the 2 arachidonic acid pathways, named after the enzymes that mediate that pathways?

Answer 4

1) Cyclooxygenase

2) Lipooxygenase

Question 5

What 2 groups of molecules are formed in the cyclooxygenase part of the arachidonic acid pathway?

Answer 5

1) Prostoglandins

2) Thromboxane

Question 6

What group of molecules are formed in the lipooxygenase part of the arachidonic acid pathway?

Answer 6

Leukotrienes

Question 7

Why is the lipooxygenase pathway important to understand for the use of NSAIDS?

Answer 7

NSAIDS block COX pathway = more arachidonic acid is forced to synthesise leukotrienes = can cause bronchoconstriction

Question 8

What 3 things do prostaglandins do in the microvasculature?

Answer 8

1) cause vasodilation
2) cause oedema
3) cause nerve sensitisation (hyperalgesia)

Question 9

Where do prostoglandins come from (which cells)?

Answer 9

1) endothelial cells

2) inflammatory cells

Question 10

What do NSAIDS do?

Think about what this means in terms of what effects they have?

Answer 10

They inhibit COX (therefore prevent prostaglandin production)

This means they will reduce pain (algesia), have anti-inflammatory effects and finally anti-pyrexial effects

Question 11

Name some NSAIDS.

Answer 11

Aspirin, indomethaxim, diclofenac, ibuprofen, naproxen

Question 12

What is a common complication of NSAIDS?

Answer 12

Gastric ulceration (a form of peptic ulcer = one which is on the inside of the stomach lining)

Question 13

What are the COX isozymes?

Answer 13

COX-1

COX-2

Question 14

What effects do COX-1 and COX-2 have on the body?

What is each produced in response to?

Answer 14

COX-1
= produced in response to normal physiological stimuli
= produces prostaglandins, prostacyclins and thromboxane
= is cytoprotective

COX-2
= produced in response to inflammatory stimuli
= does NOT produce thromboxane
= mediates inflammatory mediator production

Question 15

Why can selective COX-2 inhibitors be advantageous?

Answer 15

They allow the COX-1 pathway to carry on which is cytoprotective

Question 16

What effects can NSAIDS have on clotting?

Answer 16

They am reduce clotting if non-selective as they can interfere with TA2 production

Question 17

How can non-selective NSAID GI risks be minimised?

Answer 17

Give in combination with:

• PPI (omeprazole)
• prostaglandin agonists

Question 18

What effects can NSAIDS have on the kidneys?

Answer 18

Reduction in cytoprotective prostoglandins which results in renal vasoconstriction which leads to:

• increased BP
• fluid and Na retention

Question 19

Name some of the new COX-2 selective inhibitors?

Answer 19

Celecoxib

Paracoxib (valdecoxib pro-drug)

Question 20

What is the main disadvantage of COX-2 selective antagonists?

Answer 20

Bad for the heart

Question 21

Name a prostaglandin analogue.

Answer 21

Misoprostol

Question 22

What is another name for diclofenac?

Answer 22

Volterol