Eicosanoids

Question 1

Give examples of eicosanoids

Answer 1

Thromboxane, prostaglandin and leukotrienes

Question 2

Give examples of physiological processes mediated by eicosanoids

Answer 2

• Inflammation - Control of blood pressure - Blood clotting - Induction of labour - Fever and pain associated with inflammation - Gastro-protection (through prostaglandin synthesis by COX-1)

Question 3

Describe why omega-3 and 6 fatty acids are essential

Answer 3

These fatty acids are essential as humans are unable to desaturate (add a double bond) beyond carbon 9 and hence cannot synthesise the molecules. Therefore they must be obtained from the diet.

Question 4

Describe Eicosanoid production

Answer 4

Phospholipids are cleaved from the membrane by phospholipase A2 and become Arachidonic acid COX-1 and COX-2 act to produce prostaglandins and thromboxane. Lipooxygenases act to produce leukotrienes.

Question 5

Explain the rationale and consequences of inhibiting different portions of the eicosanoid synthesis pathway

Answer 5

Rationale: Reduce inflammation and associated pain/increased sensitivity through inhibition of COX-2 e.g. by NSAIDs Consequences: Reduces pain but inhibition of COX-1 causes the gastric lining to be exposed to gastric acid, may cause acid formation M.O.A. of corticosteroids: Glucocorticoids activate lipocortins –> Bind Ca and phospholipids which inhibit phospholipase A2. This prevents the synthesis of arachidonic acid and ultimately synthesis of leukotrienes.

Question 6

Describe Eicosanoid storage

Answer 6

Eicosanoids are not stored as they are very unstable

Question 7

Inhibiting Eicosanoid production: Benefits at different stages

Answer 7

• Corticosteroids: Inhibit the production of arachidonic acid (inhibit lipocortin production, decrease the cascade). Prevents the whole cascade from proceeding
• LTR1 antagonists: Prevent the binding of leukotrienes to their receptor, therefore reduce inflammation, oedema and bronchoconstriction
• NSAIDs: Inhibit COX, reduce prostaglandin synthesis, reducing pain and inflammation but negative effects (renal vasoconstriction and loss of mucosal protective prostaglandins)
• COXIBS