1. Why do you think aspirin is contraindicated in people with allergic asthma?

Aspirin is a NSAIDs that inhibit the synthesis of cyclooxygenase. The arachidonic will still synthesis Cyclo-oxygenase which leads to an increase in the synthesis leukotrienes.LT are potent vasoconstrictors that cause bronchospasm. Bronchospasm is contraindicated in patients with asthma.

2. Arachidonic acid is the most important precursor of the eicosanoids, but how is this fatty acid released from the cell membrane, and by which stimuli?

Arachidonic acid needs to be released from membrane phospholipids in order to start the Eicosanoid process. AA is released by three different phospholipase classes.

First is Cytosolic PLA2 (phospholipase A2)

Secretory PLA2 (Calcium dependant)

Calcium independent PLA2 (Where chemical and physical stimuli activate the calcium translocation of PLA2 to plasma membrane, this then allows the release of Arachidonic acid and so the start of the Eicosanoid synthesis.

3. Apart from prostanoids and leukotrienes, which other non-eicosanoid product of cell membrane hydrolysis is strongly involved in asthma?

Leukotrienes and Thromboxane.

4. Why would you say a COX II-inhibitor, and not a COX I-inhibitor, has a selective action in inflammatory reactions?

Cyclo-oxygenase plays a direct part in the inflammation process specifically as it synthesises PGI2, TXA and PG.

5. Give an example of the following:

A drug that inhibits each of the following enzymes:

phospholipase A; Hydrocortisone, Dexamethasone, Prednisolone.

cyclooxygenase; Aspirin, ibuprofen

lipoxygenase, Zileuton

A drug that can act antagonistically or agonistically at prostaglandin and leukotriene receptors.

Montelukast, Zafirlukast

• Aspirin inhibits platelet aggregation because it inhibits thromboxane synthesis and not prostacyclin synthesis.  How does it happen?

Thromboxane promotes platelet synthesis whereas prostacyclin inhibits platelet aggregation. As soon as a Cyclo-oxygenase inhibitor is used no platelet aggregation will occur.

• How is alprostadil advantageous in the treatment of congenital heart defects?

Alprostadil is PGE1, which induces vasodilation and inhibits platelet aggregation.

• How is misoprostol of value in the treatment and prevention of gastric ulcers?

Misoprostol is a PGE1 eicosanoid that helps protect the gastric mucosa preventing the formation of sores within the stomach lining i.e., gastric ulcers.

• Prostaglandin is possible of value in asthma.  Which PG_E2- or PGF_2A-analogues will be effective in such a case?

PGE2 would be of better value because PGF2 is a potent bronchoconstrictor.

• How is latanoprost of value in the treatment of glaucoma?

Latanoprost increase the outflow of aqueous humor.