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

Some people with asthma cannot take aspirin or NSAIDs because of what’s known as Samter’s triad -- a combination of asthma, aspirin sensitivity, and nasal polyps. NSAIDs, including aspirin, possibly cause asthma exacerbations, particularly in patients allergic to these drugs. Aspirin/NSAIDs inhibit cyclooxygenase (COX) and reduce prostaglandin synthesis, thereby reducing fever and relieving pain and inflammation. Prostaglandins are responsible for the initiation of the allergic reaction.

• 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 is an essential fatty acid and a precursor in the biosynthesis of prostaglandins,thromboxanes, and leukotrienes. The stimulation of specific cell-surface receptors activates phospholipase A2 leading to the release of arachidonic acid from the cell membrane. The arachidonic acid is then rapidly converted into active metabolites by cyclooxygenases to produce prostaglandins, prostacyclin and thromboxane, and by lipoxygenase to produce leukotrienes.

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

Arachidonic acid

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

COX-2 inhibitors are NSAIDs that selectively block the COX-2 enzyme. Blocking this enzyme inhibits the production of prostaglandins by the COX-2 which is mostly the cause of the pain and swelling of inflammation and other painful conditions.

• Give an example of the following:
• A drug that inhibits each of the following enzymes: phospholipase A; cyclooxygenase; lipoxygenase,

Dexamethasone

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

Arachidonic acid

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

Low-dose aspirin (81 mg) inhibits the enzyme Cox-1, which is responsible for producing thromboxane A-2, necessary for platelet aggregation. Thromboxane is required to facilitate platelet aggregation and to stimulate further platelet activation

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

Infusion of alprostadil (PGE1) dilates the ductus, increases pulmonary blood flow, and thereby improves oxygenation. Infants with aortic arch interruption or coarctation of the aorta are dependent on an open ductus to maintain lower body perfusion, hence Alprostadil has advantageous effects.

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

Misoprostol is a synthetic prostaglandin E1 analog that inhibits basal and nocturnal gastric acid secretion through direct stimulation of prostaglandin E1 receptors on parietal cells in the stomach. Synthetic prostaglandins such as misoprostol given orally "replace" the prostaglandins whose production is inhibited by NSAIDs and have been shown to protect the lining of the stomach from NSAID-induced ulcers.

• Prostaglandin is possible of value in asthma. Which PGE2- or PGF2A-analogues will be effective in such a case?

Prostaglandins play a role in the pathogenesis and treatment of asthma. The E prostaglandins are potent bronchodilators, whereas the F compounds are bronchoconstrictors. In addition, PGE2 prevents bronchoconstriction induced by agents such as histamine, serotonin, bradykinin, and acetylcholine.

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

It lowers pressure inside the eye that is caused by open-angle glaucoma or ocular (eye) hypertension. Latanoprost works by increasing the outflow of fluid from the eye. This lowers the pressure in the eye. Hence, the intra-ocular pressure is decreased by increasing the outflow of fluid.