Gastric mucosa, prostaglandins protection

Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase [2] and consequently the synthesis of most eicosanoids. This explains their analgesic, antipyretic, and antirheumatic effects. Frequent side effects of NSAIDs also result from inhibition of eicosanoid synthesis. For example, they impair hemostasis because the synthesis of thromboxanes by thrombocytes is inhibited. In the stomach, NSAIDs increase HCl secretion and at the same time inhibit the formation of protective mucus. Long-term NSAID use can therefore damage the gastric mucosa. 

The answer is a. (Hardman, p 914.) Misoprostol is a prostaglandin analogue of PGE with an affinity for the gastric mucosa. It stimulates the secretion of mucus and bicarbonate, enhances cell proliferation, preserves the microcirculation, and stabilizes tissue lysosomes. Misoprostol is approved by the FDA for protection against the ulcerogenic action of NSAIDs (not because it antagonizes NSAIDs). 

Efforts to synthesize stable derivatives of prostaglandins for therapeutic applications have not been very successful to date. Dino-prostone (PGE2), carboprost (15-methyl-PGF2a) and mifeprostone are uterine stimulants (p.130, 254). Misoprostol is meant to afford protection of the gastric mucosa but has pronounced systemic side effects. All these substances lack organ specificity. 

Biochemical etiology Primarily, NSAID inhibition of a gastric enzyme (COX-1) required for synthesis of prostaglandins that have a protective effect on the gastric mucosa. A contributory factor is direct mucosal damage due to the acidic chemistry of NS AlDs. 

Secretion of arachidonic acid metabolites (E series prostaglandins) to protect the gastric mucosa... 

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