Gastric mucosa, prostaglandins

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). 

Nabumetone selectively inhibits COX-2. It is metabolised into 6-methoxy-2-naphthylacetic acid (MNA), that is a potent inhibitor of COX-2. It has no inhibitory effect on COX-1 which is responsible for prostaglandin synthesis in gastric mucosa, thereby minimising the risk of problems like ulcers and hypertension. After oral administration 80% of dose is excreted in the urine. Peak plasma concentration is reached after 2.5 to 4 hours. 

PGE and PGI2 are the main prostaglandins synthesized by gastric mucosa. They decrease acid secretion and improve mucosal defense mechanism by ... 

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. 

Prostaglandins (PGs) produced by the gastric mucosa stimulate the secretion of bicarbonate and mucus and inhibit the proton pump. 

Weller, H., Weller, Ch., Gerok, W. Decreased prostaglandin E2 immu-noactivity of gastric mucosa in portal hypertension. Netherl. J. Med. 1991 38 4-12... 

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