Misoprostol pharmacology (Prostaglandin analogues), mechanism, side effects, pharmacology made easy

▪ Misoprostol is a prostaglandin analog. Prostaglandin E, produced by the gastric mucosa, inhibits secretion of acid and stimulates secretion of mucus and bicarbonate (cyto-protective effect). A deficiency of prostaglandins is thought to be involved in the pathogenesis of peptic ulcers.
▪ PGE2 and PGI2 are the major prostaglandins synthesized by the gastric mucosa. They bind to the EP3 receptor on parietal cells and stimulate the Gi protein-coupled receptor pathway, thereby, decreasing intracellular cyclic AMP and gastric acid secretion. PGE2 also can prevent gastric injury by cyto-protective effects that include stimulation of mucin and bicarbonate secretion and increased mucosal blood flow. Since NSAIDs diminish prostaglandin formation by inhibiting cyclooxygenase, synthetic prostaglandin analogs offer a logical approach to reducing NSAID-induced mucosal damage.
▪ Misoprostol, an analog of prostaglandin E1,is approved for the prevention of NSAID-induced gastric ulcers. The degree of inhibition of gastric acid secretion by misoprostol is directly related to dose; oral doses of misoprostol 100 mcg to 200 mcg significantly inhibit basal acid secretion or food-stimulated acid secretion. The usual recommended dose for ulcer prophylaxis is 200 µg four times a day.
Prophylactic use of misoprostol should be considered in patients who are taking NSAIDs and are at moderate to high risk of NSAID-induced ulcers, such as elderly patients and those with previous ulcers.
▪ Major problems in the use of misoprostol are diarrhea, abdominal cramps, uterine bleeding, abortion, and need for multiple daily doses. Patient acceptability is poor. Misoprostol is contraindicated in pregnancy, since it can stimulate uterine contractions and cause miscarriage. Dose-related diarrhea and nausea are the most common adverse effects and limit the use of this agent.
▪ The primary use of PG analogues is in the prevention and treatment of NSAID associated gastrointestinal injury and blood loss. However, PPIs are more effective, more convenient, better tolerated and cheaper.
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Chapters:
0:00 - intro
0:27 - prostaglandins analogues pharmacology
1:28 - Mechanism of action misoprostol
3:01 - Pharmacokinetics of misoprostol
3:47 - Clinical uses of misoprostol 200mcg
4:19 - Side Effects of misoprostol
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