MISOPROSTOL
Chemistry - A synthetic prostaglandin E1 analog, misoprostol occurs as a yellow, viscous liquidhaving a musty odor.
Misoprostol also has a cytoprotective effect on gastric mucosa. Probably by increasing productionof gastric mucosa and bicarbonate, increasing turnover and blood supply of gastric mucosal cells, misoprostol enhances mucosal defense mechanisms and enhances healing in response to acid-related injuries.
Other pharmacologic effects of misoprostol include, increased amplitude and frequency of uterinecontractions, stimulate uterine bleeding, and causing total or partial expulsion of uterine contents inpregnant animals.
Misoprostol acid is further biotransformed via oxidative mechanisms to pharmacologically inactivemetabolites. These metabolites, the free acid and small amounts of unchanged drug are principallyexcreted into the urine. In humans, the serum half life of misoprostol is about 30 minutes and itsduration of pharmacological effect is about 3-6 hours.
It should be used in patients with the following conditions only when its potential benefits outweigh the risks: Sensitivity to prostaglandins or prostaglandin analogs; patients with cerebral orcoronary vascular disease (although not reported with misoprostol, some prostaglandins andprostaglandin analogs have precipitated seizures in epileptic human patients, and have causedhypotension which may adversely affect these patients).
Overdosage, Acute Toxicity - There is limited information available. Overdoses in laboratoryanimals have produced diarrhea, GI lesions, emesis, tremors, focal cardiac, hepatic or renal tubularnecrosis, seizures and hypotension. Overdoses should be treated seriously and standard gutemptying techniques employed when applicable. Resultant toxicity should be treated symptomatically and supportively.
Storage, Stability, Compatibility
Misoprostol tablets should be stored in well-closed containersat room temperature. After manufacture, misoprostol has an expiration date of 18 months.Pharmacology - MISOPROSTOL
Misoprostol has two main pharmacologic effects that make it a potentially usefulagent. By a direct action on parietal cells it inhibits basal and nocturnal gastric acid secretion as wellas gastric acid secretion that is stimulated by food, pentagastrin or histamine. Pepsin secretion isdecreased under basal conditions, but not when stimulated by histamine.Misoprostol also has a cytoprotective effect on gastric mucosa. Probably by increasing productionof gastric mucosa and bicarbonate, increasing turnover and blood supply of gastric mucosal cells, misoprostol enhances mucosal defense mechanisms and enhances healing in response to acid-related injuries.
Other pharmacologic effects of misoprostol include, increased amplitude and frequency of uterinecontractions, stimulate uterine bleeding, and causing total or partial expulsion of uterine contents inpregnant animals.
Uses, Indications
Misoprostol may be useful as primary or adjunctive therapy in treating orpreventing gastric ulceration, especially when caused or aggravated by non-steroidal antiinflammatory drugs (NSAIDS). Misoprostol may be efficacious in reducing or reversing cyclosporininduced nephrotoxicity. More data is needed to confirm this effect.Pharmacokinetics - MISOPROSTOL
Approximately 88% of an oral dose of misoprostol is rapidly absorbed fromthe GI tract, but a significant amount is metabolized via the first-pass effect. The presence of foodand antacids will delay the absorption of the drug. Misoprostol is rapidly de-esterified tomisoprostol acid which is the primary active metabolite. Misoprostol and misoprostol acid arethought be equal in their effects on gastric mucosa. Both misoprostol and the acid metabolite arefairly well bound to plasma proteins (approximately 90% bound). It is not believed that misoprostolenters maternal milk, but it is unknown whether the acid enters milk.Misoprostol acid is further biotransformed via oxidative mechanisms to pharmacologically inactivemetabolites. These metabolites, the free acid and small amounts of unchanged drug are principallyexcreted into the urine. In humans, the serum half life of misoprostol is about 30 minutes and itsduration of pharmacological effect is about 3-6 hours.
Contraindications, Precautions, Reproductive Safety
Misoprostol is contraindicated duringpregnancy due to its abortifacient activity. It is not recommended to be used in nursing mothers as itpotentially could cause significant diarrhea in the nursing offspring.It should be used in patients with the following conditions only when its potential benefits outweigh the risks: Sensitivity to prostaglandins or prostaglandin analogs; patients with cerebral orcoronary vascular disease (although not reported with misoprostol, some prostaglandins andprostaglandin analogs have precipitated seizures in epileptic human patients, and have causedhypotension which may adversely affect these patients).
Adverse Effects, Warnings
The most prevalent adverse effect seen with misoprostol is GI distress, usually manifested by diarrhea, abdominal pain, vomiting and flatulence. Adverse effects areoften transient and resolve over several days or may be minimized by dosage adjustment or givingdoses with food. Potentially, uterine contractions and vaginal bleeding could occur in female dogs.Overdosage, Acute Toxicity - There is limited information available. Overdoses in laboratoryanimals have produced diarrhea, GI lesions, emesis, tremors, focal cardiac, hepatic or renal tubularnecrosis, seizures and hypotension. Overdoses should be treated seriously and standard gutemptying techniques employed when applicable. Resultant toxicity should be treated symptomatically and supportively.