Misoprostol Systematic (IUPAC) name Methyl 7-((1R,2R,3R)-3-hydroxy-2-((S,E)-4-hydroxy-4-methyloct-1-enyl)-5-oxocyclopentyl)heptanoate Clinical data Trade names Cytotec AHFS/Drugs.com MedlinePlus Pregnancy cat. X Legal status ℞ Prescription only Routes Oral, Vaginal, Sublingual Pharmacokinetic data Bioavailability extensively absorbed Protein binding 85% Metabolism de-esterified to misoprostol acid, then to prostaglandin F analogs Half-life 20–40 minutes Excretion Renal:80%
Identifiers CAS number ATC code A02 PubChem IUPHAR ligand DrugBank ChemSpider UNII KEGG ChEMBL Chemical data Formula C22H38O5 Mol. mass 382.534 g/mol SMILES & (what is this?)
Misoprostol is a drug that is used for the prevention of non steroidal anti inflammatory drug (NSAID) induced gastric ulcers, for early abortion, to treat missed miscarriage, and to induce labor. The latter use is controversial in the United States. Misoprostol was invented and marketed by G.D. Searle & Company (now Pfizer) under the trade name Cytotec (often misspelled Cyotec), but other brand-name and generic formulations are now available as well.
Pharmacologically, misoprostol is a synthetic prostaglandin E1 (PGE1) analogue.
Misoprostol is approved for use in the prevention of NSAID induced gastric ulcers. It acts upon gastric parietal cells, inhibiting the secretion of gastric acid via G-protein coupled receptor mediated inhibition of adenylate cyclase, which leads to decreased intracellular cyclic AMP levels and decreased proton pump activity at the apical surface of the parietal cell. Because other classes of drugs, especially H2-receptor antagonists and proton pump inhibitors, are more effective for the treatment of acute peptic ulcers, Misoprostol is only indicated for use by people who are both taking NSAIDs and are at high risk for NSAID induced ulcers, including the elderly and people with ulcer complications. Misoprostol is sometimes coprescribed with NSAIDs to prevent their common adverse effect of gastric ulceration (e.g. with Diclofenac in Arthrotec).
Misoprostol has other protective actions, but is only clinically effective at doses high enough to reduce gastric acid secretion. For instance, at lower doses misoprostol may stimulate increased secretion of the protective mucus that lines the gastrointestinal tract and increase mucosal blood flow, thereby increasing mucosal integrity. However, these effects are not pronounced enough to warrant prescription of misoprostol at doses lower than those needed to achieve gastric acid suppression.
However, even in the treatment of NSAIDs induced ulcers, omeprazole proved to be at least as effective as misoprostol, but significantly better tolerated, and therefore misoprostol should not be considered a first choice treatment. Misoprostol induced diarrhea and the need of multiple daily doses (typically four) are the main issues impairing adherence to therapy.
Misoprostol is commonly used for labor induction. It causes uterine contractions and the ripening (effacement or thinning) of the cervix. Misoprostol is more effective in starting labor than other drugs used for labor induction.:87 It is also significantly less expensive than the other commonly used ripening agent, dinoprostone (trade names Cervidil and Prepidil).
Oxytocin (trade names Pitocin and Syntocinon) has long been used as the standard agent for labor induction, but doesn't work well when the cervix is not yet ripe. In addition to being used alone to induce labor, misoprostol may be used in conjunction with oxytocin.
Protocols for inducing labor with misoprostol typically call for 25 μg to be administered vaginally. In countries where the only approved use of misoprostol is ulcer prevention, misoprostol is not sold in tablets smaller than 100 μg. When used for induction, the 100 μg tablet is commonly split into two or four pieces.
When Cytotec first came on the market, the label listed a contraindication that it not be used on pregnant women. In August 2000, due to increase of "off label" usage, Searle (the manufacturer of Cytotec) distributed a letter warning against the use of misoprostol in pregnant women. In addition to citing the abortifacient nature of the drug, the letter cited reports of uterine rupture and death associated with using misoprostol to induce labor. All cervical ripening and induction agents can cause uterine hyperstimulation, which can negatively affect the blood supply to the fetus and increases the risk of complications such as uterine rupture. Concern has been raised that uterine hyperstimulation that occurs during a misoprostol induced labor is more difficult to treat than hyperstimulation during labors induced by other drugs. Other rare complications include amniotic fluid embolism; a 2006 study showed that the use of drugs to induce labor nearly doubled the risk. Because the complications are rare, it is difficult to determine if misoprostol causes a higher risk than do other cervical ripening agents. One estimate is that it would require approximately 61,000 patients enrolled in randomized controlled trials to detect a clinically significant difference in serious fetal complications and approximately 155,000 patients to detect a clinically significant difference in serious maternal complications.
This letter generated much controversy over the use of misoprostol in labor inductions. The American College of Obstetricians and Gynecologists holds that substantial evidence supports the use of misoprostol for induction of labor, a position it reaffirmed in 2000 in response to the Searle letter. Misoprostol is also on the WHO essential drug list for labor induction.
Misoprostol is one of the drugs used for medical abortions in lieu of surgical evacuation. The advantages of medical abortion over surgical abortion include reduced invasiveness of the procedure, lack of risks from general anesthesia (which is sometimes used for surgical abortions), and lack of risk of secondary infertility due to scarring and intrauterine adhesions (Asherman's Syndrome). Furthermore, it is less complicated to administer and less expensive.
In many countries[which?] it is used in conjunction with mifepristone (RU-486). After mifepristone is taken orally, misoprostol is taken 24–72 hours later, causing the expulsion of the embryo and associated matter in approximately 92% of the cases. No large studies have established a protocol for the use of misoprostol alone, and the range of efficacy is 65%–93% depending on sample size, gestational age, and other test variables; Misoprostol alone may be more effective in earlier gestation. The side effects associated with the misoprostol only regimen are generally much more severe than those associated with the combined regimens. Misoprostol is used for self-induced abortions in Brazil, where black market prices exceed US $100 per dose. Illegal medically unsupervised misoprostol abortions in Brazil are associated with a lower complication rate than other forms of illegal self-induced abortion, but are still associated with a higher complication rate than legal, medically supervised surgical and chemical abortions. Failed misoprostol abortions are associated with birth defects in some cases. Poor immigrant populations in New York have also been observed to use self administered misoprostol to induce abortions, as this method is much cheaper than a surgical abortion (about $2 per dose).
Misoprostol can also be used to dilate the cervix in preparation for a surgical abortion, particularly in the second trimester (either alone or in combination with laminaria stents).
Misoprostol is also used to prevent and treat post-partum hemorrhage, but it has more side effects and is less effective than oxytocin for this purpose. However, it is inexpensive and thermostable (thus does not require refrigeration like oxytocin) making it a cost effective and valuable drug to use in the developing world.
Other gynecological uses
Although the practice remains uncommon, some gynecologists are now using low doses of misoprostol to soften the cervix prior to the insertion of intrauterine devices (especially in nulliparous women where insertion may be challenging).
A 1998 study found misoprostol to be helpful as a supplement to a vacuum pump (VED) in the treatment of erectile dysfunction, but not effective by itself. The paper concluded "The intraurethral application of misoprostol significantly improves the quality of VED-induced erections. This agent seems to be a cheap intraurethral adjunct to VED with mild to moderate local side-effects".
Misoprostol, a prostaglandin, binds to myometrial cells to cause strong myometrial contractions leading to expulsion of tissue. This agent also causes cervical ripening with softening and dilation of the cervix.
Side effects and contraindications
The most commonly reported adverse effect of taking a misoprostol 200 µg tablet by mouth four times a day to reduce the risk of NSAID induced gastric ulcers is diarrhea. In clinical trials, an average 13% of patients reported diarrhea, which was dose-related and usually developed early in the course of therapy (after 13 days) and was usually self-limiting (often resolving within 8 days), but sometimes (in 2% of patients) required discontinuation of misoprostol.
The next most commonly reported adverse effects of taking a misoprostol 200 µg tablet by mouth four times a day to reduce the risk of NSAID induced gastric ulcers are: abdominal pain, nausea, flatulence, headache, dyspepsia, vomiting, and constipation, but none of these adverse effects occurred significantly more often than when taking placebos.
Misoprostol should not be taken by pregnant women to reduce the risk of NSAID induced gastric ulcers because it increases uterine tone and contractions in pregnancy which may cause partial or complete abortions, and because its use in pregnancy has been associated with birth defects.
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- Misoprostol.org an independent website containing dosage guidelines and advice on misoprostol use.
- www.yorku.ca A York University study outlining potential links toward autism.
Precursor ProstanoidsPrecursorActiveD/JE/FIThromboxanes (TX) Leukotrienes (LT)PrecursorInitialSRS-A Nonclassic By functionlabor stimulation: (PGE2 (Dinoprostone), PGF2α (Dinoprost)) Drugs for acid related disorders: Drugs for peptic ulcer and GERD/GORD (A02B) H2 antagonists ("-tidine") Prostaglandins (E)/analogues ("-prost-")Misoprostol • Enprostil Proton-pump inhibitors ("-prazole") Other Uterotonics/labor inducers/oxytocics (G02A) Cervical ripeningErgot alkaloidsErgometrine# (+oxytocin) • Methylergometrine Contraction induction
-  The Mechanism of Action and Pharmacology of Mifepristone, Misoprostol, and Methotrexate
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