Misoprostol is a
drugA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
that is used for the prevention of non-steroidal anti-inflammatory drug (NSAID)-induced
gastric ulcerA peptic ulcer, also known as ulcus pepticum, PUD or peptic ulcer disease, is an ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful...
s, for early abortion, to treat missed miscarriage, and to
induce laborInduction is a method of artificially or prematurely stimulating labour in a woman.Common causes for induction include:* The baby is believed to be getting too big.* Postdate pregnancy, i.e. if the pregnancy has gone past the 42 week mark....
. The last use is controversial in the
United StatesThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
. Misoprostol was invented and marketed by G.D. Searle & Company (now
PfizerPfizer Incorporated is a pharmaceutical company, ranking number one in sales in the world. The company is based in New York City, with its research headquarters in Groton, Connecticut...
) under the trade name
Cytotec (often misspelled
Cyotec), but other
brand-nameA brand is a name or trademark connected with a product or producer. Brands have become increasingly important components of culture and the economy, now being described as "cultural accessories and personal philosophies".-Concepts:...
and
genericA generic drug is a drug which isproduced and distributed without patent protection. The generic drug may still have a patent on the formulation but not on the active ingredient....
formulations are now available as well.
Chemically, misoprostol is a synthetic
prostaglandinA prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....
E
1 (PGE
1) analogue.
Ulcer prevention
Misoprostol is approved for use in the prevention of NSAID-induced gastric ulcers. It acts upon gastric
parietal cellParietal cells, or oxyntic cells, are the stomach epithelium cells that secrete gastric acid and intrinsic factor.- Acid production :...
s, inhibiting the secretion of
gastric acidGastric acid is a secretion produced in the stomach. It is one of the main ditotonic solutions secreted, together with several enzymes and intrinsic factors...
via G-protein coupled receptor-mediated inhibition of
adenylate cyclaseAdenylate cyclase is a lyase enzyme. It is a part of the cAMP-dependent pathway-Types:There are ten known adenylate cyclases in mammals:* ADCY1* ADCY2* ADCY3* ADCY4* ADCY5...
, which leads to decreased intracellular cyclic AMP levels and decreased
proton pumpA proton pump is an integral membrane protein that is capable of moving protons across the membrane of a cell, mitochondrion, or other subcellular compartment.-Function:...
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 co-prescribed with NSAIDs to prevent their common adverse effect of gastric ulceration (e.g. with
DiclofenacDiclofenac is a non-steroidal anti-inflammatory drug taken to reduce inflammation and as an analgesic reducing pain in conditions such as arthritis or acute injury. It can also be used to reduce menstrual pain, dysmenorrhea...
in
ArthrotecThe combination diclofenac/misoprostol is a pharmaceutical product that contains:*Diclofenac sodium: Nonsteroidal anti-inflammatory drug with analgesic properties...
).
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
mucusIn vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. It is a viscous colloid containing antiseptic enzymes and immunoglobulins that serves to protect epithelial cells in the respiratory,...
that lines the
gastrointestinal tractThe human gastrointestinal tract , digestive tract, guts or gut is the system of organs within humans that takes in food, digests it to extract energy and nutrients, and expels the remaining matter...
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.
Labor induction
Misoprostol is commonly used to
induce laborInduction is a method of artificially or prematurely stimulating labour in a woman.Common causes for induction include:* The baby is believed to be getting too big.* Postdate pregnancy, i.e. if the pregnancy has gone past the 42 week mark....
. It causes uterine contractions and the ripening (
effacementEffacement is the shortening, or thinning, of a tissue.For example, it happens to the cervix before or during early labour. Prior to effacement, the cervix is like a long bottleneck, usually about four centimeters in length. Throughout pregnancy, the cervix is tightly closed and protected by a plug...
or thinning) of the cervix. Misoprostol is more effective in starting labor than other drugs used for labor induction. It is also significantly less expensive than the other commonly used ripening agent, dinoprostone (trade names
Cervidil and
Prepidil).
OxytocinOxytocin is a mammalian hormone that also acts as a neurotransmitter in the brain.It is best known for its roles in female reproduction: it is released in large amounts after distension of the cervix and vagina during labor, and after stimulation of the nipples, facilitating birth and...
(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 is commonly split into two or four pieces.
Controversy
In August 2000,
SearleG.D. Searle & Company or just Searle was a company focusing on life sciences, specifically pharmaceuticals, agriculture, and animal health. It is now part of Pfizer.- History :...
—the manufacturer of misoprostol—distributed a letter warning against the use of misoprostol in pregnant women. In addition to citing the
abortifacientAn abortifacient is a substance that induces abortion. Abortifacients for animals that have mated undesirably are known as mismating shots.Common abortifacients used in performing medical abortions include mifepristone, which is typically used in conjunction with misoprostol in a two-step approach...
nature of the drug, the letter cited reports of
uterine ruptureUterine rupture is a potentially catastrophic event during childbirth by which the integrity of the myometrial wall is breached. In an incomplete rupture the peritoneum is still intact. With a complete rupture the contents of the uterus may spill into the peritoneal cavity or the broad ligament...
and death associated with using misoprostol to induce labor. This letter generated much controversy over the use of misoprostol in labor inductions. Other rare complications include
amniotic fluid embolismAmniotic fluid embolism is a rare and incompletely understood obstetric emergency in which amniotic fluid, fetal cells, hair, or other debris enters the mother's blood stream via the placental bed of the uterus and triggers an allergic reaction. This reaction then results in cardiorespiratory ...
. Because these 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.
All cervical-ripening and induction agents can cause
uterine hyperstimulationUterine hyperstimulation or hypertonic uterine dysfunction is a potential complication of labor induction. It is defined as either a series of single contractions lasting 2 minutes or more or a contraction frequency of five or more in 10 minutes. Uterine hyperstimulation may result in fetal heart...
, which can negatively affect the blood supply to the fetus and increases the risk of complicaions 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.
The
American College of Obstetricians and GynecologistsThe American College of Obstetricians and Gynecologists is a professional association of medical doctors specializing in obstetrics and gynecology in the United States. It has a membership of over 52,000 and represents 90 percent of U.S...
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.
Earlier pregnancy
Misoprostol is one of the drugs used for
medical abortionA medical abortion is a type of non-surgical abortion in which a drug is used to induce the abortion. Safe and effective medical abortion methods became an alternative for first trimester pregnancy termination in the 1970s. The most widely used medication are mifepristone or methotrexate either...
s 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 often used for surgical abortions), and lack of risk of secondary
infertilityInfertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
due to scarring and intrauterine adhesions (
Asherman's Syndrome Asherman's syndrome , also called "uterine synechiae" or intrauterine adhesions , presents a condition characterized by the presence of adhesions and/or fibrosis within the uterine cavity due to scars...
). Furthermore, it is less complicated to administer and less expensive.
In many countries it is used in conjunction with
mifepristoneMifepristone is a synthetic steroid compound used as a pharmaceutical. It is used as an abortifacient in the first two months of pregnancy, and in smaller doses as an emergency contraceptive. During early trials, it was known as RU-486, its designation at the Roussel Uclaf company, which designed...
(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 abortionA self-induced abortion is an abortion performed by the pregnant woman herself, outside the recognized medical system. Although the term can include abortions induced through legal, over-the-counter medication, it also refers to efforts to terminate a pregnancy through alternative, often more...
s 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 YorkNew York is a state in the Mid-Atlantic and Northeastern regions of the United States and is the nation's third most populous. The state is bordered by New Jersey and Pennsylvania to the south, and Connecticut, Massachusetts and Vermont to the east...
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).
Later pregnancy
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
laminariaLaminaria is a genus of 31 species of brown algae , all sharing the common name "kelp". This economically important genus is characterized by long, leathery laminae and relatively large size. Some species are referred to by the common name Devil's apron, due to their shape, or sea colander, due to...
stents).
Missed miscarriage
Misoprostol is sometimes used to treat early fetal death in the absence of spontaneous
miscarriageMiscarriage or spontaneous abortion is the spontaneous end of a pregnancy at a stage where the embryo or fetus is incapable of surviving, generally defined in humans at prior to 20 weeks of gestation...
, but further research is needed to establish a safe, effective protocol.
Other gynecological uses
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. Although the practice remains uncommon, some gynecologists are now using low doses of misoprostol to soften the cervix prior to the insertion of
intrauterine deviceAn intrauterine device is a long acting reversible contraceptive birth control device placed in the uterus, also known as an IUD or a coil . Dr. Ernst Gräfenberg of Germany invented an early IUD and was the first person to market these devices...
s (especially in nulliparous women where insertion may be challenging).
Erectile dysfunction
A 1998 study found misoprostol to be helpful as a supplement to a vacuum pump (VED) in the treatment of
erectile dysfunctionErectile dysfunction is a sexual dysfunction characterized by the inability to develop or maintain an erection of the penis sufficient for satisfactory sexual performance....
, 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".
Side effects and contraindications
The most commonly reported
adverse effectIn medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect, and may result from an unsuitable or incorrect dosage or...
of taking a misoprostol 200 µg tablet by mouth four times a day to reduce the risk of NSAID-induced gastric ulcers is
diarrheaIn medicine, diarrhea , also spelled diarrhoea , is the condition of having frequent loose or liquid bowel movements. Acute diarrhea is a common cause of death in developing countries and the second most common cause of infant deaths worldwide...
. 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 painAbdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
,
nauseaNausea is the sensation of unease and discomfort in the stomach with an urge to vomit.-Causes:...
,
flatulenceFlatulence is the expulsion through the rectum of a mixture of gases that are byproducts of the digestion process of mammals and other animals. The mixture of gases is known as flatus, fart, or simply gas, and is expelled from the rectum in a process colloquially referred to as "passing gas" or...
,
headacheIn medicine a headache or cephalalgia is a symptom of a number of different conditions of the head. Some of the causes are benign while others are medical emergencies.There are a number of different classification systems for headaches...
,
dyspepsiaDyspepsia , popularly known as indigestion, meaning hard or difficult digestion, is a medical condition characterized by chronic or recurrent pain in the upper abdomen, upper abdominal fullness and feeling full earlier than expected when eating. It can be accompanied by bloating, belching, nausea...
,
vomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Undesired vomiting may result from many causes, ranging from gastritis or poisoning to brain tumors, or elevated intracranial pressure...
, and
constipationConstipation, costiveness, or irregularity is a condition of the digestive system in which a person experiences hard feces that are difficult to expel. This usually happens because the colon absorbs too much water from the food...
, but none of these adverse effects occurred significantly more often than when taking
placeboA placebo is a sham medical intervention. In one common placebo procedure, a patient is given an inert sugar pill, told that it may improve his/her condition, but not told that it is in fact inert...
s.
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.
A study published in the Journal of Immunology (June 15, 2008 online) suggests that the immunosuppressive effect of misoprostol, if given vaginally rather than orally along with RU-486 to terminate a pregnancy, is likely the reason a small number of women taking the two-drug combination have contracted a fatal bacterial infection. In animal and cell culture studies, the researchers found that misoprostol, when given directly in the reproductive tract (vaginally), suppresses key immune responses and can allow a normally non-threatening bacterium,
Clostridium sordelliiClostridium sordellii is a rare anaerobic, gram-positive, spore forming rod with peritrichous flagella that is capable of causing pneumonia, endocarditis, arthritis, peritonitis, and myonecrosis. C. sordellii bacteremia and sepsis occur rarely. Most cases of sepsis from C. sordellii occur in...
, to gain the upper hand and cause deadly infection. When absorbed through the stomach (orally), however, the drug did not compromise immune defenses or cause illness.
External links and further reading