Misoprostol-A Wonder Drug

Misoprostol is a synthetic analogue of natural prostaglandin E1. It has a very convenient and flexible drug dosing, can be administered orally, sublingually, buccally, rectally and by vaginal route. Misoprostol is useful for elective early medical abortion, cervical ripening in surgical abortion as well as in gynecological D & C, mid trimester abortion, cervical ripening and induction of labour in live or dead fetus as well as in prevention and treatment of PPH. Key words: Misoprostol; medical abortion; induction of labour; postpartum hemorrhage. DOI: http://dx.doi.org/10.3329/bjms.v10i4.9490 BJMS 2011; 10 (4): 221-225


Introduction
Misoprostol is a synthetic analogue of natural prostaglandin E 1 .It produces inhibition of gastric acid and pepsin secretion, and enhances mucosal resistance to injury.It is an effective anti ulcer agent and also has oxytocic properties.
Misoprostol was developed during 1980s and approved by FDA for the prevention of NSAIDinduced gastric ulcers in 1988.Off-label exploration of the drug for obstetric purposes began soon after its development, and the drug has been studied extensively for a number of gynecological and obstetric indications.
Misoprostol is already included in the 14th and 15th edition of WHO MODEL List of Essential Medicines because of its proven safety and ef ficacy for medical abortion and labour induction1.17th Expert committee on the selection of and use of essential medicine in Geneva on March 2009 proposed the inclusion of misoprotol for prevention of PPH 2 .
Misoprostol has a very convenient and flexible drug dosing, can be administered orally , sublingually, buccally, rectally and by vaginal route.Misoprostol is useful for elective early medical abortion, cervical ripening in surgical abortion as well as in gynecological D & C, mid trimester abortion, cervical ripening and induction of labour in live or dead fetus as well as in prevention and treatment of PPH.
The purpose of this article is to review the lar ge body of evidences supporting the uses of misoprostol in pregnancy.

Pharmacokinetics
Misoprostol is a synthetic 15 deoxy-16 hydroxy-16 methyl analog of prostaglandin E1 and is water sol-uble.The commercial preparations are available in tablets forms of 200 µgm and 100 µgm. 25 µgm tablets are now available in some countries.Misoprostol is rapidly absorbed by all routes of administrations but the most rapid action occurs when misoprostol is given orally (peak concentration after 12 min, half life 20-30 min).Misoprostol given vaginally or sublingually takes longer to start working, has a lower peak concentration after 60 min, but a more sustained effect.Thus, smaller doses are needed when misoprostol is inserted vaginally .Misoprostol is extensively absorbed, metabolized in liver and, undergoes rapid de-esterification to its free acid, i.e. misoprostol acid, which is responsible for its clinical activity and less than 1% of its active metabolite is excreted in urine 3 .

Mode of Action
Misoprostol causes uterine contractions and opening or ripening of cervix.Although prostaglandins (PGs) are highly ef fective, their ef ficacy depends on the number of PGs receptors in the uterus and this varies according to gestational age.In early pregnancy , there are few receptors and high doses of misoprostol may need to be given repeatedly in order have an effect.No problems have been reported in first trimester abortion with women who have had previous caesarean section 4 .The sensitivity of the uterus to misoprostol can be increased by giving the mifepristone (progesterone receptor blocker) 24-48 hours before misoprostol5.This is especially useful in early pregnancy, although it works in late pregnancy also.At term, there are many receptors and a small doses of misoprostol leads to strong contractions, so at term misoprostol cannot be used in women with previous caesarean as it may causes a Bangladesh Journal of Medical Science Vol. 10 No. 04 Oct'11 ruptured uterus 6,7.A Meta-analysis by Plaut et al (1999) reported a 5.6% rate of rupture with the use of misoprostol compared with 0.2% in patient attempting vaginal birth after caesarean delivery with no stimulation 6 .

Adverse Reaction
Prolonged or serious side ef fects are rare.Side effects depend on the route, dose and the indications for which misoprostol is used.
Bleeding: Vaginal bleeding during abortion induced with misoprostol is generally more intense than regular menstrual bleeding and is usually no dif ferent from that which occurs with a spontaneous abor-tion8.The mean pre-to post-abortion fall in hemoglobin varies between 0.2 and 1.0 g/dL .Prolonged and intensive bleeding affects between 1% and 10% of women9 and may necessitate emergency surgical uterine evacuation, preferably with manual vacuum aspiration.The need for transfusion has been rarely reported.Cramping: Cramping usually starts within the first few hours and may begin as early as 30 min after misoprostol administration.The pain may be stronger than that experienced during a regular period and can be present in 80%-90% of women10.Nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesia can be used for pain relief without affecting the success of the method 11,12.Fever and/or chills: Chills are a common side effect of misoprostol but are transient.Hyperthermia can be very severe13 and more common with higher doses or when the interval between doses is shorter or with oral or sublingual administration10, 14.Fever does not necessarily indicate infection.An antipyretic can be used for relief of fever, if needed.If fever or chills persist beyond 24 h after taking misoprostol, the women may have an infection and should seek medical attention.
Nausea and vomiting: About 20% of women report pregnancy-related nausea and vomiting before treatment.These symptoms may increase after misopros-tol administration.An anti-emetic can be used if needed, but symptoms will usually resolve within 2 to 6 h.Diarrhea: Diarrhea may also occur following administration of misoprostol but usually resolve within a day.

Uterine contraction abnormalities:
Induction of labour with misoprostol can cause uterine tachysystole in 10.1%, hypertonus in 10.7% and hyperstimulation syndrome in 13.8% 15.There were no dif ferences in the proportion of the subjects induced by oxytocin

Teratogenicity
The concerns about the medical safety of misoprostol emerged in early 1991 when the first case of fetal anomalies were reported in Ceara Brazil1 6,17 .The most common anomalies reported were limb defects followed by CNS anomalies, upper limb defects skeletal defects and other anomalies, such as defects of the genitalia, eyes and palate.Mobius syndrome, a rare condition characterized by the loss of function of the motor cranial nerves esp.(VI, VII & XII) is said to be associated with fetal misoprostol expo-sure18.A more commonly proposed mechanism of teratology involves vascular disruption caused by strong uterine contraction.One theory proposes that misoprostol induced contraction may bind the embryo in the area of cranial nuclei VI & VII, there by decreasing blood flow in the area, which results in hemorrhage and / or cell death in the cranial nuclei 19 .
Because estimates suggested that 5-10% of women exposed to misoprostol carried their pregnancies to term, risks of teratogenicity after failed abortion and continuing pregnancy were perceived to be high16 The relative risk of malformation appears real, epidemiological studies indicate the absolute risk is low and it is a mini teratogen means (less that 10 malformations per 1000 birth exposed to misoprostol in utero) 20.

Conclusion
Misoprostol is one the most important medication in obstetrical practice.In April 2002, the FDA finally approved a new label for the use of misoprostol during pregnancy 42 .
Misoprostol is now a legitimate part of the FDA approved regime for use with mifepristone to induce abortion in early pregnancy and is also recognized for its use for induction of labour 43 .
The increased access to and information on the use of misoprostol could help to improve women's health and decrease the morbidity and mortality associated with various obstetrics and gynecological conditions.
Misoprostol is a wonderful drug as it can be used in all trimester of pregnancy by all routes except inject able in living or dead fetus with simple dose schedule and minimum side ef fects.Its potential is especially promising in the developing world where maternal mortality is high and where an ef fective, low cost and stable prostaglandin is urgently needed.The benefits of misoprostol in settings with few resources have since been widely demonstrated.It has facilitated dif ficult challenge of evacuating a dead fetus during the second trimester of pregnancy, substituting methods that carry a high risk of morbidity and mortality 44 It has also proved its ef ficacy to prevent PPH in situation where oxytocin is not available or lose its ef fectiveness due to high ambient temperature 45 45 .There is also now evidence to correlate the increase its use with reduction of morbidity and mortality associated with abortion in countries with restrictive laws 46 .
Over the year a drug was required which could prevent PPH in periphery and can be used by trained birth attendant, which is the need of our country , so we can call it a wonder drug With the help of this article, it is hoped that dangerous misuse will be avoided and practice may be improved with a view to reduce maternal morbidity and mortality.