Misoprostol, deep History, best uses, Side effects, Dosage, and top 7 brands in Pakistan

Introduction to Misoprostol

Misoprostol is a synthetic drug that act the effects of natural prostaglandins in the body. Initially developed to protect the stomach lining from damage caused by certain medications, it is also used in obstetrics and gynecology for various purposes. These include inducing labor, managing miscarriage, performing medication abortions, preparing the cervix for surgical procedures, and treating postpartum hemorrhage.

History of Misoprostol

Misoprostol is a synthetic prostaglandin E1 analog developed to address various medical conditions, particularly in the fields of gastroenterology and obstetrics/gynecology. Its history is marked by its evolving applications and significant impact on medical practices worldwide.

Development and Approval

• 1973: Misoprostol was first synthesized by the pharmaceutical company Searle (now part of Pfizer). Initially, it was developed to address the adverse gastrointestinal effects of nonsteroidal anti-inflammatory drugs (NSAIDs), which can cause gastric and duodenal ulcers.
• 1988: Misoprostol received approval from the U.S. Food and Drug Administration (FDA) for the prevention and treatment of NSAID-induced gastric ulcers. This approval marked the drug’s official entry into the pharmaceutical market under the brand name Cytotec.

Expansion of Uses in Obstetrics and Gynecology

• Throughout the late 1980s and early 1990s, researchers began exploring misoprostol’s potential in obstetrics and gynecology due to its uterotonic properties, which could induce uterine contractions and cervical ripening.
• 1990s: Studies demonstrated that misoprostol was effective for labor induction and cervical ripening. Its ability to induce uterine contractions also led to its use in medical abortion protocols, particularly in combination with mifepristone (RU-486).
• 2000: The World Health Organization (WHO) included misoprostol on its Model List of Essential Medicines, recognizing its importance for inducing labor, managing postpartum hemorrhage, and facilitating safe medical abortions.

Medical Abortion

Misoprostol became a key component in medical abortion regimens. When used in combination with mifepristone or methotrexate, it provides a non-surgical option for terminating early pregnancies. This application has significantly increased access to safe abortion services, particularly in regions where surgical options are limited.

Postpartum Hemorrhage Management

Misoprostol’s role in managing postpartum hemorrhage (PPH) further highlighted its versatility. PPH is a leading cause of maternal mortality worldwide, and misoprostol, due to its uterotonic effects, has become an important tool in reducing blood loss after childbirth, especially in low-resource settings where access to other uterotonic agents may be limited.

Controversies and Challenges

Misoprostol’s use, particularly in abortion, has been subject to political and ethical debates. In some countries, restrictive regulations on abortion have impacted the availability and use of misoprostol for this purpose.

Despite these challenges, the drug remains a critical part of maternal health programs and reproductive health services globally.

Current Status

Today, misoprostol is widely used across multiple medical disciplines. It continues to be a staple medication for the prevention of NSAID-induced ulcers, induction of labor, medical abortion, and management of postpartum hemorrhage.

Ongoing research seeks to optimize its use, improve access, and ensure safe and effective application in various clinical settings.

Misoprostol Mechanism of action

Misoprostol is a synthetic analog of prostaglandin E1, designed to mimic the effects of naturally occurring prostaglandins in the body. Its mechanism of action can be understood through its effects on various tissues, particularly the gastrointestinal tract and the uterus.

Gastrointestinal Tract

1. Cytoprotective Effects: Misoprostol exerts a protective effect on the gastric mucosa. It binds to prostaglandin receptors on the surface of gastric parietal cells, leading to several beneficial actions:
2. Inhibition of Acid Secretion: By binding to the EP3 receptor on parietal cells, misoprostol inhibits adenylate cyclase activity, reducing cyclic AMP levels and decreasing the secretion of gastric acid.
3. Increased Mucus and Bicarbonate Production: Misoprostol stimulates the secretion of mucus and bicarbonate from epithelial cells, enhancing the mucosal barrier and protecting the stomach lining from acid damage.
4. Improved Mucosal Blood Flow: It promotes vasodilation and increases blood flow to the gastric mucosa, which helps in maintaining the integrity and repair of the gastric lining.

Uterus

1. Uterotonic Effects: Misoprostol induces uterine contractions by acting on prostaglandin receptors in the myometrium (the smooth muscle layer of the uterus). It binds primarily to the EP2 and EP3 receptors, which leads to several actions:
2. Cervical Ripening: Misoprostol softens and dilates the cervix by breaking down collagen fibers and increasing water content in the cervical tissue. This process is crucial for preparing the cervix for labor or facilitating the passage of pregnancy tissue in medical abortion.
3. Uterine Contractions: It stimulates rhythmic contractions of the uterine muscle, which can induce labor, expel uterine contents in the case of a miscarriage or abortion, and help control postpartum hemorrhage by contracting the uterus to reduce blood flow.

Systemic Effects

Vasodilation: Misoprostol’s prostaglandin activity can cause vasodilation, leading to increased blood flow in various tissues. This property is particularly beneficial in the gastrointestinal tract for maintaining mucosal blood flow.

Misoprostol Uses

Misoprostol, a synthetic prostaglandin E1 analog, is widely used in both gastroenterology and obstetrics/gynecology due to its ability to protect the gastric lining and induce uterine contractions. Here are the primary uses of misoprostol:

Prevention and Treatment of Gastric Ulcers

• NSAID-Induced Ulcers: Misoprostol is effective in preventing and treating gastric and duodenal ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs). It increases the production of protective mucus and bicarbonate in the stomach while reducing gastric acid secretion.
• Labor Induction: Misoprostol is used to induce labor in pregnant women, especially when the cervix is not yet favorable for delivery. It softens and dilates the cervix and stimulates uterine contractions.
• Cervical Ripening: Prior to labor induction, misoprostol is used to prepare the cervix, making it more conducive to labor.

Medical Abortion

• First-Trimester Abortion: Misoprostol, in combination with mifepristone or methotrexate, is used to terminate early pregnancies. Mifepristone primes the uterus by blocking progesterone, and misoprostol induces uterine contractions to expel the pregnancy tissue.
• Second-Trimester Abortion: It can be used alone or with other medications to terminate pregnancies in the second trimester.

Management of Miscarriage

• Incomplete or Missed Abortion: Misoprostol helps manage incomplete or missed miscarriages by inducing uterine contractions to expel retained pregnancy tissue, often reducing the need for surgical intervention.
• Postpartum Hemorrhage (PPH) Management:
• Prevention and Treatment: This medication is used to prevent and treat postpartum hemorrhage, a significant cause of maternal mortality. It promotes uterine contractions to control bleeding after childbirth.

Gynecological Procedures

Cervical Preparation Before Surgical Procedures: Misoprostol is sometimes used to soften and dilate the cervix before procedures such as hysteroscopy, endometrial biopsy, or intrauterine device (IUD) insertion.

Off-Label Uses

• Chronic Constipation: It also used off-label to treat chronic constipation due to its ability to stimulate smooth muscle contractions.
• Induction of Therapeutic Abortion for Medical Reasons: In certain cases, such as severe fetal anomalies or maternal health conditions, misoprostol is used to induce therapeutic abortion.

Misoprostol uses in Urdu

السر کے معافی اور علاج

– مائیسوپروسٹول معمولی طور پر غیر سٹیروئیڈی اینٹی انفلیمیٹری ڈرگز (این ایس اے آئی ڈیز) جیسے اسپرین، ایبوپروفین، اور نیپروکسن وغیرہ کے استعمال کرنے والے مریضوں کے لیے معدے اور دودھ کی نالی کے السر کے معافی اور علاج کے لیے استعمال ہوتا ہے۔ یہ دوائی معدے کی دیوار کو حفاظت فراہم کر کے معدے کو نقصان سے بچاتی ہے۔

عورتوں کی صحت اور حمل سے متعلق استعمالات

-دوائی سے حمل کے خاتمے- مائیسوپروسٹول عورت کے حمل کو ختم کرنے کے لیے استعمال کیا جاتا ہے۔ یہ رحمی دھڑکنیاں پیدا کر کے حملی ٹشو کو نکالتی ہے۔

-مسائل کی انتظامیہ

– یہ حمل کے گرنے کے طبی انتظامیہ میں استعمال ہوتا ہے تاکہ رحمی مواد کو نکالنا آسان ہو۔

-بچے کی پیدائش کو آغاز دینا

– مائیسوپروسٹول کو پیدائش کو آغاز دینے کے لیے استعمال کیا جاتا ہے۔ یہ رحم کی دھڑکنیاں پیدا کر کے رحم کے منہ کو نرم اور کھلا کرنے میں مدد فراہم کرتا ہے۔

-ہضمی نظام اور عورتوں کی صحت کے شعبے میں دیگر استعمالات

-مائیسوپروسٹول کا استعمال عموماً ہضمی نظام اور عورتوں کی صحت کے شعبے میں ہوتا ہے

Misoprostol Side effects

The use of Misoprostol may lead to several side effects, some of which are more serious than others. Here are the potential side effects associated with the use of Misoprostol:

Common Side Effects

Gastrointestinal Issues

• Diarrhea: This is one of the most common side effects, often occurring within the first few days of treatment.
• Abdominal Pain: Cramping and discomfort in the stomach area.
• Nausea: Feeling sick to the stomach.
• Vomiting: This can accompany nausea, particularly with higher doses.
• Flatulence: Increased gas and bloating.

Uterine and Reproductive System Effects

• Uterine Cramping: Misoprostol induces uterine contractions, which can cause cramping and discomfort.
• Bleeding: Increased vaginal bleeding, spotting, or irregular menstrual periods, especially when used for gynecological purposes.

Neurological Effects

• Headache: A relatively common side effect.
• Dizziness: Feeling light-headed or faint, which can be exacerbated by dehydration from diarrhea or vomiting.

Serious Side Effects

Severe Gastrointestinal Issues

• Severe Diarrhea: Leading to dehydration and electrolyte imbalance.
• Severe Abdominal Pain: Intense pain that may require medical attention.

Allergic Reactions

• Rash: Skin reactions including rashes and itching.
• Anaphylaxis: A rare but potentially life-threatening allergic reaction characterized by difficulty breathing, swelling of the face or throat, and hives.

Cardiovascular Effects

• Hypotension: Low blood pressure, especially when used in higher doses.
• Palpitations: Irregular or rapid heartbeat.

Uterine Hyperstimulation

Excessive Contractions: This can lead to complications during labor induction, including fetal distress or uterine rupture (rare).

Misoprostol Dosage

Misoprostol is used for various medical purposes, including the prevention of gastric ulcers, induction of labor, medical abortion, and management of postpartum hemorrhage. The dosage and administration route of misoprostol depends on the specific clinical indication. Below are the recommended dosages for different uses:

1. Prevention and Treatment of Gastric Ulcers

NSAID-Induced Ulcers:

• Dosage: 200 mcg orally four times a day with food.
• Alternative Dosage: 400 mcg orally twice a day if the four-times-daily regimen is not feasible.

2. Misoprostol dose for Abortion

• First Trimester (up to 12 weeks of gestation):
• Dosage: 200 mg mifepristone orally, followed by 800 mcg misoprostol vaginally, buccally, or sublingually 24-48 hours later.
• Misoprostol Alone dosage: 800 mcg vaginally, buccally, or sublingually, with a repeat dose after 3 hours if necessary.

Second Trimester (13-24 weeks of gestation):

Dosage: 400 mcg vaginally, buccally, or sublingually every 3 hours until expulsion, with a maximum of 5 doses.

3. Management of Miscarriage

Incomplete or Missed Abortion (up to 13 weeks):

Dosage: 600 mcg orally or 800 mcg vaginally, buccally, or sublingually.

4. Induction of Labor

Term Pregnancy

Dosage: 25 mcg vaginally every 6 hours, or 25 mcg orally every 2 hours. The dosage may be adjusted based on the clinical situation and institutional protocols.

Preterm Pregnancy

Dosage: Varies and should be used cautiously with close monitoring for uterine hyperstimulation.

5. Postpartum Hemorrhage (PPH)

Prevention:

Dosage: 600 mcg orally or 400 mcg sublingually immediately after delivery of the baby.

Treatment:

Dosage: 800 mcg sublingually or rectally if PPH occurs.

Administration Routes and Considerations

• Oral: Common for preventing gastric ulcers and can be used for labor induction. It typically has a slower onset and is associated with gastrointestinal side effects.
• Vaginal: Often preferred for medical abortion and labor induction due to higher efficacy and fewer gastrointestinal side effects.
• Buccal: Convenient and effective, with the tablet placed between the gum and cheek, useful for patients where vaginal administration is not acceptable.
• Sublingual: Rapid absorption with higher peak levels, useful for medical abortion but associated with more side effects.
• Rectal: Used primarily for managing postpartum hemorrhage due to ease of administration and effective absorption.

Precautions and Warnings

Misoprostol is a medication used primarily to prevent stomach ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin and ibuprofen. Here are some important precautions and warnings associated with its use:

1. Pregnancy Category X: Misoprostol should not be used during pregnancy as it can cause miscarriage, premature birth, or birth defects. It is crucial to avoid pregnancy while taking misoprostol and to use effective contraception during treatment.
2. Allergic Reactions: Individuals with a known allergy to misoprostol or prostaglandins should not use this medication as severe allergic reactions can occur.
3. Gastrointestinal Effects: It can cause diarrhea, abdominal pain, nausea, and vomiting. These symptoms are usually mild and resolve with continued use, but they can be severe in some cases. Patients with a history of inflammatory bowel disease (such as Crohn’s disease) should use misoprostol with caution due to the potential for exacerbation of symptoms.
4. Labor and Delivery: Misoprostol is sometimes used off-label to induce labor or facilitate the completion of a miscarriage. However, this should only be done under the close supervision of a healthcare provider due to the risks of uterine hyperstimulation, which can lead to fetal distress or uterine rupture.
5. Renal and Hepatic Impairment: Patients with impaired kidney or liver function should use this medicine with caution, as the medication is primarily metabolized in these organs. Adjustments to the dosage may be necessary to prevent accumulation and potential toxicity.
6. Drug Interactions: It may interact with other medications, particularly antacids containing magnesium, which can increase the risk of diarrhea. It is important to inform healthcare providers about all medications being taken, including over-the-counter drugs and supplements.

how to use misoprostol vaginally

Using misoprostol vaginally is a method commonly recommended for certain medical purposes, such as inducing labor or completing a miscarriage. Here’s a general guide on how to use misoprostol vaginally:

Preparation

1. Wash Hands: Before handling the medication, wash your hands thoroughly with soap and water to prevent any potential infection.
2. Positioning: Find a comfortable position that allows easy access to insert the medication vaginally, such as lying down with knees bent or standing with one leg raised on a chair.
3. Supplies: Gather the supplies needed, including the prescribed dose of misoprostol tablets, a lubricant (if recommended), and sanitary pads.

Administration

Inserting the Tablet

• If necessary, lubricate the tablet with water or a water-based lubricant as directed.
• Gently insert the tablet deep into the vagina using your finger. It should be placed as high up as comfortably possible, towards the cervix.
• Try to remain lying down or in a comfortable position for at least 30 minutes after insertion to allow the tablet to dissolve and absorb.

Dosage and Timing

• Follow your healthcare provider’s instructions carefully regarding the dosage and frequency of misoprostol administration vaginally. Typically, doses are spaced several hours apart.
• Misoprostol is often used in multiple doses to achieve the desired effect, such as inducing contractions or facilitating the passage of tissue.

Misoprostol price in Pakistan

Breeky Tablet 200mcg contains misoprostol which is available for Rs/ 180.8 in all Pharmacies in Pakistan.

Misoprostol brand name in Pakistan

In Pakistan, misoprostol is available under various brand names. Some Popular brands include:

Rotec Tablet 75 mg/0.2 mg– It is manufactured by SEARLE Pharmaceuticals

Arthrotec tablet 75– It is manufactured by Pfizer Pharmaceuticals

Miso Tablet 200 MCG– It is manufactured by Cipla Pharma

ST Mom Tablet 200mcg– It is manufactured by ZAFA Pharmaceutical Laboratories (Pvt.) Ltd.

Mite Tablets 200Mcg– It is Manufactured by Genix Pharma

Cytopan tablet 75mg– It is manufactured by Getz Pharma

Breeky Tablet 200mcg– It is manufactured by Sami Pharmaceuticals