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Pharmacology

Misoprostol: Its Pharmacology and Use in Obstetrics and Gynaecology

Introduction

Misoprostol is a synthetic prostanglandin E1 analogue commonly used in management of various obstetrics and gynaecology conditions as well as in the management of stomach ulcers.

Its IUPAC nomenclature is Methyl 7-[(1R,2R,3R)-3-hydroxy-2-[(1E)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate.

Pharmacokinetics

Misoprostol comes in tablet formulation and can be administered orally, buccally, sublingually, vaginally and rectally. Misoprostol is extensively absorbed through all routes of administration. It undergoes rapid de-esterification during absorption to its free acid, misoprostol acid, which is responsible for its clinical activity. This misoprostol acid is the form that is detectable in plasma, not misoprostol itself. Misoprostol acid is 81-89% bound to serum proteins, and it is primarily excreted through the kidneys.

Pharmacodynamics

Orally, onset of action is 8 minutes and its duration of action of approximately 2 hours.

Sublingually, onset of action is 11 minutes and its duration of action of approximately 3 hours.

Vaginally, onset of action is 20 minutes and its duration of action of approximately 4 hours.

Rectally, onset of action is 100 minutes and its duration of action of approximately 4 hours.

Mechanism of action

Misoprostol acts on the cervix, uterine smooth muscle cells, and the stomach.

The cervix is essentially a connective tissue organ with smooth muscle cells accounting for less than 8% of its distal part . Misoprostol causes cervical ripening (softening) and dilatation by acting on the connective tissue stroma and causing disintegration and dissolution of collagen.

Misoprostol causes contraction of uterine smooth muscle cells. It increases uterine tonicity and contractility by stimulating prostaglandin E2 receptors (EP2, EP3 and EP4 receptors) on the smooth muscle cells.
Of all the routes of administration, rectal administration shows the lowest uterine activity in terms of tonus and contractility, while vaginal administration shows the highest.

In the stomach, misoprostol has a cytoprotective effect on the gastrointestinal mucosa. It stimulates prostaglandin E1 receptors on parietal cells in the stomach to reduce gastric acid secretion. It also increases mucus and bicarbonate secretion as well as mucosal and submucosal oedema, which causes thickening of the mucosal bilayer so the mucosa can generate new cells.

There are no known drug interactions with misoprostol. The administration of NSAIDs for pain relief does not alter the efficacy of misoprostol.

Indications

  1. Cervical ripening and induction of labour
  2. Medical termination of pregnancy (either alone or in conjunction with mifepristone or methotrexate)
  3. Evacuation of the uterus in missed abortion, incomplete abortion and IUFD.
  4. Prevention and treatment of postpartum haemorrhage
  5. Cervical ripening before endometrial biopsy and hysteroscopy.
  6. Prevention of NSAID-induced gastric ulcers

The dosage of misoprostol used depends on the individual patient’s parity and indication.

Contraindications

  1. Previous allergic reaction or hypersensitivity to prostaglandin.
  2. Previous uterine surgery

Adverse effects

The most commonly adverse effects are shivering/chills, diarrhea, abdominal pain, hyperthermia, nausea, vomiting, flatulence, constipation, dyspepsia and headache. Other less common side effects include syncope, lethargy, weakness, vertigo, hypotension, sinus tachycardia, fetal bradycardia, oedema, myocardial infarction, uterine rupture, cervical laceration, fetal death, teratogenesis, pulmonary embolism, anaphylactoid reactions, and thrombosis.

Conclusion

Misoprostol is a synthetic prostanglandin E1 analogue with a myriad of applications in obstetrics and gynaecology practice and medicine in general.

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