Uterotonics

Methylergonovine is a semi-synthetic ergot alkaloid. It acts directly on uterine smooth muscle and increases the tone, rate and amplitude of rhythmic contractions, giving a rapid and sustained tetanic uterotonic effect that shortens the third stage of labor and reduces blood loss. Methylergonovine also produces vasoconstriction.

Carboprost (Hemabate) is a 15-methyl analog of prostaglandin F2α. Postpartum, the myometrial contractions it causes provide hemostasis at the placental site. It also stimulates the smooth muscle of the gut, so vomiting and diarrhea are common, can raise body temperature, and may cause transient bronchoconstriction; large doses can raise blood pressure by contracting vascular smooth muscle.

Uterine atony is the most common cause of postpartum hemorrhage, accounting for about 70% of cases. WHO recommends IV oxytocin as the first-line uterotonic for treating postpartum hemorrhage (see the Oxytocin page); if IV oxytocin is unavailable or the bleeding does not respond, it recommends IV ergometrine, oxytocin–ergometrine, or a prostaglandin drug.

Methylergonovine is labeled after delivery of the placenta for uterine atony, hemorrhage and subinvolution. It is contraindicated in hypertension and toxemia (preeclampsia) and in pregnancy, and it is not given IV routinely because of sudden hypertensive and cerebrovascular accidents. Carboprost is labeled for hemorrhage from atony that has not responded to conventional management — IV oxytocin, uterine massage and, unless contraindicated, an IM ergot. It is contraindicated in active cardiac, pulmonary, renal or hepatic disease and used cautiously in asthma. Misoprostol has also been used for serious postpartum hemorrhage, but that is outside its approved indication.

Dinoprostone is prostaglandin E2, which the fetal membranes and placenta secrete in pregnancy and which plays an important role in cervical ripening before labor. It changes the cervix’s consistency, dilation and effacement, and it stimulates production of PGF2α, which sensitizes the myometrium to oxytocin. Cervidil (vaginal insert) and Prepidil (endocervical gel) are labeled for cervical ripening at or near term when there is a medical or obstetric indication for induction.

It is used in hospital, with uterine activity, fetal status and cervical change monitored. Its main risk is uterine tachysystole with or without fetal heart rate changes; the Cervidil insert is removed for tachysystole, fetal distress, active labor, or before amniotomy. Because prostaglandins potentiate oxytocin, the insert is removed at least 30 minutes before an oxytocic is started, and Cervidil is contraindicated with IV oxytocic drugs. It also carries risks of postpartum disseminated intravascular coagulation and amniotic fluid embolism, and prostaglandins can raise intraocular pressure.

Misoprostol (Cytotec) is a prostaglandin E1 analog labeled for reducing the risk of NSAID-induced gastric ulcers in patients at high risk. It inhibits gastric acid secretion, and in animals protects the mucosa; NSAIDs deplete mucosal prostaglandins, and misoprostol can increase bicarbonate and mucus production. Its most frequent adverse effect is dose-related diarrhea.

Its boxed warning: given to pregnant women it can cause birth defects, abortion, premature birth or uterine rupture. Uterine rupture has been reported when it was given to induce labor or abortion, and the risk rises with advancing gestation and prior uterine surgery, including cesarean delivery. It is not taken by pregnant women for NSAID ulcers; women of childbearing potential take it only if at high risk, after a negative serum pregnancy test, with effective contraception, starting on the second or third day of a normal period. The label notes that cervical ripening, labor induction and treatment of serious postpartum hemorrhage are outside its approved indication and, if done, are for hospital use; its obstetric use can cause tachysystole progressing to uterine tetany and rupture. Its use with mifepristone for pregnancy termination is on the Estrogens & progestins page.