Uterotonics
High-yield Verified · Oct 2026Every uterotonic contracts more than the uterus. Knowing which other smooth muscle each one squeezes — vessels, airways or gut — is how you choose among them.
Nursing view → administration, monitoring and patient teaching
Compare: Labor drugs compared — uterotonics, tocolytics and magnesium sulfate →
Drugs
Mechanism
Methylergonovine, an ergot alkaloid, acts directly on uterine smooth muscle to increase tone, rate and amplitude of contractions — a sustained tetanic effect — and also constricts vessels. Carboprost, a PGF2α analog, stimulates myometrial contraction and gastrointestinal and bronchial smooth muscle. Dinoprostone (PGE2) ripens the cervix and, through PGF2α, sensitizes the myometrium to oxytocin. Misoprostol (PGE1) inhibits gastric acid secretion and can increase mucus and bicarbonate; it also produces uterine contractions.
Prostaglandins: one precursor, many receptors
Phospholipase A2 releases arachidonic acid, which cyclooxygenase (COX-1 and COX-2) converts to PGH2; tissue-specific enzymes then make thromboxane A2 and the stable prostaglandins (PGE2, PGI2, PGD2, PGF2). They act locally, through G protein–coupled receptors: PGE2 binds EP1–EP4 and PGF2 binds FP. COX-1 makes the housekeeping prostaglandins, including those that protect the gastric mucosa.
The drugs are analogs. Carboprost is 15-methyl PGF2α. Dinoprostone is PGE2 itself: in the myometrium its EP receptors act through membrane calcium channels and cAMP, and it promotes cervical softening, effacement and dilation, possibly through increased collagenase secretion and collagen degradation. It also stimulates PGF2α production, which sensitizes the myometrium to oxytocin. Misoprostol, a PGE1 analog, selectively binds EP2 and EP3 receptors and causes uterine contractions.
The ergot: sustained contraction, constricted vessels
Methylergonovine is a semi-synthetic ergot alkaloid. It acts directly on uterine smooth muscle, raising the tone, rate and amplitude of contractions — a rapid, sustained tetanic effect that shortens the third stage of labor and reduces blood loss. The same drug produces vasoconstriction, and WHO names hypertension as the most notable undesirable effect of ergometrine/methylergometrine, a particular risk for women with cardiovascular conditions.
That is why its labeled contraindications are hypertension and toxemia (and pregnancy), why IV use risks sudden hypertensive and cerebrovascular accidents, and why patients with coronary disease may develop myocardial ischemia from vasospasm. Ergot alkaloids are cleared mainly by hepatic metabolism; with other ergots, potent CYP3A4 inhibitors have caused vasospasm with cerebral or limb ischemia, so strong and moderate inhibitors are not given with methylergonovine.
PGF2α: the uterus, the gut and the airway
Carboprost’s myometrial contractions provide hemostasis at the placental site, and it is labeled for postpartum hemorrhage from atony that has not responded to oxytocin, massage and, unless contraindicated, an ergot. It also contracts other smooth muscle: the gut, so about two-thirds of patients have vomiting and diarrhea, and the bronchi — it may cause transient bronchoconstriction, so it is used cautiously in asthma, and active pulmonary disease is a contraindication. Its transient fever may reflect an effect on hypothalamic thermoregulation.
PGE1 and PGE2: the stomach and the cervix
Misoprostol is labeled only to reduce the risk of NSAID-induced gastric ulcers. NSAIDs inhibit prostaglandin synthesis, and a deficiency of mucosal prostaglandins may reduce bicarbonate and mucus secretion; misoprostol inhibits gastric acid secretion through prostaglandin receptors on parietal cells and can increase bicarbonate and mucus. Its commonest adverse effect, diarrhea, comes from exposure to misoprostol acid and correlates with its peak concentration. Because it also contracts the uterus, its boxed warning concerns pregnancy, and its obstetric uses are outside its approved indication. (Its use with mifepristone for pregnancy termination is on the Estrogens & progestins page; oxytocin is on the Oxytocin page.)
Prostaglandins used for cervical ripening increase the risk of tachysystole, a non-reassuring fetal heart rate and fetal hypoxemia, and they potentiate oxytocin. So oxytocin waits: the Cervidil insert is removed at least 30 minutes before an oxytocic is started (and is contraindicated with IV oxytocics), Prepidil needs a 6–12-hour interval, and misoprostol augments oxytocin especially when given less than 4 hours before it.
Comparing the drugs
Uterotonics compared
| Drug | Receptor / class | Labeled use | Avoid or caution in | Signature adverse effect |
|---|---|---|---|---|
| Methylergonovine | Ergot alkaloid (direct uterine smooth-muscle action) | Postpartum atony, hemorrhage, subinvolution | Hypertension, toxemia, pregnancy; strong/moderate CYP3A4 inhibitors | Hypertension; vasospasm |
| Carboprost (Hemabate) | PGF2α analog | Postpartum hemorrhage from atony unresponsive to conventional management | Active cardiac, pulmonary, renal or hepatic disease; caution in asthma | Vomiting and diarrhea; bronchoconstriction |
| Dinoprostone (Cervidil, Prepidil) | PGE2 (EP receptors) | Cervical ripening at or near term before induction | Prior cesarean or uterine surgery; IV oxytocics (Cervidil); caution in asthma, glaucoma | Uterine tachysystole |
| Misoprostol (Cytotec) | PGE1 analog (EP2/EP3) | Reducing the risk of NSAID-induced gastric ulcers | Pregnancy (boxed); prostaglandin allergy | Diarrhea; uterine contraction in pregnancy |
Pharmacokinetics
- Methylergonovine
- Onset immediate IV, 2–5 minutes IM, 5–10 minutes orally; oral bioavailability about 60%, probably from first-pass hepatic metabolism; mean elimination half-life about 3.4 hours.
- Misoprostol
- A prodrug, rapidly de-esterified to the active misoprostol acid, which peaks about 12 minutes after an oral dose and has a terminal half-life of 20–40 minutes; about 80% of the radioactivity appears in urine.
- Dinoprostone
- Metabolized in the tissues where it is made, half-life 2.5–5 minutes, inactivated by 15-hydroxyprostaglandin dehydrogenase; what escapes is 95% cleared on first pass through the lungs.
Uses & drug choice
- Methylergonovine — following delivery of the placenta, routine management of uterine atony, hemorrhage and subinvolution of the uterus; control of uterine hemorrhage in the second stage of labor after delivery of the anterior shoulder
- Carboprost (Hemabate) — postpartum hemorrhage due to uterine atony that has not responded to conventional management; also labeled for aborting pregnancy between the 13th and 20th weeks of gestation and related second-trimester situations
- Dinoprostone (Cervidil, Prepidil) — cervical ripening in pregnant women at or near term with a medical or obstetric indication for induction of labor
- Misoprostol (Cytotec) — reducing the risk of NSAID-induced gastric ulcers in patients at high risk of ulcer complications; its obstetric uses are outside the approved indication
Adverse effects
- Hypertension, vasospasm, myocardial ischemia (methylergonovine)
- Ergot vasoconstriction, enhanced by β-blockers; with other ergots, potent CYP3A4 inhibitors have caused vasospasm, so strong and moderate inhibitors are not coadministered.
- Bronchoconstriction (carboprost)
- PGF2α contracts bronchial smooth muscle.
- Vomiting and diarrhea
- Prostaglandin stimulation of gastrointestinal smooth muscle (carboprost, dinoprostone); misoprostol acid exposure (misoprostol).
- Fever
- A prostaglandin effect on the hypothalamus (misoprostol); with carboprost, possibly an effect on hypothalamic thermoregulation.
- Tachysystole, uterine rupture
- Prostaglandin contraction and sensitization of the myometrium to oxytocin; rupture risk rises with a scarred uterus.
- Raised intraocular pressure
- Prostaglandins, including dinoprostone, can raise intraocular pressure — hence the glaucoma caution.
Interactions
Contraindications
- Methylergonovine — hypertension, toxemia (preeclampsia), pregnancy, or hypersensitivity — Labeled contraindications — its vasoconstriction raises blood pressure, and its uterotonic effect endangers a pregnancy.
- Carboprost — hypersensitivity (including anaphylaxis and angioedema), acute pelvic inflammatory disease, or active cardiac, pulmonary, renal or hepatic disease — Labeled contraindications.
- Dinoprostone (Cervidil) — prostaglandin hypersensitivity; fetal distress where delivery is not imminent; unexplained vaginal bleeding; marked cephalopelvic disproportion; any contraindication to induction or to oxytocic drugs; previous cesarean section or other uterine surgery; six or more previous term pregnancies; concurrent IV oxytocic agents — Labeled contraindications — prolonged or stronger contractions would be unsafe for the fetus or the uterus, and dinoprostone augments oxytocin.
- Misoprostol — pregnancy, when taken to reduce the risk of NSAID ulcers; history of allergy to prostaglandins — Labeled contraindications — it can cause abortion, birth defects, premature birth or uterine rupture.
- Methylergonovine — strong or moderate CYP3A4 inhibitors (e.g., macrolide antibiotics, HIV protease inhibitors, azole antifungals) use caution — The label says not to coadminister them: with other ergots they have caused vasospasm leading to cerebral or limb ischemia.
- Carboprost or dinoprostone — history of asthma; dinoprostone — glaucoma or raised intraocular pressure use caution — Used with caution: carboprost can cause bronchoconstriction, and prostaglandins can raise intraocular pressure.
- Any uterotonic — a scarred uterus use caution — Used with caution because of the risk of uterine rupture; misoprostol is not used in the third trimester after cesarean or major uterine surgery.
High-yield
Practice questions
Q1A 31-year-old woman with preeclampsia (blood pressure 164/108 mm Hg) has ongoing heavy bleeding from uterine atony after a vaginal delivery, despite oxytocin and uterine massage. She has no history of asthma.
Which additional uterotonic is most appropriate?
- A.Methylergonovine
- B.Dinoprostone insert
- C.Misoprostol, because postpartum hemorrhage is its labeled indication
- D.Carboprost
Show answer
D. Carboprost — Carboprost is labeled for postpartum hemorrhage from atony that has not responded to oxytocin and massage, and its main cautions — asthma and active cardiopulmonary, renal or hepatic disease — do not apply here. Methylergonovine is contraindicated in hypertension and toxemia because of its vasoconstriction. Dinoprostone is labeled for cervical ripening before induction, and misoprostol’s only labeled indication is reducing NSAID-induced gastric ulcers; its use in postpartum hemorrhage is outside that indication.
Q2A 28-year-old woman receives carboprost for postpartum hemorrhage. Twenty minutes later she is coughing and wheezing, and she reports chest tightness.
What best explains her symptoms?
- A.Vasoconstriction from an ergot alkaloid
- B.A PGF2α analog contracting bronchial smooth muscle
- C.Relaxation of vascular smooth muscle causing hypotension
- D.Prostaglandin-induced relaxation of the gastrointestinal tract
Show answer
B. A PGF2α analog contracting bronchial smooth muscle — Carboprost is a 15-methyl analog of PGF2α; besides the myometrium it contracts other smooth muscle and may cause transient bronchoconstriction, which is why asthma calls for caution. Vasoconstriction is the effect of the ergot methylergonovine, not carboprost; large doses of carboprost raise rather than lower blood pressure, by contracting vascular smooth muscle; and it stimulates rather than relaxes gastrointestinal smooth muscle — the cause of its vomiting and diarrhea.
Q3A 26-year-old woman at 40 weeks with an unfavorable cervix has a Cervidil (dinoprostone) insert placed for cervical ripening before induction. Six hours later she is in active labor, and the team wants to start oxytocin.
What should happen first?
- A.Leave the insert in place and start oxytocin at once
- B.Start oxytocin and remove the insert only if tachysystole develops
- C.Remove the insert and start oxytocin at least 30 minutes later
- D.Give an IV oxytocic with the insert, because dinoprostone blocks oxytocin
Show answer
C. Remove the insert and start oxytocin at least 30 minutes later — Dinoprostone stimulates PGF2α production, which sensitizes the myometrium to oxytocin, and prostaglandins potentiate oxytocin. Cervidil is removed at the onset of active labor, and at least 30 minutes is allowed before an oxytocic is started; concurrent IV oxytocics are contraindicated. Waiting for tachysystole, or starting oxytocin with the insert in place, invites the hyperstimulation the interval is meant to prevent.
Q4A 34-year-old woman with rheumatoid arthritis and a prior bleeding gastric ulcer needs to stay on an NSAID, and her physician plans to add misoprostol.
Which plan follows the misoprostol label?
- A.Start it without precautions, because it acts only on the stomach
- B.Confirm a negative serum pregnancy test within 2 weeks, use effective contraception, and start on the second or third day of a period
- C.Avoid it in every woman of childbearing potential
- D.Take it with a magnesium-containing antacid to limit diarrhea
Show answer
B. Confirm a negative serum pregnancy test within 2 weeks, use effective contraception, and start on the second or third day of a period — Misoprostol is labeled to reduce NSAID-induced gastric ulcers in high-risk patients, but it also contracts the pregnant uterus and its boxed warning covers birth defects, abortion, premature birth and uterine rupture. A woman of childbearing potential at high risk may use it after a negative serum pregnancy test within 2 weeks, with effective contraception, starting on the second or third day of her next period — so it is not banned outright. Magnesium-containing antacids increase its diarrhea and are avoided.
Sources
- Methylergonovine maleate injection (American Regent) — FDA label: mechanism, indications, contraindications, IV warning, CYP3A4, neonatal errors — FDA / DailyMed
- Methylergonovine maleate tablets (Teva) — FDA label: indications, contraindications, breastfeeding — FDA / DailyMed
- Hemabate (carboprost) — FDA label: boxed warning, PGF2α actions, indications, contraindications, adverse reactions — FDA / DailyMed
- Cytotec (misoprostol) — FDA label: boxed warning, indication, labor and delivery, diarrhea, interactions — FDA / DailyMed
- Cervidil (dinoprostone vaginal insert) — FDA label: mechanism, contraindications, tachysystole, DIC, oxytocin interval — FDA / DailyMed
- Prepidil (dinoprostone gel) — FDA label: indication, cautions, oxytocin interval — FDA / DailyMed
- Postpartum Hemorrhage — uterine atony as the most common cause — StatPearls (NCBI)
- Misoprostol — mechanism, off-label obstetric uses, adverse effects — StatPearls (NCBI)
- Prostaglandins — receptor targets, carboprost and dinoprostone actions — StatPearls (NCBI)
- Uterine Atony — uterotonic medications and their cautions — StatPearls (NCBI)
- WHO consolidated guidelines on postpartum haemorrhage (2025) — first-line and second-line uterotonics for treatment — World Health Organization
- The use of stems in the selection of INN (-erg-, -prost) — World Health Organization
- Prostaglandin E2 (Dinoprostone) — EP receptors, cervical ripening — StatPearls (NCBI)
By LearnDrugs
Educational summary for medical students. Always verify against current prescribing information and guidelines. Not medical advice.