Uterotonic agents

Uterotonic agents are pharmacological substances that induce or enhance contractions of the uterus. These agents play a crucial role in obstetric and gynecologic care, particularly in the induction of labor, augmentation of uterine contractions during labor, control of postpartum hemorrhage (PPH), and management of incomplete or missed abortion. Uterotonics act on the uterine smooth muscle to promote coordinated contractions that help expel uterine contents and maintain uterine tone.

These drugs mimic or amplify the effects of endogenous oxytocin, prostaglandins, or ergot alkaloids. They are administered via various routes—intravenous, intramuscular, oral, sublingual, buccal, vaginal, or rectal—depending on the clinical scenario, urgency, and drug formulation.

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Clinical Applications

1. Labor induction and augmentation

2. Medical abortion (first or second trimester)

3. Postpartum hemorrhage control and prevention

4. Uterine evacuation in cases of intrauterine fetal demise (IUFD)

5. Uterine atony treatment post-delivery

6. Uterine involution acceleration post-cesarean or vaginal birth

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Classification of Uterotonic Agents by Pharmacologic Class

Class	Examples (Generic Names)	Mechanism
Oxytocin analogs	Oxytocin, Carbetocin	Activate oxytocin receptors on myometrium
Prostaglandins	Misoprostol, Dinoprostone, Carboprost	Stimulate prostaglandin receptors (EP/FP types)
Ergot alkaloids	Methylergometrine (Methylergonovine), Ergometrine	Agonists at α-adrenergic and serotonin receptors
Combination agents	Oxytocin + ergometrine (e.g., Syntometrine)	Dual mechanism (oxytocic and ergot-like)

Detailed Uterotonic Agents: Generic Profiles

1. Oxytocin

• Class: Oxytocin analog

• Formulation: Injectable (IV, IM)

• Mechanism: Stimulates uterine smooth muscle by binding to oxytocin receptors, increasing intracellular calcium

• Indications:

  • Labor induction or augmentation

  • Prevention and treatment of postpartum hemorrhage

• Dosage:

  • Induction: 1–2 mU/min IV infusion, titrated up

  • PPH: 10 IU IM after delivery or continuous infusion

• Onset: Rapid (within 1–2 minutes IV)

• Half-life: ~3–5 minutes

• Side Effects:

  • Hypotension (if bolus), uterine hyperstimulation, water intoxication (antidiuretic effect)

• Cautions:

  • Risk of uterine rupture with prolonged use or high doses

  • Contraindicated in fetal distress without imminent delivery

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2. Carbetocin

• Class: Long-acting oxytocin analog

• Formulation: Injectable (IM or IV, single dose)

• Use: Prevention of PPH after cesarean or vaginal delivery

• Dosage: 100 mcg IM or IV over 1 minute

• Advantage: Single dose equals 16 hours of uterine activity

• Brand: Duratocin®, Pabal®

• Notable Features:

  • Lower need for additional uterotonics

  • Not widely available in low-income settings

• Caution: Contraindicated in preeclampsia and cardiovascular disease

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3. Misoprostol

• Class: Synthetic prostaglandin E1 analog

• Formulation: Tablets (oral, sublingual, buccal, rectal, vaginal)

• Indications:

  • Prevention and treatment of PPH

  • Medical abortion (in combination with mifepristone)

  • Cervical ripening

• Doses:

  • PPH: 600–800 mcg orally or sublingually (prevention/treatment)

  • Abortion: 800 mcg vaginally/buccally every 3 hours (with mifepristone)

• Advantages:

  • Heat-stable and inexpensive

  • Suitable for low-resource settings

• Side Effects:

  • Fever, shivering, diarrhea, nausea, uterine rupture (rare, high doses)

• Contraindications:

  • Hypersensitivity to prostaglandins, prior cesarean or uterine surgery in second-trimester use

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4. Dinoprostone

• Class: Natural prostaglandin E2 (PGE2)

• Formulation: Vaginal insert, suppository, gel

• Indications:

  • Cervical ripening

  • Labor induction

  • Uterine evacuation (less commonly used for PPH)

• Dosage:

  • Cervical ripening: 10 mg vaginal insert (Cervidil®)

  • Gel: 0.5 mg intracervical (Prepidil®)

• Onset: Within 10 minutes (gel), up to 12 hours (insert)

• Caution:

  • Monitor fetal heart rate

  • Remove insert with hyperstimulation

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5. Carboprost Tromethamine

• Class: Prostaglandin F2α analog

• Formulation: Injectable (IM only)

• Indications:

  • Treatment of PPH due to uterine atony unresponsive to oxytocin or ergometrine

  • Abortion (2nd trimester)

• Dosage: 250 mcg IM every 15–90 minutes (max 2 mg)

• Brand: Hemabate®

• Side Effects:

  • Severe diarrhea, nausea, vomiting, fever

  • Hypertension, bronchospasm

• Contraindications:

  • Asthma, cardiovascular disease, hepatic or renal dysfunction

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6. Methylergometrine (Methylergonovine)

• Class: Ergot alkaloid

• Formulation: Injectable (IM, IV), oral

• Mechanism: α-adrenergic, dopaminergic, and serotonin receptor agonist activity leading to vasoconstriction and uterine contraction

• Indications:

  • Prevention and treatment of PPH

• Dosage:

  • 0.2 mg IM after delivery (repeat q2–4h if needed)

  • Oral 0.2 mg q6–8h for 2–7 days (not first-line)

• Caution:

  • Avoid IV administration (can cause hypertension, stroke)

  • Contraindicated in preeclampsia/eclampsia, hypertension, and cardiovascular disease

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7. Syntometrine

• Class: Combination (Oxytocin + Ergometrine)

• Formulation: Injectable (IM)

• Indications:

  • Active management of third stage of labor

  • Prevention of PPH

• Dosage: 1 mL IM after delivery

• Brand: Syntometrine®

• Contraindications:

  • Hypertension, preeclampsia, heart disease

• Adverse Effects:

  • Nausea, vomiting, increased BP, chest pain

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Comparison of Common Uterotonics

Agent	Time to Effect	Duration	Use in PPH	Use in Labor	Contraindications
Oxytocin	1–2 min (IV)	Short	Yes	Yes	Fetal distress, uterine rupture
Carbetocin	2–5 min	Long (~1 hr)	Yes	No	HTN, preeclampsia, cardiac disease
Misoprostol	10–15 min (oral)	3–6 hrs	Yes	Yes	Prior uterine scar (high dose)
Dinoprostone	10 min–12 hrs	Variable	Rarely	Yes	Asthma, glaucoma
Carboprost	5–15 min	~2 hrs	Yes	No	Asthma, HTN, renal/liver disease
Methylergometrine	2–5 min	3 hrs	Yes	No	HTN, CAD, preeclampsia

Routes of Administration

• IV infusion: Oxytocin

• IM injection: Oxytocin, Carbetocin, Methylergometrine, Carboprost

• Oral/sublingual: Misoprostol

• Vaginal/rectal: Misoprostol, Dinoprostone

• Intracervical: Dinoprostone gel

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Drug Interactions

• Vasoconstrictors: Methylergometrine + sympathomimetics → hypertension

• Magnesium sulfate: May reduce oxytocin effectiveness

• Prostaglandins: Avoid combination due to increased side effects

• Anesthetics: Volatile agents may antagonize oxytocin effect

• Ergot + protease inhibitors (e.g., ritonavir): Risk of ergot toxicity due to CYP3A4 inhibition

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Adverse Effects

System	Effects
Gastrointestinal	Nausea, vomiting, diarrhea (notably misoprostol, carboprost)
Cardiovascular	Hypertension, hypotension, tachycardia, chest pain
Respiratory	Bronchospasm (carboprost), dyspnea
Neurologic	Seizures (rare), headache
Reproductive/Uterine	Hyperstimulation, rupture, severe cramping
Other	Fever, chills, flushing (especially with prostaglandins)

Special Populations

• Pregnancy: Most uterotonics are used only in late pregnancy or labor settings

• Preeclampsia: Avoid ergot derivatives and carbetocin

• Asthma: Avoid carboprost and prostaglandin analogs

• Renal/hepatic impairment: Use with caution, especially with ergot derivatives

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Global Use and Availability

• WHO recommendations for PPH management prioritize oxytocin (10 IU IM/IV) as first-line

• Misoprostol is recommended where oxytocin is unavailable or cold chain cannot be maintained

• Carbetocin is included in updated WHO guidelines where feasible due to its single-dose advantage

• Ergot derivatives are considered second-line due to side effect profiles