Uterotonic Drugs

Uterotonic drugs make the uterus contract. They prevent and treat postpartum haemorrhage (PPH), induce and augment labour, and empty the uterus after miscarriage or termination. The main drugs are oxytocin, carbetocin, ergometrine, misoprostol, carboprost and dinoprostone. Choice depends on the setting, the time in relation to birth, blood pressure, asthma, cold chain and available skills.

Classification. Oxytocin receptor agonists (oxytocin, carbetocin); ergot alkaloids (ergometrine, methylergometrine); prostaglandins (misoprostol, carboprost, dinoprostone).

Mechanism. Oxytocin receptor agonists raise intracellular calcium in myometrial cells. Ergot alkaloids act on alpha-adrenergic and serotonin receptors and cause sustained contraction. Prostaglandins act on EP and FP receptors, ripen the cervix and contract the uterus.

Pharmacokinetics. Oxytocin acts within 1 minute intravenously and 3 to 5 minutes intramuscularly, with a half-life of 3 to 5 minutes. Carbetocin lasts about 1 hour. Ergometrine acts in 2 to 5 minutes intramuscularly. Misoprostol peaks at 30 minutes sublingually.

Storage. Oxytocin and ergometrine need 2 to 8 degrees Celsius and protection from light. Carbetocin (heat-stable form) and misoprostol tolerate room temperature, which is useful where cold chain is weak.

Uterine massage and traction. Controlled cord traction and uterine massage support active management but do not replace the drug.

• First-line. Oxytocin for prevention and treatment of PPH after vaginal and caesarean birth.
• Alternative. Carbetocin where heat stability or a single dose is needed; misoprostol when oxytocin is unavailable or injectables cannot be given, including community birth.
• Specialist. Ergometrine in normotensive women when oxytocin fails; carboprost for refractory atony in women without asthma; intrauterine misoprostol and other adjuncts.
• Emergency. Atonic PPH: massage, oxytocin, tranexamic acid 1 g intravenously, and escalate through ergometrine, carboprost and misoprostol while preparing for surgery.

Principles. Give a uterotonic to every woman at birth. Do not use ergot alkaloids or prostaglandins before the baby is delivered. Always search for other causes of bleeding (tissue, trauma, thrombin disorders) when the uterus is firm.

Contraindications. Oxytocin: hypersensitivity; use only after the diagnosis is clear in labour. Ergometrine: hypertension, pre-eclampsia, eclampsia, ischaemic heart disease, peripheral vascular disease, severe liver or kidney disease. Carboprost: asthma, active cardiac, pulmonary, renal or hepatic disease. Misoprostol: hypersensitivity.

Serious adverse effects.

• Oxytocin: hypotension and tachycardia with a rapid bolus, water retention and hyponatraemia with prolonged high-dose infusion, uterine hyperstimulation.
• Ergometrine: severe hypertension, vomiting, headache, coronary spasm.
• Carboprost: bronchospasm, diarrhoea, vomiting, flushing, fever.
• Misoprostol: shivering, fever, diarrhoea, nausea.

Major interactions. Ergometrine with CYP3A4 inhibitors (protease inhibitors, macrolides, azoles) risks ergotism, so avoid the combination. Vasoconstrictors add hypertension. Prostaglandins and oxytocin together raise hyperstimulation risk, so leave an interval.

Common prescribing errors.

• Giving oxytocin as a rapid intravenous bolus.
• Giving ergometrine to hypertensive women.
• Using prostaglandins in asthma.
• Missing the cold chain, leaving oxytocin in the heat.
• Omitting prevention at birth.

Special groups.

• Pregnancy: uterotonics are given at or after birth, or for induction under supervision.
• Breastfeeding: all compatible; ergometrine may reduce milk volume.
• Children and adolescents: dose as adults.
• Older adults: not applicable.
• Kidney and liver: avoid ergometrine in severe disease.
• East Africa: PPH is a leading cause of maternal death where access to skilled birth care is limited; oxytocin cold chain failure is common, so check storage and keep heat-stable carbetocin or misoprostol in the facility emergency set; protease inhibitor antiretrovirals raise ergometrine toxicity.

Monitoring. Blood pressure and pulse; uterine tone and blood loss measured every 15 minutes for the first hour; fluid balance and sodium with prolonged oxytocin; respiratory rate with carboprost.

Referral and escalation. Bleeding that continues after two uterotonics; shock; need for surgery, balloon tamponade or transfusion; retained placenta.

Comparison with alternative classes. Uterotonics act on the cause of most PPH (atony) and are cheap, but they work only if the uterus is the source. Tranexamic acid, tamponade and surgery address other causes or failure.