Drugs in the Third Stage of Labour: MRCOG Part 1 questions and key facts

When administered intravenously, synthetic oxytocin rapidly reaches the uterine myometrium and binds to oxytocin receptors. This binding initiates a cascade leading to increased intracellular calcium concentrations, resulting in myometrial cell contraction. Due to the direct entry into the circulation and rapid distribution, the onset of uterine contraction following an IV bolus of oxytocin (commonly given after delivery of the baby during caesarean section to prevent postpartum haemorrhage) is very quick, usually occurring within 1 minute.

The other options describe much slower onsets. 5-10 minutes is slower even than intramuscular injection, after which contractions usually begin within about 2 to 4 minutes because the drug must first be absorbed from the muscle. 15-20 minutes is closer to the time an oxytocin infusion for induction or augmentation of labour takes to produce its full effect, since the uterine response to a low-dose infusion builds up gradually over 20 to 40 minutes. 30 minutes and 60 minutes bear no relation to the onset of an intravenous bolus; a delay of that length would leave the uterus atonic throughout closure of the hysterotomy, when prompt contraction is needed to limit blood loss. The rapid onset is a key pharmacological property utilised in obstetrics.

Syntometrine is a combination medication specifically formulated for use in the active management of the third stage of labour. It contains two active ingredients: ergometrine maleate and oxytocin. Oxytocin is a synthetic version of the naturally occurring posterior pituitary hormone, which initiates strong, rhythmic uterine contractions relatively quickly. Ergometrine is an ergot alkaloid that produces a more sustained, tonic contraction of the uterus. The combination aims to achieve both rapid onset and sustained uterine contractility, which helps facilitate placental separation and delivery, constricts uterine blood vessels at the placental site, and thereby minimises blood loss, preventing or treating postpartum haemorrhage (PPH).

Misoprostol is a prostaglandin E1 analogue that also causes uterine contractions and is used for PPH prevention and treatment, often as an alternative when oxytocin/ergometrine are contraindicated or unavailable, or in lower-resource settings due to its stability and ease of administration (oral/rectal). Carboprost (a prostaglandin F2α analogue) is another potent uterotonic, typically used as a second-line agent for PPH unresponsive to oxytocin and/or ergometrine. Nifedipine is a calcium channel blocker primarily used as a tocolytic agent to suppress preterm labour contractions or to manage hypertension. Magnesium sulphate is chiefly used for seizure prophylaxis and treatment in pre-eclampsia/eclampsia and for fetal neuroprotection in preterm birth; it also has tocolytic effects. Therefore, nifedipine and magnesium sulphate have actions generally opposite to those desired in the third stage of labour.