OXYTOCIN

• Polypeptide hormone, 9 amino acids, produced mainly by the para-ventricular nucleus of the hypothalamus and released by the posterior pituitary. Also produced locally in the ovary and testis
• Differs from ADH (arginine vasopressine) in only 2 amino acids
• Circulate largely unbound in plasma
• Half life ~3-5 min
• Oestrogen increases the sensitivity of the myometrium to oxytocin, while progesterone decreases sensitivity

Action

• Stimulates spasmodic contraction of the myometrium
• Stimulates contraction of the myoepithelial cells of the breast with milk ejection

Therapeutic use

• Induction and augmentation of labour – administered by intra-venous infusion
• Active management of the third stage of labour – administered by intravenous or intramuscular injection
• Management of post-partum haemorrhage

Side-effects

• Uterine hyper-stimulation with fetal compromise
• High doses may cause titanic uterine contraction
• Fluid retention and hyponatraemia associated with high doses
• Placental abruption
• Amniotic fluid embolism
• Nausea and vomiting

ERGOMETRINE

• Ergometrine is an amine ergot alkaloid
• Stimulates contractions of uterine and vascular smooth muscle
• Therapeutic administration usually produces sustained uterine contractions followed by only short or no periods of relaxation (titanic contraction). This impedes uterine blood flow. Contraction of the myometrium around bleeding vessels at the placental site produces haemostasis.
• Vasoconstriction results in raised blood pressure through stimulation of alpha-adrenergic and serotonin receptors.
• Onset of action is rapid after IV administration with uterine contraction occurring within 1 minute and persist for 45 minutes after IV injection.
• Following IM injection, uterine contractions occur within 2-5 minutes and persist for at least 3 hours

Therapeutic use

• Active management of the third stage of labour
• Management of post-partum haemorrhage

Side-effects

• Nausea & vomiting
• Hypertension
• Vaso-constriction with tissue ischaemia

Contra-indications

• Hypertension and other cardiovascular disease

TOCOLYTICS

• Drugs that inhibit / reduce uterine contractions during pregnancy

Clinical use

• Delay pre-term delivery for 24-48h, allowing time for corticosteroids to be administered or for in-utero transfer to a centre with appropriate neonatal facilities
• Shown to reduce the proportion of deliveries occurring within 48h of commencing treatment and may prolong pregnancy for up to 7 days
• Used on their own, tocolytics do not reduce the incidence of pre-term delivery, serious morbidity or perinatal mortality

BETA-AGONISTS

• Now less commonly used because of side-effects and availability of safer alternative
• Commonest used agent is ritodrine

Side-effects

• Palpitations, tremor, nausea, vomiting, headache, restlessness, tachycardia (dose-related)
• Heart rate should not exceed 140bpm because of associated risk of pulmonary oedema. Associated with hypotension.
• Rare side-effects include pulmonary oedema (secondary to anti-diuretic effect and excessive fluid in-put), myocardial ischaemia, hyperglycaemia and hyperinsulinaemia.

Contra-indications

• Women with known cardiac disease should not be given beta agonists
• Caution in multiple pregnancy (increased risk of pulmonary oedema) and diabetes mellitus especially when corticosteroids used

CALCIUM CHANNEL BLOCKERS

• Block membrane calcium transport and reduce intra-cellular calcium
• Nifedipine appears to be better than beta-agonists in delaying delivery for up to 48h or to gestations over 34 weeks and has fewer side-effects

Side-effects

• Headache, flushing, tachycardia, palpitations, hypotension, dependent oedema, constipation, increased urinary frequency, eye pain, visual disturbance

OXYTOCIN ANTAGONISTS

• Atosiban - competitive oxytocin / vasopressin antagonist
• Associated with significant increase in the number of women remaining undelivered at 24, 48h and 7 days after commencing treatment compared to placebo
• Similar efficacy to beta agonists but with fewer cardiovascular side-effects

Side-effects

• Nausea, vomiting, tachycardia, hypotension, headache, hyperglycaemia, hot flushes, injection site reaction

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

• Inhibit prostaglandin synthesis
• Indomethacin commonly used - more effective than placebo in delaying delivery for 48h and 7 days, reducing deliveries before 37 weeks gestation and births <2500g
• Concerns about fetal risks - constriction of the ductus arteriosus, oligohydramnios, necrotising enterocolitis and intra-ventricular haemorrhage

OTHER USES OF TOCOLYSIS

• External cephalic version (ECV) - Routine tocolysis with beta-agonists appears to reduce the failure rate of ECV, especially in primigravidae
• Fetal distress associated with uterine hyper-stimulation following prostaglandin induction of labour - sub-cutaneous terbutaline is recommended