Endocrinology 8c - Pharmacology of Oxytocin
Anil Chopra
1. Describe the actions of the following drugs on the pregnant uterus and explain
how they may be exploited clinically: oxytocin, prostaglandins, ergometrine,
mefepristone. Outline the main pharmacokinetic properties of these drugs and
state what adverse effects they may each produce. Note that ß2-adrenoceptor
agonists, magnesium sulphate and type 2 cyclo-oxygenase (COX-2, type 2
prostaglandin synthase) inhibitors possess tocolytic properties.
Drugs that act on the uterus have a number of different uses. They can induce and aid
in labour (oxytocin), control post partum haemorrhages, uterin atony (loss of uterine
muscle tone), therapeutic abortion and delaying premature labour.
Oxytocics
Name – oxytocin
Usage – its main use is to induce labour
when needed. It is also used to prevent
and treat post-partum haemorrhage as
its local pressor action stops bleeding. Its
other use is to facilitate milk ejection.
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PVN
SON
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hypothalamus
anterior
lobe
neural
lobe
Mode of Action – the structure of
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oxytocin
oxytocin is very similar to that of
vasopressin. It affects a number of
Myoepithelial cells
different organs:
(mammary gland)
 Uterus
o Rhythmic contraction from
suckling
the fundus to the cervix.
milk
labour
o Dilation of cervix.
ejection
o It is released by a mechanism of positive feedback.
o Its release is Pulsatile.
o Its actions are suppressed by progesterone and enhanced by oestrogens.
o It is most marked in the late stages of pregnancy.
o Increase local prostanoid production
 Mammary gland (breasts)
o Contraction of myoepithelial cells
o Milk ejection.
 Cardiovascular
o Transient vasodilation & tachycardia
o Constriction of umbilical arteries and veins
 Renal
o Anti-diuresis & secondary hyponatraemia, i.e. vasopressin-like.
 CNS
o Causes maternal behaviour
o Causes social recognition
oestrogens
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Uterus
(cervical dilation)
uterine
contractions
Giving birth
Mating
(released on
orgasm)
in both sexes)
OT (VP)
release
in the brain
Promotes
monogamous
bonds in certain
mammalian species*
Promotes parent-offspring
bonds in certain
mammalian species*
Promotes social
recognition
memory and trust
Side Effects and Pharmacokinetics
Given i.v. or as an intranasal spray (generally when using it for milk ejection). It is distributed in
extracellular fluid and is metabolised in the liver and kidney. Its ½ life is 5 minutes.
Side effects:
 Compromised placental exchange of O2/nutrients  foetal distress
 Foetus forced against an undilated cervix  lacerations/trauma
 Uterine rupture
 Transient but serious hypotension with reflex tachycardia
 Water intoxication of mother and foetus
It has been shown that vasopressin and oxytocin receptors are expressed on reward centres.
These are dysfunctional in autism and activated when we see someone we love.
Name – ergometrine
Usage – used to treat:
- Parkinson’s disease
- Hyperprolactinaemia
- Migraine
- Late stages of labour
- Patients at high risk post partum haemorrage, i.v. after delivery of the
shoulders.
- Post-partum atony of the uterus – oral
Mode of action – it causes more prolonged series of contraction during labour and
increase myometrial tone. It causes constriction of umbilical and placental vessels.
Side Effects and Pharmacokinetics
It is administered i.v. metabolised by the liver and has a half life of 3-4 hours.
- Contra-indications
o Pregnancy prior to the 3rd stage of labour
o Pre-eclampsia and other vascular disease
Side effects
• Abdominal pain
• Hypertension
• Anginal pain
• Nausea/vomiting
Name – prostaglandins and abortifaciens.
Dinoprostone, gemeprost, carboprost
Usage – used in:
- Induction of abortion - dinoprostone
- Induction of cervical ripening – at term:
dinoprostone
- Post-partum haemorrhage in those resistant to
oxytocin and ergometrine - cabropost
Mode of Action – these stimulate
contractions throughout pregnancy and
cause ripening of the uterus by
softening the tissue.
Side Effects and Pharmacokinetics
Side Effects
• Potentiation of actions of
oxytocin
• Nausea, vomiting, diarrhoea
• Hypertension (PGF ), hypotension (PGE2)
• Pyrexia
Progesterone Receptor Blockers
Name – mifepristone
Usage – early therapeutic abortion (up to 63 days – 9 weeks) and softening and
dilation of the cervix before suction abortion.
Mode of Action – mifepristone is an antagonist at
progesterone receptors.
Side Effects and Pharmacokinetics
It is administered orally, enters cells but distributed
by binding proteins. It is metabolised by the liver
and kidney and excreted in the kidneys. Its ½ life is
around 20-40h. Side effects may
include:
- vaginal bleeding
- headache
Tocolytics
Tocolytics reduce motility by
binding to β2 adrenergic receptors in the myometrium, increasing intracellular cAMP
resulting in relaxation of the uterine muscle.
They are used to delay premature labour