UTERINE STIMULANTS AND

RELAXANTS
Dr Pratibha omkar
Additional Associate professor
Case scenario
• Mrs M aged 24yrs and 13 weeks pregnant presented
to the emergency department with abdominal
cramping and heavy vaginal bleeding and clots. Over
the past 2 days, she has experienced light spotting,
which has increased in severity that morning. Mrs M
reported fever, chills, burning on urination, nausea or
vomiting.
• On pelvic examination products of conception was
felt through OS. Doctor decides to initiate uterine
contractions followed by dilatation and evacuation.
What is the drug chosen by the doctor?
 UTERINE STIMULANTS

• Drugs which stimulate the uterine contractions

• Oxytocin, ergometrine and prostaglandins.

• They are also called oxytocic's or ecbolic.

• These drugs are useful in obstetrics.

 OXYTOCIN

• Oxytocin is a peptide hormone - posterior pituitary along

with ADH.

• Synthesized in paraventricular nuclei of the hypothalamus

• Transported along the axon and stored in the
neurohypophysis.

• Released by stimuli such as suckling, coitus

and parturition.
Actions
1. Uterus: Oxytocin contracts the uterus.
• The fundus and the body contract, while the lower segment
is relaxed.
• Force and frequency of contractions - full relaxation in
between the contractions.
• This relaxation allows adequate blood supply to the fetus.

• At full term, the uterus is highly sensitive to the effects of

oxytocin as there is an increase in the number of oxytocin
receptors.
• Estrogen enhances the synthesis of oxytocin receptors
and sensitizes the uterus to the effects of oxytocin.

• The effects are dose dependent.

• High doses - sustained contractions with no relaxation in

between, resulting in reduced blood flow to the fetus, fetal
distress and death.

• Synthetic oxytocin is used for therapeutic purpose.

 Mechanism of action

• Oxytocin receptors are G-protein coupled receptors

on myometrium when stimulates leads to generation
of IP3 and mobilization of Ca from intracellular
stores and depolarization induced activation of
voltage –sensitive Ca channels.
Breast :
• Oxytocin facilitates milk ejection by contraction of
the myoepithelium in the mammary alveoli
• Milk ejection reflex
• Suckling stimulates the release of oxytocin.
CVS:
• High doses causes vasodilatation, and decrease
in BP, reflex tachycardia and flushing

• Others: Oxytocin has mild antidiuretic effects

(urine output is reduced)
Pharmacokinetics:
• Inactive orally, generally i.m or i.v routes
• Oxytocin is given as IV infusion, nasal spray,
buccal tablets.
• It is metabolized by the liver and kidneys by
the enzyme oxytocinase.
• t1/2 6-12 mins
Uses:

• Induction of labour: Oxytocin is used to induce or augment

labour when uterine contractions are inadequate. (i.v
infusion)
• dose : 5 IU diluted in 500ml of glucose slow i.v infusion

• Uterine inertia:2- 5IU diluted in 500ml of glucose/normal

saline
• Postpartum haemorrhage:
• An alternative to ergometrine.(i.m injection
after placenta is expelled- tetanic contractions
of uterus and arrests bleeding .
• 5 IU give i.m or i.v infusion
• Milk ejection: When milk ejection is impaired in
nursing mothers
• Intranasal oxytocin spray 25-30 IU in each nostril in
sitting position 2-3 mins before nursing.

• Abortion: As an alternative to induce midtrimester

abortion
 Desamino- oxytocin

Buccal formulations:
• Induction of labor- 50IU repeated after 30 mins till
desired effects seen. Max 10 tablets (500IU)

• Uterine Inertia: 25 IU every 30 mins

• Breast engorgement and milk let down: 25-50 IU

before breast feeding.
Adverse Effects:

• Non-judicious use:
- Fetal and maternal soft tissue injury
- Rupture of uterus
- Fetal asphyxia

• Water intoxication: large doses given with saline

• Serious in pre-eclampsia
Contraindications :
• Cephalo-pelvic disproportion

• Breech presentation

• Placenta praevia and fetal distress

• Caesarean section preferred in such cases

Ergot alkaloids
 Introduction

• Produced by fungus (Claviceps purpurea) which

infects cereal crops and is responsible for sporadic
poisoning

Types :
• Ergotamine /dihydroergotamine
• Methysergide
• Bromocriptine
• Ergometrine
 Ergometrine

• Ergometrine and its derivative methylergometrine are

used as uterine stimulants.

• Ergot has been used by midwives to quicken labor since

centuries.

• Ergometrine and its analogues increase myometrial

contractions involving the fundus, the body, and the
cervical segments of the uterus.
Actions on the Uterus

• Ergometrine is a powerful uterine stimulant.

• Increase the force and frequency and duration of uterine

contractions
• All parts of the uterus including the fundus, body and the
lower segment contract.
• There is no relaxation in between contractions.
• Full term uterus is more sensitive to the actions of
ergometrine.
• CVS: weak vasoconstrictors and have low propensity to
cause endothelial damage. Raise in Bp (not significant)

• Ergometrine also causes some vasoconstriction which

helps to reduce bleeding from the uterus in postpartum
state.

• GIT: increase peristalsis

Mechanism :
• It brings about its effects by binding to
serotonin receptors.
• Partial agonist-antagonist at 5-HT2 and alpha
adrenergic receptors present on uterine
myometrium
Pharmacokinetics:
• Ergometrine is rapid and short acting.
• It can be given orally, IM or IV.
• Bioavailability is higher after sublingual and rectal
administration but erratic
• Methylergometrine in addition can be given SC.
• Metabolized in liver and excreted primarily is bile
• Ergotamine is sequestrated in tissues-produces longer
lasting actions compared to its plasma t1/2 2 hours
Uses:
1. Postpartum haemorrhage: Ergometrine is used to
control and prevent PPH.
• Dose: 0.2-0.5mg injected i.m (contraction of myometrial
meshwork compress the bleeding arteries, which stop the
bleeding
• PPH occurring- 0.5mg i.v.
• Severe bleeding – combination of ergometrine 0.5mg
with oxytocin 5IU i.m/i.v
2. To hasten uterine involution: Ergometrine is
given for 7 days.(multipara)
• Dose :0.125mg of ergometrine or
methylergometrine TDS oral 7 days
3. To prevent uterine atony-after caesarean
section.(0.2 TO 0.4mg )

3. Management of third stage labour:

ergometrine (0.2-0.5 mg)intramuscular after
the appearance of anterior shoulder
Adverse Effects
• Nausea and vomiting
• Hypertension
• Decrease milk secretion (dopaminergic action)

• Contraindications :
• Vascular disease, hypertension
• Presence of sepsis- gangrene
• Liver and kidney disease
• Pregnancy 3rd stage of labour
Prostaglandins
 PROSTAGLANDINS

• Prostaglandins are synthesized by the uterus and

play a significant role in menstruation as well as
parturition.

• PGE2 and PGF2a stimulate the contraction of both

pregnant and nonpregnant uterus.

• Sensitivity is higher during pregnancy.

• They also soften the cervix and hasten dilatation
(cervical ripening)by increasing the proteoglycan
content and changing the collagen characteristics.

• PGs produced by fetal tissues mediate initiation

and progression of labor.
PGs used in obstetrics are :
• Dinoprostone (PGE2) intravaginal or extra-amniotic
• Carboprost (15 methyl PGF2a) deep IM
• Misoprostol (Gemeprost, PGE1) intravaginal

• Prostaglandins are also involved in the pathogenesis of

dysmenorrhoea and menorrhagia.
• Hence NSAIDs are useful in relieving dysmenorrhoea and
probably menorrhagia
Uses
1. Abortion:
• First trimester:
• Dinoprostone is given intravaginally 3 hours before
dilatation- minimize trauma to cervix by reducing
resistance to dilatation

• Second trimester :
• MTP- 7-9 weeks
• Mifepristone 600mg orally –then single dose of 400
microgm misoprostol
• Gemeprost 1mg is given as vaginal pessary following
mifepristone.
3. PPH : carboprost injected i.m .
• 0.25mg every 30-120 minutes

3. Cervical priming : gels are used intravaginally to

soften the cervix and for cervical ripening prior to
induction of labor.
• 0.5mg in 2.5ml prefilled syringe

4. Induction of labour :PGs are used as alternatives to

oxytocin in toxaemia and renal failure patients
• Intravaginal tablet 3mg used
Adverse effects :
• Nausea and vomiting
• Headache
• Shivering, fever and diarrhea
• Uterine cramps
• Forceful contractions
• Fall in BP, tachycardia
• Chest pain
Uterine relaxants
(Tocolytics)
• A 22 year rashmi primigravida with 24 weeks of
gestation came to the hospital with the complains of
backpain since 1 day. There was no history of
bleeding or fluid gush.
• On abdominal inspection and pelvic examination:
• Cephalic presentation, Gravid uterus: 24cm
• Fetal heart rate :150bpm,Cervical dilatation:4cm
• Effacement 100%,Engagement 1/5.
• The doctor diagnosed the condition as preterm labour
and decides to postpone the labour. The drug
combination used for the above purpose is :
• a). Dexamethasone with oxytocin
• b). Ergometrine with oxytocin
• c). Dexamethasone with Nifedipine
• d). Enalapril and nifedipine
 Uterine Relaxants (Tocolytics)

• Drugs that reduce uterine motility and relax the uterus

• Adrenergic agonists -
Ritrodrine,Salbutamol, terbutaline and
isoxsuprine.
• Oxytocin antagonist: Atosiban
• Calcium channel blockers- Nifedipine
• Prostaglandin synthesis inhibitors-
Indomethacin and aspirin
• Miscellaneous: Magnesium sulfate,
nitroglycerine, progesterone and halothane
 Selective Beta adrenergic agonists

• Ritodrine and salbutamol and terbutaline relax the

uterus
• Suppress premature labor –

• These drugs bind to beta 2 receptors on myometrium

and activating adenyl cyclase- increase cAMP levels
dependent protein kinase – so intracellular Ca
concentration reduced- relaxation
• Salbutamol- IV infusion is started 10 mg per minute
and the dose may be gradually increased up to 40 mg
per minute.

• Alternatively ritodrine IV infusion may be started –50

mg per minute and gradually increased to 100 mg per
minute till the contractions stop.
Adverse effects :

• Anxiety , palpitation, restlessness, headache

• CVS-hypotension, arrhythmias

• Metabolic – hyperglycemia, hypokalemia and

hyperinsulinemia

• High dose: maternal morbidity and fetal pulmonary

edema
Contraindications :
• Diabetic mother heart disease receiving beta
blockers or steroids
 ATISOBAN

• Oxytocin receptor antagonist

• Approved to inhibit premature labor

• Administered 6-7mg i.v bolus followed by i.v

infusion(0.75mg/ml) for not more than 48 hours

Adverse effects:
• Nausea , vomiting
• Vasodilatation, hyperglycemia and rash
 CALCIUM CHANNEL BLOCKERS

• Act by impairing Ca entry into the myometrial cells

via voltage gated L-type channels to inhibit uterine
contractility.

• Nifedipine: sublingual 10 mg repeated every 20 mins

till contractions subside – followed by 10mg 6th hrly.
Adverse effects :
• Hypotension
• Tachycardia
• Reduced placental perfusion causing fetal hypoxia
 MAGNESIUM SULFATE

• pts with cardiac problems, diabetes, hyperthyroidism and

hypertension.

• High doses - CNS and respiratory depression.

• Also used to suppress convulsions and control the BP in

preeclampsia and eclampsia.
• Directly uncouples excitation- contraction in
myometrial cells and inhibit cellular action potential.

• A bolus dose of 2-4g is infused over 10–20 min

followed by 1g/litre infusion.

• For effective inhibition: plasma levels 6mEq/L - 7.5

Meq/L.
Adverse effects :
• Therapeutic doses-sweating, flushing
• Dry mouth, nausea
• Headache and palpitation

• >8mEq/L –patellar reflexes lost

• >10-12mEq/L-respiratory depression and arrest
• >12mEq/L-cardiac arrhythmias and arrest
Miscellaneous

• Alcohol given IV is a tocolytic but produces marked CNS

depression.

• Similarly aspirin and indomethacin are not preferred as

tocolytics because of the risk of closure of ductus arteriosus
and other adverse effects.
Uses of Tocolytics

1. To delay premature labour: Tocolytics may not always be

successful.
• Uterine contractions may be controlled for 24–48 hr
which should be utilised to prepare the foetus for preterm
birth, i.e for example, by giving glucocorticoids to bring
about early maturation of foetal lungs.
2. In threatened abortion to inhibit uterine contractions.
3. Dysmenorrhoea to suppress painful uterine contractions.
Thank you