Drugs acting on the uterus

Uterine stimulants
(oxytotics or abortifacients)
• Posterior Pituitary hormones:
Oxytocin, Desamino oxytocin
• Ergot alkaloids: Ergometrine,
methylergometrine
• Prostaglandins: PGE2, PGF2α,
misoprostol
 I. Uterine stimulants
1. Oxytocin: (nonapeptide=9 a.a peptide)
- Contracts the uterus → delivery
The uterus is insensitive to oxytocin in early
pregnancy but its sensitivity increases with
advanced pregnancy reaching maximum at time
of delivery
- Has slight ADH-like activity
- Contracts the myoepithelial cells of the breast →
milk letdown; milk ejection
 Oxytocin MOA:
- Surface receptors → stimulation of
voltage-sensitive Ca++ channels →
depolarization of uterine muscles →
contractions
- ↑ intracellular Ca++
- ↑ prostaglandin release
 Clinical uses to oxytocin:

Augmentation of labour.
- In hypotonic contractions in dysfunctional
labour (nulliparous).
- But be careful, normal progression of
labor should never be tried to hasten,
because overstimulation may cause.
Uterine rupture. Trauma of mother. Trauma
of fetus. Compromised fetal oxygenation.
 Clinical uses to oxytocin:
Post partum haemorrhage, cesarean section:
- Especially useful in hypertensive women
where ergometrine cannot be used
- Also to maintain normal tone of uterine
muscle
Breast engorgement:
- Inefficient milk ejection reflex
- Intranasal spray before suckling
 Side effects to oxytocin:
- Rupture of the uterus
Major and most serious side effect
- Hypertension
Due to its ADH-like activity
Higher dose (more than 20 ml/min) may reduce water
clearance – leading to water intoxication, coma and death
• Specific oxytocin antagonist
Atosiban, effective in the management of premature
delivery
 Ergot alkaloids
Ergometrine
Natural ergot alkaloid also called ergonovine and
methylergometrine is its derivative – an amine
alkaloid
• Recall ergots: amino acid, amine and
semisynthetic derivatives
• Amino acid alkaloids – ergotamine, ergotoxin etc.
• Amines – ergometrine
• Semisynthetic derivatives – dihydroergotamine
Claviceps purpurea
Ergot alkaloids remain the drugs of choice to
manage postpartum hemorrhage
As compared to oxytocin, ergot alkaloids are
more potent, they produce more prolonged
and sustained contractions of the uterus
and they are less toxic
Ergot alkaloids are contraindicated to be
used as inducers to delivery (associated
with high incidence of fetal distress and
mortality)
 Pharmacological Actions – ergometrine
Uterus:
• Increases force, frequency and duration of contractions
• At low dose contraction is phasic in nature with normal relaxation in
between
• But moderate increase in dose – sustained contraction occurs
• More sensitive – Gravid uterus and at puerperium
• Contractions involve lower segment also
CVS:
• Weaker vasoconstrictors than their amino acid counterparts – less chance
of developing endothelial damage
• No significant rise in BP
CNS:
• Interacts partially with dopaminergic, adrenergic and serotonergic receptors
• No significant effect in usual doses
GIT:
• High doses cause increased peristalsis
 Pharmacological Actions – ergometrine
Methylergometrine is preferred over ergometrine – higher
potency and less marked other effects
Pharmacokinetics:
• Near complete absorption form GIT
• Immediate onset of action with IV route
• Metabolized in liver and excreted in urine
• Half life – 1 to 2 hrs
Adverse effects:
• No complication in usual doses – Nausea, vomiting and rise in BP
may occur
• Decrease in milk secretion (dopaminergic)
Contraindications:
• Pregnancy before 3rdstage of labour, vascular disease,
hypertension, liver and kidney diseases
 Ergometrine – Uses
• Postpartum haemorrhage: to prevent
• Used the dose of 0.2 to 0.3 mg IM immediately
after delivery
• Continued for 4-7 days post partum
• If already PPH, use higher dose 0.5 mg IV
• Cesarean section and instrumental delivery – to
prevent uterine atone
• For normal involution: 0.125 mg orally tds for
4-7 days postpartum
 3. Prostaglandins:
• Dinoprostone (PGE2)
Vaginal pessaries, inserts and gel, tab
Abortifacient, induction of labor
• Dinoprost (PGF2α)
I.V infusion and intramniotic
Same uses as dinoprostone
 Uses of Prostaglandins
• Abortion – In early termination with
antiprogesterone (Mifepristone)
• Midtrimester abortion – extra-amniotic injection
followed byoxytocin
• Induction/augmentation of labour – intravaginal
route is preferred
• Cervical priming – intravaginal gel (cerviprime)
• Post-partum haemorrhage
 II. Uterine relaxants (Tocolytics)
Major clinical use: premature delivery
(weeks 20-36) → improve the survival of
the newborn
1. β-adrenergic agonists:
↑ cAMP → ↓ cytoplasmic Ca++
• Ritodrine I.V infusion
Most widely used
• Terbutaline, Oral, S.C, I.V
• Salbutamol
 Ritodrine
MOA: Relaxation of uterine smooth muscle by stimulation of
beta-2 receptors
Doses: 50 mg of ritodrine in 500 ml of 5% glucose solution.
Start by 10 drops per minute and increase by 5 drops every
10 minutes until uterine contractions cease
Infusion should be continued for 12-48 Hrs after cessation of
contractions
Oral therapy should be continued every 8 Hrs after food
Monitor maternal pulse, BP and FHS
Adverse effects: CVS effects like hypertension, tachycardia,
arrhythmia etc. and metabolic effects like hyperglycemia,
hyperinsulinemia and hypokalaemia – also
foetalhypoglycaemia and paralytic ileus
 Ritodrine
Contraindications:
Heart disease – Hypertension or
hypotension
Hyperthyroidism and diabetes
Antepartum hemorrhage (dilatation of the
uterine arteries may increase the bleeding)
Rupture of membrane
Tablet 10 mg / tablet or injections 10 mg/ml –
1mlor 5 ml
2. Magnesium sulfate
Action: The intracellular calcium is displaced by
magnesium ion leading to inhibition of the uterine
activity
Dosage: The initial dose is 40 cc of 10% solution
given slowly IV. The subsequent doses depend
upon the response and the development of MgSO4
toxicity so reflexes and respiratory rate should be
observed
Uses: Used for prevention of seizures in
eclampsia, not used for arrest of preterm labor for
its toxicities
3. Calcium channel blockers
Nifedepine: equal efficacy with beta-2
agonists
Dose: 10 mg every 30 minutes and
followed by 10 mg every 6 hrly
Problems: tachycardia, hypotension
and foetal hypoxia