A power point presentation on the Drugs acting on Uterus suitable for undergraduate MBBS level medical students.

1. Drugs acting on Uterus
Dr. D. K. Brahma
Department of Pharmacology
NEIGRIHMS, Shillong

2. Uterine stimulants (oxytotics or
abortifacients)
 Posterior Pituitary hormones: Oxytocin,
Desamino oxytocin
 Ergot alkaloids: Ergometrine,
methylergometrine
 Prostaglandins: PGE2, PGF2α,
misoprostol
 Miscellaneous: ethacridine and quinine

3. Oxytocin
 Hormone of Posterior pituitary. The
other hormone is vasopressin

4. Biosynthesis - Physiology
 Synthesized as cell bodies of
praventricular nucleus and
supraoptic nucleus of
hypothalumus as prohormone
 Precursor broken down to
active hormone and
neurophysin complex
 Packaged into the secretor
granules by oxytocin-
neurophysin complex
 Secreted from nerve endings
in posterior pituitary gland
(neurohypophysis)

5. Oxytocin - Physiological Role
1. Labour
2. Milk ejection reflex
3. Neurotransmission

6. Oxytocin secretion
 Sensory stimuli from cervix, vagina and
breast suckling
 Expulsive phase is triggered by sustained
distension of uterine cervix and vagina
 Oestrogen increases its secretion
 Ovarian polypeptide relaxin inhibits its
release
 ADH: Pain, haemorrhage and dehydration
increases secretion

7. Actions of Oxytocin –
Uterus
 Increase in force and frequency of contractions
 Low doses: Full relaxation occurs between the contractions, but
high doses – basal tone increases
 Mechanism - High electrical activity of myometrium cell
membrane – burst of discharges
 Very low level of motor activity in the first two trimesters - 3rd
trimester onwards – spontaneous motor activity progressively
increases and sharp rise initiates labor
 Uterine sensitivity - 8 fold increase in in last 9 weeks and 30 fold increase
in number of oxytocin receptors between early pregnancy and early labour –
estrogen
 No. of receptors and myometrium sensitivity increases late in pregnancy –
labour initiation and postpartum involution
 Increase in contraction is restricted to fundus and the body
 Non pregnant uterus are resistant to its action
 Oxytocin antagonist ATOSIBAN suppresses preterm labor

8. … Actions – contd.
Breast
 Role in milk ejection
 Breast suckling and manipulation induces oxytocin release
 Mechanism: Contractions of myoepithelial surrounding alveolar
channels in mammary gland forces milk into large collecting
sinuses – milk ejection reflex

9. Oxytocin – other effects
CVS
 No effect in low dose but at higher doses
fall in BP, reflex tachycardia and flushing
Kidney
 ADH like effect in high doses – decreased
urine output, pulmonary oedema etc.

10. Oxytocin – Mechanism of
action (OXTR)
 Specific G protein-coupled membrane receptors
related to Vasopressin (V1 and V2) receptors
 Depolarization of muscle fibres and Ca++ influx
 Human myometrium – receptors coupled to Gq
activation leads to generation of IP3 – release of Ca+
+ ions
 Increase in local prostaglandin concentration –
uterine contraction
 Kinetics:
 Being a peptide not effective orally
 Short half life – 3 to 6 minutes
 Available as injections for IM and IV use – 0.5 ml, 1 ml and 5
ml etc.

11. Clinical uses of
oxytocin
1. Induction of labour To induce or augment labor in
pregnant women
 Indications:

Premature rupture of membranes

Pre and post maturity

Intra uterine growth retardation (IUGR)

Placental insufficiency – diabetes, preeclampsia or eclampsia
 Before induction, rule out:

Abnormal fetal position

Cephalopelvic disproportion

Evidence of fetal distress

Placental abnormalities

Previous uterine surgery
Oxytocin is the drug of choice for induction of labor

12. Clinical uses of oxytocin (Pitocin
or syntocinon) – contd.
 5 IU is diluted in 500 ml of
5% glucose or 0.9% saline
– 5 milli IU/ml
 Start at low dose
progressively increase
0.2 – 2 ml/min
 Induces labour within 2 – 4
IU
 If no induction after giving
upto 30 – 40 mU/min –
higher doses are
unsuccessful
 If labour – reduce the dose
progressively
 Unitage: 1 IU of Oxytocin
= 2 mcg of pure hormone

13. Oxytocin infusion Monitoring
 Presence of Physician
 Mother and fetus monitoring – fetal and
maternal heart rate, maternal BP and strength
of contractions
 If uterine hyper stimulation – discontinue
infusion
 Higher dose (more than 20 mu/min) may
reduce water clearance – leading to water
intoxication, coma and death

14. Clinical uses of oxytocin – contd.
2. Augmentation of labour
 In hypotonic contractions in dysfunctional labour
(nulliparous) – administer as above
 But be careful, normal progression of labor should
never be tried to hasten, because over stimulation
may cause
 Uterine rupture
 Trauma of mother
 Trauma of fetus
 Compromised fetal oxygenation
 Useful in prolong latent phase of cervical dilation or arrest of
dilation

15. Clinical uses of oxytocin –
contd
3. Post partum haemorrhage, cesarean section:
 5 IU IM or slow IV for immediate response
 Especially useful in hypertensive women where
ergometrine cannot be used
 Also to maintain normal tone of uterine muscle
4. Breast engorgement:
 Inefficient milk ejection reflex
 Intranasal spray before suckling

16. 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 -
DHE
 Claviceps purpurea

17. 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

18. Ergometrine – contd.
 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 3rd
stage of labour, vascular
disease, hypertension, liver and kidney diseases

19. 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 atony
 For normal involution: 0.125 mg orally tds for
4 – 7 days postpartum

20. Prostaglandins
 PGE2 and PGF2α – tocolytics
 Uses:
 Abortion

In early termination with antiprogesterone (Mifepristone)

Midtrimester abortion – extra-amniotic injection followed by
oxytocin (1o mg/ml available)
 Induction/augmentation of labour – intravaginal
route is preferred
 Cervical priming – intravaginal gel (cerviprime)
 Post-partum haemorrhage

21. Uterine relaxants
Tocolytics

22. Tocolytics - drugs
 These are drugs that inhibit uterine
contractions
 Beta-sympathomimetics (beta-2)

Ritodrine, isoxsuprine, terbutaline and salbutamol
 Calcium channel blockers: Nifedepine
 Magnesium sulfate
 Prostaglandin inhibiting agents: Indomethacin
 Oxytocin antagonist: Atosiban
 Ethyl alcohol

23. Tocolytics
 Therapeutic uses:
 Delay or postpone labor – to allow fetus to
mature and transfer of mother to a
healthcare centre
 Threatened abortion
 Dysmenorrhoea

24. 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. & metabolic effects like hyperglycemia,
hyperinsulinemia and hypokalaemia – also foetal
hypoglycaemia and paralytic ileus

25. Ritodrine – contd.
 Contraindications:
 Heart disease - Hypertension or hypotension
 Hyperthyroidism and diabetes
 Antepartum haemorrhage (dilatation of the uterine
arteries may increase the bleeding)
 Rupture of membrane
 Preparations: available as Ritodie/yutopar
 Tablet 10 mg / tablet or injections 10 mg/ml – 1ml
or 5 ml
 Isoxsuprine (duvadilan) is available as
oral and injections (10, 20, 40 mg tablets)

26. Magnesium sulfate and
Calcium channel blockers
 Magsulf:
 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 toxicites
 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

27. Summary – must know
 Drugs used as uterine stimulants -
Classification
 Oxytocin – Mechanism of action o uterus and
its therapeutic uses
 Ergometrine – Pharmacological actions in
uterus and therapeutic uses
 Drugs used as Tocolytics – role of ritodrine
(beta-2 agonists) in arrest of labor

28. Thank you