Drugs acting on the uterus can be classified based on their effects on the endometrium or myometrium. Oxytocin is a polypeptide hormone that acts on the myometrium to stimulate contractions during labor and delivery. It is synthesized in the hypothalamus and stored/released from the posterior pituitary. Oxytocin is used to induce and augment labor, and to prevent postpartum hemorrhage. While ergot alkaloids like ergometrine are also uterotonic, oxytocin is preferred due to its more physiological action, rapid onset and short duration of effect.

1. DRUGS ACTING ON THE UTERUS
-

2.  Classification:
 Drugs ---- Endometrium or myometrium
 Endometrium--- Estrogen or progesterone and
antagonists
 Myometrium-
1. Indirectly acting- Symp or P.symp
2. Directly acting
- Ut.stimulants (oxytocics)
- Ut. Relaxants (Tocolytics)

3.  Stimulants/ Ecbolics
1. Post. Pit. Hormone- Oxytocin ( oxys – quick,Tokos-
childbirth ) /
Desamino-oxytocin
2. Ergot alkaloids- Ergometrine, Methyl ergometrine
3. Prostaglandins- PGE2, PGF2a, 15-Methyl PGF2a,
PGE1
 Tocolytics (Relaxants)
Beta 2- agonists, Ca++ blockers, Magnesium sulfate,
oxytocin antagonist- atosiban, Alcohol, Ethacridine, Quinine

4. OXYTOCIN
 Biosynthesis:
 Post Pit  Oxytocin and Vasopressin
 Synth. In hypothalumus  Transported and stored in post.
Pitutary
 Released by stimuli –coitus,parturation;suckling at breast.
 Synthesis and release is pulsatile in nature.
 Structure : It is a polypeptide similar to vasopressin
structurally differing only in 2 amino acids.

6. PHYSIOLOGICAL ROLE OF OXYTOCIN
 Oxytocin acts on uterus and mammary gland-? where as
vasopressin acts on kidney and blood vessels-?
 Oxytocin stimulates both frequency and force of
contraction.
 Only upper segment is contracted ,not lower segment.

7. • Estrogen increases sensitivity of uterus to oxytocin
• Progesterone decreases sensitivity of uterus to
oxytocin
• Decreased levels of progesterone at term leads to
initiation of parturition

8. PHARMACOKINETICS
ROA:
Orally-inactivated by trypsin
 Administerd by I.V, I.M, rarely nasal route.
 Not bound to plasma protiens
 t1/2 : 2 -5 min in pregnant,10-15 min in non
pregnant women.
 Metabolized in liver and eliminated by kidney

9. MOA
 Acts  GPCR stimulation - release of Ip3 –
activation of voltage sensitive ca channels- influx of
ca2+ - depolarisation of muscle fibres ( contraction of
uterus)
 Mammary alveoli-myoepethelial cells  contraction-
Milk ejection

11. PH. ACTIONS:
 Uterus:
 Small doses  Frequency and force
 Large doses  Sustained contraction
 Sensitivity increases as pregnancy progresses-9 fold [early &
non pregnant-resistant]
 Receptors increase- 30 times in last 9wks
 100-200 fold in labour.
 Lower segment not contracted

12.  Estrogen facilitates, progesterone inhibits
 Breast- Milk ejection only but doesn’t increase milk
production.
 CVS- no effect on BP, but higher doses cause
vasodilatation
 Kidney- ADH like
 Brain: neurotransmission

13. CLINICAL USES OF OXYTOCIN
Therapeutic uses are :
 To induce and augment labour-
 uterine inertia,
 PROM,
 DM,
 Preclampsia,
 Rh problems etc

14. CONTD.
 confirm that:
 Presentation is correct
 Foetal lungs are adequately mature
 There is no cephalopelvic disproportion
 No placenta previa
 No foetal distress and
 No uterine scar (due to previous surgery).

15. CONTD,
 Uterine inertia
o Oxytocin can be infused i.v. to augment
contractions
 Postpartum haemorrhage, Caesarean section
 5 IU injected i.m. or by i.v. infusion
 In hypertension mother

16. Diagnostic
Oxytocin challenge test: To assess foetal distress-placental
insufficiency.
Eg: IUGR,post maturity,PIH,DM.
Oxytocin sensitivity test-0.01units of oxytocin I.V with 1 mt
interval till contraction starts

17. WHY OXYTOCIN? WHY NOT ERGOMETRINE?
1. Short t ½- & slow i.v infusion
2. Action can be easily terminated
3. Normal relaxation of uterus allowed-Good
fetal oxygenation
4. Lower segment not affected-descent free
5. More of physiological action

18.  ADVERSE EFFECTS
 Maternal: Rupture uterus, water intoxication- anti
diuresis, hypotension
 Foetal: Foetal distress
CONTRAINDICATIONS:
i. Grand multipara
ii. CPD
iii. Placenta previa
iv. Malpresentation eg : Breech presentation
v. Previous LSCS
vi. Foetal distress

19. Desamino-oxytocin: synthetic analogue
Buccal formulation, uses same as oxytocin
Ergometrine /ergonovine :
 Ergometrine isolated from claviceps pupura
 synthetic :Dihydroergometrine, Methyl ergometrine
 PHARMACOKINETICS:
 Rapidly and completely absorbed by oral
Metabolised in the liver and eliminated in urine.
Liver damage increases the toxicity

20. MECHANISM OF ACTION
 Acts as agonits to alpha receptors, dopaminergic
and 5HT2 receptors and stimulate uterus

21. PHARMACOLOGICAL ACTIONS:
 Increase force, frequency of ut.contractions
 Moderate increase of dose  Basal tone increased
 Lower segment also contracts- more risk of fetal distress
asphyxia
 Methyl ergometrine more potent action on uterus and less
on CVS, CNS, GIT etc.

22. CLINICAL USES
o Management of 3rd stage Labour : After anterior
shoulder deliver PPH 0.2-0.5 mg I.M.
Contraction of myometrial blood vessels
o Prevent uterine atony[cesarian, instrument]
o To promote involution in multipara  0.125mg TDS -
7days
o Diagnosis of variant angina during Coronary angio

23.  Ad. Effects
 Nausea, vomiting,
 rise in BP - ?
 vasoconstriction
 Decreases milk secretion-?
 Dopaminergic action- inhibition of prolactin
 Abortions

24.  Contraindications :
 Vascular disease, HTN- pre eclampsia , toxemia
 Angina pectoris
 TIA
 Sepsisgangrene
 Liver and kidney disease.
 C.I.in pregnancy & early stages of labour

25. ERGOT VS OXYTOCIN
 Acts directly on
myometrium- tetanic,
loss of polarity
 Onset of action slow
 Duration of action is
long
 ADR: increased BP &
gangrene
 CI: Eclampsia, Rh –ve,
heart disease
 Physiological
contractions
 Onset is fast
 Duration is short
 ADR: rupture uterus &
hypotension
 CI: Grand multipara
ERGOT OXYTOCIN

26. PROSTAGLANDINS
 PGE2 (Dinoprostone) Vaginal application  Induce II trimester
abortion, missed abortion, ripening of cervix in near term
 15-Methyl-PGF2α (Carboprost)  II trimester abortions
 Misoprostol  with mifepristone for early abortion
 Misoprostol ( PGE1) also used in induction of labour,less
expensive and less ADR than dinoprost
 PGs also used to control PPH
 Not to be used in combination with oxy - ?
 Due to increased chance of uterine rupture

27. UTERINE RELAXANTS[TOCOLYTICS]
 Adrenergic agonists[β2]-
ritodrine,salbutamol,isoxsuprine,terbutaline,
orciprenaline etc
 Magnesium sulfate
 Ca++ channel blockers - nifedipine
 Atosiban
 Others:

28. USES
 Used to delay labour in premature labour
 Arrest threatened abortion
 In dysmenorhea
 Hospital delivery
 And time for fetal lungs to get matured- to intitate
glucocortocoid therapy

29. CONTRAINDICATIONS FOR TOCOLYTICS
 More than 37 weeks gestation
 Fetus >2500g
 Fetus in distress
 Cx dilation > 4 cm
 Ruptured membrane
 Toxemia
 Cardiac diseases
 PPH

30. CONTRAINDICATIONS FOR TOCOLYTICS
 More than 37 weeks gestation
 Fetus >2500g
 Fetus in distress
 Cx dilation > 4 cm
 Ruptured membrane
 Toxemia
 Cardiac diseases
 PPH