Oxytocin and ergot derivatives are two groups of oxytocic drugs used to induce or augment labor. Oxytocin is a nonapeptide hormone produced in the hypothalamus and posterior pituitary. It acts on uterine smooth muscle oxytocin receptors to cause contractions. Ergot derivatives are alkaloids derived from fungi that grow on rye. They exert oxytocic effects by acting on serotonin and alpha-adrenergic receptors in the uterus. Both drugs are used during labor to either induce or augment contractions, and postpartum to prevent postpartum hemorrhage. Their administration must be carefully monitored to avoid complications like uterine hyperstimulation.

1. Oxytocin and Ergot Derivatives

2. Oxytocics
“Drugs of varying chemical nature that have the
power to excite contractions of the uterine muscles”
Three groups exist:
I. Oxytocin
II. Ergot derivatives
III. Prostaglandins

3. Chemistry
A nona peptide
Meaning: Quick Birth
Similar in structure to
vasopressin
In non­mammalian
vertebrates vasotocin
performs both functions

4. Physiology
Supraoptic and
paraventricular nucleus
Transported by fast axonic
transport bound to proteins
called neurophysins
(Prohormone)
Prohormone converted
during transport
Also secreted by the
decidua, luteal cells of the
ovary and extraembryonic
fetal tissue

5. Oytocin during Parturition
Oxytocin receptors increase 30 fold while the
sensitivity increases 8 fold mostly during the last 9
weeks prior to delivery
Secretion is stimulated by sensory stimuli from
cerivcal and vaginal dilatation
Estradiol also increases secretion
Inhibited by relaxin: mediated via endogenous
opioids
Factors that primarily affect vasopressin secretion
also have some impact on oxytocin release
Released in bursts during labour

6. Contd...
A cysteine aminopeptidase in the plasma rapidly
metabolises oxytocin
A short half­life of 3 ­10 mins
Fetal oxytocin production increases during active
labor
No evidence regarding entry of oxytocin into
maternal circulation
Short half­life may explain the need for fetal
oxytocin secretion

7. Initiation Of Parturition
Parturition has three phases*
Phase 0 : Phase of uterine quiescence
Phase 1 : Preparation for labor
Phase 2 : Labor and delivery
Phase 3 : Puerperium
Phase 1: Gap junction formation between smooth muscles
of uterus and synthesis of oxytocin receptor
Oxytocin was believed to initiate parturition, current
evidence states otherwise
*N.B. : Parturition is said to begin on transion from phase 0 to phase 1

8. Oxytocin during Puerperium
Oxytocin likely causes persitent uterine
contraction preventing PPH
Oxytocin infusion increases mRNAs of genes
that encode proteins needed for uterine
involution : Interstitial collagenase, monocyte
chemoattractant protein­1, IL­8 and urokinase
plasminogen activator receptor

9. Oxytocin during Lactation

10. Oxytocin in Daily Life
Research indicates oxytocin has a role in various
behaviours, including social recognition, pair
bonding, anxiety, maternal behaviours, libido
etc...
So the hormone is called “love hormone”
Inability to secrete this hormone is linked to
sociopathy, psychopathy and general
manipulativeness

11. Mechanism of Action
G­protein coupled
receptors connected to
phosholipase C cascade
Also causes local
synthesis and release of
PG­F2α
Physiological uterine
contraction ­ fundal
contraction; cervical
relaxation

12. Pharmacokinetics
Preparations:
Synthetic oxytocin (Syntocinon, Pitocin) 5IU/ml amp
Syntometrine (Sandoz ­ Syntocinon 5U+Ergometrine 0.5mg)
Desamino oxytocin ­ Buccal tablet 50 I.U. (long half­life)
Oxytocin nasal spray – 40U/ml
Buccal and nasal spray – limited use
Circulating half­life 3 ­10 mins
Duration of action: 20 – 30 minutes
Excreted through liver and kidney
Stored at 2 – 8º C

13. Therapeutic Indications
Pregnancy Puerperium
Early (2nd Trimester) Late
Minimize blood loss
Labor Induction
Induce abortion
Control Post Partum
Labor Augmentation
Accelerate abortion Hemorrhage
Uterine Inertia
Terminate molar Manage third stage
pregnancy
of labor
Contraction stress test
Diagnostic Indications Oxytocin sensitivity test

14. CONTRAINDICATIONS
Fetal Causes Maternal Causes
Severe Grand multipara
hydrocephalus Prior uterine rupture
Malpresentation Previous classical section
Non­reassuring fetal Placenta praevia major
heart rate CPD
Active genital herpes or
cancer cervix

15. DOSAGE & ADMINISTRATION
Induction & Augmentation
2 regimens:
Low dose regimen
High dose regimen

16. Table 1. Oxytocin regimens for stimulation of labour
Regimen Starting dose Incremental increase Dosage interval
(mU/min) (mU/min) (min)
Low dose 2.5 2.5 30
5 5 30
High dose 6 6,3,1 15­40

17. Low dose regimen
Table 2. Flow and Dosage of Oxytocin Solution*
Drops/min ml/min Total amount of fluid in 30 min Dose/min
(ml) (mIU/min)
8 0.5 15 2.5
16 1 30 5
24 1.5 45 7.5
32 2 60 10
40 2.5 75 12.5
48 3 90 15
56 3.5 105 17.5
64 4 120 20
72 4.5 135 22.5
N.B. : 2.5 IU syntocinon is added to 500 ml of RL to obtain 5 mIU/ml concentration

18. Results are unsatisfactory then add 5 IU of syntocinon
to 500 ml of RL
therefore, 10mIU/ml
Table 3. Flow and dosage of Oxytocin Solution
Drops/min ml/min Total amount of fluid in Dose/min
30 min (ml) (mIU/min)
32 2 60 20
40 2.5 75 25
48 3 90 30
56 3.5 105 35
64 4 120 40
72 4.5 135 45

19. • Maximum licensed dose = 20 mIU/min
• Max dose that can be given = 40­45 mIU/min
• Time taken for the completion of the above
regimen is 6 ½ hrs
• N.B.: most of the women deliver with
the dose of 12 mIU/min

20. High dose regimen
Indicated in pregnant women in whom the volume
overload is dangerous
Advantages over low dose regimen
1. Shorter mean admission to delivery time
2. Fewer failed induction
3. Fewer cases of neonatal sepsis/ chorioamnionitis
4. Fewer incidence of forceps delivery/caesarean
section

21. Duration of Administration
End point
30 minutes
2.5/6 mIU/min
Augmentation
End point
• Adequate uterine contractions i.e., 3­4 / 10 min, each lasting for 35­40
seconds
• Satisfactory descent of the presenting part
• Satisfactory dilatation of the cervix i.e., atleast 1cm/hr

22. Monitoring*
Maternal pulse and BP, hourly
Frequency, Intensity and duration of uterine
contractions, half­hourly
Fetal Heart Rate, half­hourly
To combat uterine hyperstimulation, injection
0.25 mg terbutaline s.c. is used
* N.B.: Best done using partogram

23. Oxytocin Challenge Test
Also called Contraction Stress Test
This test checks for uteroplacental circulation
deficiency
Contractions are induced using I.V . Oxytocin infused
initially at the rate of 1mU/min and step raised every
20 min. till end point of adequate contraction is
achieved.
Fetal heart rate response and contraction rate and
intensity are recorded

24. Contd...
Contraindications
Compromised fetus
Multiple pregnancy
H/O caesarean section
Antepartum hemorrhage
Complications likely to produce preterm labor
Candidates
Intra Uterine Growth Restricted mothers
Post maturity
Diabetes
Hypertensive disorders of pregnancy

25. Interpretation
Positive test : Persistent FHR* deceleration
Negative test : No late FHR deceleration
Suspicious : Inconsistent but definite decelerations
which do not persist with every uterine contraction
Unsatisfactory : Poor recording quality and/or
inadequate uterine contraction
Hyperstimulation : Deceleration of FHR with each
uterine contraction lasting > 90 min. Or with
frequency of contraction being more than one every 2
min. (5 every 10 minutes)

26. Oxytocin Sensitivity Test
Assess irritability of uterus to oxytocin
Procedure :
0.01U given IV at the end of spontaneous
contraction
Repeated at 1min interval until induced
contraction starts (hardening)
Inference :
If contraction does not begin after 4 injections then
uterus is unlikely to be responsive to induction

27. Adverse Reactions & Complications
Uterine hyperstimulation
Hypertonia (each contraction > 60sec)
Polysystole (>6/10 min)
Uterine rupture
Water intoxication*
Occurs with rates 30­40 mIU/min
Due to vasopressin like activity
Hypotension ( iv bolus) : Due to temporary
vasodilation caused by oxytocin
Fetal distress (due to hyperstimulation)
* N.B.: Don't infuse more than 1 L fluid in 24 hours

28. Lactation and Pregnancy
No large scale study is available to arrive at
definite conclusions
Oxytocin released during lactation will cause mild
uterine contractions
Mother is protected as oxytocin receptors are not
present till late in pregnancy
The American Academy of Family Physicians states that
“If the pregnancy is normal and the mother is healthy,
breastfeeding during pregnancy is the woman' s personal
decision”

29. Ergot Derivatives
Natural alkaloid obtained from fungi Claviceps purpura,
that grows in rye
Therapeutically useful alkaloid are amide derivatives of
d­lysergic acid
Semi­synthetic derivatives are obtained from catalytic
hydrogenation of the natural alkaloids. e.g.­ Methergin
(methylergonovine)
E.g.: Ergometrine ­ Alkaloid from Ergot
Methergin – Semi­synthetic product from Lysergic acid

30. Preparations Available
Parenteral: Prefered route
Ergometrine 0.5 mg IM, 0.5 mg IV
Methergin 0.2mg IV
Oral : Rapidly absorbed, peaks at 60 – 90 min
Ergometrine ­ 0.5 – 1 mg tab
Methergin ­ 0.5 – 1 mg tab

31. Metabolism
Ergotamine is metabolised in liver by undefined
pathways
90% metabolites : excreted in bile
Traces seen in urine and feces
Ergometrine is metabolised and excreted more
rapidly than ergotamine
Plasma half­life : 30 – 120 minutes
Duration of action : 3 hrs

32. Mechanism of Action
Acts through serotonin receptors (5­HT 2) and
α­adrenergic receptors
During pregnancy, the uterine sensitivity to
ergot increases dramatically
Causes uniform contraction of uterus (non­
physiological)
In very small doses can cause rythmic
contraction of uterus
Ergonovine is more selective in affecting uterus

33. Indications*
Prophylactic: Prevent post partum hemorrhage
– given as IV 0.2mg methergin after anterior
shoulder delivery
Control bleeding after delivery (instrumental or
caesarean section or abortion)
*N.B. : Ergot derivatives must never be used prior to delivery for
induction or augmentation of labor

34. Contraindications
Multiple pregnancy
Pre­eclampsia / Eclampsia
Rh­negative mother
Cardiac disease
Severe hypertension

35. Adverse Effects
Gastro Intestinal symptoms : Nausea, Vomitting,
Diarrhoea – Activation of medullary vomitting
centre and GI serotonin receptors
Overdosage : Prolonged vasospasm – gangrene
of toes requiring amputation (rare)
Bowel infarction has been reported (very rare)
Interferes with lactation
Can precipitate MI, Stroke, Bronchospasm &
raise of BP (Vasoconstriction effects)

36. Oxytocin Ergot derivatives
Acts on physiological Acts directly on muscle cells
Mechanism of action uterine contraction system causing contraction
Onset of action Slower Faster
Duration Long sustained Short lived
1) Prophylactically stop 1) Induction of labor
hemorrhage postpartum 2) Augmentation of labor
Uses 2) Stop hemorrhage after 3) Stop Post Partum
instrumental delivery, etc... Hemorrhage
GI symptoms, rise in BP, Uterine Hyperstimulation,
Adverse effects Stroke, Gangrene of toes Anti­diuresis, Uterine
(rare), etc.. rupture, etc...