4. OXYTOCIN
PHARMACOLOGY:-
Oxytocin is a non-peptide
In 1950, DE VIGNEAUD and coworkers did
the Nobel prize winning workn on structure of
Oxytocin.
It is synthesized in the Supraoptic and
paraventricular nuclei of the Hypothelamus.
5. By Nerve Axons it is transported from the
Hypothelamus to the Posterior Pituitary
where it is stored and eventually released.
Half life:- 3-4 minutes
Duration of action:-Approximately 20
minutes
It is rapidly metabolized and degenerated
by Oxytocinase.
6. MODE OF ACTION
Myomatrial oxytocin receptors increases the
contaction maximum during labour.
Oxytocin acts through receptor and voltage
mediated calcium channels to initiate
myomatrial contractions
It stimulates amniotic and decidual
prostaglandin production
Bound intracellular calcium is eventually
mobilized from the sarcoplasmic reticulam to
activate the contractile protein.
7. The uterine contractions are physiological
i.e. causing fundal contraction with
relaxation of the cervix.
8. PREPARATIONS USED
Synthetic oxytocin (Syntocinon/ sandoz):-
it is widely used
Having only oxytocin effect without vaso
compressior action
Available in Ampules containing 5 IU/ML
Syntometrine :-
A combination of Syntocinon 5 units and
ergometrine 0.5 mg
9. Desamino oxytocin:-
It is not inactivated by oxytocinase
50-100 times more effective than
oxytocin
It is used as buccal tablets containing 50
IU
Oxytocin Nasal solution :-
Contains 40 units / mL
10. EFFECTIVENESS
IN FIRST TRIMETER:-
Uterus is almost refractory to oxytocin
IN SECOND TRIMESTER:-
Relative refractoriness persists
so it supplements other abortifacient agents in
induction of abortion
IN LATE TRIMESTER & DURING LABOUR:-
It is highly sensitive even in small doses
Oxytocin loses its effectiveness unless
preserved at temp. of 2 to 8 â.
12. THERAPEUTIC
1. PREGNANCY:-
EARLY:
To accelerate abortion ( inevitable/ missed,
to expedise expulsion of hydatiform mole)
To stop bleeding following evacuation of the
uterus
Used as a adjunct to induction of abortion
along with other abortifacient agents (PGE1/
PGE2)
13. LATE:
To induce labour
To ripen the cervix before induction
2.LABOUR:-
Augmentation of labour
Uterine inertia
Inactive management of third stage of
labour
Following expulsion of placenta as an
alternative to ergometrine
14. 3. PEURPERIUM:-
To minimise blood loss
To control hemorrhage
DIAGNOSTIC
Contraction stress test (CST)
Oxytocin sensitivity test (OST)
16. LABOUR:-
All the containdications of pregnancy
Obstructed labour
Incoordinated uterine contractions
Fetal distress
ANY TIME:-
Hypovolemic state
Cardiac disease
17. DANGERS OF OXYTOCIN
Uterine hyperstimulation
Uterine rupture
Water intoxication
Hypotention
Antidiuresis (when more than 40-50 mIU/min)
1. MATERNAL
19. ROUTE OF ADMINISTRATION
Controlled intravenous route is widely used
Bolus IV or IM 5-10 units after the birth of
baby as an alternative to ergometrine
IM- Preparation used is Ergometrine
Buccal tablets / Nasal spray- Limited use
on trial basis
21. CONTROLLED
INTRAVENOUS INFUSION
Ideally by infusion pump
Fluid load should be minimum
Started at low dose rates (1-2 mIU/min)
and increased gradually
For Induction of labour
For Augmentation of labour
22. FOR INDUCTION OF LABOUR
PRINCIPLES:
Because of safety, the oxytocin should be started
with a low dose and is escalated at an interval of
20-30 minutes where there is no response.
When the optimal response is achieved
(Uterine contraction sustained for about 45
seconds and numbering 3 contractions in 10
minutes), the administration of the particular
concentration in mU/min is to be continued.
This is called oxytocin titration technique.
23. The objective of oxytocin administration is not
only to initiate effective uterine contractions but
also to maintain the normal pattern of uterine
activity till delivery and at least 30-60 minnutes
beyond that.
CALCULATION OF INFUSED DOSE
In terms of milliunits per minute
24. INDICATION FOR
STOPPING THE INFUSION
Abnormal uterine contraction (
Hyperstimulation, Polysystole)
Increased tonus between contraction
Evidence of fetal distress
Appearance of unexpected maternal
symptoms
25. ERGOT DERIVATIVES
Out of many ergot derivatives, two are
used extensively as oxytocics:
1. Ergometrine
2. Methergine
26. CHEMISTRY
Ergometrine is an alkaloid
Isolated by Dudley and Moir in 1935 from
ergot, a fungus, Claviceps purpura, that
develops commonly in cereals like
musturd, wheat
The akloids are detoxified in liver and
eliminated in the urine
Methergine is semi-synthetic product
derived from lysergic acid
27. MODE OF ACTION
Ergometrine directly acts on myomatrium
It excites uterine contractions
Which comes so frequently one after other
with increasing intensity
That the uterus passes in to a state of
spasm without any relaxation inbetween
28. EFFECTIVENESS
Keeping the physiological functions in
mind, It should not be used in the induction
of abortion or labour
It is highly effective for hemostasis- to stop
bleeding from the uterine sinuses, either
following delivery or abortion
29. Methergine is somewhat slow than
ergometrine
Methergine produces response in 96
seconds
Where as ergomtrine takes 55 seconds
when administered intravenously
30. MODE OF ADMINISTRATION
Ergometrine and Methergine can be used
parentrally or orally
As it produces tetanic contactions, the
preparation should only be used either in late
second stage of labour ( delivery of anterior
shoulder) or following delivery of the baby
Syntometrine should always be administered
intramuscularly
31. COMPOSITIONS OF
ERGOT PREPARATIONS
Ergometrine: Ampule 0.25 to 0.50 mg and
tablet 0.5 to 1 mg
Methergine: Ampule 0.124 to 0.250 mg and
tablet 0.124 to 0.5 mg
Syntometrine:
Ampule 0.5 mg ergometrine+
5 units syntocinon
35. HAZARDS
Nausea/ vomiting
Rise of blood pressure
Interfere with lactation by lowering prolactin
level
Prolonged use can lead gangrene because
of vasoconstriction
36. PROSTAGLANDINS
Prostaglandins are the derivatives of
prostanoic acid from which they derive their
names.
They have property to act as âLOCAL
HORMONESâ
Prostaglandins were first described and
named by Von Euler in 1935
37. CHEMISTRY
Prostaglandins are 20-carbon carboxylic
acids with a cyclopentane ring which are
formed from polyunsaturated fatty acids.
Of the many variesties , PGE2 and PGF2a
are exclusively used in clinical practices
38. SOURCES
Sythesized from one of the essential fatty
acid, archidonic acid, which is widely
destributed throughout body
In the female these are identified in
menstrual fluid, endomatrium, decidua and
amniotic membrane
39. USE IN OBSTETRICS
Induction of abortion
Termination of molar pregnancy
Induction of labour
Cervical ripenning prior to induction of
labour / abortion
Augmentation (acceleration) of labour
Management of atonic postpartum
hemorrhage
Medical management of tubal pregnancy
41. MECHANISM OF ACTION
Both the PGE2 and PGF2a have got an
oxytocic effect on the pregnant uterus
The probable mechanism of action is
change in myomatrial permiability and/or
alteration of membrane bound Ca++
PGs also sensitise myomatrium to oxytocin
42. PGE2 is at least 5 times more potent than
PGF2a
PGF2a acts predominantly on the
myomatrium
While PGE2 acts mainly on the cervix
43. ADVANTAGES
Powerfull oxitocic effect irrespective of
duration of gestation
Induction of labour
Induction of abortion
No antidiuretic effect like oxytocin
Augmentation of labour
44. DISADVANTAGES
Costly compared to oxytocin
Nausea /vomiting
Diarrhoea
Pyrexia
Tachycardia
Chills
Tachysystole
Risk of uterine rupture
45. PREPARATIONS
Vaginal tablet- dinoprostone 3 mg 6-8
hourly max. 6 mg
Vaginal pessary- dinoprostone 10 mg over
24 hours, removed when cervical ripening
is adequate
Prostine ( dinoprostone ) gel- 500 ug in to
cervical canal
Parentral route
52. DOSES:-
Oral 10-20 mg every 3-6 hours
SIDE EFFECTS:-
Maternal hypotension, headache,
flushing, nausea
COMBINED THERAPY:-
With betamimetics or MgSO4 should
be AVOIDED
53. MAGNASIUM SULPHATE
MODE OF ACTION:-
It acts by competetive inhibition to
calcium ion
Direct depresant effect on uterine
muscles
54. DOSES:-
4-6 g IV over 20-30 minutes followed by
infusion of 1-2 g/ hr
To continue tocolysis for 12 hours ...after
the contractions have stopped
Poor tocolytic effect
CONTRAINDICATION:-
Myasthenia gravis and impaired renal
function
60. MODE OF ACTION:-
Activation of intracellular enzymes..
reduces intracellular free ca++....reduces
interaction of actin and myosin......leads to
smooth muscle relaxation
61. DOSES:-
RITODRINE... 50 ug/min IV,
increased by 50 ug every 10 min until
contractions cease.
Infusion is continued for about 12 hours
after the contraction cease
TERBUTALINE...0.25 mg subcutneously
every 3 to 4 hours....
64. OXYTOCIN ANTAGONIST
ATOSIBAN
MODE OF ACTION:-
Blocks myomatrial oxytocin
receptors. It inhibits intracellular calcium
release, release of PGs and there by
inhibits myomatrial contractions