Oxytocics and tocolytics

This topic contains Oxytocics in obsterics- oxytoxin, ergot derivatives, prostaglandins; Tocolytic agents- calcium channel blockers, Magnasium sulphate, indomethacin and sulindac, betamimetics, oxytocin antagonist, nitric oxide donors.

1. PHARMACOTHERAPEUTICS IN
OBSTETRICS

2. OXYTOCICS IN OBSTETRICS
DEFINITION
“Oxytocics are the drugs of varying
chemical nature that have the power
to excite contractionsof the uterine
muscles.”

3. CLASSIFICATION
1. OXYTOCIN
2. ERGOT
DERIVATIVES
3. PROSTA-
GLANDINS

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 Supraopticand
paraventricular nucleiof the Hypothelamus.

5. By Nerve Axonsit is transportedfrom the
Hypothelamus to the Posterior Pituitary
where it is storedand 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 receptorsincreases the
contaction maximum during labour.
Oxytocin acts through receptor and voltage
mediated calcium channelsto initiate
myomatrial contractions
It stimulates amniotic and decidual
prostaglandin production
Bound intracellular calciumis eventually
mobilizedfrom 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 ℃.

11. INDICATIONS
In pregnancy, labour as well as peurpeium
THERAPEUTIC DIAGNOSTIC

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 (PGE
1/
PGE
2)

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)

15. CONTRAINDICATIONS
PREGNANCY:-
Grandmultipara
Contracted pelvic
Previous cesarean section/ Hysterotomy
Malpresentation

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

18. DANGERS OF OXYTOCIN
Fetal distress
Fetal hypoxia
Placental insufficiency
2. FETAL

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

20. METHODS OF ADMINITRATION
OF OXYTOCIN
Controlled intravenous infusion
Intramuscular

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
Methergineis 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

32. INDICATIONS
A. PROPHYLACTIC:-
Active management of 3
rd
stage of labour
B. THERAPEUTIC:-
To stop atonic uterine bleeding
Following delivery, abortion, expulsion of
hydatiform mole

33. CONTRAINDICATIONS
A. PROPHYLACTIC:-
Suspected multiple pregnancy
Organic cardiac diseases
Severe pre-eclampsia
Rh-negative mother

34. B. THERAPEUTIC:-
Heart disease
severe hypertensive disorders

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 “LOCAL
HORMONES”
Prostaglandins were first described and
named by Von Euler in 1935

37. CHEMISTRY
Prostaglandins are 20-carbon carboxylic
acidswith a cyclopentane ringwhich are
formed from polyunsaturated fatty acids.
Of the many variesties , PGE
2and PGF
2a
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

40. CONTRAINDICATIONS
Hypersensitivity to compound
Uterine scar
Active cardiac, pulmonary, renal, hepatic
disease
Hypotension
Bronchial asthma

41. MECHANISM OF ACTION
Both the PGE
2and PGF
2a 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. PGE
2is at least 5 times more potent than
PGF
2a
PGF
2a acts predominantly on the
myomatrium
While PGE
2acts 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

46. TOCOLYTIC AGENTS

47. DEFINITION
“A medication that can inhibit labor, slow
down or halt the contractions of the uterus.”

48. INDICATIONS
Pre-term labour
Premature birth

49. CONTRA-INDICATIONS
Acute fetal distress
Maternal cardiac rhythm disturbance
Any cardiac disease
Poorly controlled diabetes
Thyrotoxicosis
Hypertension

50. CLASSIFICATION
Calcium channel blockers
Magnasium sulphate
Indomethacin and Sulindac
Betamimetics
Oxytocin antagonist
Nitric oxide donors

51. CALCIUM CHANNEL BLOCKERS
Ex:Nifidipine
Nicardipine
Verapamil
MODE OF ACTION:-
Nifedipine blocks the entry of calcium
inside the cell. It is equally effective to
MgSO
4

52. DOSES:-
Oral 10-20 mg every 3-6 hours
SIDE EFFECTS:-
Maternal hypotension, headache,
flushing, nausea
COMBINED THERAPY: -
With betamimetics or MgSO
4 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

55. SIDE EFFECTS:-
MATERNAL
Nuasea/ vomiting
Flushing
Headache
Muscle weakness
Pulmonary edema (rarely)
NEONATAL
Lethargy
Hypotonia
Respiratory depression (rare)

56. INDOMETHACIN
Cyclo Oxygenase inhibitor
SULINDAC
Another NSAIDS is also
used...As it has less placental
transfer

57. MODE OF ACTION:-
Reduces synthesis of PGs, thereby
reduces intracellular free ca++, uterine
contractions
DOSE:-
Loading dose 50 mg PO followed by
25 mg every 6 hrs for 48 hrs
CONTRAINDICATIONS:-
Hepatic disease,active peptic ulcer,
coagulation disorders

58. MATERNAL SIDE EFFECTS: -
Heart burn
Asthma
GI bleeding
Thrombocytopenia
Renal injury
FETAL SIDE EFFECTS:-
Constrictions of ductus arteriosis
indirect: oligohydramnios
Neonatal pulmonary disese
IUGR

59. BETAMIMETICS
Terbutaline
Ritodrine
Isoxsuprine
(Effective for 48 hours to allow time
for steroids and antibiotics to work)

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....

62. MATERNAL SIDE EFFECTS: -
Headache
Palpitation
Pulmonary edema
Hypotension
Cardiac failure
Hyperglycemia
Hypokalemia
Even death

63. FETAL SIDE EFFECTS:-
Tachycardia
Heart failure
IUFD
NEONATAL SIDE EFFECTS: -
Hypoglycemia
Intraventricular hemorrhage

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

65. DOSE:-
300 ug/min IV
SIDE EFFECTS:-
Nuasea/ vomiting
Chest pain

66. NITRIC OXIDE DONORS
GYCERYL TRINITRATE
MODE OF ACTION:-
Smooth muscle relaxant
SIDE EFFECTS:-
May cause cervical ripening
Headache

67. THANK YOU...