5.oxytocics

Pharmacology of oxytocics

1. Compiled by: Prof. Anwar Baig
OXYTOCICS
1
Prepared by: Mirza Anwar Baig
M.Pharm (Pharmacology)
Anjuman I Islam's Kalsekar Technical Campus,
School of Pharmacy.
New Panvel,Navi Mumbai

2. Compiled by: Prof. Anwar Baig
OXYTOCICS
•
Oxytocics are the drugs of varying
chemical nature that have the power to
stimulate the contraction of uterine
muscles.
•
Also called Uterotonics
•
The introduction of oxytocic drugs for
the treatment of Post Partum
Hemorrhage (PPH) has been regarded as
“
one of the enduring achievements of
modern science
”
.

2

3. Compiled by: Prof. Anwar Baig
DRUGS PRODUCING UTERINE

CONTRACTIONS( Oxytocic Drugs )
1.
OXYTOCIN
2.
ERGOT ALKALOIDS

Ergometrine (Ergonovine)
3.
PROSTAGLANDINS
a) PGE2
b) PGF2
α

4.
MISCELLANEOUS
Quinine
Emetine
Alcohol
Ethacridine
3

4. Compiled by: Prof. Anwar Baig
1.
Oxytocin
i.Synthesis of Oxytocin:
•
Is a posterior pituitary hormone
secreted
by the posterior pituitary
gland.
•
Oxytocin
secretion
occurs by sensory
stimulation from cervix ,vagina , and
from suckling at breast.
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5. Compiled by: Prof. Anwar Baig
ii. Secretion of oxytocin:

5

6. Compiled by: Prof. Anwar Baig
iii.
Pharmacodynamics
UTERUS
•
Oxytocin acts through
G protein-coupled receptors
and the
phosphoinositide -calcium second-messenger system to
contract uterine smooth muscle.
•
Oxytocin also stimulates the release of
prostaglandins
and
leukotrienes
that augment uterine contraction.
•
Oxytocin in
small doses
increases both the
frequency and
the force of uterine contractions
.

•
At
higher doses
, it produces
sustained contraction
.
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7. Compiled by: Prof. Anwar Baig
i
•
These contractions resemble the
normal

physiological contractions of uterus
(contractions followed by relaxation)
•
Immature uterus is
resistant
to oxytocin.
•
Contract uterine smooth muscle only at
term.
•
Sensitivity
increases
to 8 fold in last 9
weeks and 30 times in early labor.
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8. Compiled by: Prof. Anwar Baig
Mechanism of action
The interaction of endogenous or administered
oxytocin , with myometrial cell membrane receptor
promotes the influx of ca
++
from extra cellular
fluid and from S.R in to the cell , this
increase
in
cytoplasmic
calcium
,stimulates uterine contraction .
8

9. Compiled by: Prof. Anwar Baig 9

10. Compiled by: Prof. Anwar Baig
BREAST
•
Oxytocin also causes contraction of
myoepithelial cells surrounding mammary
alveoli, which leads to
milk ejection
.

•
Used in breast engorgement
KIDNEYS
•
At high concentrations, oxytocin has
weak
antidiuretic and pressor
activity due to
activation of vasopressin receptors.
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11. Compiled by: Prof. Anwar Baig
iv.
Pharmacokinetics of oxytocin
Absorption ,Metabolism and Excretion
•
Not effective orally
•
Administered intravenously
•
Also as nasal spray
•
Not bound to plasma proteins
•
Catabolized by liver & kidneys
•
Half life = 5 minutes
•
Duration of
action-20min
•
Stored at 2-8
0
C
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12. Compiled by: Prof. Anwar Baig
v. Therapeutic Uses of Oxytocin
1. Induction & augmentation of labor (slow I.V infusion)
Uterine inertia
Incomplete abortion
Post maturity
2. Post partum uterine hemorrhage (I.V drip)
3. Impaired milk ejection
One puff in each nostril 2-3 min before nursing
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13. Compiled by: Prof. Anwar Baig
vi.Side Effects:

a)
Hypertension
b)
Uterine rupture
c)
Fetal death(ischaemia)
d)
Water intoxication
e)
Neonatal jaundice

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14. Compiled by: Prof. Anwar Baig
2.
Ergot Alkaloids
•
Ergot is the natural alkaloid of
Claviceps purpurea
that
grows on rye, wheat and other grains.
•
Ergometrine (Ergonovine)
•
Methylergonovine
i. Chemistry
•
The ergot alkaloids are derivatives of the
tetracyclic
compound
6-methylergoline.

•
The first pure ergot alkaloid ergotamine was obtained
in 1920, followed by the isolation of
ergometrine/ergonovine in 1932.
•
The
therapeutically useful
natural alkaloids are
amide
derivatives of
d
-lysergic acid.
•
Semi-synthetic derivatives
are obtained from
catalytic
hydrogenation of the natural alkaloids
.
e.g.- Methergin (methylergonovine)
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15. Compiled by: Prof. Anwar Baig
ii. Pharmacodynamics:
a. Effects on the Uterus
•
Alkaloid derivatives induce
TETANIC CONTRACTION
of uterus without relaxation in between. These does
not resemble the normal physiological contractions
•
It causes contractions of uterus as a whole i.e.
fundus and cervix (tend to compress rather than to
expel the fetus)
(
Difference between oxytocin & ergots)

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16. Compiled by: Prof. Anwar Baig
b. Vascular effects:
Direct peripheral vasoconstriction
In large doses causes damage to capillary
endothelium.
Example: Ergotamine and DHE
c. Gastrointestinal effect:

Increased in peristaltic activity.
d. Miscellaneous effect:

5HT partial agonist
5HT selective antagonist
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17. Compiled by: Prof. Anwar Baig
iii.P
harmacokinetics
•

Absorbed orally from GIT(tablets)
•
Usually given I.M
•
Extensively metabolized in liver.
•
90% of metabolites are excreted in bile

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18. Compiled by: Prof. Anwar Baig
iv.
THERAPEUTIC
USES:
1.
POSTPARTUM

HEMORRHAGE
:
-
•
The uterus at term is
extremely sensitive
to the stimulant
action of ergot and even moderate doses produce a
prolonged and powerful spasm of the muscle quite
unlike

natural labor.
•
Therefore, ergot derivatives should be used
only for
control
of late
uterine

bleeding
and should never be given before
delivery.
•
Oxytocin is the
preferred

agent
for control of postpartum
hemorrhage but if this is ineffective,
ERGOMETRINE
(0.2
mg ) is given intramuscularly.
•
It is usually effective within 1
–
5 minutes and is less toxic
than other ergot derivatives for this application.
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19. Compiled by: Prof. Anwar Baig
v.
Side effects
:
a) Nausea, vomiting, diarrhea
b) Hypertension
c) Vasoconstriction of peripheral blood Vessels (toes &
fingers)
d)
Gangrene
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20. Compiled by: Prof. Anwar Baig
vi. Contraindications:

a) 1
st
and 2
nd
stage of labor
b) vascular disease
c) impaired hepatic and renal functions
vii.Precautions:

a) Cardiac diseases
b) Hypertension
c) Multiple pregnancy
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21. Compiled by: Prof. Anwar Baig
Difference b/w Oxytocin and Ergometrine
Ergometrine
Oxytocin
Tetanic contraction;
doesn't resemble
normal physiological
contractions
Resembles normal
physiological
contractions
Only in P.partum
hemorrhage
*
To induce &
augment labor.
*
Post partum
hemorrhage
Moderate onset
Long duration of
action
Rapid onset
Shorter duration of
action
Character
Contractions
Uses
Onset and
Duration
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22. Compiled by: Prof. Anwar Baig
3.
PROSTAGLANDINS (PGE
2
& PGF
2
α
)
i. MECHANISM OF ACTION
:
•
Contract uterine smooth muscle
Difference between PGS and Oxytocin:
1.
PGS contract uterine smooth muscle not only at
term(as with oxytocin), but throughout pregnancy.
2.
PGS soften the cervix; whereas oxytocin does not.
3.
PGS have longer duration of action than oxytocin.
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23. Compiled by: Prof. Anwar Baig
PG analogues & Common
Preprations
PGE
1
(methyl ester)
–
MISOPROSTOL
PGE
2

–
DINOPROSTONE
(NOTE: less toxic, more effective so widely used.)
PGF
2
ά
- DINOPROSTONE TROMETHAMINE
PGF
2
ά

(methyl analogue)
–
CARBOPROST

Preparations:
Tablet
:
0.5mg dinoprostone (prostinE
2
)
Vaginal suppository
:
20mg PGE
2
/50mg PGF
2
ά
lipid base
Vaginal pessary
:
3mg PGE
2
ProstinE
2
gel
:
500
μ
g into cervical canal, below internal OS/1-
2mg in the posterior fornix.
Parenteral:-
PGE
2
- ProstineE
2
1mg/ml
PGF
2
ά
-ProstinF
2
ά
(Dinoprost tromethamine) 5mg/mlMethyl analogue of PGF2ά - Carboprost 2.5mg/10ml vial
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24. Compiled by: Prof. Anwar Baig
ii. Therapeutic uses
1.
Induction of abortion (pathological)
*
*

2.
Induction of labor (fetal death in utero)
3.
Postpartum hemorrhage
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25. Compiled by: Prof. Anwar Baig
iii. Side Effects
a)
Nausea , vomiting
b)
Abdominal pain
c)
Diarrhea
d)
Bronchospasm (PGF2
α
)
e)
Flushing (PGE2)

25

26. Compiled by: Prof. Anwar Baig
iv. Contraindications:
a)
Mechanical obstruction of
delivery
b)
Fetal distress
c)
Predisposition to uterine
rupture
v. Precautions:
a)
Asthma
b)
Multiple pregnancy
c)
Glaucoma
d)
Uterine rupture
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27. Compiled by: Prof. Anwar Baig
Difference B/w Oxytocin and Prostaglandins
Prostaglandins
Oxytocin
Duration of
action
Contraction through
out pregnancy
Only at term
Longer
Soften the cervix
Does not soften the
cervix
Shorter
Character
Contraction
Cervix
uses
i. Used for
abortion
in 2
nd
trimester of
pregnancy.
ii.Used as vaginal
suppository for
induction of labor
i.Not used for
abortion
ii.Used for induction
and augmentation of
labor and post
partum hemorrhage
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28. Compiled by: Prof. Anwar Baig
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