OXYTOCICS

Prepared by: Mirza Anwar Baig

M.Pharm (Pharmacology)
Anjuman I Islam's Kalsekar Technical Campus,
School of Pharmacy.
New Panvel,Navi Mumbai

Compiled by: Prof. Anwar Baig 1

 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”.

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 DRUGS PRODUCING UTERINE
CONTRACTIONS( Oxytocic Drugs )
1. OXYTOCIN
2. ERGOT ALKALOIDS
Ergometrine (Ergonovine)
3. PROSTAGLANDINS
a) PGE2
b) PGF2α

4. MISCELLANEOUS
Quinine
Emetine
Alcohol
Ethacridine

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 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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ii. Secretion of oxytocin:

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 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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 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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 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 .

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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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 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 0C

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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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vi.Side Effects:

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

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 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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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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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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iii.Pharmacokinetics

• Absorbed orally from GIT(tablets)

• Usually given I.M

• Extensively metabolized in liver.

• 90% of metabolites are excreted in bile

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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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v.Side effects:
a) Nausea, vomiting, diarrhea
b) Hypertension
c) Vasoconstriction of peripheral blood Vessels (toes &
fingers)
d) Gangrene

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vi. Contraindications:
a) 1st and 2nd 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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 Difference b/w Oxytocin and Ergometrine
Character Ergometrine Oxytocin
Contractions Tetanic contraction; Resembles normal
doesn't resemble physiological
normal physiological contractions
contractions

Uses Only in P.partum *To induce &

hemorrhage augment labor.
*Post partum
hemorrhage
Onset and Moderate onset Rapid onset
Duration Long duration of Shorter duration of
action action

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 3.PROSTAGLANDINS (PGE2 & PGF2α)

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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 PG analogues & Common Preprations
PGE1 (methyl ester) – MISOPROSTOL
PGE2 – DINOPROSTONE
(NOTE: less toxic, more effective so widely used.)
PGF 2ά- DINOPROSTONE TROMETHAMINE
PGF2ά (methyl analogue) – CARBOPROST

Preparations:
Tablet: 0.5mg dinoprostone (prostinE2)
Vaginal suppository: 20mg PGE2 /50mg PGF2ά lipid base
Vaginal pessary: 3mg PGE2
ProstinE2 gel: 500μg into cervical canal, below internal OS/1-
2mg in the posterior fornix.
Parenteral:-
PGE2 - ProstineE2 1mg/ml
PGF2ά-ProstinF2 ά(Dinoprost tromethamine) 5mg/ml
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Methyl analogue of PGF2ά- Carboprost 2.5mg/10ml vial
ii. Therapeutic uses
1. Induction of abortion (pathological)**

2. Induction of labor (fetal death in utero)

3. Postpartum hemorrhage

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iii. Side Effects

a) Nausea , vomiting
b) Abdominal pain
c) Diarrhea
d) Bronchospasm (PGF2α)
e) Flushing (PGE2)

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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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 Difference B/w Oxytocin and Prostaglandins

Character Prostaglandins Oxytocin

Contraction Contraction through Only at term

out pregnancy

Cervix Soften the cervix Does not soften the

cervix
Duration of Longer Shorter
action
uses i. Used for abortion i.Not used for
in 2nd trimester of abortion
pregnancy. ii.Used for induction
ii.Used as vaginal and augmentation of
suppository for labor and post
induction
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by: Prof. Anwar Baig partum27 hemorrhage
THANK YOU

Compiled by: Prof. Anwar Baig