OXYTOCIC

OXYTOCIC / UTEROTONIC
Stimulation
UTERUS CONTRACTION

* Oxytocin
* Derivat Ergot alkaloids
* Derivat Prostaglandin

Oxytocin
(Posterior pituitary hormone)

Oxytocin secretion occurs

by sensory stimulation from cervix, vagina , and from suckling at breast

Pharmacokinetic :
* Route of administration : i.v & buccal absorption
Also as nasal spray (impaired milk ejection)
* Swallowed inactive
* Not bound to plasma protein
* Catabolized by the kidneys & liver
* Circulating t 1/2 : 5 minutes

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Mechanism of action :

Interaction myometrial cell membrane receptor promotes the influx of Ca++ from extra cellular
fluid and from S.R in to the cell

cytoplasmic calcium

Stimulates uterine contraction

Pharmacodynamic :
Alters transmembrane ionic currents in myometrial smooth muscle cells & myoepithelial cells of
mammary alveoli

Uterine contraction & leads to milk ejection

- adrenoceptor agonist, Mg SO4 , inhalation anesthetic

Uterus

Stimulates both the frequency and force of uterine contractility particularly of the fundus
segment of the uterus

The 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 & 30 times in early labor

Clinically oxytocin is given only uterine cervix is soft & dilated

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Clinical application :
* Diagnostic : placental circulatory condition
* Therapeutic :
= Induce labor (slow i.v infusion)
= Augment dysfunctional labor for :
1. Conditions requiring early vaginal delivery:
Rh problem, maternal diabetes,
preeclampsia & post maturity
2. Uterine inertia
3. Incomplete abortion
* Therapeutic
= Post partum uterine hemorrhag (i.v drip)
(ergometrine is often used)
= Impaired milk ejection
One puff in each nostril 2-3 min before nursing
= Preparation available : Syntocinon & pitocin

Adverse reaction :
* Maternal death hypertensive episodes
* Uterine rupture
* Water intoxication
* Fetal death
* Afibrinogenemia

Contra indication :
* Fetal distress
* Prematurity
* Abnormal fetal presentation
* Cephalo-pelvic disproportion

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* Other predispositions for uterine rupture

* Using sympathomimetic agents

Precautions
Multiple pregnancy
Previous sectio caecarean
Hypertension

Ergot alkaloids
Adrenoceptors
ERGOT ALKALOIDS

Dopamine receptors
5-HT receptors
Histamine

Claviceps purpurea

Acetylcholine
Tyramine

Pharmacokinetics:

Variably absorbed from g.i.t

Ergotamine:
- oral dose > i.m
- Speed of absorption & peak blood level
improved by caffeine
Amine alkaloids:
- Ergonovine / ergometrine / methylergonovine
- Also absorbed from rectum, buccal cavity, aerosol inhaler
- After i.m : slow absorption but reliable
- Metabolism : liver
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Pharmacodynamics:
Stimulant effects on the uterus:

Combine agonist, 5-HT receptors

Changes dramatically pregnancy

( Dominance 1 receptors as pregn. progresses)

Sensitivity:

uterus at term > earlier pregnancy > non pregnancy

Small doses: rhytmic contraction & relaxation

Higher doses: powerfull & prolonged contraction

Ergonovine / methylergonovine:

more selective uterus

(Drug of choice : obstetric application)
Stimulant effects on the uterus:

Alkaloid derivatives induce TETANIC CONTRACTION without relaxation in between (not like
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??

Clinical application:

For control of late uterine bleeding

(Post-partum hemorrhage/ PPH)

Should never be given before delivery

Given at the time of delivery of placenta

or immediately afterward
if bleeding is significant
Side effects : Nausea, vomiting, BP

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Toxicity:
g.i.t disturbancies : diarrhea, nausea, vomiting activation of medullary vomiting center
& g.i.t serotonin receptors more dangerous prolonged vasospasm
(toes & fingers gangrene amputation)
Therapy: infusion of large doses
of nitroprusid or nitroglycerin
C.I: vascular disease & collagen disease

Contra indication:
1) Induction of labour:
1st and 2nd stage of labor
2) Vascular disease
3) Severe hepatic & renal impairment
4) Severe hypertension

Difference b/w oxytocin & ergometrine

Character

Oxytocin

Ergometrine

Contractions

Resembles normal physiological

contractions

Tetanic contraction ; doesn't resemble

normal physiological contractions

Uses

To induce & augment labor

Only in post partum hemorrhage

*Post partum hemorrhage

Onset

Rapid onset

and Duration

Shorter duration

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Moderate onset
of action

Long duration of action

Prostaglandin
Uterotonic (PGE2 & PGF2)
Clinical application:
1.

Induction of abortion (pathological)**

2.

Induction of labor (fetal death in utero)

3.

Postpartum hemorrhage

A. Abortion

PGE2 & PGF2 : 1 st & 2 nd trimester abortion proteoglycan & changing biophysical

properties of collagen soften the cervix

PGE2 & PGF2 : produced abortion in 80 % of cases rate), i.m, i.v, intravaginal

Success rate dose, duration of infusion & parity of the woman

Dose-limiting side efect : vomiting, diarrhea,

hyperthermia & bronchoconstriction

Synthetic PGF2 analogue :

Carboprost tromethamine (i.m)
& multiple dose
Vaginal suppositoria :
direct affects the collagenase
Dinoprost tromethamine (derivat PGE2 ) :
Single 40 mg intra-amniotic injection
complete abortion 20 hours
S.E: cardiovascular collaps/anaphylactic shock,
pulmonary hypertension ultrasonic guidance

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B. Facilitation of labor

PGE2 & PGF2 PGF2 more potent than PGE2

PGF2 has more g.i.t toxicity than PGE2

Success rate = oxytocin

G.i.t side effect > oxytocin

PGE2 & PGF2 pass fetoplacental barrier fetal toxicity uncommon

Oral PGE2 = oxytocin i.v

PGE2 & PGF2 have no antidiuretic effect induction labor in woman : preeclampsia,
cardiac & renal disease

Uterine fetal death prostglandin alone or + oxytocin

Side Effects:
Nausea , vomiting
Abdominal pain, diarrhea
Bronchospasm (PGF2)
Flushing (PGE2)

Contra indications:
Mechanical obstruction of delivery
Fetal distress
Predisposition to uterine rupture

Precautions:

Asthma

Multiple pregnancy
Glaucoma
Uterine rupture

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Difference b/w oxytocin and prostaglandins

Character

Oxytocin

Prostaglandins

Contraction

Only at term

Contraction through
out pregnancy

Cervix

Does not soften

the cervix

Soften the cervix

Character

Oxytocin

Prostaglandins

Duration
action

of

Uses

Shorter

Induce & augment

labour & post partum
hemorrhage

Longer

Induce abortion
2nd trimester
pregnancy

in
of

Used as vaginal suppository

for induction of labor

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TOCOLYTIC
Action and Uses
Relax the uterus & arrest threatened abortion or delay premature labor

Tocolytic (Magnesium sulfate / Mg2SO4)

Mechanism of action:
Displaced intracellular calcium leading to inhibition of the uterine activity

Clinical application:
Prevention of seizures in eclampsia, not used for arrest of preterm labor for its toxicites
The initial dose is 40 cc of 10% solution given slowly i.v
The subsequent doses: depend upon the response & the development of MgSO4 toxicity so
reflexes and respiratory rate should be observed

Side effects:
-

Respiratory depression
Weakness diplopia
Muscular paralysis
Cardiac arrest
Dosis > 5o mg associated with neonatal brain damage

-adrenoceptor agonists
Tocolytic (-Adrenoceptor agonists)
Ritodrine, i.v. drip
Selective 2 receptor agonist
used specifically as a uterine relaxant

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Mechanism of action
Activate enzyme adenylate cyclase the level of cAMP reducing intracellular calcium level

Side effects:
Pulmonary edema
Hyperglycemia
Hypokalaemia
Hypotension, myocardial ischaemia
Tachycardia (high dose), arrythmia
Nausea, vomiting
Flushing, Sweating,
Tremor

Ca++ channel blockers

(nifedipine)
Tocolytic (Ca++ channel blockers) e.g., nifedipine

Causes relaxation of myometrium

Markedly inhibits the amplitude of spontaneous & oxytocin-induced contractions

Side effects

Transient hipotension

Headache, dizziness, hypotension

Flushing, constipation

Ankle edema, coughing

Wheezing, tachycardia

Tocolytic (prostaglandin synthetase inhibitors)

The depletion of prostaglandins prevents stimulation of uterus

NSAID,s e.g. Indomethacin, Aspirin, Ibuprofen

Nonspecific COX inhibitor, prostaglandin synthetase inhibitor

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Prostaglandins myometrial gap junctions Ca through transmembrane influx

from the sarcolemma

Side Effects: Primary Pulmonary Hypertension, premature PDA closure, predispose to

bleeding ( thromboxane A2)

Side effects
Hepatitis
Renal failure

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