K-45 Pharmacology of Uterotonics & Tocolytics

Prof.Dr.dr.
Jazanul Anwar SpFK
Department of Pharmacology and Therapeutics

Faculty of Medicine,
Universitas Sumatera Utara
OXYTOCIC / UTEROTONIC AGENTS
1. Giving tone to the uterine muscle.
2. An agent that overcomes relaxation of the

muscular wall of the uterus.
Direct action on Stimulation of

uterus smooth muscle prostaglandin
synthesis
At terminal stage of pregnancy

( oxytocin receptor in myometrium)
Uterine contraction
Cervix dilatation & stretching of vagina

Stimulation
UTERINE CONTRACTION
Induction/augment dysfunctional labor

Control of post partum hemorhage
Incomplete abortion/abortion therapeutic
Oxytocin
Derivate of Ergot Alkaloids
Derivate of Prostaglandin
Oxytocin
Oxytocin is a synthetic compound. It is

identical to the natural hormone which is
found in the posterior pituitary. It causes
potent and selective stimulation of
uterine and mammary gland smooth
muscle.
Pitocin, Syntocinon
Pharmacoynamics
Oxytocin stimulates the contraction
of the uterus by increasing
sodium permeability of uterine
myofibrils.
UTEROTONIC (OXYTOCIN)
Pharmacodynamic :
Alters transmembrane ionic currents in
myometrial smooth muscle cells &
myoepithelial cells of mammary alveoli
Uterine contraction &

leads to milk ejection
Uterine contraction
Cervix dilatation &

stretching of vagina
Stimulation of cervix & vagina
oxytocin secretion
OXYTOCIN
(Posterior pituitary hormone)
Pharmacokinetic :
Oxytocin is destroyed in the GI tract and must be
given either IV, IM, SQ, or by nasal spay.
* RoA : i.v & buccal absorption
* Swallowed inactive
* Not bound to plasma protein
* Catabolized by the kidneys & liver
* Circulating t 1/2 : 5 minutes
Clinical pharmacology :
Therapeutic :
Induce labor
Augment dysfunctional labor for :
1. Conditions requiring early vaginal delivery:
Rh problem, maternal DM, preeclampsia
2. Uterine inertia
3. Incomplete abortion
Adverse reaction :
* Maternal death hypertensive episodes

* Uterine rupture
* Water intoxication
* Fetal death
* Afibrinogenemia
Contraindication :
Fetal distress
Prematurity
Abnormal fetal presentation
Cephalo-pelvic disproportion
Other predispositions for uterine rupture
Using sympathomimetic agents
UTEROTONIC (ERGOT ALKALOIDS)
Adrenoceptors
ERGOT ALKALOIDS
Dopamine receptors
5-HT receptors
Produced by
Histamine
Claviceps purpurea
Acetylcholine
Tyramine
PHARMACOKINETICS:
Variably absorbed from g.i.t
Amino acid alkaloids (ergotamine):

oral dose > i.m
Speed of absorption & peak blood
level improved by caffeine
Drug Interactions or
Contraindications:
Avoid using vasoconstrictors with
oxytocin as it can result in
hypertension.
PHARMACOKINETICS:
Amine alkaloids
(ergonovine / ergometrine) :
Also absorbed from rectum,
buccal cavity, aerosol inhaler
After i.m : slow absorption (reliable)
Metabolism : liver
PHARMACODYNAMICS:
STIMULANT EFFECTS ON THE UTERUS:
Combine agonist, 5-HT receptors
Changes dramatically pregnancy
( dominance 1 receptors as
pregn.progresses)
Sensitivity:
uterus aterm > earlier pregn. > non pregn.
PHARMACODYNAMICS:
STIMULANT EFFECTS ON THE UTERUS:
Small doses: rhytmic contr. & relaxation

Higher doses: powerful & prolonged contr.
Ergonovine : more selective uterus
(drug of choice : obstetric application)
CLINICAL APPLICATION:
For control of late uterine bleeding

(Post-partum hemorrhage)
Should never be given before delivery
Given at the time of delivery of placenta

or immediately afterward
if bleeding is significant
Derivate of Ergot Alkaloids
SIDE EFFECTS :
Nausea, vomiting,
Blood Pressure
TOXICITY:
Gastrointestinal disturbancies:
diarrhea, nausea,
vomiting

activation of medullary vomiting center &
gastrointestinal serotonin receptors
prolonged vasospasm
(gangrene amputation)
Therapy: infusion of large doses of
nitroprusid or nitroglycerin
CONTRA INDICATION :
Obstructive vascular disease &

collagen disease
Derivate of Prostaglandin
UTEROTONIC (PGE2 & PGF2)
Contractile effects
Release of calcium ions
the frequency & strength of

uterine contraction
A. ABORTION
PGE2 & PGF2 (i.v )

produced abortion in 80 % of cases rate
PGF2 (intra-amniotic): success rate 100 %
Adverse effects < i.v

Other road of administration :
i.m, intravaginal
B. FACILITATION OF LABOR
PGE2 & PGF2 pass fetoplacental barrier

fetal toxicity uncommon
Oral PGE2 superior than oral oxytocin,

but = oxytocin i.v
B. FACILITATION OF LABOR
PGE2 & PGF2 have no antidiuretic effect

induction labor in woman :
preeclampsia, cardiac & renal disease
Uterine fetal death

prostglandine alone or + oxytocin
TOCOLYTIC AGENTS
Zain-Hamid R & Anwar Y, Faculty of Medicine,

TOCOLYTIC AGENTS
Suppress
UTERINE CONTRACTION
Inhibition, delaying or halting labor

TOCOLYTIC AGENTS
Magnesium sulphate
(MgSO4)
Adrenergic agents
(terbutaline, ritodrine)
Calcium Channel blockers

(verapamil, nifedipine)
Prostaglandin synthetase inhibitor

(indomethacin)
Magnesium sulphate
(MgSO4)
Magnesium sulphate
(MgSO4)
Acts as a calcium antagonist &

membrane stabilizer
( the force of contraction)
Prophylaxis for preeclampsia

(1st line therapy)
Prevent seizures continued for
12-24 hours after delivery
Magnesium sulphate
(MgSO4)
Route of Administration: oral & i.v

SIDE EFFECTS:
Feeling of extreme warmth, perspiration,
flushing, nausea, vomiting, blurred vision,
lightheadedness, lethargy, nasal stiffness,
constipation, affects the reflexes,
and slow breathing,
chest pain (taking together with other tocolytic)
Magnesium sulphate
(MgSO4)
TOXICITY:
Hypoxia, respiratory depression,
cardiac arrest
CONTRA INDICATION:
Heart block, myocardial infarction,
myasthenia gravis, renal impairment
Adrenergic agents
Adrenergic agents
Level of cAMP via adenylate cyclase
level of free calcium ions
smooth muscle relaxation

Terbutaline & ritodrine
or stop uterine contraction
Preterm labor
Route of Administration:
oral & i.v, subcutaneus
controlled infusion pump
(to give continuous low dose of terbutaline)
SIDE EFFECTS:
Nervousness, restlessness, insomnia
headache, rapid heart rate, nausea,
hyperglycemia, hypokalemia,
and pulmonary edema, shortness of breath,
chest pain
WARNING:
Cardiac dysrhythmia, cardiac disease,
hypertension or thyrotoxicosis,
shortness of breath, chest pain or
contraction still exist during
administration of terbutaline & ritodrine
Calcium ions
Entering smooth muscle cells
the force of smooth muscle contraction

or stop contraction of uterus
Delay labor
(used for occasional uterus irritability)
Route of Administration: oral
SIDE EFFECTS:
Facial flushing, headache, nausea,

palpitation, lightheadedness
EFFECTS TO THE NEWBORN:
No serious side effects have been note

(indomethacin)

(indomethacin)
Synthesis of prostaglandin
the frequency & strength of

uterine contraction
Indomethacin
Recommended as a tocolytic
in preterm labor at << 32 weeks
of gestation

Indomethacin
Route of Administration: oral, suppository

SIDE EFFECTS:
Abdominal discomfort, nausea,

vomiting, depression & dizziness
Indomethacin
WARNING:
Pregnant woman who has a story of
bleeding disorders, aspirin sensitivity &
kidney problems
Indomethacin
EFFECTS TO THE NEWBORN:
Have serious side effects on the foetus

Contraindications to Tocolysis
Fetus is older than 37 weeks gestation

Fetus weighs more than 2500g
Fetus is in acute distress or has passed (or
has a fatal anomaly)
Dilation is greater than 4 cm
Chorioamnionitis or intrauterine infection is
present
Mother has severe Pregnancy-
induced_hypertension, eclampsia, active
vaginal bleeding, a cardiac disease, or another
condition which indicates that the pregnancy
should not continue. Fetus is older than 37
weeks gestation

K-45 Pharmacology of Uterotonics &amp; Tocolytics

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Prof.Dr.dr.

Jazanul Anwar SpFK

Department of Pharmacology and Therapeutics

1. Giving tone to the uterine muscle.

2. An agent that overcomes relaxation of the

Direct action on Stimulation of

At terminal stage of pregnancy

Cervix dilatation & stretching of vagina

Induction/augment dysfunctional labor

Derivate of Ergot Alkaloids

Oxytocin is a synthetic compound. It is

Uterine contraction &

Cervix dilatation &

Stimulation of cervix & vagina

* Maternal death hypertensive episodes

Amino acid alkaloids (ergotamine):

STIMULANT EFFECTS ON THE UTERUS:

Small doses: rhytmic contr. & relaxation

For control of late uterine bleeding

Should never be given before delivery

Given at the time of delivery of placenta

Obstructive vascular disease &

Release of calcium ions

the frequency & strength of

PGE2 & PGF2 (i.v )

Adverse effects < i.v

PGE2 & PGF2 pass fetoplacental barrier

Oral PGE2 superior than oral oxytocin,

PGE2 & PGF2 have no antidiuretic effect

Uterine fetal death

Zain-Hamid R & Anwar Y, Faculty of Medicine,

Inhibition, delaying or halting labor

Calcium Channel blockers

Prostaglandin synthetase inhibitor

Acts as a calcium antagonist &

Prophylaxis for preeclampsia

Route of Administration: oral & i.v

Level of cAMP via adenylate cyclase

level of free calcium ions

smooth muscle relaxation

or stop uterine contraction

Entering smooth muscle cells

the force of smooth muscle contraction

or stop contraction of uterus

Route of Administration: oral

Facial flushing, headache, nausea,

EFFECTS TO THE NEWBORN:

No serious side effects have been note

Zain-Hamid R & Anwar Y, Faculty of Medicine,

Zain-Hamid R & Anwar Y, Faculty of Medicine,

the frequency & strength of

Zain-Hamid R & Anwar Y, Faculty of Medicine,

Route of Administration: oral, suppository

Abdominal discomfort, nausea,

EFFECTS TO THE NEWBORN:

Have serious side effects on the foetus

Fetus is older than 37 weeks gestation

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