27/10/2014

DRUG OF UTERUS
Pharmacology Department

TUJUAN BELAJAR
Mahasiswa akan dapat :
Menjelaskan mekanisme dan faktor yang
mempengaruhi kontraksi uterus
Menjelaskan jenis dan aspek farmakologi obat
uterotonika
Menjelaskan dan aspek farmakologi obat
uterolitik
Menjelaskan penggunaan klinis obat-obat
yang mempengaruhi kontraksi uterus

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Factors affecting uterus smooth muscle activity

Excitation
Factor
Inhibition
Receptor
Cholinergic
Adrenergic
Hormones
Female sex
Neurohypophyseal
Autocoids
Histamine
5-HT
PG-NP
PG-P
Peptides
Ion channels

Muscarinic
Alpha1

Beta2

Estrogen
Oxytocin
Vasopressin

Progestins

H1
5-HT2
F2alpha
E2,F2alpha
Substance P
Ca2+ ch.activator

H2(rat/mouse)
E2
I2
VIP(NP,early P)
Ca2+entry blocker

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MEKANISME KONTRAKSI
Stimulus Sensorik
Serviks
Vagina
Kel. mammae

Perangsangan saraf

Na+
Ca+

OKSITOSIKA
OKSITOSIN

KONTRAKSI

OBAT
OTONOM

: Depolarisasi
: Eksitasi (Excitation Contraction Coupling

OKSITOSIKA
= Obat yang merangsang kontraksi uterus
Intensitas
Frekuensi
MENINGKAT

OKSITOSIN
ERGOT DAN ALKALOID ERGOT
PROSTAGLANDIN

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OKSITOSIN
Oksitosin
Hipofisis Post-or

Anti Diuretik H
Vasopresin

Stimulasi Pada :
Serviks
Vagina
Mammae

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FD TERHADAP UTERUS
Reseptor berada pada miometrium
Meningkatkan frekuensi dan intensitas kontraksi

Sebanding dengan kadar estrogen

Berbanding terbalik dengan kadar progesteron

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
Clinically oxytocin is given only when uterine
cervix is soft and dilated
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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FD TERHADAP KEL. MAMMAE

Kontraksi mioefitel

Milk ejection Reflex

Atau Milk let down

ASI mudah keluar

Mengurangi Pembengkakan mammae

FD TERHADAP CV
Dosis berlebihan : vasodilatasi 
> Tekanan darah menurun
Pada dosis obstetrik Efek terhadap
pembuluh darah tidak nyata

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Kehamilan muda

Plasenta memproduksi
Enzim Sistilamino peptidase
Atau Oksitosinase

Inaktivasi oksitosin

FARMAKOKINETIK
Diberikan secara parenteral > baik
Oral
TABLET HISAP (Not too effective)
ok absorbsi cepat pada mukosa mulut-bukal
Intranasal : Spray hidung
Selama hamil oksitosinase meregulasi kadar
oksitosin di uterus
Waktu paruh : 12-17 menit
Ekskresi : Ginjal dan hati

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CLINICAL Use
 Drug of choice to Induction & augmentation of

labor






(slow I.V infusion)

Mild preeclampsia
Uterine inertia
Incomplete abortion
Post maturity
Maternal diabetes

 Post partum uterine hemorrhage  IV drip

 Impaired milk ejectionPromote lactation
o One puff in each nostril 2-3 min before
nursing

Side Effects:
Maternal death due to:

serious hypotension with associated
tachycardia

Uterine rupture

Fetal death(ischaemia)

water intoxication

Action on the kidney

Weak vasopressin-like anti diuretic action

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Contraindications
o
o
o
o
o

Hypersensitivity
Prematurity
Abnormal fetal position
Evidence of fetal distress
Cephalopelvic disproportion

Precautions
 Multiple pregnancy
 Previous c- section
 Hypertension

CONTOH OBAT
IM/IV : Pitocin 10 usp/unit/ml
Nasal : Intra nasal spray
40 usp/unit/ml
Oral
: Tablet hisap/ sublingual
(Sadopart) 200 usp/unit/tab

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CONTOH SEDIAAN
OKSITOSIN
oxytocin s* (ampul)
Pitogin* (ampul 10 iu/ml)
Syntocinon* (ampul : 10 iu/2 ml)

1. Induksi partus aterm (drug of choose: oksitosisn)

10 unit + 1 lt D 5% (10 m unit/ml)

RESPON
NEGATIVE

TIDAK boleh dipakai pada kala I dan II

PD MISSED AB : PG ok merangsang
Kontraksi uterus pada setiap UK

Infus : 0,2 ml/mt

15
0,1-0,2 ml/mt
15

15
2 ML/MT (maks)
PROSES PARTUS

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ALKALOID ERGOT
ASAL

Jamur Claviceps Purpurea

(butir rye dari gandum)

Sclerotium
(Zat padat warna ungu)

Sumber Ergot
ERGOTOKSIN
(First isolation)

Ergocristine
Ergocrnine
alfa ergocryptine
Beta ergocryptine

PEMBAGIAN
BERDASARKAN EFEK DAN STRK KIMIA
Alkaloid asam amino
Prototip : Ergotamin
Alkaloid murni pertama : ERGOTAMININ (tdk aktif )
diubah menjadi ergotamin (aktif)
Derivat alk. Dihidro asam amino
Prototip : Dihidro-Ergotamin
Alkaloid amin
Prototip : ERGONOVIN=Ergometrin
Untuk obtetrik : METILERGONOVIN (methergine)

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FARMAKOKINETIK
(ergonovin)
ABSORBSI
Pd GIT : cepat dan
sempurna.
kadar puncak plasma
: 10x lebih tinggi dari
ergotamin
metabolisme cepat

METABOLISM
Extensively metabolized
in liver
ELIMINASI
90% : MELALUI
EMPEDU
Urin sedikit
eliminasi paling cepat

FARMAKODINAMIK thd uterus

Meningkatkan kontraksi
Efeknya sebanding dengan
Maturasi dan UK
Dosis kecil
Meningkatkan
frekuensi dan amplitudo

Dosis besar

Tetanik : peningkatan
tonus istirahat

relaksasi

kontraktur

Uterus belum matur dapat bereaksi

ERGONOVIN bereaksi paling kuat

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Effects on the Uterus

Alkaloid derivatives induce TETANIC
CONTRACTION of uterus without
relaxation in betweennot like normal
physiological contractions
It causes contractions of uterus as a whole
i.e. fundus and cervixtend to compress
rather than to expel the fetus

FARMAKODINAMIK THD cv
Vasokonstriktor perifer
Merusak endothel kapiler

Bendungan darah
trombosis

GANGREN

ERGOTAMIN paling kuat

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INDIKASI

uterotonika : Post partum hemorrhage

infertilitas
galaktorea
kelainan haid (meno-metrorrhagika)
parkinson
BROMOKRIPTINE
AWAS ESO

ESO
ERGOTISME
AKUT
GIT : mual, muntah,
diare
Kulit dingin
Nadi lemah, cepat
Bingung
tidak sadar

KRONIS
DOSIS BESAR AKAN
MENINGKATKAN
SENSITIVITAS
Perub. Peredaran darah
ekstremitas
ektremit. Pucat, dingin,
kebas
Nyeri tungkai bawah :
jalan/ istirahat

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ESO-2

Trombus
emboli
Gangren
takikardia
Bradikardia
peningkatan/penurunan
TD
kejang, hemiplegia
miosis menetap

SEBAGAI OABT
MIGREN JANGAN
TAKUT KARENA
ESO JARANG

KONTRA INDIKASI

Induction of labour
1st and 2nd stage of labor
vascular disease
Severe hepatic and renal impairment
Severe hypertension

arteritis sifilisika
Arteriosklerosis
penyakit jantung koroner
Tromboplebitis

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CONTOH OBAT
METHERGIN
methilergonovin maleat : tab. 0,2 mg dan amp :
0,2 mg/ml
METHIL ERGOMETRIN
metherinal*
Myomergin*
Spasut*
Metilat*

PROSTAGLANDIN
BE FOUND IN
Uterus, cairan mens
Ovarium
Cairan semen laki-laki
Hamil (amnion, umbili
kus, darah ibu)

Dlm obstetrik
PGE

PGF

PGE2

PGF-2alfa

Proses persalinan

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FARMAKODINAMIK thd uterus

Meningkatkan kontraksi
PGF : uterus hamil/tidak (berespon)
PGE2 : uterus hamil berespon lebih kuat dari PGF,
tetapi pd uterus tidak hamil : RELAKSASI
Kisaran dosis-respon sempit shg mudah
HIPERTONI
SOLUSI : Intensine observation and titration dosage
(step by step)
Hamil tua (prepartum) efeknya = OKSITOSIN
PD seviks (vaginal sup) : pematangan servik tanpa
mempengaruhi motilitas uterus
U/ STIMULASI PARTUS

Difference between PG and Oxytocine

PGS contract uterine smooth muscle not only at
term(as with oxytocin), but throughout pregnancy.
PGS soften the cervix; whereas oxytocin does not.
PGS have longer duration of action than oxytocin.

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FARMAKODINAMIK THD cv
PGF 2 : Vasokonstriksi  hipertensi
PGE 2: Vasodilatasi  hipotensi

Pada dosis
BESAR

FD THD GIT DAN

HIPOTHALAMUS
GIT
Stumulasi otot polos :
mual
muntah
diare
HIPOTHALAMUS
Peningkatan suhu
(relatif)

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CLINICAL USE
 Induction of abortion (pathological)
 Induction of labor (fetal death in utero)
 Postpartum hemorrhage

ESO

Vomitus, diare
Perubahan DJJ
cervical fistul, Ruftur SBR
Fever
Hipotensi/Hipertensi
Pening
Perdarahan
Bronchospasm (PGF2)
Flushing (PGE2)

AWAS
.

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CONTRA INDICATION

Mechanical obstruction of delivery

Fetal distress

Predisposition to uterine rupture
PRECOUTION

Asthma
Multiple pregnancy
Glaucoma
Uterine rupture
Penyakit paru
Penyakit hati dan ginjal

CONTOH SEDIAAN
DINOPROSTONE (Prostin E2*)
Vaginal sup. (PGE2)
Indikasi : Induksi kontraksi uterus
induksi partus tapi servik masih
tertutup misal :
Case : missed abortion and mola
hidatidosa
Mesoprostol, cytotec
DINOPROST TROMETHAMINE
Amp. Intra amnion
CARBOPROST TROMETHAMINE
amp (PGF2) im. 250 ug/ml

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TOKOLITIKA
menghambat kontraksi uterus
(uterorelaksan)
menurunkan frekuensi dan intensitas
kontraksi
Jenis Obat
Mempengaruhi reseptor
Merangsang Beta 2 reseptor
Menurunkan derajat beta 1 reseptor

Calcium chanel Blocker

Prostaglandin synthetase inhibitors

INDIKASI
Mencegah partus prematurus
Buka OUE : < 4 cm biasanya SUKSES
Memperlambat persalinan
pada proses transpor ke RS
Pada persiapan OP
MENGURANGI FETAL DISTRESS

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EFFECT ON RECEPTOR
Mechanism of action
- adrenocept or agonists
Bind to -adrenoceptors  activate enzyme
Adenylate cyclase increase in the level of
cAMP reducing intracellular calcium level.

Side effects:

Tremor

Nausea , vomiting

Flushing

Sweating

Tachycardia (high dose)

Hypotension

Hyperglycemia

Hypokalaemia

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KONTRA INDIKASI

post partum
Arterial bleeding
PJI, IMA
Glukoma
Penyakit cerebrovask

CONTOH SEDIAAN OBAT

RITODRINE (Yutopar*)
amp : 10 mg/ml atau tab. 10 mg
ISOXSUPRINE tab 20 mg
Terbutalin
FENOTEROL (OBAT ASMA)

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CALCIUM CHANNEL BLOCKERS

Nifedipine

Causes relaxation of myometrium

Markedly inhibits the amplitude of spontaneous and oxytocininduced contractions
Side Effect
Headache, dizziness
Hypotension
Flushing
Constipation
Ankle edema
Coughing
Wheezing
Tachycardia

Prostaglandin synthetase inhibitors

The depletion of prostaglandins prevents
stimulation of uterus

NSAID,s

Indomethacin

Aspirin

Ibuprofen

Side Effect

Ulceration

Premature closure of ductus arterious

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