k23 - Uterotonika Dan Tokolitik-1

8/10/2019 k23 - Uterotonika Dan Tokolitik-1

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DRUG OF UTERUS

Pharmacology Department

TUJUAN BELAJAR

Mahasiswa akan dapat :

Menjelaskan mekanisme dan faktor yang

mempengaruhi kontraksi uterus

Menjelaskan jenis dan aspek farmakologi obatuterotonika

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

Factor

Receptor

Cholinergic

Adrenergic

Hormones

Female sex

Neurohypophyseal

Autocoids

Histamine

5-HT

PG-NP

PG-P

Peptides

Ion channels

Excitation

Muscarinic

Alpha1

Estrogen

Oxytocin

Vasopressin

H1

5-HT2

F2alpha

E2,F2alpha

Substance P

Ca2+ ch.activator

Inhibition

Beta2

Progestins

H2(rat/mouse)

E2

I2

VIP(NP,early P)

Ca2+entry blocker


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MEKANISME KONTRAKSI

KONTRAKSI

Stimulus Sensorik

Serviks

Vagina

Kel. mammae

Perangsangan saraf

OKSITOSIN

OBAT

OTONOM

OKSITOSIKA

Na+ : Depolarisasi

Ca+ : Eksitasi (Excitation Contraction Coupling

OKSITOSIKA

= Obat yang merangsang kontraksi uterus

Intensitas

Frekuensi MENINGKAT

OKSITOSIN

ERGOT DAN ALKALOID ERGOT

PROSTAGLANDIN


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OKSITOSIN

Hipofisis Post-or

Vasopresin

Anti Diuretik H

Oksitosin

Stimulasi Pada :

Serviks

Vagina Mammae


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FD TERHADAP UTERUS Reseptorberada 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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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 beforenursing

CLINICAL Use

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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Contraindicationso Hypersensitivity

o Prematurity

o Abnormal fetal position

o Evidence of fetal distress

o 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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ALKALOID ERGOTASAL Jamur Claviceps Purpurea

(butir rye dari gandum)

Sclerotium

(Zat padat warna ungu)

Sumber Ergot

Ergocristine

Ergocrnine

alfa ergocryptine

Beta ergocryptine

ERGOTOKSIN

(First isolation)

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

Dosis besar

Uterus belum matur dapat bereaksi

ERGONOVIN bereaksi paling kuat

relaksasiMeningkatkan

frekuensi dan amplitudo

Tetanik : peningkatan

tonus istirahat kontraktur


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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

ERGOTAMIN paling kuat

Bendungan darah

trombosisGANGREN


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INDIKASI uterotonika : Post partum hemorrhage

infertilitas

galaktorea

kelainan haid (meno-metrorrhagika)

parkinson

BROMOKRIPTINE

AWAS ESO

ESO

ERGOTISMEAKUT

GIT : mual, muntah,

diare

Kulit dingin Nadi lemah, cepat

Bingung

tidak sadar

KRONIS

DOSIS BESAR AKAN

MENINGKATKAN

SENSITIVITAS

Perub. Peredaran darahekstremitas

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, umbilikus, darah ibu)

PGE

PGF-2alfaPGE2

PGF

Dlm obstetrik

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 mudahHIPERTONI

SOLUSI : Intensine observation and titration dosage

(step by step) Hamil tua (prepartum) efeknya = OKSITOSIN

PD seviks (vaginal sup) : pematangan servik tanpamempengaruhi motilitas uterus

U/ STIMULASI PARTUS

Difference between PG and Oxytocine

PGS contract uterine smooth muscle not only atterm(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

HIPOTHALAMUSGIT

Stumulasi otot polos :

mual

muntahdiare

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 cyclaseincrease 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 oxytocin-

induced 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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k23 - Uterotonika Dan Tokolitik-1

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