Rozaimah Zain-Hamid & Yazanul Anwarocw.usu.ac.id/course/download/1110000106-reproductive-system/rps... · OXYTOCIC / UTEROTONIC AGENTS Zain-Hamid R & Anwar Y, Faculty of Medicine,

Rozaimah Zain-Hamid & Yazanul Anwar

Department of Pharmacology and TherapeuticsFaculty of MedicineFaculty of Medicine,

Universitas Sumatera Utara

OXYTOCIC / UTEROTONIC AGENTS

Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara


Stimulation

UTERINE CONTRACTION

Stimulation

UTERINE CONTRACTION

Induction/augment dysfunctional laborg yControl of post partum hemorhage

Incomplete abortion/abortion therapeuticIncomplete abortion/abortion therapeuticZain-Hamid R & Anwar Y, Faculty of Medicine,



O t iOxytocin

Derivate of Ergot AlkaloidsDerivate of Ergot Alkaloids

Derivate of Prostaglandin


Oxytocin



Stimulation of prostaglandin

Direct action on uterus smooth muscle prostaglandin

synthesisuterus smooth muscle

At terminal stage of pregnancy ( oxytocin receptor in myometrium)

Uterine contraction

( oxytocin receptor in myometrium)

Uterine contraction

Cervix dilatation & stretching of vaginaZain-Hamid R & Anwar Y, Faculty of Medicine,


Cervix dilatation & stretching of vagina

Uterine contraction

C i dil t ti &Cervix dilatation & stretching of vagina

Stimulation of cervix & vaginaStimulation of cervix & vagina

oxytocin secretion


OXYTOCIN(P i i i h )(Posterior pituitary hormone)

Pharmacokinetic :* RoA : i.v & buccal absorption

* Swallowed → inactive* Not bound to plasma protein

* Catabolized by the kidneys & liver Catabolized by the kidneys & liver* Circulating t 1/2 : 5 minutes


UTEROTONIC (OXYTOCIN)

Pharmacodynamic :Pharmacodynamic :Alters transmembrane ionic currents in

myometrial smooth muscle cells & myoepithelial cells of mammary alveoliy p y

Uterine contraction & leads to milk ejectionleads to milk ejection



Clinical pharmacology :

Diagnostic : placental circulatory conditionplacental circulatory condition

= Preparation available : Syntocinon & pitocin



Clinical pharmacology :Therapeutic :

Clinical pharmacology :

Induce laborAugment dysfunctional labor for :Augment dysfunctional labor for :

1.Conditions requiring early vaginal delivery:Rh problem maternal DM preeclampsiaRh problem, maternal DM, preeclampsia

2. Uterine inertia3 Incomplete abortion3. Incomplete abortion



Adverse reaction :

* Maternal death → hypertensive episodes* Uterine rupture Uterine rupture

* Water intoxication* F t l d th* Fetal death

* Afibrinogenemia



Contraindication :Contraindication :Fetal distress

PrematurityAb l f t l t tiAbnormal fetal presentation

Cephalo-pelvic disproportion

Other predispositions for uterine ruptureUsing sympathomimetic agentsUsing sympathomimetic agents


Derivate of Ergot Alkaloids


UTEROTONIC (ERGOT ALKALOIDS)

ERGOT ALKALOIDSα Adrenoceptors

ERGOT ALKALOIDSDopamine receptors

5 HT t5-HT receptorsProduced by

Claviceps purpureaHistamine

AcetylcholineAcetylcholine

Tyramine



PHARMACOKINETICS:PHARMACOKINETICS:

Variably absorbed from g.i.t

Amino acid alkaloids (ergotamine):

oral dose > i.m

S d f b ti & k bl dSpeed of absorption & peak blood level improved by caffeine



PHARMACOKINETICS:PHARMACOKINETICS:

Amine alkaloidsAmine alkaloids (ergonovine / ergometrine) :

Al b b d f tAlso absorbed from rectum, buccal cavity, aerosol inhaler

After i.m : slow absorption (reliable)

Metabolism : liverMetabolism : liverZain-Hamid R & Anwar Y, Faculty of Medicine,



PHARMACODYNAMICS:PHARMACODYNAMICS:

STIMULANT EFFECTS ON THE UTERUS:

Combine α agonist, 5-HT receptorsCh d ti llChanges dramatically → pregnancy

(↑ dominance α1 receptors as pregn progresses)pregn.progresses)

Sensitivity: uterus aterm > earlier pregn. > non pregn.



PHARMACODYNAMICS:PHARMACODYNAMICS:


Small doses: rhytmic contr. & relaxation


Small doses: rhytmic contr. & relaxation

Higher doses: powerful & prolonged contr.

Ergonovine : more selective → uterus(drug of choice : obstetric application)( g pp )



CLINICAL APPLICATION:CLINICAL APPLICATION:

For control of late uterine bleeding(Post-partum hemorrhage)

Sh ld b i b f d liShould never be given before delivery

Given at the time of delivery of placentaGiven at the time of delivery of placentaor immediately afterward if bleeding is significantif bleeding is significant



SIDE EFFECTS :SIDE EFFECTS :

Nausea, vomiting,

↑↑ Blood Pressure



TOXICITY:Gastrointestinal disturbancies:

diarrhea, nausea,vomitingvomiting

activation of medullary vomiting center & y ggastrointestinal serotonin receptors

prolonged vasospasmprolonged vasospasm(gangrene → amputation)

Therapy: infusion of large doses of py gnitroprusid or nitroglycerin



CONTRA INDICATION :

Obstructive vascular disease &

collagen diseasecollagen disease


Derivate of Prostaglandin


UTEROTONIC (PGE2 & PGF2α)

Contractile effectsContractile effects

Release of calcium ions

the frequency & strength of uterine contractionuterine contraction



A. ABORTIONA. ABORTIONPGE2 & PGF2α

1 st & 2 nd trimester abortion

↑ proteoglycan & changing biophysical properties of collagenchanging biophysical properties of collagen

ft th isoften the cervixZain-Hamid R & Anwar Y, Faculty of Medicine,



A. ABORTIONA. ABORTION

PGE2 & PGF2α (i.v )produced abortion in ± 80 % of cases rate

PGF2α (intra amniotic): success rate ± 100 %PGF2α (intra-amniotic): success rate ± 100 %

Adverse effects < i.vAdverse effects i.v

Other road of administration : i i t i li.m, intravaginal



A. ABORTION

Success rate

A. ABORTION

dose, duration of infusion & parity of the woman

Dose-limiting side effects

vomiting, diarrhea, hyperthermia & bronchoconstrictionbronchoconstriction



A. ABORTION

Dinoprost tromethamine ( der. PGF2α ) :

A. ABORTION

single 40 mg intra-amniotic injection

l t b ti 20 hcomplete abortion → 20 hours

Side Effects:Side Effects: cardiovascular collaps/anaphylactic shock,

pulmonary hypertension → ultrasonic guidancepulmonary hypertension → ultrasonic guidanceZain-Hamid R & Anwar Y, Faculty of Medicine,



A. ABORTION

Carboprost tromethamine (i.m) & multiple dose

Synthetic PGE2 analogue : vaginal suppositoria g pp

direct affects the collagenase



B. FACILITATION OF LABOR

PGE2 & PGF2α → PGF2α > potent than PGE2

PGF α has more g i t toxicity than PGEPGF2α has more g.i.t toxicity than PGE2

Success rate = oxytociny

G.i.t side effect > oxytocin



B. FACILITATION OF LABOR

PGE2 & PGF2α → pass fetoplacental barrier

fetal toxicity uncommon

Oral PGE2 superior than oral oxytocin, but = oxytocin i.vbut o ytoc



B FACILITATION OF LABORB. FACILITATION OF LABOR

PGE & PGF α have no antidiuretic effectPGE2 & PGF2α have no antidiuretic effect

induction labor in woman :induction labor in woman : preeclampsia, cardiac & renal disease

Ut i f t l d thUterine fetal death

prostglandine alone or + oxytocinprostglandine alone or + oxytocinZain-Hamid R & Anwar Y, Faculty of Medicine,


TOCOLYTIC AGENTS


TOCOLYTIC AGENTS

Suppress

UTERINE CONTRACTIONUTERINE CONTRACTION

Inhibition, delaying or halting labor


TOCOLYTIC AGENTSMagnesium sulphate

(MgSO4)

β Adrenergic agentsβ d e e g c age ts(terbutaline, ritodrine)

Calcium Channel blockers(verapamil, nifedipine)

Prostaglandin synthetase inhibitor(i d th i )(indomethacin)


Magnesium sulphate(MgSO4)( g 4)


Magnesium sulphate(MgSO4)(MgSO4)

Acts as a calcium antagonist &Acts as a calcium antagonist & membrane stabilizer

( the force of contraction)( the force of contraction)

Prophylaxis for preeclampsia (1st line therapy)(1st line therapy)

Prevent seizures continued for 12 24 h ft d li12-24 hours after delivery



Route of Administration: oral & i.v

SIDE EFFECTS: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)Zain-Hamid R & Anwar Y, Faculty of Medicine,



TOXICITY:

H i i t d iHypoxia, respiratory depression, cardiac arrest

CONTRA INDICATION:

Heart block, myocardial infarction, myasthenia gravis, renal impairmentmyasthenia gravis, renal impairment


Magnesium sulphate(M SO )(MgSO4)

EFFECTS TO THE NEWBORN:

Baseline heart rate, drowsy, weak cry,

sucking rate in the early postpartum period

Strict monitoring for mother & newborn


β Adrenergic agents(terbutaline ritodrine)(terbutaline, ritodrine)


β Adrenergic agents (terbutaline, ritodrine)

Level of cAMP via adenylate cyclase

level of free calcium ions

smooth muscle relaxationZain-Hamid R & Anwar Y, Faculty of Medicine,


smooth muscle relaxation

Terbutaline & ritodrineTerbutaline & ritodrine

or stop uterine contraction

Preterm labor



Route of Administration: oral & i.v, subcutaneuso a & , subcuta eus

controlled infusion pump(to give continuous low dose of terbutaline)(to give continuous low dose of terbutaline)



SIDE EFFECTS:Nervousness, restlessness, insomnia

headache rapid heart rate nauseaheadache, rapid heart rate, nausea,hyperglycemia, hypokalemia,

d l d h t f b thand pulmonary edema, shortness of breath, chest pain



WARNING:Cardiac dysrhythmia cardiac diseaseCardiac dysrhythmia, cardiac disease,

hypertension or thyrotoxicosis, shortness of breath, chest pain or

contraction still exist duringcontraction still exist during administration of terbutaline & ritodrine


Terbutaline


Fast heart rate,

hi h l bl d ft bi thhigh or low blood sugar after birth

Strict monitoring for mother & newborn


Calcium Channel blockersCalcium Channel blockers(verapamil, nifedipine)


Calcium Channel blockers(verapamil nifedipine)(verapamil, nifedipine)

Calcium ionsCalcium ions

Entering smooth muscle cells

the force of smooth muscle contractionZain-Hamid R & Anwar Y, Faculty of Medicine,



or stop contraction of uterusor stop contraction of uterus

Delay labor (used for occasional uterus irritability)(used for occasional uterus irritability)



Route of Administration: oralRoute of Administration: oral

SIDE EFFECTS:SIDE EFFECTS:

Facial flushing, headache, nausea,Facial flushing, headache, nausea, palpitation, lightheadedness


Calcium Channel blockersCalcium Channel blockers(verapamil, nifedipine)

EFFECTS TO THE NEWBORN:EFFECTS TO THE NEWBORN:

No serious side effects have been noteNo serious side effects have been note


Prostaglandin synthetase inhibitorProstaglandin synthetase inhibitor(indomethacin)


Prostaglandin synthetase inhibitor(i d th i )(indomethacin)

Synthesis of prostaglandin

the frequency & strength of uterine contractionuterine contraction


IndomethacinIndomethacin

Recommended as a tocolyticRecommended as a tocolytic in preterm labor at << 32 weeks

of gestation



R t f Ad i i t ti l itRoute of Administration: oral, suppository

SIDE EFFECTS:

Abdominal discomfort, nausea, vomiting, depression & dizziness



WARNINGWARNING:Pregnant woman who has a story of g y

bleeding disorders, aspirin sensitivity & kid blkidney problems




Have serious side effects on the foetus



Documents

Rozaimah Zain-Hamid & Yazanul Anwarocw.usu.ac.id/course/download/1110000106-reproductive-system/rps... · OXYTOCIC / UTEROTONIC AGENTS Zain-Hamid R & Anwar Y, Faculty of Medicine,