Venkataramu – OXYTOCICS (Oxytocin, Ergot, PGs)

Vijay Kumar - AntiHTN, Diuretics, Tocolytics, TERATOLOGY

Vishwanath – Anesthesia & Analgesia

OXYTOCICSOXYTOCICS

Venkataramu.B.S9term, MIMS

““OXYTOCICSOXYTOCICS

are the drugs of varying are the drugs of varying chemical nature that chemical nature that have the power to excite have the power to excite contraction of the contraction of the uterine musclesuterine muscles.”.”

OXYTOCICS

OXYTOCINERGOT

DERIVATIVESPROSTAGLANDINS

Ergometrine & Methergin E2&F2E2&F2άά

PGEPGE2 2 & &

PGFPGF22άά

Oxytocin: physiologyOxytocin: physiology

Human hypothalamusHuman hypothalamus

Diagram depicts a sagittal section through the Diagram depicts a sagittal section through the hypothalamus and pituitary gland.hypothalamus and pituitary gland.

The The posterior pituitary consists of axon posterior pituitary consists of axon terminals of magnocellular neurons terminals of magnocellular neurons arising in the supraoptic and arising in the supraoptic and paraventricular nuclei of the paraventricular nuclei of the hypothalamus. hypothalamus.

●

●●●

During lactationDuring lactation……

oxytocinoxytocin

mechanoreceptors mechanoreceptors in the in the nipple/ areolanipple/ areola

hypothalamic hypothalamic neuronal activityneuronal activityMILK EJECTIONMILK EJECTION

SucklingSuckling

Axon terminals

Axon terminals

myo

epith

elia

l

myo

epith

elia

l

cells

cells

con

trac

t

cont

ract

STIMULUS

RESPONSE

During parturition…During parturition… oxytocin is the oxytocin is the primary mediatorprimary mediator of myometrial of myometrial

contractility during labor.contractility during labor. During the During the second half of pregnancysecond half of pregnancy, uterine , uterine

smooth muscle shows an increase in the expression smooth muscle shows an increase in the expression of of oxytocin receptors(100-200fold) and becomes oxytocin receptors(100-200fold) and becomes increasingly sensitiveincreasingly sensitive to the stimulant action of to the stimulant action of endogenous oxytocin. endogenous oxytocin.

Stimulates PG synthesis. Stimulates PG synthesis. Physiological uterine contractionPhysiological uterine contraction - fundal - fundal

contraction; cervical relaxation. (law of polarity contraction; cervical relaxation. (law of polarity maintained)maintained)

Cervical and vaginal dilatation results in an acute Cervical and vaginal dilatation results in an acute release of oxytocin from the posterior pituitary in a release of oxytocin from the posterior pituitary in a process known as the process known as the Ferguson reflexFerguson reflex..

BSORPTION, METABOLISM, AND BSORPTION, METABOLISM, AND EXCRETIONEXCRETION

IntravenouslyAA (controlled infusion) for initiation for initiation and augmentation of labor. and augmentation of labor.

intramuscularlyintramuscularly -control of postpartum bleeding. -control of postpartum bleeding. Buccal & nasal spray- Limited use.Buccal & nasal spray- Limited use. Preparations: Preparations:

o Synthetic oxytocin (Syntocinon, Pitocin) 5IU/ml ampSynthetic oxytocin (Syntocinon, Pitocin) 5IU/ml ampo Syntometrine (Sandoz - Syntocinon 5U+Ergometrine Syntometrine (Sandoz - Syntocinon 5U+Ergometrine

0.5mg)0.5mg)o Desamino oxytocin - Buccal tablet 50 I.U.Desamino oxytocin - Buccal tablet 50 I.U.o Oxytocin nasal spray – 40U/mlOxytocin nasal spray – 40U/ml

Oxytocin is not bound to Oxytocin is not bound to plasma proteinsplasma proteins and is and is eliminated by the kidneys and livereliminated by the kidneys and liver..

Circulating half-life of Circulating half-life of max. 5 minutesmax. 5 minutes. (avg 3-. (avg 3-4min)4min)

Duration of Duration of action-20minaction-20min Stored at 2-8 Stored at 2-8 00C C

PharmacodynamicsPharmacodynamicsUTERUSUTERUS Oxytocin acts through Oxytocin acts through G protein-coupled G protein-coupled

receptorsreceptors and the and the phosphoinositide -phosphoinositide -calcium calcium secondsecond-messenger system to contract uterine -messenger system to contract uterine smooth musclesmooth muscle. .

Oxytocin also stimulates the Oxytocin also stimulates the release of release of prostaglandinsprostaglandins and and leukotrienesleukotrienes that augment that augment uterine contractionuterine contraction. .

Oxytocin in Oxytocin in small dosessmall doses increases both the increases both the frequency and the force of uterine frequency and the force of uterine contractionscontractions. .

At At higher doseshigher doses, it produces , it produces sustained sustained contractioncontraction..

BREASTBREAST Oxytocin also causes contraction of Oxytocin also causes contraction of

myoepithelial cells surrounding myoepithelial cells surrounding mammary alveoli, which leads to mammary alveoli, which leads to milk milk ejectionejection..

Without oxytocin-induced contraction, Without oxytocin-induced contraction, normal lactation cannot occur. normal lactation cannot occur.

KIDNEYSKIDNEYS At high concentrations, oxytocin has At high concentrations, oxytocin has

weak antidiuretic and pressorweak antidiuretic and pressor activity due to activation of vasopressin activity due to activation of vasopressin receptors.receptors.

Toxicity Toxicity ““serious toxicity is rareserious toxicity is rare” when ” when

oxytocin is used judiciously. oxytocin is used judiciously.

excessive uterinestimulation

Hypertonia(↑duration)

uterine rupture..

Polysystole(>6 in 10min)

placental abruption

fetal distress

STIMULATION

HYPER

Grand multipara, MalpresentationContracted pelvisPrior uterine scar(hyterotomy)

NOTE: These complications can be detected NOTE: These complications can be detected

early by means ofearly by means of

standard standard fetal monitoring equipmentfetal monitoring equipment. .

Pul. EdemaPul. EdemaHeart FailureHeart Failure

water water Intoxication-Intoxication-

hyponatremiahyponatremia

AntidiuresisAntidiuresis excessive fluid excessive fluid

retentionretention

activation of activation of vasopressinvasopressin

receptorsreceptors--

Seizures & death

Inadvertent activation of Inadvertent activation of vasopressinvasopressin receptors receptors--

30-40mIU/min

40-50IU/min

To avoid hypotension, oxytocin isTo avoid hypotension, oxytocin is

administered intravenously as administered intravenously as

dilute solutions at a dilute solutions at a controlled rate.controlled rate.

OXYTOCIN BOLUS HYPOTENSION

Transient vasodilation

INDICATIONSINDICATIONS

THERAPEUTICTHERAPEUTIC

PREGNANCY LABOUR PUERPERIUM

EARLY LATE

-To accelerate Abortion(inevitable, Missed).-Molar preg.-To stop bleeding.-Induction of Abortion.

To induce labour.

For cervical ripening.

Augmentation of labour.

Uterine inertia.

Active management of 3rd stage

To minimise blood loss.

Control PPH

DIAGNOSTICContraction stress test (CST)

Oxytocin sensitivity test (OST)

CST/CST/oxytocinoxytocin challenge testchallenge test During the antepartum period, oxytocin induces During the antepartum period, oxytocin induces

uterine contractions that uterine contractions that transiently reduce transiently reduce placental blood flow to the placental blood flow to the fetusfetus. .

The The oxytocin challenge testoxytocin challenge test measures the measures the fetal heart fetal heart rate responserate response to a standardized to a standardized oxytocin infusionoxytocin infusion and provides information about and provides information about placental circulatory placental circulatory reservereserve. .

An abnormal response (+test) , seen as An abnormal response (+test) , seen as late late decelerationsdecelerations in the fetal heart rate, indicates in the fetal heart rate, indicates fetal fetal hypoxia and may warrant immediate cesarean hypoxia and may warrant immediate cesarean delivery.delivery.

Interpretation- Interpretation- PositivePositive Suspecious Suspecious Negative Negative

UnsatisfactoryUnsatisfactory HyperstimulationHyperstimulation

Contraction stress test (CST)

Assess Assess irritability of uterusirritability of uterus to oxytocin to oxytocin Procedure – Procedure – 0.01U given IV at the end of 0.01U given IV at the end of

spontaneous contractionspontaneous contraction Repeated at 1min interval until induced Repeated at 1min interval until induced

contraction starts (hardening)contraction starts (hardening) Inference- Inference- failure of ut.contraction after 4 inj failure of ut.contraction after 4 inj

signifies uterus is unlikely to be signifies uterus is unlikely to be responsive to induction.responsive to induction.

ContraindicationsContraindications

PREGNANCY

Grand multipara

malpresentation

contracted pelvis

cephalopelvic disproportion

prior uterine scar (hysterotomy)

LABOUR

All cont. in preg.

+ Obstructed

labour Incoordinate

uterine contraction

FETAL DISTRESS

prematurity

ANY TIME

Hypovolemic state

Cardiac disease

Methods of Methods of administrationadministration

Controlled Controlled intravenous intravenous InfusionInfusion

1-4mU/min (↑gradually)1-4mU/min (↑gradually). .

INTRAMUSCULAR

For induction of labourFor induction of labour Principle: Principle: Start with LOW DOSE, escalate to achieve Start with LOW DOSE, escalate to achieve

optimal responseoptimal response

(3contraction in 10min each lasting 45sec)(3contraction in 10min each lasting 45sec) Maintain the dose- Maintain the dose- oxytocin titration technique.oxytocin titration technique. OBJECTIVEOBJECTIVE- Maintain normal pattern of uterine - Maintain normal pattern of uterine

activity till delivery and 30-60min beyond that.activity till delivery and 30-60min beyond that.

NOTE: NOTE:

Start with 4mU/min & ↑every 20minStart with 4mU/min & ↑every 20min

Semi-Fowlers position - avoid venecaval Semi-Fowlers position - avoid venecaval compression.compression.

Calculation of dose delivered in Calculation of dose delivered in milliunits(mU) & its correlation with milliunits(mU) & its correlation with drop rate per minutedrop rate per minuteUnits of oxytocin Units of oxytocin mixed in 500ml mixed in 500ml Ringer solutionRinger solution

1unit=1000 1unit=1000 miliunits(mU)miliunits(mU)

Drops per minuteDrops per minute

(15drops=1ml)(15drops=1ml)

15 30 15 30 60 60

In terms of mU/minIn terms of mU/min

11

22

88

2 4 2 4 8 8

4 8 4 8 16 16

16 32 16 32 64 64

NOTE: In majority of cases, max. response is seen with 16 mU/min i.e 2U in 500ml RL at 60 drops per min

CalculationCalculation

500ml contains 1I.U. i.e 1000mU of 500ml contains 1I.U. i.e 1000mU of oxytocinoxytocin

So 1ml containsSo 1ml contains

1000mU X 1ml1000mU X 1ml = = 2mU 500ml500ml1ml = 2mUAlso 1ml~15drops

Table showing Table showing convenient regimeconvenient regime

Dose of oxytocinDose of oxytocin Solution Solution used used

Escalating Escalating Drop rate at Drop rate at intervals of intervals of 20-30min 20-30min

To start with 1unitTo start with 1unit

If no response-If no response-2units2units

If still no response-If still no response-8units8units

500ml 500ml Ringer Ringer solutionsolution

-do--do-

-do--do-

15-30-6015-30-60

15-30-6015-30-60

15-30-6015-30-60

OBSERVATION DURING OBSERVATION DURING OXYTOCIN INFUSIONOXYTOCIN INFUSION

RATE of flow – calculating drops/min RATE of flow – calculating drops/min Uterine contraction - Finger tip Uterine contraction - Finger tip

palpation (hardening)palpation (hardening) Intra uterine pressure:-peak Intra uterine pressure:-peak

50to60mmHg resting 10to15mmHg50to60mmHg resting 10to15mmHg FHRFHR Assessment of progress of labour.Assessment of progress of labour.

Indications for stopping the Indications for stopping the oxytocin infusionoxytocin infusion

Nature of uterine contractions-Nature of uterine contractions- abnormal uterine contractions occurring abnormal uterine contractions occurring

frequently (every 2 min or less )frequently (every 2 min or less ) lasting more than 60sec(hyperstimulation)lasting more than 60sec(hyperstimulation) ↑↑tonus in between contractionstonus in between contractions

Fetal distressFetal distress Maternal complicationsMaternal complications ~•~•~•~~•~•~•~

Ergot Alkaloids Ergot Alkaloids

• Ergot is the Ergot is the natural alkaloid of of Claviceps purpureaClaviceps purpurea that grows on rye, wheat and other grains.that grows on rye, wheat and other grains.

ChemistryChemistry• The ergot alkaloids are derivatives of the The ergot alkaloids are derivatives of the tetracyclic tetracyclic

compound compound 6-methylergoline.6-methylergoline.

• The first pure ergot alkaloid ergotamine was obtained The first pure ergot alkaloid ergotamine was obtained in 1920, followed by the isolation of in 1920, followed by the isolation of ergometrine/ergonovine in 1932. ergometrine/ergonovine in 1932.

• The The therapeutically usefultherapeutically useful natural alkaloids are natural alkaloids are amide derivatives of amide derivatives of dd-lysergic acid. -lysergic acid.

• Semi-synthetic derivatives are obtained from catalytic hydrogenation of the natural alkaloids. e.g.- Methergin (methylergonovine)

PHARMACOKINETICS of PHARMACOKINETICS of

Ergometrine & metherginErgometrine & methergin

Absorption

ORAL

PARENTERAL(IM,IV)

rapidly absorbed peak concentrations (plasma) -60 to 90min

PREFERED ROUTE

PreparationPreparation ampoulesampoules tabletstablets

ErgometrErgometrineine

0.25mg/ 0.25mg/ 0.5mg0.5mg

0.5-0.5-1.0mg1.0mg

methermethergingin

0.2mg0.2mg 0.5-0.5-1.0mg1.0mg

SyntometriSyntometrine (sandoz)ne (sandoz)

0.5mg 0.5mg Ergometrine+ 5U-syntocinon

-:Composition of ergot preparations:-

METABOLISM, EXCRETIONMETABOLISM, EXCRETIONErgotamineErgotamine is is metabolized in the livermetabolized in the liver by largely by largely undefined pathwaysundefined pathways..• 90% of the metabolites are 90% of the metabolites are excreted in the bileexcreted in the bile. . • Only traces of unmetabolized drug are found in urine Only traces of unmetabolized drug are found in urine

and feces.and feces.Ergometrine (Ergonovine) Ergometrine (Ergonovine) andand methergin methergin

((methylergonovine)-methylergonovine)-• ErgometrineErgometrine (Ergonovine) is metabolized and/or (Ergonovine) is metabolized and/or

eliminated more rapidly than is ergotamine. eliminated more rapidly than is ergotamine. • The half-life (plasma) - 0.5 and 2 hours.The half-life (plasma) - 0.5 and 2 hours.• Duration of action - 3hrsDuration of action - 3hrs

RouteRoute ErgometriErgometrinene

MetherginMethergin

IVIV 45-60sec45-60sec 95sec95sec

IMIM 6-7min6-7min 7min7min

OralOral 10min10min 10min10min

Onset of action

Pharmacodynamics:Pharmacodynamics:MECHANISM OF ACTION-MECHANISM OF ACTION-

Serotonin Receptor (5-HTSerotonin Receptor (5-HT22)+++ Mixed partial )+++ Mixed partial agonist Adrenoceptor++ agonist Adrenoceptor++ effectseffects

DIRECTLY ON MYOMETRIUM (Uterine Smooth DIRECTLY ON MYOMETRIUM (Uterine Smooth Muscle) Muscle)

• Sensitivity of the uterus to the stimulant effects of ergot Sensitivity of the uterus to the stimulant effects of ergot increases dramatically during pregnancy - increasing increases dramatically during pregnancy - increasing dominance of receptors as pregnancy progresses. dominance of receptors as pregnancy progresses.

• Non-physiological action Non-physiological action i.e uniform contraction of i.e uniform contraction of uterus (loss of polarity).uterus (loss of polarity).

• In very small doses, ergot preparations can evoke In very small doses, ergot preparations can evoke rhythmic contraction and relaxation of the uterus. rhythmic contraction and relaxation of the uterus.

• At higher concentrations, these drugs induce At higher concentrations, these drugs induce powerful powerful and prolonged contracture - STATE OF SPASMand prolonged contracture - STATE OF SPASM

• Ergonovine is more selectiveErgonovine is more selective than other ergot than other ergot alkaloids in affecting the uterus and is the agent of alkaloids in affecting the uterus and is the agent of choice in obstetric applications of these drugs. (Onset of choice in obstetric applications of these drugs. (Onset of action - 55sec by i.v.)action - 55sec by i.v.)

The uterine smooth muscle fibers when contracted compress traversing blood vessels –Principle for its clinical use.

INDICATION - INDICATION - THERAPEUTICTHERAPEUTIC

POSTPARTUM HEMORRHAGE-

• The uterus at term is The uterus at term is extremely sensitiveextremely sensitive to the to the stimulant action of ergot and even moderate stimulant action of ergot and even moderate doses produce a doses produce a prolonged and powerful spasm prolonged and powerful spasm of the muscle quite unlike natural laborof the muscle quite unlike natural labor. .

• Therefore, ergot derivatives should be used Therefore, ergot derivatives should be used only only forfor control of late uterine bleeding control of late uterine bleeding and should and should never be given before deliverynever be given before delivery. .

• Oxytocin is the preferred agent for control of Oxytocin is the preferred agent for control of postpartum hemorrhage but if this is ineffective, postpartum hemorrhage but if this is ineffective, ERGOMETRINEERGOMETRINE(0.2 mg ) is given (0.2 mg ) is given intramuscularly. intramuscularly.

• It is usually effective within 1–5 minutes and is It is usually effective within 1–5 minutes and is less toxic than other ergot derivatives for this less toxic than other ergot derivatives for this application.application.

PROPHYLACTICPROPHYLACTIC::

AFTER DELIVERY OF ANT. AFTER DELIVERY OF ANT.

SHOULDERSHOULDER// FOLLOWING DELIVERY OF FOLLOWING DELIVERY OF BABYBABY

at the time ofat the time of delivery of delivery of the placenta.the placenta.

CAUTIONSCAUTIONS

ToxicityToxicity• Most common - Most common - gastrointestinal disturbances: gastrointestinal disturbances:

diarrhea, nausea, and vomitingdiarrhea, nausea, and vomiting. (Activation of . (Activation of the medullary vomiting center and of the the medullary vomiting center and of the gastrointestinal serotonin receptors )gastrointestinal serotonin receptors )

• Precipitate MI, STROKE, BRONCHOSPASM & Precipitate MI, STROKE, BRONCHOSPASM & raise in BP (Vasoconstrictive action) raise in BP (Vasoconstrictive action)

• More dangerous toxic effect of overdosage is More dangerous toxic effect of overdosage is prolonged vasospasm → prolonged vasospasm → gangrenegangrene of toes of toes and requires amputation.and requires amputation.

• Bowel infarctionBowel infarction has also been reported and has also been reported and may require resection. may require resection.

• Interferes with LACTATION (↓prolactin)Interferes with LACTATION (↓prolactin)

ContraindicationsContraindications

PROPHYLACTICPROPHYLACTIC• Suspected multiple gestationSuspected multiple gestation• Organic cardiac diseaseOrganic cardiac disease• Severe pre-eclampsia, eclampsiaSevere pre-eclampsia, eclampsia• Rh-negative motherRh-negative mother

THERAPEUTICTHERAPEUTIC• Heart disease or severe hypertensive Heart disease or severe hypertensive

disordersdisorders~•~•~•~•~•~•~~

20-Carbon carboxylic acids with 20-Carbon carboxylic acids with Cyclopentane ring Cyclopentane ring

Formed by PUFAFormed by PUFA

Prostaglandins

Prostanoic acidProstanoic acid

2468

10

12 14 16 18

20

PGE2PGF2ά

COOH

PGE1

SYNTHES

SYNTHES

IS

IS

& ACTIO

N

& ACTIO

N

Lungs & liver

Lungs & liver

PGF2ά- acts predominantly on myometrium

PGE2- on the cervix due to collagenolytic property

LOCAL HARMONES

The The amnionamnion synthesizes synthesizes PGE2 and and decidua – – PGF2ά During pregnancy, the transport of prostaglandins from the During pregnancy, the transport of prostaglandins from the amnion to maternal tissues is amnion to maternal tissues is limitedlimited by expression of the by expression of the inactivating enzymes, inactivating enzymes, prostaglandin dehydrogenaseprostaglandin dehydrogenase (PGDH) in (PGDH) in the chorion. the chorion. Late in pregnancy synthesis is increased by increased Late in pregnancy synthesis is increased by increased phospholipase-A2 and prostaglandin -H-synthase-type 2 phospholipase-A2 and prostaglandin -H-synthase-type 2 (PGHS-2) activity. (PGHS-2) activity. During labor, PGDH levels decline and amnion-derived During labor, PGDH levels decline and amnion-derived prostaglandins can influence membrane rupture and uterine prostaglandins can influence membrane rupture and uterine contractility. contractility.

“ “PGs action is independend of the period of gestation”.PGs action is independend of the period of gestation”.

-vePGDH

-vephospholipase-A2phospholipase-A2

PGHS-2PGHS-2

+

PROSTAGLANDIN

USES IN OBSTETRICSUSES IN OBSTETRICSINDUCTION OF ABORTION – MTP / Missed abortion.INDUCTION OF ABORTION – MTP / Missed abortion.

11ststtrimester - misoprostol vaginally with the other drugs;trimester - misoprostol vaginally with the other drugs; mid-trimesters:- all analogues are usefulmid-trimesters:- all analogues are useful

Terminate MOLAR PREGNANCY (vaginal misoprostol 400Terminate MOLAR PREGNANCY (vaginal misoprostol 400μμg, g, 3hr before evacuation)3hr before evacuation)

INDUCTION / ACCELERATIONINDUCTION / ACCELERATION OF LABOUR prefered in IUD, OF LABOUR prefered in IUD, shorter period of gestation, elderly primigravidashorter period of gestation, elderly primigravida

Cervical ripening / dilatation – abortion, labour, diagnosticCervical ripening / dilatation – abortion, labour, diagnostic

Atonic PPH (refractory cases - step2)-Atonic PPH (refractory cases - step2)-

carboprost carboprost 250 250 μμg i.m/ Misoprostal 1000g i.m/ Misoprostal 1000μμg PRg PR

Tubal-ectopic pregnancy (carboprost for salpingocentesis)Tubal-ectopic pregnancy (carboprost for salpingocentesis)

PG analogues & Common ROAPG analogues & Common ROAPGE1 (methyl ester) – MISOPROSTOL (vaginal, oral, rectal)PGE2 – DINOPROSTONE (vaginal, extra amniotic) (NOTE: less toxic, more effective so widely used.)PGF 2ά- DINOPROSTONE TROMETHAMINE

PGF2ά (methyl analogue) – CARBOPROST (i.m., intra/extra-amniotic) -:Preparations:-Tablet-0.5mg dinoprostone (prostinE2)Vaginal suppository- 20mg PGE2 /50mg PGF2ά lipid baseVaginal pessary- 3mg PGE2

ProstinE2 gel- 500μg into cervical canal, below internal OS/1-2mg in the posterior fornix.

-:Parenteral:-PGE2 - ProstineE2 1mg/mlPGF2ά-ProstinF2 ά(Dinoprost tromethamine) 5mg/mlMethyl analogue of PGF2ά- Carboprost 2.5mg/10ml vial

Side effectsSide effectsSYSTEMICSYSTEMIC

NVD NVD BronchospasmBronchospasmFall in BP, tachycardia, chest painFall in BP, tachycardia, chest painShivering, fever, malaiseShivering, fever, malaise

LOCALLOCALUnduly forceful uterine contractionsUnduly forceful uterine contractionsUterine cramps Uterine cramps Tachysystole (uterine hyperstimulation) Tachysystole (uterine hyperstimulation) Uterine rupture (rare but use is avoided in previous LSCS)Uterine rupture (rare but use is avoided in previous LSCS)Meconium passage.Meconium passage.Cervical laceration (when used as an abortifacient)Cervical laceration (when used as an abortifacient)Vaginal bleedingVaginal bleeding

CONTRAINDICATIONCONTRAINDICATION

Hypersensitivity to the drugHypersensitivity to the drug

Uterine scarUterine scar

Bronchial asthmaBronchial asthma

Heart diseasesHeart diseases

MisoprostolMisoprostol((PGEPGE11) - Important points) - Important points““Used for cervical ripening.”Used for cervical ripening.”It is rapidly absorbed and more effective than oxytocin It is rapidly absorbed and more effective than oxytocin or dinoprostone for induction of labour.or dinoprostone for induction of labour.

TransvaginalTransvaginal – induction of labour – induction of labour 5050μμg every 3hrs to a max. of 6 doses g every 3hrs to a max. of 6 doses

oror

2525μμg every 3hrs to a max of 8 doses.g every 3hrs to a max of 8 doses. OrallyOrally - 50 - 50μμg every 4hrsg every 4hrs

No evidence of teratogenicity / carcinogenic effects.No evidence of teratogenicity / carcinogenic effects.

Advantages over PGEAdvantages over PGE22- cheap, stable at room temp., - cheap, stable at room temp., long shelf life, easy to administer, less side effects. long shelf life, easy to administer, less side effects. Induction delivery interval is short. Need of oxytocin Induction delivery interval is short. Need of oxytocin augmentation is less. Failure of induction is less.augmentation is less. Failure of induction is less.

TTHHAANNKK YYOOUU☻