are the drugs of varying chemicalare the drugs of varying chemical
nature that have the power tonature that have the power to
excite contraction of theexcite contraction of the
uterine musclesuterine muscles.”.”
Oxytocin: physiologyOxytocin: physiology
Human hypothalamusHuman hypothalamus
Diagram depicts a sagittal section through the hypothalamus andDiagram depicts a sagittal section through the hypothalamus and
pituitary gland.pituitary gland.
TheThe posterior pituitary consists of axon terminals ofposterior pituitary consists of axon terminals of
magnocellular neurons arising in the supraopticmagnocellular neurons arising in the supraoptic
and paraventricular nuclei of the hypothalamus.and paraventricular nuclei of the hypothalamus.
During lactationDuring lactation……
in thein the nipple/ areolanipple/ areola
neuronal activityneuronal activity
MILK EJECTIONMILK EJECTION
During parturition…During parturition…
oxytocin is theoxytocin is the primary mediatorprimary mediator of myometrialof myometrial
contractility during labor.contractility during labor.
During theDuring the second half of pregnancysecond half of pregnancy, uterine smooth, uterine smooth
muscle shows an increase in the expression ofmuscle shows an increase in the expression of oxytocinoxytocin
receptors(100-200fold) and becomes increasingly sensitivereceptors(100-200fold) and becomes increasingly sensitive toto
the stimulant action of endogenous oxytocin.the stimulant action of endogenous oxytocin.
Stimulates PG synthesis.Stimulates PG synthesis.
Physiological uterine contractionPhysiological uterine contraction - fundal contraction; cervical- fundal contraction; cervical
relaxation. (law of polarity maintained)relaxation. (law of polarity maintained)
Cervical and vaginal dilatation results in an acute release ofCervical and vaginal dilatation results in an acute release of
oxytocin from the posterior pituitary in a process known asoxytocin from the posterior pituitary in a process known as
thethe Ferguson reflexFerguson reflex..
BSORPTION, METABOLISM, ANDBSORPTION, METABOLISM, AND
IntravenouslyAA (controlled infusion) for initiation andfor initiation and
augmentation of labor.augmentation of labor.
intramuscularlyintramuscularly -control of postpartum bleeding.-control of postpartum bleeding.
Buccal & nasal spray- Limited use.Buccal & nasal spray- Limited use.
o Synthetic oxytocin (Syntocinon, Pitocin) 5IU/ml ampSynthetic oxytocin (Syntocinon, Pitocin) 5IU/ml amp
o Syntometrine (Sandoz - Syntocinon 5U+Ergometrine 0.5mg)Syntometrine (Sandoz - Syntocinon 5U+Ergometrine 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 toOxytocin is not bound to plasma proteinsplasma proteins and isand is eliminated byeliminated by
the kidneys and liverthe kidneys and liver..
Circulating half-life ofCirculating half-life of max. 5 minutesmax. 5 minutes. (avg 3-4min). (avg 3-4min)
Duration ofDuration of action-20minaction-20min
Stored at 2-8Stored at 2-8 00
Oxytocin acts throughOxytocin acts through G protein-coupled receptorsG protein-coupled receptors andand
thethe phosphoinositide -phosphoinositide -calcium secondcalcium second-messenger system-messenger system
to contract uterine smooth muscleto contract uterine smooth muscle..
Oxytocin also stimulates theOxytocin also stimulates the release ofrelease of prostaglandinsprostaglandins andand
leukotrienesleukotrienes that augment uterine contractionthat augment uterine contraction..
Oxytocin inOxytocin in small dosessmall doses increases both theincreases both the frequency andfrequency and
the force of uterine contractionsthe force of uterine contractions..
AtAt higher doseshigher doses, it produces, it produces sustained contractionsustained contraction..
Oxytocin also causes contraction of myoepithelialOxytocin also causes contraction of myoepithelial
cells surrounding mammary alveoli, which leads tocells surrounding mammary alveoli, which leads to
milk ejectionmilk ejection..
Without oxytocin-induced contraction, normalWithout oxytocin-induced contraction, normal
lactation cannot occur.lactation cannot occur.
At high concentrations, oxytocin hasAt high concentrations, oxytocin has weakweak
antidiuretic and pressorantidiuretic and pressor activity due to activation ofactivity due to activation of
vasopressin receptors.vasopressin receptors.
““serious toxicity is rareserious toxicity is rare” when oxytocin is used” when oxytocin is used
(>6 in 10min)
Prior uterine scar
NOTE: These complications can be detectedNOTE: These complications can be detected
early by means ofearly by means of
standardstandard fetal monitoring equipmentfetal monitoring equipment..
Pul. EdemaPul. Edema
Heart FailureHeart Failure
excessive fluidexcessive fluid
activation ofactivation of
Inadvertent activation ofInadvertent activation of vasopressinvasopressin
To avoid hypotension, oxytocin isTo avoid hypotension, oxytocin is
administered intravenously asadministered intravenously as
dilute solutions at a controlled rate.dilute solutions at a controlled rate.
PREGNANCY LABOUR PUERPERIUM
-To stop bleeding.
To induce labour.
Contraction stress test (CST)
Oxytocin sensitivity test (OST)
CST/CST/oxytocinoxytocin challenge testchallenge test
During the antepartum period, oxytocin induces uterineDuring the antepartum period, oxytocin induces uterine
contractions thatcontractions that transiently reduce placental blood flowtransiently reduce placental blood flow
to theto the fetusfetus..
TheThe oxytocin challenge testoxytocin challenge test measures themeasures the fetal heart ratefetal heart rate
responseresponse to a standardizedto a standardized oxytocin infusionoxytocin infusion and providesand provides
information aboutinformation about placental circulatory reserveplacental circulatory reserve..
An abnormal response (+test) , seen asAn abnormal response (+test) , seen as late decelerationslate decelerations inin
the fetal heart rate, indicatesthe fetal heart rate, indicates fetal hypoxia and may warrantfetal hypoxia and may warrant
immediate cesarean delivery.immediate cesarean delivery.
Interpretation-Interpretation- PositivePositive SuspeciousSuspecious
Negative UnsatisfactoryNegative Unsatisfactory
Contraction stress test (CST)
AssessAssess irritability of uterusirritability of uterus to oxytocinto oxytocin
Procedure –Procedure –
0.01U given IV at the end of spontaneous0.01U given IV at the end of spontaneous
Repeated at 1min interval until inducedRepeated at 1min interval until induced
contraction starts (hardening)contraction starts (hardening)
failure of ut.contraction after 4 inj signifiesfailure of ut.contraction after 4 inj signifies
uterus is unlikely to be responsive to induction.uterus is unlikely to be responsive to induction.
All cont. in preg.
For induction of labourFor induction of labour
Start with LOW DOSE, escalate to achieveStart 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 activity till- Maintain normal pattern of uterine activity till
delivery and 30-60min beyond that.delivery and 30-60min beyond that.
Start with 4mU/min & ↑every 20minStart with 4mU/min & ↑every 20min
Semi-Fowlers position - avoid venecaval compression.Semi-Fowlers position - avoid venecaval compression.
Calculation of dose delivered in milliunits(mU) &Calculation of dose delivered in milliunits(mU) &
its correlation with drop rate per minuteits correlation with drop rate per minute
Units of oxytocin mixed inUnits of oxytocin mixed in
500ml Ringer solution500ml Ringer solution
1unit=1000 miliunits(mU)1unit=1000 miliunits(mU)
Drops per minuteDrops per minute
15 30 6015 30 60
In terms of mU/minIn terms of mU/min
2 4 82 4 8
4 8 164 8 16
16 32 6416 32 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
500ml contains 1I.U. i.e 1000mU of oxytocin500ml contains 1I.U. i.e 1000mU of oxytocin
So 1ml containsSo 1ml contains 1000mU X 1ml1000mU X 1ml == 2mU
1ml = 2mU
Table showing convenient regimeTable showing convenient regime
Dose of oxytocinDose of oxytocin Solution usedSolution used
Drop rate atDrop rate at
intervals ofintervals of
To start with 1unitTo start with 1unit
If no response-2unitsIf no response-2units
If still no response-8unitsIf still no response-8units
500ml Ringer500ml Ringer
OBSERVATION DURINGOBSERVATION DURING
OXYTOCIN INFUSIONOXYTOCIN INFUSION
RATE of flow – calculating drops/minRATE of flow – calculating drops/min
Uterine contraction - Finger tip palpation (hardening)Uterine contraction - Finger tip palpation (hardening)
Intra uterine pressure:-peak 50to60mmHg restingIntra uterine pressure:-peak 50to60mmHg resting
Assessment of progress of labour.Assessment of progress of labour.
Indications for stopping the oxytocinIndications for stopping the oxytocin
Nature of uterine contractions-Nature of uterine contractions-
abnormal uterine contractions occurring frequentlyabnormal uterine contractions occurring frequently
(every 2 min or less )(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 AlkaloidsErgot Alkaloids
• Ergot is theErgot is the natural alkaloid ofof Claviceps purpureaClaviceps purpurea that growsthat grows
on rye, wheat and other grains.on rye, wheat and other grains.
• The ergot alkaloids are derivatives of theThe ergot alkaloids are derivatives of the tetracyclic compoundtetracyclic compound
• The first pure ergot alkaloid ergotamine was obtained in 1920,The first pure ergot alkaloid ergotamine was obtained in 1920,
followed by the isolation of ergometrine/ergonovine in 1932.followed by the isolation of ergometrine/ergonovine in 1932.
• TheThe therapeutically usefultherapeutically useful natural alkaloids arenatural alkaloids are
amide derivatives ofamide derivatives of dd-lysergic acid.-lysergic acid.
• Semi-synthetic derivatives are obtained from
catalytic hydrogenation of the natural alkaloids.
e.g.- Methergin (methylergonovine)
METABOLISM, EXCRETIONMETABOLISM, EXCRETION
ErgotamineErgotamine isis metabolized in the livermetabolized in the liver by largelyby largely
undefined pathwaysundefined pathways..
• 90% of the metabolites are90% of the metabolites are excreted in the bileexcreted in the bile..
• Only traces of unmetabolized drug are found in urine and feces.Only traces of unmetabolized drug are found in urine and feces.
Ergometrine (Ergonovine)Ergometrine (Ergonovine) andand metherginmethergin ((methylergonovine)-methylergonovine)-
• ErgometrineErgometrine (Ergonovine) is metabolized and/or eliminated more(Ergonovine) is metabolized and/or eliminated more
rapidly than is ergotamine.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 ErgometrineErgometrine MetherginMethergin
IVIV 45-60sec45-60sec 95sec95sec
IMIM 6-7min6-7min 7min7min
OralOral 10min10min 10min10min
Onset of action
MECHANISM OF ACTION-MECHANISM OF ACTION-
Serotonin Receptor (5-HTSerotonin Receptor (5-HT22)+++ Mixed partial agonist)+++ Mixed partial agonist
Adrenoceptor++ effectsAdrenoceptor++ effects
DIRECTLY ON MYOMETRIUM (Uterine Smooth Muscle)DIRECTLY ON MYOMETRIUM (Uterine Smooth Muscle)
• Sensitivity of the uterus to the stimulant effects of ergot increasesSensitivity of the uterus to the stimulant effects of ergot increases
dramatically during pregnancy - increasing dominance of receptorsdramatically during pregnancy - increasing dominance of receptors
as pregnancy progresses.as pregnancy progresses.
• Non-physiological actionNon-physiological action i.e uniform contraction of uterus (loss ofi.e uniform contraction of uterus (loss of
• In very small doses, ergot preparations can evoke rhythmicIn very small doses, ergot preparations can evoke rhythmic
contraction and relaxation of the uterus.contraction and relaxation of the uterus.
• At higher concentrations, these drugs induceAt higher concentrations, these drugs induce powerful andpowerful and
prolonged contracture - STATE OF SPASMprolonged contracture - STATE OF SPASM
• Ergonovine is more selectiveErgonovine is more selective than other ergot alkaloids in affectingthan other ergot alkaloids in affecting
the uterus and is the agent of choice in obstetric applications ofthe uterus and is the agent of choice in obstetric applications of
these drugs. (Onset of action - 55sec by i.v.)these drugs. (Onset of action - 55sec by i.v.)
The uterine smooth muscle fibers when contracted
compress traversing blood vessels –Principle for its
INDICATION -INDICATION - THERAPEUTICTHERAPEUTIC
• The uterus at term isThe uterus at term is extremely sensitiveextremely sensitive to the stimulant actionto the stimulant action
of ergot and even moderate doses produce aof ergot and even moderate doses produce a prolonged andprolonged and
powerful spasm of the muscle quite unlike natural laborpowerful spasm of the muscle quite unlike natural labor..
• Therefore, ergot derivatives should be usedTherefore, ergot derivatives should be used only foronly for control ofcontrol of
late uterine bleedinglate uterine bleeding and shouldand should never be given beforenever be given before
• Oxytocin is the preferred agent for control of postpartumOxytocin is the preferred agent for control of postpartum
hemorrhage but if this is ineffective,hemorrhage but if this is ineffective,
ERGOMETRINEERGOMETRINE(0.2 mg ) is given intramuscularly.(0.2 mg ) is given intramuscularly.
• It is usually effective within 1–5 minutes and is less toxic thanIt is usually effective within 1–5 minutes and is less toxic than
other ergot derivatives for this application.other ergot derivatives for this application.
AFTER DELIVERY OF ANT.AFTER DELIVERY OF ANT.
FOLLOWING DELIVERY OFFOLLOWING DELIVERY OF
at the time ofat the time of delivery of thedelivery of the
• Most common -Most common - gastrointestinal disturbances:gastrointestinal disturbances: diarrhea, nausea,diarrhea, nausea,
and vomitingand vomiting. (Activation of the medullary vomiting center. (Activation of the medullary vomiting center
and of the gastrointestinal serotonin receptors )and of the 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 isMore dangerous toxic effect of overdosage is prolongedprolonged
vasospasm →vasospasm → gangrenegangrene of toes and requires amputation.of toes and requires amputation.
• Bowel infarctionBowel infarction has also been reported and may requirehas also been reported and may require
• Interferes with LACTATION (↓prolactin)Interferes with LACTATION (↓prolactin)
• Suspected multiple gestationSuspected multiple gestation
• Organic cardiac diseaseOrganic cardiac disease
• Severe pre-eclampsia, eclampsiaSevere pre-eclampsia, eclampsia
• Rh-negative motherRh-negative mother
• Heart disease or severe hypertensive disordersHeart disease or severe hypertensive disorders
20-Carbon carboxylic acids with20-Carbon carboxylic acids with
Cyclopentane ringCyclopentane ring
Formed by PUFAFormed by PUFA
Prostanoic acidProstanoic acid
12 14 16 18
PGF2ά- acts predominantly on myometrium
PGE2- on the cervix due to collagenolytic property
TheThe amnionamnion synthesizessynthesizes PGE2 andand decidua –– PGF2ά
During pregnancy, the transport of prostaglandins from theDuring pregnancy, the transport of prostaglandins from the
amnion to maternal tissues isamnion to maternal tissues is limitedlimited by expression of theby 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 increasedLate in pregnancy synthesis is increased by increased
phospholipase-A2 and prostaglandin -H-synthase-type 2phospholipase-A2 and prostaglandin -H-synthase-type 2
(PGHS-2) activity.(PGHS-2) activity.
During labor, PGDH levels decline and amnion-derivedDuring labor, PGDH levels decline and amnion-derived
prostaglandins can influence membrane rupture and uterineprostaglandins can influence membrane rupture and uterine
““PGs action is independend of the period of gestation”.PGs action is independend of the period of gestation”.
USES IN OBSTETRICSUSES IN OBSTETRICS
INDUCTION OF ABORTION – MTP / Missed abortion.INDUCTION OF ABORTION – MTP / Missed abortion.
trimester - 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)-
carboprostcarboprost 250250 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 ROA
PGE1 (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)
Tablet-0.5mg dinoprostone (prostinE2)
Vaginal suppository- 20mg PGE2 /50mg PGF2ά lipid base
Vaginal pessary- 3mg PGE2
ProstinE2 gel- 500μg into cervical canal, below internal OS/1-2mg in the posterior
PGE2 - ProstineE2 1mg/ml
PGF -ProstinF (Dinoprost tromethamine) 5mg/ml
Side effectsSide effects
Fall in BP, tachycardia, chest painFall in BP, tachycardia, chest pain
Shivering, fever, malaiseShivering, fever, malaise
Unduly forceful uterine contractionsUnduly forceful uterine contractions
Uterine crampsUterine 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
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 oxytocinIt 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 dosesg every 3hrs to a max. of 6 doses
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 oxytocinInduction delivery interval is short. Need of oxytocin
augmentation is less. Failure of induction is less.augmentation is less. Failure of induction is less.