Venkataramu – OXYTOCICS
(Oxytocin, Ergot, PGs)
Vijay Kumar - AntiHTN, Diuretics,
Tocolytics, TERATOLOGY
Vishwanath – Anest...
OXYTOCICSOXYTOCICS
Venkataramu.B.S
9term, MIMS
““OXYTOCICSOXYTOCICS
are the drugs of varying chemicalare the drugs of varying chemical
nature that have the power tonatur...
Oxytocin: physiologyOxytocin: physiology
Human hypothalamusHuman hypothalamus
Diagram depicts a sagittal section through the hypothalamus andDiagram depicts a sagittal section through the hypothalamus...
During lactationDuring lactation……
oxytocinoxytocin
mechanoreceptorsmechanoreceptors
in thein the nipple/ areolanipple/ ar...
During parturition…During parturition…
 oxytocin is theoxytocin is the primary mediatorprimary mediator of myometrialof m...
BSORPTION, METABOLISM, ANDBSORPTION, METABOLISM, AND
EXCRETIONEXCRETION
 IntravenouslyAA (controlled infusion) for initia...
PharmacodynamicsPharmacodynamics
UTERUSUTERUS
 Oxytocin acts throughOxytocin acts through G protein-coupled receptorsG pr...
BREASTBREAST
 Oxytocin also causes contraction of myoepithelialOxytocin also causes contraction of myoepithelial
cells su...
ToxicityToxicity
 ““serious toxicity is rareserious toxicity is rare” when oxytocin is used” when oxytocin is used
judici...
Pul. EdemaPul. Edema
Heart FailureHeart Failure
waterwater
Intoxication-Intoxication-
hyponatremiahyponatremia
Antidiuresi...
To avoid hypotension, oxytocin isTo avoid hypotension, oxytocin is
administered intravenously asadministered intravenously...
INDICATIONSINDICATIONS
THERAPEUTICTHERAPEUTIC
PREGNANCY LABOUR PUERPERIUM
EARLY LATE
-To accelerate
Abortion
(inevitable, ...
CST/CST/oxytocinoxytocin challenge testchallenge test
 During the antepartum period, oxytocin induces uterineDuring the a...
Contraction stress test (CST)
 AssessAssess irritability of uterusirritability of uterus to oxytocinto oxytocin
 Procedu...
ContraindicationsContraindications
PREGNANCY
 Grand
multipara
 malpresentation
 contracted
pelvis
 cephalopelvic
dispr...
Methods ofMethods of
administrationadministration
ControlledControlled intravenousintravenous InfusionInfusion
1-4mU/min (...
For induction of labourFor induction of labour
 Principle:Principle:
 Start with LOW DOSE, escalate to achieveStart with...
Calculation of dose delivered in milliunits(mU) &Calculation of dose delivered in milliunits(mU) &
its correlation with dr...
CalculationCalculation
 500ml contains 1I.U. i.e 1000mU of oxytocin500ml contains 1I.U. i.e 1000mU of oxytocin
 So 1ml c...
Table showing convenient regimeTable showing convenient regime
Dose of oxytocinDose of oxytocin Solution usedSolution used...
OBSERVATION DURINGOBSERVATION DURING
OXYTOCIN INFUSIONOXYTOCIN INFUSION
 RATE of flow – calculating drops/minRATE of flow...
Indications for stopping the oxytocinIndications for stopping the oxytocin
infusioninfusion
 Nature of uterine contractio...
Ergot AlkaloidsErgot Alkaloids
• Ergot is theErgot is the natural alkaloid ofof Claviceps purpureaClaviceps purpurea that ...
PHARMACOKINETICS ofPHARMACOKINETICS of
Ergometrine & metherginErgometrine & methergin
Absorption
ORAL
PARENTERAL(IM,IV)
ra...
METABOLISM, EXCRETIONMETABOLISM, EXCRETION
ErgotamineErgotamine isis metabolized in the livermetabolized in the liver by l...
Pharmacodynamics:Pharmacodynamics:
MECHANISM OF ACTION-MECHANISM OF ACTION-
Serotonin Receptor (5-HTSerotonin Receptor (5-...
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 isThe uterus at term is extrem...
PROPHYLACTICPROPHYLACTIC::
AFTER DELIVERY OF ANT.AFTER DELIVERY OF ANT.
SHOULDERSHOULDER//
FOLLOWING DELIVERY OFFOLLOWING ...
CAUTIONSCAUTIONS
ToxicityToxicity
• Most common -Most common - gastrointestinal disturbances:gastrointestinal disturbances: diarrhea, nause...
ContraindicationsContraindications
PROPHYLACTICPROPHYLACTIC
• Suspected multiple gestationSuspected multiple gestation
• O...
20-Carbon carboxylic acids with20-Carbon carboxylic acids with
Cyclopentane ringCyclopentane ring
Formed by PUFAFormed by ...
SYNTHESIS
SYNTHESIS
&
ACTION
&
ACTION
Lungs & liverLungs & liver
PGF2ά- acts predominantly on myometrium
PGE2- on the cervix due to collagenolytic property
LOCAL HARMONES
TheThe amnionamnion synthesizessynthesizes PGE2 andand decidua –– PGF2ά
During pregnancy, the transport of prostaglandins ...
PROSTAGLANDIN
USES IN OBSTETRICSUSES IN OBSTETRICS
INDUCTION OF ABORTION – MTP / Missed abortion.INDUCTION OF ABORTION – MTP / Missed ab...
PG analogues & Common ROAPG analogues & Common ROA
PGE1 (methyl ester) – MISOPROSTOL (vaginal, oral, rectal)
PGE2 – DINOPR...
Side effectsSide effects
SYSTEMICSYSTEMIC
NVDNVD
BronchospasmBronchospasm
Fall in BP, tachycardia, chest painFall in BP, t...
CONTRAINDICATIONCONTRAINDICATION
Hypersensitivity to the drugHypersensitivity to the drug
Uterine scarUterine scar
Bronchi...
MisoprostolMisoprostol((PGEPGE11) - Important points) - Important points
““Used for cervical ripening.”Used for cervical r...
TT HHAA NNKK YY OOUU
☻
Oxytocics finalised-110713081015-phpapp02
Oxytocics finalised-110713081015-phpapp02
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Oxytocics finalised-110713081015-phpapp02

  1. 1. Venkataramu – OXYTOCICS (Oxytocin, Ergot, PGs) Vijay Kumar - AntiHTN, Diuretics, Tocolytics, TERATOLOGY Vishwanath – Anesthesia & Analgesia
  2. 2. OXYTOCICSOXYTOCICS Venkataramu.B.S 9term, MIMS
  3. 3. ““OXYTOCICSOXYTOCICS 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.”.” OXYTOCICS OXYTOCIN ERGOT DERIVATIVES PROSTAGLANDINS Ergometrine & Methergin E2&F2E2&F2άά PGEPGE22 && PGFPGF22άά
  4. 4. Oxytocin: physiologyOxytocin: physiology Human hypothalamusHuman hypothalamus
  5. 5. 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. ● ●●●
  6. 6. During lactationDuring lactation…… oxytocinoxytocin mechanoreceptorsmechanoreceptors in thein the nipple/ areolanipple/ areola hypothalamichypothalamic neuronal activityneuronal activity MILK EJECTIONMILK EJECTION SucklingSuckling Axon term inals Axon term inals m yoepithelialcells m yoepithelialcells contract contract STIMULUS RESPONSE
  7. 7. 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..
  8. 8. BSORPTION, METABOLISM, ANDBSORPTION, METABOLISM, AND EXCRETIONEXCRETION  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.  Preparations:Preparations: 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 CC
  9. 9. PharmacodynamicsPharmacodynamics UTERUSUTERUS  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..
  10. 10. BREASTBREAST  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. KIDNEYSKIDNEYS  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.
  11. 11. ToxicityToxicity  ““serious toxicity is rareserious toxicity is rare” when oxytocin is used” when oxytocin is used judiciously.judiciously. excessive uterine stimulation Hypertonia (↑duration) uterine rupture.. Polysystole (>6 in 10min) placental abruption fetal distress S T I M U L A T I O N HYPER Grand multipara, Malpresentation Contracted pelvis Prior uterine scar (hyterotomy) NOTE: These complications can be detectedNOTE: These complications can be detected early by means ofearly by means of standardstandard fetal monitoring equipmentfetal monitoring equipment..
  12. 12. Pul. EdemaPul. Edema Heart FailureHeart Failure waterwater Intoxication-Intoxication- hyponatremiahyponatremia AntidiuresisAntidiuresis excessive fluidexcessive fluid retentionretention activation ofactivation of vasopressinvasopressin receptorsreceptors-- Seizures & death Inadvertent activation ofInadvertent activation of vasopressinvasopressin receptorsreceptors-- 30-40mIU/min 40-50IU/min
  13. 13. 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. OXYTOCIN BOLUS HYPOTENSION Transient vasodilation
  14. 14. 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 DIAGNOSTIC Contraction stress test (CST) Oxytocin sensitivity test (OST)
  15. 15. 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 HyperstimulationHyperstimulation
  16. 16. 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 contractioncontraction  Repeated at 1min interval until inducedRepeated at 1min interval until induced contraction starts (hardening)contraction starts (hardening)  Inference-Inference- 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.
  17. 17. 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
  18. 18. Methods ofMethods of administrationadministration ControlledControlled intravenousintravenous InfusionInfusion 1-4mU/min (↑gradually)1-4mU/min (↑gradually) .. INTRAMUSCULAR
  19. 19. For induction of labourFor induction of labour  Principle:Principle:  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. NOTE:NOTE: Start with 4mU/min & ↑every 20minStart with 4mU/min & ↑every 20min Semi-Fowlers position - avoid venecaval compression.Semi-Fowlers position - avoid venecaval compression.
  20. 20. 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 (15drops=1ml)(15drops=1ml) 15 30 6015 30 60 In terms of mU/minIn terms of mU/min 11 22 88 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
  21. 21. CalculationCalculation  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 500ml500ml 1ml = 2mU Also 1ml~15drops
  22. 22. Table showing convenient regimeTable showing convenient regime Dose of oxytocinDose of oxytocin Solution usedSolution used EscalatingEscalating Drop rate atDrop rate at intervals ofintervals of 20-30min20-30min 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 solutionsolution -do--do- -do--do- 15-30-6015-30-60 15-30-6015-30-60 15-30-6015-30-60
  23. 23. 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 10to15mmHg10to15mmHg  FHRFHR  Assessment of progress of labour.Assessment of progress of labour.
  24. 24. Indications for stopping the oxytocinIndications for stopping the oxytocin infusioninfusion  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 ~•~•~•~~•~•~•~
  25. 25. 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. ChemistryChemistry • The ergot alkaloids are derivatives of theThe ergot alkaloids are derivatives of the tetracyclic compoundtetracyclic compound 6-methylergoline.6-methylergoline. • 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)
  26. 26. PHARMACOKINETICS ofPHARMACOKINETICS of Ergometrine & metherginErgometrine & methergin Absorption ORAL PARENTERAL(IM,IV) rapidly absorbed peak concentrations (plasma) -60 to 90min PREFERED ROUTE PreparationPreparation ampoulesampoules tabletstablets ErgometrineErgometrine 0.25mg/0.25mg/ 0.5mg0.5mg 0.5-0.5- 1.0mg1.0mg metherginmethergin 0.2mg0.2mg 0.5-0.5- 1.0mg1.0mg SyntometrineSyntometrine (sandoz)(sandoz) 0.5mg0.5mg Ergometrine + 5U- syntocinon -:Composition of ergot preparations:-
  27. 27. 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
  28. 28. Pharmacodynamics:Pharmacodynamics: 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 polarity).polarity). • 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.)
  29. 29. The uterine smooth muscle fibers when contracted compress traversing blood vessels –Principle for its clinical use.
  30. 30. INDICATION -INDICATION - THERAPEUTICTHERAPEUTIC POSTPARTUM HEMORRHAGE- • 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 deliverydelivery.. • 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.
  31. 31. PROPHYLACTICPROPHYLACTIC:: AFTER DELIVERY OF ANT.AFTER DELIVERY OF ANT. SHOULDERSHOULDER// FOLLOWING DELIVERY OFFOLLOWING DELIVERY OF BABYBABY at the time ofat the time of delivery of thedelivery of the placenta.placenta.
  32. 32. CAUTIONSCAUTIONS
  33. 33. ToxicityToxicity • 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 resection.resection. • Interferes with LACTATION (↓prolactin)Interferes with LACTATION (↓prolactin)
  34. 34. 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 disordersHeart disease or severe hypertensive disorders ~•~•~•~~•~•~•~
  35. 35. 20-Carbon carboxylic acids with20-Carbon carboxylic acids with Cyclopentane ringCyclopentane ring Formed by PUFAFormed by PUFA Prostaglandins Prostanoic acidProstanoic acid 2468 10 12 14 16 18 20 PGE2 PGF2ά COOH PGE1
  36. 36. SYNTHESIS SYNTHESIS & ACTION & ACTION Lungs & liverLungs & liver
  37. 37. PGF2ά- acts predominantly on myometrium PGE2- on the cervix due to collagenolytic property LOCAL HARMONES
  38. 38. 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 contractility.contractility. ““PGs action is independend of the period of gestation”.PGs action is independend of the period of gestation”. -ve PGDH -ve phospholipase-A2phospholipase-A2 PGHS-2PGHS-2 +
  39. 39. PROSTAGLANDIN
  40. 40. USES IN OBSTETRICSUSES IN OBSTETRICS INDUCTION OF ABORTION – MTP / Missed abortion.INDUCTION OF ABORTION – MTP / Missed abortion. 11stst 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)
  41. 41. 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) -:Preparations:- 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 fornix. -:Parenteral:- PGE2 - ProstineE2 1mg/ml PGF -ProstinF (Dinoprost tromethamine) 5mg/ml
  42. 42. Side effectsSide effects SYSTEMICSYSTEMIC NVDNVD BronchospasmBronchospasm Fall in BP, tachycardia, chest painFall in BP, tachycardia, chest pain Shivering, fever, malaiseShivering, fever, malaise LOCALLOCAL 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
  43. 43. CONTRAINDICATIONCONTRAINDICATION Hypersensitivity to the drugHypersensitivity to the drug Uterine scarUterine scar Bronchial asthmaBronchial asthma Heart diseasesHeart diseases
  44. 44. 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 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 oxytocinInduction delivery interval is short. Need of oxytocin augmentation is less. Failure of induction is less.augmentation is less. Failure of induction is less.
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