3 OXYTOCIN (SyntocinonR) SynthesisIt is a posterior pituitary hormone secreted by the posterior pituitary gland, which is originally synthesized by the hypothalamus.Oxytocin secretion occurs by sensory stimulation from areas of the cervix ,vagina , and by suckling at the breast.
6 Pharmacokinetics of oxytocin Absorption, Metabolism and ExcretionNot effective orallyAdministered intravenously*Also as nasal spray (to improve milk ejection, minutes before breast feeding)Not bound to plasma proteinsCatabolized by liver & kidneysHalf life = 5 minutes*S.C or IM difficult to monitor
7 Role of oxytocin Uterus Stimulates both the frequency and force of uterine contractility particularly of the fundus segment of the uterus.These contractions resemble the normal physiological contractions of uterus (contractions followed by relaxation)
8 Immature uterus is resistant to oxytocin. Causes the contraction of at-term uterine smooth muscles only.Sensitivity increases to 8 fold in the last 9 weeks and 30 times in early labor.Clinically oxytocin is given only when uterine cervix is soft and dilated. see next slide
9 Oxytocin isn’t used at this stage oxytocin is not given to induce abortion because the cervix is not dilated (too early)before labor the cervix is closedOxytocin isn’t used at this stageAt term the cervix is fully dilatedOxytocin is used at this stage
10 Oxytocin stimulates Ca++ to interact with its receptor Mechanism of actionIntracellular fluidExtracellular fluidOxytocinOxytocin stimulates Ca++ to interact with its receptorMyometrial cellContraction occursCa++ ReceptorN.B. Oxytocin also causes the release of Ca++ from the sacroplasmic reticulum
11 Therapeutic Uses of Oxytocin Induction & augmentation of labor(remember only slow IV infusion)Mild preeclampsia (a serious condition developing in late pregnancy, characterized by sudden hypertension, proteinuria, and edema)Uterine inertia (Uterine atony)Incomplete abortionPost maturity (post-term fetus)Maternal diabetes
12 Therapeutic Uses of Oxytocin (continue) Postpartum uterine hemorrhage(IV drip)(ergometrine is often used nowadays)Impaired milk ejectionOne puff in each nostril 2-3 min before nursing
13 Uterine rupture (occurs at high doses) Hypertension Side effectMaternal death due toUterine rupture (occurs at high doses)HypertensionWater intoxication B/C it is a weak antidiureticFetal death due toConstiction of placental blood vessels Ischemia
14 Contraindications Hypersensitivity to oxytocin PrematurityEvidence of fetal distressAbnormal fetal position horizontalCephalopelvic disproportion
15 Cephalopelvic disproportion Fetus’s head is much larger than the pelvic outlet.
16 *to avoid rupture of the uterus precautionMultiple pregnancyHypertensionPrevious cesarean section**to avoid rupture of the uterus
18 Effects on the UterusAlkaloid derivatives induce TETANIC CONTRACTION of uterus without relaxation in between (unlike the normal physiologic contractions)It causes contractions of the uterus as a whole i.e. fundus and cervix (tends to compress rather than actually expelling the fetus)Not used anymore for labor augmentation.
20 Ergot alkaloids (pharmacokinetics) Absorption fate and excretionAbsorbed orally from the GIT (tablets)Usually given IMNOT given IV because it causes severe vasoconstrictionExtensively metabolized in the liver90% of metabolites are excreted in bileUterus responds to Ergots more than Oxytocin
21 Clinical usesPostpartum hemorrhage (used only at the 3rd stage of labor, when the baby’s head or shoulder start to appear)
22 Preparations If used I.V ↑↑↑↑ blood pressure ergometrine 0.5 mg oxytocin 5.0SyntometrineI.MIf used I.V ↑↑↑↑ blood pressure
23 Why should we use this combination ? Ergots have slow onset of action (7min) but have a long half-life.Yet, oxytocin has a fast onset of action, 1-2 minutes, with a short half-life.
24 Side effects Nausea, vomiting, diarrhea Hypertension because contraction of blood vesselsVasoconstriction of peripheral blood vessels ( toes & fingers) which can lead Gangrene
25 Contraindications: Induction of labour 1st and 2nd stage of labor vascular diseaseSevere hepatic and renal impairmentSevere hypertension
26 PROSTAGLANDINS (PGE2 & PGF2α) Therapeutic uses 1. Induction of abortion (pathological)**(used because the uterus is sensitive to PGs in early stages).2. Induction of labor (fetal death in utero)3. Postpartum hemorrhage
27 Difference between PGS and Oxytocin: PGs contract uterine smooth muscle not only at term(as with oxytocin), but throughout pregnancy.PGs soften the cervix; whereas oxytocin does not.PGs have longer duration of action than oxytocin.N.B. PGs at low doses physiologic contractionat high doses Tetanic contraction
28 Side Effects Nausea , vomiting Abdominal pain Diarrhea Bronchospasm (PGF2α)Flushing (PGE2).P.S. PGE2 causes vasodilation of the mother’s vessels thus leading to cutaneous flushing. Yet, there is vasoconstriction of the umbilical cord’s vessels.PGE2 is used as a vaginal suppository for cervical dilation and softening.
29 Contraindications:Mechanical obstruction of deliveryFetal distress (due to umbilical cord vessels’ vasocontriction)Predisposition to uterine rupturePrecautions:AsthmaMultiple pregnancyGlaucomaUterine rupture
30 Difference B/W Oxytocin and Prostaglandins CharacterContraction through out pregnancyOnly at termContractionsoften the cervixDoes not soften the cervixCervix
31 Cont’d Prostaglandins Oxytocin Character Longer Shorter Duration of actionInduce abortion in 2nd trimester of pregnancy.Used as vaginal suppository (PGE2) for induction of laborInduce and augment labour and post partum hemorrhageuses
32 Difference b/w Oxytocin and Ergometrine CharacterTetanic contraction ; doesn't resemble normal physiological contractionsResembles normal physiological contractionsContractionsOnly in postpartum hemorrhageTo induce &augment labor.*Post partum hemorrhageUsesModerate onsetLong duration of actionRapid onsetShorter duration of actionOnset and Duration
34 DRUGS PRODUCING UTERINE RELAXATION (Tocolytic Drugs) Action and UsesRelax the uterus and arrest threatened abortion or delay premature labor.1. β-ADRENOCEPTOR AGONISTS**Ritodrine, i.v. dripSelective β2 receptor agonist used specifically as a uterine relaxant.Tocolytic drugs: drugs that cause inhibition of premature labor.
35 β- adrenoceptor agonists e.g. β2 selective agonists: ritodrine Mechanism of actionBind to β-adrenoceptors activating the enzyme adenylate cyclase increasing the level of cAMP reducing intracellular calcium level.As the pregnancy progresses there is gradual increase of uterine β2 receptors. This is an attempt to increase β2 responsiveness to its agonist, an important role for the stability of fetal growth.
36 Side effects:TremorNausea , vomitingFlushingSweatingTachycardia (high dose)HypotensionHyperglycemiaHypokalaemia
37 2.CALCIUM CHANNEL BLOCKERS Nifedipine Causes relaxation of the myometriumMarkedly inhibits the amplitude of spontaneous and oxytocin-induced contractions.