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Premium member Presentation Transcript Tocolytics & Oxytocic Drugs: Tocolytics & Oxytocic Drugs Dr Sadia Batool Shahid Senior lecturer Pharmacology Dept IMDC: Drugs affecting Uterine Motility Oxytocic drugs : These drugs stimulate uterine smooth muscles , produce contractions, during pregnancy. Tocolytic Drugs: These drugs relax uterine smooth musclesOxytocic Drugs: Oxytocic Drugs An agent that promotes rapid labor by stimulating contractions of the myometrium Uterine stimulants or abortifacientsOxytocic Agents: Oxytocic Agents Oxytocin (Posterior Pituitary hormones) Ergot alkaloids Ergometrine Ergonovine Methylergometrine Prostaglandins PGE2 PGF2 α M isoprostol Miscellaneous Quinine Emetine Alcohol EthacridineOxytocin: Oxytocin Post Pituitary secretes Oxytocin and Vasopressin Oxytocin is synthesized in hypothalumus and transported and stored in post. Pitutary Released after distension of the cervix and vaginal birth Required for Letdown or milk ejection reflexOxytocin: Oxytocin Chemistry Nine AA peptide hormone secreted by posterior pituitary & released in to circulation, also prepared synthetically. Pharmacokinetics: Destroyed in GIT so not given orally. Given I/V or by Nasal spray. Not PPB Eliminated by kidney & liver. t 1/2 --- 5 minutes .Pharmacodynamics-Oxytocin: Pharmacodynamics-Oxytocin Acts through GPCR Activation leads to generation of IP3 Intracellular Ca++ mobilization from stores Activation of voltage sensitive calcium channels Small doses increase Frequency and force of uterine contraction Large doses cause sustained contraction Mammary alveoli- myoepethelial cells contraction At high conc. action on Vasopressin receptorsSlide 8: Pharmacological Effects: Uterus: Small doses—Increases both the frequency & force of contraction. Large doses: Sustained contraction. Mammary Gland: Contraction of myoepithelial cells sorrounding mammary alveoli produces milk ejection. Without oxytocin induced contraction lactation can not occur. At high doses weak Antidiuretic & pressor activity due to action on Vasopressin receptorsSlide 9: Therapeutic Uses: Facilitation of labor at term– I/V infusion Reinforcement of Labor Induction of labor for conditions requiring early vaginal delivery. I/V infusion To control bleeding ( Postpartum uterine hemorrhage )after vaginal or cesarean delivery– I/M injection Incomplete abortion Impaired milk ejection-- intranasal 6. Oxytocin Challenge Test An oral derivative of Oxytocin – Demoxytocin is under studies .Slide 10: ADVERSE EFFECTS: Serious toxicity is rare if used judiciously. Fetal A/E Fetal distress,placental abruption or death Maternal A/E Uterine rupture Fluid retention , Water intoxication Hyponatremia , heart failure , seizures & death. Bolus Inj. can produce hypotension, so used as infusion at a controlled rate.PROSTAGLANDINS: PROSTAGLANDINS DINOPROSTONE (Synthetic PGE 2 ) Given intravaginally as a gel or tablet. Given extra- amniotically as a solution 1st pass metabolism in lungs—95% Metabolized in local tissues. Metabolites excreted in urine. Some absorption directly through cervix & lymphatics in to maternal circulation . t ½ 2.5-5 minSlide 12: MOA & Effects of Dinoprostone : Stimulation of G protein coupled PGE 2 receptors so contraction of myometrium Ripening of cervix: due to direct effect on cervical collagenase resulting in softening Has natriuretic effect & no Antidiuretic effect Superior to oxytocin for women with pre- eclampsia , as no fluid retention.Slide 13: Therapeutic Uses of Dinoprostone : Facilitation of labor at term (softening of cervix) Induction of labor Abortifacient As vaginal suppository alone or with Oral mifepristone or oral Misoprostol Adverse Effects: Nausea, Vomiting, diarrhea Incomplete abortion Increased blood lossSlide 14: CARBOPROST :15 methyl PGF 2 Analog. Therapeutic Use : Induction of labor To control PPH , not managed by conventional methods– I/M For 2 nd trimester abortion ,Single intra-amniotic injection Adverse effects : Vomiting ,diarrhea Transient rise of temperature , Bronchoconstriction Fetal toxicity is uncommonSlide 15: Gameprost & Misoprostol (Synthetic PGE 1 ) Given intravaginally as a gel or tablet .Slide 16: ERGOT ALKALOIDS: NaturalAmine Ergot Alkaloid Ergonovine ( Ergometrine ): Synthetic Ergoderivatitve (properties similar to Ergotmetrine ) Methyl Ergometrine (Methyl Ergonovine ) :Ergot Alkaloids: Ergot Alkaloids Mechanism of Oxytocic effects : Agonistic effect on 1 receptors in myometrium Partial agonistic effect on 5HT 2 receptorsPharmacological Effects: Pharmacological Effects The sensitivity of the uterus to the stimulant effect increases dramatically during pregnancy. As the pregnancy progresses there is increasing dominance of 1 receptors. So at term uterus is more sensitive . Small doses provoke rhythmic contractions & relaxation. Increase both the frequency & amplitude of contractions Higher doses induce powerful & prolonged contraction.Slide 19: Therapeutic Uses: Postpartum Hemorrhage Contraindications: Hypertension Sepsis.Slide 20: Adverse Effects: Nausea, Vomiting. Increase in Blood Pressure. Decreased milk secretionTOCOLYTICS: TOCOLYTICS Definition: These are the drugs , which relax uterine muscles & inhibit uterine contractionsTocolytics: Tocolytics They are used to arrest premature labor. They can delay delivery for 48 hrs, this time can be used To administer Glucocorticoid (Inj. Betamethasone )to mother for maturation of the fetal lung---formation of surfactant ,to decrease risk of RDS. To make it possible that baby is born where facility of neonatal ICU is availableSlide 23: Classification- Tocolytic drugs 2 Selective Stimulants Ritodrine , salbutamol ( Main drugs used ) Oxytocic Antagonist Atosiban Other drugs Magnesium sulphate . Calcium channel blockers: Nifedipine Inhalational Anesthetic (Halothane) COX inhibitors: IndomethacinSlide 24: Ritodrine (Selective 2 stimul ant) It is the drug of choice for arresting pre mature labor. Arrests premature labor in selected patients (Between 22-33 weeks) In otherwise uncomplicated pregnancies can delay premature labor for 48 hrs Delay in labour allows To administer Glucocorticoid ( Betamethasone )to mother so as to mature the fetal lung---formation of surfactant ,to decrease RDS To make it possible that baby is born where facility of neonatal ICU is available. Initially I/V bolus then I/V infusion. Albuterol & Terbutaline may also be used.Slide 25: Complications: Mother: Pulmonary oedema . Anxiety: Restlessness, Headache. Neonate: Hypoglycemia Ileus . Contraindications: DM, Heart disease. Patient on β Blocker or steroids.Slide 26: Oxytocic Antagonist: Atosiban Atosiban is a modified form of oxytocin It antagonizes the effects of oxytocin at its receptors. As oxytocin stimulates the uterine contractions , atosiban relaxes the uterine smooth muscle Alternative to 2 selective stimulants Used as tocolytic in premature labor Given by I/V infusion for 2-48 hrs ,Never for more than 48 hrs Efficacy more than 2 selective stimulantsSlide 27: Magnesium sulphate . MOA: Given by I/V Infusion. Suppression of uterine contractions Controls Blood Pressure in toxemia of pregnancy. Adverse Effects: Cardiac Arrhythmias Muscular Paralysis CNS & Resp. depression of mother & Neonate C/I with B antagonists.Slide 28: Halothane (Inhalational anesthetic) Relaxes uterine smooth muscles Use Manipulation of fetus (Version) in prenatal period Postnatally for delivery of placenta. Adverse Effects Prolonged Labor Increased blood loss and inhibition of uterine contractions during parturition . You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.