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Chapter 64

Chapter 64. Drugs That Affect Uterine Function. Drugs That Affect Uterine Function. Three main categories: Uterine relaxants (tocolytics) Uterine relaxation Suppression of preterm labor Uterine stimulants (oxytocics) Uterine contraction Induction/augmentation of labor

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Chapter 64

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  1. Chapter 64 Drugs That Affect Uterine Function

  2. Drugs That Affect Uterine Function • Three main categories: • Uterine relaxants (tocolytics) • Uterine relaxation • Suppression of preterm labor • Uterine stimulants (oxytocics) • Uterine contraction • Induction/augmentation of labor • Control of postpartum bleeding • Induction of abortion • Drugs used to decrease menorrhagia (heavy menstrual bleeding)

  3. Preterm Birth • Before 37 weeks’ gestation • Leading cause of infant morbidity and neonatal mortality • United States: 12.5% of all live births • Premature births account for 75% of all neonatal mortalities and 50% of congenital neurologic deficits • Most common neonatal respiratory distress syndrome

  4. Uterine Relaxants (Tocolytics) • Used to delay delivery • Average delay: only 48 hours • If used with glucocorticoids, the glucocorticoids can accelerate lung development • Also used to buy time to treat infection

  5. Control of Myometrial Contraction • Regulated by multiple mediators • Beta-adrenergic agonists • Oxytocin • Prostaglandins • Four classes of drugs: all decrease the availability of phosphorylated light chain • Beta-adrenergic antagonists, calcium channel blockers, cyclooxygenase (COX) inhibitors, and oxytocin-receptor antagonists

  6. Uterine Relaxants (Tocolytics) • Beta2-selective adrenergic agonist • Terbutaline (Brethine) • Beta2-selective adrenergic agonist • Not approved by FDA for this use • Nifedipine (Procardia, Adalat, Nifedical) • Can suppress labor for up to 48 hours • Efficacy equals that of terbutaline, and safety is superior

  7. Uterine Relaxants (Tocolytics) • Indomethacin (Indocin) • Second-line tocolytic • Higher risk for neonatal complications • Prolonged renal insufficiency, bronchopulmonary dysplasia, necrotizing enterocolitis, and periventricular leukomalacia • Nitroglycerin, a nitric oxide donor

  8. Uterine Relaxants (Tocolytics) • Atosiban • Oxytocin: receptor antagonist • Magnesium sulfate • High dose does not prevent or delay preterm birth but does increase infant mortality • Was previously used readily • Low-dose magnesium sulfate may reduce the risk of cerebral palsy without increasing mortality

  9. Drugs Used to Promote Cervical Ripening • Dinoprostone (Prepidil, Cervidil) • Dinoprostone gel • Dinoprostone vaginal inserts (Cervidil) • Misoprostol (Cytotec) • Not approved for this use

  10. Uterine Stimulants (Oxytocics) Prostaglandins: Dinoprostone and Misoprostol (can also induce labor) • Dinoprostone • Most widely used for cervical ripening • Shortens duration of labor, allows reduced dosage of oxytocin, decreases need for cesarean section • Can also induce abortion • Misoprostol • Not approved for cervical ripening • More convenient and less expensive than dinoprostone • Higher incidence of uterine tachysystone

  11. Uterine Stimulants (Oxytocics) • Three groups of uterine stimulants • Oxytocin • Ergot alkaloids • Prostaglandins

  12. Uterine Stimulants (Oxytocics) • Oxytocin (Pitocin) • Peptide hormone produced by the posterior pituitary • Increases the force, frequency, and duration of uterine contractions • Uterus becomes progressively more responsive to oxytocin throughout pregnancy • Facilitates labor, but unclear whether it can initiate labor

  13. Uterine Stimulants (Oxytocics) • Oxytocin (Pitocin) (cont’d) • Physiologic and pharmacologic effects • Uterine stimulation • Milk ejection • Water retention • Precautions and contraindications • Uterine rupture may occur • Women with active genital herpes • Adverse effect:water retention/intoxication

  14. Uterine Stimulants (Oxytocics) • Ergot alkaloids: ergonovine and methylergonovine • Dried preparation of Claviceps purpurea • Stimulate adrenergic, dopaminergic, and serotonergic receptors • Not used to induce labor (sustained contractions) • Can cause constriction of arterioles and veins and risk of severe hypertension • Used to control postpartum bleeding

  15. Uterine Stimulants (Oxytocics) • Ergot alkaloids: ergonovine and methylergonovine (cont’d) • Therapeutic uses • Postpartum bleeding (not responsive to oxytocin and carboprost tromethamine) • Augmentation of labor • Migraine • Adverse effects (IV administration) • Hypertension

  16. Uterine Stimulants (Oxytocics) • Carboprost tromethamine (Hemabate) • Preferred agent for controlling postpartum hemorrhage • Causes intense uterine contractions • Adverse effects • GI reactions • Vomiting and diarrhea • Fever • Vasoconstriction • Constriction of the bronchi

  17. Drugs for Menorrhagia • Tranexamic acid • Menorrhagia • Trauma patients • Adverse effects and interactions • NSAIDs • Combination oral contraceptives • Levonorgestrel-releasing intrauterine system

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