Drugs That Affect Uterine Function Chapter 64 Drugs That Affect Uterine Function 1

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) 2

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 3

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 4

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 5

Uterine Relaxants (Tocolytics) Beta2-selective adrenergic agonist Terbutaline (Brethine) 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 6

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 7

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 8

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

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 10

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

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 12

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 13

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 14

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 15

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 16

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