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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Chapter 64
Drugs That Affect Uterine Function
2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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)
3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Drugs Used to Promote Cervical Ripening
Dinoprostone (Prepidil, Cervidil) Dinoprostone gel Dinoprostone vaginal inserts (Cervidil) Misoprostol (Cytotec)
Not approved for this use
10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Uterine Stimulants (Oxytocics)
Three groups of uterine stimulants Oxytocin Ergot alkaloids Prostaglandins
12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Drugs for Menorrhagia
Tranexamic acid Menorrhagia Trauma patients Adverse effects and interactions
NSAIDs Combination oral contraceptives Levonorgestrel-releasing intrauterine system