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

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) 2

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 3

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 4

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 5

6. 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

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 7

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 8

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

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 10

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

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 12

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 13

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 14

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 15

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 16

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