Antenatal & Perinatal Pharmacology Flashcards
Describe the changes and expectations associated with the FDA’s Pregnancy and Lactation Labeling Final Rule that became effective June 30, 2015
Instead of former letter category indicating risk in pregnancy, now must use narrative sections/subsections for pregnancy (pregnancy exposure registry, risk summary, clinical considerations, data), lactation (risk summary, clinical considerations, data), and females/males of reproductive potential (pregnancy testing, contraception, and infertility)
Strategies for prevention of RDS prior to preterm delivery
Corticosteroids are used to promote lung maturation and increase surfactant production (via increased transcription of surfactant proteins in alveolar type 2 pneumocytes)
Options include betamethasone or dexamethasone
Treatment of RDS in newborns
CPAP
IPPV (nasal intermittent positive pressure ventilation)
If acidotic or otherwise not improving, intubation and exogenous surfactant administration
5 drugs used to stimulate labor (uterotonics)
Misoprostol Dinoprostone Carboprost Oxytoxin Ergot alkaloids
MOA of misoprostol
Synthetic prostaglandin E1 analog
[Replaces PG loss in stomach during NSAID therapy, induces uterine contractions, and maintains PDA patency]
Clinical indications for misoprostol
NSAID-induced gastric ulcer prevention
Termination of intrauterine pregnancy if <70 days gestation — in combo with mifeprestone
Off label: cervical ripening, labor induction, incomplete abortion, post-partum hemorrhage
[contraindications include pregnancy (unless aborting), and previous C-section]
Maternal and fetal side effects of misoprostol
Maternal: oral administration may lead to N/V, abd pain, chills; intravaginal administration may lead to tachysystole, prolonged uterine contractions, and uterine rupture
Fetal: hypoxia d/t tachysystole or prolonged uterine contractions
MOA of dinoprostone
Synthetic prostaglandin E2 analog
[induces uterine contractions; promotes cervical ripening; can be used for pregnancy termination from 12th through 20th week of gestation]
Maternal and fetal AEs of dinoprostone
Maternal: back pain, N/V, diarrhea, chills, abd pain, flushing, dizziness, warm feeling in vagina, and FEVER unresponsive to NSAIDs during abortion
Fetal: hypoxia d/t tachysystole or prolonged uterine contractions during labor/delivery
MOA of carboprost
Synthetic prostaglandin F2a analog
[induces uterine contractions, prolonged duration of action]
Clinical indications for carboprost
Used to induce abortion by stimulating uterine contractions between 13-20 weeks of pregnancy if failure of another for expulsion of fetus, premature rupture of membranes with previable fetus and inefficient activity
Post-partum hemostasis for refractory bleeding
[contraindications include hypersensitivity, acute PID, active cardiac, pulmonary, renal, or hepatic dysfunction]
AEs of carbaprost
Vasoconstricting effects may lead to HTN and pulmonary edema
Can cause chills but tends to reduce body temperature (unlike PGE2)
Also causes dizziness, heartburn, choking sensation, cough, blurred vision, rash, breast tenderness, dysmenorrhea-like pain, perforated uterus or cervix, UTI
Exogenous oxytocin may be given to increase force, frequency, and duration of uterine contractions by binding to GPCRs linked to Ga(q)-dependent pathways. It may also be used for post-partum hemostasis for refractory bleeding. What are the maternal side effects of exogenous oxytocin?
Water intoxication
The ergot alkaloids used as uterotonics include ergonovine and ethyl-ergonovine. What is their MOA?
Stimulates adrenergic, dopaminergic, and serotonergic receptors
Causes dose-dependent prolonged/tonic uterine contraction as well as constriction of arterioles and veins
Ergot alkaloids could be used to augment labor, but this is not recommended because of prolonged contractions that cause maternal and fetal trauma. What is the primary indication of their use in the setting of labor/delivery?
Postpartum use to increase uterine tone and decrease bleeding; administered AFTER delivery
AEs of ergot alkaloids
Significant AEs in clinic are rare; may lead to HTN associated with N/V, headache, convulsion, death
Historically St. Anthony’s fire — mania, psychosis, vomiting, dry gangrene
There are currently no FDA-approved drugs available in the US for the suppression of labor (tocolytics). However, there are options that may be used in clinical practice “off-label”. What 5 drugs may be used to delay preterm labor (tocolytics)?
Terbutaline Indomethacin Nifedipine MgSO4 Atosiban
Management of preterm premature rupture of membranes in gestational age <24 weeks
Expectant management or induction of labor
Single corticosteroid course may be considered
No consensus on use of tocolytics
Management of preterm premature rupture of membranes in gestational age 24-31 weeks
Expectant management
Single corticosteroid use
No consensus on tocolytics
Magnesium sulfate for neuroprotection may be considered
Management of preterm premature rupture of membranes in gestational age 32-34 weeks
Expectant management
Single corticosteroid course
Management of preterm premature rupture of membranes in gestational age >34 weeks
Plan delivery; labor induction unless contraindicated
Single corticosteroid course may be considered up to 36 weeks
Drug that effectively prevents eclamptic seizures and may decrease risk for cerebral palsy; currently the long-term drug of choice for tocolysis in the US
Magnesium sulfate
MOA of magnesium sulfate in tocolysis
Thought to inhibit ACh release at uterine neuromuscular junctions
Maternal and fetal AEs of magnesium sulfate used for tocolysis
Maternal: skin flushing, palpitations, headaches, depressed reflexes, respiratory depression, impaired cardiac conduction
Fetal: muscle relaxation, rarely CNS depression
Terbutaline mechanism of tocolytic action
Beta-2 agonist — Increases cAMP, leads to K+ channel-mediated hyperpolarization, dephosphorylation of myosin light chains
[delays labor for 2-7 days but no evidence of benefit to fetus and mother experiences side effects]
Maternal and fetal AEs of terbutaline
Maternal: cardiac arrhythmias, pulmonary edema, myocardial ischemia, hypotension, tachycardia, SOB, hyperglycemia, hyperinsulinemia, antidiuresis, altered thyroid function, hypokalemia, tremor, nervousness, N/V
Fetal: tachycardia, hyperinsulinemia, fetal hyperglycemia, neonatal hypoglycemia, hypocalcemia, hypotension, myocardial and septal hypertrophy, myocardial iscemia, ileus
Nifedipine mechanism of tocolytic action
CCB — Blocks calcium influx through voltage-gated calcium channels
[considered preferable to other tocolytic agents but need more research]
Maternal and fetal AEs of nifedipine
Maternal: flushing, HA, dizziness, nausea, transient hypotension, transient tachycardia, palpitations
Fetal: none noted
Indomethacin mechanism of tocolytic action
NSAID/prostaglandin synthetase inhibitor — blocks synthesis of PGF2a (a potent stimulator of uterine contractions)
Maternal and fetal AEs with indomethacin
Maternal: nausea, heartburn, gastritis, proctitis with hematochezia, impairment of renal function, increased postpartum hemorrhage, HA, dizziness, depression
Fetal: constriction of ductus arteriosus, pulmonary HTN, reversible decrease in renal function with oligohydramnios, intraventricular hemorrhage, hyperbilirubinemia, necrotizing enterocolitis
Atosiban mechanism of tocolytic action
Oxytocin inhibitor
Maternal and fetal AEs with atosiban
Maternal: transient HA and nausea, possible allergic rxn
Fetal: none confirmed
Use of a tocolytic drug is NOT associated with a clear reduction in perinatal or neonatal mortality/morbidity. Of the available agents, _____ or _____ appear to be the best choices currently available in the US
Nifedipine; indomethacin
Synthetic PGE1 similar to misoprostol administered parenterally to maintain a patent ductus arteriosus
Alprostadil
Adverse effects of alprostadil used to maintain PDA
Pyrexia, hypotension, tachycardia, apnea
2 drugs that may be used to close a PDA
Indomethacin
Ibuprofen
AEs of NSAIDs used to close PDA
Decreased kidney function —> oliguria, edema, mild HTN
4 drugs used in management of HTN in pregnancy
First line (moderate HTN): alpha-methyldopa, oral labetalol
Second line (severe HTN): parenteral labetalol, hydralazine, sodium nitroprusside
[note: ALL ACEIs and ARBs are contraindicated]
MOA of alpha-methyldopa used to tx HTN in pregnancy
Alpha-2 agonist
MOA of labetalol used to tx HTN in pregnancy
Alpha/beta blocker
MOA of hydralazine used to tx HTN in pregnancy
Arterial vasodilator
MOA of sodium nitroprusside used to tx HTN in pregnancy
Arterial and venous vasodilator
Which of the following would be administered first to induce uterine contractions (prior to cervical dilation)?
A. Carboprost B. Dinoprostone C. Ergonovine D. Misoprostol E. Oxytocin
D. Misoprostol
Which of the following is administered to induce uterine contractions after cervical dilation?
A. Carboprost B. Dinoprostone C. Ergonovine D. Misoprostol E. Oxytocin
E. Oxytocin
Which of the following rapidly terminates postpartum bleeding?
A. Carboprost B. Ergonovine C. Misoprostol D. Atosiban E. Terbutaline
B. Ergonovine
Which of the following could be given to hasten lung development?
A. Beclamethasone B. Cortisol C. Cortisone D. Dexamethasone E. Mifeprestone
D. Dexamethasone
Which of the following maintains a PDA until surgical repair?
A. Alprostadil B. Carboprost C. Dinoprostone D. Indomethacin E. Misoprostol F. Nifedipine
A. Alprostadil
