Lecture 1: Ante- and Perinatal Pharm Flashcards
Describe the change in collagen fibers that occurs with cervical ripening?
- Phase 1: collagen fibers are well-organized and uniform-size
- Phase 2: fibril size is less uniform with more spacing between disorganized fibers to allow for ↑ in mechanical compliance of the cervix
What are the clinical indication for using the synthetic PGE1 analog, Misoprostol?
- Termination of intrautrine pregnancy if <70 days in combo w/ mifepristone
- NSAID-induced gastric ulcer prevention
List 4 off-label uses for Misoprostol?
- Cervical ripening
- Labor induction in pt without cervical dilation
- Incomplete abortion
- Post-partum hemorrhage
How do the pharmacokinetics of Misoprostol differ from Dinoprostone?
- Misoprostol = stable at room temp; oral w/ onset in 30 mins
- Dinoprostone = needs to be refrigerated and much more expensive
What are some of the maternal AE’s associated with oral administration of Misoprostol?
- N/V
- Diarrhea
- Abdominal pain
- Chills + shivering
What are some of the maternal AE’s associated with intravaginal administration of Misoprostol?
- Uterine contractions occurring too rapidly
- Prolonged uterine contractions
- Uterine rupture
What is an AE associated with Dinoprostone when used during abortion?
Fever UNRESPONSIVE to NSAIDs
What is the MOA of Carboprost?
Synthetic prostaglandin F2α analog
What are the clinical indications for the prostaglandin F2α analog, Carboprost?
- Induce abortion by stimulating uterine contractions btw 10-30 wks, if failure of another for expulsion of fetus, premature rupture of membranes w/ previable fetus and inefficient activity
- Post-partum hemostasis for refractory bleeding
What is the route of administration for the prostaglandin F2α analog, Carboprost?
Must be given by deep IM injection
What are the contraindications for using the prostaglandin F2α analog, Carboprost?
- Hypersensitivity
- Acute PID
- Active cardiac, pulmonary, renal, or hepatic dysfunction
What are some of the major AE’s assoc. w/ the prostaglandin F2α analog, Carboprost?
- HTN and pulmonary edema since potent vasoconstrictor (unlike vasodilator PGE2)
- Chills/shivering but tends to reduce body temp (unlike PGE2)
- Perforated uterus or cervix + UTI’s + blurred vision + asthma
What are the clinical indications for using oxytocin?
- Induction of labor once cervix is dilated****
- Post-partum hemostasis for refractory bleeding****
How is oxytocin administered?
IV w/ infusion pump, requires careful monitoring
The use of oxytocin is contraindicated for the induction of labor in what 2 scenarios?
- If lungs are not mature
- Cervix is not ripe –> rupture
What is a maternal AE associated w/ oxytocin?
Water intoxication
Ergot alkaloids work by stimulating what 3 types of receptors?
- Adrenergic
- Dopaminergic
- Serotonergic
What are the effects of ergot alkaloids on both the uterus and the vasculature?
- Uterus = prolonged/tonic uterine contractions
- Vasculature = constricts aterioles and veins
What is the post-partum use of ergot alkaloids?
- Used to ↑ uterine tone + ↓ bleeding; given after delivery
- Second choice for limiting post-partum bleeding (oxytocin = 1st)
What are the significant AE’s associated with Ergot Alkaloids?
- IV results in HTN
- N/V and HA followed by convulsions and possibly death
Contraindications for the use of ergot alkaloids include what?
HTN and hypersensitivity
What are 4 indications for antenatal corticosteroids in women between 24 to <36 weeks of gestation?
- Threatened pre-term labor
- Anterpartum hemorrhage
- Preterm rupture of membranes
- Conditions requiring C-section –> pre-eclampsia and HELLP
What are the 2 choices of antenatal corticosteroids which can be given over 48 hours to induce fetal lung maturation (route of admin. and dosing interval)?
- Betamethasone —> 2 doses by IM injection; 24 hr intervals
- Dexamethasone —> 4 doses by IM injection; 12 hr intervals
Why not administer cortisol to induce fetal lung maturation?
- The placenta metabolizes (inactivates) to cortisone
- Placenta is rich in 11β-HSD-2
- This means the mother could be given cortisol without causing AE’s to the fetus!
What is the magnesium sulfate used for during the peri-natal period?
- Used to prevent eclamptic seizures
- Used for neuroprotection; appears to ↓ risk for cerebral palsy
- Drug of choice for short-term (up to 48 hrs) tocolysis (suppression of labor)in women areat riskofpreterm delivery within 7 days
What is the MOA of magnesium sulfate used as a tocolytic?
Thought to inhibit ACh release at uterine NMJ’s
What are the maternal and fetal AE’s associated w/ magnesium sulfate?
- Maternal = skin flushing, palpitations, HA’s, depressed reflexes, respiratory depression, impaired cardiac conduction
- Fetal = muscle relaxation, rarely CNS depression
*Think about what inhibiting ACh at NMJ’s would do!
What is the recommendation for the use of magnesium sulfate according to the American College of Obstetricians and Gynecologists?
- Support the short-term (usually <48 hours) use in obstetric care
- Prevent and tx of seizures in preeclampsia or eclampsia
- Fetal neuroprotection before anticipated preterm (<32 weeks)
- Short-term delivery prolongationofpregnancy(up to 48 hrs)
What drug class does Terbutaline belong to and what is its tocolytic MOA?
- β2-agonist
- ↑ cAMP, leads to K+-channel mediated hyperpolarization, and dephosphorylation of myosin light chains
What are the contraindications for Terbutaline?
- Cardiac arrhythmias
- Poorly controlled thyroid disease or DM
Terbutaline can be used to delay labor for how long?
For 2-7 days, but no evidence of benefit to fetus and mother experiences side effects
What are some of the major maternal AE’s associated with Terbutaline?
- Cardiac arrhythmias + MI + tachycardia
- Pulmonary edema + SOB
- HYPOtension
- HYPERglycemia + HYPERinsulinemia + antidiuresis
- Altered thyroid function
- HYPOkalemia
What is the FDA warning/Regulatory report associated with injectable and oral terbutaline use as a tocoyltic?
- Injectable form should not be used in pregnant women for prevention or prolonged tx (beyond 48-72 hrs) of preterm labor because of potential maternal heart problems and death
- Oral form should not be used at all because it has not been shown to be effective and has similar safety concerns
What is the MOA of the tocolytic action of the CCB, Nifedipine?
Blocks Ca2+ influx thru voltage-gated Ca2+ channel –> ↓ contraction
What are the contraindications for using Nifedipine?
- Cardiac disease
- Use caution w/ renal disease and maternal hypotension (<90/50 mmHg)
- Avoid concomitant use w/ magnesium sulfate (can cause lethal CV “collapse”)
What are the maternal AE’s associated w/ Nifedipine?
- Flushing + HA + dizziness + nausea
- Transient hypotension
- Transient tachycardia
- Palpitations
What are the conchrane evidence-based conclusions for the use of the CCB, Nifedipine as a tocolytic?
Are preferable to other tocolytic agents compared, mainly β-mimetics
What is the tocolytic MOA of Indomethacin?
Blocks synthesis of PGF2α, a potent stimulator of uterine contractions
What are 2 contraindications for the use of Indomethacin as a tocolytic?
Significant renal or hepatic impairment
What are some of the maternal AE’s associated w/ Indomethacin?
- Nausea + HA+ heartburn + gastritis
- Proctitis w/ hematochezia
- Impairment of renal function
- ↑ postpartum hemorrhage
- Dizziness + depression
What are 6 of the fetal AE’s associated with Indomethacin?
- Constriction of ductus arteriosus
- Pulmonary HTN
- Reversible decrease in renal function w/ oligohydramnios
- Intraventricular hemorrhage
- HYPERbilirubinemia
- Necrotizing enterocolitis
A meta-analysis concluded that what tocolytic was the best choice?
Indomethacin
What is the MOA of the tocolytic, Atosiban?
Blocks action of oxytocin, a hormone that stimuates uterine contractions during labor and delivery
What are the maternal AE’s associated with the oxytocin inhibitor, Atosiban?
Transient HA and nausea
Which 2 tocolytics appear to be the best choices currently available in the US?
Nifedipine (CCB) or Indomethacin (NSAID)
After birth the ductus arteriosus should close spontaneously within a few days due to what 2 factors?
- Construiction caused by ↑ oxygen tension
- ↓ circulating PGE2 due to its metabolism in lungs
What drug class does Alprostadil belong to, route of administration, and what is it used for?
- Synthetic PGE1 similar to misoprostol for parenteral administration
- Maintains PDA
What are the 2 indication for using Alprostadil in an infant?
- Pre-term infants w/ congenital heart defects –> allows them to mature sufficienctly to cope w surgery
- Heart defects –> used to maintain PDA to sustain pulmonary and systemic blood flow
What are 4 AE’s associated w/ parenteral administration of Alprostadil to an infant?
- Pyrexia (fever)
- HYPOtension
- Tachycardia
- Apnea
What are some of the sign/sx’s of a clinically significant PDA in an infant?
- Poor eating, which leads to poor growth
- Sweating w/ crying or eating
- Persisten fast breathing or breathlessness
- Easy tiring
- Rapid HR
What are the drugs used for closure of a PDA?
- Classically indomethacin
- But now often ibuprofen
What are AE’s associated with using NSAIDs (indomethacin or ibuprofen) for closure of PDA?
- ↓ kidney function
- Oliguria
- Edema
- Mild HTN
What are the 2 first-line drugs for moderate HTN in pregnancy and which class does each belong to?
- Oral α-methyldopa (α2-agonist)
- Oral labetolol (α/β-blocker)
What are the 3 second line agents used for severe HTN in pregnancy?
- Parenteral labetolol (α/β-blocker)
- Hydralazine (arterial vasodilator)
- Sodium nitroprusside (arterial + venous vasodilator)
