Lecture 1: Ante- and Perinatal Pharm Flashcards

1
Q

Describe the change in collagen fibers that occurs with cervical ripening?

A
  • 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
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2
Q

What are the clinical indication for using the synthetic PGE1 analog, Misoprostol?

A
  • Termination of intrautrine pregnancy if <70 days in combo w/ mifepristone
  • NSAID-induced gastric ulcer prevention
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3
Q

List 4 off-label uses for Misoprostol?

A
  • Cervical ripening
  • Labor induction in pt without cervical dilation
  • Incomplete abortion
  • Post-partum hemorrhage
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4
Q

How do the pharmacokinetics of Misoprostol differ from Dinoprostone?

A
  • Misoprostol = stable at room temp; oral w/ onset in 30 mins
  • Dinoprostone = needs to be refrigerated and much more expensive
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5
Q

What are some of the maternal AE’s associated with oral administration of Misoprostol?

A
  • N/V
  • Diarrhea
  • Abdominal pain
  • Chills + shivering
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6
Q

What are some of the maternal AE’s associated with intravaginal administration of Misoprostol?

A
  • Uterine contractions occurring too rapidly
  • Prolonged uterine contractions
  • Uterine rupture
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7
Q

What is an AE associated with Dinoprostone when used during abortion?

A

Fever UNRESPONSIVE to NSAIDs

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8
Q

What is the MOA of Carboprost?

A

Synthetic prostaglandin F2α analog

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9
Q

What are the clinical indications for the prostaglandin F2α analog, Carboprost?

A
  • 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
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10
Q

What is the route of administration for the prostaglandin F2α analog, Carboprost?

A

Must be given by deep IM injection

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11
Q

What are the contraindications for using the prostaglandin F2α analog, Carboprost?

A
  • Hypersensitivity
  • Acute PID
  • Active cardiac, pulmonary, renal, or hepatic dysfunction
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12
Q

What are some of the major AE’s assoc. w/ the prostaglandin F2α analog, Carboprost?

A
  • 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
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13
Q

What are the clinical indications for using oxytocin?

A
  • Induction of labor once cervix is dilated****
  • Post-partum hemostasis for refractory bleeding****
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14
Q

How is oxytocin administered?

A

IV w/ infusion pump, requires careful monitoring

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15
Q

The use of oxytocin is contraindicated for the induction of labor in what 2 scenarios?

A
  • If lungs are not mature
  • Cervix is not ripe –> rupture
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16
Q

What is a maternal AE associated w/ oxytocin?

A

Water intoxication

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17
Q

Ergot alkaloids work by stimulating what 3 types of receptors?

A
  • Adrenergic
  • Dopaminergic
  • Serotonergic
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18
Q

What are the effects of ergot alkaloids on both the uterus and the vasculature?

A
  • Uterus = prolonged/tonic uterine contractions
  • Vasculature = constricts aterioles and veins
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19
Q

What is the post-partum use of ergot alkaloids?

A
  • Used to ↑ uterine tone + ↓ bleeding; given after delivery
  • Second choice for limiting post-partum bleeding (oxytocin = 1st)
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20
Q

What are the significant AE’s associated with Ergot Alkaloids?

A
  • IV results in HTN
  • N/V and HA followed by convulsions and possibly death
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21
Q

Contraindications for the use of ergot alkaloids include what?

A

HTN and hypersensitivity

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22
Q

What are 4 indications for antenatal corticosteroids in women between 24 to <36 weeks of gestation?

A
  • Threatened pre-term labor
  • Anterpartum hemorrhage
  • Preterm rupture of membranes
  • Conditions requiring C-section –> pre-eclampsia and HELLP
23
Q

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)?

A
  • Betamethasone —> 2 doses by IM injection; 24 hr intervals
  • Dexamethasone —> 4 doses by IM injection; 12 hr intervals
24
Q

Why not administer cortisol to induce fetal lung maturation?

A
  • 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!
25
Q

What is the magnesium sulfate used for during the peri-natal period?

A
  • 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
26
Q

What is the MOA of magnesium sulfate used as a tocolytic?

A

Thought to inhibit ACh release at uterine NMJ’s

27
Q

What are the maternal and fetal AE’s associated w/ magnesium sulfate?

A
  • 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!

28
Q

What is the recommendation for the use of magnesium sulfate according to the American College of Obstetricians and Gynecologists?

A
  • 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)
29
Q

What drug class does Terbutaline belong to and what is its tocolytic MOA?

A
  • β2-agonist
  • ↑ cAMP, leads to K+-channel mediated hyperpolarization, and dephosphorylation of myosin light chains
30
Q

What are the contraindications for Terbutaline?

A
  • Cardiac arrhythmias
  • Poorly controlled thyroid disease or DM
31
Q

Terbutaline can be used to delay labor for how long?

A

For 2-7 days, but no evidence of benefit to fetus and mother experiences side effects

32
Q

What are some of the major maternal AE’s associated with Terbutaline?

A
  • Cardiac arrhythmias + MI + tachycardia
  • Pulmonary edema + SOB
  • HYPOtension
  • HYPERglycemia + HYPERinsulinemia + antidiuresis
  • Altered thyroid function
  • HYPOkalemia
33
Q

What is the FDA warning/Regulatory report associated with injectable and oral terbutaline use as a tocoyltic?

A
  • 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
34
Q

What is the MOA of the tocolytic action of the CCB, Nifedipine?

A

Blocks Ca2+ influx thru voltage-gated Ca2+ channel –> ↓ contraction

35
Q

What are the contraindications for using Nifedipine?

A
  • Cardiac disease
  • Use caution w/ renal disease and maternal hypotension (<90/50 mmHg)
  • Avoid concomitant use w/ magnesium sulfate (can cause lethal CV “collapse”)
36
Q

What are the maternal AE’s associated w/ Nifedipine?

A
  • Flushing + HA + dizziness + nausea
  • Transient hypotension
  • Transient tachycardia
  • Palpitations
37
Q

What are the conchrane evidence-based conclusions for the use of the CCB, Nifedipine as a tocolytic?

A

Are preferable to other tocolytic agents compared, mainly β-mimetics

38
Q

What is the tocolytic MOA of Indomethacin?

A

Blocks synthesis of PGF2α, a potent stimulator of uterine contractions

39
Q

What are 2 contraindications for the use of Indomethacin as a tocolytic?

A

Significant renal or hepatic impairment

40
Q

What are some of the maternal AE’s associated w/ Indomethacin?

A
  • Nausea + HA+ heartburn + gastritis
  • Proctitis w/ hematochezia
  • Impairment of renal function
  • postpartum hemorrhage
  • Dizziness + depression
41
Q

What are 6 of the fetal AE’s associated with Indomethacin?

A
  • Constriction of ductus arteriosus
  • Pulmonary HTN
  • Reversible decrease in renal function w/ oligohydramnios
  • Intraventricular hemorrhage
  • HYPERbilirubinemia
  • Necrotizing enterocolitis
42
Q

A meta-analysis concluded that what tocolytic was the best choice?

A

Indomethacin

43
Q

What is the MOA of the tocolytic, Atosiban?

A

Blocks action of oxytocin, a hormone that stimuates uterine contractions during labor and delivery

44
Q

What are the maternal AE’s associated with the oxytocin inhibitor, Atosiban?

A

Transient HA and nausea

45
Q

Which 2 tocolytics appear to be the best choices currently available in the US?

A

Nifedipine (CCB) or Indomethacin (NSAID)

46
Q

After birth the ductus arteriosus should close spontaneously within a few days due to what 2 factors?

A
  • Construiction caused by ↑ oxygen tension
  • circulating PGE2 due to its metabolism in lungs
47
Q

What drug class does Alprostadil belong to, route of administration, and what is it used for?

A
  • Synthetic PGE1 similar to misoprostol for parenteral administration
  • Maintains PDA
48
Q

What are the 2 indication for using Alprostadil in an infant?

A
  • 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
49
Q

What are 4 AE’s associated w/ parenteral administration of Alprostadil to an infant?

A
  • Pyrexia (fever)
  • HYPOtension
  • Tachycardia
  • Apnea
50
Q

What are some of the sign/sx’s of a clinically significant PDA in an infant?

A
  • Poor eating, which leads to poor growth
  • Sweating w/ crying or eating
  • Persisten fast breathing or breathlessness
  • Easy tiring
  • Rapid HR
51
Q

What are the drugs used for closure of a PDA?

A
  • Classically indomethacin
  • But now often ibuprofen
52
Q

What are AE’s associated with using NSAIDs (indomethacin or ibuprofen) for closure of PDA?

A
  • ↓ kidney function
  • Oliguria
  • Edema
  • Mild HTN
53
Q

What are the 2 first-line drugs for moderate HTN in pregnancy and which class does each belong to?

A
  • Oral α-methyldopa2-agonist)
  • Oral labetolol (α/β-blocker)
54
Q

What are the 3 second line agents used for severe HTN in pregnancy?

A
  • Parenteral labetolol (α/β-blocker)
  • Hydralazine (arterial vasodilator)
  • Sodium nitroprusside (arterial + venous vasodilator)