Lecture 1: Ante- and Perinatal Pharm

Question 1

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

Answer 1

• 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

Question 2

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

Answer 2

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

Question 3

List 4 off-label uses for Misoprostol?

Answer 3

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

Question 4

How do the pharmacokinetics of Misoprostol differ from Dinoprostone?

Answer 4

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

Question 5

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

Answer 5

• N/V
• Diarrhea
• Abdominal pain
• Chills + shivering

Question 6

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

Answer 6

• Uterine contractions occurring too rapidly
• Prolonged uterine contractions
• Uterine rupture

Question 7

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

Answer 7

Fever UNRESPONSIVE to NSAIDs

Question 8

What is the MOA of Carboprost?

Answer 8

Synthetic prostaglandin F2α analog

Question 9

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

Answer 9

• 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

Question 10

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

Answer 10

Must be given by deep IM injection

Question 11

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

Answer 11

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

Question 12

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

Answer 12

• 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

Question 13

What are the clinical indications for using oxytocin?

Answer 13

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

Question 14

How is oxytocin administered?

Answer 14

IV w/ infusion pump, requires careful monitoring

Question 15

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

Answer 15

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

Question 16

What is a maternal AE associated w/ oxytocin?

Answer 16

Water intoxication

Question 17

Ergot alkaloids work by stimulating what 3 types of receptors?

Answer 17

• Adrenergic
• Dopaminergic
• Serotonergic

Question 18

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

Answer 18

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

Question 19

What is the post-partum use of ergot alkaloids?

Answer 19

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

Question 20

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

Answer 20

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

Question 21

Contraindications for the use of ergot alkaloids include what?

Answer 21

HTN and hypersensitivity

Question 22

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

Answer 22

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

Question 23

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)?

Answer 23

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

Question 24

Why not administer cortisol to induce fetal lung maturation?

Answer 24

• 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!

Question 25

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

Answer 25

- 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 are**at risk**of**preterm delivery within 7 days**

Question 26

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

Answer 26

Thought to **_inhibit_ ACh release** at **uterine NMJ's**

Question 27

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

Answer 27

- **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!

Question 28

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

Answer 28

- 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) - **S****hort-term delivery prolongation**of**pregnancy**(**up to 48 hrs**)

Question 29

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

Answer 29

- **β2**-agonist - **↑ cAMP**, leads to K⁺-channel mediated **hyperpolarization**, and **dephosphorylation** of **myosin light chains**

Question 30

What are the contraindications for Terbutaline?

Answer 30

- **Cardiac arrhythmias** - **Poorly controlled thyroid disease** or **DM**

Question 31

Terbutaline can be used to delay labor for how long?

Answer 31

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

Question 32

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

Answer 32

- Cardiac arrhythmias + MI + tachycardia - Pulmonary edema + SOB - HYPOtension - HYPERglycemia + HYPERinsulinemia + antidiuresis - Altered thyroid function - HYPOkalemia

Question 33

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

Answer 33

- **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

Question 34

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

Answer 34

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

Question 35

What are the contraindications for using Nifedipine?

Answer 35

- **Cardiac disease** - Use **caution** w/ **renal disease** and **maternal hypotension** (\<90/50 mmHg) - **Avoid** concomitant use w/ **magnesium sulfate** (can cause **lethal** CV "collapse")

Question 36

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

Answer 36

- Flushing + HA + dizziness + nausea - Transient **hypotension** - Transient **tachycardia** - **Palpitations**

Question 37

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

Answer 37

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

Question 38

What is the tocolytic MOA of Indomethacin?

Answer 38

**Blocks** synthesis of **PGF₂**α, a **potent** stimulator of uterine contractions

Question 39

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

Answer 39

Significant **renal** or **hepatic** impairment

Question 40

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

Answer 40

- Nausea + HA+ heartburn + gastritis - **Proctitis** w/ **hematochezia** - **Impairment** of **renal function** - ↑ **postpartum hemorrhage** - Dizziness + depression

Question 41

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

Answer 41

- **Constriction** of **ductus arteriosus** - **Pulmonary HTN** - **Reversible** decrease in **renal function** w/ **oligohydramnios** - **Intraventricular hemorrhage** - **HYPERbilirubinemia** - **Necrotizing enterocolitis**

Question 42

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

Answer 42

**Indomethacin**

Question 43

What is the MOA of the tocolytic, Atosiban?

Answer 43

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

Question 44

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

Answer 44

**Transient HA** and **nausea**

Question 45

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

Answer 45

**Nifedipine (CCB)** or **Indomethacin** **(NSAID****)**

Question 46

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

Answer 46

- **Construiction** caused by ↑ **oxygen tension** - ↓ **circulating** **PGE₂** due to its **metabolism** in **lungs**

Question 47

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

Answer 47

- Synthetic **PGE1** similar to misoprostol for **parenteral** administration - **Maintains PDA**

Question 48

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

Answer 48

- **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

Question 49

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

Answer 49

- **Pyrexia** (fever) - **HYPO**tension - **Tachycardia** - **Apnea**

Question 50

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

Answer 50

- **Poor eating**, which leads to **poor growth** - **Sweating** w/ **crying** or **eating** - **Persisten fast breathing** or **breathlessness** - **Easy tiring** - **Rapid HR**

Question 51

What are the drugs used for closure of a PDA?

Answer 51

- Classically **indomethacin** - But now often **ibuprofen**

Question 52

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

Answer 52

- **↓ kidney function** - Oliguria - Edema - Mild HTN

Question 53

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

Answer 53

- _Oral_ **α-methyldopa** (α₂-agonist) - _Oral_ **labetolol** (α/β-blocker)

Question 54

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

Answer 54

- **_Parenteral_** **labetolol** (α/β-blocker) - **Hydralazine** (arterial vaso**dilator**) - **Sodium nitroprusside** (arterial + venous vaso**dilator**)