Parturition and Obstetric Pharmacology - Menon

Question 1

What is a tocolytic drug? Name (7) classes of tocolytics.

Answer 1

Tocolytic = used to inhibit or arrest uterine contractions

1. Progestins (prophylaxis)
2. Andrenergic (beta-2) receptor agonists
3. MgSO4
4. Ca channel blockers
5. COX inhibitors
6. Oxytocin receptor antagonists
7. NO donors

Question 2

Which beta agonist is often used as a tocolytic agent? What are its main side effects?

About how long can it be used before it becomes ineffective?

Answer 2

Terbutaline

AE: tachycardia, hypotension, pulmonary edema

Only effective for 48 hours

Question 3

What calcium channel blocker is commonly used as a tocolytic agent?

Answer 3

Nifedipine

Question 4

What is the tocolytic mechanism of action of MgSO4?

Give a major contraindication (hint: calcium)

Answer 4

Calcium channel antagonist (probably)

Don’t use longer than 5-7 days. Hypocalcemia and fetal bone defects may occur if used longer than that

Question 5

Which COX inhibitor might be used to arrest preterm labor?

Why is this generally considered a bad idea?

Answer 5

Indomethacin

It may decrease platelets and close the ductus arteriosus. Never use in a term pregnancy.

Question 6

What is dinoprostone? Give indications and adverse effects.

What is misoprostol? Give indications and adverse effects.

Answer 6

Dinoprostone: PGE2 analog. Used to promote ripening and dilation of the cervix (induction of labor). AE: uterine hyperstimulation.

Misoprostol: PGE1 analog. Used for cervical ripening (labor induction) . Also used in the treatment of incomplete or missed abortion. AE: uterine hyperstimulation and rupture (rare)

Question 7

What is the drug of choice for induction, augmentation, and resolution of labor?

What is its half-life?

What are its main side effects?

Answer 7

oxytocin - used for induction, augmentation of labor, and post-partum hemorrhage

12-15 minutes

Antidiuretic effects (structural similarity to ADH), hypotension, and reflex tachycardia

Question 8

Name two drugs commonly used for the treatment of post-partum hemorrhage.

Answer 8

Oxytocin and Ergonovine

Question 9

How is **ergonovine **used?

What is the mechanism of action of ergonovine?

What are its adverse effects?

Answer 9

Prevention and treatment of post-partum hemorrhage and post-abortion hemorrhage.

Produces sustained contractions of uterine smooth muscle

AE: naus/vom, increased blood pressure, decreased pain threshold

Question 10

Uterine changes in pregnancy: hyperplastic or hypertrophic?

How much larger does the uterus become?

Answer 10

Both. Hyperplasia predominates early, hyperplasia predominates late.

Pre: 40-70 grams; Post: 1200 grams

Question 11

What cell-cell interaction increases in the uterus during pregnancy?

Approximately what percentage of the maternal circulation is dedicated to the gravid uterus?

Answer 11

Increased gap junctions

17% of cardiac output

Question 12

Are myometrial cells mainly under hormonal or nervous control?

Why are gap junctions important to the function of the gravid uterus?

Answer 12

Neither. They are capable of contracting spontaneously.

The myometrium needs to contract in synchrony. Gap junctions enable this.

Question 13

Describe the development of the labor phenotype. Focus on the predominant hormone before and after labor phenotype development and the effect this has on uterine makeup and function.

Answer 13

Shift from progesterone dominance to estrogen dominance:

Progesterone dominance

• Inhibition of intracellular calcium entry
• Inhibition of calcium release from the sarcoplasmic reticulum
• Membrane hyperpolarization (potassium channels)
• Inhibits expression of contraction-associated protein genes

Estrogen dominance

• Increased gap junctions (contraction synchrony)
• Increased prostaglandin and oxytocin receptor expression in myometrium

Question 14

List (4) contraction-associated-proteins (CAPs) that are upregulated in the labor phenotype

Answer 14

connexin-43 (gap junction protein)

oxytocin receptor

CRH receptor

COX-2

Question 15

What triggers labor?

Answer 15

Nobody really knows for sure but (probably multifactorial)… some theories:

• fetal adrenal glad maturity (fetal signal)
• increased maternal estrogens
• increased prostaglandins
• increase in CAPs

Question 16

Define labor

How many stages?

Answer 16

Regular contractions leading to cervical dilation over time

4 stages

Question 17

Describe the first stage of labor

Answer 17

Divided into two parts: latent phase and active phase

Latent: contration with slow cervical dilation (early)

Active: contractions with active cervical dilation (later)

Question 18

Describe the second stage of labor

Answer 18

Starts with completion of dilation. Ends with delivery of the fetus.

Question 19

Describe the third stage of labor

Answer 19

Starts after delivery of the fetus. Ends with delivery of the placenta.

Most hemorrhage occurs here.

Question 20

Describe the fourth stage of labor

Answer 20

Lasts for one hour following delivery of the placenta

Constant myometrial contraction limits blood loss

Question 21

Define preterm labor

Discuss identifiable risk factors

Answer 21

delivery between 20-37 weeks gestation

Risks:

• Infections and periodontal disease
• Smoking
• Genetics (personal history, family history)
• Cervical shortening and decreased uterine space (multiple fetuses is a major risk)
• Low pre-pregnancy weight, ethnicity, socioeconomic disadvantage

Question 22

Approximately how many weeks gestation is considered ‘viability’?

A child born at 22 weeks has approximately what chance of zero chronic morbidity?

Answer 22

24 weeks

0% (6% chance of survival overall)

Question 23

What is the leading cause of maternal mortality?

Answer 23

Post-partum hemorrhage

Question 24

Define post-partum hemorrhage in terms of blood loss

During what stage of (normal) labor does the majority of blood loss occur?

What causes the majority of hemorrhage during post-partum hemorrhage? How might we treat this?

Answer 24

>500mL blood loss after vaginal delivery

>1000mL blood loss after a cesarean delivery

Stage 3 (does staging apply during cesarean delivery?)

Stage 4: atony of the uterus leads to excessive blood loss. Rx: uterine massage (think less massage, more punching) and oxytocin/prostaglandins/ergot alkaloid. Like most problems in life, this can also be solved with drugs and violence.

Question 25

Give several risk factors for post-partum hemorrhage

Answer 25

• precipitous labor
• large fetal weight
• multifetal gestation
• polyhydramnios prolonged labor
• retained placenta
• grand multiparity
• intrauterine infection
• uterine relaxation agents

Question 26

What is the etiology of Sheehan Syndrome?

Answer 26

Hypovolemia from obstetrical blood loss leading to pituitary dysfunction and/or necrosis (due to hypoperfusion of the pituitary gland)

Symptoms vary and may be delayed - think of any/all signs of pituitary insufficiency