Tocolytic Therapy for Acute Preterm Labor: Cook

Question 1

Which racial demographic is 2x as likely to have a preterm birth as white women?

Answer 1

African Americans

Question 2

What is the leading cause of perinatal morbidity/mortality?

Answer 2

Preterm birth

Question 3

How do microorganisms in the upper genital tract initiate preterm labor?

Answer 3

Activate immune response—> cytokines and prostaglandins —> uterine contractions and weakening of amniotic membranes

Question 4

If tocolytics have NOT been shown to decrease the chance of preterm birth, what are they good for?

Answer 4

They have been shown to temporarily inhibit uterine contractions.

Question 5

What is the primary goal of tocolytics?

Answer 5

::Give time to administer glucocorticoids to reduce the risk of prematurity related complications such as respiratory distress syndrome, necrotizing enterocolitis, and intraventricular hemorrhage.
::Secondarily, allows time to transport mother to a facility capable of providing more advanced neonatal care.

Question 6

When do you cease tocolytic therapy?

Answer 6

When your primary/secondary goals have been met and the pros of tocolytic tx are outweighed by drug exposure risk. Generally by week 34 of gestation.

Question 7

The MOA of Mg sulfate as a tocolytic is not completely understood. What DO we know about its action?

Answer 7

Functions at the extracellular and intracellular levels by decreasing the availability of Ca2+ by blocking membrane and intracellular Ca2+ channels, which decreases myometrial contractility.

Question 8

Is Mg sulfate shown to be more efficacious than other tocolytics, given that it is the most widely used tocolytic even today?

Answer 8

No.

Question 9

When is Mg sulfate contraindicated?

Answer 9

Renal insufficiency (excreted by kidneys) and myasthenia gravis.

Question 10

What are the common (up to 60% of pts) side effects of Mg sulfate?
What is the most common first sign of toxicity?

Answer 10

flushing, nausea, blurry vision, h/a, lethargy, HypoT, pulm. edema.
Loss of patellar reflexes is the first sign of toxicity, followed by decr. urine output.

Question 11

What are some possible risks to the fetus caused by Mg sulfate?

Answer 11

Depressed GI and respiratory function.

Question 12

So if Mg sulfate is not more efficacious than other tocolytics, why does anyone use it?

Answer 12

Neuroprotective. Reduces risk of cerebral palsy and gross motor deficit by almost 50% in preterm births.

Question 13

Why were Beta mimetics pulled from the market for use in the US as tocolytics?

Answer 13

Maternal cardiotoxicity and death.

Question 14

In a word, how do beta mimetics work to reduce uterine contractility?

Answer 14

beta-receptor adrenergic agonists, relaxing smooth muscle, including the myometrium. Binding of the receptor initiates a cascade including adenylyl cyclase and protein kinase. This cascade decreases the availability of intracellular calcium and the activity of myosin light-chain kinases, thus suppressing myometrial contractility.

Question 15

Which beta mimetic is used in the US most often as a tocolytic, off label?
What are its negative side effects in the mother?
When are beta-mimetics contraindicated?

Answer 15

Terbulaline.
SFX: tachycardia, tremor, dyspnea, chest discomfort, palpitations, hyperglycemia.
Contraindications: known cardiac disease, poorly controlled diabetes, meternal HR > 120bpm, significant symptoms such as chest pain/dyspnea.

Question 16

What tocolytic is associated with decreased NICU admissions and shorter NICU stays, decreased rates of respiratory distress, intraventricular hemorrhage, and necrotizing enterocolitis.

Answer 16

Nefidepine (calcium channel blocker)

Question 17

Which tocolytic has the least severe side effects, by comparision to the others?
What are its common and rare side effects?

Answer 17

Nefidepine
SFX: flushing, nausea, h/a, dizziness, and palpitations.
Rare but severe: pulm edema, hypoxia, MI, a-fib, severe hypotension.
Monitor for hypotension to prevent fetal hypoxia.

Question 18

Administer CCBs with caution in conjunction with this tocolytic to avoid cardiovascular collapse.

Answer 18

Mg Sulfate

Question 19

How do prostaglandins induce labor?

Answer 19

Form gap junctions in myometrium that increase intracellular calcium and facilitate myometrial contractility.

Question 20

What are the fetal limitations of using indomethacin (non-selective COX inhibitor)

Answer 20

Prolonged use may result in premature restriction of fetal ductus arteriosus.

Question 21

How does atosiban work?
Is it efficacious?
Is it better than the other tocolytics?
Side effects?

Answer 21

A oxytocin receptor antagonist, it blocks oxytocin from binding to its receptor and downregulates the number of receptors, thus decreasing myometrial contractility.
It works, compared to placebo, but not better than the other tocolytics. Does not improve M&M in the fetus compared to other tocolytics.
Limited side effects, limited placental transport for fetus.

Question 22

What is the most common drug used for the induction of labor?
What are its side effects/limitations?

Answer 22

Oxytocin (Pitocin)
Can cause overstimulation of the myometrium leading to exhaustion of the muscle and inability to control postpartum hemorrhage.
Antidiuretic effect can also cause water intoxication and hyponatremia.

Question 23

What is considered the most important indicator in the success of labor induction?

Answer 23

Cervical ripening

Question 24

How do prostaglandins induce labor?

Answer 24

Block progesterone (maintains pregnancy) and cause a local inflammatory response. Synthetic PGE2 also causes cervical ripening. 
Soften cervix.

Question 25

List the 3 prostaglandin preparations in use to soften the cervix.
What are their limitations to use with oxytocin?

Answer 25

Dinoprostone
Carboprost tromethamine
Misoprostol- most rapid action

Limitations:
::Don’t use them when using oxytocin. Wait 6 hrs before using oxytocin.
::Not recommended for use when mom has uterine scars from previous cesarean birth.