Drugs acting on Uterus

Question 1

• Drugs used for cervical ripening are

Answer 1

prostaglandins

dinoprostone and misoprostol

Question 2

DINOPROSTONE (PGF2) AND MISOPROSTOL (PGE1)

MOA

Answer 2

• Dinoprostone and misoprostol ripen the cervix by several
mechanisms
• Additionally, they stimulate uterine contractions
• They are administered to promote cervical ripening in
women with unfavorable cervixes
• This alone initiates labor in many women, and REMOVES the need for oxytocin

Question 3

DINOPROSTONE analog of?
ADMIN?

MISOPROSTOL analog of?
admin?

Answer 3

Dinoprostone
• Synthetic preparation of PGE2
• Available as vaginal insert, and cervical gel
Misoprostol
• PGE1 analog
• Can be administered intravaginally, orally or sublingually

Question 4

PROSTAGLANDINS: AE

Answer 4

• Tachysystole
• Fever
• Chills
• Vomiting
• Diarrhea

Question 5

what is the prefered agent for labor induction?

Answer 5

• Oxytocin is the preferred pharmacologic agent for
inducing labor when the cervix is favorable or ripe
• A ripening agent should be used before oxytocin in
women with unfavorable cervixes

Question 6

OXYTOCIN MOA

PK?

Answer 6

• Oxytocin acts via G protein coupled receptors
• Activation of oxytocin receptors leads to activation of
phospholipase C and release of calcium from the SR
• Activation of oxytocin receptors also activates voltagegated
Ca2+ channels
• Ca2+ activates MLCK resulting in myometrial contraction
• Oxytocin also increases prostaglandin synthesis, which
further stimulates uterine contractions

PK:
IV for labor induction
IM

Question 7

OXYTOCIN AE

Answer 7

• Serious toxicity is rare
• Excessive stimulation of uterine contractions before
delivery can cause fetal distress, placental abruption, or
uterine rupture
• High concentrations of oxytocin can activate vasopressin
receptors and thus cause excessive fluid retention, or
water intoxication, leading to hyponatremia, heart failure,
seizures, and death

Question 8

oxytocic drugs that manage postpartum hemorrhage?

Answer 8

• Oxytocin
• Ergot alkaloids
• Prostaglandins

Question 9

First-line treatment for postpartum hemorrhage

Answer 9

OXYTOCIN
iv OR im

• also ERGOT ALKALOIDS, PROSTAGLANDINS

Question 10

ERGOT ALKALOIDS:
METHYLERGONOVINE
what is it?

Answer 10

• Partial agonist at a-adrenergic receptors and some
serotonin receptors
• The sensitivity of the uterus to the stimulant effects of
ergot alkaloids increases dramatically during pregnancy

Question 11

METHYLERGONOVINE AE

CI

Answer 11

• Severe adverse effects are minimal
• Adverse reactions may include:
• Hypertension
• Headache
• Nausea
• Vomiting
• Chest pains

Contraindications:
• Angina pectoris
•Myocardial infarction
• Pregnancy
• Cerebrovascular accident
• Ischemic attack
• Hypertension

Question 12

PROTAGLANDINS
analogs?
PK?

Answer 12

Carboprost Tromethamine
• PGF2alpha analog
• Given IM
Misoprostol
• PGE1 analog
• Given vaginally or orally

Question 13

how do you manage preterm labor?

Answer 13

•Management of preterm labor typically includes bed rest,

tocolytics and glucocorticoids (if gestational age is

Question 14

whats the leading cause of neonatal mortality?

Answer 14

• Preterm birth is the leading cause of neonatal mortality in
the US

Question 15

whats the role of Uterine Relaxants (TOCOLYTICs)

Answer 15

• The primary purpose of tocolytic therapy is to delay delivery to allow glucocorticoids given to the mother to achieve their maximum effect
• Glucocorticoids accelerate maturation of fetal lungs and
decrease risk of neonatal respiratory distress syndrome,
intracranial bleeding, and mortality

Question 16

UTERINE RELAXANTS (TOCOLYTICS)

Answer 16

Most commonly used
-magnesium sulfate, 
-indomethacin,
- nifedipine
• Atosiban
• beta2-adrenoceptor agonists
• There is no tocolytic of first choice

Question 17

MAGNESIUM SULFATE MOA

AE

Answer 17

•Widely used as the primary tocolytic agent
• It has similar efficacy to terbutaline with far better
tolerance
•Magnesium sulfate uncouples excitation-contraction in
myometrial cells through inhibition of cellular action potentials

AE:
• The mother should be monitored for toxic effects, such as
respiratory depression or cardiac arrest
•Magnesium sulfate (small molecule) crosses the placenta and may lead to
respiratory and motor depression of the neonate

Question 18

INDOMETHACIN

USE IN LABOR?

Answer 18

• Prostaglandins stimulate uterine contractions during
normal labor
• Therefore NSAIDs are used to delay preterm labor
• Indomethacin is the main NSAID for this use

Question 19

INDOMETHACINE AE

Answer 19

• Infrequent maternal side effects
• Indomethacin crosses the placenta and can cause
oligohydraminos due to a decrease in fetal renal blood
flow if used for more than 48 hours
• Indomethacin can also cause premature closure or
constriction of the ductus arteriosus
• This effect is more common after 32 weeks’ gestation:
indomethacin is therefore not recommended after 32
weeks

Question 20

NIFEDIPINE

MOA

Answer 20

• Calcium channel blocker
• Blocks entry of Ca2+ into myometrial cells, thereby
inhibiting contractility
• Effective and safe
• Compared with other tocolytics nifedipine is associated
with a more frequent successful prolongation of pregnancy
• Adverse effects include maternal tachycardia, palpitations,
flushing, headaches, dizziness, and nausea

Question 21

ATOSIBAN moa

Answer 21

• Competitive antagonist at oxytocin receptors

* Not available in the US

Question 22

b2-ADRENOCEPTOR AGONIST: MOA

Answer 22

• Activation of B2-adrenoceptors on myometrium activates
adenylyl cyclase. This causes a rise in cAMP which in turn
activates PKA
• PKA phosphorylates smooth-muscle myosin light chain
kinase (SmMLCK)
• Phosphorylation of SmMLCK results in a lower affinity of
SmMLCK for the Ca2+-calmodulin complex
• As a result, SmMLCK dose not phosphorylate myosin,
and the myometrial smooth muscle relaxes

Question 23

b2-ADRENOCEPTOR AGONIST: AE

Answer 23

• Palpitations, tremor, nausea, vomiting, nervousness,
anxiety, chest pain, shortness of breath, hyperglycemia,
hypokalemia, and hypotension
• Serious complications: pulmonary edema, cardiac insufficiency, arrhythmias, myocardial ischemia, and
maternal death

Black Box Warning and Contraindication to the
terbutaline label to warn about the risk of use for preterm
labor
• The decision was based on reports of deaths and serious
adverse reactions following administration of terbutaline to
pregnant women
• The use of injectable terbutaline should be limited to a
maximum of 72 hours to treat preterm labor
• Oral terbutaline should not be used to prevent or treat preterm labor