Gynecologic and Obstetric

Pharmacology I:
Drugs for Labor and delivery

Tanchun Wang Ph.D

Tanchun.wang4@touro.edu

2017 Tanchun Wang. Reproduction for non-profit educational use by TouroCOM students
permitted, all other rights reserved. Distribution and/or duplication for
1 any other purposes
 Learning Objectives

1. Review purpose of Tocolytic therapy. Identify

drugs used for preterm labor. Review the MOA,
clinical application and major toxicities.

2. Describe treatment principles for drug

induced cervical ripening and Labor induction.
Identify drugs and review the MOA, clinical
application and major toxicities.

3. Review principles for drug treatment for

Preeclampsia and Eclampsia. Identify drugs and
review the MOA, toxicity and their clinical
applications.
2
 Objective 1

Review purpose of Tocolytic therapy. Identify

drugs used for preterm labor. Review the
MOA, clinical application and major
toxicities.

3
 Preterm labor and Tocolytic therapy
Tocolytics (anti-contractions/labor
suppressants): medications used to suppress
preterm labor when delivery would result in
premature birth.

Preterm labor: Cervical changes and uterine

contractions between 20-37 weeks gestation.

Purpose of Tocolytic therapy:

1. Postpone delivery at least 48 hours to allow the
maximum effect of antenatal steroid
administration.
2. Allow transportation of mother to facilities that
are adequately equipped for labor and delivery.
 Myometrium contraction during labor
prostaglandins
oxytocin

MOA of Tocolytics:
Ferguson reflex
1. 2-agonistcAMP(-)MLCK(-)contraction
2. Ca2+channel blockers
3. Mg2+ 5
Major Tocolytic drugs

Terbutaline
Magnesium sulfate
Nifedipine
Indomethacin

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7
 Objective 2

Describe treatment principles for drug

induced cervical ripening and Labor
induction. Identify drugs and review the
MOA, clinical application and major
toxicities.

8
 Labor induction

Labor induction: the artificial initiation of

Dr. Edward H. Bishop
labor prior to its spontaneous onset.

Indications for labor induction: Beyond 42

weeks gestation, Pregnancy induced
hypertension (~80% of induction) and
Prelabor rupture of membranes.

When Bishop score is less than 6, a cervical

ripening drug it is recommended before labor
induction.
 Cervical ripening and Labor
induction

Physiology MOA:

1. Cervical ripening: prostaglandins E2 and

F2collagenase, elastase in the
cervixcervix thinning and dilation

2. Oxytocin secreted by posterior

pituitaryFerguson reflexPGE2, Oxytocin
binds to Gq coupled receptors initiates
uterine contraction
 Cervical ripening and Labor
induction

Physiology MOA:

1. Cervical ripening: prostaglandins E2 and

F2collagenase, elastase in the cervix
cervix thinning and dilation

2. Oxytocin secreted by posterior

pituitaryFerfuson reflexPGE2, Oxytocin
bind to Gq coupled receptors initiate
uterine contraction
Cervical ripening and Labor induction

Prostaglandins:
Dinoprostone (PGE2)
Misoprostol (PGE1)
Carboprost (PGF2)

Oxytocin

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Prostaglandins
MOA:
1. activities of collagenasecervial ripening.
2. Potentiate Ca2+ channel and intracellular
Ca2+ level uterine contraction

Rx:
1. Dinoprostone (PGE2): only available
prostaglandin in U.S for labor induction.
2. Misoprostol(PGE1): Labor induction,Not available
in U.S.
3. Carboprost (PGF2):Induction of labor in cases of
intrauterine fetal death/terminate pregnancies.
Use to control postpartum hemorrhage
SE:
Uterine Hyperstimulation. 13
Oxytocin

MOA:
Binds to oxytocin receptor (Gq coupled)
intracellular Ca2+ concentrationmyometrial
contraction. Stimulates placenta and
endometrium PG production (Ferguson reflex)

Rx: Labor induction and treat postpartum

hemorrhage.

. SE: Uterine hyperstimulation. Water

intoxication: hyponatremia, confusion, coma.
Fetal distress and Uterine rupture.

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Practice Question 1: A 27-year-old female is
pregnant for the first time at her 39th week of
gestation. She has been in labor for the past 3
hours, her cervix has remained 90% effaced and
8 cm dilated. There is no sign of fetal distress but
her contractions are poor. A drug is given to the
patient increase uterine contractility. The drug
mimics an endogenous peptide hormone and
works by binding to Gq coupled receptors. Which
of the following drugs fits the description?

A. Dinoprostone
B. Misoprostol
C. Carboprost
D. Terbutaline
E. Oxytocin
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Practice Question 1: A 27-year-old female is
pregnant for the first time at her 39th week of
gestation. She has been in labor for the past 3
hours, her cervix has remained 90% effaced and
8 cm dilated. There is no sign of fetal distress but
her contractions are poor. A drug is given to the
patient increase uterine contractility. The drug
mimics an endogenous peptide hormone and
works by binding to Gq coupled receptors. Which
of the following drugs fits the description?

A. Dinoprostone
B. Misoprostol
C. Carboprost
D. Terbutaline
E. Oxytocin
16
 Objective 3

Review principles for drug treatment for

Preeclampsia and Eclampsia. Identify drugs
and review the MOA, toxicity and their
clinical applications.

17
 Preeclampsia and Eclampsia

Preeclampsia: Gestational hypertention

(developed after 20 weeks gestation) with
proteinuria (over 300mg/day).

Preeclampsia may progress to Eclampsia

(seizure superimposed on Preeclampsia).
Eclampsia is a medical emergency.

Ca2+ supplements (1g/day) and low dose

aspirin(75-81 mg/day) significantly decrease the
risk of developing Preeclampsia.

Drug therapy is indicated for patient with BP

above 160/110 mm Hg.
Akhigbe RE., Niger Med J 2014 Jan; 55(1): 86.
 Drug treatment for Preeclampsia
and Eclampsia
Hydralazine+Labetalol
Methyldopa
Nifedipine
Magnesium sulfate

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 Antihypertension drugs and Pregnancy
MOA Antihypertension Agents Indication in Pregnancy

ACEI/ARBs, -Prils, sartan, Aliskiren Contraindication

renin inhibitor
Beta/alpha olol- selective Labetalol and
blockers Labetalol-1 and block Methyldopa are preferred
Methyldopa-2 agonist
Ca2+ channel -dipine Ca2+ channel in Nifedipine is commonly
blockers vascular smooth muscle used
Direct Hydralazine, Nitroprusside Hydralazine is preferred
vasodilators Diazoxide
Diuretics Thiazides Can be used

Magnesium sulfate: DOC for Preeclampsia, risk of progress to Eclampsia

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 Magnesium sulfate
Glutamate
MOA:
1. Anticonvulsant: Blocks NMDA receptor
seizure threshold and block the effect of
GlutamateLimits massive neuronal
depolarization.
NMDA

2. Vasodilation:Blocks L-type voltage gated

Ca2+ channelvascular smooth muscle
relaxation. Increases endothelium production of
PGI2 and NO

Rx: DOC for Preeclampsia and eclampsia

AG Euser et al., Stroke. 2009 Apr; 40(4): 11691175.

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 Hydralazine and Labetalol
MOA:
Hydralazine: Direct vasodilator in arteries and
arteriolesdramatic in BP.
Hydralazine, Labetalol: and nonselective blockerCO, HR,
Isoniazid,
Procainamide and PVRin BP

Rx: Preeclampsia/Hypertension in pregnancy

. SE:
Hydralazine: hypotension, tachycardia. Lupus-like
syndrome especially for slow acetylators

22
Methyldopa
MOA:
Activate 2 adrenergic receptors in CNS
sympathetic outflowin BP

Rx: Preeclampsia/Hypertension in pregnancy

. SE:
Direct coombs-positive hemolytic anemia

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Practice Question 2: A 25-year-old pregnant female
at 26 weeks gestation was hospitalized with new
onset of seizure. On physical exam, the patient
shows significant amount of edema of the upper
extremities and face. She has high blood
pressure reading of 165/110 mmHg. A 24 hour
urine sample analysis shows proteinuria. Which
of the following drug therapy would be most
appropriate for this patient?

A. Diazepam
B. Phenytoin
C. Valproic acid
D. Magnesium sulfate
E. Lisinopril 24
Practice Question 2: A 25-year-old pregnant female
at 26 weeks gestation was hospitalized with new
onset of seizure. On physical exam, the patient
shows significant amount of edema of the upper
extremities and face. She has high blood
pressure reading of 165/110 mmHg. A 24 hour
urine sample analysis shows proteinuria. Which
of the following drug therapy would be most
appropriate for this patient?

A. Diazepam
B. Phenytoin
C. Valproic acid
D. Magnesium sulfate
E. Lisinopril 25
 Summary

Tocolytics Cervical Preeclampsia and

ripening/Labor Eclampsia
induction
Terbutaline Dinoprostone Hydralazine/
Magnesium Oxytocin Labetalol
sulfate Mythyldopa
Nifedipine Nifedipine
Indomethacin Magnesium
sulfate

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 Review of Objectives

1. Review purpose of Tocolytic therapy. Identify

drugs used for preterm labor. Review the MOA,
clinical application and major toxicities.

2. Describe treatment principles for drug

induced cervical ripening and Labor induction.
Identify drugs and review the MOA, clinical
application and major toxicities.

3. Review principles for drug treatment for

Preeclampsia and Eclampsia. Identify drugs and
review the MOA, toxicity and their clinical
applications. 27