Drugs used in Pregnancy (2)

Dr. Heba Alshaeri

[email protected]
Office:2-61

MSc in Women’s Health Nursing Advanced Pharmacology

1st Year MSNW 215
(2023-2024)
 Students Learning Outcomes
• Recognize the drugs used in pregnancy in the
following conditions:
üHypertension
üHematological disorders
üAsthma
üEpilepsy
üDiabetes mellitus
• Discuss the antimicrobials therapy that can be used
during the pregnancy.
• Explain the mechanism of action, indications,
contraindications and side effects.
Drugs used in Epilepsy
Epilepsy (also called epileptic seizure disorder) is a chronic brain disorder
characterized by recurrent (≥ 2) seizures that are unprovoked (ie, not related to
reversible stressors) and that occur > 24 hours apart.

A seizure is an abnormal, unregulated electrical discharge that occurs within

the brain’s cortical gray matter and transiently interrupts normal brain
function.
 Antiepileptic Drugs
• The dose of antiseizure drugs may have to be increased during
pregnancy to maintain therapeutic levels.
• If women get enough sleep and antiseizure drug levels are kept in the
therapeutic range, seizure frequency does not usually increase during
pregnancy, and pregnancy outcome is good; however, risks of the
following are slightly increased:
• Preeclampsia
• Fetal growth restriction
• Stillbirth
• These risks may be related to the seizure disorder as well as use of
antiseizure drugs.
 Mechanisms of Antiepileptic Drugs
• Antiepileptic drugs (AEDs) are believed to suppress the formation or
spread of abnormal electrical discharges in the brain.
The classic AEDs actions via three mechanisms:
(1) inhibition of the sodium or calcium influx responsible for neuronal
depolarization,
(2) enhancing inhibitory γ-aminobutyric acid (GABA) neurotransmission,
and
(3) inhibition of excitatory glutamate neurotransmission.

Antiseizure medications suppress seizures but do not “cure” or “prevent” epilepsy.

 Antiepileptic Drugs
• Carbamazepine
• Levetiracetam
• Lamotrigine
• Phenobarbital
• Phenytoin
• Valproate

Clinicians should use the lowest possible dose of antiseizure

drugs and as few different antiseizure drugs as possible.
 Carbamazepine

• Hemorrhagic disease of the newborn

àwhich can be prevented if pregnant women take vitamin K by mouth
every day for a month before delivery or if the newborn is given an
injection of vitamin K soon after birth.

• Risk of congenital malformations including neural tube defects

 Lamotrigine

• No substantial increased risk of birth defects (dosage up to 600

mg/day).
• Compatible with with pregnancy

Levetiracetam
• Minor bone abnormalities seen in animals.
• No substantial increased risk in humans.
• Compatible with with pregnancy.
 Phenobarbital

• Increased risk of birth defects, including neural tube defects (such as

spina bifida).
• Bleeding problems in the newborn.

• Taken during pregnancy, phenobarbital may reduce the physiologic

jaundice neonates commonly have, àbecause the drug induces
neonatal hepatic conjugating enzymes.
 Phenytoin
• Congenital malformations (eg, cleft lip, genitourinary defects such as
hypospadias and cardiovascular defects).
• Bleeding problems in the newborn.

**Fetal Hydantoin Syndrome (FHS) include IUGR with small head

circumference, dysmorphic facies, orofacial clefts, cardiac defects, and
distal digital hypoplasia with small nails

• Persistent risk of congenital malformations despite folic acid

supplementation.
 Valproic Acid

• Major congenital malformations.

(eg, neural tube defects such as meningomyelocele; cardiac,
craniofacial, and limb defects).

• Persistent risk of congenital malformations despite folic acid

supplementation.
 Antiepileptic Drugs
• Risk of hemorrhagic disease of the newborn (erythroblastosis
neonatorum) may be increased by in utero exposure to certain
antiseizure drugs (eg, phenytoin, carbamazepine, phenobarbital);
however, if prenatal vitamins with vitamin D are taken and vitamin K
is given to the neonate, hemorrhagic disease is rare.
• All antiseizure drugs increase the need for supplemental folic acid;
à 4 mg is given orally once a day.
Ideally, it is started before conception.
• Taking folic acid supplements before conception helps reduce risk of
neural tube defects.
Drugs used in Diabetes Mellitus
(DM)
 Types of Diabetes Mellitus

The ADA recognizes four clinical

classifications of diabetes:

Type 1 diabetes Type 2 diabetes Diabetes due to other

(insulin-dependent (noninsulin-dependent Gestational diabetes causes such as genetic
diabetes mellitus) diabetes mellitus) defects or medications.
 Diabetes During Pregnancy

• Gestational diabetes.
It is more common among the following:
• Obese women
• Women with a family history of diabetes
• It will increase fetal and maternal morbidity and mortality.
• Neonates are at risk of respiratory distress
hypoglycemia, hypocalcemia, hyperbilirubinemia, polycythemia, and
hyperviscosity.
Cont..
Poor control of preexisting (pregestational) or gestational diabetes during
organogenesis (up to about 10 weeks gestation) increases risk of the following:
• Major congenital malformations
• Spontaneous abortion
Poor control of diabetes later in pregnancy increases risk of the following:
• Fetal macrosomia (usually defined as fetal weight > 4000 grams or > 4500 grams
at birth)
• Preeclampsia
• Shoulder dystocia
• Cesarean delivery
• Stillbirth
üGestational diabetes can result in fetal macrosomia even if blood glucose is kept
nearly normal.
 Treatment of Diabetes Mellitus in
Pregnancy
• Close monitoring
• Tight control of blood glucose
• Management of complications

Preconception counseling and optimal control of diabetes before,

during, and after pregnancy minimize maternal and fetal risks, including
congenital malformations.
To minimize risks, clinicians should do all of the
following:
• Involve a diabetes team (eg, physicians, nurses, nutritionists, social
workers) and a pediatrician.

• Promptly diagnose and treat complications of pregnancy, no matter

how trivial

• Plan for delivery and have an experienced pediatrician present

• Ensure that neonatal intensive care is available

During pregnancy
• Women with type 1 or 2 should monitor their blood glucose levels at
home. During pregnancy, normal fasting blood glucose levels are
about 76 mg/dL (4.2 mmol/L).

Goals of treatment are:

• Fasting blood glucose levels at < 95 mg/dL (< 5.3 mmol/L)
• 2-hour postprandial levels at ≤ 120 mg/dL (≤ 6.6 mmol/L)
• No wide blood glucose fluctuations
• Glycosylated hemoglobin (HbA1c) levels at < 6.5%
 Insulin
• Insulin is the traditional first-choice drug for blood sugar control
during pregnancy
à because it cannot cross the placenta and provides more predictable
glucose control.
• It is used for types 1 and 2 diabetes and for some women with
gestational diabetes.
• Human insulin is used if possible because it minimizes antibody
formation.
• Insulin antibodies cross the placenta, but their effect on the fetus is
unknown.
 Types of Insulin

Intermediate- Slow, long

Rapid acting Short acting acting acting
(lispro) (regular)
(NPH) (glargine)

*Dosage regimens must be individualized.

**Regular insulin may also be given by I.V. infusion
Types of Insulin
Cont..
• In some women with long-standing type 1 diabetes, hypoglycemia
does not trigger the normal release of counterregulatory hormones
(catecholamines, glucagon, cortisol, and growth hormone)àtoo
much insulin can trigger hypoglycemic coma without premonitory
symptoms.

• All pregnant women with type 1 should have glucagon kits and be
instructed (as should family members) in giving glucagon if severe
hypoglycemia (indicated by unconsciousness, confusion, or blood
glucose levels < 40 mg/dL [< 2.2 mmol/L]) occurs.
Oral Hypoglycemic Drugs
• Metformin is being used to manage diabetes in
pregnant women because of the ease of
administration (pills compared to injections), low cost,
and single daily dosing.

• Several studies have shown that metformin is safe

during pregnancy and that it provides control
equivalent to that of insulin for women with
gestational diabetes.

• It cause neonatal hypoglycemia

Cont..
• For women with type 2 diabetes before pregnancyà insulin is most
often preferred.

• Oral hypoglycemics taken during pregnancy may be continued

postpartum during breastfeeding, but the infant should be closely
monitored for signs of hypoglycemia.
 Management of Complications
• Retinopathy requires that an ophthalmologic examination be done every
trimester.
• If proliferative retinopathy is noted at the first prenatal visit,
photocoagulation should be used as soon as possible to prevent
progressive deterioration.

• Nephropathy, particularly in women with renal transplants, predisposes to

gestational hypertension.
• Risk of preterm delivery is higher if maternal renal function is impaired or if
transplantation was recent.
• Prognosis is best if delivery occurs ≥ 2 years after transplantation.
Cont..
• Congenital malformations of major organs are predicted by elevated
HbA1c levels at conception and during the first 8 weeks of pregnancy.
• If the level is ≥ 8.5% during the 1st trimester, risk of congenital
malformations is significantly increased, and targeted
ultrasonography and fetal echocardiography are done during the 2nd
trimester to check for malformations.
• If women with type 2 diabetes take oral hypoglycemic drugs during
the 1st trimester, fetal risk of congenital malformations is unknown
Labor and delivery
Timing of delivery depends on fetal well-being.
• Women are told to count fetal movements during a 60-minute period
daily (fetal kick count) and to report any sudden decreases to the
obstetrician immediately.
• Antenatal testing is begun at 32 weeks; it is done earlier if women
have severe hypertension or a renal disorder or if fetal growth
restriction is suspected.
Cont..
Type of delivery is usually spontaneous vaginal delivery at term.
• Risk of stillbirth and shoulder dystocia increases near term.
• Thus, if labor does not begin spontaneously by 39 weeks, induction is
often necessary.
• Dysfunctional labor, fetopelvic disproportion, or risk of shoulder
dystocia may make cesarean delivery necessary.
Cont..
• Blood glucose levels are best controlled during labor and delivery by
a continuous low-dose insulin infusion.
• If induction is planned, women eat their usual diet the day before and
take their usual insulin dose.
• On the morning of labor induction, breakfast and insulin are withheld,
baseline fasting plasma glucose is measured, and an IV infusion of
5% dextrose in 0.45% saline solution is started at 125 mL/hour, using
an infusion pump.
• Initial insulin infusion rate is determined by capillary glucose level.
Postpartum

• After delivery, loss of the placenta, which synthesizes large amounts

of insulin antagonist hormones throughout pregnancy, decreases
the insulin requirement immediately.

• Women with gestational diabetes and many of those with type 2

require no insulin postpartum.

• For women with type 1, insulin requirements decrease dramatically

but then gradually increase after about 72 hours.
Cont..
• During the first 6 weeks postpartum, the goal is tight glucose control.

• Glucose levels are checked before meals and at bedtime.

• Breastfeeding is not contraindicated but may result in neonatal

hypoglycemia if oral hypoglycemics are taken.

• Women who have had gestational diabetes should have a 2-hour oral
glucose tolerance test with 75 g of glucose at 6 to 12 weeks
postpartum to determine whether diabetes has resolved.
 Infectious Disease in Pregnancy
• Most common maternal infections (eg, UTIs, skin and respiratory tract
infections) are usually not serious problems during pregnancy.

• Maternal infections that can damage the fetus include:

cytomegalovirus infection, herpes simplex virus infection, rubella,
toxoplasmosis, hepatitis B, and syphilis.

• Give antibacterials to pregnant patients only when there is strong

evidence of a bacterial infection and only if benefits of treatment
outweigh risk, which varies by trimester.
Activity

Group Discussion
about the
Antibacterials J
Antibacterials
 Antibacterials
1-Aminoglycosides such as Gentamicin, Amikacin.
• These antibiotics bind to the 30S ribosome, thereby inhibiting bacterial
protein synthesis.
• It may be used during pregnancy to treat pyelonephritis but treatment
should be carefully monitored to avoid maternal or fetal damage.
• Ototoxicity à resulting in deafness

2-Cephalosporins such Ceftriaxone.

• They inhibit enzymes in the cell wall of susceptible bacteria, disrupting cell
wall synthesis.
• are generally considered safe.
Cont..
3-Chloramphenicol
• Even in large doses, does not harm the fetus; however, neonates cannot
adequately metabolize chloramphenicol, and the resulting high blood
levels may lead to circulatory collapse (gray baby syndrome).

4-Fluoroquinolones such as Ciprofloxacin.

• Are not used during pregnancyà they tend to have a high affinity for bone
and cartilage and thus may have adverse musculoskeletal effects
(arthralgia).
 Cont..
5-Macrolides such as Azithromycin are generally considered safe.
• Binding to the 50S subunit of the ribosome, they inhibit bacterial protein
synthesis.

6-Metronidazole use during the 1st trimester used to be considered

controversial; however, in multiple studies, no teratogenic or mutagenic
effects were seen.

7-Nitrofurantoin is not known to cause congenital malformations.

• It is contraindicated near term because it can cause hemolytic anemia in
neonates.
Cont..
8-Penicillins such as amoxicillin/clavulonic acid are generally considered safe.
• They destroy the cell wall of some bacteria.
•
9-Sulfonamides are usually safe during pregnancy.
• However, long-acting sulfonamides cross the placenta and can displace bilirubin
from binding sites.
• These drugs are often avoided after 34 weeks gestation because neonatal
kernicterus is a risk.

10- Tetracyclines such as Doxycycline

• Cross the placenta and are concentrated and deposited in fetal bones and teeth,
where they combine with calcium and impair development.
• They are not used from the middle to the end of pregnancy.
References
The Teratogen Information System
• https://deohs.washington.edu/teris/

• https://www.msdmanuals.com/home/women-s-health-issues/pregnancy

• Linda E. McCuistion, et al, (2021). Pharmacology: A Patient-centered Nursing, 10th

Edition, Elsevier Inc.

• Gerald G. Briggs , et al, (2015). A Reference Guide to Fetal and Neonatal Risk Drugs
in Pregnancy and Lactation, Eleventh Edition, Wolters Kluwer.

• Bonham CA, Patterson KC, Strek ME: Asthma outcomes and management during
pregnancy. Chest 153(2):515-527, 2018. doi:10.1016/j.chest.2017.08.029