Drug Use During Pregnancy

And Lactation
 Pregnancy and lactation
Pregnancy is a dynamic state: mother & fetus undergo
physiologic changes that influence drug effects.

In the pregnant woman, physiologic changes alter drug

pharmacokinetics & drug effects are less predictable than in
the non pregnant state.
 Maternal – placental – fetal
circulation
Drug ingested by the pregnant women reach the fetus through the maternal
– placental – fetal circulation, which is completed about the third week
after conception.

Arterial blood pressure carries blood & drugs to the placenta.

Drugs readily cross the placenta by passive diffusion.

Placental transfer begins approximately the fifth week after conception.

Drug s enter the fetal circulation. Drug molecules are distributed in 2 ways:
Most are transported to the liver, where they are metabolised, metabolism
occurs slowly because the fetal liver is immature in quantity & quality of
drug – metabolizing enzymes.

Drug metabolized by the fetal liver are excreted by fetal kidneys into
amniotic fluid.

Excretion is slow & inefficient owing to immature development of fetal

kidneys.

Other drug molecules are transported directly to the heart, which then
distributes them to the brain & coronary arteries.

Drug enter the brain easily because the BBB is poorly developed in the
fetus.

Approximately half of the drug – containing blood is then transported

through the umbilical arteries to the placenta, where it re – enters the
maternal circulation.
Fetal growth chart
Drug effects on the fetus:
Fetus exposed to any drugs circulating in maternal blood, is
very sensitive to drug effects because it has few plasma
proteins that can bind drug molecules, & has a weak capacity
for metabolizing & excreting drugs.

Once drug molecules reach the fetus, they may cause

teratogenicity or other adverse effects.

It is most likely to occur when drugs are taken during the first
trimester of pregnancy, when fetal organs are formed.
Cont..
Drugs taken during 2nd & 3 rd trimesters, adverse effects are
usually manifested in the neonate or infant as growth
retardation, respiratory problems, infection or bleeding.

Both therapeutic & non therapeutic drugs may affect the fetus.
 Teratogens
A substance, organism, physical agents or deficiency state capable of
inducing abnormal structure or function such as:

 Gross structural abnormalities

 Functional deficiencies
 Intrauterine growth restriction
 Behavioral aberrations
 Demise
 Teratogenic Factors

 Timing of exposure
 Developmental stage during exposure
 Maternal dose and duration
 Maternal pharmacokinetics
 Genetic factors/phenotypes
 Interactions between agents
 Therapeutic drugs:
Adrenergics: oral & parentral adrenergics may inhibit uterine
contractions during labor; cause hypokalemia, hypoglycemia & pulmonary
edema in mother & hypoglycemia in the neonate.

Analgesics, opioid: use of codeine in the 1st trimester has been

associated with congenital defects; decrease uterine contractility; may
cause respiratory depression in the neonate.

Angiotensin – Converting Enzyme (ACE) inhibitors: can

cause fetal & neonatal morbidity & death; exposure in 2nd & 3rd trimester
include hypotension, neonatal skull hypoplasia, anuria, renal failure &
death.
 Cont..
Angiotensin II Receptor Blocker (ARBs): these drugs should be
discontinued as soon the pregnancy is detected.

Antianginal Agents (Nitrates): the drug lower BP & may decrease

blood supply to the fetus.

Antianxiety & Sedative – Hypnotic Agents: if taken in 1st

trimester – cause physical malformation, in labor – cause sedation,
respiratory depression, hypotonia, lethargy, tremors & sucking difficulties
in neonates.
 Cont..
Antibacterials: Aminoglycosides – are nephrotoxic & ototoxic .
 Fluoroquinolones are cotraindicated.
 Nitrofurantoin should not be used during late pregnancy because of
possible hemolytic anemia in the neonate.
 Sulfonamides should not be used in last trimester because they may cause
kernicterus in the neonate.
 Tetracyclines – contraindicated because they interfere with the
development of bone and teeth.

Antifungals: contraindicated.

Anticholinergics: scopolamine cause respiratory depression in

neonates & may contribute to neonatal hemorrhage.
 Cont..

Anticoagulants: warfarin causes fetal hemorrhage, spontaneous

abortion.

Anticonvulsants: causes physical abnormalities in their offspring.

Antidepressants: associated with teratogenicity & embryotoxicity

when given in large doses.
Antihistamines: teratogenic effects.

Antihypertensive: methyldopa decreased BP for about 48hr

hydralazine is safe & others effects are unknown.
Cont..
Antimanic agents: in neonate , causes bradycardia, cyanosis, diabetes
insipidus, hypotonia & ECG abnormalities.

Antipsychotics: can cause abnormal reflexes & jaundice in the neonate

& hypotension in the mother. E.g. Phenothiazines. Fetal effects of newer
drugs are unknown.

Aspirin (CI): it prolongs gestation, labor & antepartum & postpartum

hemorrhage in women and fetal effects include low birth weight, &
incidence of still birth & neonatal death.

Beta – adrenergic blocking agents: It may cause maternal &

neonatal bradycardia, hypoglycaemia, apnea, low birth weight. E.g
Propranolol
 Cont..
CCB: diltiazem causes fetal death, skeleton abnormalities. Fetal effects of
most of the drugs are unknown.

Corticosteroids: Systemically crosses placenta. Exposure in early

pregnancy may produce cleft palate , still births & decreased fetal size.
Inhaled corticosteroids cause less adverse effects in the fetus b/c of less
systemic absorption. Betamethasone is used to promote fetal production of
surfactant to increase lung maturity in the preterm infant.

Digoxin: Fetal toxicity & neonatal death occurred only with maternal
overdose otherwise is apparently safe for use in pregnancy. Monitoring of
serum drug levels and other parameters are essential.

Diuretics: causes fetal & neonatal jaundice, thrmbocytopenia,

hyperbilirubinemia. Like thiazides, Loop diuretics may decrease plasma
volume and blood flow to the placenta and fetus.
They are not effective in prevention or tratment of pregnancy induces
hypertension (preeclampsia).
 Cont..
Dyslipidemics (CI): HMG-CoA reductase- FDA category X drug
Cholestyramine and colestipol are considered safe as they are not
systemically absorbed.

NSAIDs (All drugs are FDA category D in the third

trimester or near delivery): avoided especially in 3rd trimester
because it can cause bleeding, intracranial bleeding, renal impairment &
failure. Ibuprofen should generally be avoided and Diclofenac is
contraindicated.
 If taken near delivery, maternal effects include delayed onset of labor &
increased risk of excessive bleeding.

Thyroid hormone: cause tachycardia in fetus, drug should not be

continued during pregnancy. Levothyroxine does not cross the placenta
and seems safe in appropriate dosages and as a replacement therapy in
hypothyroid women can be continued through pregnancy.
 Non – therapeutic drugs:

Alcohol: contraindicated. Heavy intake cause fetal alcohol syndrome.

Caffeine: high doses may cause cardiac dysrhythmias in the fetus.

Cigareete smoking: contraindicated, effects include increased fetal,

neonatal & infant mortality; decreased birth weight & length; shortened
gestation; & increased complications of pregnancy.

 Nicotine causes vasoconstriction & decreases blood flow to the fetus.

Carbon monoxide decreases the oxygen available to the fetus. Chronic
fetal hypoxia may occur.
Cont..
Cocaine: cause maternal vasoconstriction, tachycardia, hypertension,
cardiac dysrhythmias & seizures. These effect may impair fetal growth,
neurologic development during the 1st & 2nd trimester. In the 3rd trimester
increased uterine contractility, vasoconstriction & decreased blood flow in
the placenta.

Marijuana: impairs formation of DNA & RNA, also decreases oxygen

supply of mother & fetus.

Heroin: it causes pregnancy induced hypertension, 3rd trimester bleeding,

complication of labor & delivery.
 Drugs used during labor &
delivery at term

At the end of the gestation, labor usually begins spontaneously & proceeds
through delivery of the neonate.

In some instances, prostaglandins preparations are administered

intravaginally to promote cervical ripening & induce labor. for eg: prepidil,
cirvidil formulations of dinoprostone.
Oxytocics:

 it stimulates uterine contraction to initiate labor & promotes letdown of

breast milk to the nipples in lactation.

 Pitocin is a synthetic form used to induce labor at or near full – term

gestation & to augment labor when uterine contractions are weak&
ineffective.

 It also can be used to prevent or control uterine bleeding after delivery or to

complete an incomplete abortion.

 It is contraindicated for antepartum use in the presence of fetal distress ,

cephalopelvic disproportion, preterm labor, placenta previa, previous
uterine surgery, & severe preeclampsia.

 Methergine is used for management of post-partum hemorrhage related to

uterine atony.
Analgesics:

 parentral opioid analgesics are used to control discomfort & pain during
labor & delivery.

 Can cause sedation & respiratory depression in the mother & neonate.

 Meperidine causes less neonatal depression than other opioid analgesics.

 Butorphanol is widely used. If neonatal respiratory depression occurs, it

can be reversed by naloxone (narcan).

 Duramorph is a long – acting morphine that provides analgesia upto 24hrs

after injection.

 Regional analgesia is achieved by the epidural injection of opioids or

preservative free morphine. For eg: fentanyl.
Anesthetics:

 local anesthetics used to control discomfort & pain.

 With regional anesthesia, the mother is usually conscious & comfortable, &
the neonate is rarely depressed. For eg: bupivacaine.
 Pregnancy – associated symptoms
and their management
Anemias: 3 types of anemia are common during pregnancy.
Physiologic anemia: results from expanded blood volume.

Iron deficiency anemia: long term nutritional deficiency.

 Iron supplements are usually given. Should be given with food to reduce
the gastric irritation.
 Citrus juice enhance absorption.

Megaloblastic anemia: folic acid deficiency.

 Constipation: Occurs during pregnancy, probably from decreased
peristalsis.

 Preferred treatment, increase exercise & intake of fluids & high - fiber
foods.

 Laxative is safe for the fetus because it is not absorbed systemically. For
e.g. metamucil

 Mineral oil should be avoided because it interferes with absorption with fat
soluble vitamins.

 Reduced absorption of vitamin k can lead to bleeding in newborns.

 Castor oil should be avoided because it can cause uterine contractions.

 Strong laxatives or any laxative used in excess may initiate uterine

contractions and labor.
 Gastroesophageal reflux disease: Occurs in the later
months of pregnancy.

 Nonpharmacologic interventions include small meals; not eating for 2 -3

hrs before bedtime; avoiding caffeine; gas – producing foods &
constipation; & sitting in an upright position.

 Antacids may be used because little systemic absorption occurs. For e.g
Cimetidine, ranitidine or sucralfate.
Gestational diabetes: Most women without risk factors, or
whose initial test was normal, should be tested between 24 & 28 weeks of
gestation.

 Initial management includes nutrition & exercise, calorie restriction for

obese women, & daily self – monitoring of blood glucose levels.

 If its ineffective, recombinant human insulin is needed to keep blood sugar

levels as nearly as possible.

 Oral antidiabetic drugs are generally contraindicated.

 These women may revert to a nondiabetic state when pregnancy ends.

 Nausea and vomiting: Occurs especially early pregnancy.
 Dietary management & maintaining fluid & electrolyte balance are
recommended.

 Antiemetic drugs should be given only if nausea & vomiting are severe
enough to threaten the mother’s nutritional or metabolic status.
 Pregnancy – induced hypertension:

It includes preeclampsia & eclampsia, conditions that endanger the lives of

mother & fetus.

 Preeclampsia occurs during the last 10 weeks of pregnancy, during labor,

or within the 48hrs after delivery.

 Drug therapy includes intravenous hydralazine or labetalol for BP control

& magnesium sulfate for prevention or treatment of seizures.
Selected infections:
 Group B streptococcal infectios: affect during late pregnancy, urinary
tract infections or amnionitis may occur, because of serious consequences
of infection with group B streptococci, pregnant women should have a
vaginal culture at 35 – 37 weeks of gestation.

 Treatment should be initiated during labor, often with ampicillin 2gm

intravenously as a loading dose, then 1gm IV every 4 hrs until delivery.
 HIV infection: Can be transmitted to the fetus & neonate, treatment is
needed to reduce transmission.

 Oral zidovudine monotherapy has been used for several years, after 14
weeks of gestation.

 During labor, IV AZT is given until delivery. After delivery, the infant
should be given AZT for 6 weeks, with or without other anti-AIDS drugs.

 Antiretroviral therapy (HAART) is being used for the pregnant women.

 Women with HIV infection AIDS should be encouraged to avoid

pregnancy.
Urinary tract infection: occurs during pregnancy and may
include asymptomatic bacteriuria, cystitis, & pyelonephritis.

For the treatment Amoxicillin, cephalexin, & nitrofurantoin are used.

hospitalization & an IV cephalosporin may be needed for management of

pyelonephritis.
 Management of chronic disease
during pregnancy:
Asthma: Associated with complications in pregnancy, including
preeclampsia, perinatal death, low birth rates.

 Treatment drugs include orally inhaled beta II agonists (for e.g. albuterol or
metaproterenol) & anti – inflammatory agents (e.g. cromolyn or
beclomethasone).
 Diabetes mellitus: hormonal changes during pregnancy have
diabetogenic effects that may cause or aggravate diabetes.

 Diabetic women who become pregnant, maintaining normal or near blood

sugar levels is required because poor glycemic control increases the risk of
birth defects.

 Management include: if oral anti diabetic drugs are taken by a women

should be discontinued as soon as pregnancy detected.

 Contraindicated. Glyburide used in some womens after 11 weeks of

gestation.

 Insulin is the choice of drug. Its requirement decreases during the 1st
trimester & increases in 2nd & 3rd trimester.
 Hypertension: Chronic hypertension is associated with increased
maternal & fetal risks.

 Methyldopa is 1st choice because it has not been associated with adverse
effects on the fetus or neonate.

 With beta blocker fetal or neonatal bradycardia, hypotension have been

reported.

 ACE inhibitors are contraindicated in pregnancy from some sources while

other says they can be used during the 1st trimester but should then be
discontinued because of potential renal damage in the fetus.
 Seizure disorders: antiepileptic drugs are known to be
teratogens, they must often be taken during pregnancy because seizures
may also be harmful to mother & fetus.

 Birth defects 2 – 3 times higher in fetuses exposed to AEDs than in those

not exposed.

 If an AED is required then plasma drug level should be checked monthly.

Assessment: Assess each female client of reproductive age for
possible pregnancy. If the client is pregnant, assess status in relation to
pregnancy, as follows:

 Length of gestation.
 Use of prescription, over – the – counter, herbal, nontherapeutic, & illegal
drugs.
 Acute & chronic health problems that may influence the pregnancy or
require drug therapy.
 With premature labor, assess length of gestation, the frequency & quality of
uterine contractions, the vaginal bleeding or discharge, & the length of
labor.
 When spontaneous labor occurs in normal, full term pregnancy, assess
frequency & quality of uterine contractions, fetal heart rate & quality &
maternal BP.
 Assess antepartum women for intention to breastfeed.
 Pharmacist Diagnosis:
Risk for injury: damage to fetus or neonate from maternal ingestion of
drugs.

Noncompliance related to ingestion of nonessential drugs during

pregnancy.

Risk for injury related to possible damage to mother or infant during the
birth process.

Deficient knowledge: drug effects during pregnancy & lactation.

 Planning/ Goals
The client will:

 Avoid unnecessary drug ingestion when pregnant or likely to become

pregnant.

 Use nonpharmacologic measures to relieve symptoms associated with

pregnancy or other health problems when possible.

 Obtain optimal care during pregnancy, labor & delivery, & the postpartum
period.

 Avoid behaviors that may lead to complications of pregnancy & labor &
delivery.

 Breast – feed safely & successfully if desired.

 Interventions
Use nondrug measures to prevent the need for drug therapy during
pregnancy.

Provide optimal prenatal care & counseling to promote a healthy

pregnancy.

Help clients & families cope with complications of pregnancy, including

therapeutic abortion.

Counsel candidates for therapeutic abortion about methods & expected

outcomes;
 Evaluation
Observe & interview regarding actions taken to promote reproductive &
general health.

Observe & interview regarding compliance with instructions for promoting

& maintaining a healthy pregnancy.

Interview regarding ingestion of therapeutic & non – therapeutic drugs

during pre pregnant, pregnant & lactating states.

Observe & interview regarding the health status of the mother & neonate.
 General guidelines:
Give medication only when clearly indicated, weighing
anticipated benefits to the mother against the risk of harm to
the fetus.

When drug therapy is required, the choice of drug should be

based on the stage of pregnancy & available drug information.
During the 1st trimester, for eg: an older drug that has not been
associated with teratogenic effects is usually preferred over a
newer drug of unknown teratogenicity.

Any drugs used during pregnancy should be given in the

lowest effective doses & for the shortest effective time.
 FDA Pregnancy Categories
• Category A

Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of
pregnancy (and there is no evidence of risk in later trimesters).

Category B

Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-
controlled studies in pregnant women.

Category C

Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-
controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite
potential risks.

Category D

There is positive evidence of human fetal risk based on adverse reaction data from investigational or
marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant
women despite potential risks.

Category X

Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of
human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks
involved in use of the drug in pregnant women clearly outweigh potential benefits.