This document discusses drug use during pregnancy and lactation. It covers principles of therapy during pregnancy and lactation, emphasizing using the lowest effective dose for shortest time. Physiologic and pharmacokinetic changes in pregnancy that affect drug distribution and metabolism are described. The fetal circulation is explained, along with how drugs can affect the fetus. Drugs are categorized based on safety in pregnancy. Common issues in pregnancy like anemia and constipation are also covered.

2. Drug Use in
Pregnancy and lactation (1)
By
M.H.Farjoo M.D. , Ph.D.
Shahid Beheshti University of Medical Sciences

3. Drug Use in Pregnancy and lactation (1)
 Introduction
 Principles of Therapy
 Physiologic – pharmacokinetics Changes
 Maternal – Fetal Circulation
 Drug Effects On The Fetus
 Drug Categories in Pregnancy
 Fetal Therapeutics
 Dietary Supplements
 Pregnancy-Associated Problems

4. Introduction
 Drug use during pregnancy and lactation requires
special consideration because both the mother and the
child are affected.
 Few drugs are considered safe, and drug use is
generally contraindicated.
 Many pregnant or lactating women take drugs for
acute or chronic disorders or habitual use of alcohol
and tobacco.

5. Principles of Therapy: Pregnancy
 Give medications only when clearly indicated,
weighing benefits to the mother against the risks to
the fetus.
 Any drugs used during pregnancy should be given in
the lowest effective doses and for the shortest
effective time.
 The choice of drug should be based on the stage of
pregnancy and drug information.

6. Principles of Therapy: Pregnancy
 During the first trimester, an older safe drug is
preferred over a newer drug of unknown
teratogenicity.
 Counsel pregnant women about the use of
immunizations during pregnancy.
Teratogenicity is the ability of a
substance to cause abnormal
fetal development when taken by
pregnant women

7. Principles of Therapy: Pregnancy
 Live virus vaccines (measles, mumps, polio, rubella)
should be avoided because of possible harmful effects
to the fetus.
 Inactive virus vaccines (influenza, rabies, hepatitis B)
and toxoids (diphtheria, tetanus) are considered safe
for use.
 Hyperimmune globulins can be given to pregnant
women who are exposed to hepatitis B, rabies,
tetanus, or varicella.

8. Principles of Therapy: Pregnancy
 Hyperimmune immunoglobulin are IGIVs with high
titers of antibodies against viruses or toxins.
 Hyperimmune IGIVs are available for hepatitis B
virus, rabies, tetanus, and digoxin overdose.
 Intravenous administration of the hyperimmune
globulins reduces risk or severity of infection.

9. Principles of Therapy: Lactation
 Most systemic drugs taken by the mother reach the
infant in breast milk.
 For some, the amount of drug is too small for others
effects are unknown or potentially adverse.
 Give medications only when clearly indicated.
 For contraindicated drugs, the mother should stop the
drug or stop breast feeding.

10. Principles of Therapy: Lactation
 Any drugs used during lactation should be given in
the lowest effective dose for the shortest effective
time.
 Stopping breast feeding during maternal drug therapy
is not recommend unless necessary.
 In some instances, mothers may pump and discard
breast milk while receiving therapeutic drugs, to
maintain lactation.
 Women with HIV infection should not breast-feed.
The virus can be transmitted to the nursing infant.

11. Physiologic – Pharmacokinetics Changes
 Physiologic Change:
 50% Increase in plasma volume and body water.
 Pharmacokinetic Change:
 Water soluble drugs are distributed and “diluted” more
than in the nonpregnant state.
 Drug dosage requirements may increase.
 This effect may be offset by other pharmacokinetic
changes of pregnancy.

12. Physiologic – Pharmacokinetics Changes
 Physiologic Change:
 Increased weight (~14 Kg) and body fat
 Pharmacokinetic Change:
 Fat-soluble drugs are distributed more widely.
 Drugs distributed to fatty tissues tend to linger in the
body because they are slowly released from storage
sites.

13. Physiologic – Pharmacokinetics Changes
 Physiologic Change:
 Albumin production↑; however, serum levels↓ because
of plasma volume expansion.
 Many plasma protein-binding sites are occupied by
hormones that increase during pregnancy.
 Pharmacokinetic Change:
 More free drug is available for therapeutic or adverse
effects on the mother and for placental transfer to the
fetus.
 A given dose of a drug is likely to produce greater
effects than it would in the nonpregnant state.

14. Protein binding Pic.

15. Protein binding Pic.

16. Physiologic – Pharmacokinetics Changes
 Physiologic Change:
 Renal blood flow & GFR↑, (because CO↑).
 Pharmacokinetic Change:
 Excretion of drugs by the kidneys↑, especially those
excreted unchanged in the urine (digoxin, lithium).
 In late pregnancy, the increased size of the uterus
decreases renal blood flow in supine position.
 This results in decreased excretion and prolonged
effects of renally excreted drugs.

17. Maternal – Fetal Circulation
 On the maternal side, arterial blood pressure carries
blood and drugs to the placenta.
 Drugs readily cross the placenta, mainly by passive
diffusion.
 Placental transfer begins the 5th week of conception.
 For drugs given regularly, fetal blood contains 50% -
100% of the drug in maternal blood.
 In fetal circulation, large amounts of drug is active
because albumin is low, so most of drug is free.

18. Maternal – Fetal Circulation
 In fetal blood, most drugs are transported to the liver,
for metabolization.
 Metabolism is slow because the fetal liver is immature.
 Drugs metabolized by the fetal liver are excreted by
fetal kidneys into amniotic fluid.
 Excretion is inefficient owing to immature fetal
kidneys.
 The fetus swallows some amniotic fluid, and some
drug molecules are recirculated.

19. Maternal – Fetal Circulation
 Drug molecules are also distributed to the brain.
 Drugs enter the brain easily because the blood–brain
barrier is poorly developed in the fetus.
 Umbilical arteries transport half of the drug-
containing blood to the placenta where reenters the
maternal circulation.
 Thus, the mother can metabolize and excrete some
drug molecules for the fetus.

20. Drug Effects On The Fetus
 The fetus is very sensitive to any drugs, and drugs may
cause teratogenicity or other adverse effects.
 Teratogenicity most likely occurs during the first
trimester, when fetal organs are formed.
 During the 2nd and 3rd trimesters, adverse effects are:
growth retardation, respiratory problems, or bleeding.

21. Drug Effects On The Fetus
 Overall, effects are determined mainly by:
 The type and amount of drugs
 The duration of exposure
 The level of fetal growth and development when
exposed to the drugs.
 Both therapeutic and nontherapeutic drugs may affect
the fetus.

22. Drug Categories in Pregnancy
 Category A:
 Adequate studies in human demonstrate no risk.
 Category B:
 Animal studies indicate no risk, but there are no
adequate studies in human.
 Animal studies show adverse effects, but adequate
studies in human have not demonstrated a risk.

23. Drug Categories in Pregnancy
 Category C:
 A potential risk, when:
 Animal studies have not been performed or,
 Animal studies indicated no adverse effects and,
 There are no data from human studies.
 These drugs may be used when potential benefits
outweigh the potential risks.

24. Drug Categories in Pregnancy
 Category D:
 There is evidence of human fetal risk, but the
potential benefits to the mother may be acceptable.
 Category X:
 Studies in animals or humans or adverse reaction
reports or both have demonstrated fetal
abnormalities.
 The risk of use in a pregnant woman clearly
outweighs any possible benefit.

25. Fetal Therapeutics
 A few drugs are given to the mother for their effects
on the fetus:
 Digoxin for fetal tachycardia or heart failure
 Levothyroxine for hypothyroidism
 Penicillin for exposure to maternal syphilis
 Prenatal Betamethasone to promote surfactant
production in preterm infants.

26. Dietary Supplements
 Pregnancy increases nutritional needs and vitamin
and mineral supplements are commonly used.
 Folic acid supplementation is especially important, to
prevent neural tube birth defects (spina bifida).
 Such defects occur early in pregnancy, often before
the woman realizes she is pregnant.

27. Dietary Supplements
 It is recommended that all women of childbearing
potential ingest folic acid at least 400 mcg daily.
 In addition, pregnancy increases folic acid needs by 5
to 10 fold and deficiencies are common.
 A supplement is usually needed to supply adequate
amounts.
 For deficiency states, 1 mg or more daily may be
needed.

28. Pregnancy-Associated Problems
 Anemia
 Constipation
 Gastroesophageal Reflux
 Gestational Diabetes
 Nausea & Vomiting
 Pregnancy-Induced Hypertension

29. Anemia
 Three types of anemia are common during
pregnancy:
 Physiologic
 Iron- deficiency
 Megaloblastic
Results from expanded
blood volume
• Iron preparations should be given
with food to decrease gastric
irritation.
• Citrus juices enhance absorption
Caused by folic acid deficiency

30. Constipation
 Constipation occurs from decreased peristalsis.
 Treatment, if effective, is to increase exercise and
intake of fluids and high-fiber foods.
 If a laxative is required, a bulk forming agent is the
most physiologic because it is not absorbed.
 A stool softener or an occasional saline laxative (milk
of magnesia) may also be used.

31. Constipation
 Mineral oil should be avoided because it interferes
with absorption of 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.

32. Gastroesophageal Reflux
 Often occurs in the later months of pregnancy.
 Nonpharmacologic interventions (eating small meals;
avoiding gas producing food and drinks) are
recommended.
 Antacids may be used if necessary, because little
systemic absorption occurs.
 Cimetidine, ranitidine, or sucralfate may also be used.

33. Gestational Diabetes
 Some women first show signs of diabetes during
pregnancy (gestational diabetes).
 Women without risk factors, or whose test was
normal, should be tested between 24 and 28 weeks of
gestation.
 Initial management is intervention in nutrition and
exercise, and calorie restriction for obese women.
 If drug is necessary, insulin is used.

34. Gestational Diabetes
 Oral antidiabetic drugs are generally contraindicated,
although acarbose, metformin, and miglitol are
almost safe.
 These women may revert to a nondiabetic state when
pregnancy ends.
 They are at increased risk for development of overt
diabetes within 5 to 10 years.
 Gestational diabetes usually subsides within 6 weeks
after delivery.

35. Nausea & Vomiting
 Dietary management and maintaining fluid and
electrolyte balance are recommended.
 Antiemetic drugs should be given only if nausea and
vomiting threaten the mother’s nutritional status.
 Dimenhydrinate, 50 mg every 3 to 4 hours, are
thought to have low teratogenic risks.
 Pyridoxine (vitamin B6) also may be helpful (10 to
25 mg daily).

36. Pregnancy-Induced Hypertension
 Pregnancy-induced hypertension are preeclampsia
and eclampsia.
 They endanger the lives of mother and fetus.
 Preeclampsia occurs during the last 10 weeks of
pregnancy, during labor, or within the first 48 hr after
delivery.
 It is manifested by edema, hypertension, and
proteinuria.

37. Pregnancy-Induced Hypertension
 Drug therapy includes IV hydralazine or labetalol for
blood pressure and magnesium sulfate for seizures.
 Eclampsia, occurs if preeclampsia is not treated
effectively.
 Delivery of the fetus is the only known cure for
preeclampsia or eclampsia.

40. Thank you
Any question?