Pharmacologic and clinical points about drug use during pregnancy and nursing.

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?