Drug use in pregnancy and lactation

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

3. Drug Use in Pregnancy and lactation (2)
 Autonomic system
 Analgesics
 Antihypertensives
 Chemotherapeutics
 CNS
 Anticoagulants
 Endocrine
 Antiemetics
 Antihistamines
 Digoxin
 Dyslipidemics
 “Azole” Drugs
 Anti Acne preparations

4. Autonomic System: Adrenergics
 Several adrenergics were teratogenic in animal
studies.
 They are in OTC decongestants, cold remedies, and
appetite suppressants.
 Some adrenergics may retard labor; and cause
hypoglycemia in the mother and in the neonate.
 Oral albuterol and oral or IV terbutaline relax uterine
muscles and inhibit preterm labor.

5. Autonomic System: Anticholinergics
 Effects on the fetus depend on the maturity of its
parasympathetic nervous system.
 Atropine crosses the placenta rapidly with IV
injection and may cause respiratory depression in the
neonate.

6. Analgesics: Opioids
 Maternal addiction to opioids causes neonatal
withdrawal symptoms.
 Use of codeine during the first trimester has been
associated with congenital defects.
 Opioids decrease uterine contractility in labor and
slow progress toward delivery.

7. Analgesics: Opioids
 They may cause respiratory depression in the
neonate.
 Meperidine (Pethidine) causes less neonatal
respiratory depression than other opioids.
 Respiratory depression can be reversed by naloxone.

8. Analgesics: NSAIDs
 NSAIDs should generally be avoided, especially
during the third trimester.
 All of them are category D in the third trimester.
 Near delivery, they cause delayed onset of labor and
risk of excessive bleeding.
 Diclofenac and aspirin are contraindicated in pregnant
women.

9. Analgesics: NSAIDs
 If taken in the third trimester, fetal side effects
include:
 Prenatal constriction or postnatal nonclosure of the
ductus arteriosis
 Impaired function of the tricuspid valve in the
heart
 Pulmonary hypertension
 Degenerative changes in the myocardium
 Impaired platelet function with resultant bleeding

10. Analgesics: NSAIDs
 Continued from previous slide:
 Intracranial bleeding
 Renal impairment or failure
 Oligohydramnios
 GI bleeding or perforation
 Increased risk of necrotizing enterocolitis.

11. Antihypertensives
 No teratogenic effects have been reported for
Methyldopa.
 Neonates of mothers receiving methyldopa may have
decreased blood pressure for 48 hr.
 Hydralazine is considered safe.

12. Antihypertensives: ACE Inhibitors
 The drugs should be discontinued as soon as
pregnancy is detected.
 With exposure during the second and third trimesters
they may cause: skull hypoplasia, renal failure, and
death.
 Infants exposed to the drugs in utero should be
closely observed for hypotension, oliguria, and
hyperkalemia.

13. Antihypertensives: Beta Blockers
 Teratogenicity has not been reported, but problems
may occur during delivery.
 These include neonatal bradycardia, apnea,
hypoglycemia, low Apgar scores, and low birth
weight.
 Neonatal effects may last up to 72 hr.

14. Antihypertensives: Ca2+ Blockers
 Diltiazem caused fetal death, skeletal abnormalities,
and increased risk of stillbirths.
 Nifedipine caused developmental toxicity in animals.
 There is a potential risk of inadequate blood flow to the
placenta and the fetus.

15. Antihypertensives: Thiazide Diuretics
 Thiazides decrease plasma volume and decrease
blood flow to the placenta.
 They cause: jaundice, thrombocytopenia, fluid and
electrolyte imbalances, and impaired carbohydrate
metabolism.
 Thiazides are not indicated for treatment of dependent
edema caused by uterine enlargement.
 They also are not effective in prevention or treatment
of preeclampsia.

16. Antihypertensives: Loop Diuretics
 Loop diuretics are not considered teratogenic, but
animal studies indicated fetal death.
 Loop diuretics may decrease plasma volume and
blood flow to the placenta and fetus.

17. Chemotherapeutics: Antibacterials
 Penicillins and Cephalosporins cross the placenta but
apparently are safe.
 Trimethoprim, often in combination with
sulfamethoxazole, is contraindicated during the first
trimester.
 It is a folate antagonist and interferes with folic acid
metabolism in the fetus.

18. Chemotherapeutics: Antibacterials
 Fetal serum levels of Aminoglycosides may reach
50% of maternal levels.
 There is potential harm because the drugs are
nephrotoxic and ototoxic.

19. Chemotherapeutics: Antibacterials
 Clindamycin should be used only when infection with
B. fragilis is suspected.
 Fluoroquinolones are contraindicated in pregnancy.
 No fetal abnormalities have been reported for
Erythromycin.
 In animal studies, adverse fetal effects were reported
with clarithromycin but not with azithromycin.
 Clarithromycin is contraindicated if a safer alternative
is available.

20. Chemotherapeutics: Antibacterials
 Nitrofurantoin should not be used during late
pregnancy because of possible hemolytic anemia in
the neonate.
 Sulfonamides should not be used during the last
trimester because they cause kernicterus.
 Tetracyclines are contraindicated and interfere with
development of teeth and bone in the fetus.
 Vancomycin is not recommended because fetal
effects are unknown.

21. Chemotherapeutics: Anti TB
 These drugs are recommended for treatment of active
tuberculosis.
 Prophylaxis can be delayed until delivery.
 Isoniazid, ethambutol, and rifampin were
embryocidal or teratogenic in animal studies.
 However they are used if necessary.
 Pregnant women taking INH should also take
pyridoxine supplementation.

22. Chemotherapeutics: Anti TB
 Treatment of Latent Tuberculosis Infection (LTBI):
 INH is used for LTBI.
 For HIV-positive women with higher risks of
progression to active TB, treatment should not be
delayed.
 For those with lower risks, treatment can begin after
delivery.
 Pyrazinamide and streptomycin are contraindicated
during pregnancy.

23. Chemotherapeutics: Antivirals & Antifungals
 Most systemic antivirals were teratogenic in animal
studies.
 No well-controlled studies support their use in
pregnancy.
 An exception is zidovudine and other anti HIV drugs
to prevent transmission of HIV to the fetus.
 Systemic antifungals are generally contraindicated.

24. CNS: Antianxiety
 These drugs should generally be avoided.
 If taken during the first trimester, they may cause
physical malformations.
 During labor, they cause tremor, respiratory
depression, hypotonia, and sucking difficulties in the
neonate.

25. CNS: Antidepressants & Antipsychotics
 TCAs and SSRIs have been associated with
teratogenicity when given in large doses.
 MAO inhibitors, were associated with growth
retardation in animal studies.
 Phenothiazines are not teratogenic.
 Use near term may cause abnormal reflexes and
jaundice in the neonate.

26. CNS: Antimanic
 Lithium concentrations in fetus are similar to those of
the mother.
 Cardiac and other birth defects may occur.
 In the neonate, lithium causes bradycardia, cyanosis,
diabetes insipidus, hypotonia and hypothyroidism.
 Most of these effects resolve within 1 to 2 weeks.

27. Anticoagulants
 Heparin does not cross the placenta and has not been
associated with congenital defects.
 It is the anticoagulant of choice during pregnancy.
 Warfarin causes fetal hemorrhage, spontaneous
abortion, stillbirth, and congenital anomalies.
 If pregnancy occurs during warfarin therapy, discuss
the possibility of terminating the pregnancy.

28. Endocrine: Corticosteroids
 Animal studies indicate that large doses of cortisol
early in pregnancy produces cleft palate.
 Chronic maternal ingestion during the first trimester
has shown a 1% incidence of cleft palate in humans.
 Infants of women who received large amounts of
corticosteroids during pregnancy should be closely
observed for adrenal insufficiency.
 Inhaled corticosteroids are less likely to cause adverse
effects.

29. Endocrine: Thyroid Gland
 Levothyroxine does not cross the placenta and seems
safe in appropriate dosages.
 When given to hypothyroid women, the drug should
be continued through pregnancy.
 Radioactive iodide (and any other radioactive drug)
and iodine is contraindicated during pregnancy.

30. Endocrine: Antidiabetics
 Insulin is the only antidiabetic drug recommended for
use during pregnancy.
 Sulfonylureas except glyburide are teratogenic in
animals.
 Acarbose, metformin, and miglitol are category B.

31. Antiemetics
 None of the available antiemetic drugs has been proven
safe.
 If drug therapy is necessary dimenhydrinate is safer
than others.

32. Antihistamines
 H1 blockers should generally not be used during the
third trimester.
 H2 blocker agents, are considered acceptable for
treatment of gastroesophageal reflux.

33. Digoxin
 Digoxin is apparently safe for use during pregnancy.
 Fetal toxicity and neonatal death have occurred with
maternal overdose.
 Serum drug levels must be closely monitored during
pregnancy.
 Digoxin is given to the mother for treatment of fetal
tachycardia and heart failure.

34. Dyslipidemics
 Cholestyramine and colestipol are considered safe
because they are not absorbed orally.
 HMG-CoA reductase inhibitors (statins) are
contraindicated during pregnancy (category X).
 They can be given to women of childbearing age only
if they are highly unlikely to become pregnant and are
informed of hazards.

35. “Azole” drugs
 All azoles (miconazole, ketoconazole, etc.) are
contraindicated because of teratogenicity and
malformations.
 Metronidazole is contraindicated during the first
trimester.
 Mebendazole and pyrantel are contraindicated during
pregnancy.

36. Anti Acne preparations
 Retinoids (etretinate and isotretinoin) are
contraindicated in pregnancy (teratogenicity).
 Contraception must be used 1 month before, and
during therapy, and one menstrual cycle after
treatment.
 A pregnancy test must be done within 2 weeks before
therapy.
 Therapy must begin on the 2nd or 3rd day of the next
menstrual period.

38. Thank you
Any question?