This document discusses drug use in pregnancy. It notes that until the 20th century, doctors believed the uterus shielded the fetus, but thalidomide caused birth defects, showing drugs can affect the fetus. The fetal period from weeks 3-8 post-conception has the greatest risk of malformations. Most drugs cross the placenta. Minimizing drug use, dose, and number is advised. Teratogens can cause structural abnormalities or functional impairments. The risk must be balanced with treating medical conditions in the mother.

1. DRUG USE IN PREGNANCY
General Principles
Dr.B.Nagaraju
Research Scholar
Department of Pharmacology

2. HIStory
Until the middle of 20th
century physicians
believed that the uterus provided a
protected environment for the fetus and a
shield from the external environment

3. HIStory
NM Gregg –Australian Physician
 Women who contracted rubella-gave birth to
infant with specific birth defect
 Could external environment affect fetal
outcome?

4. Thalidomide disaster
 Phocomaelia [deformed babies]
 Teratogenicity
 Promulgation of drug regulations in
1962 by US FDA
 Testing for teratogenicity

5. British National Formulary
“NO DRUG IS SAFE BEYOND ALL
DOUBT IN EARLY PREGNANCY”
Minimize the risk to the fetus while
Not denying the effective treatment

6. HOW DRUGS CAN AFFECT
FETUS?
Most drugs with molecular weight less
than 1000 can cross placental barrier.
Factors influencing drug effect

Environment

Genetic

Time of exposure

7. PRE – EMBRYONIC PHASE
 Days 0-14 post conception
 Blastocyst- a cluster of undifferentiated cells
Embryonic discs
 Exposure to teratogen “All or nothing”

8. Embryonic Phase
 Weeks 3-8 post-conception
 Organogenesis (fourth week)
 Greatest potential to cause gross
malformation

9. Fetal Phase
 Week 9 post-conception - birth
 Growth of structures and development of
normal physiological functions
 General growth retardation or interfere with
functional development within specific organ
system

10. Drugs Taken by Men
 Drugs that are excreted in semen
eg.Finasteride.
 Griseofulvin may damage sperm cells

11. WHO IS AT RISK ?
 Women recently conceived
 At or around the time of conception
 Before confirmation

12. MINIMISING RISK
 Use as few drugs as possible
USE DRUGS
 LOWEST EFFECTIVE DOSE
 MINIMUM IN NUMBER
 LEAST POTENTIAL TO CAUSE DAMAGE
 Remember! Use of most drugs in pregnancy is
unlicensed

13. EXAMPLES OF WARNINGS

14. PRESCRIBING IN
PREGNANCY
 Treatment should only be given if it is clearly
necessary.
 Balance the risk and benefit.
 Treatment should be stopped as soon as
possible.

15. PRESCRIBING IN
PREGNANCY
 Teratogen in non-pregnant women of child
bearing age should also be avoided.
 New drugs are best avoided.
 If this is not possible, ensure that the patient
is fully aware of the dangers.

16. PHARMACOKINETICS IN
PREGNANCY
 Increased total body water
 Liver metabolism
 Renal blood flow
 Decreased plasma protein concentrations

17. TERATOGEN
“ an agent is a teratogen, if its administration
to the pregnant mother directly or indirectly
causes structural or functional abnormalities
in the fetus or in the child after birth, which
may not be apparent until later life”

18. EFFECTS OF TERATOGENS
 Chromosomal abnormalities
 Impairment of implantation of the conceptus.
 Resorption or abortion of the early embryo.
 Structural malformations.
 Intrauterine growth retardation.

19. EFFECTS OF TERATOGENS
 Fetal death.
 Functional impairment in the neonate e.g.
deafness.
 Behavioral abnormalities.
 Mental retardation.

20. Principles Of Teratogenesis
 Timing of exposure
 Exposure to a teratogen in the first three
months structural malformations.
 Exposure after the first three months --
growth defects.

21. Principles of Teratogenesis
 Differences in susceptibility
 Maternal and fetal susceptibility to a drug is
different.
 A drug does not need to cross the placenta to
affect the fetus.

22. Principles of Teratogenesis
 Genetic variation
 risk can differ among individuals as a result
of genetic variation in drug metabolism.

23. Principles of Teratogenesis
 Teratogenesis in humans
 Pharmacokinetic and metabolic differences
between animals and humans has led to
drugs being falsely identified as teratogenic
in humans following animal tests.

24. Principles of Teratogenesis
 Dose response relationships
 Teratogenic effects --- dose dependent.
 Dose response curve is steep.
 Depends on time of administration after
conception and the cumulative exposure
rather than the extent and rate of drug
transfer across the placenta.

25. Categorization of drugs
 Depending on its effect on fetus
 Category A
 Taken by large no. of pregnant women and no
proven direct or indirect harmful effects observed.
eg.Methyldopa, Pencillins, Paracetamol

26. Categorization of drugs
 Category –B

Drugs taken by limited no. of pregnant women
and women of child bearing age and no direct
and indirect harmful effects been observed.
eg. Norfloxacin, Cetrizine, Pyrazinamide
 Category –C

Drugs which,owing to their pharmacological
effects,have caused or may be suspected to
cause harmful effects to fetus.
eg.Rifampicin, Propylthiouracil,

27. Categorization of drugs
 Category –D
 Drugs which have caused,are suspected to have
caused,or may be expected to cause ,an
increased incidence of human fetal
malformations or irreversible damage.
eg. Phenytoin, Carbamezapine,Danazol
 Category –x
 Drugs that have such a high risk of causing
permanent damage to the fetus that they should
not be used in pregnancy or when there is a
possibility of pregnancy.
eg. Thalidomide, Finasteride,

28. General care of pregnant women
 Morning sickness
 Pyridoxine
 Non pharmacological aids like
acupressure, bands.

29. General care of pregnant women
 Gastro-oesophageal reflux
 Two-third of the pregnant women suffer from
gastro-oesophageal reflux --- later stages.
 Antacid preparations --- Ca carbonate and
combination of Al and Mg salts.

30. General care of pregnant women
 Avoid products with a high sodium content
 Antacid preparations containing alginate
--- advisable.
 H2 antagonists are not licensed.

31. General care of pregnant women
 Headache and backache
 Paracetamol safe to use throughout
pregnancy.
 Codeine and dihydrocodeine co-formulated
with paracetamol can be used --- may
cause depression of respiration in new
born babies if taken near term.
 Aspirin and ibuprofen --- avoided.

32. General care of pregnant women
 Constipation
 Increase fluid intake and fibre in diet.
 Bulk forming laxatives and lactulose - could
be tried.
 Docusate --- safe.
 Senna --- not teratogenic but use in later
stages may cause uterine contractions.

33. General care of pregnant women
 Haemorrhoids
 Haemorrhoidal cream or ointment -
bismuth oxide.
 Ice pack.
 Prevention of recurrence of constipation.

34. General care of pregnant women
 Candidiasis (thrush)
 Vaginal candidiasis --- 2 – 10 times more
frequent.
 Imidazole antifungals effective but not
licensed.

35. General care of pregnant women
 Varicose veins, edema, and muscle
cramps
 10 – 20% of pregnant women.
 Upto 80% suffer with leg edema and one
third experience cramps in calf muscles in
late pregnancy.
 Resting with their legs elevated.
 Ca and K reduces leg cramps.

36. General care of pregnant women
 Pruritis
 Affects 20% of pregnant women.
 Oily calamine lotion.

37. General care of pregnant women
 Stretch marks & hyperpigmentaiton
 Exercise
 After pregnancy --- tretinoin.

38. General care of pregnant women
 Coughs and colds
 Avoid products containing systemic
sympathomimetic decongestants.

39. Treatment Due to Chronic Disorders
 Bronchial asthma
 Epilepsy
 Hypertension
 Tuberculosis
 Diabetes mellitus
 Depression

40. Transient Medical Problems in
Pregnancy
 Urinary tract infections
 Vulvovaginitis
 Respiratory tract infections
 Influenza

41. Common Drugs Used in Pregnancy
 Antibiotics
Relatively Caution Relatively
Safe advised contraindicated
Pencillins Trimethoprim/ Tetracycline
Sulfamethoxazole
Cephalosporins Metranidazole Fluoroquinolones
Erythromycin Aminoglycosides
Chloramphenical

42. Common Drugs Used in Pregnancy
 Analgesic antinflammatory medication
 Paracetamol
- non teratogenic
 Aspirin
- no adverse effects reported
during first trimester
- use with caution in third trimester

43. Common Drugs Used in Pregnancy
 Cold medications
Decongestants
Phenylephrine & pseudoephedrine
-no risk of teratogenic shown in human
 Antihistamines
Chlorpheniramine,diphenhydramine

44. Common Drugs Used in Pregnancy
 H2 Receptor antagonists
-no teratogenic reports in human
 Proton pump inhibitors
 Antihelminthics
single dose of albendazole and mebendazole
is said to be safe.

45. Common Drugs Used in Pregnancy
 Laxatives
Bisacodyl
 Antiemetics
 Metoclopramide is safe to use
 Domperidone

46. Antimalarials
 Chloroquine is drug of choice for
prophylaxis
 Quinine ,Mefloquine
 Pyrimethamine- sulfadoxine

47. Antituberculosis
 Isoniazid, Ethambutol- safe
 Rifampicin –little risk in late pregnancy
 Streptomycin –avoid use

48. CONCLUSION
 Untreated disease condition in pregnancy can
lead to hazardous effect
 Risk benefit analysis
 Choose the appropriate drug
 Avoid unnecessary exposure
 Choose the drug with least teratogenicity.
 Educate patient before starting the treatment