Drug therapy during pregnancy requires special consideration due to the physiological changes in pregnancy and potential effects on fetal development. Many drugs can cross the placenta and harm the fetus, so they should only be used if necessary. The FDA categorizes drug safety in pregnancy from A to X based on animal and human studies. Category X drugs like warfarin and thalidomide are known human teratogens and absolutely contraindicated in pregnancy. Commonly used drugs include acetaminophen, antibiotics, and asthma medications, while illicit drugs like cocaine are known to cause serious complications. Precautions include assessing risks and benefits for both mother and fetus.

1. DRUG THERAPY IN PREGNANCY
Dr Manjuprasad
Moderator : Dr Ravichandra.V
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2. Overview
• Introduction
• Physiological changes during pregnancy
• Placental transfer of drugs
• Critical period in fetal development and teratogenesis
• FDA categories of drug use in pregnancy
• Commonly used drugs
• Conclusion
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3. Introduction
• More than 50% of pregnant women take prescription or
nonprescription (over-the-counter) drugs or use social drugs
(such as tobacco and alcohol) or illicit drugs at some time
during pregnancy, and use of drugs during pregnancy is
increasing.
• In general, drugs should not be used during pregnancy unless
absolutely necessary because many can harm the fetus.
• About 2 to 3% of all birth defects result from drugs that are
taken to treat a disorder or symptom.
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4. PHYSIOLOGICAL CHANGES DURING PREGNANCY
• BMR increases by 15-20%, weight gain – 11kg, postural changes
• GIT changes:- decreased gastric motility & emptying, nausea &
vomiting
• CVS changes:- CO increases by 40%, plasma volume by 45%, low
DBP
• Decreased serum albumin levels
• Hyper coagulability of blood
• Increased GFR & renal blood flow
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5. 5

6. PLACENTAL TRANSFER OF DRUGS
• Rate of transfer of drug across depends on:-
▫ Lipid solubility
▫ Ionization of drug
▫ Molecular size
▫ PPB
▫ pH difference – [7.0 vs 7.4]- ionic trapping of weak basic
drugs - morphine
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7. • Further, placenta is capable of metabolizing drugs
▫ Is of little relevance to the mother
▫ But has protective effect on fetus
Eg:- prednisolone & hydrocortisone are metabolized to
inactive compounds ( prednisone, cortisone )- safer for fetus
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8. Effect of toxic drugs on fetus
• No effect
• Little effect
• Serious fetal toxicity
• Spontaneous abortion
• Death
• Fetal malfunction / malformation
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9. Harmful effects depend on
• Nature of drug, dose & its route
• Stage of pregnancy at which drug is administered
• Genetic constitution &
susceptibility of fetus
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10. • Directly on the fetus- abnormal development [ birth defects or
death]
• Alter the function of the placenta - by constricting blood vessels
reducing the blood supply of oxygen and nutrients to the fetus –
underweight & underdeveloped baby.
• Contract uterus:-
- reducing the blood supply to fetus
-triggering pre-term labor and delivery.
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11. • Gestation may be divided into 4 stages:-
▫ Stage of blastocyst formation
 0- 16 days
 A teratogen may either kill embryo by inhibiting cell
division
 If embryo survives exposure to drug – subsequent
development normal
 ALL or NONE phenomena
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12. Stage of organogenesis
• 17 – 60 days
• A teratogen given during this stage – gross structural
malformation
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13. ▫ Final stage of histogenesis & maturation
 Fetus receives adequate supply of nutrients – growth &
development
 Teratogens – deleterious effects on growth & development
 Eg:- DES – dysplasia , vaginal cancer in the female
offspring
Exposure to androgens – masculinization of female
fetus
▫ Short labour delivery stage
 Drug administered during this phase – risk of neonatal
toxicity
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14. 14

15. ‘terato’ ; ‘genesis’
• Originally used – describe congenital malformation grossly
visible at birth & caused by a teratogen
• Now definition includes ‘structural, biochemical and
behavioral abnormalities’
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16. A teratogen to be called as teratogen
• It should result in characteristic set of malformation
• Exert its effect in particular stage of fetal development
• Show dose dependent incidence
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17. HISTORY OF THALIDOMIDE
• Originally developed in Germany in 1954
• Introduced as hypnotic & sedative in 1957
• Even recommended in pregnancy as a ‘safe hypnotic’
• Teratogenic testing only in mice embryo cells was done
• In 1961- 1st phocomelia case was reported
• Drug was withdrawn in 1961
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18. 18

19. FDA CATEGORIES FOR DRUG USE IN PREGNANCY
• 1979, FDA developed a system determining teratogenic risk of
drugs based on animals & human studies
Divided drugs into 5 categories
• Category A
• Category B
• Category C
• Category D
• Category X
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20. Category A
• Drugs in this category have controlled studies in
pregnant women that have failed to demonstrate harm
to the fetus in the first trimester & have no evidence of
further risk in later trimesters.
• folic acid & vitamin B12
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21. Category B
• Animal studies have failed to demonstrate a risk to the fetus
and but there are no adequate and well controlled studies in
pregnant women
• acetaminophen, insulin & famotidine
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22. Category-C
• Animal reproduction studies have shown an adverse effect on
the fetus and there are no adequate & well-controlled studies in
humans,
• But potential benefits may warrant use of the drug in pregnant
women despite potential risks
• Pseudoephedrine, fluconazole, ciprofloxacin, fexofenadine,
escitalopram, fluoxetine, and bupropion
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23. Category D
• There is positive evidence of human fetal risk based on adverse
reaction data from controlled studies in pregnant humans,
• but potential benefits may warrant use of the drug in pregnant
women despite potential risks
• Example: phenytoin.
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24. Category -X
• Adequate, well controlled or observational studies have been
done in pregnant women or in animals and have demonstrated
positive evidence of fetal abnormalities.
• The use of the product is contraindicated in women who are or
may become pregnant.
• warfarin, medroxyprogesterone, estrogens & methotrexate
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25. DRUGS WITH PROVEN TERATOGENIC EFFECTS
• PHENYTOIN
▫ Fetal hydantoin syndrome
▫ Cleft lip, cleft palate &
congenital heart disease
• Vitamin A derivatives:-
▫ Isotretinoin, etretinate
▫ Significant risk of spontaneous abortion & risk of many
significant anomalies
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26. ACEIs
▫ Renal damage – used in 2nd & 3rd trimester –
oligohydraminos
▫ Anomalies of face, limbs & lungs
VALPROATE & CARBAMAZEPINE
• Spina bifida
• Anencephaly
• Encephalocele
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27. WARFARIN
• Fetal warfarin syndrome
• Nasal hypoplasia, depressed nasal bridge & hemorrhagic
disorders in fetus
NSAIDS
• Premature closure of ductus arteriosus
• Oligohydraminos
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29. DRUGS TERATOGENIC EFFECTS
Tetracycline Anomalies of teeth & bone
Chloramphenicol Gray Baby Syndrome
Sulfonamides Hyperbilirubinemia , Jaundice & Kernicterus
Aminoglycosides Ototoxicity
Danazol & other
Androgenic drugs
Masculinization of female fetus
DES Vaginal carcinoma in female off springs during teens
Oral Hypoglycemic
drugs
Neonatal Hypoglycemia
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30. PRECAUTIONS WHILE PRESCRIBING FOR WOMEN OF
REPRODUCTIVE AGE
• Enquire whether she is pregnant / likely to be in near future
Advised to avoid conception for certain period of time with
certain drugs
• Isotretinoin – 1 month
• Mefloquine – 3 months
• Cytotoxic drugs – 1 year
• Must be informed to use contraceptive measures when a
teratogenic drug is prescribed
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31. PRECAUTIONS WHILE PRESCRIBING DURING
PREGNANCY
• Treat minor ailments without drugs
• Doctor must know the safety potential of the drug he prescribes
• Always prefer drug which has been in market over a longer time
than a new drug
• Make dose adjustment
• Discourage patient from OTC drug use
• Centered on benefit verses risk potential [ epilepsy]
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32. COMMONLY USED DRUGS IN PREGNANCY
ANALGESICS & ANTIPYRETICS:-
• Acetaminophen, phenacetin , aspirin
• Use of NSAIDs avoided towards end of pregnancy – premature
closure of ductus arteriosus
ANTIEMETICS:-
• Antihistaminics – cyclizine, meclizine
• Ondansetron
ANTIBIOTICS:-
• Beta lactam antibiotics safe
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33. • Nitrofurantoin is safe
• Erythromycin is safe ; estolate salts are avoided
ANTIAMOEBIC DRUGS:-
• Metronidazole can be used
ANTIMALARIALS
• Chloroquine can be used Rx of acute attacks
• Quinine – - chloroquine resistant malaria
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34. ANTI TB DRUGS
• isoniazid & ethambutol are safe
• Rifampicin avoided as far as possible due to hepato-toxicity
may be used as a 3rd drug
• Streptomycin is CI – ototoxicity
ANTIFUNGAL DRUGS
• Nystatin & miconazole – safe in pregnancy
• Ketoconazole - CI
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35. ANTIASTHMA DRUGS
• Beta agonists[inhaled], glucocorticoids[inhaled]
CARDIAC DRUGS
• Digoxin & quinidine
ANTIHYPERTENSIVES
• Methyldopa is DOC
• Labetalol IV for sudden decrease in BP
ANTICOAGULANT
• Heparin
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36. ANTIHELMINTHES:-
• Piperazine, pyrantel
ANTIEPILEPTICS:-
• Adequate seizure control necessary for both fetus & mother
health
• Phenytoin, phenobarbiturate, carbamazepine
• Valproate- CI in pregnancy
• Here benefits outweighs risk
• Folic acid supplementation given
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37. • COUGH- codeine, diphenhydramine, dextromethorphan
• HEART BURN- non systemic antacids
• CONSTIPATION:- milk of magnesia, glycerin, bisacodyl
• THYROTOXICOSIS:- Propylthiouracil
• HYPOTHYROIDISM- Thyroxine
• Vaccines
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38. SOCIAL DRUGS IN PREGNANCY
Cigarette smoking
• LBW
• Defects of heart, brain & face
• Risk of SIDS, placenta previa, abruptio placenta
• Risk of PROM, preterm labour, miscarriages & spontaneous
abortion
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39. Alcohol
• Fetal alcohol syndrome
• Incidence – 1 in 2000 live birth
• Facial defects, microcephaly, MR, IUGR, miscarriages
Caffeine
• Found in beverages, soft drinks
• Evidences suggest that consuming caffeine during pregnancy
possess a little/ no risk
• At high dose – decreases fetal blood flow & iron absorption
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40. Illicit drugs
• Cocaine & opiod
• Serious complication in developing fetus & unborn
• Constricts blood vessels- reduces blood flow to fetus
• IUGR, miscarriages, preterm delivery
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41. CONCERN WITH OTC DRUGS
• In India due to easy availability of drugs & poor health services
Increased proportion of self medication for common
complaints
• Hence consumers always face a threat to unwanted ADRs &
drug- drug interations
• Many OTC drugs are unsafe during pregnancy
• Women who are / may be / planning to be pregnant must
consult a doctor before taking any OTC drug
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42. CONCLUSION
• The unique nature of physiology of pregnancy makes
treating chronic & acute disorders a challenge
• As doctors, it is necessary to counsel patients with
complete, accurate and current information on the risks and
benefits of using medications during pregnancy
• Prescribe drugs that have been in use over newer
alternatives
• Rx must always be centered on benefit versus risk
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43. REFERENCES
 Pharmacological aspects of therapeutics – Goodman and Gilman – 12th edition
 Principles of pharmacology Sharma and Sharma 2nd edition
 Rang & Dale 7th edition
 Textbook of medical pharmacology – Dr.Padmaja Udaykumar – fourth edition
 Pharmacology & pharmacotherapeutics – R.S. Satoskar, S.D.Bhandarkar,
Nirmala.N.Rege
 http://www.merckmanuals.com/home/womens_health_issues/drug_use_during_preg
nancy/drug_use_during_pregnancy.html
 Basic and clinical pharmacology – Katzung 13th edition
 Journals from web
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44. THANK YOU
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