The document discusses drug therapy in pregnancy and its complexities. It notes that treatment options are limited due to the direct impact of maternal ailments on the fetus. The thalidomide tragedy of the early 1960s showed certain drugs can be potent teratogens and led to improved drug regulation. The effects of drugs on the embryo, fetus or neonate vary and can include serious fetal toxicity, spontaneous abortion or fetal malformations depending on factors like the timing of exposure during pregnancy. The placenta allows some drugs to transfer to the fetus depending on their properties and other factors. Proving a drug is a teratogen requires meeting specific criteria around its effects. Prescribing drugs during pregnancy requires considering the risk-benefit ratio

1. DRUG THERAPY IN PREGNANCY
Developed By
DR.MOUTUSI DATTA (MBBS,MD)
MEDICAL OFFICER - GRADE IV THS

2. INTRODUCTION
 Treatment options are limited
 Maternal ailment - direct impact on fetus
 Drug therapy in pregnancy is a situation
of complex decisiveness

3. TRAGEDY OF THALIDOMIDE
o Tragedy in early 1960 is a landmark in drug history
o Safe & effective hypnotic and antiemetic
o Potent teratogen - phocomelia
o Thalidomide disaster led to the establishment
of drug regulatory mechanism

5. EFFECTS OF DRUGS ON THE EMBRYO, FETUS, OR NEONATE
o May vary -
o No effect
o Little
o Serious - fetal toxicity
o Spontaneous abortion
o Death
o Fetal malformations.

6. PATHOPHYSIOLOGICAL BASIS OF DRUGS AFFECTING FETUS
 Directly teratogenic
 Placental function alteration
 Changing myometrial activity
 Altered biochemical & functional dynamics

7. FETAL EFFECTS FROM DRUGS DEPEND ON
Time - when drug is taken in pregnancy.
< 3 weeks : all or none effect
3 - 8 weeks : true teratogenecity , covert embryopathy
9th week to term : altered growth , biochemical &
physiological functions

8. Vulnerability of unborn child

11. PHARMACOKINETICS OF DRUGS DURING PREGNANCY
 Absorption - decreased GI motility causes increased drug absorption.
 Intramuscular absorption of drug is more rapid due to increased blood flow
 Distribution - protein binding is decreased
 Causes increased free drug to be available.
 Plasma and extracellular fluid volume expands
 Increased volume of drug distribution

12. PHARMACOKINETICS
•Metabolism : Increased
• hepatic microsomal enzymes undergo induction
•Excretion :
• In the 3rd trimester increased renal blood flow & GFR causes
some drugs to clear the body faster.

13. PLACENTAL DRUG TRANSFER
o The placenta is not a complete barrier:
o Some drugs are stopped
o Some drugs(in fact most) are not
o Ways drugs are transfered across:
o Simple diffusion
o Active transport

14. TRANSFER DEPENDS ON SEVERAL FACTORS
o Physiochemical property of the drug
o pH difference
o Molecular weight
o Protein binding capabilities
o Lipid solubility
o Period of time drug remains in maternal bloodstream
o Half life

15. Characteristics of molecules that crosses
placental barrier

16. TRANSFER DEPENDS ON SEVERAL FACTORS
• Pathological processes of the placenta
• Gestational age (3rd
Trimester): Increased blood flow
to the placenta
• Decreased thickness
• Increased surface area

18. TERATOGENECITY
• Terato - ‘monster’ ; Gen –’producing’
• Six major teratogenic mechanism :
• Folate mechanism alteration
• Neural crest cell disruption
• Endocrine disruption
• Oxidative stress
• Vascular disruption
• Specific receptor or enzyme mediated

19. FDA SYSTEM OF DRUG CATEGORIES IN PREGNANCY

20. WHY TERATOGENIC AGENTS SOMETIMES
DIFFICULT TO IDENTIFY?

21. o INCIDENCE OF CONGENITAL ANOMALIES IS GENERALLY LOW
o Animal Tests May Not Be Reliable
o Prolonged Or Increased Exposure Maybe Required
o Effects Maybe Delayed Or Not Recognized
o Behavioral Effects Are Difficult To Document
o Controlled Experiments Cannot Be Done On Humans

22. • Documentation is incomplete
• Only in a limited number of drugs is the teratogenic
effects known or proven.
• Lack of proof of teratogenicity does not mean a drug is
safe in pregnancy
• May mean there is a lack of research or information.

23. DRUG THERAPY DURING PREGNACY
• Centered on risk/benefit ratio
• Effects of some medication are known
• Unknown-
• New medications
• Different combinations
No drug is absolutely safe

24. RECENT STUDIES
• 75% of pregnant patients use 3-10 different
drugs(prescription or OTC) during their pregnancy
• OTC drugs were used 4 times that of prescription drugs

25. TYPES OF DRUGS USED COMMONLY BY
PREGNANT PATIENTS
• Dietary supplements
• Antiemetics
• Antacids
• Sedatives
• Hypnotics
• Antibiotics
• Antihistamines
• Analgesics
• Tobacco
• ETOH

26. PROVING A DRUG AS A TERATOGEN
3 criteria must be met:
1. Drug must cause a characteristic set of malformations
2. It must act during a specific window of vulnerability i.e.
3-8 weeks of gestation
3. The incidence of malformations should increase with
increased dosage & duration of exposure

27. SAFER MODE OF PRESCRIBING IN PREGNANCY
• Do not start any medication unless clearly indicated
• Do not discontinue medicines that successfully
maintain the maternal condition
• Ask about and document non- prescription medications

28. Safer mode of prescribing in pregnancy
• Have a pregnancy medication reference available
• Use older medicines with longer record of use
• Report adverse outcomes

29. Pharmacotherapeutic decision making during pregnancy

30. EDUCATION OF PREGNANT PATIENTS
• Provide accurate information with rationales
• Information sould be current and based on evidence
• Establish environment conducive to exchange of
information – trust
• Explain potential harm / risks

31. SELF TREATMENT WITH DRUGS DURING PREGNANCY
SELF TREATMENT OF ANY ILLNESSES SHOULD BE DISCOURAGED
WOMEN SHOULD BE INSTRUCTED TO KEEP A COMPLETE RECORD OF
ALL MEDICATIONS TAKEN

32. Examples of known teratogens

33. Thank you