TERATOGENIC DRUGS

1. Teratogenecity
&
Safety of drugs in
pregnancy
by:ABHISHEK BHARTI
Roll no :17005

2. DEFENITION:Teratogenecity is the capacity of a
drug to cause foetal abnormalities when
administered to pregnant mother.
Teratogenic effect include maformation,
IUGR,miscarriage and neurocognitive delay.

3. Drug can affect the foetus at 3 stages
1. Fertilization & implantation(Conception to
17 days)-teratogenecity is unlikely ,all or
none effect.Either failure of pregnancy or no
teratogenecity.
2. During organogenesis( 18-55 days)-Most
vulnerable period for
teratogenesis.Spontaneous abortion & gross
deformities are produced.
3. After organogenesis(in 2nd & 3rd trimester)-
Develpomental & functional abnormalities
can occur.

4. FACTORS AFFECTING DRUG
EXPOSURE TO FETUS
LIPID SOLUBILITY
• Lipophilic drugs readily across placenta and
enter fetal circulation.
• Highly ionized drugs cross placenta slowly and
achieve very low concentration in the fetus.
MOLUCULAR SIZE
• Drugs with smaller molecular weight cross
placenta easily

5. Drugs with molecular weight more with 1000
crosses placenta poorly.
Eg : An important clinical application of this
property is choice of heparin as an
anticoagulant in pregnancy.Because it is a
large molecule, heparin is unable to cross
placenta.
pH
Maternal blood has a pH of 7.4 whereas fetal
blood is 7.3,basic drugs with a pKa above 7.4
will be more ionized in fetal
compartment,leading to fetal trapping and
higher fetal level

6. PROTEIN BINDING
• If a compound is very lipid soluble,it will not
be affected greatly by protein binding.
• If a drug is poorly lipid soluble and is ionised
,its transfer is slow and will be impeded by its
binging to maternal plasma proteins.
PLACENTAL TRANSPORTER
Many transporters have been identified in
placenta which affect drug transfer to foetus.
Eg: P-Glycoprotein transporter pumps back
variety of drugs into maternal circulation.

7. PLACENTAL and FETAL DRUG METABOLISM
• Placenta itself act as a semipermeable barrier
and a site of metabolism for some drugs
passing through it. Eg : several types of
aromatic oxidation reaction like hydroxylation
,N- dealkylation,demethylation occur in
placenta.
• Drugs that cross placenta enter fetal
circulation via umbilical vein.About 60%
umbilical venous blood enter fetal liver and
drug may be partially metabolised there.

8. TERATOGENIC MECHANISMS
• Drugs can act directly on the fetus causing
damage,abnormal development or death.
• They can alter the function of placenta by
causing vasoconstriction and reducing oxygen
and nutrient supply to fetus leading to fetal
growth restriction
• They can cause forcefull contraction of uterus
,indirectly injuring fetus by reducing blood
supply or triggering preterm labor.

9. FDA Teratogenic Risk Categories
Category A :Adequate,well-controlled studies in
pregnant women shows no risk to fetus in
any trimester of pregnancy.
Eg :Methyldopa, Penicillins, paracetamol
Category B : Well controlled studies in pregnant
women have not shown an increased risk of
fetal abnormality despite adverse findiing in
animals.Chances of fetal harm are remote
but remains a possibility.
Eg :Ibuprofen ,Cetrizine ,pyazinamide

10. Category C :Risk cannot be ruled out.Adequate
well controlled studies are lacking but animal
studies have shown a risk to fetus .There is a
chance of harm to fetus if drug is administered
during pregnancy,but the potential benefit
may outweigh the potential risk.
Eg : Rifampicin,fluoxetin
Category D :There is positive evidence of human
fetal risk but the benefits from use in
pregnant women may be accepted despite the
risk.The drug may be accepted if needed in a
life threatning situation or serious disease for
which safer drugs cannot be used or are
ineffective.

11. Category X : Studies in animals and human or
investigational or post marketing reports have
demostrated positive evidence of fetal risk
and risk clearly outweighs any possiblebenefit
to patient.
These drugs are contraindicated in women
who are or may become pregnant.Drugs in
this group are ACE inhibitors ,Lithium
,Methotrexate , Valproic acid, Mifepristone
,Alcohol,Danazol ,Isotretinoin etc.

12. Common drug and their
teratogenecity
1. Thalidomide : Limb deformities called
phocomelia
Phocomelia

13. 2. Retinoic Acid or vit A derivatives: Isotrenoin
causes
Craniofacial dysmorphisms
Cleft palate
Thymic aplasia
neural tube defects
3.Lithium causes
Foetal goiter
Ebstein anamoly
Neonatal hypotonia

14. 4.Phenytoin causes
Fetal hydantoin syndrome characterised by
hypoplastic phalenges , cleft
palate,microcephaly
5.ACE inhibitors cause
Fetal hypotension
ranal failure
oligohydromnios
6.Alcohol causes
fetal alcohol syndrome – low IQ and growth
retardation

15. 6. Warfarin causes foetal warfarin syndrome
hypoplasia of nose,eyes, socket.
7. Tetracycline causes brown discoloration of
deciduos teeth,inhibition of bone growth etc
8.Streptomycin and kanamycin are associated
with congenital deafness.

18. Thankyou
for listening