This document discusses teratogens and teratogenic drugs. It begins by defining a teratogen as an agent that can disturb fetal development. It then discusses the FDA pregnancy categories and mechanisms of action of teratogenic drugs. Specific examples of teratogenic drugs are given for different categories, along with their mechanisms and potential effects on the fetus. The document stresses the importance of carefully considering drug use during pregnancy and providing counseling on risks and benefits.

1. 1. NURUL MIZA SHASHEIHA BINTI ABDUL MUTALIB
2. NURUL HUSNA BINTI MURYADI
3. WAN FATHIAH NASUHA BT WAN NUSDRI
4. NURFATIN AFIQAH BT MOHD BADRONDIN
5. ZATEEL FAHADA BT RUSLI
6. NURUL FIRDAUS BT HANAFEE
7. NURUL SAHIIRAH BT AHMAD ROFI
8. WAN FARAH NASUHA BT WAN MUHAMMAD HUSNI

2. INTRODUCTION
• WHAT IS TERATOGEN ?
• TERATOGENIC DRUG
• FDA PREGNANCY CATEGORIES
• GENERAL MECHANISMS OF ACTION OF
TERATOGENIC DRUGS
• TERATOGENIC MECHANISMS OF MEDICAL
DRUGS

3. TERATOGEN
• Is an agent that can
disturb the
development of the
embryo or fetus
• Teratogens halt the
pregnancy or
produce a
congenital
malformation
• Include radiation,
maternal infections,
chemicals, and
drugs.
• directly or indirectly,
causes a structural or
functional change in the
fetus or child if it is
administrated to pregnant
mother
• If mother is taking this
drug, It can be either
stopped, switched or
reduced to the lowest
dose possible
• typically during sensitive
periods of fetal
development
• depending on the
particular teratogenic
process and target organ
TERATOGENIC
DRUG

4. FDA PREGNANCY CATEGORIES
CATEGORY A
• failed to
demonstrat
e a risk to
the fetus in
the first
trimester of
pregnancy
• no evidence
of risk in
later
trimesters
CATEGORY C
• shown an
adverse effect
on the fetus
• no adequate
and well-
controlled
studies in
humans
• potential
benefits may
warrant the
use of drug
despite
potential risks.
CATEGORY D
• positive
evidence of
human fetal
risk based on
adverse
reaction data
• potential
benefits may
warrant use of
the drug in
pregnant
women
despite
potential risks
CATEGORY B
• failed to
demonstrate
a risk to the
fetus
• no adequate
and well-
controlled
studies in
pregnant
women.
CATEGORY X
• demonstrates
fetal
abnormalities
• positive
evidence of
human fetal
risk based on
adverse
reaction data
• the risks
involved in use
of the drug in
pregnant
women
CATEGORY N
• FDA has
not
classified
the drug.

5. POSSIBLE SITES OF
ACTION OF TERATOGEN
DIRECT
TOXIC
ACTION
• FETUS:
-Direct toxicity.
-Metabolites toxic.
-Indirectly toxic, e.g.
anti-metabolites, anti-
vitamin.
-Pharmacodynamic
actions, e.g. on
cardiovascular system.
-Endocrine balance
altered
• FAETOPLACENTAL
UNIT:
-Umbilical cord, e.g.
spasm.
-Amniotic fluid volume
change.
-Faetal or maternal
placental blood flow.
-Placental transfer of
• MOTHER:
-Nutritional changes,
e.g. vitamin or
mineral deficiencies.
-Biochemical
changes with
secondary effects on
the foetus, e.g.
hyperglycaemia.
-Endocrine balance
• FATHER:
-Sperm changes
INDIRECT
TOXIC
ACTION
• Cause malformation
-interfering with
faetal metabolism
• Drugs:
-folic acid
antagonists
-antiepileptic drugs

6. TERATOGENIC MECHANISMS OF
MEDICAL DRUGS
• Folate antagonism
• Neural crest cell disruption
• Endocrine disruption
• Oxidative stress
• Vascular disruption and specific
receptor
• Enzyme-mediated teratogenesis

7. •Analgesic
•Anticonvulsant
•Anticoagulant
•Antidepressant
•Antithyroid
•Vitamin A
•Metal toxic
•Sedative/ hypnotics
•Aminoglycosides

8. • Gastroschisis
• Decrease prostaglandin  decrease uterine
contraction delayed onset of labor & prolonged
period of pregnancy
• During delivery severe bleeding because aspirin
decrease platelet aggregation

9. • Fetal hydantoin syndrome :
 cranio facial malformation:
-Cleft lip and palate
-Broad nasal bridge
-Ocular hypertelorism
-Abnormal ears
 congenital heart disease
 limb malformation
 mental and growth retardation

10. • Fetal wafarin syndrome:
-Nasal hypoplasia
-Bone stippling
-Bilateral optic atrophy
-Mental retardation
• Respiratory distress syndrome
• Fetal and maternal hemorrhage

11. • Cleft palate
• Defect in abdomen
• Adrenal hypoplasia
• Cardiovascular defect

12. • Fetal goiter

13. • Cranio-facial dysmorphism
• Cleft palate
• Thymic aplasia
• Neural tube defect ( spina bifida cystic )

14. • Hypotonia
• Cyanosis
• Lethargy
• Poor respiratory

15. • Cleft lip and palate
• Inguinal hernia
• Congenital heart disease
• Pyloric stenosis
• Breathing difficulties

16. • Congenital deafness
• Ototoxicity

17. TERATOGENIC
DRUGS IN SECOND
TRIMESTER OF
PREGNANCY

18. ACE INHIBITORS
DIAZEPAM

19. 1) ACE INHIBITOR
MECHANISM OF ACTIONS
Produce vasodilatation by
1-inhibitting formation of
angiotensin 11
2- breakdown bradykinin

20. PHARMACOLOGICAL ACTION
 Mixed vasodilator
 In cases of heart failure, cardiac output is
maintained / even increase
 Increase renal blood flow BUT decrease glomerular
filtration rate decrease glomerular
hypertension

21. THERAPEUTIC USES
USED IN
 Hypertension
 Heart failure
 Myocardial infarction

22. SIDE EFFECTS
 IF USED IN 2ND – 3RD TRIMESTER OF PREGNANCY
1- fetal hypotension
2- renal failure
3- oligohydromnios
4- death
3rd tri

23. 2) DIAZEPAM
 Centrally acting spasmolytic drug
 It facilitates action of GABA in CNS
 It acts as GABA synapse and produce sedation at
doses required to reduce muscles tone

24. PHARMACOKINETICS
 ABSORPTION:
- Delayed and decreased when administered with a
moderate fat meal
 DISTRIBUTION
- Highly bound to plasma protein
- Cross blood brain barrier
- Cross placental barrier
- Found in milk

25.  METABOLISM
N-demythylated
Diazepam N-desmethyldiazepam
further metabolised
hydroxylated
temazepam oxazepam
 Temazepam and oxazepam are largely eliminated
by glucoronidation

26. ELIMINATION
 The initial distribution phase is followed by
prolonged elimination phase

27. SIDE EFFECTS
 RISKS OF…
1) cleft palate
2) cardiac and circulatory defects

30. 1) TETRACYCLINE
 Protein synthesis inhibitor
 Inhibit the binding of aminoacyl-tRNA to the mRNA-
ribosomes complex
Aminoacyl-tRNA mRNA-ribosomes complex
by binding to the 30S ribosomal subunit in mRNA
translation complex

31. SIDE EFFECTS
 IN PREGNANCY…..
 dental discolouration in chilren
 maternal hepatotoxicity with large parenteral doses

32. 2) ACE INHIBITORS
 AS IN SECOND TRIMESTER
 Ace inhibitors in 2nd trimester

33. 3) CHLORAMPHENICOL
 Bacteriostatic drug that stop bacterial growth by
inhibiting protein synthesis
 Prevent protein chain elongation by inhibiting
peptidyl transferase activity of bacterial chromosome
 Intravenous chloramphenicol use has been associated
with Gray Baby syndrome
 This occur in newborn infants because they liver
enzymes not yet fully developed
chloramphenicol remains
unmetabolised in body

34. ADVERSE EFFECTS
 Hypotension
 Cyanosis
The condition can be prevented by using the drug at
recommended doses & monitoring blood levels
Gray Baby Syndrome

35. 4) AMINOGLYCOSIDES
 EG: GENTAMICIN, STREPTOMYCIN
 Have several potential antibiotic mechanisms
 They interfere with the proofreading process
increased rate of error in synthesis with
premature termination
 Inhibition of ribosomal translocation
peptidyl tRNA moves from A-site to P-
site
 Disrupt the integrity of the bacterial cell membrane

36.  Aminoglycosides are in pregnancy category D
 They may cause auditory or vestibular nerve damage

37. 5) SULFAMETHOXAZOLE,
TRIMETHOPRIM
 Sulfonamide bacteriostatic antibiotic
 Structural analogs and competitive antagonist of PABA
 Inhibit normal bacterial utilisation of PABA for the
synthesis of folic acid
 Used as a bacteriostatic antibiotic in prophylaxis and
treatment of urinary tract infections

38.  Trimethoprim binds to dihydrofolate redustase and
inhibit reduction of DHF to THF
 Sulfamethoxazole inhibit dihydrofolate synthetase

39. TERATOGENIC EFFECTS
 1) NEONATAL HAEMOLYSIS
 2)METHAEMOGLOBINAEMIA

40. •BE CAREFUL IN TAKING DRUGS DURING
PREGNANCY
•ALL CLINICIANS INCLUDING PHARMACISTS ARE
RESPONSIBLE TO COUNSEL PATIENTS WITH
COMPLETE , ACCURATE AND CURRENT
INFORMATION ON THE RISKS AND BENEFITS OF
USING MEDICATIONS DURING PREGNANCY