Teras-”monster” Gensis-”producing”
A teratogen is defined as any agent that results in structural or functional abnormalities (malformation ) in the fetus, or in the child after birth, as a consequence of maternal exposure during pregnancy.
Birth defects are known to occur in 3- 5% of all newborns.
They can do direct damage to the fetus, causing abnormal development.
Teratogens jagadisha T V. and its effects in fetal development
1. Teratogens
Dr. Jagadisha T.V., M.Sc., PGDGT., PhD
Assistant Professor
Department of Life Sciences (Genetics)
Kristu Jayanti College (Autonomous)
(Reaccredited A++ Grade by NAAC with CGPA 3.78/4)
K. Narayanapura, Kothanur Post, Bangalore - 560 077
Karnataka, INDIA.
Ph.-No: 8892698143/9449442521,
E-mail:jagadisha.tv@kristujayanti.com
ORCID ID: https://orcid.org/0000-0002-0596-7830
ResearchGate: https://www.researchgate.net/profile/Jagadish-T-V
Vidwan: https://vidwan.inflibnet.ac.in/profile/404275
2. • Teras-”monster” Gensis-”producing”
• A teratogen is defined as any agent that results in
structural or functional abnormalities (malformation ) in the
fetus, or in the child after birth, as a consequence of
maternal exposure during pregnancy.
• Birth defects are known to occur in 3- 5% of all newborns.
• They can do direct damage to the fetus, causing
abnormal development.
Introduction
3. • Alcohol and cocaine are examples of taratogens.
• Exposure to the teratogen affects the fetus or embryo in a variety
of ways, such as the duration of exposure,
1. The amount of teratogenic substance,
2. The stage of development the embryo or fetus is in during the exposure.
affect the embryo or fetus in several ways,
• Causing physical malformations,
• Problems in the behavioral or emotional development of the child
• Decreased intellectual quotient (IQ) in the child.
4. Causes of teratogenesis
• Abnormal development may be caused by errors in genetic programming, from
environmental agents/factors
• About 7 % of all live birth defects are due to prenatal exposure to radiation,
environmental factors, chemicals, and drugs.
• Abnormalities caused by genetic events, e.g. mutation in genes, structural
changes in chromosomes, and aneuploidies, etc. are called malformations
• Abnormalities caused by environmental agents are called disruptions.
• The environmental factors may be either biological (e.g. viruses and parasites)
or non biological such as physical factors (e.g. temperature, radiation) and
chemical factors (e.g. drug, chemicals and nutritional imbalances).
5. • The agents responsible for the disruptions are called
teratogens.
• Mutagens and carcinogens also are the causes of
abnormal development but their mode of action differ.
• Teratogens are agents that affect the embryo at dose levels.
They are harmless to adult organisms and do not
permanently damage the genetic material.
• Mutagens are agents that alter the genes,
• Carcinogens are agents that lead to excessive growth and
loss of differentiation, generally in adult tissue.
6. Teratogens are classified into four types:
1. Physical agents
2. Metabolic conditions
3. infection
4. Drugs and chemicals
7. A list of some teratogenic agents causing birth defects
Natural Teratogens Some poisonous plants like Skunk
cabbage veratrum, Ionizing
radiations
Pharmaceutical Teratogens Thalidoamide ,Tetracycline,
Streptomycin ,Valproic acid,
Warfarin Diethylstilbestrol, Retionic
acid, Pencillin
Industrial Teratogens Lead, Methyl, mercury, Cadmium,
Arsenic
Microbial Teratogens Treponema pallidum (syphilis),
Coxsackie virus, Herpes simplex,
Rubella (German measles),
Cytomeagalo virus (CMV)
Metabolic conditions in the mother Diabetes, Auto immune disease
(including Rh incompatibility),
Phenylketonuria, Dietary deficiencies,
malnutrition
8.
9. Microbial teratogens
• This class of teratogens includes infectious
microorganisms.
• These microbes affect 1-5% of all live
births and are among the leading causes
of neonatal morbidity and mortality.
• General symptoms include premature birth,
growth retardation, neurological
abnormalities, damage of the eye, liver, heart
and ear along with bone lesions.
10. Rubella
• Abnormal babies are born to women suffering from Rubella
(German measles) during the first five weeks of pregnancy.
• The abnormalities include, cataracts, glaucoma, cardiac
malformations, hearing loss and mental retardation. The mode of
action of the pathogen can be direct viral effects or damage to immune
response.
• In 1969, Rubella vaccine was introduced. Since then the cases of
congenital Rubella syndrome have decreased significantly .
Cytomegalovirus (CMV) & Herpes simplex
Cytomegalovirus infection early in gestation is fatal while infection of later
embryos might lead to blindness, deafness, cerebral palsy and mental
retardation. CMV damage including hepatitis, gestational prematurity,
anemia. Mode of action of CMV is similar to that of rubella virus, i.e. cell
lysis and immune response.
12. What is Warfarin?
Warfarin is an oral coumarin anticoagulant widely
used to control and prevent thromboembolic
disorders.
Warfarin is clinically available as a racemic mixture
of R- and S-warfarin. The S-enantiomer has 3–5
times greater anticoagulation potency than its
optical congener R-warfarin.
13. Mechanism of Action
Warfarin acts by antagonizing the antihemorrhagic
effect of vitamin K.
It inhibits hepatic synthesis of vitamin K dependent
coagulation factors II, VII, IX, and X by inhibiting
vitamin K1 -2,3 epoxide reductase, preventing
vitamin K from being reduced to its active form.
14. Pharmacokinetic
The oral bioavailability of warfarin is nearly 100%.
It is highly bound (approximately 99%) to plasma
protein, mainly albumin. (The high degree of protein binding is
one of several mechanisms whereby other drugs interact with warfarin)
Warfarin is distributed to the liver, lungs, spleen,
and kidneys. It does not appear to be distributed to
breast milk in significant amounts. It crosses the
placenta and is a known teratogen.
The duration of anticoagulant effect after a single
dose of warfarin is usually 5-7 days.
15. Dosage and Administration
Adults: PO 2-5 mg/day initially; adjust daily dose
according to PT or INR determinations. Usual
maintenance dose is 2-10 mg/day.
The IV dosages would be the same as those would
be used orally. Administer as a slow bolus injection
over 1 to 2 min in a peripheral vein.
16. Warfarin Monitoring
Prothrombin time (PT) — The most commonly used
test to measure the effect of warfarin. It measures
the time it takes for the clotting mechanism to
progress. Normal range (12–15 seconds).
International Normalized Ratio (INR) — The INR is a way
of expressing the PT in a standardized way; this ensures that results obtained
by different laboratories can be reliably compared.
The longer it takes the blood to clot, the higher the
PT and INR. In most cases the target INR range
will be 2 to 3, although other ranges may be chosen
if there are special circumstances.
21. HISTORY
➢ Developed by German pharmaceutical
company Grünenthal in Stolberg
➢ Introduced as a Sedative drug in the late 1950s
➢ Was found to act as an effective tranquilizer and
painkiller and was proclaimed a "wonder drug" for
insomnia, coughs, colds and headaches.
➢ Found to be an effective antiemetic which had
an inhibitory effect on morning sickness, and so
thousands of pregnant women took the drug to
relieve their symptoms
22. THALIDOMIDE–THESLEEPINGPILL
Hailed as a "wonder drug" that provided a
"safe, sound sleep".
However the drug was also found to cure
morning sickness in pregnant women
Was available as OTC drug
23. CHEMISTRYOF THALIDOMIDE
➢ Thalidomide, a-(N-phthalimido) glutarimide,
➢ Consists of ringed structure with an asymmetric carbon
in the glutarimide ring.
➢ Exists as an equal mixture of S-(-) and R-(+)enantiomers.
➢ These enantiomers rapidly get interconverted under
physiological conditions
➢ Thalidomide is sparingly soluble in water and ethanol,
which to date had prevented its availability as an
intravenous formulation
24. PHARMACOKINETICS
➢ Absorption and Elimination
➢ Absorbed in GIT, not affected by food consumption
➢ Metabolized through a nonenzymatic pathway,
undergoing spontaneous hydrolysis in the blood and
tissues
➢ Found to be present in semen, not clear if it is in breast
milk
➢ Eliminated from the body in about 5-7 hours (not through
feces) (only a very small amount is metabolized by
cytochrome P-450)
25. DAMAGE
➢ 10,000-12,000 thalidomide babies
➢ 46 affected countries
➢ 40%of victims died within a year of birth
➢ Today, there are approximately 5000
thalidomide survivors.
26. SYMPTOM PATTERN
➢ Phocomelia i.e. abnormal limbs
➢ Amelia i.e. missing limbs
Other Teratogenic Effects :
➢ Abnormal number of digits
➢ Missing/malformed eye and ear
➢ Anal atresia
➢ Brain damage/autism
➢
➢
➢ spinal cord defects
Cleft lip or palate
Heart, Kidney ,GIT and Genital defects
