Chinmaya Keshari Sahoo, B.Ramesh and N.Jagan Mohan
Research Scholar,Department of Pharmaceutics,Osmania University College of Technology, Osmania University,Hyderabad,A.P.
Princeton College of Pharmacy,Korremula, R.R.Dist, A.P, India
The production of gross structural malformations/abnormalities during foetal development due to drug induced is known as teratogenesis. The placenta does not strictly constitute a barrier and any drug can cross it to greater/lesser extent.Hence the drug effect on embryo is irreversible. Most birth defects about 70% occur with no recognizable causative factor. Drug or chemical exposures during pregnancy are believed to account for only about 1% of all foetal malformations.
Keywords: Teratogenesis, embryo, pregnancy
Mammalian foetal development passes through 3 phases.Drugs can affect the foetus at three stages such as blastocyst formation(0-16days),organogenesis(17-60days) and histogenesis and maturation of function(60days onwards).
Blastocyst formation:Cell division is the main process occurring during blastocyst formation.During this phase drugs can cause death of embryo by inhibiting cell division.Alcohol may affects in this stage.
Organogenesis:In organogenesis the structural organization of organ of embryo occurs in aproper sequence.It is the most vulnerable period of deformities.The drug can interfere with the cellular processes of division, migration and development. Histogenesis and maturation of function:The foetus is dependent on an adequate supply of nutrients and development is regulated by variety of hormones.Gross structural malformations do not raise from exposure of mutagens at this stage ,but drugs that interfere with supply of nutrients or with the hormonal milieu may have deleterious effect on growth and development.
Some teratogenic drugs and their effect.
1.Aspirin: Premature closure of ductus arteriosus
3.ACE inhibitors: Oligohydramnios,renal failure
4.Androgen: Masculinisation in female
5.Carbamazepine: Neural tube defect
6.Corticosteroids: Cleft palate and congenital cataract
7.Estrogen: Testicular atropy in male
9.Indomethacin: Premature closure of ductus arteriosus
10.Lithium: Foetal goiter
11.Methotrexate: Multiple defect,foetal death
12.Phenytoin: Microcephaly,hypoplastic phalanges
13.Penicillamine: Loose skin
14.Stilboestrol: Vaginal carcinoma in teenage offspring,vaginal adenosis in female foetus.
15.Tetracycline: Staining of bones and teeth
16.Thalidomide: Phocomelia,heart defect,gut atresia
17.Valproate: Neural tube defect andspinabifida
18.Warfarin: Saddle nose,defects in limbs and eyes
Testing of teratogenicity:
In Vitro method:Based on the culture of cells,organs and whole embryo.
In Vivo method:Pregnant females are dosed at various levels during the critical period of organogenesis and fetuses are examined for structural abnormalities.
From the above review emphasizes on teratogenic effect and various teratogenic drugs and its effects.