Читать книгу Clinical Pharmacology and Therapeutics - Группа авторов - Страница 95

It is during this period that the developing embryo shows great sensitivity to the teratogenic effects of drugs. A teratogen is any substance (virus, environmental toxin or drug) that produces deformity. Before discussing the teratogenic properties of certain drugs, the following points must be appreciated:

1 Teratogenesis in humans is very difficult to predict from animal studies because of considerable species variation. Thalidomide, the most notorious drug teratogen of recent times, showed no teratogenicity in mice and rats

2 Serious congenital deformities are present in 1–2% of all babies; therefore, a drug is only readily identified as teratogenic if its effects are frequent, unusual and/or serious. A low‐grade teratogen that infrequently causes minor deformities is likely to pass unnoticed

Table 1.8 Drugs that are known to be teratogenic.

Drug	Deformity
Danazol	Virilisation of female foetus
Lithium	Cardiac (Ebstein's complex)
Phenytoin	Craniofacial; limb
Carbamazepine	Craniofacial; limb
Retinoids	Central nervous system
Valproate	Neural tube; neurodevelopment
Diethylstilbestrol (stilboestrol)	Adenocarcinoma of vagina in teenage years
Warfarin	Multiple defects; chondrodysplasia punctata

Table 1.8 lists some drugs that are known to be teratogenic. It is important to emphasise that, even for known teratogens, first trimester use often results in a normal baby, e.g. phenytoin is teratogenic in about 4% of exposures and warfarin in up to 5%. Also, there will be occasions, such as the use of warfarin in women with prosthetic heart valves, where the risks to the mother of not using the drug outweigh the risks of exposure in the foetus. The greatest risk of teratogenesis occurs at a time when a woman might not even be aware that she is pregnant.