How thalidomide is teratogenic

The thalidomide molecule exists in two forms called isomers (R and S), which are mirror images of each other. Only one (the S form) is terato-genic, and the other (R) is responsible for the sedative action. Unfortunately the liver converts the R form into the teratogenic S form and so the R form could not be used as a safe drug. It now seems that the three-dimensional shape of the molecule of thalidomide is crucial for it to be a teratogen. Only the S form of the thalidomide molecule fits into a particular section of DNA in the nucleus of the cell. It is thought that this interferes with the production of substances called growth factors. Some of the growth factors affected are those involved with the growth of new blood vessels. This is crucial in the development of an embryo: once structures such as limbs start to form, they must be supplied with blood. Other growth factors will be required for the development of limb buds. This particular effect explains why thalidomide is so potent but also so specific to the embryo.

The discovery of how thalidomide causes birth defects has suggested a potential use for it as an anti-cancer drug. The growth of blood vessels is an important part of the development of tumours, which if it were stopped would limit their invasion of tissues and therefore the spread through the body.

The case of thalidomide therefore illustrates another principle in relation to our use of chemicals: there are no safe drugs, only safe ways of using them. In addition to the Paracelsus principle regarding the dose of the chemical, we have to consider how chemicals are administered or the circumstances of exposure. There are certain conditions such as pregnancy or during breastfeeding when exposure to chemicals of any type is unwise or should be reduced as much as possible. There are patients such as the elderly or very young children whose dose may need to be reduced or to whom the drug may not be administered. There are also some genetic factors that make individuals sensitive to a particular drug or group of drugs, which should not be administered to such individuals (see pp. 71-2 on hydralazine). We now have the information to be able to adopt a more flexible approach and make the use of chemicals much safer, at least in some cases.

The final chapter in the thalidomide story is not yet closed. Further research with the drug has revealed that the mechanism that underlies its teratogenic action may be used to advantage in the treatment of cancer. It also has other effects which make it potentially a unique drug for the treatment of leprosy, HIV, and certain serious diseases affecting the mucous membranes (such as those lining the gastrointestinal tract and vagina). Its use in the treatment of leprosy, unfortunately, resulted again in malformations because of inadequate control. It is also being investigated for use in the treatment of tuberculosis.

Thus despite the fact that thalidomide caused such terrible effects in newborn babies, it may yet prove to be a very useful drug under the right circumstances for the treatment of serious diseases and not in women who are liable to become pregnant.

100 Pregnancy Tips

100 Pregnancy Tips

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