Thalidomide
Thalidomide is a medication originally introduced in the late 1950s as a sedative, but it was later linked to severe birth defects in newborns when taken by pregnant women. The tragic outcomes included malformations of limbs and other serious congenital issues, leading to the term "thalidomide babies." As a result of this discovery, thalidomide was withdrawn from the market in many countries. However, in recent years, thalidomide has been repurposed for therapeutic uses, particularly in treating conditions like leprosy, certain cancers, and complications from immune diseases. Its ability to inhibit the formation of new blood vessels makes it valuable in cancer treatment, especially for patients who have relapsed after chemotherapy. Despite its therapeutic potential, the drug poses risks of severe birth defects if used by pregnant women, necessitating strict regulations and patient education. The history of thalidomide underscores the importance of monitoring and safeguarding drug use to prevent repeating past tragedies.
Thalidomide
DEFINITION: A drug that previously had been used as a sedative and then was banned for many years because of its severe effects on the developing fetus but found application in the treatment of conditions such as Hansen's disease (leprosy), multiple myeloma, skin conditions, and complications of human immunodeficiency virus / acquired immunodeficiency syndrome (HIV/AIDS).
ANATOMY OR SYSTEM AFFECTED: Arms, blood vessels, feet, hands, immune system, legs
Indications and Procedures
In 1961, a link was established between the use of thalidomide, a mild sedative, and an increase in the frequency of severe defects in newborn babies in Germany, Great Britain, and other countries around the world where the drug had been in use. The “thalidomide babies” had minor defects of the fingers or toes but had major malformations of the limbs, resulting in incomplete or even missing arms and legs. The defects resembled those of a rare genetic disorder known as phocomelia (“seal limb”). Following the tragic discovery that thalidomide was a potent teratogen (a substance that causes a birth defect), the use of the drug was discontinued.
Thalidomide may be a useful therapeutic agent in a number of conditions, including Hansen's disease (leprosy), several other dermatologic disorders, different types of cancer, and acquired immunodeficiency syndrome (AIDS). The Food and Drug Administration (FDA) in the United States approved thalidomide for use in the treatment of Hansen's disease. Studies have demonstrated that thalidomide can inhibit in vitro angiogenesis, the process of formation of new blood vessels. Since many types of cancers require the development of new blood vessels for their continued growth, thalidomide may be especially useful in cases where conventional treatments have ceased to be effective. Its use may be indicated in patients either relapsing after high-dose or who are developing serious side effects and cannot tolerate additional chemotherapy. Thalidomide is especially useful in treating bone marrow cancers.
Uses and Complications
Since thalidomide is such a powerful angiogenesis inhibitor, it is being used in disorders requiring anti-angiogenic therapy. Successful treatments have been made in cases of ovarian cancer, breast cancer, carcinoma, renal melanoma, chronic graft-versus-host disease, and multiple myeloma. In some cases, the effectiveness of thalidomide increased when accompanied by other treatments, including immunotherapy, chemotherapy, and surgery.
Thalidomide appears to have few side effects in its new applications, but its return to medical respectability has raised the specter of “thalidomide babies” again. Adverse effects noted in a few patients have included lethargy, constipation, and peripheral neuropathy. The potential problems associated with thalidomide causing a further round of severe birth defects may be a more serious consequence.
Perspective and Prospects
The outbreak of thalidomide-related birth defects in the 1950s and 1960s led to the creation of surveillance programs in many countries. Unfortunately, medical standards and safeguards are not uniform, and there appeared to be an increase in birth defects associated with the new applications of thalidomide in South America at the beginning of the twenty-first century. It is necessary to regulate and monitor closely the prescription, dispensing, and use of the drug. Counseling patients of childbearing age is an especially critical component if the tragedy of thalidomide’s history is not to be repeated. This issue was of great concern in the 2010s in Brazil, which was seeing the effects of the administration of thalidomide on children born throughout the first decades of the twenty-first century. In 2018, researchers in the US published their finding that thalidomide caused birth defects by degrading SALL4, a key cell protein involved in fetal development.
Bibliography
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