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Ophthalmology => Macular Degenrtion => Thalidomide
Thalidomide
INTRODUCTION
Thalidomide, drug introduced in 1953, initially prescribed for its sedative properties and widely used by women to alleviate the nausea and vomiting common in the early stages of pregnancy. Thalidomide gained notoriety in 1961 when it was found to cause severe malformations in the growing fetus such as stunted development or the complete absence of limbs. More than 10,000 children were born with these disabling abnormalities before the drug was taken off the market. This disaster triggered more rigorous government regulations for drug testing. Today thalidomide is used in the treatment of leprosy, and experimentally in bone-marrow transplant patients and certain immune system disorders.
HISTORY
Thalidomide was first produced by Chemie Grunenthal, a German pharmaceutical company. By the late 1950s the drug was widely used as a tranquilizer in Germany, Britain, and other countries. The drug was never sold in the United States because marketing was delayed when the Food and Drug Administration's (FDA) review of its application for approval revealed evidence of nerve damage with long-term thalidomide use. During this delay, reports emerged from Europe of severe birth defects in children born to women who took thalidomide while pregnant. Eventually, the clear connection between thalidomide usage and birth defects was firmly established and thalidomide was withdrawn from commercial distribution worldwide in 1961.
A single dose of thalidomide taken only 34 to 50 days after a woman's last menstruation before pregnancy is enough to hurt a developing fetus. This period is crucial for the development of the fetus's limbs and major organ systems. In addition to stunted or missing limbs, other organs susceptible to malformation from thalidomide use during this sensitive period include the ears, lip, palate, eyes, heart, spine, respiratory tract, gastrointestinal tract, kidneys, and reproductive tract.
The mechanism of thalidomide's negative effects has not been established, but some evidence suggests it may be related to the drug's ability to inhibit the formation of new blood vessels. Growing tissue needs an adequate blood supply to furnish it with needed nutrients and oxygen. Inadequate blood circulation would impair growth and development.
The thalidomide disaster mobilized American support for the Drug Amendments Act of 1962. Among other issues, this legislation strengthened the FDA's role in overseeing the drug development process. The FDA began to require that pharmaceutical companies determine that a new drug does not affect fetal development before the drug can be approved for sale in the United States.
IIIRECENT USES While its commercial distribution was halted, thalidomide continued to be used in experimental studies for a variety of diseases. A series of studies beginning in the mid-1960s showed that thalidomide was effective in treating a leprosy-related disorder, erythema nodosum leprosum (ENL). A serious skin disorder, ENL usually develops in leprosy patients after they begin taking antibiotics to combat the leprosy-causing bacterium Mycobacterium leprae. ENL is believed to be caused by an abnormal immune reaction to the killed bacteria.
The FDA approved thalidomide for the treatment of ENL in July 1998, at the same time placing unprecedented restrictions on the drug's use. Under these restrictions, thalidomide can only be obtained from selected doctors and pharmacies that have agreed to follow a strict protocol designed to prevent birth defects from the drug. Both men and women taking the drug must use birth control during sexual intercourse, and women must also agree to undergo periodic pregnancy tests.
Thalidomide's success in treating ENL, although not fully understood, triggered extensive studies into the drug's effects on the immune system. Some studies suggest that thalidomide reduces the production of tumor necrosis factor-alpha (TNF-a), a protein made by immune cells that may cause problems such as wasting, or chronic weight loss, when produced in excessive amounts. Thalidomide has also been proven to heal painful canker sores in the mouth of patients with acquired immune deficiency syndrome (AIDS) or other patients with impaired immune systems. Canker sores in these patients do not heal as readily as in people with normal immune systems, and the sores make eating difficult.
Early evidence suggests that thalidomide effectively suppresses the body's rejection of donor bone marrow that sometimes occurs in bone-marrow transplant patients. Thalidomide is also being studied as a possible treatment for various cancers and other diseases because of its ability to inhibit growth of new blood vessels. This inhibition could slow or completely prevent growth of cancerous tumors that require new blood vessels in order to thrive.
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