thalidomide

= = = = =**As with any medication these prilosec aspect effects vary in their severity and what may be mild to at least one person may lead to a more serious reaction in others. If you do get any of these prilosec facet effects then it's terribly important that you contact your doctor once potential before they perhaps begin to harm your health in different ways in which. [|side effects prilosec]Thalidomide**=

Seongyeol Lee
Today the word "Thalidomide" has sharply contrasting meanings for different people. To the many children born in the early 1960’s with severe birth defects due to their mothers’ use of the drug, it is a vile word, representative of the unnecessary pain in their lives due to severe deformities. To patients suffering from illnesses such as Hansen’s disease or severe sores due to AIDS, Thalidomide is a miracle drug, helping to alleviate their suffering. The controversy surrounding the current use of this drug is intense. The FDA, whose guidelines were substantially affected by the thalidomide catastrophe of the 1960’s, is caught in between, with the duty of weighing the severe risks posed by the drug, with the potential benefits it has to alleviate a variety of illnesses. (1)

Thalidomide, a glutamic acid derivative was first described in 1953 by Ciba, a Swiss pharmaceutical firm. The company first marketed the drug as an anticonvulsant to be used in the treatment of epilepsy. It did not prove to be effective for this purpose, but it did show promise in its ability to cause sleep. Therefore, it came to be marketed as a hypnotic, sedative, and tranquilizer. Its action was prompt, and it provided a deep sleep without causing a hangover. Additionally, it was unable to be used for suicide, as taking large doses did not cause death. It was found to induce a more healthy sleep than other sleeping pills because its mechanism of action was different – it turned on the part of the brain that tells the body to sleep rather than shutting down the part of the brain that tells the body to stay awake. Thalidomide quickly became West Germany’s most popular sleeping pill and was being prescribed to pregnant women to treat morning sickness. By the end of the 1950’s, it was being marketed by 14 pharmaceutical companies in 46 different countries. (2)

When the FDA received an application from the William S. Merrell Company, the liscensee of Chemie Grunenthal that wanted to market thalidomide in the United States, the file was given to pharmacologist Frances Kelsey, MD, a new medical reviewer for the FDA, and it was considered to be a rather straightforward case. Kelsey, however, was worried that, though the drug was being used throughout Europe, too little information about its side effects was known. Additionally, she found it odd that the drug affected experimental animals differently from humans – no harmful effects had been found in experiments done on animals, but the drug also did not have the beneficial effect of making the animals sleepy. Kelsey withstood the pressure of the drug manufacturers to push through the approval of the drug. (3)

However, It was found that mothers who had taken the drug during the first trimester, when the limb buds of the fetus are formed, produced children with a wide range of deformities. The most well known pattern was phocomelia - absence of most of the arm with the hands extending flipper-like from the shoulders. Another frequent arm malformation was radial aplasia – absence of the thumb and the adjoining bone in the lower arm. Similar limb malformations occurred in the lower extremities. The babies almost always had both sides affected and often had both the arms and the legs malformed. Besides the limbs, the drug caused malformations of the eyes and ears, heart, genitals, kidneys, digestive tract (including lips and mouth), and nervous system. (4)

It was soon discovered that only one particular optical isomer of thalidomide caused the teratogenicity.(figure1) The pair of enantiomers, while mirror images of each other, cause different effects although it is now known that the "safe" isomer can be converted to the teratogenic isomer once in the human body. The (R) enantiomer is effective against morning sickness but the (S) is teratogenic. The enantiomers can interconvert (racemize) in vivo that is, if a human is given pure (R)-thalidomide or (S)-thalidomide, both isomers will later be found in the serum – therefore, administering only one enantiomer will not prevent the teratogenic effect. (5)

Most recently, there have been studies showing that the treatment of multiple myeloma, an incurable bone marrow cancer that accounts for 2 percent of cancer-related deaths, is another possible use for the drug. In a study conducted last year at the University of Arkansas, one-third of the eighty-four patients who had failed to respond to other therapies improved, and two went into complete remission. The possible mechanisms of action of thalidomide, its in vivo metabolites, or both, in myeloma are being extensively studied. (6)

References (1) A.F. Gunnison and R. Jaeger. Thalidomide: Lessons from the Past - Adina Fisher: Toxicology. Retrieved September 5, 2005 (2) Warren, Randolph. "The Many Faces of Thalidomide." Thalidomide Victims Association of Canada website: [] (3) Randall, Teri. "Thalidomide Has 37-Year History." JAMA 263 (1990): 1474 (4) "Thalidomide." Center for the Evaluation of Risks to Human Reproduction (CERHR) website: [] (5) Mariana Lazarini, Fabiola Traina, Sheila M. Winnischofer, Fernando F. Costa, Mary Luci S. Queiroz, Sara T. Olalla Saad. Effects of thalidomide on long-term bone marrow cultures from patients with myelodysplastic syndromes: Induction of IL-10 expression in the stromal layers Leukemia Research, In Press, Corrected Proof, Available online 20 April 2011 (6) Anderson, Kenneth; Raje, Noopur. "Thalidomide – A Revival Story." New England Journal of Medicine 341 (1999): 1606-8.