Thalidomide

From Academic Kids

Thalidomide is a drug which was sold during the 1950s and 1960s as a sleeping aid and to pregnant women as an antiemetic to combat morning sickness and other symptoms. It was synthesized in West Germany in 1953 and marketed by the Stolberg-near-Aachen-based pharmaceutical company Grnenthal from October 1, 1957 to 1961, mainly in Germany and Britain. It was available in around fifty countries, although not in the United States, under at least forty different names (such as Talimol, Kevadon, Nibrol, Sedimide, Quietoplex, Contergan, Neurosedyn, etc.).

It was later (1960–61) found to be teratogenic in fetal development, most visibly as a cause of amelia or phocomelia as the drug is an angiogenesis inhibitor — interfering with blood vessel development, especially if taken during the first 25 to 50 days of pregnancy. Around 15,000 fetuses were damaged by Thalidomide, of whom about 12,000 in 46 countries were born with birth defects, with only 8,000 of them surviving past the first year of life. Most of these survivors are still alive, nearly all with disabilities caused by the drug. In 2003, a World Health Organization newsletter cited evidence that the disabilities and deformities in many Thalidomide survivors may be passed on to the survivor's own children through DNA, but many discount this as scientifically unfounded. Those deformed by Thalidomide are sometimes referred to (or self-described) as thalidomiders.

Thalidomide was banned for its intended use but it has been found to be effective for other indications. The FDA has approved thalidomide, under a restricted access system, for the treatment of erythema nodosum leprosum (ENL) associated with leprosy (Hansen's Disease). As of 2001, thalidomide was in clinical trials as an antineoplastic agent, in HIV related symptoms by reducing inflammation (blocking TNF), for advanced multiple myeloma, prostate cancer, glioblastoma, and Crohn's disease. Australian researchers began a trial of the controversial drug in April 2002, involving 224 cancer patients over a two-year period. The study found Thalidomide sparked a doubling of the number of T cells in patients. This allowed their own immune system to attack and fight the cancer.

Contents

The thalidomide tragedy

Thalidomide had passed safety tests performed on animals, primarily because the proper tests — particularly those involving pregnant animals — had not been correctly administered or simply were not done. A court trial revealed that some tests were either conducted inadequately, or the results were faked. However, many animal trials were done by independent agencies and licensees in several countries before Thalidomide was approved, and few revealed any side effects. In some tests, dosages of over 600 times the normal human dosage had no effect at all on rodents.

The failure of these tests to discover the drug's disastrous consequences highlighted the inadequacy of testing methodologies in use at that time. This resulted in an intensive increase in animal testing across a broad range of species in varying stages of pregnancy and lifecycle. In fact, later tests did demonstrate that administering thalidomide to some strains of pregnant rats reduces the number in the litter by 50%, and giving it to rabbits produces characteristic deformities in the offspring. If adequate or non-animal testing had been done, thalidomide might never have been approved to be sold anywhere. Some opponents of animal testing still cite thalidomide (some would say incorrectly) as an example of the ineffectiveness of such testing.

In 1960, Chemie Grnenthal decided to expand into the United States, and applied to the Food and Drug Administration for approval to sell the drug. This approval was not expected to be controversial, and the case was given to the agency's newest reviewer, Frances Oldham Kelsey. Kelsey had previously done animal toxicity research (including effects in pregnancy), and refused to clear thalidomide for sale until she obtained better documentation of its effects, especially in light of some unusual neurological side effects being reported in Britain. In fact, the testing had not been performed adequately, and satisfactory documentation was not forthcoming.

Though the US marketer William S. Merrell Company was increasing pressure to have it cleared for sale, Kelsey held out for more toxicity data before coming to a decision. The decision was pre-empted by births throughout the world giving evidence of thalidomide's effect on the embryo, and the manufacturers quickly withdrew their application. Kelsey's delay probably prevented thousands of deformities in the US, and made her a national hero. In August 1962, Kelsey was awarded the President's Award for Distinguished Federal Civilian Service (at the time, the highest civilian award in the US) by President John F. Kennedy.

Technical details

Missing image
Thalidomide_structure.png
Image:thalidomide_structure.png

Thalidomide (C13H10N2O4; phthalimido-glutarimide; one of a number of systematic names is 2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione) is a sedative and hypnotic drug. Thalidomide was synthesized at Chemie Grünenthal in West Germany in 1953.

Thalidomide is racemic — that is, it contains both left and right handed isomers in equal amounts: one enantiomer is effective against morning sickness, and the other is teratogenic. It should be noted that the enantiomers are converted to each other in vivo. That is, if a human is given D-thalidomide or L-thalidomide, both isomers can be found in the serum. Hence, administering only one enantiomer will not prevent the teratogenic effect in humans.

The drug is most toxic if taken orally and is a mild carcinogen. Other symptoms can include peripheral neuritis, numbness, paresthesias in the extremities, peripheral neuropathy, mental confusion, unsteadiness, hypotension, and absent reflexes. Excessive dosages can lead to pulmonary oedema, atelectasis or aspiration pneumonia, and refractory hypotension.

Famous thalidomide children

Brett Nielsen, is a musician. His career in sound began over 25 years ago in commercial radio and television. He lives in Mullumbimbi, Australia with his wife and 3 kids. Brett is the first Australian thalidomide child.

Terry Wiles' life was documented in the book "On Giant's Shoulders: The Story of Terry Wiles" (ISBN 0723001464) by Marjorie Wallace, as well as in a movie by the same name adapted from the book.

Tony Melendez is a guitarist who was born without arms as a result of his mother having taken Thalidomide during pregnancy. He plays only with his feet.

Thomas Quasthoff is an internationally acclaimed bass-baritone who describes himself : "1.34 meters tall, short arms, seven fingers - four right, three left - large, relatively well formed head, brown eyes, distinctive lips; profession: singer."

External links

fr:Thalidomide he:תלידומיד ja:サリドマイド nl:Thalidomide pl:Thalidomid

Navigation

Academic Kids Menu

  • Art and Cultures
    • Art (http://www.academickids.com/encyclopedia/index.php/Art)
    • Architecture (http://www.academickids.com/encyclopedia/index.php/Architecture)
    • Cultures (http://www.academickids.com/encyclopedia/index.php/Cultures)
    • Music (http://www.academickids.com/encyclopedia/index.php/Music)
    • Musical Instruments (http://academickids.com/encyclopedia/index.php/List_of_musical_instruments)
  • Biographies (http://www.academickids.com/encyclopedia/index.php/Biographies)
  • Clipart (http://www.academickids.com/encyclopedia/index.php/Clipart)
  • Geography (http://www.academickids.com/encyclopedia/index.php/Geography)
    • Countries of the World (http://www.academickids.com/encyclopedia/index.php/Countries)
    • Maps (http://www.academickids.com/encyclopedia/index.php/Maps)
    • Flags (http://www.academickids.com/encyclopedia/index.php/Flags)
    • Continents (http://www.academickids.com/encyclopedia/index.php/Continents)
  • History (http://www.academickids.com/encyclopedia/index.php/History)
    • Ancient Civilizations (http://www.academickids.com/encyclopedia/index.php/Ancient_Civilizations)
    • Industrial Revolution (http://www.academickids.com/encyclopedia/index.php/Industrial_Revolution)
    • Middle Ages (http://www.academickids.com/encyclopedia/index.php/Middle_Ages)
    • Prehistory (http://www.academickids.com/encyclopedia/index.php/Prehistory)
    • Renaissance (http://www.academickids.com/encyclopedia/index.php/Renaissance)
    • Timelines (http://www.academickids.com/encyclopedia/index.php/Timelines)
    • United States (http://www.academickids.com/encyclopedia/index.php/United_States)
    • Wars (http://www.academickids.com/encyclopedia/index.php/Wars)
    • World History (http://www.academickids.com/encyclopedia/index.php/History_of_the_world)
  • Human Body (http://www.academickids.com/encyclopedia/index.php/Human_Body)
  • Mathematics (http://www.academickids.com/encyclopedia/index.php/Mathematics)
  • Reference (http://www.academickids.com/encyclopedia/index.php/Reference)
  • Science (http://www.academickids.com/encyclopedia/index.php/Science)
    • Animals (http://www.academickids.com/encyclopedia/index.php/Animals)
    • Aviation (http://www.academickids.com/encyclopedia/index.php/Aviation)
    • Dinosaurs (http://www.academickids.com/encyclopedia/index.php/Dinosaurs)
    • Earth (http://www.academickids.com/encyclopedia/index.php/Earth)
    • Inventions (http://www.academickids.com/encyclopedia/index.php/Inventions)
    • Physical Science (http://www.academickids.com/encyclopedia/index.php/Physical_Science)
    • Plants (http://www.academickids.com/encyclopedia/index.php/Plants)
    • Scientists (http://www.academickids.com/encyclopedia/index.php/Scientists)
  • Social Studies (http://www.academickids.com/encyclopedia/index.php/Social_Studies)
    • Anthropology (http://www.academickids.com/encyclopedia/index.php/Anthropology)
    • Economics (http://www.academickids.com/encyclopedia/index.php/Economics)
    • Government (http://www.academickids.com/encyclopedia/index.php/Government)
    • Religion (http://www.academickids.com/encyclopedia/index.php/Religion)
    • Holidays (http://www.academickids.com/encyclopedia/index.php/Holidays)
  • Space and Astronomy
    • Solar System (http://www.academickids.com/encyclopedia/index.php/Solar_System)
    • Planets (http://www.academickids.com/encyclopedia/index.php/Planets)
  • Sports (http://www.academickids.com/encyclopedia/index.php/Sports)
  • Timelines (http://www.academickids.com/encyclopedia/index.php/Timelines)
  • Weather (http://www.academickids.com/encyclopedia/index.php/Weather)
  • US States (http://www.academickids.com/encyclopedia/index.php/US_States)

Information

  • Home Page (http://academickids.com/encyclopedia/index.php)
  • Contact Us (http://www.academickids.com/encyclopedia/index.php/Contactus)

  • Clip Art (http://classroomclipart.com)
Toolbox
Personal tools