Blog on Thalidomide Tragedy
Thalidomide Drug Disaster 1953
WHAT IS THALIDOMIDE
Thalidomide was first developed by CIBA. A Swiss pharmaceutical company in the early 1950s, and subsequently introduced as contergen by Chemi Grunenthal. . It was advertised as having sedative, hypnotics and anti-emetics actions and thoughts to having no toxic side effects. Thalidomide remains one of the most feared and notorious, drugs in the world. The thalidomide caused limb deformaties but also affected ear, eye, genitals, and other internal organs such as the kidney, heart, and intestines As well as, the central nervous system, and nervous system of the embryo, including causing facial palaries. Thalidomide was damage to these tissue occurs. In a less time, window early in embryonic development. The thalidomide tragedy highlighted species difference in drugs action and resulted in regulation that changed the way all drugs were tested for side effects and safety.
However, unlike today’s level of rigorous testing , the drugs Was not analyzed for any potentially dangerous teratogenic effects. Such work raise the possibility of producing analogs or synthesizing new forms of thalidomide that maintain the clinical benefits eradicate the teratogenic side effects.
HISTORICAL BACKGROUND
Thalidomide was first marketed by the Chemie Grunenthal company is Germany in 1957. as a nonaddictive, nonbarbiturate sedative and hypnotics. It was advertised as having sedative, hypnotic, and also antiemetic action and through to have no toxic effect. Thalidomide was also widely used to treat morning sickness in pregnant women.A UK Government warning was not issued until May 1962.Thalidomide was, by 1961, distributed in 46 countries around the world, including the UK, Germany, Ireland, Australia, Sweden, Brazil and Canada. This drugs then had becomes over the counter drugs in west Germany on Octomber 1,1957.
THE THALIDOMIDE TRAGEDY
Thalidomide was initial marketed within the late 1950s as a sedative and was used in the treatment of nausea in pregnant women. Inside some years of the widespread use of sedative-hypnotic in Europe, Australia, and Japan, about 10,000 kids were born with phocomelia, resulting in the ban of thalidomide in most countries in 1961. The thalidomide caused limb deformaties but also affected ear, eye, genitals, And other internal organs such as the kidney, heart, and intestines As well as, the central nervous system, and nervous system of the embryo, including causing facial palaries. Thalidomide was damage to these tissue occurs. In a less time, window early in embryonic development. The thalidomide tragedy highlighted species difference in drugs action and resulted in regulation that changed the way all drugs were tested for side effects and safety.
Thalidomide was not formally distributed in the United States between 1957 and 1961 as Dr. Frances Kelsey of the FDA deniel its approval because of the side effect of peripheral neuropathy that had been experienced in some patients taking thalidomide over a long period in Britain and Germany and her concerns over its safety during pregnancy. Dr Kelsey was awarded associate degree unearned membership to the Society of Toxicology in celebration of its fiftieth day in 2011.
MECHANISM OF ACTION-THALIDOMIDE
Thalidomide as a first established as agent with Antiangiogenic properties thalidomide and IMiDs inhibits the production of interleukin (IL)-6 which is growth factor for the proliferation of myeloma cells. Thalidomide cause the widespread, and sometimes catastrophic, damage to the forming embryo? Over 30 models/hypotheses of thalidomide’s mechanism of action have been proposed since the thalidomide tragedy was first described in 1961.
THALIDOMIDE TODAY
After being discovered to be effective as a treatment for leprosy in 1965. Gained FDA approval & reintroduced in market 1998 for ENL. Gained FDA approval for MDS associated with 5q syndrome in 2005 & for multiple myeloma in 2006. It also used as part of the treatment regimen for multiple myeloma, bone marrow overproduced white blood cells. And also used HIV, arthritis and some cancer.
ADVERSE EFFECT OF THALIDOMIDE DRUGS
Teratogenesis: “Species-specific” teratogebesis.
Non-teratogenic in animal models of rate, mice, hamster & Chick embryos.
CNS effect: sedative, tremors, peripheral (sensory) Neuropathy.
Hypersensitivity: Skin rashes, urticaria, eosinophilia.
GIT: Constipation.
Impact on the craniate once taken by pregnant women:
Bilateral limb atrophy (legs, arms or both) - a condition called phocomelia.
• Bilateral limb absence (Amelia).
• Missing fingers or toes
• Abnormalcy of the fingers or toes.
• Additional fingers or toes.
• Total or partial hearing impairment.
• Partial or total vision loss.
• Disfunction (usually facial muscles).
Malformation of the epithelial duct.
Malformation of the small intestine(most of the time fatal, before or shortly after birth).
Malformation or absence of the orifice.
Important organs injury (most of the time fatal, before shortly once birth).
Death.
THALIDOMIDE AND PREGNANCY
In the 1950s, scientists failed to apprehend that the results of a drug might be passed through the placental barrier and damage a vertebrate within the female internal reproductive organ, therefore the use of medications throughout physiological condition wasn’t strictly controlled. And within the case of thalidomide, no tests were done involving pregnant women.
As the drug was listed beneath such a large amount of totally different names in 49 countries, it took 5 years for the affiliation between thalidomide taken by pregnant women and the impact on their children to be created. A UK Government warning wasn’t issued till 1962.
One reason why researchers and doctors were slow to form this affiliation was thanks to the big selection of changes to vertebrate development. Limbs, internal organs including the brain, eyesight and hearing might all be affected.
Later, they found that the impact on development was joined to once throughout pregnancy the drug was taken, and effects only occurred between 20 and 37 days after conception. After that, thalidomide had no effect on the fetus.
Another reason why it took so long to ascertain the link to thalidomide was that a number of the injury caused by the drug was terribly the same as bound genetic conditions that have effect the upper or lower limbs.
REFERENCE
Neil vargesson ,Thalidomide, ResearchGate,(2017).P.467-477.
https://www.slideshare.net/KajalPradhan4/the-thalidomide-tragedypptx
Student Name: Jadhav Rajesh Bhagwan
Student ID: 012/012023
Qualification: M. Pharm (Pharmacology)
e-Mail ID: rajeshjadhav5600@gmail.com
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