Thalidomide

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Thalidomide

• By Student Name
• For Leo Donovan
• 11 Chemistry

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• Thalidomide was one of the biggest medical
  tragedies of modern times. The images of children
  born with shrunken limbs still haunt anyone who
  sees them, and the tragedy is not over. Those
  children are adults today, still coping with
  their disability.
• -BBC News

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What is Thalidomide?

• Thalidomide was developed by Grünenthal
  pharmaceuticals in October 1st, 1957 in Germany.
• It was an effective tranquilizer painkiller
  was declared a "wonder drug" for insomnia,
  coughs, colds headaches.
• Also found to be an effective antiemetic having
  an inhibitory effect on morning sickness, and so
  thousands of pregnant women took the drug to
  relieve their symptoms.

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• It was not realized that thalidomide molecules
  could cross the placental wall affecting the
  fetus until it was too late

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The 2-D Model of Thalidomide

• Oxygen
• Carbon
• Nitrogen

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A 3-D Model of Thalidomide
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Functional Groups
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Names

• Thalidomide was often referred to as a wonder
  drug that provided safe, sound sleep.
• Formula Name- C13 H10 N2 O4
• Systematic (IPUAC) Name-
• (RS)-2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(
  2H)-dione

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R-Thalidomide S-Thalidomide

• The pair of enantiomers are mirror-image
  isomers of each other but cause different
  effects. Although it is now known that the "safe"
  isomer can be converted to the teratogenic isomer
  once its in the human body.

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Isomers continued

• Laboratory tests showed that in some animals the
  'S' enantiomer was tetragenic but the 'R' isomer
  was an effective sedative. See Link
• It is now known that only one of the optical
  isomers is created. Both enantiomers are formed
  in an equal amount in blood. So, even if the'R'
  isomer had been created, the disaster would not
  have been averted.

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Thalidomide Catastrophic Drug

• Thalidomide was a catastrophic drug with tragic
  side effects. It became the killer and disabler.
• More than 10,000 babies in 46 countries were born
  with deformities.
• When thalidomide was taken during pregnancy, Any
  part of the fetus that was in development at the
  time of ingestion could be deformed.

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Birth Defects

• For those babies who survived, birth defects
  included
• -Deafness
• -Blindness
• -Disfigurement
• -Cleft palate
• -Internal disabilities
• -Phocomelia (most affected)

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CATASTROPHIC THALIDOMIDE
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Pros of Thalidomide

• Studies suggest that thalidomide can slow/stop
  the spread of cancer of the brain, breast, colon
  and prostate, as well as multiple myeloma (a
  cancer of the marrow of the bone).
• Thalidomide interferes with
• the formation of blood vessels. Cancers that
  spread have many blood vessels that need to be
  nourished, thus stopping the supply will kill the
  cancer cell.

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Thalidomide Multiple Myeloma Treatment

• Thalidomide was first tested in humans as a
  treatment of multiple myeloma in 1996 due to its
  antiangiogenic activity.
• The combination of thalidomide and other drugs is
  now one of the most common treatments for
  patients with newly diagnosed multiple myeloma,
  with an improved response rate of up to 60-70 !!

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Pros Continued...

• Thalidomide is also used to reduce the size of
  blisters in the mouth caused by AIDS.

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Side effects of Thalidomide as a modern cancer
drug

• Sleepiness, drowsiness, constipation, skin rash,
  severe headaches, stomach aches.
• Numbness pain in your arms, hands, legs and
  feet.
• Dizziness, nausea, giddiness or nervousness at
  higher doses, shivering and buzzing in the ears,
  depression or mood-swings.

Severe Birth Defects
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Thalidomide in Canada

• Thalidomide was banned in Canada in 1962.
• Since August 4, 2010, Canada authorizes the use
  of thalidomide (THALOMID) in the treatment of
  patients with multiple myeloma who are 65 years
  of age or older.

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References

• Bennett, CL - Thalidomide associated with cancer
  http//jama.ama-assn.org/content/296/21/2558.3
• BBC News - Thalidomide 40 years on
  http//news.bbc.co.uk/2/hi/uk_news/2031459.stm
• Ligham, Alex (April 2000), Optical Isomerism In
  Thalidomide
  http//www.chm.bris.ac.uk/motm/thalidomide/optical
  2iso.html
• Benegbi,Mercédes- Canadian Tragedy
• http//www.thalidomide.ca/the-canadian-tragedy/
• Foggo, Daniel ThalidomideA second chance?
  Retrieved online 2009
• http//www.bbc.co.uk/science/horizon/2004/thalidom
  ide.shtml
• Victims Association of Canada Thalidomide
• http//www.thalidomide.ca/thalidomideajd_1805_en/