Week 6 - Thalidomide

Question 1

Barbiturate Tranquilisers

Answer 1

• Powerful sedatives but serious side-effects
• e.g. Nembutal addiction, tolerance
• low margin of safety - overdose concerns

Question 2

Issues with pregnancy?

Answer 2

• sleep diruption
• Insomnia very common, nausea related
• Severity often increases with gestational age

Question 3

How was thalidomide discovered?

Answer 3

• accidentally discovered trying to produce antibiotic peptides.
• commenced animal testing in rats to find application
• no signs of toxicity in rats
• Inactive in classic sedative tests (righting reflex)

Question 4

Thalidomide trials

Answer 4

• human trials were horribly inadequate and involved basically no trials on pregnant women
• little to no follow up on patient monitoring
• distributed to company employees free of charge
• when shipped overseas there was no further trials with no toxicologists bought on board

Question 5

Distribution

Answer 5

• First sold in 1957 as Contergan in Germany

- 1961 it was the top selling sedative in Germany

Question 6

Problem? (Thalidomide)

Answer 6

• 1956 Earless daughter born from Grunenthal worker
• No link identified 10 months before marketing of drug :(
• Dizziness, Memory Loss, Numb hands and feet, GI tract pain and constipation all reported in first year.
  All met with denial

Question 7

Big Problem? (Thalidomide)

Answer 7

• Epidemic of children being born with “seal limbs” or Phocomelia, a normally very rare condition.
• 1960, Australia, several cases of seal limbs in babies of mothers prescribed thalidomide
• 1957 - 1962 10000 malformed babies likely as a result of thalidomide.
• Grunenthal finally recall drug

Question 8

Phocomelia

Answer 8

• ## Small or absent ears, small eyes, CNS (autism and low IQ), Heart, Kidneys, GI- tract

Question 9

Drug reform

Answer 9

• High level of care needed when developing new new drugs
• The birth of modern toxicology
• Need for a governing body on the regulation of drug production and laws