Lecture 14 Flashcards
1
Q
where was thalidomide founded
A
- Chemie Grünenthal GmbH,
personal products company - Founded in Germany in 1946
- Many former Nazis in company
2
Q
who discovered thalidomide
A
- Wilhelm Kunz, Grunenthal chemist
- Discovered thalidomide (by-product while making antibiotic peptides)
- commenced testing on rats, mice, guinea pigs
- inactive in classic sedative tests (righting reflex)
3
Q
What was the infamous Grunenthal ‘jiggle cage’?
A
- 8 mice treated with sedatives (e.g. barbiturates) or thalidomide (hypnotic)
are less active (less H2 gas released) than drug-free controls - measure H2 release with hydrogen detector
- Reduction of H+ at electrode releases hydrogen gas
- platinum electrode dips into acid when mice move or jiggle the cage
4
Q
what were the symptoms reported after the 1st year of distrabution
A
- Dizziness
- Memory loss
- Blood pressure loss
- Cold hands and feet
- Numb hands & feet
- GI-tract pain & constipation
5
Q
what epidemic unfolded due to thalidomide
A
- Phocomelia: seal limbs, absent or ill formed upper or lower limbs
- amelia: both upper and lower limbs are affected
- rare condition
6
Q
Who made the link between thalidomide and the epidemic
A
- William McBride
- drug removed from hospital pharmacy
- dec 1961 famous letter in BMJ
7
Q
how many babies did thalidomide effect
A
- 10,000 malformed babies worldwide
- excludes miscarriages and still births
- high mortality rate in newborns
8
Q
what was the window of susceptibility for a thalidomide toxicity
A
- Day-20 to Day-36 post-fertilization
- Day 34 to Day 50 after last menstrual cycle
- 1 pill sufficient within this period
9
Q
Disability Issues in Ageing Thalidomiders
A
- Musculoskeletal Problems
- pain
- dental complications
- sensory deficits
- general health
- mental health
10
Q
how did thalidomide make a comback ?
A
- Used to slow down body wasting in leprosy victims
- Also to prevent weight loss &
mucocutaneous ulcers in HIVinfected patients - cancer
