Lecture 13 Flashcards
What is Thalidomide/Contergan?
It was a drug marked in the 1950s to alleviate morning sickness in pregnant woman
What was the issue with Thalidomide/Contergan?
It ended up causing thousands of infants to be born with phocomelia which is the severe malformation of limbs
When Thalidomide/Contergan withdrawn and what is it now used for?
-Withdrawn in 1961
-now used to treat leprosy and multiple myeloma as an orphan drug
What is potential drug teratogenicity?
It is the ability of a substance to cause birth defect
Why are animals used in toxicity testing
Because they are the most reliable testing source in the absence of human data
Toxixty tests depend on?
-The type of substance
-Regulations of the country
-The use of the test agent
How does tissue-specific toxicity occur?
Usually occurs from specific interactions between the test substance and a particular biological system
Considerations for toxicity testing:
-Biological considerations
-Physio-chemical properties of test substance
Biological considerations for toxicity testing includes:
-Species, strain, and sex of test animal
-Metabolic and physiological similarity to humans
-Duration of toxicity testing
-Number and diet of test animals
Physico-chemical properties of test substance includes:
-Structure
-Vapour pressure
-pKa (acid dissociation constant)
-Solubility (water vs fat)
-Melting point
-Purity
Compounds which undergo toxicity testing are divided into?
- Intended for administration to humans
- Non intended for administration to humans
Examples of substances intended for administration to humans:
-Pharmaceuticals
-Food additives
-Drug additives
Examples of substances non-intended for administration to humans:
-Biocides(pesticides)
-Environmental contaminants
-Industrial chemical
-Household chemical
-Natural toxins
Preclinical testing can be done on what?
-Animals
-Animal models of human disease
-Isolated organs
-Cell cultures
How does toxicity ratings work?
It goes from 1 to 6
1 being super toxic and 6 being practically non toxic
Reasons tests may vary between laboratories:
-Differing genotype or phenotype of sample population
-Difference in tested range of animal species
-Influence of environmental factors
-Mode of drug administration
What a slightly toxic agent?
-Ethanol
-Has a high LD50 value
Chronic exposure of ethanol results in what?
It triggers severe side effects in various tissues based on drastic metabolic disturbances
Example of a super toxic agent?
-Botulinum toxin
-Has an extremely low LD50 value
What bacteria is botulinum toxin produced by?
Clostridium botulinum
What can exposure to botulinum toxin cause?
Sever food poisoning called Botulism
How does Botulinum toxin work?
It is a protein that binds to cholinergic nerve terminals which inhibits the release or Achieve by degrading key proteins for the vesicular docking process
What is a dose-response curve?
Can determine the concentration of an agent that causes the median lethal dose
What alternative approach can be used for reduce the number of animals in toxicity testing?
Fixed Dose procedure
