Drug development Flashcards
What is target selection?
Could be receptors, enzymes, or transport proteins
then finding a lead by using automated screening against libraries
What is lead selection?
Exploratory toxicology and safety, then preclinical development, then clinical development
What are the default rodents used?
Rats
What are the default non-rodents used?
Beagles
What are the three dose groups for toxicology?
Low- no toxicology
Intermediate
High- toxicology expected in target organ
What is clinical pathology?
Haematology and clinical chemsitry, kidney and liver function and coagulation
What are the goals of non-clinical safety evaluations?
That toxicity is on target and not going anywhere else, that it is reversible, toxicokinetics, maximum toxic dose and minimum affective dose, dose selection for humans and identification of specific monitoring requirements
What physiological functions initially have to be investigated for undesirable effects from a drug?
Cardiovascular system
Central nervous system
Respiratory
What is the purpose of phase 1 clinical trials?
Finding out if it is safe, how well it is tolderated and what pharmacokinetic properties it has
What is the purpose of phase 2 trials?
Finding out how much should be given to be effective and how well the treatment actually works
What is the purpose of phase 3 trials?
Has several thousand patients and definitive results are needed, they are multi centre and multi national which makes logistics a lot harder
What is the purpose of phase 4 trials?
Post marketing surveillance- when rare or long term adverse effects are detected when it is on the market
What is biologics?
Antibody based medicine, vaccines, RNAi, cell based or gene therapy
How is selection of a relevant animal model important when using biopharmaceuticals?
Human proteins will cause a large reaction in animals that won’t tell you anything, which is different to small molecules drugs
How is the anticipation of risk different for biopharmaceuticals compared to small molecule drugs?
Thourough understanding of the infusion reaction and the cytokine storm is needed
Cytokine release syndrome
How is cytokine release syndrome prevented?
Receptor interaction and occupancy must be measured in preclinical trials
drug can’t be given to large groups of people at once
What is immunotherapy?
Form of cancer treatment that uses the immune system to attack cancer cells in the same way it would attack bacteria or a virus
What are checkpoint inhibitors?
Releasing a natural brake on your immune system so that T cells can recognise and attack tumours
What is CAR T cell therapy?
Chimeric antigen receptor therapy- scientists engineer a patients own immune cells to make a new protein which turns them into supercharged cancer fighters
What is IL-2?
Growth factor of T cells and white blood cells
Used as immunotherapy until it was found it harmed the patients more than the cancer itself
