Guest Lecture Flashcards
what are important things to know before taking a drug? (3)
1) safe?
2) work?
3) side effects?
what are alternatives to animal models? (3)
1) isolate cells
2) purified enzymes
3) computer models
what animals are most procedures done on?
mice and rats
what area of studies are non-human primate models especially important?
neuroscience (ie neurodegeneration)
how are animals governed?
institutional animal care and use committees (IACUCs)
what do research/teaching involving the use of animals a UBC need to conform to?
UBC Policy #91 (Research and Teaching Involving Animals)
- need to get approval from UBC committee
how do we help ensure that things are standard across UBC animal care facilities?
UBC has an IACUC Safety Operating Procedures (SOPs)
- need to develop SOPs and submit them to IACUC
- lots of SOPs already exist too
what are the three R’s?
1) Replacement
2) Reduction
3) Refinement
how does the Post Approval program at UBC work?
1) clinical vet visit
2) IACUC visit
3) lab-specific Continuing Review
what is “replacement”?
conscious and living vertebrates must be replace by non-sentient alternatives
what is “reduction”?
reduce the number of animals needed
Fixed Dose Procedure
alternative to LD50 tests where fewer animals used
what is “refinement”?
procedures have to be refined to reduce the incidence or severity of suffering
how do rabbits need to be accomodated?
given bedding material, boxes and tubes
how do rodents need to be accomodated?
given nesting material
how do monkeys need to be accomodated?
given branches to climb, swings, ropes and platforms
how can obese mice overeat?
lack of leptin gene
- can be used to study type II diabetes
SCID mice
severe combined immunodeficiency (lacks T and B lymphocytes and immunoglobulins)
humanised mouse
delete mouse genes and add human genes
why are pigs good models?
similar anatomic and physiologic characteristics to humans (good surgical model)
- good for preclinical toxicological safety studies
why are dogs good?
- passive and good size
- pharmacokinetics very predictive of humans
how are zebrafish used?
toxicology testing, embryology, developmental studies
what are important things to consider in experimental design?
1) sample size + controls
2) route of administration
what administration route is “bad”?
intraperitoneal route (IP) - inject into body cavity
what needs to be defined carefully for in vivo pharmacology studies?
1) dose-response relationship
2) time course (onset and duration of response)
three core battery to be tested?
1) CNS
2) cardiovascular
3) respiratory
why are clinical trials important?
many species are poorly predictive of human specific drug metabolism and clearance
acute toxicity
toxicity produced when administered in one or more doses during a period less than 24 hours
pharmacokinetics
drug levels are plotted at timed intervals
how many species needs to be tested first?
at least two mammalian species, including a non-rodent species when reasonable
how many days do animals need to be observed after pharmaceutical administration?
14
what are the two horizontal lines in a pharmacokinetic plot?
MTC - minimum toxic concentration
MEC - minimum effective concentration
- want it in between
in pharmacokinetics, what is the area called where the graph goes up?
absorption phase
in pharmacokinetics, what is the area called where the graph goes down?
elimination phase
what are the axises in pharmacokinetics?
plasma concentration and time
