Veterinary drugs and residues Flashcards
What can chloramphenicol cause?
aplastic anemia
what can diehtylstilbsetrol cause?
bone marrow toxicity
carcinogen
What can metronidazole cause?
carinogen
teratogen
what can nitrofurazone cause
carcinogen
what can phenylbutasone cause?
blood dyscrasias
carcinogen
what can sulfonamides cause?
hypersensitivity
thyroid tumors
What can penicillin cause?
hypersensitivity
What are 4 issues with antimicobial use in food animals?
- resistance in pathogens
- resistence in commensal bacteria
- changes in food animal flora (more enteric pathogens)
- effect of drug residues on human enteric flora
What was the issue with diclofenac?
it killed vultures. was cheap and used for cattle that are not slaughtered (NSAID). vultures are uniquely suscpetible
Who approves drugs for veterinary use?
Health Canada
Health products and food branch
veterinary drugs directorate
Does the veterinary drugs directorate regulate drug use?
no. but performs human health risk assessments?
What does the CFIA do with respect ti drugs?
- tests drug residues in food
2. approves biologics (vaccines, antibodies etc)
What are 6 pre-market steps in approval of vet drugs?
- human safety
- clinical efficacy
- safety in intended species
- safety to the environmetn
- manufacturing and quality control!
- labelling
What are subchronic toxicity studies?
- 2 species of lab animals used (rodent and non-rodent)
- drug administered orally every day) 3-12 months
- low, medium and high dose groups
- minimum 2 animals (10 of each sex) per group
What are chronic toxicity studies?
like subchornic but >12 months
What are examples of special studies
- carcinogenicity tests
- reproductive tests
- teratogenicity tests
- genetic toxicity tests
(others: immunotoxicity, neurotoxicity, endocrine changes)
What are three studies for human safety testing?
- subchronic
- chronic
- special
tests
What are three studies for human safety testing?
- subchronic
- chronic
- special
tests
What does human safety (microbiology) evaluate?
- spectrum of activity
- antimicrobial resistance
- effect on target animal gut flora
- effects on human gut flora
- impact on human medicine
What are three aspects of human safety testing?
- toxicology and pharmacology
- microbiology
- drug residues and metabolism
What aspects of spectrum of activity of a drug are considered?
activity to
- target animal pathogens
- food-borne pathogens
- commensal bacteria
What aspects of antimicrobial resistance are examined in new drugs?
- mechanism of AMR
- mechanism of AMR transfer
- rate of AMR development
- cross resistance to other antimicrobials
What affects on animal gut flora are evaluated?
if zoonotic pathogens in gut increase
if there are changes in fecal shedding
(changes usually transient)
What is the microbiological acceptable daily intake?
the concentration of drug in food residues that is required to cause changes in the gut flora (human)
What is the acceptable daily intake?
the amount of drug that can be consumed by a human over a lifetime with no adverse effects
all drug residues in food (parent compond + metabolites must result in human intake
How is the ADI (acceptable daily intake) determined?
- toxicology and microbiology data
What is NOEL
No observable effect level (NOEL)
What is NOEL
No observable effect level (NOEL)
what is the no observable effect level (NOEL)
highest dose in the most susceptible species that does not cause any adverse effects (rabbits or rats)
How do you calculate ADI
NOEL divided by a safety factor (usually 100)–10 for intraspecies variability, 10 for interspecies variability
What is microbial ADI?
for antimicrobial only
the lowest concentration of drug that can cause changes in the human gut flora
What is the maximum residue limit?
determines how much drug residue is allowed in food
How is the total residue limit determined?
total residue limit=ADI/food consumption factor
What is the maximum residue limit?
the maximum amount of drug MARKER RESIDUE allowed in tissue
What is the maximum residue limit based on?
based on a ratio of the marker residue to the total residue limit
What is the maximum residue limit based on?
based on a ratio of the marker residue to the total residue limit
What is a withdrawal period
- period of time from last treatment until an animal can be slaughtered/milk/eggs used for consumption
What is the withdrawal period determined to be?
amount of time for the marker residue coencentration in the slowest animals treated with that drug to fall below the maximum residue limit
What is an issue with the withdrawal period?
have to follow the label!
What might make a carcass suspect?
- injection site lesions
2. evidence of pathology or illness
Who determines if the processing plant will take the milk?
processing plant and they can have different levels-even if the residue is below the MRI is may not be accepted
what are some factors that ensure that drugs are very safe?
- extensive testing
- 100x safety factor
- very high food consumption assumed
- withdrawal periods are based on residues from slowest depleting animals
