Q 3: veterinary pharmaceuticals Flashcards Preview

Y2 T1 Toxicology 200 > Q 3: veterinary pharmaceuticals > Flashcards

Flashcards in Q 3: veterinary pharmaceuticals Deck (35)
Loading flashcards...

drugs and hormones in livestock

• animal health
• animal welfare
• economic return
Meets the need of producing more
food on less land with fewer farmers
• Made intensive livestock-rearing


Functional Classification
of Vet Drugs and Hormones

Antibiotics to control disease and promote
• Hormone and hormone-like substances
• Beta-agonists
• Topical antiseptics, bactericides, fungicides
• Antiparasitic drugs: anthelmintic,
• Ionophores to alter stomach
• Thyreostats
• NSAIDS and tranquilizers


-how are they used

• Therapeutically – treatment of
• Prophylactically – to prevent disease
(especially in intensive farming)
• Growth promotion – increase
efficiency of feed use


how are hormones used

Natural hormones or synthetic
• Natural hormones used to control
reproductive cycle
• Both used to increase feed efficiency
and give leaner meat at reduced cost
to producer


what are the common antibiotics used

Tetracyclines: tetracycline,
chlortetracycline, oxytetracycline
• Ionophores: monensin, lasalocid
• Macrolides: erythromycin, tylosin,
tilmicosin, tulathromycin
• Penicillin and Beta-Lactams:
penicillin-G, amoxicillin, ampicillin
• Sulfas: sulfamethazine, sulfadiazine
• Aminoglycosides: neomycin,
• Lincosamides: lincomycin,


what are the common Hormones

Natural hormones: – 17β-estradiol – Testosterone – Progesterone
• Synthetic hormones: – Zeranol – Trenbolone acetate – Melengestrol acetate
• Most applied as implanted pellets
• MGA applied as a feed additive


Antimicrobial Resistance in
Microorganisms AMR

AMR occurs when a AM substance is
no longer effective in killing or
inhibiting the growth of a pathogenic
• Probability of AMR increases with the
length of time of exposure.
• Some strains contain resistance to
AM, survive and reproduce to confer
resistance to further generations and
possibly to other micro-organisms.
• The focus is usually on resistant
bacteria, therefore the term
“antibiotic resistance”.


AMR: What are the Issues?

Increasing occurrence of AMR
poses a threat to our ability to fight
human and animal infections.
• Effective antibiotics become fewer
in number.
• Treatment becomes more
challenging and more expensive.
“The rise of antimicrobial resistance is a global health crisis. Medicine is losing more and
more mainstay antimicrobials as pathogens develop resistance. …With few replacement
products in the pipeline, the world is heading towards a post-antibiotic era in which
common infections will once again kill. …This will be the end of modern medicine as we
know it.”


Timeline of New Drug Development and AMR

1928: Penicillin (Fleming)
• 1930’s: Sulfonamide antibiotics
• 1940’s: Penicillin mass produced
• 1950’s &1960’s: 2nd gen drugs (phenicols,
• 1980’s & 1990’s: fewer new drugs, most
variations on older drugs
• Time between introduction and
development of AMR decreasing


AMR: How Does it Develop?

. Use in agri-food industries to
treat specific diseases or to
prevent illnesses and
promote growth
2. Over-use or inappropriate
use of AM in human
3. Environmental


What is being done to fight AMR?

The WHO suggests the following:
Policy makers can help by:
• strengthening resistance tracking and laboratory capacity
• regulating and promoting appropriate use of medicines
Policy makers and industry can help by:
• fostering innovation and research and development
• Promoting cooperation and information sharing among all
Health workers and pharmacists can help by:
• enhancing infection prevention and control
• only prescribing and dispensing antibiotics when truly needed
• prescribing and dispensing the right antibiotic(s) to treat the illness


Governmental Efforts to Fight AMR

The fight against AMR has become highly politicized
• There are may vested interests in industry that fight regulations
• Some attempts to collaborate with industry to “voluntarily” reduce AM
use, especially for growth promotion purposes: US FDA Guidance #213
• California just enacted (October 10) legislation to require a
veterinarian’s prescription for therapeutic antibiotic uses in livestock,
ban other uses (including low-dosage levels used to prevent diseases),
and require that data be collected on antibiotic us
• In Canada, Health Canada has responded by:
– strengthening surveillance systems that monitor AMR
– strengthening the responsible use of antimicrobials in human and veterinary medicine
– strengthen regulations for veterinary medicines and medicated feeds
– encourage practices that reduce use of antibiotics


DES, Hormones and
International Trade
The “Hormone Dispute” with the EU

• 1950’s to 1980’s: Diethylstilbestrol
(DES) incidents >> negative public
• 1988: The EU banned the use of some
natural and synthetic hormones used
a growth promoters and banned them
from imported meats and products
• The US and Canada considered this a
restrictive trade practice and have
fought the ban through the WTO
• Internal ban lead to “black market”,
alleged involvement of the “Mafia”
and a murder of a veterinarian in
• Natural Hormones – 17β-Estradiol – Testosterone – Progesterone
• Synthetic Hormones – Zeranol – Trenbolone acetate – Melengestrol acetate


Intrinsic resistance:

Ability of microorganisms to
thrive in presence of AM due to inherent


Acquired resistance:

Development of AMR due to
mutation and acquisition of genetic material from
other micro-organisms


Horizontal gene transfer:

transfer of genetic
material between organisms other than usual
reproduction by mobile DNA elements via plasmids
or bacteriophages.


when did antibiotic discovery and production peak



DES, Hormones and
International Trade

Diethylstilbestrol (DES)
• Non steroidal synthetic estrogen (female
sex hormone) and anabolic agent
• First synthesized in 1938 by Leon Golberg
but not patented
• Was given to pregnant women to prevent
complications during pregnancy
• Found to cause cancer and other
complications in mothers and children
• Given to cattle, chickens, sheep to
stimulate growth and improved feed
utilization (1954-1980)
• US “Delaney Clause”: ban use of cancercausing
substances in food production
• Other anabolics developed: melengestrol,
trenbolone, zeranol


European Attitudes Towards Drugs in

Europeans willing to pay more for
their food and support small farmers
• 1950’s: Paris Les Halles porters
ingesting DES from eating chicken
• 1980: DES in baby food in Italy and
• Past wrong decisions: thalidomide
(1962), DES (1971)
• Other “crises”: Mad cow disease
(BSE), dioxins in feed


• World Trade Organization (WTO)

– determines rules governing international
– settles disputes


Sanitary and Phytosanitary Standards

– scientifically justifiable standards
– based on perceived need to protect human,
animal, plant health



1985: EU banned use of hormones for growth
promotion in livestock production in EU
• 1989: EU bans imported meat and products
produced using banned products; US takes
retaliatory trade measures
• 1996: US and Canada take dispute to WTO;
authorized to retaliate
• 1997-2008: Numerous reviews and reports;
back-and-forth on scientific evidence
• 2009: US and EU sign MOU to settle dispute:
EU to allow non-hormone-treated beef from
US in exchange for relaxation of penalties
• 2011: US removes sanctions
• 2012: The EU ratifies agreement


“Raised without the use of
hormones or steroids”
A certain fast-food chain started an ad
campaign in 2013 with the slogan “Better

Trying to respond to consumer feedback on
desire to have more transparency on where food
was coming from and who was raising it
• Started with slogan “Better Beef”
• Cdn beef producers not happy
• Implication was that beef produced by using
standard practices was inferior
• Using hormones aid in producing beef using less
feed and land area
• Changed slogan to “Raised without the use of
hormones or steroids”
• Antibiotics used for treatment of disease only
but some news articles imply no antibiotics used
at all
• Beef sourced from Australia, Montana and
Vegreville, AB (Spring Creek Farms)


Method of Production Claims:
Canadian Guidelines

Regulations require that labels and claims “be
accurate, truthful and not misleading”
Raised without the use of added hormones:
• No hormones shall be administered in any
way to the animal that forms the food
• Applies to animals where use is permitted
• “Hormone free” is misleading
• “No growth stimulants is misleading
Raised without the use of antibiotics:
• No antibiotics given from birth to harvest
• Vitamins and minerals OK but low levels
• Veterinary biologicals are permitted:
– vaccines, antisera, antimicrobial feed


Health Canada
Veterinary Drugs Directorate

• Assess potential hazards to human
• Conducts risk assessments
• Ensures drugs meet strict quality and
manufacturing standards and
• Evaluates safety and effectiveness of
drugs to use with livestock
• Ensures proper labelling


Canadian Food Inspection Agency

• Responsible for: food safety, animal
health and plant health
• Inspects federally registered
• National Chemical Residue
Monitoring Program: Conducts
sampling and analyses of samples to
ensure compliance with standards
• About 90% of samples analyzed by
contract labs, balance by CFIA labs
• Centre for Veterinary Drug Residues
in Saskatoon


Risk Assessment for Vet
Drugs and Hormones

Health Canada – Veterinary Drugs
• Reviews pharmacokinetic and
metabolic study data
• Reviews human
toxicity/carcinogenicity data to set
Allowable Daily Intakes (ADI)
• Establishes Total Residue Levels
(TDL) based on dietary patterns
• Establishes Maximum Residue
Limits (MRLs)
• Sets appropriate
withdrawal/withholding times
• In some cases, a drug or hormone is


Maximum Residue Limits

No adverse health effects over a
lifetime of eating foods with MRL
levels of residues
• MRLs only apply to edible tissues
• Banned substances: no MRL
• Use scientific assessments from
other countries
• Try to harmonize MRLs with other


Banned Substances

Some drugs and hormones have been banned due to adverse effects:
• Chloramphenicol: broad-spectrum antibiotic associated with aplastic
anaemia, a usually fatal blood disorder affecting the bone marrow; no known
safe dose
• Nitrofurans: broad-spectrum antibiotic considered carcinogenic
• Clenbuterol and derivatives: Used to treat respiratory infections in horses and
to promote growth in livestock; associated with food poisoning incidents in
China and Europe
• Diethylstilbestrol: a synthetic oestrogen; used as growth promoter; banned in
Europe late 1970s due to concerns about cancer; led to banning of other
oestrogenic compounds


Sampling Approaches

Monitoring or Data Gathering
o non-biased, probe for problems,
profile information
o healthy animals, carcasses not
• Surveillance
o limited directed, identify suspected
o suspect animals, carcasses held
• Compliance
o directed, deal with identified
o sample 5 subsequent shipments to
ensure compliance
• Total Diet (Food Basket) Studies


Key Aspects of Residue
Analyses in Animal Matrices

Extensive range of drugs
– great variation in structures,
physicochemical properties, biological
• Range of concentrations: < 0.001 - >
100 ug/kg
• Complexities of the matrices
• Different stabilities and need for
marker compounds (metabolites)
• Variations in ratios of parent
compounds to metabolites between


The IDEAL Analytical Procedure

Wide applicability to analytes and
• Wide analytical range of concentrations
• Sensitive (detection limit < regulatory
• Precise, accurate and selective
• Unambiguous identification
• Minimal sample preparation
• High sample throughput
• Low cost per sample
• Small capital investment


Real World: Different Kinds
of Analytical Methods

Methods are optimized for specific
• Screening
– identify samples without
• Quantitation
– determine concentration of
• Confirmation
– unambiguous identification of


Screening for Drug Residues

• Quickly and cheaply identify those
samples that do NOT contain the
target residues
• Allow the negative samples to
safely enter the food system
• Pass along suspect samples for
additional testing: confirmation and
• Many antibiotics are detected in
suspect carcasses using on-site
antimicrobial growth inhibition
• Laboratory screening using
chemical testing methods


Confirmation and
Quantitation of Residues

A violative result requires:
Present and identified and
concentration exceeds the
Regulatory Limit (“zero” or MRL)
• Need an appropriate method that
gives full or complementary
information enabling identification
of a substance with high confidence
• Generally done by instrumental
methods using Mass Spectrometer