Q 3: veterinary pharmaceuticals Flashcards

1
Q

drugs and hormones in livestock

A
• animal health
• animal welfare
• economic return
Meets the need of producing more
food on less land with fewer farmers
• Made intensive livestock-rearing
possible
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2
Q

Functional Classification

of Vet Drugs and Hormones

A
Antibiotics to control disease and promote
growth
• Hormone and hormone-like substances
• Beta-agonists
• Topical antiseptics, bactericides, fungicides
• Antiparasitic drugs: anthelmintic,
coccidiostats
• Ionophores to alter stomach
microorganisms
• Thyreostats
• NSAIDS and tranquilizers
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3
Q

Antibiotics

-how are they used

A
• Therapeutically – treatment of
infections
• Prophylactically – to prevent disease
(especially in intensive farming)
• Growth promotion – increase
efficiency of feed use
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4
Q

how are hormones used

A
Natural hormones or synthetic
analogues
• Natural hormones used to control
reproductive cycle
• Both used to increase feed efficiency
and give leaner meat at reduced cost
to producer
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5
Q

what are the common antibiotics used

A
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,
gentamycin
• Lincosamides: lincomycin,
clindamycin
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6
Q

what are the common Hormones

used

A

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

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7
Q

Antimicrobial Resistance in

Microorganisms AMR

A
AMR occurs when a AM substance is
no longer effective in killing or
inhibiting the growth of a pathogenic
microorganisms.
• 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”.
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8
Q

AMR: What are the Issues?

A

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.”

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9
Q

Timeline of New Drug Development and AMR

A
1928: Penicillin (Fleming)
• 1930’s: Sulfonamide antibiotics
• 1940’s: Penicillin mass produced
• 1950’s &1960’s: 2nd gen drugs (phenicols,
macrolides)
• 1980’s & 1990’s: fewer new drugs, most
variations on older drugs
• Time between introduction and
development of AMR decreasing
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10
Q

AMR: How Does it Develop?

A
. 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
medicine
3. Environmental
contamination
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11
Q

What is being done to fight AMR?

A

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
stakeholders
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

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12
Q

Governmental Efforts to Fight AMR

A

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
e
• 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

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13
Q

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

A
• 1950’s to 1980’s: Diethylstilbestrol
(DES) incidents >> negative public
sentiment
• 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
Belgium
• Natural Hormones – 17β-Estradiol – Testosterone – Progesterone
• Synthetic Hormones – Zeranol – Trenbolone acetate – Melengestrol acetate
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14
Q

Intrinsic resistance:

A

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

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15
Q

Acquired resistance:

A

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

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16
Q

Horizontal gene transfer:

A

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

17
Q

when did antibiotic discovery and production peak

18
Q

DES, Hormones and

International Trade

A
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
19
Q

European Attitudes Towards Drugs in

Foods

A
Europeans willing to pay more for
their food and support small farmers
• 1950’s: Paris Les Halles porters
ingesting DES from eating chicken
necks
• 1980: DES in baby food in Italy and
France
• Past wrong decisions: thalidomide
(1962), DES (1971)
• Other “crises”: Mad cow disease
(BSE), dioxins in feed
20
Q

• World Trade Organization (WTO)

A

– determines rules governing international
trade
– settles disputes

21
Q

Sanitary and Phytosanitary Standards

SPS

A

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

22
Q

Timeline

A

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

23
Q
“Raised without the use of
hormones or steroids”
A certain fast-food chain started an ad
campaign in 2013 with the slogan “Better
Beef”
A

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)

24
Q

Method of Production Claims:

Canadian Guidelines

A

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
product
• 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
ingredients

25
Health Canada | Veterinary Drugs Directorate
``` • Assess potential hazards to human health • Conducts risk assessments • Ensures drugs meet strict quality and manufacturing standards and potency • Evaluates safety and effectiveness of drugs to use with livestock • Ensures proper labelling ```
26
Canadian Food Inspection Agency
``` • Responsible for: food safety, animal health and plant health • Inspects federally registered establishments • 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 ```
27
Risk Assessment for Vet | Drugs and Hormones
``` Health Canada – Veterinary Drugs Directorate • 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 banned ```
28
Maximum Residue Limits | MRLs
``` 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 jurisdictions ```
29
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
30
Sampling Approaches
``` Monitoring or Data Gathering o non-biased, probe for problems, profile information o healthy animals, carcasses not detained • Surveillance o limited directed, identify suspected problems o suspect animals, carcasses held • Compliance o directed, deal with identified problems o sample 5 subsequent shipments to ensure compliance • Total Diet (Food Basket) Studies ```
31
Key Aspects of Residue | Analyses in Animal Matrices
``` Extensive range of drugs – great variation in structures, physicochemical properties, biological activity • 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 species ```
32
The IDEAL Analytical Procedure
``` Wide applicability to analytes and matrices • Wide analytical range of concentrations • Sensitive (detection limit < regulatory limit) • Precise, accurate and selective • Unambiguous identification • Minimal sample preparation • High sample throughput • Low cost per sample • Small capital investment ```
33
Real World: Different Kinds | of Analytical Methods
``` Methods are optimized for specific purposes: • Screening – identify samples without residues • Quantitation – determine concentration of residues • Confirmation – unambiguous identification of residues ```
34
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 quantitation • Many antibiotics are detected in suspect carcasses using on-site antimicrobial growth inhibition tests • Laboratory screening using chemical testing methods ```
35
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 ```