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FOOD 525 > Veterinary Drug Residues > Flashcards

Veterinary Drug Residues Flashcards

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1
Q

Why are veterinary drug residues hard to control?

A

Drinking water, feedstuffs, or by dipping animals - Route of administration is most difficult to control which will lead to large variation on controlling the amount of drug received by each animal prior to slaughter.

Used typically in high-density animal holding operations.

e.g., antimicrobials and anabolic agents

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2
Q

Why are anabolic agents used?

Veterinary drug residue

A
  • Mixed with feed to exert effect on animal’s metabolism
    • Before used as implant in ear (e.g., DES in cattle)
      • Not used presently

Usually steroid-like products analogous to testosterone.

Accelerate the growth rate of the animal

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3
Q

Why are antimicrobials used?

A
  • Mixed with feed at sub-therapeutic concentrations to suppress growth of natural bacteria that live in the GI tract
  • Prophylactic treatment
  • Result is improved feed utilization and weight gain.
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4
Q

List 4 pathogens derived from multicelluar animal parasites.

A
  • Protozoa
  • Fungi
  • Bacteria
  • Viruses

Goal: To reduce sub-therapeutic infections that alter the immune system of production animals and reduce vulnerability to bacterial/parasitic infection.

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5
Q

Growth promoting antimicrobials are considered to be safe if […]

A

included at low concentrations in animal feeds

Sufficient to provide a prophylactic (used to prevent disease) effect.

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6
Q

What is the purpose of antibiotics?

A
  • to selectively inhibit the growth of pathogenic micro-organisms, particularly bacteria
  • to reduce sub-therapeutic infections that alter the immune system of production animals, reducing vulnerability to bacterial or parasitic infections
    • e.g., mastitis in dairy cows
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7
Q

Name 4 antimicrobial agents.

A
  • Chloramphenicol: treatment of systemic salmenelosis (calves, pigs)
    • Still used in some cases, but regulated under rigorous requirements.
  • Sulphonamide drugs: treatment of systemic bacterial in pigs (pneumonia)
  • Tetracycline: employed at sub-therapeutic doses as growth promoting feed additives (fish).
  • Nitrofurans: antibacterial agents used in poultry production; broad spectrum and metabolized quickly

Require FDA approval.

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8
Q

What is the purpose for antibiotic usage in food systems for human consumption?

A
  • To reduce sub-therapeutic infections that alter the immune system of production animals, reducing vulnerability to bacterial or parasitic infections
    • e.g., mastitis in dairy cows
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9
Q

~90% of antimicrobials used in agriculture are for: [2]

A
  • Growth promotion
  • Prophylaxis
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10
Q

What are the two classes of growth promoters?

A
  • Antimicrobial
  • Anabolic agents
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11
Q

What are the two types of antibiotics?

A
  • Antibiotics kill or stop the growth of microorganisms
    • Kill = bactericidal
    • Stop growth/suppress proliferation = bacteriostatic
      • Cold storage could be considered a bacteriostatic process
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12
Q

What is a limited or narrow spectrum antibiotic?

A

If effective against a single organism or disease condition

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12
Q

Why use antibiotics in animal feed?

A

The high stocking density of domestic produced animals and finfish makes it possible for the ready transmission of bacterial disease.

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12
Q

What is an extended spectrum antibiotic?

A

If effective mainly against Gram-positive or Gram-negative bacteria

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12
Q

What is a broad-spectrum antibiotic?

A

One that will have bacteri-ostatic or –cidal effect on a wide range of Gram-positive or Gram-negative bacteria.

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13
Q

Are fish more susceptible to disease?

A
  • Unlike land animal husbandry practices, the diagnosis of disease among a population of fish usually requires immediate administration of antimicrobials to the entire stock.
    • This is referred to as the “batch” method of antimicrobial application which is needed because it is very difficult to isolate the infected fish for treatment.

Residual feed will sink to the bottom and remain there. They will continue to contribute to the development of antibiotic resistance unless washed out.

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14
Q

Are there antibiotic residues in fish/meat animals?

A

Yes, if effective wash-out times are not followed before marketing the animal.

Each antibiotic and how it’s applied has a specific wash-out period that must be followed to remove residues from flesh.

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15
Q

Describe the theory of antibiotic attack.

A
  • to target microbial functions and structures that are different from the host.
  • aim to interfere with the normal cellular functions of bacteria and fungi so as to prevent further infection of the host.
  • Interfere with cell wall biosynthesis, membrane function, DNA replication, DNA transcription, and RNA translation or protein synthesis
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16
Q

What are the biological functions of antibiotics? [4]

A

Inhibition of synthesis of:

  • cell wall (i.e., peptidoglycan in bacteria)
  • protein synthesis
  • essential metabolites
  • nucleic acids (i.e., DNA and RNA)
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17
Q

Antibiotics interfere with: [4]

A
  • cell wall biosynthesis
  • membrane function
  • DNA replication and transcription
  • RNA translation/protein synthesis
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18
Q

Why were previously used growth-promoting antibiotics banned from use?

A
  • Very effective at killing bacteria but are also retained in the food and have an antimicrobial effect on gut microbiome in humans
    • This is why they were banned - the carry-over effect on the human microbiome.
Notice many are banned 25 years ago.
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19
Q

Beta-lactams are effective against […]

A

Gram-positive bacteria

E.g., Streptococcus; Staphylococcus; Enterococcus

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20
Q

What is the mechanism of action of beta-lactams?

a.k.a. penicillins

A

Bactericidal: inhibit cell wall synthesis

Disruption of cell wall synthesis results in cell lysis and cell death.

ampicillin (a semi-synthetic); amoxicillin (semi-synthetic)

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21
Q

Describe the structure of beta-lactams.

a.k.a. penicillins

A

The beta-lactams are named after the characteristic ring structure that they all share.

The green arrow shows the bond that is broken by the beta-lactamases that are synthesized by many penicillin-resistant bacteria (e.g. agents that will destroy penicillins.) Cold temperatures can also affect the stability of this bond and therefore the efficacy of the antibiotic.

Recall: beta-lactamases in pUC8 plasmid that confers ampicillen resistance

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22
Q

When were beta-lactams introduced?

A

In the 1940s, produced by the fungus Penicillium chrysogenum

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23
Q

What do penicillins bind?

A
  • The bacterial cell wall peptidoglycan

Disruption of cell wall synthesis results in cell lysis and bacterial cell death.

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24
Q

The binding of penicillins to the bacterial cell wall inhibits

A

the cross linking process

Disruption of cell wall synthesis results in cell lysis and bacterial cell death.

25
Q

Describe the structure of the bacterial cell wall.

A
  • A structure not found in eukaryotes
  • Made of a complex polymeric material called peptidoglycan which contains both amino acids and amino sugars.
    • The amino sugars are of two kinds: (1) N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG)
26
Q

What are the two kinds of amino sugars that comprise peptidoglycan, in addition to amino acids?

A
  • N-acetylmuramic acid (NAM)
  • N-acetylglucosamine (NAG)
27
Q

Describe the use of beta-lactams in aquaculture.

A
  • Use of penicillins in aquaculture is poorly documented in the literature
  • At present, Penicillin/ampicillin are not approved for use in aquatic food species in North America
  • Penicillins are effective at treating against bacterial-kidney disease (BKD) and fish tuberculosis/microbacteriosis in salmon
28
Q

Penicillins are effective at treating bacterial-kidney disease and tuberculosis/microbacteriosis in salmon.

At present, these antibiotics are not approved for use in aquaculture.

What are the limitations associated with penicillins? [3]

A
  • Penicillins and ampicillin are (1) unstable at low pH and (2) rapidly metabolized and excreted by fish.
  • Also (3) unstable in low temperatures.
29
Q

How can penicillin be degraded in animal and fish tissues?

A

Freezing will degrade penicillin (e.g., a decline in concentration that reaches 37% of original)

This is relevant because fresh-caught fish are immediately put on ice.

30
Q

What detection methods exist for detecting penicillin?

A

HPLC and the ‘Charm’ assay

Harder to extract antibiotic from lipid from fish for quantification because they are unsaturated oils (compared to saturated fats in ruminants) - oil matrix vs. saturated fat matrix

31
Q

Describe tetracycline.

A
  • Stops many essential functions of bacteria
  • Binds to Ca and Mg divalent ions and Aluminium to form insoluble complexes
    • The strong affinity for Ca is the cause for discoloration of permanent teeth and tooth enamel in children
Not used primarily (still used) anymore due to concerns with antibiotic resistance as well as its strong affinity for binding divalent ions. When bound to divalent ions it does not function as an antimicrobial.

Wide spectrum antimicrobial agent for Gram-negative and Gram-positive bacteria & protozoa.

32
Q

What detection methods exist for tetracycline?

What is the minimum detection in fish tissue?

A
  • HPLC with cartridge extraction and analysis on an octadecylsily stationary phase with internal standard
    • Minimum detection in fish tissue is 0.05 ppm
33
Q

Tetracyclines are effective in […]

A
  • Gram-negative and Gram-positive bacteria & protozoa.

Bacteriostatic activity

34
Q

Describe use of tetracyclines in aquaculture.

A
  • Use in aquaculture following discovery of chlorotetracycline in 1947
  • Currently approved for use in Canada, US, and Japan
  • Given as a prophylactic at 8mg/kg feed for 5 days
35
Q

What is the mechanism of action of tetracyclines?

A
  • Tetracyclines inhibit bacterial protein synthesis by blocking the attachment of the transfer RNA-amino acid to the ribosome.
    • More precisely they are inhibitors of the codon-anticodon interaction.
    • Tetracyclines can also inhibit protein synthesis in the host, but are less likely to reach the concentration required because eukaryotic cells do not have a tetracycline uptake mechanism.

Binds to Ca and Mg divalent ions and
Al to form insoluble complexes.

Bacteriostatic activity effective against a wide spectrum of Gram-positive and Gram-negative bacteria & protozoa.

36
Q

Tetracyclines can also inhibit protein synthesis in the host - why is this not a concern?

A

Eukaryotic cells do not have a tetracycline uptake mechanism

37
Q

What was the first antimicrobial agent?

A
  • Sulfanilamide

Anti-metabolite antimicrobials - bacteriostatic - broad range activity against Gram-positive and Gram-negative bacteria.

38
Q

Describe the structure of sulfanilamide.

A

Bacteriostatic - Broad range activity against Gram-positive and Gram-negative bacteria.

39
Q

What is the mode of action of sulfanilamide?

A
  • Being analogues of para-aminobenzoic acid, they competitively inhibit formation of folic acid synthesis
    • Block the final step in the conversion of para-aminobenzoic acid to folic acid so they block nucleotide and protein synthesis in bacteria but not mammals.

Broad range bacteriostatic activity against Gram-positive and Gram-negative bacteria.

40
Q

Describe how sulfonamides are used in combination therapy.

A
  • Sulfonamindes used in combination with Trimethoprim gives a potentiated sulfonamide which (1) blocks two distinctive steps in folic acid metabolism and (2) prevents emergence of resistant strains.

Sulfonamides have established resistance, hence combination therapy.

Used to be effective in isolation prior to resistance. Broad range bacteriostatic activity against Gram-positive and Gram-negative bacteria.

41
Q

List some sulfonamides used in aquaculture. [6]

A
  • Sulfamethazine
  • Sulfadizine
  • Sulfanilamide
  • Sulfamerazine
  • Metorpim
  • Trimethoprim
42
Q

Sulfamerazine is effective in treating […].

A

Bacterial kidney disease in fish

43
Q

Why are potentiated sulfonamides necessary?

A
  • Spontaneous resistance of Sulfamerazine occurs which results in the need to use potentiated sulfonamides (e.g., Trimetoprim)
44
Q

What is the method of detection of sulfonamides?

A

Chromatographic (HPLC) methods are used to detect and quantify analysis

45
Q

Describe the use of sulphonamides in aquaculture.

A
  • Sulphonamides are used as therapeutic and prophylaxis agents in fish farming against Gram-positive cocci and Gram-negative bacilli
46
Q

Describe the elimination half life of SDM and SMM. Where are residues found in the highest concentration?

A
  • Sulphadimethoxine (SDM) elimination half-life = 24.5h; (32.6h for SMM)
  • Residues found in highest concentration in the bile and lowest in muscle tissue;
  • No drug detectable after 32 days post-dose.

Can be detected after elimination half-life, but not quantified.

47
Q

What is the mode of action of quinolones?

Antibiotic

A
  • Bactericidal - DNA synthesis inhibitors.
  • Binds to A subunit of DNA gyrase (topoisomerase) and prevents supercoiling of DNA, thus inhibiting DNA synthesis

Gram positive cocci and urinary tract infections

48
Q

Quinolones are effective against […]

A

Gram positive cocci and urinary tract infections

49
Q

Nalidixic acid is the basis for quinolone antibiotics. It is effective against […]
What is the mode of action?

A
  • Gram positive and Gram-negative bacteria
    • In lower concentrations - bacteriostatic
    • In higher concentrations - bactericidal

Oxolinic and nalidixic acids also are affective against fungi, protozoa and protozoans.

50
Q

Describe the use of Oxolinic acid in aquaculture.

A
  • Administered orally (12 mg/kg/day) to cultured fish in Canada to prevent infection from Vibrio and Aeromonas species

Vibrio is the species that initiates bacterial kidney disease. HPLC is not as effective for quantifying the residues of this drug.

51
Q

What bioassays are used to detect quinolone antibiotics?

A

Microbiological inhibition assays

52
Q

It is common practice in the fish industry, particularly in developing countries, to use large amounts of antibiotics to prevent infection.

Is this heavy use of prophylactic antibiotics in aquaculture a growing problem for human and animal health?

A
  • The antibiotics used are often non-biodegradable and remain in the aquaculture environment for long periods of time. This encourages the growth of bacteria which can survive in the presence of antibiotics - antibiotic resistant bacteria.
  • Eventually, this process could lead to increased antibiotic resistance in the ‘disease-causing’ bacteria (pathogens) of fish.
  • The properties which make bacteria resistant can also be transferred to human and animal pathogens, leading to increased infectious disease in fish, animals and humans alike.
  • When antibiotics are mixed with fish food, residual antibiotics may be found in fish products and fish meat.
  • People who eat these products will be inadvertently consuming antibiotics, leading to changes in their normal microbial environment, or ‘microflora’ and making them more susceptible to bacterial infection
53
Q

What is antimicrobial resistance?

A

A natural or acquired defense mechanism of bacteria threatened by substances that will kill or inactivate them

Facilitated by the application of antimicrobials that otherwise would not be there.

54
Q

How is antimicrobial resistance achieved?

A
  • Plasmids, transposons and integrons (mobile genetic elements),
  • Efflux (decreasing the concentration of antimicrobial inside the target cell by pumping out the drug. (e.g. Tetracycline)
55
Q

What is HACCP?

A

Education of public, food producers, processors, and food service facility employees on efficient quality assurance and control systems

56
Q

Describe how the risk of antimicrobial resistance can be controlled.

A

A global effort to curb the over-use of antibiotics in the rearing of finfish is essential to prevent these detrimental effects to human health from antibiotic resistance in food-animal products

Application of antibiotics is not regulated the same in all countries.

Consequently, AMR is a huge global concern.

57
Q

What are anabolic agents?

A
  • Used in veterinary medicine are naturally occurring steroids, (no longer permitted for use as growth promoters in Canada, but used in other countries)
  • Steroid hormones are synthetic products identical to endogenous male and female sex hormones.
  • Often used in castrated animals (males are aggressive and hard to deal with if not castrated)
  • Important role in growing animals, development of muscle tissue.
  • Some evidence that residue concentrations of steroid hormones (in fat) do not exceed those that occur naturally provided adequate washout period is followed.

Endocrine disruptors - act like estrogen and disrupt the biological activity of endogenous estrogen.

58
Q

What are anthelmintic agents?

A
  • Prophylactic use to prevent and treat parasitic diseases in food-producing animals, (e.g. GI and lung worms, liver flukes)
    * e.g., Ivermectin, a broad spectrum used in cattle, pigs and sheep.
59
Q

Describe the range of Anthelmintic agents.

A

Broad spectrum

60
Q

What are coccidiostats?

A

Ionophores used for control of coccidiosis (gut parasites in young poultry)

No longer approved but were a big part of poultry production.

61
Q

Regarding antibiotics, the CFIA and provincial governments should monitor [2]

Requirement for Accurate and Precise analysis methods for detection and quantification of antibiotic/anabolic residues.

A
  • Antibiotic medication
  • Antibiotic withdrawal times

Testing for compliance with nationally & internationally set standards.

Surveillance for veterinary drug residues show that traces of these compounds can and sometimes arise in food

62
Q

Compare Gram-negative and Gram-positive bacteria.

A

FOOD 525 (10 decks)

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