Definitions in veterinary chemotherapy

Definitions in veterinary chemotherapy

Chemotherapy

The treatment of disease by means of chemicals that have a specific toxic effect upon the disease-producing microorganisms or that selectively destroy cancerous tissue.

The treatment of cancer using specific chemical agents or drugs that are selectively destructive to malignant cells and tissues.

The treatment of disease using chemical agents or drugs that are selectively toxic to the causative agent of the disease, such as a virus or other microorganism.

Antibiotics

                A drug used to treat bacterial infections. Antibiotics have no effect on viral infections. Originally, an antibiotic was a substance produced by one microorganism that selectively inhibits the growth of another.

                Any of a large group of chemical substances, as penicillin or streptomycin, produced by various microorganisms and fungi, having the capacity in dilute solutions to inhibit the growth of or to destroy bacteria and other microorganisms, used chiefly in the treatment of infectious diseases.

                 A substance, such as penicillin, that is capable of destroying or weakening certain microorganisms, especially bacteria or fungi, which cause infections or infectious diseases. Antibiotics are usually produced by or synthesized from other microorganisms, such as molds. They inhibit pathogens by interfering with essential intracellular processes, including the synthesis of bacterial proteins. Antibiotics do not kill viruses and are not effective in treating viral infections.

“Subtherapeutic” refers to the use of antibiotics in a preventative manner. For example, veterinarians use antibiotics to prevent disease at vulnerable times, such as weaning, when animals are very susceptible to disease that can kill them quickly, sometimes in less than 24 hours. Rather than wait for a full-blown infection to manifest and spread throughout the entire herd, some producers, under the careful supervision of veterinarians, may give a group of cattle an antibiotic to prevent an outbreak. Many times it is easier to control the total herd health through the early prevention of a contagious illness.

“Pre-slaughter withdrawal period / Milk discard time” means the time after cessation of administration of the sponsored compound for residue of carcinogenic concern in the edible product to deplete to the concentration that will satisfy the operational definition of noresidue.

Withdrawal period: The interval between the last administration of a veterinary medicinal product to animals under normal conditions of use and the production of foodstuff from such animals to ensure that such foodstuffs do not contain residues in quantities in excess of the maximum residue limits laid down.

ADI: Acceptable Daily Intake: The estimate of the residue, expressed in terms of weight units per kilogram of bodyweight that can be ingested daily over a lifetime without any appreciable health risk.

MRL: Maximum Residue Limit: The maximum concentration of a marker residue in an animal tissue (e.g. liver, kidney, muscle or fat) or animal product resulting from the use of a veterinary medicinal product (expressed in mg/kg or μg/kg on a fresh weight basis) that is legally permitted on or in a food within the EU.

Marker residue: An analyte that is suitable to test for the presence of residues in a tissue. The marker residue can be the parent drug or any of its metabolites/degradation products or a combination of any of these. The marker can also be a chemical derivative of one or several of the residue components. The relationship of the marker residue to the concentration of the residues of concern in the standard edible tissues must be known (ratio marker residues/residue of concern). The MRL reflects the upper concentration of marker residue in the target tissues which is permitted.

Total residue: The term refers to the total drug related residues. The total residues normally include all drug-related residues (parent drug together with metabolites). The total residues are usually determined in radiometric residue depletion studies. Measurement of total residues in standard edible tissue is normally not required for generic products where the metabolic profile and the ratios of parent compound/marker substance to the total residues are well established. In these cases, total residues in the edible tissues and in the food basket can be estimated by use of this information. The same principles also apply where the drug related residues with a specific biological activity (toxicologically, microbiologically or pharmacologically active residues) are to be estimated.

Residues of toxicological concern: For an exposure estimate based on a toxicological ADI, the relevant residue is the residue of toxicological concern. It normally includes all drug-related compounds (parent drug together with metabolites) and, in most cases, it is identical to the total residues as measured in radiometric studies. However, if an individual residue component or fraction of the total residues has been demonstrated as being toxicologically inactive, it is possible to discount it from the total residues (e.g. bound residues or any other fraction of residues that is not orally bioavailable, or known toxicologically inactive metabolites).

Residues of pharmacological concern: For an exposure estimate based on a pharmacological ADI, the relevant residue is the residue of pharmacological concern. It usually refers to the parent compound plus other pharmacologically active residue components (if there are any). In the absence of data on the pharmacological activity of individual residue components, it is assumed that the total residue is pharmacologically active and that the pharmacological activity of the total residues, i.e. any metabolites/degradation product equals that of parent compound.

Residues of microbiological concern: For an exposure estimate based on a microbiological ADI, the relevant residue is the sum of residues with microbiological activity. In most cases it is identical to the residues as measured in microbiological assays. In the absence of such data, the total residues may be used or, alternatively, the sum of the individual residue components which are known to possess antimicrobial activity. Hereby it is assumed that microbiological potential of the total residues or the metabolites/ degradation products, respectively, equals that of parent compound.

Minimum inhibitory concentrations (MICs) are defined as the lowest concentration of antimicrobial that will inhibit the visible growth of a micro-organism after overnight incubation. MICs are used by diagnostic laboratories, mainly to confirm resistance, but most often as a research tool to determine the in-vitro activity of new antimicrobials, and data from such studies have been used to determine MIC breakpoints. Minimum inhibitory concentrations (MICs) are considered the `gold standard’ for determining the susceptibility of organisms to antimicrobials and are therefore used to judge the performance of all other methods of susceptibility testing. MICs are used in diagnostic laboratories to confirm unusual resistance, to give a definitive answer when a borderline result is obtained by other methods of testing, or when disc diffusion methods are not appropriate, for example when determining the susceptibility of coagulase negative staphylococci to teicoplanin. The range of antibiotic concentrations used for determining MICs is universally accepted to be in doubling dilution steps up and down from 1 mg/L as required. The MIC is defined as the lowest concentration of a drug that will inhibit the visible growth of an organism after overnight incubation (this period is extended for organisms such as anaerobes, which require prolonged incubation for growth).

Minimum bactericidal concentrations (MBCs) the lowest concentration of antimicrobial that will prevent the growth of an organism after sub-culture on to antibiotic free media. MBC determinations are undertaken less frequently and their major use has been reserved for isolates from the blood of patients with endocarditis. The agar dilution method is an amended version of the procedure described in the BSAC Guide to Sensitivity Testing and can be adapted for determining the minimum bactericidal concentration (MBC) of an antimicrobial for an organism and can be truncated for use as a `breakpoint ‘ method.