Uses of veterinary medicines

The most recently reported UK results on surveillance for veterinary drug residues in meat and animal products show that traces of these compounds can, and sometimes do, arise in food. As all of these compounds are biologically potent in order to be effective in use, it is necessary to ensure that any residual activity in a food product does not present a risk to the consumer. The use of veterinary medicines inevitably leads to the presence of trace residues in food and the purpose of toxicological safety evaluation is to determine at what concentration the residues of a particular compound becomes a cause for concern with regard to human health. Thus, dose-response relationships have to be established and used to determine the concentration of a dmg at which the risks to human health become acceptable and are outweighed by the benefits from the use of the drug. This is in essence the process involved in the setting of Acceptable Daily Intakes (ADIs) and... 

EMEA Report July 14, 1999 Antibiotic Resistance in the European Union Associated with Therapeutic use of Veterinary Medicines. 

For a more detailed account of the actions and uses of veterinary medicines the reader is referred to the books of Dun and Morton, also to the forthcoming work on Veterinary Therapeutics by Professor George Brown. 

The use of veterinary medicines in food-producing animals raises concerns regarding the potential for the occurrence of residues in milk or in carcasses at slaughter. A 2007 poll of European consumers on food safety issues indicated that concern about the presence of such residues received a high ranking. Such concerns include residues of antimicrobial compounds, which constitute the largest class of approved veterinary compounds administered to farmed livestock globally. 

Survey on Use of Veterinary Medicinal Products in Third Countries [available (login required) at https / /secure, fera.defra.gov.uk/vetdrugsean/index.cfm ... 

McEvoy " reviewed the legislative framework controlling the use of veterinary medicines and zootechnical feed additives in the EU. From a contamination perspective, problem compounds include sulfonamides, tetracyclines, nitroimidazoles, nitrofurans, ionophore coccidiostats, and nicarbazin. The literature on each of these was reviewed and examples of interventions to minimize contamination were given. Examples of contaminants include naturally occurring and synthetic toxic enviromnental compounds (e.g. mycotoxins and dioxins) that may contaminate feed raw materials. Zootechnical feed additives and veterinary medicines may also contaminate unmedicated feeding stuffs due to carry over during feed production. Contaminated feed can cause deleterious health effects in the animals and, through secondary exposure of consumers to products derived from these animals, may be harmful to people. 

The current practice in animal husbandry is the wide use of veterinary medicines, which serve not... 

Veterinary drugs are a broad group of pharmaceuticals exhibiting many different chemical and therapeutic properties [1]. The use of veterinary medicinal products in food-producing animals may leave residues of fhe parent compounds, their metabolites, or conjugates in food products derived from treated animals. 

Veterinary Potential or Fiorfenicol. The absolute ban on the use of chloramphenicol ia food producing animals ia the United States and Canada has accentuated the need for an effective broad spectmm antibiotic ia animal food medicine. Fiorfenicol and other antibiotics commonly used ia veterinary medicine have been evaluated in vitro against a variety of important veterinary and aquaculture pathogens. Some of these data ate shown in Tables 4 and 5, respectively. Fiorfenicol was broadly active having MICs lower than those of chloramphenicol in each of the genera tested (Table 4). Florfenicol was also superior to chloramphenicol, thiamphenicol, oxytetracycline [79-57-2] ampicillin [69-53-4] and oxolinic acid [14698-29-4] against the most commonly isolated bacterial pathogen of fish in Japan (Table 5) (37). 

Health and Safety Factors. The LD q of anhydrous sodium thiosulfate for mice is 7.5 0.752 g/kg (40). Because of low toxicity, it can be safely used iu veterinary medicine. Sodium thiosulfate pentahydrate is affirmed as a GRAS indirect and direct human food ingredient under the Federal Food, Dmg, and Cosmetic Act (41) (see Food additives). 

Condensation of 0,0-diethyl chlorothiophosphate with 2-isopropyl-6-methylpyrimidin-4(3//)-one gives the powerful insecticide dimpylate (1045) (57HCA1562). It is used in veterinary medicine (58MI21301), in particular for topical application, with or without added DDT, in cases of blowfly strike in sheep. 

Note that some treatment operations choose a pollution prevention technique to dispose of the float. This involves feeding the float to animals. When this is done for the situation where the feed animals are used for human consumption, organic compounds such as chitosan, carrageenan, lignosulfonic acid,or their derivatives can be used. Use only compounds that are approved by the Food and Drug Administration (FDA) Office of Veterinary Medicine. 

The pharmaceutical industry has developed and studied a number of anabolic steroids for use in veterinary medicine and in rehabilitation from injuries that are accompanied by deterioration of muscles. The ideal agent would be one that possessed the anabolic properties of testosterone without its androgenic (masculinizing) effects. Methandrostenolone (Dianabol) and stanozolol are among the many synthetic anabolic steroids that require a prescription. 

Commission Regulation (EC) No. 1084/2003 of 3 June 2003 concerning the examination of variations to the terms of a marketing authorisation for medicinal products for human use and veterinary medicinal products granted by a competent authority of a Member State... 

The authorisation of veterinary medicines containing a new chemical entity for use in food-producing animals involves a two-stage application process (i) an application to establish MRLs and (ii) an application for a marketing authorisation. 

APPLICATION FOR THE ESTABLISHMENT OF MRL(s) FOR AN ACTIVE SUBSTANCE TO BE USED IN VETERINARY MEDICINAL PRODUCTS IN ACCORDANCE WITH COUNCIL REGULATION (EEC)... 

Phencyclidine (l-[l-phenylcyclohexyl] piperidine, PCP) was originally developed as an intravenous anesthetic in the 1950s. Used for this indication, it causes a trance-like state without loss of consciousness and was hence classified as a dissociative anesthetic. However, it was soon withdrawn from human use because it produced unpleasant hallucinations, agitation, and delirium. The product was later used in veterinary medicine. Ketamine, a chemically closely related substance, was developed to replace PCP and is stiU in use as a dissociative anesthetic in children. Ketamine is less potent than PCP, and its effects are of shorter duration. However, it may also cause hallucinations (see the section on ketamine in Chapter 7, Club Drugs ). Much of the ketamine sold on the street (special K, cat Valium) has been diverted from veterinarians offices. 

EMEA/CVMP/127/95 final Note for guidance— In-use stability testing of veterinary medicinal products (March 1996)... 

A number of different adjuvant preparations have been developed (Table 13.13). Most preparations also display some associated toxicity and, as a general rule, the greater the product s adjuvanticity, the more toxic it is likely to be. A few different adjuvants may be used in veterinary medicine however (for safety reasons), aluminium-based products are the only adjuvants routinely used in human medicine. Application of many of the aggressive adjuvant materials is reserved for selected experimentation purposes in animals. 

Chloramphenicol (CAP) is a broad-spectrum antibiotic that was widely used in veterinary medicine. Since 1994 the use of CAP is banned in the EU because of certain toxicological problems (i.e., aplastic anemia and the grey baby syndrome ) observed in its administration to humans [ 107] that have prompted the establishment of a zero tolerance for the presence of these residues in meat and animal products. As a consequence, many efforts have been made to develop sensitive methodologies capable of detecting CAP residues or its metabolites. 

A series of 7-diazabicycloalkyl quinolones has been prepared and found to exhibit excellent broad spectrum activity against important veterinary pathogenic bacteria [105], The structures of several of these interesting bicyclic analogues (76) as well as MIC data are summarized in Table 6.28. Compound (76e) (danofloxacin), which also exhibits excellent p.o. and s.c. activity in a mouse protection model for Pasteurella multocida [ 106], is undergoing development for use in veterinary medicine. It has been shown to exhibit excellent bioavailability properties in cattle, swine and poultry [107] and is efficacious in models for the treatment of respiratory diseases in food-producing animals [108],... 

The allenic PGF2a analogs fenprostalene (116) and prostalene (117) are closely related to enprostil and are used in veterinary medicine for the synchronization of estrus. As in the synthesis of enprostil (Scheme 18.39), the allenic a-side chain is... 

For the synthesis of Diels-Alder adducts a morphinan-6,8-diene system, as present in thebaine, is indispensable. Older publications started from thebaine and methyl vinyl ketone (but-3-en-2-one), yielding, after a Grignard reaction with propylmagnesium bromide, etorphine (13), a 6,14-endoethenomorphinan that is over 1000x as active as morphine and is used in veterinary medicine (Scheme 5.10). 

A series of monoclonal antibodies were generated that can bind dimetridazole (269) and other nitroimidazole drugs used in veterinary medicine. An extraction procedure was developed for these nitroimidazoles that is compatible with a competition ELISA method, based on binding of these antibodies to the drugs. As little as 1 ng of 269 could be detected in turkey muscle by this method552. 

---