Pharmacologic considerations in the management of peripartum conditions in the cow.

As is true with the use of drugs in veterinary medicine in general, there are many controversial issues in the management of peripartum conditions in the cow. For example, the use of PG versus antibacterial drugs in the management of postpartum uterine infections has advocates for the use of either approach. Intrauterine versus systemic administration of antibacterial drugs for the prophylaxis or treatment of postpartum metritis is another area of debate. Clearly, more research is needed in this area. Equally clearly, however, the research results that are available are being disregarded on a daily basis. In considering this discussion of the use of drugs in the peripartum period, one is struck by the frequency that optimum drug therapy of a condition relies on the extralabel use of nonapproved preparations. What guidelines are available to the practitioner in this regard? One example is lack of availability of appropriate dosage regimens or withdrawal times for food derived from treated animals. Unfortunately, pharmacokinetic and residue studies that would aid in establishing guidelines generally are not available and, in most instances, are not forthcoming. Extrapolation of data from other species to the ruminant or extrapolation of information from one drug to a related compound (such as prediction of residue and withdrawal data from an approved aminoglycoside, dihydrostreptomycin, to another unapproved drug, gentamicin) is fraught with difficulties. The need for research in this area is obvious, and lack of such information is one of the major dilemmas in trying to establish rational drug therapy in the food-producing animal. Recent developments in drug therapy have led to innovative approaches for the management of peripartum and other diseases in cattle. The use of PG in the treatment of reproductive disorders, so commonplace and widely accepted in contemporary veterinary practice, is a relatively recent approach that continues to be refined with the development of new, more potent, more specific PG analogs. What will be the role of ceftiofur, a potent, third-generation cephalosporin that currently is approved only for the treatment of respiratory infections in cattle, in the management of reproductive tract infections? The fluoroquinolones, which represent a novel approach to the control of infectious diseases, are being increasingly used in veterinary and human medicine, and one may predict that these powerful antimicrobial drugs will find application in bovine practice, including for the treatment of peripartum infections. Pharmacologic manipulation of immune and defense mechanisms also is an approach with some promise.(ABSTRACT TRUNCATED AT 400 WORDS)     

Canine mammary gland tumors.

The National Consensus Group recommends that all women with tumors larger than 1 cm be offered chemotherapy regardless of tumor histology of lymph node status. This recommendation is to ensure that everyone at risk for failing, even though the risk may be low in women with relatively small tumors and favorable histology, has a choice and receives the benefit of adjuvant chemotherapy. This type of treatment recommendation may also be made in dogs based on recognized, well-accepted prognostic factors such as tumor size, stage, type, and histologic differentiation. Based on the limited clinical information available in veterinary medicine, the drugs that are effective in human breast cancer, such as cyclophosphamide, 5-fluorouracil, and doxorubicin, may also have a role in the treatment of malignant mammary gland tumors in dogs. Randomized prospective studies are needed, however, to evaluate the efficacy of chemotherapy in dogs with high-risk mammary gland tumors and to determine which drugs and protocols are the most efficacious. Until such studies are performed, the treatment of canine mammary gland tumors will be based on the individual oncologist's understanding of tumor biology, experience, interpretation of the available studies, and a little bit of gut-feeling. Table 2 is a proposal for treatment guidelines for malignant canine mammary gland tumors according to established prognostic factors, results from published veterinary studies, and current recommendations for breast cancer treatment in women.     

Pathophysiology,diagnosis and treatment of neonatal sepsis

Sepsis is a major cause of death in neonatal foals and, in recent years, significant progress in the understanding of the underlying pathophysiology has been made. To achieve a successful outcome, early diagnosis and treatment focusing on supporting vital functions and neutralising the effects of the causative organisms are essential. The pharmacokinetics of many drugs differ in neonatal foals and more information for appropriate dosing of antimicrobial and anti‐inflammatory drugs for neonatal foals is now available to guide clinicians in choosing the best dosages. Prevention remains difficult and focuses on early recognition while prophylactic use of antimicrobials is discouraged.     

Pharmacokinetics of veterinary drugs in laying hens and residues in eggs: a review of the literature

Poultry treated with pharmaceutical products can produce eggs contaminated with drug residues. Such residues could pose a risk to consumer health. The following is a review of the information available in the literature regarding drug pharmacokinetics in laying hens, and the deposition of drugs into eggs of poultry species, primarily chickens. The available data suggest that, when administered to laying hens, a wide variety of drugs leave detectable residues in eggs laid days to weeks after the cessation of treatment.     

Food Animal Residue Avoidance Databank (FARAD): a pharmacokinetic-based information resource

The Food Animal Residue Avoidance Databank (FARAD) is a pilot project funded through the USDA Extension Service. It represents a major effort to compile into a single source large amounts of information on veterinary pharmaceutics, pharmacokinetics and physiochemical properties of drugs and other chemicals used in livestock production. FARAD is a computer-based system consisting of five data and numerous command files that access the data files to facilitate rapid input and retrieval of the desired information. The data files include proprietary information on all pharmaceutical products approved for use in food animals in the United States; physicochemical information on more than 100 chemicals contained in the databank; regulatory information pertaining to tolerance and action levels of chemical residues in animal products and allowable concentrations of drugs in feed; pharmacokinetic rate and volume constants pertinent to residue depletion modeling in a variety of species; bibliographic citations to which all of the information contained in the databank is referenced. All of the information in FARAD is currently available through three regional access centers in the United States, and direct computer access to the data may become available in the future.     

Geriatric pharmacology.

When faced with the geriatric dog or cat, the practitioner should consider the following: 1. Avoid using any drugs at all unless there are definite therapeutic indications. If the patient has some degree of renal insufficiency, try to select drugs that are hepatically metabolized and excreted in bile rather than eliminated by the kidneys (eg, doxycycline, tolfenamic acid). If hepatic insufficiency is present, select drugs that do not undergo metabolism before renal excretion (eg, penicillins, cephalosporins). 2. If therapeutic drug monitoring is available, tailor the drug dosage regimen to that specific patient (eg, phenobarbital, digoxin, amino-glycosides). 3. If therapeutic drug monitoring is unavailable, determine if there are clinically proven adjusted dosage regimens for specific drugs. The package insert on human pharmaceutics often gives guidelines for adjusting dosages in geriatric patients. 4. If the drug has not been sufficiently studied to have dosage adjustment recommendations, determine if there is sufficient information about its kinetics to estimate the proper drug dose in a geriatric patient. Some general guidelines for commonly used drugs in geriatric veterinary patients are provided in Table 1. In general, if the Vd changes in your patient, change the dose. If the elimination half-life changes, change the dosing interval. 5. Carefully monitor treated patients for signs of efficacy and toxicity.     

The ACVD task force on canine atopic dermatitis (XXI): antihistamine pharmacotherapy.

Antihistamines frequently are recommended by veterinary dermatologists for symptomatic treatment of pruritus associated with canine atopic dermatitis (AD), perhaps because of their moderate success in some human patients with AD. A critical review of the literature describing antihistamine use in canine AD reveals that the majority of published, peer-reviewed studies are open, uncontrolled or partially-controlled trials. Such studies vary widely in reported efficacy, from perhaps 0 to 75% of patients, even using the same drug. The few blinded placebo-controlled trials available have failed to confirm efficacy of these drugs to relieve the pruritus of canine AD. Some studies indicate that synergistic effects could occur with concurrent use of essential fatty acid supplements. Consequently, at the time of this writing, there is insufficient evidence to conclude for or against the efficacy of antihistamines for treatment of canine AD. Additional blinded, randomized and controlled trials with larger numbers of patients are necessary to establish which of the antihistamine drugs currently available, if any, are truly efficacious for canine AD. Nevertheless, present clinician consensus suggests that several different antihistamine drugs should be evaluated in sequence, for 7-14 days each, in canine patients with AD.     

Alternatives to conventional antimicrobial drugs: a review of future prospects

BACKGROUND: Growing antimicrobial resistance poses the threat that before long no suitable drugs will be available for treatment of common infections. This review examines promising new strategies for treatment and control of microbial diseases, with an emphasis on staphylococcal infection. NEW DRUGS AND TARGETS: Advances in microbial genomics have provided tools identifying many new targets for antimicrobial drugs. Of particular interest amongst these are inhibition of microbial efflux pump activity, interruption or diversion of riboswitches controlling bacterial metabolism, and metagenomics, which allows analysis of genes from unculturable organisms. BIOLOGICAL APPROACHES: Advances are also being made in biological systems for disease control, with the exploitation of antimicrobial peptides to attack micro-organisms and modulate immune responses, and the use of bacteriophages or their lysins to eliminate bacteria. There are new approaches in the development and targeting of vaccines and immunoglobulin preparations based on advanced knowledge of microbial physiology and immunoregulation. WORKING WITH THE BIOME: With increasing recognition of the value of the normal microbiota in modulating immunity and the establishment of pathogens, there is growing interest in understanding the mammalian microbiome. Strategies are being developed to promote or maintain the normal microbiota, including the use of probiotics, and there is re-evaluation of the potential of bacterial interference. LOOKING AHEAD: Whilst these approaches are likely to generate new methods of disease control, few will yield usable products within the near future. There will be a continuing need for careful use of existing drugs based on firm diagnosis, rigorous hygiene and prudent antimicrobial stewardship.     

Antimicrobial chemotherapy in the dog

This paper presents the rationale for the use of antimicrobial therapy in the dog according to the body system or organ in which an infection is located. In so doing, it correlates information on the abilities possessed by the different groups of antimicrobial drugs to penetrate sites of infection in particular body tissues. It also presents information on the clinical results reported after the use of particular antimicrobial drugs in the treatment of infections involving specific body systems and organs. The information provided on dose rates is qualitative rather than quantitative.     

Prolonged remission after immunosuppressive therapy in six dogs with pemphigus foliaceus

Limited information is available on the long-term outcome of treatment of pemphigus foliaceus in dogs. The purpose of this study is to report that a prolonged remission can occur after discontinuation of immunosuppressive regimens in some animals with this disease. Six dogs were diagnosed with pemphigus foliaceus based on suggestive clinical signs and histopathology. These patients were treated either with immunosuppressive doses of oral glucocorticoids or with a combination of oral glucocorticoids and azathioprine. After clinical signs underwent complete remission, which occurred 1.5-5 months after immunosuppression was initiated, the drugs were tapered progressively and eventually withdrawn. The total duration of immunosuppressive therapy varied between 3 and 22 months. Skin lesions of pemphigus foliaceus did not recur for 1.5-6 years after treatment was stopped. These observations suggest that, in some dogs with pemphigus foliaceus, immunosuppression can lead to long-term remission of skin lesions, and that discontinuation of treatment is not necessarily followed by a recurrence of clinical signs.     

Formulation and (bio)availability problems of drug formulations in birds.

Most drugs used for the treatment of birds are not formulated for birds. Therefore the availability of drugs for birds and their administration routes largely depend on formulations available for man, mammals and to some extent poultry. The problems with the application of existing formulations, the drug concentrations and the many different avian species are discussed. The desire of the avian veterinarian for the combination of several active compounds presents special problems. This again requires extra data on the interactions in galenic, pharmaceutic, pharmacokinetic and dynamic phases, which are generally not readily available.     

Experimental uses of flunixin meglumine and phenylbutazone in food-producing animals

Presently, in the United States, there are no nonsteroidal anti-inflammatory drugs, except aspirin, that are approved for use in animals intended for food production. Use of phenylbutazone, flunixin meglumine, and dipyrone for treatment of food animals may be considered in special circumstances. Such use requires strict adherence to FDA guidelines for extra-label use of drugs. Flunixin meglumine and phenylbutazone have been shown to have a favorable influence on the course and outcome of certain diseases. This report reviews information concerning the pharmacology, pharmacokinetics, and therapeutics of phenylbutazone and flunixin as they have been used on an experimental basis in food animals.     

Homeopathy: an effective and risk-free alternative to conventional pharmacotherapy? Part 1: Hahnemann and his teaching]

The article considers the attractions and dangers of homeopathic therapy from the view of a pharmacologist. Homeopathic drugs may exert pharmacodynamic (but also toxic) effects at low dilutions (D0-D6), but there is no scientific proof for specific effects of higher dilutions except for substances with a high toxic potential. Most homeopathic drugs have no reasonable basis for clinical use but, in case of toxic compounds, especially those with carcinogenic or allergic potential, homeopathy may bear risks for the animal and, because of residues in food animals, also for humans. Thus, homeopathic treatment should not be used when effective conventional treatments are available, and the use of homeopathic drugs with toxic potential should be avoided.     

ACVIM small animal consensus statement on safe use of cytotoxic chemotherapeutics in veterinary practice

The purpose of this report is to offer a consensus opinion of ACVIM oncology diplomates and technicians on the safe use of cytotoxic chemotherapeutics in veterinary practice. The focus is on minimizing harm to the personnel exposed to the drugs: veterinary practitioners, veterinary technicians, veterinary staff, and pet owners. The safety of the patient receiving these drugs is also of paramount importance, but is not addressed in this statement. Much of the information presented is based on national recommendations by Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, United States Pharmacopeia, and other published regulations. These directives reflect an abundance of caution to minimize exposure to medical personnel, but large‐scale studies about the consequences of long‐term occupational exposure are not available in veterinary medicine. Challenges in the delivery of optimal treatment safely and economically to veterinary patients in general practice without access to a veterinary oncologist or other specialist, because of costs or proximity, remain.     

Mycobacterial disease in a population of 339 cats in Great Britain: II. Histopathology of 225 cases, and treatment and outcome of 184 cases

This study investigated 339 cases of feline mycobacterial infection, with histopathology findings from 225 cases, and treatment and outcome information from 184 cases. Tissue samples from cats with cutaneous lesions or suspicious masses at exploratory laparotomy were submitted to the Veterinary Laboratories Agency for mycobacterial culture over a 4-year period to December 2008. The study reviewed the files for information about histopathology, treatment and outcome, and blindly reviewed histopathological changes (including staining for acid-fast bacteria [AFB]) in a sub-set of 45 cases. When a cat is suspected of having a mycobacterial infection, accurate identification of the species involved helps to determine possible treatment options and prognosis. The study confirmed that histopathology and the presence of AFB are useful tools in the recognition of mycobacterial infection. Unfortunately, they did little to help determine the species of mycobacteria involved. The study identified a group of cats that were negative for AFB at the primary laboratory, but from which mycobacteria could be cultured; commonly Mycobacterium bovis or Mycobacterium microti. The study also identified a group of cats which where culture negative, despite typical signs of mycobacterial infection and positive AFB staining. Many cases responded favourably to treatment (56% of the cases where information was available), and many cats gained complete remission (42%). However, relapses were common (64%) and often followed by pulmonary and/or systemic spread that may have resulted from treatment with short courses of single drugs. This study shows that the diagnosis and treatment of feline mycobacteriosis is complex and challenging.     

Osteoarthritis in the cat: 2. how should it be managed and treated?

PRACTICAL RELEVANCE: Osteoarthritis (OA) is very common in the cat and in many cases is associated with significant long-term pain, which limits mobility and activity, and severely compromises the animal's quality of life. CLINICAL CHALLENGES: The treatment of chronic arthritic pain is a major challenge and many analgesic drugs used in other species are not licensed, not available or not tested for use in the cat. Many older cats with painful OA have some degree of chronic kidney disease (CKD) and many clinicians are reluctant to use non-steroidal anti-inflammatory drugs (NSAIDs) in these animals because of the potential for nephrotoxicity. EVIDENCE BASE: There are several publications that show that meloxicam is an effective NSAID for the cat and can be used long-term. It is easy to administer and there is published evidence that meloxicam can actually slow the progression of CKD in this species. Many other drugs are used to treat chronic pain in the cat but there is no documented evidence of their efficacy in OA. Unlike the dog, there is limited evidence for the effectiveness of omega-3 fatty acid-rich diets in managing feline OA and further work is required. There is no published data as yet for the usefulness or otherwise of nutraceuticals (glucosamine and chondroitin) in managing feline OA; studies in the authors' clinic suggest some pain-relieving effect. Research into environmental enrichment as a way of improving quality of life in cats with painful OA is lacking, but it is an approach worth using where possible. Modifications to the environment (eg, provision of comfortable bedding and ramps) are also important.     

Modes of local drug delivery to the musculoskeletal system.

A number of methods for the local delivery of drugs to musculoskeletal tissues in the horse are now available. Further research is required to document the disposition of drugs delivered by such methods and to correlate this information with efficacy. Perhaps the greatest potential area for the methods discussed is the treatment of synovial and bone infections. To be able to provide high and sustained therapeutic concentrations of antimicrobials to the site of infection should increase the chances of success in such cases. These methods of drug delivery need to be used in conjunction with other management procedures, however, including bacterial culture and sensitivity procedures, systemic antimicrobials, surgical drainage, removal of dead bone or surgical implants, establishment of fracture stability, use of autogenous bone grafts, systemic NSAIDs, and rest.     

Resistance studies of erythromycin and rifampin for Rhodococcus equi over a 10-year period

This study sought to determine whether an increase in resistance of Rhodococcus equi to the antibiotics rifampin and erythromycin occurred over a 10-year period. This was carried out by the use of E test strips for rifampin and erythromycin to determine the MIC (minimum inhibitory concentration) values of Rhodococcus equi to this combination of antibiotics.The findings of this study indicated that there was an increase in resistance of Rhodococcus equi to rifampin and erythromycin over the 10-year period. The MIC for rifampin increased from 0.081 μg/ml in 1996 to 0.187 μg/ml in 2006 and from 0.258 μg/ml for erythromycin during the years prior to 2000 to 0.583 μg/ml in 2006.This finding suggests that there may be a problem in the treatment of Rhodococcus equi infections in foals in the future, particularly as the number of drugs available for treatment of Rhodococcus equi infection is limited because of the intracellular capabilities of this bacterium. Antibiotics used in its treatment have to be able to penetrate the polysaccharide cell wall of Rhodococcus equi as well as the alveolar macrophages in which the bacterium is capable of surviving.     

Animal health in organic agriculture: new guidelines and perspectives for food animal practitioners

In the last decade, the organic agriculture in Switzerland has been substantially increased due to the interest of consumer and financial incentives of the federation. Ruminants take directly or indirectly the largest part from grassland used within the organic managed surfaces. As the contacts between veterinary practice and organic agriculture has increased, the potential for veterinary activity in this area has developed considerably. The organic agriculture guidelines stipulate that all the preventive measures should be taken in feeding, keeping and breeding to insure animal health safety. This requires veterinary services for herd management. The organic status of a farm affects veterinary practice also in the form of alternative therapy/drugs administration and measures like dehorning and tail-docking. An important point in organic managed herds requests that treatment of animals should depend on alternative medical preparations or procedures based on veterinarian's experience and also on the therapeutic effect on the animal species concerned as well as on the disease. However, there are no restrictions on the veterinarian to use registered drugs as long as no alternative therapy, according to experience and possible success, is available to treat the animals. The prophylactic administration of allopathic veterinary drugs is not permissible. Further features in organic farms regarding the use of drugs are the keeping of withholding/withdrawal time, the documentation and the treatment frequency tolerated by organic marketing. Despite the above measures, the animal health has a priority regardless of its organic status. Although management of organic farms represent a unique responsibility, there are still obvious deficits in the education of veterinary practitioners for this new situation. However, in the future the extension of veterinary activity to include the alternative medical therapy should be regarded for the practitioner as a challenge and an opportunity at the same time.