Gastroprotectants in small animal veterinary practice – a review of the evidence. Part 1: cyto‐protective drugs

Diverse drugs with presumed cytoprotective effect have been used therapeutically in small animal veterinary practice for various gastro‐intestinal conditions such as oesophagitis, gastric ulceration, gastritis or chronic gastro‐enteropathies. Their efficacy has been doubted in human medicine, raising similar questions in the veterinary field. The aim of this review was to assess the current evidence on the efficacy and safety of these drugs in dogs and cats. Through a systematic review of the literature, we identified 37 articles on the use of misoprostol, sucralfate and other gastroprotectants in dogs and cats. There was evidence to support use of misoprostol in the prevention of aspirin‐induced gastroduodenal mucosal injury in dogs, and for use of sucralfate in the prevention of acid‐induced oesophagitis in cats. However, the overall quality of evidence supporting the use of these drugs in small animal patients was poor. In contrast, there was evidence of important adverse effects, especially drug interaction and gastro‐intestinal signs. We therefore recommend prescribing these drugs with caution until further well‐conducted studies reveal a useful gastroprotectant effect.     

Antiviral therapy for ocular viral disease.

Ophthalmic manifestations of viral disease are commonly encountered in veterinary practice. Although the number of antiviral agents is rapidly increasing, the efficacy of many of these drugs against animal viral pathogens may not be known. Furthermore, some of these newer medications may, in fact. be toxic to animal patients. Continued research on the efficacy of these medications in treating viral diseases of veterinary importance is warranted.A thorough review of the ever-growing body of literature is imperative before instituting any new or unknown antiviral therapy.At this time, feline HSV-1 infections remain the most well understood of the ocular viral infections that veterinary practitioners may be called on to treat. Ironically, the number of antiviral agents proven to be effective in naturally occurring clinical cases of FHV-I remains quite limited. With new medications being investigated, this paucity of information on efficacious antiviral therapeutic agents will hopefully improve.     

Thrombolytic Therapy in Dogs and Cats

Objective: To review the thrombolytic agents most commonly used in humans, their mechanisms of action, potential uses, adverse effects, and reports of their use in dogs and cats.
Human data synthesis: Thrombolytic agents avaliable in human medicine include streptokinase, urokinase, tissueplasminogen activator (t-PA), single-chain urokinase plasma activator (scu-PA) and anisoylated plasminogen-strep-tokinase activator complex (APSAC). These agents were originally used for the management of proximal deep vein thrombosis and severe pulmonary embolism but more recently, use of these drugs has been extended to include the treatment of acute peripheral arterial disease, cerebrovascular disease (stroke) and acute coronary thrombosis. The most predictable side effect associated with the use of thrombolytic therapy is hemorrhage.
Veterinary data synthesis: Clinical experience with thrombolytic agents in small animals is limited to streptokinase and t-PA. It is possible, that as in humans, canine and feline patients with PTE and right ventricular dysfunction may benefit from thrombolytic therapy but there are no veterinary studies to support this theory to date. Successful use of streptokinase has been documented in a small number of canine patients with systemic thromboembolism. ⁶³ Thrombolytic therapy is relatively efficacious in cats with aortic thromboemboli but is associated with a high mortality rate. ^59,60,64 With regard to use of t-PA in veterinary medicine, the small number of animals treated with varying protocols makes it impossible to provide safe and effective dose recommendations at this time.
Conclusions: Future goals for thrombolytic therapy in veterinary medicine include determination of more specific clinical indications, as well as design of effective protocols that minimize mortality and morbidity.     

Drugs in salmonid aquaculture – A review

In contrast to mammalian therapeutics, the use of pharmaceutical substances is rather limited in fish. It is basically restricted to anaesthetic agents and anti-infective agents for parasitic and microbial diseases. Anaesthetic agents are used primarily in fish farm and laboratory settings to provide analgesia and immobilization of fish for minor procedures. The anti-infective agents are used for controlling disease and the choice of drug depends on efficacy, ease of application, human safety, target animal safety including stress to the fish, environmental impact, regulatory approval, costs, and implications for marketing the fish. In this article, the major drugs used in salmonids in North America and Europe will be reviewed and some insight into future directions for drug development and use for the salmonid industry will be introduced. The mechanisms of action, pharmacokinetics, side effects, and uses of the drugs are emphasized.     

In vitro antimicrobial activity of marbofloxacin and enrofloxacin against bacterial strains isolated from companion animals

Fluoroquinolones were originally developed for the Gram-negative aerobic spectrum, but the newer generation agents are also highly effective against some Gram-positive pathogens and cause few adverse effects. Owing to these characteristics, fluoroquinolones are often used in first line therapy in small animal practice. However, their widespread use has raised concern over emerging bacterial resistance. In this study we evaluated the in vitro efficacy of two fluoroquinolones, marbofloxacin and enrofloxacin, on field strains isolated from clinical infections between 2002 and 2005. Our data show that most of the isolates are still sensitive to both antimicrobials and marbofloxacin was more effective than enrofloxacin, especially against P. aeruginosa and beta-Streptococci (P < 0.01). beta-Streptococci demonstrated the greatest resistance to the two study drugs.     

New chemotherapy agents in veterinary medicine.

Several anticancer drugs have been added to the therapeutic armamentarium in recent years. Some of these agents are traditional drugs with a long history of use in human oncology. Increased sophistication in clinical trial design in veterinary oncology has allowed the incorporation of agents previously viewed as excessively toxic. Other agents have been developed more recently. This article summarizes the veterinary experience with two older alkylating agents, lomustine and streptozocin, and newer compounds ifosfamide and gemcitabine. The published literature regarding veterinary use of these agents is limited, and the reader is advised to contact a veterinary oncologist for current guidelines when contemplating use of these agents.     

Pharmacological approaches towards rationalizing the use of endoparasitic drugs in small animals

Parasitic diseases are an important health concern to small animal veterinarians worldwide, and their zoonotic potential is also of relevance to human medicine. The treatment and control of such conditions relies heavily on pharmaceutical intervention using a range of antiparasitic drugs and/or their biologically active metabolites. Broad spectrum agents have been produced, although narrow and even monospecific drugs are used in some situations. Their efficacy may depend on dosage, the target pathogen(s), the host species and/or the site of infection. Optimal use of antiparasitics requires a detailed consideration of the pharmacokinetic and pharmacodynamic properties of the drugs in specific clinical contexts. This review summarizes the present status of knowledge on the metabolism, and physicochemical and pharmacological properties of the major antiparasitic drugs currently used in small animal veterinary practice. In addition, data relevant to therapeutic dosage, efficacy and clinical indication/contraindication, particularly in relation to combination drug therapy, are included.     

兽用抗菌增效剂制剂的研究进展

抗菌增效剂属于人工合成的二氨基嘧啶类药物，此类药物与抗菌药物联合使用时会以特定的机制来增强抗菌药的药物活性。近年来，由于抗生素的广泛使用甚至滥用导致细菌耐药的问题日益显现，通过加入抗菌增效剂而研制出的新制剂可以提高抗菌药在动物体内的利用率、降低药物用量、增强药物疗效、降低兽药残留及减少细菌耐药性。文章分析了近年来甲氧苄啶、二甲氧苄啶和艾地普林与各类抗生素的联合使用制备的制剂产品，发现其对疾病的治疗效果普遍优于单独使用抗生素。同时，配合中药的使用对细菌耐药的问题有显著改善，为后期抗菌增效剂的研究打开新的局面。随着对兽药制剂的研究，其不再局限于简单的剂型，通过运用新技术、新材料研制出的制剂，针对不同的给药部位和给药途径可以对病患进行更精准的治疗，减少药物达到靶部位的时间，增加患病部位的药量，此思路可为后续的研发方向提供支持和参考。文章将对抗菌药-抗菌增效剂联用制剂的研发情况进行综述。     

Glucocorticoids in the cat

Glucocorticoids are one of the two main classes of hormones, along with mineralocorticoids, which are secreted from the adrenal cortex. Since the discovery of the anti‐inflammatory properties of the natural glucocorticoid hydrocortisone, a large number of artificial glucocorticoids have been synthesized to attempt to increase efficacy and decrease side effects. These drugs are now considered one of the most commonly prescribed agents in veterinary practice. The effect of these drugs has been shown to vary significantly between species. Cats appear to tolerate glucocorticoids well, resulting in these drugs being recommended for a wide variety of conditions; however, there are few studies on the effects of glucocorticoids in cats. In this paper we review some of the available literature on glucocorticoid use in the cat.     

Pharmacology and therapeutics of non-steroidal anti-inflammatory drugs in the dog and cat: 2 Individual agents

The general pharmacology of the non-steroidal anti-inflammatory drugs (NSAIDs) used in dogs and cats has been described in part 1 of this review (Lees and others 1991). This paper outlines the properties of the individual agents as they are used in small animal practice. The NSAIDs which have been used extensively in small animals include the older agents such as Aspirin, cinchophen and phenylbutazone. These agents have previously been used empirically by extrapolation of dosages from other species and by clinical experience. Studies are now available which provide a scientific rationale for the dosage rate recommended. A number of new drugs have recently been licensed for use in the dog or may be licensed in the near future. These include flunixin, carprofen and tolfenamic acid and the data generated from these products provides very useful information for formulating I effective dosage regimens. There are also some NSAIDs such as piroxicam which have been investigated in the dog because they have particular properties which may be of use in common clinical conditions and others, such as Paracetamol and Ibuprofen, which are readily available to the public and which owners may administer to dogs or cats at toxic doses.     

Nonsteroidal drugs used in the treatment of inflammation

An understanding of the basic mechanisms of inflammation aids in providing rational therapy to our patients. This article discusses both the inflammatory process and drugs used to reduce its intensity. The commonly used drug aspirin, as well as other less frequently employed medications, are described. There is an emphasis on clinical use of these agents, including appropriate dosages and precautions.     

Pharmacokinetic/pharmacodynamic relationships of antimicrobial drugs used in veterinary medicine

The rise in incidence of antimicrobial resistance, consumer demands and improved understanding of antimicrobial action has encouraged international agencies to review the use of antimicrobial drugs. More detailed understanding of relationships between the pharmacokinetics (PK) of antimicrobial drugs in target animal species and their action on target pathogens [pharmacodynamics (PD)] has led to greater sophistication in design of dosage schedules which improve the activity and reduce the selection pressure for resistance in antimicrobial therapy. This, in turn, may be informative in the pharmaceutical development of antimicrobial drugs and in their selection and clinical utility. PK/PD relationships between area under the concentration time curve from zero to 24 h (AUC(0-24)) and minimum inhibitory concentration (MIC), maximum plasma concentration (C(max)) and MIC and time during which plasma concentrations exceed the MIC have been particularly useful in optimizing efficacy and minimizing resistance. Antimicrobial drugs have been classified as concentration-dependent where increasing concentrations at the locus of infection improve bacterial kill, or time-dependent where exceeding the MIC for a prolonged percentage of the inter-dosing interval correlates with improved efficacy. For the latter group increasing the absolute concentration obtained above a threshold does not improve efficacy. The PK/PD relationship for each group of antimicrobial drugs is 'bug and drug' specific, although ratios of 125 for AUC(0-24):MIC and 10 for C(max):MIC have been recommended to achieve high efficacy for concentration-dependent antimicrobial drugs, and exceeding MIC by 1-5 multiples for between 40 and 100% of the inter-dosing interval is appropriate for most time-dependent agents. Fluoroquinolones, aminoglycosides and metronidazole are concentration-dependent and beta-lactams, macrolides, lincosamides and glycopeptides are time-dependent. For drugs of other classes there is limited and conflicting information on their classification. Resistance selection may be reduced for concentration-dependent antimicrobials by achieving an AUC(0-24):MIC ratio of greater than 100 or a C(max):MIC ratio of greater than 8. The relationships between time greater than MIC and resistance selection for time-dependent antimicrobials have not been well characterized.     

Advances in Exotic Mammal Clinical Therapeutics

It is imperative that the veterinarian treating exotic companion mammals stay abreast of the latest developments relating to medications and drug delivery approaches for safety and efficacy. Sustained-release formulations of commonly used drugs, as well as newer routes for administration of therapeutic agents, allow the veterinarian treating exotic companion mammals to reduce the stress associated with drug administration. Interactions can occur between vehicle and drugs when formulations are compounded; therefore, research studies are warranted regarding potential problems associated with these formulations. However, newer studies have been published that provide the basis for exploring the use of different vehicles, frequency of dosing, and drug delivery techniques for various classes of drugs in exotic mammals. The goals of this review are to not only evaluate new medications or uses for medications in companion exotic mammal patients but also review new methods of drug delivery that might be useful to the veterinarian who treats these animals.     

Role of prokinetic drugs for treatment of postoperative ileus in the horse

All horses undergoing coeliotomy for an acute abdominal crisis are at risk of developing ileus and should receive therapy aimed at promoting gastrointestinal function by restoring fluid and electrolyte balance. Adequate analgesia and prevention against peritonitis, bacteraemia and endotoxaemia should be provided. Horses that at the time of surgery have a strangulating or non-strangulating small intestinal obstruction should be considered to be at greater risk of developing a persistent ileus that is refractory to treatment than those horses with lesions involving the large intestine. In horses considered to be at greater risk of developing a persistent ileus, the use of prokinetic agents should be considered. Agents that may be used to improve gastrointestinal motility include adrenergic receptor antagonists, cholinergic agonists, benzamides, dopamine antagonists, macrolide antimicrobials, opiate receptor agonists and antagonists, somatostatin analogues and local anaesthetics. There are limited studies into the use of these agents in the horse. Until further research provides more information on motility disorders following intestinal surgery and the efficacy of prokinetic agents in this species, only selective use of some of these drugs can be recommended.     

Emerging therapeutic agents for transmissible spongiform encephalopathies: a review

Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative disorders associated with misfolding of prion protein, from PrPC to PrPSc. Different types of experimental studies have resulted in a better understanding of the pathogenesis of the prion diseases. Genetic and molecular properties of PrP isoforms have been explained but the conformational conversion of the PrPC isoform to the PrPSc isoform has not yet been entirely elucidated. However, a number of possible therapeutic agents have been tried and some have proven to be effective against TSEs but most have limitations in terms of toxicity and pharmacokinetics. Congo red (CR), anthracyclines, and polyanionic dextran sulfate have limited ability to cross the blood-brain barrier and may be toxic. The efficacy of polyene antibiotics seems to be restricted to certain scrapie strains. Tetrapyrroles and tetracyclines with low toxicities and favorable pharmacokinetics could be useful in preventing PrPSc accumulation. Compounds like branched polyamines, Cp-60, analogs of CR, quinacrine and chlorpromazine, beta-sheet breaker peptides and inhibitory peptides, active immunization using recombinant PrP and passive immunization with anti-PrP antibodies, have potential use as therapeutic agents but would need further research and clinical trials.     

Pre-purchase testing for drugs in horses: A review

The use of medications to mask defects of wind, limb or temperament in horses offered for sale can be a problem for purchasers, and for veterinarians performing pre-purchase examinations. Drugs which may be used in this way include the phenylbutazone-like drugs, cotricosteroids, local anaesthetics, and tranquilizers. If skillfully used, no signssuggestive of medication by these agents will be detectable by the examining veterinarian. In the absence of information on the medications status of an animal, the usefulness of a pre-purchase examination may be limited.These limitations can be circumvented by the analysis of blood or more expecially blood and urine samples from such horses. Current analytical methodology allows the detection of many medications in blood, and of virtually all significant medications if blood and urine samples are available. Such analysis, therefore, allows the veterinary practitioner to offer a significantly better pre-purchase test, and protects both the veterinarian and the purchaser.     

Challenges of Cardiopulmonary Bypass—A Review of the Veterinary Literature

Cardiopulmonary bypass (CPB) has been used in veterinary medicine in experimental surgery and to address congenital and acquired diseases. We review the veterinary literature and expose common challenges of CPB in dogs and cats. Specifically, we describe the most specific elements of this technique in veterinary patients. The variety in animal size has made it difficult to standardize cannulation techniques, oxygenators, and priming volumes and solutions. The fact that one of the most common cardiovascular disorders, mitral valve disease, occurs predominantly in small dogs has limited the use of bypass in these patients because of the need for small, low prime oxygenators and pumps that have been unavailable until recently. Coagulation, hemostasis, and blood product availability have also represented important factors in the way CPB has developed over the years. The cost and the challenges in operating the bypass machine have represented substantial limitations in its broader use.     

Principles of chemotherapy

Chemotherapeutic agents can be used to increase both the length and the quality of the lives of patients with a wide variety of neoplastic diseases. The therapeutic index for many of these agents is very narrow; thus, close attention must be paid to proper dosing and timing of treatment. Proper patient selection is also critical for successful chemotherapy treatment. If the clinician is familiar with the agents being used, then toxicities can often be anticipated and then treated, or in some cases prevented, to ensure continued quality of life. The purpose of this article is to review the basic principles for the safe and effective use of various chemotherapeutic agents in the treatment of neoplastic diseases.     

弓形虫病治疗药物的研究进展

弓形虫病是一种呈全球分布的重要的人兽共患寄生虫病,能感染包括人在内的所有温血动物。目前对该病的防控主要依赖药物。临床上联合使用磺胺嘧啶与乙胺嘧啶是目前治疗弓形虫病的黄金标准,但该疗法具有一定的毒副作用,且长期使用易产生耐药性。因此,针对弓形虫病的药物研究一直是研究热点。螺旋霉素、甲氧苄啶－磺胺甲噁唑等常作为替代药物用于弓形虫病的治疗,但均具有不同的局限性。因而,人们将研究重点转移到天然产物上。研究以植物提取物为主,通过筛选具有抗弓形虫的活性分子,并对其进行适当的化学修饰,可增强抗虫活性,降低毒副作用。在动物提取物中,某些动物的毒液具有抗弓形虫活性,可作为候选药物。随着研究手段的提升,一些原有药物的新活性不断被发现。在"旧"药新用研究方向,一方面以亲缘关系为标准,针对其他抗寄生虫药物进行抗弓形虫活性探索;另一方面以药物作用靶点为标准,对治疗其他疾病的药物进行抗弓形虫活性研究。文章对弓形虫病临床用药史、天然产物的开发及"旧"药新用这3个方面进行综述,以期为抗弓形虫病药物的研究提供新的思路。     

The use of corticosteroids to treat ocular inflammation.

Corticosteroids are invaluable therapeutic agents for treatment of ocular inflammation in small animal patients. The use of potent anti-inflammatory agents carries with it the risk of some side effects, however. Although some of these may be lessened by topical or subconjunctival administration, these routes are associated with specific ocular side effects about which the practitioner must be aware. With judicious use, corticosteroids remain a mainstay for the prevention and treatment of many painful and potentially blinding ocular diseases.