Systemic antimicrobial therapy in foals

Antimicrobial agents are commonly used in neonatal foals for the treatment or prevention of sepsis. However, due to concerns about the development of antimicrobial resistance and increasing pressure on veterinarians to rationalise antimicrobial use, we should be trying to reduce the unnecessary use of antimicrobials. This article reviews many of the important considerations when selecting an antimicrobial for use in neonatal foals. Firstly, we consider general differences in neonatal pharmacology and physiology. Secondly, we review common antimicrobial drugs and their indications. Finally, we review antimicrobial stewardship.     

Medical Management of Recurrent Seizures in Dogs and Cats

The problem of recurrent seizures is a common and challenging one in veterinary medical practice. The pathophysiology and pharmacologic suppression of focal seizure activity have been studied extensively in basic research settings, yet little is known of the genesis, modulation, and termination of generalized seizures, the most common form of seizures noted to occur in companion animals. Knowledge concerning the pharmacokinetic fate of anticonvulsant drugs currently used in veterinary medicine is adequate, though prospective clinical studies of the efficacy of these drugs in the treatment of various types of seizures are lacking. This study will review the available literature regarding the pharmacology, use, and side effects of anticonvulsant drugs currently available for control of recurrent seizures in companion animals. Alternative anticonvulsant drugs will also be described.     

Effects of pharmacological agents on gastrointestinal motility

The control mechanisms of gastrointestinal motility are complex. Extrinsic neurohormonal effects modulate an intrinsic system, often called the "gut brain," composed of nervous and neuropeptide components. To exert pharmacologic influence on GI motility, use is made of agents that mimic the external control system. Agents that stimulate opioid receptors, block adrenoceptors, block or facilitate acetylcholine action, or antagonize the action of prostaglandins are used to effect changes in GI motility. The major indications for pharmacologic intervention are to increase motility in constipation, to reduce it in most cases of diarrhea, and to restore propulsive coordination in postoperative ileus. In cases of clinical colic the primary requirement is control of pain. Agents used for this purpose may adversely affect motility, and choice requires knowledge of their actions in this respect. In addition, drugs used for other purposes, anthelmintics for instance, may also influence gut motility. A synopsis of the actions of the agents commonly employed in GI motility control and some associated drugs are displayed in Table 3. Recent advances in the understanding of drug action on the gut should help in the selection of drugs for clinical use.     

A survey of some drugs commonly used in the camel

Specific recommendations for drug dosages for the camel are rare and doses for this species are usually extrapolated from those recommended for other species. The pharmacology and toxicity of drugs likely to be used in the camel needs to be further studied to ensure the efficacy and safety of these drugs in this species.Most of the reported work is on the chemotherapeutic efficacy of a few drugs long in use in other species against trypanosomiasis, mange and gastrointestinal nematodes. Areas of study most deficient are pharmacodynamics, pharmacokinetics and drug metabolism. The anatomical, physiological and biochemical peculiarities of the camel warrant more pharmacological and toxicological studies in this species.This article surveys the literature on the pharmacology, toxicity and therapeutic uses of some antiparasitic and antibacterial drugs and central nervous system depressants commonly used in the camel. It appears that camels are more susceptible to the toxic action of some trypanocidal drugs than other species. In certain cases they may metabolize some drugs differently. In general, the camel appears to be a good subject for analgesics and anaesthetics.     

Diseases in neonatal foals. Part 1: The 30 day incidence of disease and the effect of prophylactic antimicrobial drug treatment during the first three days post partum

Reasons for performing study: Neonatal diseases have been grouped and analysed but up‐to‐date statistically significant information about the incidence and prevalence of diseases in foals is limited. Since the 1950s it has been a common management practice to administer a 3 day course of antimicrobial drugs to neonatal foals. This was shown to significantly reduce the incidence of infections (Platt 1977). Since then management practices have improved and it is widely believed that prophylactic antimicrobial drugs are no longer necessary in foal rearing. Objectives: To determine the 30 day incidences or prevalences (depending on case definition) of various diseases and conditions in the neonatal foal and ascertain the influence of a prophylactic 3 day treatment on the frequency of infections. Methods: The population consisted of Thoroughbred foals born on stud farms in the Newmarket (UK) area in 2005 (n = 1031). Depending on the stud farm's practice in the use of prophylactic antimicrobial drugs, 2 groups of newborn foals (treated and untreated) were identified and followed for 30 days. Results: The 30 day incidences of infectious diseases under study were between 0.2% (osteomyelitis) and 5.85% (systemic disease with diarrhoea). The overall incidence for ‘total infectious diseases’ was 8.27%. The most commonly observed noninfectious condition was limb deformities (12.11% of all foals). There was no significant difference in the incidence of infectious diseases between the 2 groups. Conclusion: Infectious diseases are still an important problem in neonatal foals requiring further investigation as to which factors other than antimicrobial prophylaxis are relevant for disease prevention. Potential relevance: The results provide an up‐to‐date overview about the frequencies of various neonatal foal diseases. They do not support the traditional prophylactic use of antimicrobials to prevent infectious diseases in healthy newborn foals. However, it should be noted that this study was not a randomised controlled trial and therefore does not provide the strongest possible evidence for this conclusion.     

Aspects of pharmacology in the neonatal foal

Other therapeutic agents used in foals for specific diseases are discussed elsewhere. The marked effect of species, age, and degree of maturity on drug metabolism in the neonate reinforces the danger of interspecies extrapolation of pharmacology, the need for information specific for the foal, and the necessity for monitoring drug levels in the individual. Suggested antimicrobial doses are listed in Tables 3, 4, and 6. Recommended doses of anticonvulsants and sedatives are listed in Table 8 and in the article "Intensive Care of the Neonatal Foal." The following are recommendations for drug therapy in the neonate: Avoid unnecessary administration of drug to the dam at parturition because of possible placental transfer of the drug with subsequent effects on the neonate. If possible, avoid unnecessary drug therapy in foals under 30 days of age. Select a drug that undergoes minimal biotransformation (hepatic metabolism) and is not highly protein bound. Owing to probable immunodeficiency in the neonate, broad-spectrum, bactericidal drugs are preferred for treatment of life-threatening infections. Every attempt should be made to identify the etiologic agent so that drug therapy can be based on cultures and sensitivity test results to maximize the benefit-risk ratio. Parenteral (intramuscular or intravenous) drug administration is preferable to oral. Avoid drugs that are known oxidants, which may produce hemolysis or methemoglobinemia. In general, the same or a slightly higher initial dose should be employed in the neonate, but it should be given less frequently than in the adult if it has a high potential to cause toxicity. When possible, individual monitoring of serum levels of potentially toxic drugs should be employed in premature and newborn foals unless specific drug pharmacokinetics are known for that age group.     

Research Progress on Reproductive Toxicology

With the deepening of modern biological science,obstetrics,pharmacology and toxicology intersect penetration with each other,thus gradually make the development of reproductive toxicology.Reproductive toxicology include two parts:Reproductive toxicology and developmental toxicology,it is a method focused on exploring whether there are influences of environmental and drugs factors on parental reproductive functions and the development of offspring.In this paper,the injury effects of test drugs on the reproductive cytogenesis,fertilization of egg cell,embryogenesis,pregnancy,childbirth,breast-feeding and development of newborn pups were summarized.     

繁殖毒理学研究进展

随着现代生物科学研究的不断深入,产科学、药理学和毒理学相互交叉渗透,使得繁殖毒理学逐渐发展起来。繁殖毒理学包括生殖毒理学和发育毒理学,是探究环境、药物等因素对亲代的生殖功能及子代发育过程是否有影响的一门科学。本文就繁殖毒理学所探讨的受试物对试验动物的生殖细胞发生、卵细胞受精、胚胎形成、妊娠、分娩、哺乳过程及初生幼仔发育的损害作用等进行综述。     

Clinical pharmacology of nervous system diseases.

The well-developed defense barriers of the CNS and the expense of drug therapy limit the pharmacologic options for the treatment of neurologic diseases in horses. New approaches to controlling inflammation in the CNS are improving the outcomes of bacterial meningitis. The appropriate treatment of EPM remains controversial. More research is needed to evaluate the pharmacokinetics and pharmacodynamics of drugs in the CNS of the horse. Behavioral pharmacology has become fashionable in human and small animal medicine, but it needs to be evaluated for the potential of unethical use in performance horses.     

Clinical pharmacology of nonsteroidal anti-inflammatory drugs in dogs

OBJECTIVES: To discuss the clinical pharmacology of currently licensed veterinary NSAIDs and to review gastrointestinal and renal adverse effects as well as drug-drug interactions that have been reported with these drugs. To review the use of NSAIDs in the peri-operative setting and their use in patients with osteoarthritis. To further review the reported effects of NSAIDs on canine articular cartilage and liver as well as the clinical relevance of a washout period. DATABASES USED: PubMed, CAB abstracts and Google Scholar using dog, dogs, nonsteroidal anti-inflammatory drugs and NSAID(s) as keywords. CONCLUSIONS: A good understanding of the mechanisms by which NSAIDs elicit their analgesic effect is essential in order to minimize adverse effects and drug-drug interactions. Cyclooxygenase (COX) is present in at least two active isoforms in the body and is the primary pharmacologic target of NSAIDs. Inhibition of COX is associated with the analgesic effects of NSAIDs. COX is present in the gastrointestinal tract and kidneys, along with other areas of the body, and is also the likely reason for many adverse effects including gastrointestinal and renal adverse effects. The newer veterinary approved NSAIDs have a lower frequency of gastrointestinal adverse effects in dogs compared to drugs such as aspirin, ketoprofen and flunixin, which may be due to differential effects on the COX isoforms. There are currently no published reports demonstrating that the newer NSAIDs are associated with fewer renal or hepatic adverse effects in dogs. NSAIDs remain the cornerstone of oral therapy for osteoarthritis unless contraindicated by intolerance, concurrent therapies or underlying medical conditions. NSAIDs are also effective and frequently used for the management of post-operative pain.     

The future of veterinary therapeutics: a glimpse towards 2030

The purpose of this article is to make an educated guess as to what veterinary pharmacology will look like in two decades. By examining the past, it is evident that change is incremental unless a transforming discovery occurs. In the last few decades, such events have dramatically changed medicine and pharmacology, however they have not percolated through the system to the effect that novel drugs have replaced our traditional armamentarium. The effect of six transforming technologies (continued advances in computer technology, microfluidics, nanotechnology, high-throughput screening, control and targeted drug delivery, pharmacogenomics) on veterinary therapeutics is examined. These should lead toward more efficacious and safer drugs across most therapeutic classes due to both increases in our knowledge base as well as more efficient drug development. Shorter term improvements in drug delivery should be seen. Although this growth in technology would portend major advances over the next few decades, economic and regulatory constraints must still be overcome for these new drugs or therapeutic approaches to become common practice.     

基于UPLC-MS/MS技术研究濒死状态下新生羔羊血清代谢物变化

基于流行病学的角度,旨在初步探索与新生羔羊疾病相关的代谢标识物。本研究采用病理对照试验设计,利用高效液相色谱串联质谱比较病危临死新生羔羊与健康新生羔羊（相同日龄）的血清代谢差异。结果显示：两组血清代谢物能得到较好区分,共鉴定出13种差异代谢物,KEGG富集分析显示,这些差异代谢物主要富集在氨基酸生物合成和代谢通路上。羔羊濒死过程中血清内源性代谢物发生明显改变,可为新生羔羊疾病诊断标识物的筛选和构建提供基础。     

Serum Metabolic Analysis of Antemortem Neonatal Goats Using the Approach of UPLC-MS/MS

This study aimed to explore the metabolic differences in sera of antemortem neonatal goats based on an epidemiological perspective. A case-control design was used to discover the metabolic differences in serum between the dead newborn goats suffered from a disease and healthy goats at the same age by using UPLC-MS/MS. A total of 13 compounds were significantly different between healthy and dead newborn goats. KEGG analysis showed that these differential produced metabolites mainly involved the synthesis and catabolism of amino acids. The differential produced metabolites in serum are important for us to understand the agonal reaction at the metabolic level when neonatal goats suffering from a disease. This study also provides an advanced research basis for the establishment of disease-related biomarkers for neonatal goats which may suffer from a disease.     

Therapeutics for rabbits.

A variety of pharmacologic agents are currently available to treat house rabbits. In many cases, dosages are based on extrapolation from other species or empirical data. Dosing in rabbits is further complicated by individual variation. An understanding of rabbit physiology and the pharmacology of prescribed medications helps ensure that the agents are used as effectively and safely as possible. In this article, basic rabbit pharmacobiology is reviewed and techniques for drug administration are described. A formulary for house rabbits is provided.     

Newborn calf welfare: A review focusing on mortality rates

Calf mortality control is vitally important for farmers, not only to improve animal welfare, but also to increase productivity. High calf mortality rates can be related to larger numbers of calves in a herd, employee performance, severe weather, and the neonatal period covering the first 4 weeks of life. Although the basic premise of preventing newborn calf mortality is early detection and treatment of calves at risk for failure of passive transfer of immunoglobulins, calf mortality due to infectious diseases such as acute diarrhea increases in the presence of these physical and psychological stressors. This suggests that farmers should not ignore the effects of secondary environmental factors. For prevention rather than cure, the quality of the environment should be improved, which will improve not only animal welfare but also productivity. This paper presents a review of the literature on newborn calf mortality and discusses its productivity implications.     

Pharmacokinetics of hexobarbital, sulphadimidine and chloramphencoliin neonatal and young pigs.

Half-life and apparent specific volume of distribution of hexobarbital, sulphadimidine and chloramphenicol were investigated in newborn, 1, 3, 5 and 8 weeks old pigs. Hexobarbital sleeping time and plasma concentration of hexobarbital at recovery were measured in the same age groups. The half-life of hexobarbital and chloramphenicol was long in newborn pigs but decreased fast during the first week after birth. From 1 to 8 weeks after birth the decrease was less pronounced. The half-life of sulphadimidine increased during the first 3 weeks of life, but in 1 and 3 weeks old pigs the amount of N⁴-acetylated sulphadimidine in plasma at 200 min. after the injection was higher than in the newborn pigs.The apparent specific volume of distribution of hexobarbital, sulphadimidine and chloramphenicol was changed in different ways from birth to 8 weeks of age.The hexobarbital sleeping time was very long in the newborn pigs and decreased until 3 weeks of age. The concentration of hexobarbital in plasma at recovery was unchanged from birth to 8 weeks of age.The concentration of chloramphenicol metabolites in plasma 100 min. after the injection increased very fast during the 8 weeks of observation. The concentration of N⁴-acetylated sulphadimidine in plasma at 200 min. after the injection increased from birth to 1 week of age, then it decreased.The data are stressing that the neonatal pig is a convenient model for pharmacokinetic testing of drugs used as pharmacotherapeutics in neonatal life.     

Clinical pharmacology and therapeutic uses of non-steroidal anti-inflammatory drugs in the horse

Weak organic acids possessing anti-inflammatory, analgesic and antipyretic properties--commonly known as aspirin-like drugs--have been used in equine medicine for almost 100 years. These non-steroidal anti-inflammatory drugs (NSAIDs) may be classified chemically into two groups; the enolic acids such as phenylbutazone and carboxylic acids like flunixin, meclofenamate and naproxen. All NSAIDs have similar and possibly identical modes of action accounting for both their therapeutic and their toxic effects. They block some part of the cyclo-oxygenase enzyme pathway and thereby suppress the synthesis of several chemical mediators of inflammation, collectively known as eicosanoids. The available evidence indicates that some of the newer NSAIDs have a reasonable safety margin but further studies are required. The toxicity of phenylbutazone in the horse has been investigated very thoroughly in recent years and it has been shown to cause renotoxicity and, most significantly, ulceration of the gastrointestinal tract when relatively high doses are administered. Several factors may predispose towards phenylbutazone toxicity in the horse, including breed and age, but high dosage is considered to be particularly important. The absorption into, and fate within, the body of NSAIDs are considered and particular attention is drawn to the ways in which these pharmacokinetic properties relate to the drugs' toxicity and clinical efficacy. In reviewing current knowledge of the clinical pharmacology of this important group of drugs, it is hoped to provide the clinician with a rational, scientific basis for their safe and effective use in equine practice.     

Pediatric emergencies.

The unique anatomic and physiologic characteristics of neonatal and pediatric patients make diagnosis, monitoring, and treatment a challenge.Adult parameters cannot be relied on in these patients, and an awareness of these unique characteristics is essential for any practitioner with a neonatal and pediatric patient base. In addition, many laboratory and pharmacologic data differ dramatically in neonates compared with adults of the same species.Familiarity with these variations is essential in the monitoring and treatment of the neonatal and pediatric illness, such as hypovolemia, shock, and sepsis.     

A RATIONAL APPROACH TO THE USE OF DRUGS FOR SEDATION AND RESTRAINT OF THE LARGER MAMMALS

During the last decade, a number of drugs have become available which, when used separately, or when combined with another have facilitated the handling and movement of nervous or aggressive animals. These drugs are usually grouped according to their principal properties into narcotics, such as Etorphine and Fentanyl, sedatives such as Azaperone and Xylazine and anaesthetics such as Phencyclidine and Alphaxalone. This is a somewhat loose terminology as the properties of a number of these agents when used at different dose rates or in different species may place them into more than one of these groups. Knowledge of the clinical pharmacology of these drugs and of the different responses found amongst the various orders of mammals is necessary if the effect required is to be accurately and safely obtained. Narcotics for instance are contra-indicated in the Felidae on account of their severe excitatory side-effects but in some carnivore families the milder side-effects can be overcome by combining the narcotic with a sedative. This paper sets out to describe these different effects and to show that an understanding of them is important when selecting the appropriate drugs for a particular case.     

Molecular evidence for transplacental transmission of Theileria equi from carrier mares to their apparently healthy foals

The intra-erythrocytic parasite Theileria equi is one of two tick-transmitted causative agents of equine piroplasmosis. Piroplasms of T. equi can be transmitted across the equine placenta and once a horse is infected, it appears to remain a lifelong carrier, since anti-theilerial drugs suppress but do not eliminate the parasite. Carrier mares may transmit the organism to their offspring and this may result in abortion or neonatal piroplasmosis, but observations by some researchers suggest that foals may be born as carriers yet remain apparently healthy. Using a T. equi-specific oligonucleotide probe, we have determined that transplacental transmission occurs early in equine foetal development and that carrier mares may give birth to healthy carrier foals. Investigation of parasite levels and the effect of maternal colostrum on the newborn suggests that colostral T. equi antibody may act to suppress parasitaemia in the newborn, reducing the incidence of clinical neonatal piroplasmosis.