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1.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to control acute and chronic pain as well as to manage oncologic and neurologic diseases in human and veterinary patients. Despite ongoing research and efforts to improve the safety and efficacy of existing drugs, adverse effects such as gastrointestinal irritation, renal and hepatic toxicity, interference with hemostasis, and reproductive problems persist. The true incidence of NSAID-induced adverse effects in animals is unknown, but is likely underestimated, because cats and dogs may be more sensitive than humans to NSAIDs due to alterations in drug metabolism, absorption, and enterohepatic recirculation. NSAIDs produce both analgesia and toxic adverse effects primarily by inhibiting cyclooxygenase (COX), thereby decreasing the production of prostaglandins that signal inflammation and pain as well as mediate physiologic functions such as platelet aggregation, gastric protection, and electrolyte balance in the kidney. The presence of at least 2 COX isoforms may account for variability in NSAID efficacy and toxicity both within and among species. This paper reviews and evaluates the published literature on the safety, pharmacology, uses, and complications of a subclass of COX-1-sparing drugs, the coxibs, in veterinary medicine. Coxibs and other COX-1-sparing drugs provide a clinically useful improvement over traditional NSAIDs, but data are incomplete and more in vivo species-specific, target-tissue, and clinical studies are needed.  相似文献   

2.
Some results are given from a long-term study of possible changes in drug action in growing animals. It was found that the changes were of different character according to the drug studied, amongst other factors. A non-parallelity in changes of toxic effects and therapeutic effects of some drugs during aging appears to be important. The influence of age on effects in drug interactions is of great interest. All the findings show that it will be very difficult to correct for dose with respect to developmental changes in animals without further pharmacodynamic and pharmacokinetic studies in this field of pharmacology.  相似文献   

3.
Cats are popular pets but until recently their perioperative and traumatic pain was seriously underestimated and under treated. There are several causes of this under treatment. First, it may be difficult to detect pain in cats, because they do not demonstrate overt pain-associated behaviour. Secondly, there are relatively few analgesic drugs with market authorization for cats. Thirdly, cats have an unfortunate reputation for toxicity from analgesic drugs, particularly opioid-induced mania and classical non steroidal anti inflammatory drug toxicity. Fourthly, cats are deficient in some metabolic pathways used to metabolise analgesic drugs in other species; this may lead to genuine toxicity or to lack of effect. Recently, understanding of feline behaviour and physiology has improved, leading to better clinical management of this enigmatic species. Behavioural methods are proving to be the best means of assessing pain, and knowledge of unique feline physiology has enabled rational treatment protocols to be developed specifically for cats.  相似文献   

4.
Recent publications dealing mainly with the kinetics of antiparasitic and antibacterial agents, NSAIDs, and other drugs in camels are briefly reviewed. The kinetic data for most of these drugs indicated that they have longer absorption and elimination half-lives and slower systemic clearance in the camel compared to other animals. This corroborates earlier reports that suggested that the activities of drug-metabolizing enzymes and the capacity to biotransform and eliminate xenobiotics is lower in camels than in other ruminants. There is a clear need to establish basic kinetic data for the camel in order to avoid extrapolation of drug dosage regimens and withdrawal times from data for other animals, as this may result in irrational use of drugs in camels.  相似文献   

5.
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.  相似文献   

6.
Pharmacodynamics (PDs) is the science of drug action on the body or on microorganisms and other parasites within or on the body. It may be studied at many organizational levels--sub-molecular, molecular, cellular, tissue/organ and whole body--using in vivo, ex vivo and in vitro methods and utilizing a wide range of techniques. A few drugs owe their PD properties to some physico-chemical property or action and, in such cases, detailed molecular drug structure plays little or no role in the response elicited. For the great majority of drugs, however, action on the body is crucially dependent on chemical structure, so that a very small change, e.g. substitution of a proton by a methyl group, can markedly alter the potency of the drug, even to the point of loss of activity. In the late 19th century and first half of the 20th century recognition of these facts by Langley, Ehrlich, Dale, Clarke and others provided the foundation for the receptor site hypothesis of drug action. According to these early ideas the drug, in order to elicit its effect, had to first combine with a specific 'target molecule' on either the cell surface or an intracellular organelle. It was soon realized that the 'right' chemical structure was required for drug-target site interaction (and the subsequent pharmacological response). In addition, from this requirement, for specificity of chemical structure requirement, developed not only the modern science of pharmacology but also that of toxicology. In relation to drug actions on microbes and parasites, for example, the early work of Ehrlich led to the introduction of molecules selectively toxic for them and relatively safe for the animal host. In the whole animal drugs may act on many target molecules in many tissues. These actions may lead to primary responses which, in turn, may induce secondary responses, that may either enhance or diminish the primary response. Therefore, it is common to investigate drug pharmacodynamics (PDs) in the first instance at molecular, cellular and tissue levels in vitro, so that the primary effects can be better understood without interference from the complexities involved in whole animal studies. When a drug, hormone or neurotransmitter combines with a target molecule, it is described as a ligand. Ligands are classified into two groups, agonists (which initiate a chain of reactions leading, usually via the release or formation of secondary messengers, to the response) and antagonists (which fail to initiate the transduction pathways but nevertheless compete with agonists for occupancy of receptor sites and thereby inhibit their actions). The parameters which characterize drug receptor interaction are affinity, efficacy, potency and sensitivity, each of which can be elucidated quantitatively for a particular drug acting on a particular receptor in a particular tissue. The most fundamental objective of PDs is to use the derived numerical values for these parameters to classify and sub-classify receptors and to compare and classify drugs on the basis of their affinity, efficacy, potency and sensitivity. This review introduces and summarizes the principles of PDs and illustrates them with examples drawn from both basic and veterinary pharmacology. Drugs acting on adrenoceptors and cardiovascular, non-steroidal anti-inflammatory and antimicrobial drugs are considered briefly to provide a foundation for subsequent reviews in this issue which deal with pharmacokinetic (PK)-PD modelling and integration of these drug classes. Drug action on receptors has many features in common with enzyme kinetics and gas adsorption onto surfaces, as defined by Michaelis-Menten and Langmuir absorption equations, respectively. These and other derived equations are outlined in this review. There is, however, no single theory which adequately explains all aspects of drug-receptor interaction. The early 'occupation' and 'rate' theories each explain some, but not all, experimental observations. From these basic theories the operational model and the two-state theory have been developed. For a discussion of more advanced theories see Kenakin (1997).  相似文献   

7.
Choice of an analgesic for gastrointestinal pain requires consideration of the cause of the pain, desired duration of pain relief, need for sedation, and potential side effects and toxicity, particularly in light of other drugs being used and effects on the gastrointestinal tract. It is imperative that close monitoring be continued to ensure that surgical lesions or worsening conditions are detected. Recent research in the field may lead to new drugs, drug combinations, and avenues of treatment that minimize the side effects of these drugs while maximizing their efficacy.  相似文献   

8.
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.  相似文献   

9.
This review provides a tutorial for individuals interested in quantitative veterinary pharmacology and toxicology and offers a basis for establishing guidelines for physiologically based pharmacokinetic (PBPK) model development and application in veterinary medicine. This is important as the application of PBPK modeling in veterinary medicine has evolved over the past two decades. PBPK models can be used to predict drug tissue residues and withdrawal times in food‐producing animals, to estimate chemical concentrations at the site of action and target organ toxicity to aid risk assessment of environmental contaminants and/or drugs in both domestic animals and wildlife, as well as to help design therapeutic regimens for veterinary drugs. This review provides a comprehensive summary of PBPK modeling principles, model development methodology, and the current applications in veterinary medicine, with a focus on predictions of drug tissue residues and withdrawal times in food‐producing animals. The advantages and disadvantages of PBPK modeling compared to other pharmacokinetic modeling approaches (i.e., classical compartmental/noncompartmental modeling, nonlinear mixed‐effects modeling, and interspecies allometric scaling) are further presented. The review finally discusses contemporary challenges and our perspectives on model documentation, evaluation criteria, quality improvement, and offers solutions to increase model acceptance and applications in veterinary pharmacology and toxicology.  相似文献   

10.
Research in anthelmintic pharmacology faces a grim future. The parent field of veterinary parasitology has seemingly been devalued by governments, universities and the animal industry in general. Primarily due to the success of the macrocyclic lactone anthelmintics in cattle, problems caused by helminth infections are widely perceived to be unimportant. The market for anthelmintics in other host species that are plagued by resistance, such as sheep and horses, is thought to be too small to sustain a discovery program in the animal health pharmaceutical industry. These attitudes are both alarming and foolish. The recent history of resistance to antibiotics provides more than adequate warning that complacency about the continued efficacy of any class of drugs for the chemotherapy of an infectious disease is folly. Parasitology remains a dominant feature of veterinary medicine and of the animal health industry. Investment into research on the basic and clinical pharmacology of anthelmintics is essential to ensure chemotherapeutic control of these organisms into the 21st century. In this article, we propose a set of questions that should receive priority for research funding in order to bring this field into the modern era. While the specific questions are open for revision, we believe that organized support of a prioritized list of research objectives could stimulate a renaissance in research in veterinary helminthology. To accept the status quo is to surrender.  相似文献   

11.
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.  相似文献   

12.
Although there is sufficient information on the pharmacology and therapeutic application of the antimicrobial drugs to permit their effective use, they are still often misused in canine practice. This paper collates the data on drug dose rate/plasma concentration relationships observed in dogs after the administration of specific members of the major antimicrobial drug groups and on the possible impact of drug disposition (distribution and elimination) on therapeutic effect. Some information gleaned from studies in other animal species is added.  相似文献   

13.
A common feature of human and veterinary pharmacokinetics is the importance of identifying and quantifying the key determinants of between‐patient variability in drug disposition and effects. Some of these attributes are already well known to the field of human pharmacology such as bodyweight, age, or sex, while others are more specific to veterinary medicine, such as species, breed, and social behavior. Identification of these attributes has the potential to allow a better and more tailored use of therapeutic drugs both in companion and food‐producing animals. Nonlinear mixed effects (NLME) have been purposely designed to characterize the sources of variability in drug disposition and response. The NLME approach can be used to explore the impact of population‐associated variables on the relationship between drug administration, systemic exposure, and the levels of drug residues in tissues. The latter, while different from the method used by the US Food and Drug Administration for setting official withdrawal times (WT) can also be beneficial for estimating WT of approved animal drug products when used in an extralabel manner. Finally, NLME can also prove useful to optimize dosing schedules, or to analyze sparse data collected in situations where intensive blood collection is technically challenging, as in small animal species presenting limited blood volume such as poultry and fish.  相似文献   

14.
Pharmacogenetics, the study of genetic determinants of response to drug therapy, is likely the ultimate way to establish the right drug and dose for each patient, thereby optimizing efficacy and minimizing toxicity. Despite the fact that this branch of pharmacology is still in its infancy as a science, a number of important discoveries have already contributed to improved pharmacotherapy in human and veterinary patients.  相似文献   

15.
The rational therapy of cardiovascular disease in horses requires a thorough knowledge of the pharmacology and pharmacokinetics of several specific drugs (digitalis, digoxin). Calcium solutions, dopamine, and dobutamine are frequently used to treat congestive heart failure in horses. Quinidine, procainamide, lidocaine, and propranolol are used to treat a variety of supraventricular and ventricular arrhythmias. Furosemide, a highly potent loop diuretic, is used to eliminate edema and promote diuresis. A thorough understanding of the applied pharmacology, dosage recommendations, toxicity, and practical considerations must be attained before these drugs can be used effectively.  相似文献   

16.
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.  相似文献   

17.
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.  相似文献   

18.
There are several means whereby dosage schedules for clinical use may be set, some more appropriate and scientific than others! The challenge of the 21st century must be for colleagues in the pharmaceutical industry, those serving registration bodies and academic colleagues to pool their expertise with the objective of designing dosage schedules for clinical use, which are based on the application of sound scientific principles appropriate for each drug class. In this Roundtable Session colleagues of international standing will review (a) pharmacological and other sources of variability in the responses to drugs; (b) the advantages and limitations of pre‐clinical studies for dose selection; (c) the roles of population PK and population PK/PD together with Monte Carlo simulations in dosage regimen selection; (d) Bayesian approaches to dosage selection and (e) regulatory guidelines on the type and extent of studies required for selecting dosages. There is no unanimity amongst stakeholders on either the principles or the methods underlying dosage schedule design. Dose titration studies have long been the principal means of fixing doses but PK‐PD and population PK‐PD studies are now challenging more traditional approaches. The papers and discussion in this Roundtable Session will provide a critical basis for future advances in this crucial area of therapeutic drug usage. Getting the doses right means that the patient will receive maximum benefit, in terms of optimal efficacy with minimal toxicity, and hence correct dosing will contribute enormously to animal welfare.  相似文献   

19.
Differences between neonatal and adult animals in their response to drugs can usually be attributed to altered disposition (ie, distribution, metabolism and excretion) processes during the neonatal period. These alterations affect the plasma concentrations as well as the concentrations of drug attained at the receptor site. Some characteristics of the neonatal period include greater absorption from the gastrointestinal tract, lower extent of plasma protein binding, increased apparent volume of distribution of drugs that distribute in extracellular fluid or total body water, increased permeability of the 'blood-brain' barrier and slower elimination of many drugs. The hepatic microsomal oxidative reactions and glucuronide conjugation are deficient metabolic pathways for a varying period of time, usually up to six weeks after birth or even longer in some species. Decreased metabolism can affect the duration of action of lipid-soluble drugs. Functional immaturity of the kidneys decreases the renal excretion of polar drugs and drug metabolites. Overall renal function appears to reach maturity within two weeks after birth in ruminant species and pigs, while maturation may take at least four weeks in other species of domestic animals. Considerable physiological and biochemical development takes place during the first five days after birth with maturation continuing more slowly over the succeeding five weeks. The time it takes for any process to reach functional maturity depends on the process in question and varies with the species of animal. The absorption, disposition and pharmacological response to drugs during the first 24 h after birth may be unique to that time and, because of lack of information, are impossible to predict.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

20.
In order to provide a consistent system for laboratory production of embryos, the characteristics of immature camel oocyte must first be described. The objective of this study was to define ultrastructural features of immature camel oocyte. Ovaries were obtained from camels at a local abattoir, and then transported to the laboratory within 2 h. Camelus cumulus oocyte complexes (COCs) were aspirated from 2-6 mm follicles using a 22-gauge needle. Excellent and good quality COCs were selected and prepared for transmission electron microscopy study using a cavity slide. The fine structure of camel oocyte is morphologically similar to that of other mammalian oocytes. However, some minor differences exist between COC of camel and other mammalian species. Different size and shape of membrane-bound vesicles, lipid droplet, mitochondria and cortical granules were distributed throughout the ooplasm. Discrete or in association with endoplasmic reticulum, Golgi complexes were observed in the periphery of the oocytes. The majority of the oocytes were in the germinal vesicle stage.  相似文献   

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