Veterinary Clinical Pharmacology Research Articles

PREVALENCE OF THE ABCB1-1Δ GENE IN NONDOMESTIC SPECIES OF THE CANIDAE FAMILY.

The ABCB1 gene is responsible for encoding the P-glycoprotein (P-gp) efflux transporter that prevents accumulation of exogenous substances in the body by utilizing ATP hydrolysis to transport these substances against their concentration gradient. In dogs, homozygous or heterozygous mutations for the previously described ABCB1-1Δ mutation lead to ineffective P-gp efflux transport function and puts the animal at risk for potentially devastating adverse drug effects. The purpose of this study was to evaluate ABCB1-1Δ gene mutation status in species belonging to the Canidae family, including each of the following: maned wolf (Chrysocyon brachyurus), gray wolf (Canis lupus), red wolf (Canis rufus), coyote (Canis latrans), dingo (Canis lupus dingo), New Guinea singing dog (Canis lupus dingo), arctic fox (Vulpes lagopus), and fennec fox (Vulpes zerda). These species were chosen based on an evolutionary study conducted by Belyaev that noted foxes, bred for temperament, tended to have similar behaviors seen in the modern-day dog. Wolves, known predecessors to the modern dog, were also included. In the current study, a buccal swab was performed on each animal and then tested at Washington State University's Veterinary Clinical Pharmacology Lab, where they were tested according to previously published methods validating buccal swab samples and polymerase chain reaction (PCR) -based genetic analysis. Knowledge of Canidae species ABCB1-1Δ gene mutation status allows for safe and effective therapeutic treatment of nondomestic animals, ensuring any anticipated adverse drug events are prevented. All eight species were found to have the wild-type ABCB1 gene and thus, expected to have normally functioning P-gp efflux transporters. Although these data can be used to guide clinical decision making, because of a small sample size, a more robust study is necessary to assess Canidae ABCB1-1Δ mutation status comprehensively.

Effect of using an audience response system on learning environment, motivation and long-term retention, during case-discussions in a large group of undergraduate veterinary clinical pharmacology students

Background: Teaching methods that provide an opportunity for individual engagement and focussed feedback are required to create an active learning environment for case-based teaching in large groups.Aims: A prospective observational controlled study was conducted to evaluate whether the use of an audience response system (ARS) would promote an active learning environment during case-based discussions in large groups, have an impact on student motivation and improve long-term retention.Methods: Group A (N = 83) participated in large group case discussions where student participation was voluntary, while for group B (N = 86) an ARS was used. Data collection methods included student and teacher surveys, student focus group interviews, independent observations and 1-year post-course testing.Results: Results indicated that the use of an ARS provided an active learning environment during case-based discussions in large groups by favouring engagement, observation and critical reflection and by increasing student and teacher motivation. Although final exam results were significantly improved in group B, long-term retention was not significantly different between groups.Conclusions: It was concluded that ARS use significantly improved the learning experience associated with case-based discussions in a large group of undergraduate students.

Postexposure management and treatment of anthrax in dogs—Executive councils of the American academy of veterinary pharmacology and therapeutics and the American college of veterinary clinical pharmacology

Dogs are generally at low risk of developing disease following exposure to anthrax. When disease does occur, it appears associated with oral exposure to the bacteria leading to massive swelling of the head, neck, and mediastinal regions. Death is due to toxemia and shock. For animals at high risk, such as search and rescue dogs with a known exposure, doxycycline at 5 mg/kg orally once daily for 45 to 60 days is suggested as a prophylactic treatment. Additional information on the diagnosis, prevention, and treatment of the disease in dogs is presented.

Information Technology in Veterinary Pharmacology Instruction

Veterinary clinical pharmacology encompasses all interactions between drugs and animals and applies basic and clinical knowledge to improve rational drug use and patient outcomes. Veterinary pharmacology instructors set educational goals and objectives that, when mastered by students, lead to improved animal health. The special needs of pharmacology instruction include establishing a functional interface between basic and clinical knowledge, managing a large quantity of information, and mastering quantitative skills essential to successful drug administration and analysis of drug action. In the present study, a survey was conducted to determine the extent to which veterinary pharmacology instructors utilize information technology (IT) in their teaching. Several IT categories were investigated, including Web-based instructional aids, stand-alone pharmacology software, interactive videoconferencing, databases, personal digital assistants (PDAs), and e-book applications. Currently IT plays a largely ancillary role in pharmacology instruction. IT use is being expanded primarily through the efforts of two veterinary professional pharmacology groups, the American College of Veterinary Clinical Pharmacology (ACVCP) and the American Academy of Veterinary Pharmacology and Therapeutics (AAVPT). The long-term outcome of improved IT use in pharmacology instruction should be to support the larger educational mission of active learning and problem solving. Creation of high-quality IT resources that promote this goal has the potential to improve veterinary pharmacology instruction within and across institutions.

The role of the clinical pharmacologist in animal health.

Like most scientific disciplines, pharmacology is replete with subspecialties. Certainly most scientists recognize the value of animal studies in drug development for human pharmaceuticals. However, animals as the target species also represent a major focus of investigation. According to recent estimates, in the United States for the year 2000, 98.1 million cattle, 59.8 million pigs, and 1.5 billion chickens existed. Added to that estimate were companion animals, including 4 million horses, 59 million cats, and 52.9 million dogs. The estimate does not include the so-called "minor" species, such as 7 million sheep and 320,000 acres of freshwater fish production. In most respects, the medical needs of these animals are addressed in a manner parallel to that of human medicine. One such parallel, with certain distinct differences from its human counterpart, is veterinary clinical pharmacology.

Ocular antimicrobial therapy in small animal practice

ABSTRACTAccurate diagnosis is essential in the selection of any therapeutic regime. In this paper the common ocular infections of dogs and cats are described, and the available therapeutic agents and their pharmacokinetics and spectra of activity are discussed. Sponsored by the Association for Veterinary Clinical Pharmacology and Therapeutics

What is new in veterinary clinical pharmacology?

What is new in veterinary clinical pharmacology?

Book Reviews

Book reviewed in this article:VETERINARY APPLIED PHARMACOLOGY AND THERAPEUTICS:G. C. Brander and D. M. Pugh.PRINCIPLES OF DRUG DISPOSITION IN DOMESTIC ANIMALS: THE BASIS OF VETERINARY CLINICAL PHARMACOLOGY:J. D. Baggot

Book Reviews

Book reviewed in this article:Principles of Drug Disposition in Domestic Animals: the basis of veterinary clinical pharmacology by J. D. Baggot.Veterinary Pharmacology and Therapeutics 4th Edition. Edited by L. M. Jones, N. H. Booth and L. E. McDonald.Atlas of Veterinary Ophthalmic Surgery By S. I. Bistner, G. Aguirre and G. Batik. W. B. Saunders

An introduction to principles of veterinary clinical pharmacology: the elimination of drugs. 2. Mechanisms of drug elimination.

Abstract Extract Drug elimination refers to all the processes that operate to reduce the effective concentration of drug in the body fluids. Metabolism, storage and excretion are the three mechanisms whereby drugs are ultimately removed from their sites of action. Most drugs undergo metabolic transformation in the body — i.e., biotransformation — to more polar products with diminished or no activity. The principal site of drug biotransformation is the liver. However, biotransformation may also take place to varying extents in other tissues, including the intestinal mucosa, the blood plasma and the renal epithelium, and by the action of gut microflora. The most common pathways of drug metabolism involve oxidation, reduction, hydrolysis and conjugation. Very often a drug is subjected to several competing pathways simultaneously, and the extent of formation of the various metabolites depends on the relative rates of the various metabolic processes. In addition, metabolic reactions frequently proceed sequentially; oxidation, reduction), or hydrolysis reactions are followed by conjugation of products of the initial reaction. Numerous factors may influence the metabolism and, consequently, the activity of a chemical agent. These factors include dose and frequency of administration of the drug, species and strain of animal, route of administration, diet and nutritional status, liver and kidney function, age of animal, time of day, chronic administraton and the previous or concurrent administration of, or exposure to, certain chemical agents that may inhibit or induce important metabolic processes. The effects of biotransformation are complex. Usually the metabolites formed are more polar, less lipid-soluble, more ionized at physiological pH values, and are distributed in a smaller volume than the parent drug. For these reasons drug metabolism frequently leads to an accelerated termination of pharmacological activity. Often, metabolic alteration of structure is a prerequisite, to efficient clearance by the excretory organs. Many drug conjugates are excreted into urine and bile by carrier-mediated transport mechanisms which allow foreign compounds to be cleared very rapidly from plasma. Deposition and storage of drugs in, fat depots, in the reticuloendothelial system and in bone play significant roles in the removal from the circulation of lipid-soluble agents, colloidal substances and heavy metals, respectively. Removal of unchanged drug from the body via the kidney is the principal route of elimination of drugs that are water-soluble; this includes organic electrolytes that are predominantly ionized at the physiological pH reaction. The excretion rate of a drug depends upon the volume of distribution and extent of plasma protein binding of the drug and the following renal factors: glomerular filtration rate, extent of non-ionic back-diffusion of the drug from glomerular ultrafiltrate to blood plasma (pH and pKa dependent) and degree of carrier-mediated excretion or reabsorption by the renal tubules. Variation in each of these factors can produce clinically significant changes in action of certain drugs, but changes in glomerular filtration rate will alter significantly the duration of action of all drugs that are eliminated from the body mainly by renal excretion. A drug may be excreted by the liver cells into bile and then pass into the intestine. Species variation in the extent of bilary excreton of drugs is likely to occur with compounds of molecular weight between 300 and 500 (Williams, 1971 Williams, R. T. 1971. “Species variations in drug biotransformations”. In Fundamentals of Drug Metabolism and Drug Disposition, Edited by: LaDu, B. N., Mandel, H. G. and Way, E. L. 187–205. Baltimore: Williams & Wilkins. In [Google Scholar]). The main importance of the biliary route of excretion is for the elimination of certain organic anions and cations that cannot be reabsorbed from the intestine because they are ionized at the intestinal reaction. It is evident that comprehensive appreciation of what occurs followng drug administration to either man or animals is possible only when pharmacokinetic analyses complement pharmacodynamic studies.

An introduction to principles of veterinary clinical pharmacology: the elimination of drugs. 1. Rate of drug elimination.

An introduction to principles of veterinary clinical pharmacology: the elimination of drugs. 1. Rate of drug elimination.

An introduction to principles of veterinary clinical pharmacology: the absorption of drugs.

Abstract Extract In order to act and produce effects, unless it acts topically at the site of action, a drug must be absorbed into the blood. The rate of absorption depends upon the route, of administration and physicochemical characteristics of the drug. The physicochemical properties that affect the absorption of a compound are lipid and water solubility, degree of ionization, chemical stability of the drug and molecular weight. A substance will probably be well absorbed if it is lipid-soluble and at the same time also soluble to some extent in water, if it is not completely ionized, and, finally, if its molecular weight is not excessively high (Keberle, 1971 Keberle, H. 1971. Physico-chemical factors of drugsaffecting absorption, distribution and excretion. Acta Pharmac. Tox., 29(suppl. 3): 3047–3047. [Google Scholar]).

An introduction to principles of veterinary clinical pharmacology: general principles.

Abstract Extract A drug is a chemical substance that acts in a biological system to preferentially give a beneficial pharmacological or chemotherapeutic effect. The effects of drugs are well documented and drugs are sometimes classified on the basis of their principal effect. With certain exceptions most drugs are thought to produce their effects by combining with enzymes, cell membranes, or other specialized functional components of cells. The effects of a drug in a biological system must be regarded as ultimate consequences of physico-chemical interaction between the drug and functionally important molecules in the living organism, that is, receptor sites (Goldstein et al, 1968 Goldstein, A., Aronow, L. and Kaiman, S. M. 1968. Principles of Drug Action: The Basis of Pharmacology, 1–30. New York: Harper and Row. [Google Scholar]). Morphine and its surrogates, for example, produce their major effects on the central nervous system and the bowel. Structurally, the narcotic analgesics may be thought of as N-methyl piperidine compounds with bulky ring substituents. Receptor attachment (Beckett and Casy, 1954 Beckett, A. H. and Casy, A. F. 1954. Synthetic analgesics: stereochemical considerations. J. Pharm. Pharmac., 6: 986–1001. [Google Scholar]) and analgesic activity (Gero, 1954 Gero, A. 1954. Science, 119: 112–114. Cited by Cutting, W. C. (1969), in Handbook of Pharmacology, 4th ed. p. 631. Appleton-Century-Crofts, New York. [Google Scholar]) are related to the γ-phenyl-N-methyl piperidine moiety of morphine, methadone, pethidine and their derivatives. The attachment of drug to receptors usually involves ionic and other relatively weak, reversible bonds. Occasionally, firm covalent bonds are involved and the, drug effect is only slowly reversible. An example of drug-receptor interaction through formation of a covalent bond is the long-lasting inhibition of the Cholinesterase enzymes by organic phosphates and carbamates.