Pharmacotherapeutic aspects of medication of birds

This review covers current knowledge of the pharmacodynamics and pharmacokinetics of drugs in avian species. Special attention has been paid to inter-species differences in relation to metabolic elimination, anatomy and physiology of the digestive and respiratory system, and differences in drug distribution. Intra-species differences attributable to physicochemical aspects of the drug preparation and physiological conditions of the avian patient can also influence drug efficacy. The consequences of the choice of a particular method of drug administration on pharmacokinetics are also considered.     

Clinical chemistry of companion avian species: a review

Birds have evolved alternate physiologic strategies to contend with dehydration, starvation, malnutrition, and reproduction. Basic anatomic and functional differences between birds and mammals impact clinical chemistry values and their evaluation. Interpretation of the results of standard biochemical analyses, including BUN, alanine aminotransferase, aspartate aminotransferase, creatine kinase, gamma glutamyltransferase, bilirubin, ammonia, alkaline phosphatase, cholesterol, bile acids, glucose, albumin, globulins, calcium, phosphorus, prealbumin (transthyretin), fibrinogen, iron, and ferritin, is reviewed and discussed in relation to these physiological differences. The use and interpretation of alternative analytes appropriate for avian species, such as uric acid, biliverdin, glutamate dehydrogenase, and galactose clearance, also are reviewed. Normal avian urine and appropriate use of urinalysis, an integral part of laboratory diagnosis in mammalian species that frequently is omitted from avian diagnostic protocols, is discussed.     

Differential ammonia metabolism and toxicity between avian and mammalian species,and effect of ammonia on skeletal muscle: A comparative review

Comparative aspects of ammonia toxicity, specific to liver and skeletal muscle and skeletal muscle metabolism between avian and mammalian species are discussed in the context of models for liver disease and subsequent skeletal muscle wasting. The purpose of this review is to present species differences in ammonia metabolism and to specifically highlight observed differences in skeletal muscle response to excess ammonia in avian species. Ammonia, which is produced during protein catabolism and is an essential component of nucleic acid and protein biosynthesis, is detoxified mainly in the liver. While the liver is consistent as the main organ responsible for ammonia detoxification, there are evolutionary differences in ammonia metabolism and nitrogen excretory products between avian and mammalian species. In patients with liver disease and all mammalian models, inadequate ammonia detoxification and successive increased circulating ammonia concentration, termed hyperammonemia, leads to severe skeletal muscle atrophy, increased apoptosis and reduced protein synthesis, altogether having deleterious effects on muscle size and strength. Previously, an avian embryonic model, designed to determine the effects of increased circulating ammonia on muscle development, revealed that ammonia elicits a positive myogenic response. Specifically, induced hyperammonemia in avian embryos resulted in a reduction in myostatin, a well‐known inhibitor of muscle growth, expression, whereas myostatin expression is significantly increased in mammalian models of hyperammonemia. These interesting findings imply that species differences in ammonia metabolism allow avians to utilize ammonia for growth. Understanding the intrinsic physiological mechanisms that allow for ammonia to be utilized for growth has potential to reveal novel approaches to muscle growth in avian species and will provide new targets for preventing muscle degeneration in mammalian species.     

Evaluation of plasma (1-->3) beta-D-glucan concentrations in birds naturally and experimentally infected with aspergillus fumigatus

Avian aspergillosis, most often caused by Aspergillus fumigatus, is a common and devastating disease affecting a range of bird species. Early diagnosis is difficult and often unreliable. The current study evaluated the utility of measuring (1-->3)-beta-D-glucan (BG) concentrations in avian plasma samples to aid in the diagnosis of aspergillosis. We evaluated a commercially available BG assay (Fungitell, Beacon Diagnostics) using 178 plasma samples from naturally infected, experimentally infected, and aspergillosis-free birds. Although there was variation in BG concentration, as reflected by high standard deviations, seabirds with confirmed aspergillosis had the highest mean BG concentrations (M = 3098.7 pg/dl, SD = 5022.6, n = 22) followed by companion avian species and raptors with confirmed aspergillosis (M = 1033.8 pg/dl, SD = 1531.6, n = 19) and experimentally infected Japanese quail (Coturnix japonica; M = 1066.5 pg/dl, SD = 1348.2, n = 17). Variation in severity of disease, differences among species of birds with and without disease, and also different levels in environmental exposure likely contribute to the differences among avian groups. The overall sensitivity and specificity of the BG test for diagnosis of aspergillosis in birds was 60.0 and 92.7%, respectively, with an overall optimized avian cut-offvalue of > or = 461 pg/dl for positive disease. Our findings suggest that, although BG concentrations are highly variable between and within different avian groups, it could serve as a useful adjunctive diagnostic test for aspergillosis that is applicable to multiple avian species in some settings, particularly as a negative predictor of infection.     

Genetic variation of highly pathogenic H5N1 avian influenza viruses in Vietnam shows both species-specific and spatiotemporal associations

Domestic poultry act as a reservoir for persistent H5N1 endemicity in Vietnam, and the circulation of poultry flocks across farms and to market is thought to drive the spatial movement and evolution of avian influenza viruses. Using a dataset of complete or nearly full genomic sequences from highly pathogenic H5N1 avian influenza viruses collected in domestic poultry in Vietnam from 2003 to 2007, we explore potential differences in genetic characteristics according to species of isolation and the spatiotemporal characteristics of the viruses. Clustering algorithms and ANOVA indicate that H5N1 viruses in Vietnam show differences in the amount of genetic change that chicken viruses experience as compared to duck viruses, with duck viruses showing higher rates of molecular evolution on all eight of influenza's gene segments. There also exist distinct patterns of genetic differentiation according to the year in which they were isolated. These findings suggest that genetic evolution of avian influenza viruses is continuous through time but could also be mediated by the species in which the viruses occur, information that has implications for prevention efforts.     

Antiviral efficacy of oseltamivir against avian influenza virus in avian species

Avian influenza is one of the most contagious viral diseases in bird species and, increasingly, interspecies transmission to mammalian species has been reported. Prevention and eradication of avian influenza virus (AIV) infection in birds may require vaccines as part of a comprehensive program including biosecurity, culling, diagnostics, and surveillance. However, for valuable bird species in zoos, novel eradication strategies are needed, including antiviral treatments. The present study evaluated the anti-influenza efficacy of the potent neuraminidase inhibitor oseltamivir in avian species using the orders Galliformes (chickens) and Anseriformes (ducks). Viral replication of low pathogenic AIV was significantly reduced in the chicken model and completely reduced in the duck model. Anti-influenza drug administration to valuable bird species with an appropriate extrapolation approach could be useful for control of AIV in combination with active surveillance and vaccination strategies. Further, evaluation of oseltamivir against highly pathogenic avian influenza (HPAI) using avian models would be needed to optimize the oseltamivir application guideline for HPAI control.     

Morphometry of the heart of budgerigars (Melopsittacus undulatus), Alisterus parrots (Alisterus s scapularis) and common buzzards (Buteo buteo)

In order to establish data and reference values for the thickness of the myocardium and the length of the left and the right ventricle of the avian heart, the hearts of 14 budgerigars (Melopsittacus undulatus), five Alisterus parrots (Alisterus s scapularis) (also known as Australian king parrot) and 10 common buzzards (Buteo buteo) of both sexes were examined according to a standard protocol. In order to compare the results of birds of different sizes all data were related to the size of the bird's body (length of the sternum) and the results of the measurements of the myocardial thickness in relation to the length of the heart. Results of different zones were compared by means of statistical methods within one species. Besides that a comparison between the different species was performed. Only minor significant differences were noted.     

Pharmacokinetics of tobramycin in ducks and sex-related differences

The aims of the present study were to determine the disposition of tobramycin after single intravenous (IV) and intramuscular (IM) injections in ducks, and to establish any sex-related differences. Tobramycin sulfate was administered as a 2.5% water solution in a cross-over design at a dose of 5 mg/kg to 12 healthy ducks (six males and six females). Concentrations of the drug in serum were determined by a microbiological assay. The serum pharmacokinetic values for tobramycin were best represented using a one- or two-compartment open model, depending on the method of administration. Non-compartment analysis was also performed after IV administration. Tobramycin had a low degree of distribution and a relatively fast elimination. The mean volume of distribution in ducks (males and females) was higher than that reported in pigeons but lower than in chickens, with a slower rate of elimination. The IM injection resulted in a fast and complete absorption. The rate of elimination after IM administration was about twice as slow as in other avian species. Sex-related variations in tobramycin pharmacokinetics were similar to those reported for kanamycin and apramycin in hens and roosters.     

Attempted photodynamic therapy against patagial squamous cell carcinoma in an African rose-ringed parakeet (Psittacula krameri).

A 5-yr-old female African rose-ringed parakeet (Psittacula krameri) presented with an ulcerated mass in the medial postpatagial area of the right wing. Biopsy specimens of the mass demonstrated a well-differentiated squamous cell carcinoma. Photodynamic therapy resulted in tumor cell necrosis and initial reduction in tumor burden, but complete remission was not achieved. Based on this and other avian cases, it appears that photodynamic therapy designed to eradicate squamous cell carcinoma in avian species using protocols modeled after canine, feline, and human photodynamic therapy protocols may not be useful. It is hypothesized that differences in light penetration, photosensitizing agent pharmacokinetics, and wound healing properties in avian species necessitate alteration of photodynamic therapy protocols if this treatment modality is to be effective in avian oncology.     

The diagnostic utility of serum protein electrophoresis.

Routine serum protein electrophoresis is recognized as the most reliable assessment of avian protein profiles in health and disease and has replaced biochemical determination of albumin and A:G ratio in the ability to predict abnormalities of clinical significance. The importance of considerable species differences to the overall interpretation of avian electrophoresis is well established and constitutes a continued challenge to the avian specialist and to the providing laboratories to continue the pursuit of species-specific, even age- and gender-specific, reference ranges. Patterns for various diseases continue to emerge as more scrutiny is applied to the use of this tool in avian diagnostics for overall health assessment as an adjunct to specific disease diagnosis and for both prognostic and therapeutic monitoring.     

Diagnosis of eastern equine encephalitis by immunohistochemistry in two flocks of Michigan ring-neck pheasants

The diagnosis of eastern equine encephalitis (EEE) virus infection in avian species is relatively difficult when compared with other species. There are no characteristic histologic lesions in the avian brain that would serve to distinguish EEE from infections with, for example, Newcastle disease or highly pathogenic avian influenza virus. Traditionally, virus isolation (VI) and/or hemagglutination inhibition (HI) has been used for a definitive diagnosis of EEE in birds. Recently, we developed an immunohistochemistry (IHC) technique for confirmatory diagnosis of EEE infection in equine brain. This test also detected EEE virus in formalin-fixed avian brain. VI confirmed IHC finding in two cases of EEE in ring-neck pheasants. IHC is a rapid, sensitive test for confirming and differentiating a histopathologic diagnosis of EEE in avian species and should be considered as an alternative test to VI or HI.     

Dietary Considerations for Atherosclerosis in Common Companion Avian Species

Atherosclerosis is a disease that occurs in many avian species commonly presented to veterinarians. Many risk factors for atherosclerosis are well defined in mammals but not in avian species. Dietary nutrients can play a large role in reducing the severity and prevalence of atherosclerosis in both avian and mammalian species. Information on the effect of dietary nutrients on atherosclerosis in Falconiformes and other birds of prey is extremely limited as no studies were identified by the authors. Dietary cholesterol can be fed to induce the development of atherosclerosis in avian species that consume nonanimal protein. Diets containing high levels of omega-3 fatty acids reduce the prevalence and severity of atherosclerosis, with fish oil being more effective than α-linolenic acid. The presence of dietary cholesterol results in higher levels of dietary protein, increasing the prevalence and severity of atherosclerosis, but if dietary cholesterol is absent, there is a subsequent decrease in atherosclerosis. Pectin in the diet decreased the occurrence of atherosclerosis but also decreased the availability of nutrients owing to faster ingesta passage rates. Feed restriction has also been found to decrease the prevalence of atherosclerosis in birds. It should be noted that many studies have found nutrient interaction effects on the development of atherosclerosis, with some being “neutralizing” or negative, so caution should be observed when manipulating avian diets. The objective of this article is to review the effects of dietary nutrients on atherosclerosis.     

Peculiarities of pharmacokinetics in young animals

In young animals, especially in newborns, absorption, distribution, metabolism and elimination of drugs differ markedly from adults. Respective differences and the cause of these differences are described, including some examples of drug pharmacokinetics in young and adult animals of different species. However, the estimation of pharmacokinetic differences and their pharmacological consequences in young animals is not generally possible, because published data on characteristics of pharmacokinetics in young animals are available only for relatively few drugs. Furthermore, such estimation is complicated by an interaction of different pharmacokinetic processes. Thus, a generally accepted adaptation of dosage schedules for drugs in young animals cannot be offered as yet. In any event, veterinarians should consider the age-dependency of drug pharmacokinetics when drugs, dosages and dosage intervals for treatment of young animals are chosen.     

Host range of avian influenza virus in free-living birds

Isolation of avian influenza virus (AIV) has been reported from 12 orders and 88 species of free-living birds. Most isolations are reported from species in the orders Anseriformes and Charadriiformes and it is recognized that species in Anseriformes represent important reservoirs of AIV. Morbidity and mortality among free-living birds attributable to AIV infection are rare, but differences in prevalence of AIV occur within and between avian species. Seasonal variation has been reported from free-living and sentinel ducks with peak AIV infection occurring in late summer and early fall. Prevalence of AIV is age-related, with highest isolation rates reported from juvenile birds. Differences in susceptibility to AIV infection among species have been demonstrated under experimental conditions. The dynamics and epidemiology of species-related variation in populations of free-living birds require further study.     

Factors that affect drug disposition in food-producing animals during maturation.

Drugs administered to neonatal food-producing animals (cattle, sheep, goats, swine) may exhibit significantly different pharmacokinetic/disposition characteristics than they do in adult animals of the same species. Undesirable consequences such as suboptimum therapeutic concentrations, toxic effects, and violative tissue residues may result if adult dosage regimens are employed in young animals. Using selected drugs as examples, this paper reviews factors that contribute to differences in drug disposition in newborn vs adult animals. Immaturity of mechanisms involved in drug absorption, especially from gastrointestinal and parenteral sites of administration, and of drug distribution to sites such as plasma proteins, adipose tissue, and fluid compartments are considered. The role of developmental changes in drug biotransformation in the liver and other tissues and the maturation of excretory mechanisms, primarily from the kidney, in the increased rate of drug clearance during maturation is described. Pharmacokinetic studies with specific drugs in the target species are an important approach to establishing rational drug use in immature food-producing animals.     

Pharmacotherapy for Behavioral Disorders in Pet Birds

The effective use of psychoactive medications in avian patients is limited by the lack of controlled studies. Appropriate dosages, predictable therapeutic effects, pharmacokinetic data, and information about toxicity are often lacking. A variety of psychoactive agents have been used in avian patients to treat disorders such as feather chewing or picking, self-mutilation of soft tissue, and anxiety, but larger clinical trials and placebo-controlled trials are needed to determine efficacy and safety of these agents. The decision to use psychoactive medication in an avian patient and the choice of medication should be based on existing data for the particular species and an understanding of the drug’s mechanisms and indications. For any behavioral disorder, the need for pharmaceutical intervention requires the following: a thorough physical examination and baseline pretreatment laboratory testing, as indicated by physical examination findings and symptoms; an established diagnosis based on complete behavioral and medical histories; a signed owner consent statement; a behavior modification plan with appropriate environmental modifications; knowledge of the drug, side effects, indications, and mechanisms of action; and realistic expectations about treatment outcomes. Use of antipsychotic agents, serotonin reuptake inhibitors, tricyclic antidepressants, opioid antagonists, benzodiazepines, and hormonal therapies are described.     

Organic matrix composition and ultrastructure of eggshell: a comparative study.

1. The avian eggshell is a biomineralised composite ceramic consisting of calcium carbonate embedded in an organic matrix. Matrix components are supposed to be involved in the control of mineralisation, crystallographic texture and biomechanical properties of eggshell. 2. The structure and eggshell matrix composition of various domesticated bird species were compared to gain insight into the universality of the eggshell mineralisation process. 3. The SDS-PAGE profiles of soluble eggshell matrix were specific within groups of birds (a: laying hen, breeder hen, quail, pheasant and possibly turkey; b: guinea fowl; c: duck and goose) but some of the protein bands were common to all groups. 4. Analogies between species were confirmed by Western blotting using hen protein antibodies. Ovocleidin-17 (OC-17) and ovalbumin were revealed in all species (except quail for OC-17). Lysozyme was present only in hen eggshell. Another egg white protein: ovotransferrin showed a positive signal in hens, turkey and quail. Osteopontin was observed in laying and breeder hens and quail. 5. Different proteoglycans were localised to discrete regions within the eggshell. Dermatan sulphate was observed within the matrix of the calcified shell of all species except quail which contained chondroitin-6-sulfate. Keratan sulphate was observed in mammillary bodies of breeder and laying hen, quail, pheasant and turkey while chondroitin sulphate was also present in guinea fowl and duck. 6. The general structural organisation of the different avian eggshells was similar but specific differences were observed in the ultrastructure of the mammillary layer. Species of the same taxonomic family could be grouped according to their structural analogies: breeder hen, turkey and pheasant resembled that of the domestic fowl. Guinea fowl was unique. Goose and duck were quite similar with large and confluent mammillary bodies. 7. Some matrix components are therefore common to eggshells of various species but more information is needed to relate differences in matrix composition between taxonomic groups with differences in ultrastructure.     

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.     

Partial cloning of CYP2C23a genes and hepatic protein expression in eight representative avian species

Large interspecies differences in avian xenobiotic metabolism have been revealed by microsome‐based studies, but specific enzyme isoforms in different bird species have not yet been compared. We have previously shown that CYP2C23 genes are the most induced CYP isoforms in chicken liver. In this study, we collected partial CYP2C23a gene sequences from eight avian species (ostrich, blue‐eared pheasant, snowy owl, great‐horned owl, Chilean flamingo, peregrin falcon, Humboldt penguin, and black‐crowned night heron) selected to cover the whole avian lineage: Paleognathae, Galloanserae, and Neoaves. Genetic analysis showed that CYP2C23 genes of Galloanserae species (chicken and blue‐eared pheasant) had unique characteristics. We found some duplicated genes (CYP2C23a and CYP2C23b) and two missing amino acid residues in Galloanserae compared to the other two lineages. The genes have lower homology than in other avian lineages, which suggests Galloanserae‐specific rapid evolutionary changes. These genetic features suggested that the Galloanserae are not the most representative avian species, considering that the Neoaves comprise more than 95% of birds. Moreover, we succeeded in synthesizing an antipeptide polyclonal antibody against the region of CYP2C23 protein conserved in avians. However, comparative quantitation of CYP2C23 proteins in livers from six species showed that expression levels of these proteins differed no more than fourfold. Further study is needed to clarify the function of avian CYP2C23 proteins.