Pharmacology

Pharmacology is all about keeping a bird alive for long enough, and providing a safe, therapeutic medication, at a safe and appropriate level, route and frequency, to maintain a minimum inhibitory concentration (MIC) for the relevant pathogen, for sufficient time to destroy the pathogen or to enable the host to mount a successful immune response to it. Whilst the principles of emergency and support care as learnt on companion animals may be applied, they will need to be adapted to the special requirements of avian patients. Until recently all avian dose rates have been based on companion animal or poultry dose rates. Only now when further evidence-based trials have been conducted, do we know that there is great interspecies variation in elimination rates of drugs, and hence recommended doses and frequency of administration. Very few medications are licensed for birds in general, let alone for specific species, so use of drugs 'off label' is typically unavoidable. Clinicians should always bring this to clients' notice and seek their written permission to use such medications. It must not be forgotten that medications safe and efficacious in one species may be lethal in another.

Physiology of Metabolism and Body Temperature

Birds have a higher body temperature (40–42°C) and a higher metabolic rate than mammals. Flight and maintenance of high body temperature mandate this requirement. In general terms the rate of metabolic processes increases with body temperature. However, the maintenance of a higher body temperature (41°C, rather than 37.5–39°C) is extremely expensive. Birds use 20–30 times more energy to maintain body temperature than reptiles do. Both respiration and circulation have developed amazing adaptations to get energy and oxygen to cells and metabolic waste products away from cells far more efficiently than in mammals. Body temperature is regulated by controlling heat loss (insulation from plumage) and increasing heat production by shivering when cold or panting or gular fluttering when over-hot. Birds can operate heat exchange systems in their legs to increase or decrease body temperature loss.

Hyperthermia

In general terms most birds have adaptations which enable them to cope with loss of body temperature for periods of time. However, birds have very little tolerance for hyperthermia, dying rapidly at temperatures > 46°C.

Basics of Pharmacotherapy

Medication of birds is achieved via the same routes as in mammals, except administration tends to be required more frequently. However, as more and more is learnt about pharmacodynamics in birds, it is evident that there is significant variation in rates of drug disposition and clearance between even similar species of birds. Optimal use of medication requires a specific diagnosis, sensitivity to the pathogen (by testing or anticipation), consideration of toxicities, knowledge of pharmacokinetics and pharmacodynamics of the drug, appropriate administration, simultaneous support, good husbandry, consideration of anatomical and physiological differences between species and other considerations. Moreover, it is well recognised that the pharmacokinetics can be significantly altered by the disease process, especially when disease affects organs which are involved in absorption, biotransformation and excretion.

Allometric Scaling

If a required drug dosage has to be estimated this should be based on 'metabolic extrapolation' - otherwise known as allometric scaling. In essence it is the bird's metabolic rate, rather than its weight which is used to calculate the expected required dose rate. Of course there is a relationship between weight and metabolic rate and in turn dose rate. Metabolic rate is related more closely to an animal's surface area than its weight. As an animal's metabolic rate increases (i.e., speed of metabolic processes in the body), understandably the half-life of any drug decreases, i.e., it is eliminated more rapidly and would be required to be administered more frequently.

Basal metabolism. All birds have a high basal metabolic rate (BMR). Passerines in particular have a very high level (50–60% higher than non-passerines of the same size).

 BMR = K(W^0.75)
K is a theorectical constant for kilocalories required per 24 hour and varies with respect to species.
K is 129 for passerines and 78 for non-passerines, whilst in mammals it is 70.

The formula reflects the relationship between mass and surface area (from which heat is lost). Clinicians will be familiar with the fact that BMR relates to basic body functional requirements. Increased physical activity, breeding, rearing, moulting etc. will all require increased levels of energy.

The Basal Metabolic Rate (BMR) is on occasions also referred to as the 'minimum energy cost' (MEC in kilocalories) utilised per day and may be calculated as:

 MEC = K x W^0.75

We can take this a step further: we can divide the BMR by the bodyweight, to give a specific MEC (SMEC) in units of kcal/kg/day:

 SMEC = K x W^0.75/W
where K is the constant equal to the kilocalories used in 1 day by a hypothetical 1 kg animal, and W is the animal's mass in kg.

Calculation of dosage. The appropriate dose of a drug will depend on its pharmacokinetics, i.e., its route of absorption, metabolism and clearance. Perhaps the most important single factor in this is the surface area to volume ratio of the individual patient. Smaller creatures require higher levels than larger ones.

 E = (W / 100)^0.75 x D
where W = weight of bird in grams, D = dose of drug recommended for cat/dog (mg/kg) and E = dose of drug for the bird of a specific weight (W) in mg.

The differences found in pharmacokinetics between endothermic animals are often predominantly related to surface area or metabolic weight; however, they may also vary with respect to metabolic pathways. The fate of a drug in the body (protein binding, volume of distribution, biotransformation and excretion) can differ between species or groups of animals. Whilst there is little variation between species in the manner in which 'polar compounds' (e.g., gentamicin) are excreted, there is wide inter-species variation and unpredictability associated with biotransformation of extensively metabolised drugs such as chloramphenicol and sulphonamides.

Allometric scaling can be usefully applied to predict dosages required with respect to patient size, but it does not take into account variations in metabolic pathways.

Therapeutic Techniques - Routes of Administration

Drinking Water

This is the least reliable route and is rarely recommended. This can only be used in birds which are drinking well, a consistent and predictable amount and where the medication is accepted voluntary (i.e., no bad taste), when administered in drinking water.

 Flock versus individual therapy - very rarely is flock treatment recommended, unless it is preventive therapy e.g., anthelmintics in food or water. The disadvantages of flock therapy are counter-balanced by the benefit of avoiding the stress of repeated handling and administration.

In Food

The drug must be mixed well and the patient must be prepared to eat a soft diet. This is often a problem with pet psittacines as they are only prepared to eat their own normal seed-based food. A good principle when educating new pet parrot clients is to maintain their bird's willingness to eat soft food off a spoon as it would have done during rearing. If the new owner always gives them a soft food treat off a spoon on a weekly basis then if at any stage during the bird's life medication (or even just supplementary vitamins) are indicated, this can be achieved by the owner off a spoon at home. In raptors, this is generally easy as medication can often be secreted within a piece of meat. For groups such as waterfowl and poultry it is also easy as drugs may be mixed with soaked bread, or layers of mash, etc.

Gavage Tube

This is effective, may be stressful, is easily achieved in a hospital situation and can combine with supplementary feeding (as is required for many sick birds). Some owners may be reluctant or unable to perform this themselves.

Parenterally

 Intramuscularly: Pectoral most reliable, renal portal system renders leg injections less reliable. In smaller birds one may have a limited area to inject, especially if injections need to be administered 3–4 times per day, possibly with several different medicaments. May cause tissue necrosis in sternum (? affect future flight ability), cause pain, increase non-specific soft tissue enzymes.

 Subcutaneously poorly absorbed, no advantage in using this route, may be improved by addition of hyaluronidase. The technique is used commonly in small chicks.

 Intravenously: Easily achieved if intravenous catheter present, repeated intravenous injections are not realistic without a catheter.

 Local infusion, e.g., sinus flushing: can be very useful, and often easily achieved by the owner in a home environment.

 Intratracheally via oropharynx or nebulisation.

 Topically:

 Creams and ointments not often suitable as liable to damage feather structure. Oil-based preparations should not be used.

 Drugs mixed with DMSO for percutaneous absorption.

 Eye drops, preferable to ointments for same reason as topical creams. Beware use of topical steroid-containing eye drops in birds as these will cause systemic side effects.

 Powders, e.g., ectoparasitic preparations.

Recommended Drug Dosages

Whilst in the past clinicians were encouraged to extrapolate required dose rates from production, companion or poultry medicine, there are now a number of excellent formularies available. As scientific quantitative research is undertaken more and more accurate dosages are calculated for different species with different drugs. Evidence-backed, published dose rates should be used wherever they are available. When treating any condition, a specific diagnosis must be made, and the most appropriate medication for the condition and patient species should be employed. The route and frequency of medication must be appropriate. The stress caused by therapy should be considered against the possible benefits achieved.

Nursing, Fluid and Nutritional Support

For sick avian patients to be adequately cared for and treated a number of key factors need to be provided.

Stress

Whilst it is essential to administer the correct medication, for an adequate period in a safe manner, the concurrent stress associated with this should be minimised and managed so as to optimise the chances of a successful outcome.

Biosecurity

When managing all avian patients, whether as inpatients, or outpatients, it is vital to consider the risks of transfer of infectious and contagious diseases between concurrent or subsequent patients. This is of particular concern when dealing with apparently well patients who may be infected by pathogens which are spread by faecal or feather dust. In such cases simply examining and handling a bird can result in long-term (e.g., 2 years for psittacine beak and feather disease) contamination of the clinical environment and hence the creation of a risk to many future patients. In view of this, any hospital facility should have a structured, written and recorded 'modus operandi' to manage all such risks. A key element of any such plan will be the isolation of any hospitalised patients from each other, until such time as the patient is proven to not be affected by any infectious disease. In view of the risk of 'air-spread infection', hospitalised birds should be maintained in their own air space. This can be achieved by the use of individually vented or extracted containers, into which bird cages may be placed. Even so, staff should be aware of the risk of transfer of infection when birds are taken out for handling, medication etc., and also for the transfer of infection by fomites, including hands, clothing and equipment. Where possible, patients with infectious diseases should be nursed at home, so as to reduce the risk to other patients. Staff members who may potentially be exposed to avian pathogens outside of work (e.g., bird collections, in particular poultry), should either take special precautions (change of clothing on arrival at work) or not be involved in managing inpatients.

Structured Nursing Care Plans

Each patient under care should have a nursing care plan created. This plan will take into account the metabolic rate of the species, any fluid and nutritional shortfall prior to admission, additional fluid or nutritional needs arising due to illness, reproduction, growth, malabsorption or excessive excretion. The plan will also take into account the nutritional density of the diet, which must be of appropriate type for the species and patient. Sick or injured birds are generally considered to be 10% dehydrated at the time of admission. The patient should be provided with half the deficit, plus maintenance (100 ml/kg/24hr) in the first day of admission, with 25% plus maintenance in the second and third days. Such fluid intake is the sum of that administered parenterally plus that given with food by mouth. Foods suitable for both gavage administration to the critical patient and voluntary ingestion by a recovering patient, must be readily available. The fluid and food requirements must be able to be provided in a manner so as to minimise stress to the patient (in terms of frequency and volumes of administration). In general terms the number of times a bird is caught and handled each day should be minimised, so long as all needs (medication, food and fluids) can be met with reduced handling.

Good clinical records must be kept for all inpatients, with the essential requirement for daily weight checks and recording being addressed. Any inpatient must be supported in a manner that maintains or increases the body-weight, day on day, with increased food provision if weight maintenance is not being achieved.

Provision of an Appropriate Environment

All inpatients should be maintained in accommodation in which they can be readily caught, handled, assessed, at an appropriate temperature (generally 29–32°C (85–90°F) for sick birds) and humidity. Carers should be aware that when a bird knows it is being observed, it will not behave naturally; therefore, remote visual assessment is useful. Any special environmental requirements, e.g., water to bathe in or eat food from for waterfowl must be provided. Where they are not stressed or disturbed by noise (e.g., barking dogs), smells (e.g., ferrets), sights (predatory animals, e.g., snakes or raptors). The accommodation in which they are kept must be readily cleanable or disposable.

Diagnostic Sampling

Birds hide the signs of illness for as long as possible, but once ill the rate of pathogenesis is typically very rapid, so a specific diagnosis should always be sought, so as to optimise the prognosis. Bird illness is typically multifactorial: the discovery of one diagnosis does not exclude the possibility of additional diagnoses. The diagnostic work-up will involve collection of a detailed history, visual and physical examination, collection of clinical pathology samples (haematology, biochemistry, serology), radiography, plus additional diagnostic tests as required, e.g., ultrasonography, endoscopy, electrocardiogram (ECG), fluoroscopy, computed tomography (CT), magnetic resonance imaging (MRI), plus monitoring response to therapy. It is only when all these aspects are considered together that a full diagnosis is likely to be achieved. Those samples which can be collected and analysed prior to handling the bird (e.g., faeces) should be, so that as much as possible is known prior to causing stress to the bird. The stress involved in sample collection, especially from a sick bird, is minimised by conducting this under anaesthesia or sedation. Prior to sampling, advice should be sought from the diagnostic laboratory, in respect of:

 Do they test exotic animal samples and do they have normal ranges?

 Which samples do they require?

 Are there any postprandial, diurnal or delay or postal effects that you should be aware of, prior to sampling?

Samples required will include faeces, blood, aspirates, fine-needle aspiration (FNA) etc. Blood will be collected from superficial ulnar, jugular or medial tarsal veins. The maximum blood volume collection is 0.9–1.3 ml/100 g bodyweight. It is generally advantageous to make a blood smear, as well as an EDTA and heparin sample. Avian erythrocytes do not metabolise glucose, so citrate samples are not required. Aspirates, cytological smears or swab samples may be collected from any normal or abnormal tissue, or orifice (e.g., crop, nares, choana, mouth, ear canal, conjunctiva, preen gland, cloaca, any dermal lesion). Prior to sampling, all equipment, medications etc., should be made ready, such that anaesthesia or handling time is absolutely minimised. In view of the urgent requirement for quality-controlled diagnostic results, where quality can be assured in-house, such sampling is advantageous compared with external testing.

References

1.  Altman RD, Clubb SL, et al. eds. Avian Medicine and Surgery. Philadelphia, Pennsylvania: Saunders, 1997.

2.  Carpenter JW. Exotic Animal Formulary. 3rd ed. Philadelphia, Pennsylvania: Elsevier Saunders, 2005.

3.  Chitty J, M Lierz M, eds. BSAVA Manual of Raptors, Pigeons and Passerine Birds. Gloucester: British Small Animal Veterinary Association, 2008.

4.  Harcourt-Brown N, Chitty J, eds. BSAVA Manual of Psittacine Birds. 2nd ed. Gloucester: British Small Animal Veterinary Association 2005.

5.  Harrison GJ, Harrison LR, et al. eds. Avian Medicine: Principles and Application. Lake Worth, Florida: Wingers, 1994.

6.  Samour J, ed. Avian Medicine. 2nd ed. London: Elsevier. 1997.