Glucocorticoids are among the most effective anti-inflammatory and antipruritic drugs available. Glucocorticoids are also rapidly effective in treating several important immune-mediated diseases (Whitley and Day, 2011) as well as many neoplastic conditions. However, chronic systemic glucocorticoid treatment is accompanied by several common, serious and dose-dependent adverse effects, such as polyuria, polydipsia, alopecia, muscle weakness, panting, lethargy and obesity. Several of these adverse effects appear to be of greater concern to pet owners than to the animals themselves. Systemic glucocorticoid treatment is also associated with less common, non-dose-dependent and unpredictable (stochastic) side effects such as diabetes mellitus or thromboembolic disease, which have significant implications for animal welfare. It is not possible to separate the beneficial effects of glucocorticoids from their adverse effects; however, reducing systemic exposure through topical, local and inhaled delivery may alter the balance between the beneficial and adverse effects.

There are very few objective studies examining the optimal doses or dosing intervals for any glucocorticoids for any conditions in dogs or cats. There are wide inter-subject variations in plasma concentrations after administration, which suggest variable drug absorption. Furthermore, no relationship has been demonstrated between these plasma concentrations (unbound or total concentration) and clinical response. As many glucocorticoid effects are due to alteration of gene transcription, their biological activities exceed the plasma half-lives of the drugs. Different glucocorticoids have varying biological half-lives and are presented in varying formulations, which also affect their duration of action and tissue targeting. For example, a single dose of a long-acting ester of methylprednisolone is capable of altering ACTH stimulation testing in dogs for at least 5 weeks (Kemppainen et al., 1981).

Considerations before using glucocorticoids

Many problems that develop with glucocorticoid use arise when a treatment plan is not discussed with the pet owner at the time these drugs are initially prescribed. It is worthwhile considering the following questions before glucocorticoids are used (adapted from Thorn, 1966):

• How serious is the underlying disorder when compared with the predictable adverse effects of glucocorticoids?
• Is the patient likely to be predisposed to more severe, stochastic complications of glucocorticoid therapy (e.g. diabetes mellitus)?
• What is the starting glucocorticoid dose and the predicted length of treatment; when and how will this be adjusted?
• Which glucocorticoid preparation would minimize the adverse effects while retaining the beneficial effects?
• Are there other types of treatment that could be used to minimize the glucocorticoid dose?

Considerations when using glucocorticoids

• Starting doses: Although doses reported in this Formulary and other texts do provide a useful starting point when choosing an initial dose, given the lack of published evidence for many doses and the individual variability in response, glucocorticoids should ultimately be used to the desired effect. Providing the side effects are acceptable, there is no strict maximum dose for glucocorticoids, but it may be wise to obtain the guidance of a relevant veterinary specialist when using doses above those reported in this Formulary. The duration and magnitude of hypothalamic–pituitary–adrenal axis suppression caused by daily oral administration of a glucocorticoid varies based on species, individual, dose, formulation and specific pharmacokinetics of the glucocorticoid used. Larger individuals within a given species generally need proportionately lower doses on a mg/kg basis to achieve the same biological effect. For this reason, some authors dose on a mg/m2 basis in some medium to large patients. Pharmacological studies evaluating effects of glucocorticoids in cats are lacking. Currently, recommended dosing regimens for cats vary considerably. The predominant opinion, however, is that the cat requires a higher dose than the dog (on a mg/kg basis) (Lowe et al., 2008). Adverse effects of glucocorticoids are very likely in all treated animals and it is worthwhile warning owners about them. A client information leaflet is available to BSAVA members for this purpose.
• Adjusting doses: As there are few studies comparing protocols for tapering immunosuppressive or anti-inflammatory therapy with glucocorticoids, it is appropriate to adjust the therapy according to laboratory or clinical parameters. For example, cases with immune-mediated haemolytic anaemia should have their therapy adjusted following monitoring of their haematocrit. Most of the beneficial effects of glucocorticoids are seen in the short term. If the expected benefits are not apparent, then either the dose needs to be increased until limited by adverse effects, or alternative drugs and/or treatment modalities added and the dose of glucocorticoids reduced. Doses can be reduced to alternate-day therapy as soon as clinical control of the disease is achieved – regardless of the dose needed to achieve control. Although alternate-day dosing of medium-acting glucocorticoids (such as prednisolone) is accepted clinical practice, it assumes that the beneficial effects of these drugs last longer than the side effects. Evidence for this assumption is very limited and whether alternate-day dosing really avoids suppression of the hypothalamic–pituitary–adrenal axis while retaining beneficial therapeutic effect is debatable. Consideration should also be given to using short-acting glucocorticoids in ‘pulse doses’ to control acute recurrences of disease. Protracted use of any topical glucocorticoid can lead to thinning of the skin and owners should be advised of this possibility.

When not to use glucocorticoids

Glucocorticoids should not be given to animals with disc disease, hypercalcaemia, cutaneous or subcutaneous masses or large lymph nodes without a specific diagnosis and indication to do so. The use of glucocorticoids in most cases of shock is of no benefit and may be detrimental. Glucocorticoids are not analgesics; if animals are in pain then analgesics are required.

References

Kemppainen RJ, Lorenz MD and Thompson FN (1981) Adrenocortical suppression in the dog after a single dose of methylprednisolone acetate. American Journal of Veterinary Research 42: 822-824

Lowe AD, Campbell KL and Graves T (2008) Glucocorticoids in the cat. Veterinary Dermatology 19: 40-47

Thorn GW (1966) Clinical considerations in the use of corticosteroids. New England Journal of Medicine 274: 775-781

Whitley NT and Day MJ (2011) Immunomodulatory drugs and their application to the management of canine immune-mediated disease. Journal of Small Animal Practice 52: 70-85