Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

GLUCOCORTICOSTEROIDS
coated formulation is not yet determined. Further
studies of budesonide are indicated before it can be
recommended for use in dogs or cats. Fluticasone is a
glucocorticoid that can be administered via the inhalational
route for example to cats with allergic bronchial
disease using a standard pediatric spacer with a cat face
mask.
Topical cutaneous forms of glucocorticoid would
include acetonide or valerate esters of hydrocortisone,
prednisolone, betamethasone and dexamethasone.
Topical ocular preparations of dexamethasone or prednisolone
formulated as various esters are available. The
absorption of these varies, and the agent selected will
depend upon whether the disease process is intraocular,
corneal or subconjunctival. Alcohol-based formulations
are most readily absorbed, while acetate esters are more
readily absorbed by cornea and conjunctiva than succinate
or phosphate esters.
Clinical applications
The clinical indications for glucocorticoids are in the
treatment of inflammatory, immune-mediated (autoimmune)
or neoplastic (e.g. lymphoma, mast cell tumor)
disease, for adjunct therapy in hypoadrenocorticism,
and in the emergency management of acute anaphylaxis,
shock, asthma, heat stroke or trauma of the central
nervous system (controversial).
The major anti-inflammatory application of systemic
glucocorticoid therapy in companion animals is for
cutaneous hypersensitivity disease. A recent evidencebased
review has suggested that there is a firm basis for
the use of oral glucocorticoids in the management of
canine atopic dermatitis. Immunosuppressive glucocorticoid
therapy is still the mainstay of treatment for
immune-mediated or autoimmune diseases in these
species (e.g. immune-mediated hemolytic anemia
(IMHA) and thrombocytopenia, immune-mediated
polyarthritis, autoimmune skin diseases, IBD) and forms
part of the multidrug protocols used for chemotherapy
of round cell neoplasia. Topical corticosteroids are
employed in the management of some immunemediated
or inflammatory ocular diseases.
Mechanism of action
The mechanism of action of the glucocorticoid drugs
reflects the effects of endogenously produced glucocorticoid
hormones described above, but synthetic glucocorticoids
have greater glucocorticoid activity and less
mineralocorticoid activity than endogenous cortisol.
The only synthetic glucocorticoids with mineralocorticoid
activity are hydrocortisone, cortisone and prednisolone,
which have a relative mineralocorticoid potency
of 1.0, 0.8 and 0.25 respectively.
Formulations and dose rates
Glucocorticoids may be administered topically, orally
or by intravenous, intramuscular or intralesional (e.g.
subconjunctival) injection. The main consideration in
clinical administration of glucocorticoid drugs is to
achieve an appropriate clinical response, without inducing
the range of corticosteroid side effects.
An appropriately potent agent, with an appropriate
duration of action, should be selected for any individual
case. The dose rates for achieving an anti-inflammatory
or immunosuppressive effect are well defined for the
various disease indications but, for the most commonly
administered agent (oral prednisolone), an antiinflammatory
dose is generally considered to be 0.25–
0.5 mg/kg q.12 h or 0.5–1.0 mg/kg q.24 h for the dog,
and 1–2 mg/kg q.12 h or 2 mg/kg q.24 h for the cat.
The initial anti-inflammatory dose would be administered
for an ‘induction period’ of 5–7 days and then
tapered to a maintenance dose. For example, a maintenance
dose of 0.25–0.5 mg/kg q.12 h for 5–7 days may
be used for the dog, followed by glucocorticoid administration
for a withdrawal period at a dose of 0.5–
1.0 mg/kg every other day. In some cases, alternate-day
therapy may be extended to every third or fourth day.
The cat is considered more ‘steroid resistant’ (to the
immunosuppressive rather than the adrenosuppressive
effects of glucocorticoids) than the dog, which may
reflect reduced expression of glucocorticoid (dexamethasone)-binding
receptors in the tissues (skin and liver)
of this species. A recommended immunosuppressive
dose of prednisolone for the cat is therefore 2.2–6.6 mg/
kg q.12 h, and for the dog 1.0–2.0 mg/kg q.12 h. Some
authors recommend that these doses are given as a
single daily dosage in the morning (dog) or evening
(cat).
The duration of therapy will depend upon the individual
patient and disease entity being treated but in
order to avoid side effects, glucocorticoids should be
administered for the shortest period possible. In some
diseases, combination therapy with other agents may be
possible and permit reduced doses of glucocorticoids to
be used (e.g. concurrent administration of azathioprine
and prednisolone in canine IMHA).
Following administration of an induction protocol
(typically 10–28 days for an immunosuppressive
regimen), the glucocorticoids should be gradually tapered
towards an alternate-day maintenance regimen, but only
when there is clear evidence of disease remission. For
example, in a dog given an induction dose of 1.0 mg/kg
of prednisolone q.12 h (for 10–28 days), a tapering protocol
might consist of stepwise dose reduction to
0.75 mg/kg q.12 h (10–28 days), to 0.5 mg/kg q.12 h
(10–28 days), to 0.25 mg/kg q.12 h (10–28 days) to
0.25 mg/kg q.24 h (10–28 days). This may be followed
263