Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

HYPOADRENOCORTICISM
if any glucocorticoid activity. Mineralocorticoids act at
the distal convoluted tubule to increase sodium resorption
as well as increasing potassium and hydrogen
excretion in exchange for sodium.
Formulations and dose rates
The recommended dose of DOCP is 2.2 mg/kg by intramuscular or
subcutaneous injection every 25 d. Plasma electrolyte, urea and creatinine
concentrations can be monitored every 2 weeks to determine
the duration of action and to help individualize the dose. Once stabilized,
it is prudent to check electrolytes every 3–6 months. While the
manufacturer recommends 2.2 mg/kg/25 d and this is generally
accepted as producing reliable mineralocorticoid control, in one study
lower doses of between 1.4 and 1.9 mg/kg were found to be effective
in controlling electrolyte concentrations. The same study also
suggested that dose interval could range between 14 and 35 d in
individual dogs. While it seems likely that there is room for some
individualization of the dose, it is worth noting that the vast majority
of dogs appear to have stable and adequate mineralocorticoid supplementation
when receiving 2.2 mg/kg of DOCP every 3–4 weeks.
Additionally DOCP appears to be an extremely effective mineralocorticoid
and once the dose has been individualized, the dose rate and
frequency remain unchanged over years.
As DOCP has predominantly mineralocorticoid activity, all dogs and
cats treated with it should receive concurrent glucocorticoid supplementation.
As this is a replacement for physiological requirements,
the dose of glucocorticoid should be much lower than the traditional
anti-infl ammatory dose rates. As a general guide, the daily glucocorticoid
requirement for dogs and cats is the equivalent of approximately
0.2 mg/kg/24 h of cortisol or 0.04 mg/kg/24 h of prednisolone. Consequently
tablet size tends to dictate that in cats and at least small
dogs, cortisone acetate is the preferred method of oral glucocorticoid
supplementation.
Pharmacokinetics
The pharmacokinetics of DOCP have not been reported
in dogs or cats. It is injected intramuscularly as a micro-
crystalline depot for slow dissolution into the circulation.
In dogs, DOCP usually has a duration of action of
21–30 days.
Adverse effects
Adverse effects of DOCP are generally a result of overdosing
although occasionally irritation at the site of
injection may occur.
Known drug interactions
● Patients may develop hypokalemia if DOCP is
administered concurrently with amphotericin B or
potassium-depleting diuretics such as thiazides and
furosemide.
● DOCP should be used cautiously in patients receiving
digoxin.
Dexamethasone
Dexamethasone is a synthetic adrenal steroid with
markedly potentiated glucocorticoid activity (approximately
30 times that of hydrocortisone) and little
mineralocorticoid activity. The soluble esters of dexamethasone
can be given intravenously and some clinicians
advocate its parenteral use in the acute management
of hypoadrenocorticoid patients. A detailed discussion
of its pharmacology can be found in Chapter 11 (Glucocorticosteroids
and antihistamines).
Prednisolone
Prednisolone is a synthetic adrenal steroid with moderately
potentiated glucocorticoid activity (approximately
five times that of hydrocortisone) and less than 10% of
hydrocortisone’s mineralocorticoid activity. Some clinicians
advocate its use as a glucocorticoid supplement in
the long-term management of hypoadrencorticism. A
detailed discussion of its pharmacology can be found in
Chapter 12 on immunomodulatory therapy.
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