Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

HYPOADRENOCORTICISM
CH 2 OH
21
CH 2 OH
CH 2 OH
O
2
3
C
H 3 C 20
12 18
HO
17
11 13
H 3 C
1 19 C D
9
14
10
8
A B
G: 1
M: 1
5
7
4
6
O
OH
16
15
O
H 3 C
O
H 3 C
G: 1
M: 1
C
O
OH
O
HO
H 3 C
H 3 C
C
G: 5
M: 0.1
O
OH
Hydrocortisone (cortisol)
Cortisol
Prednisone
CH 2 OH
OH
CH 2 OH
CH 2 OH
HO
H 3 C
C
O
OH
O
CH
C
O
HO
H 3 C
C
O
OH
H 3 C
CH 3
H 3 C
H 3 C
O
F
G: 30
M: 0
O
G: 0.3
M: 3000
O
F
G: 13
M: 125
Dexamethasone
Aldosterone
Fludrocortisone
Fig. 22.2 Structure of natural and synthetic corticosteroids with their relative glucocorticoid (G) and
mineralocorticoid (M) potency.
with equipotent glucocorticoid and mineralocorticoid activity which
can be administered parenterally.
In adrenalectomy patients it can be given as a bolus before and
after surgery (4–5 mg/kg) or, in the author’s opinion, preferably as a
continuous infusion of 0.5 mg/kg/h starting 1 h before induction and
continuing for 12–24 h postoperatively. At this time it should be
reduced to 0.25 mg/kg/h for a further 24 h or until the dog is
eating and drinking and able to be changed to oral steroid
supplementation.
In dogs with spontaneous hypoadrenocorticism which require supportive
fl uid therapy HSS should be given at a dose of 0.5 mg/kg/h
until normal gastrointestinal function has returned, the dog is eating
and drinking normally and can be changed to oral steroid
supplementation.
As there is potential for HSS to adhere to plastic or glass at low
concentrations, it is best to administer it in its own fl uid bag made up
to a concentration of 1 mg/mL. As HSS is incompatible with a variety
of different solutions, including ampicillin sodium, it is best to dilute
the HSS in normal saline.
Pharmacokinetics
As a water-soluble derivative of hydrocortisone, HSS
can be administered intravenously. In humans HSS is
relatively rapidly metabolized with excretion complete
within 12 h of administration.
In normal dogs, stable plasma cortisol concentrations
of approximately 750–900 nmol/L and 350–385 nmol/
L were achieved within 3 h of starting a continuous
intravenous infusion of HSS at 0.625 mg/kg/h and
0.313 mg/kg/h respectively. In dogs with hyperadrenocorticism
the values were reduced by approximately
50% while in hypoadrenocorticoid patients, cortisol
values were significantly higher. These variations in
plasma cortisol concentrations in dogs with altered
adrenal function suggest a positive correlation between
previous cortisol exposure and the rate of metabolism
of administered steroids.
Adverse effects
In humans there have been rare reports of anaphylactic
reactions to the intravenous administration of HSS.
Cortisone acetate
Mechanism of action
Cortisone is a synthetic steroid with an 11-keto
substitution. Once absorbed, it is rapidly activated to
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