DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1228 and error and must be the lowest that will achieve the
desired effect. When the therapeutic goal is relief of
painful or distressing symptoms not associated with an
immediately life-threatening disease, complete relief is
not sought, and the steroid dose is reduced gradually
until worsening symptoms indicate that the minimal
acceptable dose has been found. Where possible, the
substitution of other medications, such as nonsteroidal
anti-inflammatory drugs, may facilitate tapering the
glucocorticoid dose once the initial benefit of therapy
has been achieved. When therapy is directed at a lifethreatening
disease (e.g., pemphigus or lupus cerebritis),
the initial dose should be a large one aimed at
achieving rapid control of the crisis. If some benefit is
not observed quickly, then the dose should be doubled or
tripled. After initial control in a potentially lethal disease,
dose reduction should be carried out under conditions
that permit frequent accurate observations of the
patient. It is always essential to weigh carefully the relative
dangers of therapy and of the disease being treated.
SECTION V
HORMONES AND HORMONE ANTAGONISTS
The lack of demonstrated deleterious effects of a single dose
of glucocorticoids within the conventional therapeutic range justifies
their administration to critically ill patients who may have adrenal
insufficiency. If the underlying condition does result from
deficiency of glucocorticoids, then a single intravenous injection of
a soluble glucocorticoid may prevent immediate death and allow
time for a definitive diagnosis to be made. If the underlying disease
is not adrenal insufficiency, the single dose will not harm the patient.
In the absence of specific contraindications, short courses of
high-dose systemic glucocorticoids also may be given for diseases
that are not life threatening, but the general rule is that long courses
of therapy at high doses should be reserved for life-threatening disease.
In selected settings, as when a patient is threatened with permanent
disability, this rule is justifiably violated.
In an attempt to dissociate therapeutic effects from undesirable
side effects, various regimens of steroid administration have
been used. To diminish HPA axis suppression, the intermediate-acting
steroid preparations (e.g., prednisone or prednisolone) should be
given in the morning as a single dose. Alternate-day therapy with
the same glucocorticoids also has been employed because certain
patients obtain adequate therapeutic responses on this regimen.
Alternatively, pulse therapy with higher glucocorticoid doses (e.g.,
doses as high as 1 to 1.5 g/day of methylprednisolone for 3 days)
frequently is used to initiate therapy in patients with fulminant,
immunologically related disorders such as acute transplantation
rejection, necrotizing glomerulonephritis, and lupus nephritis. The
benefit of such pulse therapy in long-term maintenance regimens
remains to be defined.
Replacement Therapy. Adrenal insufficiency can result
from structural or functional lesions of the adrenal cortex
(primary adrenal insufficiency or Addison’s disease)
or from structural or functional lesions of the
anterior pituitary or hypothalamus (secondary adrenal
insufficiency). In developed countries, primary adrenal
insufficiency most frequently is secondary to autoimmune
adrenal disease, whereas tuberculous adrenalitis
is the most frequent etiology in developing countries.
Other causes include adrenalectomy, bilateral adrenal
hemorrhage, neoplastic infiltration of the adrenal glands,
acquired immunodeficiency syndrome, inherited disorders
of the steroidogenic enzymes, and X-linked
adrenoleukodystrophy (Carey, 1997). Secondary adrenal
insufficiency resulting from pituitary or hypothalamic
dysfunction generally presents in a more insidious
manner than does the primary disorder, probably
because mineralocorticoid biosynthesis is preserved.
Acute Adrenal Insufficiency. This life-threatening disease
is characterized by GI symptoms (nausea, vomiting,
and abdominal pain), dehydration, hyponatremia,
hyperkalemia, weakness, lethargy, and hypotension. It
usually is associated with disorders of the adrenal rather
than the pituitary or hypothalamus, and it sometimes
follows abrupt withdrawal of glucocorticoids used at
high doses or for prolonged periods.
The immediate management of patients with acute adrenal
insufficiency includes intravenous therapy with isotonic sodium
chloride solution supplemented with 5% glucose and corticosteroids
and appropriate therapy for precipitating causes such as infection,
trauma, or hemorrhage. Because cardiac function often is reduced
in the setting of adrenocortical insufficiency, the patient should be
monitored for evidence of volume overload such as rising central
venous pressure or pulmonary edema. After an initial intravenous
bolus of 100 mg, hydrocortisone (cortisol) should be given by continuous
infusion at a rate of 50-100 mg every 8 hours. At this dose,
which approximates the maximum daily rate of cortisol secretion in
response to stress, hydrocortisone alone has sufficient mineralocorticoid
activity to meet all requirements. As the patient stabilizes, the
hydrocortisone dose may be decreased to 25 mg every 6-8 hours.
Thereafter, patients are treated in the same fashion as those with
chronic adrenal insufficiency.
For the treatment of suspected but unconfirmed acute adrenal
insufficiency, 4 mg of dexamethasone sodium phosphate can be substituted
for hydrocortisone because dexamethasone does not crossreact
in the cortisol assay and will not interfere with the
measurement of cortisol (either basally or in response to the cosyntropin
stimulation test). A failure to respond to cosyntropin in this
setting is diagnostic of adrenal insufficiency. Often, a sample for the
measurement of plasma ACTH also is obtained because it will provide
information about the underlying etiology if the diagnosis of
adrenocortical insufficiency is established.
Chronic Adrenal Insufficiency. Patients with chronic
adrenal insufficiency present with many of the same
manifestations seen in adrenal crisis but with lesser
severity. These patients require daily treatment with
corticosteroids (Coursin and Wood, 2002).