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

1230 mineralocorticoid used is fludrocortisone acetate (0.05-0.2 mg/day).
Many experts also administer table salt to infants (one-fifth of a teaspoon
dissolved in formula daily) until the child is eating solid food.
Therapy is guided by gain in weight and height, by plasma levels of
17-hydroxyprogesterone, and by blood pressure. Elevated plasma
renin activity suggests that the patient is receiving an inadequate dose
of mineralocorticoid. Sudden spurts in linear growth often indicate
inadequate pituitary suppression and excessive androgen secretion,
whereas growth failure suggests overtreatment with glucocorticoid.
The ability to detect classical CAH (21-hydroxylase deficiency)
prenatally has made possible the treatment of affected
females with glucocorticoids in utero, potentially eliminating the
need for genital surgery to correct the virilization of the external genitalia.
To suppress fetal adrenal androgen production effectively and
consequent virilization, glucocorticoid therapy (e.g., dexamethasone,
20 μg/kg taken daily orally by mothers at risk) must be initiated
before 10 weeks of gestation, before a definitive diagnosis of CAH
can be made. The genotype and sex of the fetus then are determined,
and steroid therapy is stopped if the sex is male or there is at least one
wild-type allele for 21-hydroxylase. If genotyping reveals an affected
female, steroid therapy is continued until delivery. A large-scale
study currently is in progress to determine if exposure to glucocorticoids
in utero has developmental consequences. To date, no adverse
effects on developmental milestones and cognitive development have
been noted; however, increased shyness and internalization behavior
have been observed in small pilot study and will need to be reevaluated
in the larger trial. Potential maternal side effects include hypertension,
weight gain, edema, and mood changes.
SECTION V
HORMONES AND HORMONE ANTAGONISTS
Therapeutic Uses in Nonendocrine Diseases. Outlined
next are important uses of glucocorticoids in diseases
that do not directly involve the HPA axis. The disorders
discussed are not inclusive; rather, they illustrate the
principles governing glucocorticoid use in selected diseases
for which glucocorticoids are more frequently
employed. The dosage of glucocorticoids varies considerably
depending on the nature and severity of the
underlying disorder. For convenience, approximate
doses of a representative glucocorticoid (generally prednisone)
are provided. This choice is not an endorsement
of one particular glucocorticoid preparation over other
congeners but is made for illustrative purposes only.
Rheumatic Disorders. Glucocorticoids are used widely in the treatment
of a variety of rheumatic disorders and are a mainstay in the
treatment of the more serious inflammatory rheumatic diseases, such
as systemic lupus erythematosus, and a variety of vasculitic disorders,
such as polyarteritis nodosa, Wegener’s granulomatosis, Churg-
Strauss syndrome, and giant cell arteritis. For these more serious
disorders, the starting dose of glucocorticoids should be sufficient
to suppress the disease rapidly and minimize resultant tissue damage.
Initially, prednisone (1 mg/kg per day in divided doses) often is used,
generally followed by consolidation to a single daily dose, with subsequent
tapering to a minimal effective dose as determined by the
clinical picture.
Although they are an important component of treatment of
rheumatic diseases, glucocorticoids are often used in conjunction
with other immunosuppressive agents such as cyclophosphamide
and methotrexate, which offer better long-term control than steroids
alone. The exception is giant cell arteritis, for which glucocorticoids
remain superior to other agents. Caution should be exercised in the
use of glucocorticoids in some forms of vasculitis (e.g., polyarteritis
nodosa), for which underlying infections with hepatitis viruses
may play a pathogenetic role. Although glucocorticoids are indicated
in these cases, there is at least a theoretical concern that glucocorticoids
may complicate the course of the viral infection by suppressing
the immune system. To facilitate drug tapering and/or conversion
to alternate-day treatment regimens, the intermediate-acting glucocorticoids
such as prednisone and methylprednisolone are generally
preferred over longer-acting steroids such as dexamethasone.
In rheumatoid arthritis, because of the serious and debilitating
side effects associated with chronic use, glucocorticoids are used as
stabilizing agents for progressive disease that fails to respond to first-line
treatments such as physiotherapy and nonsteroidal anti-inflammatory
agents. In this case, glucocorticoids provide relief until other, sloweracting
antirheumatic drugs, such as methotrexate or agents targeted
at tumor necrosis factor, take effect. A typical starting dose is 5-10 mg
of prednisone per day. In the setting of an acute exacerbation, higher
doses of glucocorticoids may be employed (typically 20-40 mg/day
of prednisone or equivalent), with rapid taper thereafter. Complete
relief of symptoms is not sought, and the symptomatic effect of small
reductions in dose (decreases of perhaps 1 mg/day of prednisone
every 2-3 weeks) should be tested frequently while concurrent therapy
with other measures is continued, to maintain the lowest possible
prednisone dose. Alternatively, patients with major symptomatology
confined to one or a few joints may be treated with intra-articular
steroid injections. Depending on joint size, typical doses are 5-20 mg
of triamcinolone acetonide or its equivalent.
In noninflammatory degenerative joint diseases (e.g.,
osteoarthritis) or in a variety of regional pain syndromes (e.g., tendinitis
or bursitis), glucocorticoids may be administered by local injection
for the treatment of episodic disease flare-up. It is important to use a
glucocorticoid that does not require bioactivation (e.g., prednisolone
rather than prednisone) and to minimize the frequency of local steroid
administration whenever possible. In the case of repeated intraarticular
injection of steroids, there is a significant incidence of painless
joint destruction, resembling Charcot’s arthropathy. It is
recommended that intra-articular injections be performed with intervals
of at least 3 months to minimize complications.
Renal Diseases. Patients with nephrotic syndrome secondary to minimal
change disease generally respond well to steroid therapy, and
glucocorticoids clearly are the first-line treatment in both adults and
children. Initial daily doses of prednisone are 1-2 mg/kg for 6 weeks,
followed by a gradual tapering of the dose over 6-8 weeks, although
some nephrologists advocate alternate-day therapy. Objective evidence
of response, such as diminished proteinuria, is seen within
2-3 weeks in 85% of patients, and >95% of patients have remission
within 3 months. Cessation of steroid therapy frequently is complicated
by disease relapse, as manifested by recurrent proteinuria.
Patients who relapse repeatedly are termed steroid-resistant and
often are treated with other immunosuppressive drugs such as azathioprine
or cyclophosphamide. Patients with renal disease secondary
to systemic lupus erythematosus also are generally given a
therapeutic trial of glucocorticoids.