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

1232 Ocular Diseases. Ocular pharmacology, including some consideration
of the use of glucocorticoids, is discussed in Chapter 64.
Glucocorticoids frequently are used to suppress inflammation in the
eye and can preserve sight when used properly. They are administered
topically for diseases of the outer eye and anterior segment and
attain therapeutic concentrations in the aqueous humor after instillation
into the conjunctival sac. For diseases of the posterior segment,
intraocular injection or systemic administration is required.
Generally, ocular use of glucocorticoids should be supervised by an
ophthalmologist.
A typical prescription is 0.1% dexamethasone sodium phosphate
solution (ophthalmic), 2 drops in the conjunctival sac every
4 hours while awake, and 0.05% dexamethasone sodium phosphate
ointment (ophthalmic) at bedtime. For inflammation of the
posterior segment, typical doses are 30 mg of prednisone or equivalent
per day, administered orally in divided doses.
Topical glucocorticoid therapy frequently increases intraocular
pressure in normal eyes and exacerbates intraocular hypertension
in patients with antecedent glaucoma. The glaucoma is not
always reversible on cessation of glucocorticoid therapy. Intraocular
pressure should be monitored when glucocorticoids are applied to
the eye for >2 weeks.
Topical administration of glucocorticoids to patients with
bacterial, viral, or fungal conjunctivitis can mask evidence of progression
of the infection until sight is irreversibly lost. Glucocorticoids
are contraindicated in herpes simplex keratitis because progression
of the disease may lead to irreversible clouding of the cornea. Topical
steroids should not be used in treating mechanical lacerations and
abrasions of the eye because they delay healing and promote the
development and spread of infection.
SECTION V
HORMONES AND HORMONE ANTAGONISTS
Skin Diseases. Glucocorticoids are remarkably efficacious in the
treatment of a wide variety of inflammatory dermatoses. As a result,
a large number of different preparations and concentrations of topical
glucocorticoids of varying potencies are available. A typical regimen
for an eczematous eruption is 1% hydrocortisone ointment
applied locally twice daily. Effectiveness is enhanced by application
of the topical steroid under an occlusive film, such as plastic wrap;
unfortunately, the risk of systemic absorption also is increased by
occlusive dressings, and this can be a significant problem when the
more potent glucocorticoids are applied to inflamed skin.
Glucocorticoids are administered systemically for severe episodes
of acute dermatological disorders and for exacerbations of chronic
disorders. The dose in these settings is usually 40 mg/day of prednisone.
Systemic steroid administration can be lifesaving in pemphigus,
which may require daily doses of up to 120 mg of
prednisone. Further discussion of the treatment of skin diseases is
presented in Chapter 65.
Gastrointestinal Diseases. Glucocorticoid therapy is indicated in
selected patients with inflammatory bowel disease (chronic ulcerative
colitis and Crohn’s disease; Chapter 47). Patients who fail to respond
to more conservative management (i.e., rest, diet, and sulfasalazine)
may benefit from glucocorticoids; steroids are most useful for acute
exacerbations. In mild ulcerative colitis, hydrocortisone (100 mg) can
be administered as a retention enema with beneficial effects. In more
severe acute exacerbations, oral prednisone (10-30 mg/day) frequently
is employed. For severely ill patients—with fever, anorexia,
anemia, and impaired nutritional status—larger doses should be used
(40-60 mg prednisone per day). Major complications of ulcerative
colitis or Crohn’s disease may occur despite glucocorticoid therapy,
and glucocorticoids may mask signs and symptoms of complications
such as intestinal perforation and peritonitis.
Budesonide, a highly potent synthetic glucocorticoid that is
inactivated by first-pass hepatic metabolism, reportedly exhibits
diminished systemic side effects commonly associated with glucocorticoids.
Oral administration of budesonide in delayed-release capsules
(ENTOCORT, 9 mg/day) facilitates drug delivery to the ileum and
ascending colon; the drug also has been used as a retention enema in
the treatment of ulcerative colitis.
Hepatic Diseases. The use of corticosteroids in hepatic disease has
been highly controversial. Glucocorticoids clearly are of benefit in
autoimmune hepatitis, where as many as 80% of patients show
histological remission when treated with prednisone (40-60 mg daily
initially, with tapering to a maintenance dose of 7.5-10 mg daily after
serum transaminase levels fall). The role of corticosteroids in alcoholic
liver disease is not fully defined; the most recent meta-analysis
of previously published reports failed to establish a beneficial role of
corticosteroids, even in patients with severe disease (Rambaldi et al.,
2008). Further studies are needed to confirm or refute the role of
steroids in this setting. In the setting of severe hepatic disease, prednisolone
should be used instead of prednisone, which requires
hepatic conversion to be active.
Malignancies. Glucocorticoids are used in the chemotherapy of acute
lymphocytic leukemia and lymphomas because of their antilymphocytic
effects. Most commonly, glucocorticoids are one component
of combination chemotherapy administered under scheduled protocols.
Glucocorticoids once were frequently employed in the setting
of hypercalcemia of malignancy, but more effective agents, such as
the bisphosphonates, now are the preferred therapy.
Cerebral Edema. Corticosteroids are of value in the reduction or prevention
of cerebral edema associated with parasites and neoplasms,
especially those that are metastatic. Although corticosteroids are frequently
used for the treatment of cerebral edema caused by trauma
or cerebrovascular accidents, controlled clinical trials do not support
their use in these settings.
Miscellaneous Diseases and Conditions. Sarcoidosis. Corticosteroids
are indicated therapy for patients with debilitating symptoms or lifethreatening
forms of sarcoidosis. Patients with severe pulmonary
involvement are treated with 10-20 mg per day of prednisone, or an
equivalent dose of alternative steroids, to induce remission. Higher
doses may be required for other forms of this disease. Maintenance
doses, which often are required for long periods of time, may be as low
as 5 mg/day of prednisone. These patients, like all patients who require
chronic glucocorticoid therapy at doses exceeding the normal daily
production rate, are at increased risk of secondary tuberculosis; therefore,
patients with a positive tuberculin reaction or other evidence of
tuberculosis should receive prophylactic antituberculosis therapy.
Thrombocytopenia. In thrombocytopenia, prednisone (0.5 mg/kg) is
used to decrease the bleeding tendency. In more severe cases, and for
initiation of treatment of idiopathic thrombocytopenia, daily doses of
prednisone (1-1.5 mg/kg) are employed. Patients with refractory
idiopathic thrombocytopenia may respond to pulsed high-dose glucocorticoid
therapy.
Autoimmune Destruction of Erythrocytes. Patients with autoimmune
destruction of erythrocytes (i.e., hemolytic anemia with a positive