Page 726 - Basic _ Clinical Pharmacology ( PDFDrive )

712 SECTION VII Endocrine Drugs

TABLE 39–2 Some therapeutic indications for the use of glucocorticoids in nonadrenal disorders.

Disorder Examples
Allergic reactions Angioneurotic edema, asthma, bee stings, contact dermatitis, drug reactions, allergic rhinitis, serum sickness, urticaria
Collagen-vascular Giant cell arteritis, lupus erythematosus, mixed connective tissue syndromes, polymyositis, polymyalgia rheumatica,
disorders rheumatoid arthritis, temporal arteritis
Eye diseases Acute uveitis, allergic conjunctivitis, choroiditis, optic neuritis
Gastrointestinal diseases Inflammatory bowel disease, nontropical sprue, subacute hepatic necrosis
Hematologic disorders Acquired hemolytic anemia, acute allergic purpura, leukemia, lymphoma, autoimmune hemolytic anemia, idiopathic
thrombocytopenic purpura, multiple myeloma
Systemic inflammation Acute respiratory distress syndrome (sustained therapy with moderate dosage accelerates recovery and decreases
mortality)
Infections Acute respiratory distress syndrome, sepsis
Inflammatory conditions Arthritis, bursitis, tenosynovitis
of bones and joints
Nausea and vomiting A large dose of dexamethasone reduces emetic effects of chemotherapy and general anesthesia
Neurologic disorders Cerebral edema (large doses of dexamethasone are given to patients following brain surgery to minimize cerebral
edema in the postoperative period), multiple sclerosis
Organ transplants Prevention and treatment of rejection (immunosuppression)
Pulmonary diseases Aspiration pneumonia, bronchial asthma, prenatal prevention of infant respiratory distress syndrome, sarcoidosis
Renal disorders Nephrotic syndrome
Skin diseases Atopic dermatitis, dermatoses, lichen simplex chronicus (localized neurodermatitis), mycosis fungoides, pemphigus,
psoriasis, seborrheic dermatitis, xerosis
Thyroid diseases Malignant exophthalmos, subacute thyroiditis
Miscellaneous Hypercalcemia, mountain sickness

Treatment for transplant rejection is a very important applica- is a function of the dosage and the genetic background of the
tion of glucocorticoids. The efficacy of these agents is based on patient. In the face, rounding, puffiness, fat deposition, and
their ability to reduce antigen expression from the grafted tissue, plethora usually appear (moon facies). Similarly, fat tends to be
delay revascularization, and interfere with the sensitization of redistributed from the extremities to the trunk, the back of the
cytotoxic T lymphocytes and the generation of primary antibody- neck, and the supraclavicular fossae. There is an increased growth
forming cells. of fine hair over the face, thighs and trunk. Steroid-induced punc-
tate acne may appear, and insomnia and increased appetite are
Toxicity noted. In the treatment of dangerous or disabling disorders, these
changes may not require cessation of therapy. However, the under-
The benefits obtained from glucocorticoids vary considerably. lying metabolic changes accompanying them can be very serious
Use of these drugs must be carefully weighed in each patient by the time they become obvious. The continuing breakdown
against their widespread effects. The major undesirable effects of of protein and diversion of amino acids to glucose production
glucocorticoids are the result of their hormonal actions, which increase the need for insulin and over time result in weight gain;
lead to the clinical picture of iatrogenic Cushing’s syndrome (see visceral fat deposition; myopathy and muscle wasting; thinning of
later in text). the skin, with striae and bruising; hyperglycemia; and eventually
When glucocorticoids are used for short periods (<2 weeks), it osteoporosis, diabetes, and aseptic necrosis of the hip. Wound
is unusual to see serious adverse effects even with moderately large healing is also impaired under these circumstances. When diabetes
doses. However, insomnia, behavioral changes (primarily hypo- occurs, it is treated with diet and insulin. These patients are often
mania), and acute peptic ulcers are occasionally observed even resistant to insulin but rarely develop ketoacidosis. In general,
after only a few days of treatment. Acute pancreatitis is a rare but patients treated with corticosteroids should be on high-protein
serious acute adverse effect of high-dose glucocorticoids. and potassium-enriched diets.

A. Metabolic Effects B. Other Complications
Most patients who are given daily doses of 100 mg of hydrocorti- Other serious adverse effects of glucocorticoids include peptic
sone or more (or the equivalent amount of synthetic steroid) for ulcers and their consequences. The clinical findings associated
longer than 2 weeks undergo a series of changes that have been with certain disorders, particularly bacterial and mycotic infec-
termed iatrogenic Cushing’s syndrome. The rate of development tions, may be masked by the corticosteroids, and patients must