Page 727 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 39 Adrenocorticosteroids & Adrenocortical Antagonists 713

be carefully monitored to avoid serious mishap when large doses Contraindications & Cautions
are used. Severe myopathy is more frequent in patients treated
with long-acting glucocorticoids. The administration of such A. Special Precautions
compounds has been associated with nausea, dizziness, and weight Patients receiving glucocorticoids must be monitored carefully for
loss in some patients. These effects are treated by changing drugs, the development of hyperglycemia, glycosuria, sodium retention
reducing dosage, and increasing potassium and protein intake. with edema or hypertension, hypokalemia, peptic ulcer, osteopo-
Hypomania or acute psychosis may occur, particularly in patients rosis, and hidden infections.
receiving very large doses of corticosteroids. Long-term therapy with The dosage should be kept as low as possible, and intermittent
intermediate- and long-acting steroids is associated with depression administration (eg, alternate-day) should be used when satisfactory
and the development of posterior subcapsular cataracts. Psychiatric therapeutic results can be obtained on this schedule. Even patients
follow-up and periodic slit-lamp examination are indicated in such maintained on relatively low doses of corticosteroids may require
patients. Increased intraocular pressure is common, and glaucoma supplementary therapy at times of stress, such as when surgical
may be induced. Benign intracranial hypertension also occurs. In dos- procedures are performed or intercurrent illness or accidents occur.
2
ages of 45 mg/m per day or more of hydrocortisone or its equivalent,
growth retardation occurs in children. Medium-, intermediate-, and B. Contraindications
long-acting glucocorticoids have greater growth-suppressing potency Glucocorticoids must be used with great caution in patients with
than the natural steroid at equivalent doses. peptic ulcer, heart disease or hypertension with heart failure,
When given in larger than physiologic amounts, steroids such certain infectious illnesses such as varicella and tuberculosis,
as cortisone and hydrocortisone, which have mineralocorticoid psychoses, diabetes, osteoporosis, or glaucoma.
effects in addition to glucocorticoid effects, cause some sodium
and fluid retention and loss of potassium. In patients with normal Selection of Drug & Dosage Schedule
cardiovascular and renal function, this leads to a hypokalemic,
hypochloremic alkalosis and eventually to a rise in blood pressure. Glucocorticoid preparations differ with respect to relative anti-
In patients with hypoproteinemia, renal disease, or liver disease, inflammatory and mineralocorticoid effect, duration of action,
edema may also occur. In patients with heart disease, even small cost, and dosage forms available (Table 39–1), and these factors
degrees of sodium retention may lead to heart failure. These should be taken into account in selecting the drug to be used.
effects can be minimized by using synthetic non-salt-retaining
steroids, sodium restriction, and judicious amounts of potassium A. ACTH versus Adrenocortical Steroids
supplements. In patients with normal adrenals, ACTH was used in the past to
induce the endogenous production of cortisol to obtain similar
C. Adrenal Suppression effects. However, except when an increase in androgens is desir-
When corticosteroids are administered for more than 2 weeks, able, the use of ACTH as a therapeutic agent has been abandoned.
adrenal suppression may occur. If treatment extends over weeks Instances in which ACTH was claimed to be more effective than
to months, the patient should be given appropriate supplemen- glucocorticoids were probably due to the administration of smaller
tary therapy at times of minor stress (twofold dosage increases amounts of corticosteroids than were produced by the dosage of
for 24–48 hours) or severe stress (up to tenfold dosage increases ACTH.
for 48–72 hours) such as accidental trauma or major surgery.
If corticosteroid dosage is to be reduced, it should be tapered B. Dosage
slowly. If therapy is to be stopped, the reduction process should In determining the dosage regimen to be used, the physician must
be quite slow when the dose reaches replacement levels. It may consider the seriousness of the disease, the amount of drug likely
take 2–12 months for the hypothalamic-pituitary-adrenal axis to to be required to obtain the desired effect, and the duration of
function acceptably, and cortisol levels may not return to normal therapy. In some diseases, the amount required for maintenance of
for another 6–9 months. The glucocorticoid-induced suppression the desired therapeutic effect is less than the dose needed to obtain
is not a pituitary problem, and treatment with ACTH does not the initial effect, and the lowest possible dosage for the needed
reduce the time required for the return of normal function. effect should be determined by gradually lowering the dose until
If the dosage is reduced too rapidly in patients receiving glu- a small increase in signs or symptoms is noted.
cocorticoids for a certain disorder, the symptoms of the disorder When it is necessary to maintain continuously elevated plasma
may reappear or increase in intensity. However, patients without corticosteroid levels to suppress ACTH, a slowly absorbed par-
an underlying disorder (eg, patients cured surgically of Cushing’s enteral preparation or small oral doses at frequent intervals are
disease) also develop symptoms with rapid reductions in cortico- required. The opposite situation exists with respect to the use
steroid levels. These symptoms include anorexia, nausea or vomit- of corticosteroids in the treatment of inflammatory and allergic
ing, weight loss, lethargy, headache, fever, joint or muscle pain, disorders. The same total quantity given in a few doses may be
and postural hypotension. Although many of these symptoms more effective than that given in many smaller doses or in a slowly
may reflect true glucocorticoid deficiency, they may also occur absorbed parenteral form.
in the presence of normal or even elevated plasma cortisol levels, Severe autoimmune conditions involving vital organs must
suggesting glucocorticoid dependence. be treated aggressively, and undertreatment is as dangerous