Page 723 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 39 Adrenocorticosteroids & Adrenocortical Antagonists 709

patients to behavioral or somatic disorders, such as depression or protein-binding affinity, side chain stability, rate of elimination,
obesity and metabolic syndrome. and metabolic products. Halogenation at the 9 position, unsatu-
ration of the Δ1–2 bond of the A ring, and methylation at the
SYNTHETIC CORTICOSTEROIDS 2 or 16 position prolong the half-life by more than 50%. The Δ1
compounds are excreted in the free form. In some cases, the agent
Glucocorticoids have become important agents for use in the treat- given is a prodrug; for example, prednisone is rapidly converted to
ment of many inflammatory, immunologic, hematologic, and other the active product prednisolone in the body.
disorders. This has stimulated the development of many synthetic
steroids with anti-inflammatory and immunosuppressive activity. Pharmacodynamics

Pharmacokinetics The actions of the synthetic steroids are similar to those of cor-
tisol (see above). They bind to the specific intracellular receptor
Pharmaceutical steroids are usually synthesized from cholic acid proteins and produce the same effects but have different ratios of
obtained from cattle or steroid sapogenins found in plants. Fur- glucocorticoid to mineralocorticoid potency (Table 39–1).
ther modifications of these steroids have led to the marketing of
a large group of synthetic steroids with special characteristics that
are pharmacologically and therapeutically important (Table 39–1; CLINICAL PHARMACOLOGY
Figure 39–3).
The metabolism of the naturally occurring adrenal steroids has A. Diagnosis and Treatment of Disturbed Adrenal
been discussed above. The synthetic corticosteroids (Table 39–1) are Function
in most cases rapidly and completely absorbed when given by mouth. 1. Adrenocortical insufficiency
Although they are transported and metabolized in a fashion similar to a. Chronic (Addison’s disease)—Chronic adrenocortical insuf-
that of the endogenous steroids, important differences exist. ficiency is characterized by weakness, fatigue, weight loss, hypo-
Alterations in the glucocorticoid molecule influence its affinity tension, hyperpigmentation, and inability to maintain the blood
for glucocorticoid and mineralocorticoid receptors as well as its glucose level during fasting. In such individuals, minor noxious,

TABLE 39–1 Some commonly used natural and synthetic corticosteroids for general use. See Table 61–2 for
dermatologic corticosteroids.
Activity 1
Equivalent Oral
Agent Anti-Inflammatory Topical Salt-Retaining Dose (mg) Forms Available
Short- to medium-acting glucocorticoids
Hydrocortisone (cortisol) 1 1 1 20 Oral, injectable, topical
Cortisone 0.8 0 0.8 25 Oral
Prednisone 4 0 0.3 5 Oral
Prednisolone 5 4 0.3 5 Oral, injectable
Methylprednisolone 5 5 0.25 4 Oral, injectable
Meprednisone 2 5 0 4 Oral, injectable
Intermediate-acting glucocorticoids
Triamcinolone 5 5 3 0 4 Oral, injectable, topical
Paramethasone 2 10 0 2 Oral, injectable
Fluprednisolone 2 15 7 0 1.5 Oral
Long-acting glucocorticoids
Betamethasone 25–40 10 0 0.6 Oral, injectable, topical
Dexamethasone 30 10 0 0.75 Oral, injectable, topical
Mineralocorticoids
Fludrocortisone 10 0 250 2 Oral
Desoxycorticosterone 0 0 20 Injectable, pellets
acetate 2
1 Potency relative to hydrocortisone.
2
Outside United States.
3
Triamcinolone acetonide: Up to 100.