Adrenocortical steroid therapy

Today, it is well known that the introduction of a chlorine or fluorine atom at the C-9 position of the natural adrenal substances cortisone and hydrocortisone (and of their dehydro-analogues) markedly enhances the anti-inflammatory activity of these agents, and is accompanied by a striking increase in both salt and water retention [14]. These undesirable side effects, which are manifested generally by 9-halo-steroids, preclude their use systemically in the management of disorders that are normally responsive to adrenocortical steroid therapy. 

Minimum tolerated dose. This concept is not so common as the one above, but it applies to longterm adrenocortical steroid therapy against inflammatory or immunological conditions, e.g. in asthma and some cases of rheumatoid arthritis, when the dose that provides symptomatic relief may be so high that serious adverse effects are inevitable if it is continued indefinitely. The patient must be persuaded to accept incomplete relief on the groxmds of safety. This can be difficult to achieve. 

Hydrocortisone, USP, Hydrocortisone. 11/3,17.21-tri-hydraxyprcgn-4-cnc-3.2().dionc. is the primary natural glu-vocorlieoid in humans. Despite the large number of synthetic glucocorticoids, hydrocortisone, its esters, and its salts rc-in.tin a mainstay of modem adrenocortical steroid therapy iind Ihe standard for comparison of all other glucocorticoids and mineraliKorticoids (sec Table 2.3-8). It is used for all the indications mentioned above. Its esters and. salts illustrate Ihe principles of chemical modification to modify pharmacokinetic use shown in Figure 2.3-6. The commercially available salts and esters (sec Fig. 23-30) include... 

Decadron Dexametha- sone USP 0.5, 0.75, 4 mg Tablet Replacement therapy in adrenocortical deficiency, antiinflammatory A synthetic adrenocortical steroid-potent antiinflammatory effects Calcium phosphate, lactose, magnesium stearate, starch Merck Co. (Roxane Laboratories and Par)... 

It is reasonable to use proprietary names when dosage, and therefore pharmaceutical bioavadability, are critical so that small variations in the amoimt of drug available for absorption can have big effects on the patient, e.g. drugs with low therapeutic ratio, digoxin, hormone replacement therapy, adrenocortical steroids (oral), antiepileptics, cardiac anti-arrhythmics, warfarin. Also, with the introduction of complex formulations, e.g. sustained-release, it is important clearly to identify these, and use of proprietary names has a role. 

Treat with adrenocortical steroids before thyroid therapy in coexisting hypothyroidism and hypoadrenalism. 

Cathro and Coyle (C4) have described the second pregnancy of a woman who had already given birth to an infant with adrenal hypoplasia. The first infant died of respiratory failure 18 hours after birth and postmortem examination revealed very small adrenal glands but no other detectable endocrine abnormality. During the latter part of the second pregnancy, the maternal estriol excretion was low (1 mg/24 hours), an expected finding since 16a-OH-DHA produced by the fetus is an important precursor of estriol (D6, D9) (Section 4.1.1.). Evidence for adrenocortical insufficiency in the infant was obtained from the low level of cortisol in the umbilical cord blood. The infant was satisfactorily treated at birth with steroid therapy. 

Corticosteroids (Table 11) are synthetic adrenocortical steroids with antiinflammatory actions and effects, and are used in numerous disorders including bronchial asthma. For example, beclomethasone dipropionate (Beclovent, 85 meg 3 to 4 times daily), dexamethasone sodium phosphate (Decadron phosphate), and triamcinolone acetonide (Azmacort), which are not bronchodilators and are not indicated for rapid rehef of acute asthma, are used in bronchospastic states intractable to an adequate trial of conventional therapy. 

Side effects of topical administration of steroids have been reviewed recently (124 ). Further cases with Cushing s syndrome secondary to topical steroid therapy have been reported (131 ). It was shown that treatment with less than 50 g of clobetasol propionate ointment per week has no suppressive effect on the adrenal cortex. When more than SO g of ointment per week was used, a significant number of patients owed adrenocortical suppression (4 ). 

Pharmacology The naturally occurring adrenal cortical steroids have both anti-inflammatory (glucocorticoid) and salt-retaining (mineralocorticoid) properties. These compounds are used as replacement therapy in adrenocortical deficiency states and may be used for their anti-inflammatory effects. 

Type E (Ending of use) reactions, where discontinuation of chronic therapy is too abrupt, e.g. of adrenal steroid causing rebound adrenocortical insufficiency, of opioid causing the withdrawal syndrome. 

An interesting clinical complication in the use of AG is that the decreased levels of cortisol cause increased secretion of adrenocorticotropic hormone (ACTH) by feedback stimulation of the pituitary gland, which will overcome the steroid synthesis inhibition of AG. This tendency must be overcome by coadministration of hydrocortisone. In spite of considerable clinical literature on the usefulness of AG in the treatment of advanced breast cancer and adrenocortical carcinoma, the only approved indication for AG in the United States (1990) is therapy for Cushing s syndrome. 

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