Adrenocortical steroid

The adrenal cortex synthesizes corticosteroids (glucocorticoids and mineralocor-ticoids), which differ in activities. In humans, cortisol is the main glucocorticoid, and aldosterone is a main mineralocorticoid. Steroid therapy causes severe potential side effects, hence a careful consideration is always exercised before starting therapy. These are used in variety of disorders such as rheumatic disorder, renal disease, allergic manifestation, bronchial asthma, skin diseases, infectious diseases, malignancy, and hepatic diseases. 

Corticosteroids have a range of activity. They have potent antiinflammatory and immunosuppressive activity. Many synthetic drugs are available as corticosteroids. In appropriate doses, these are used as replacement therapy in adrenal insufficiency. The topical application of corticosteroids is safer when compared with systemic use. Corticosteroids should be used in smaller doses for the shortest duration of time. A high dose may be used for life-threatening syndromes or diseases. A tapering pattern of withdrawal should be followed to avoid complications of sudden withdrawal. Systemic therapy is indicated in a variety of conditions. These are administered by intraarticular injections with aseptic conditions for rheumatoid arthritis and osteoarthritis. In skin diseases, such as eczema, contact dermatitis, and psoriasis, corticosteroids are used topically. In some cases, steroids are combined with antimicrobial substances such as neomycin. 

Corticosteroids should be used cautiously in the presence of congestive heart failure, myocardial infarction, hypertension, diabetes mellitus, epilepsy, glaucoma, hepatic disorders, osteoporosis, peptic ulceration, and renal impairment. Children are more susceptible to these adverse effects. To avoid cardiovascular collapse, steroids must be given slowly by intravenous injection. Large doses produce Cushing s syndrome (with moon face and sometimes hirsutism). 

It has been emphatieally and logieally determined to elassify the steroidal hormone products belonging speeifically to the adrenal cortex (z.e., adrenocortical steroids) into two major groups the corticosteroids (viz., glucocorticoids and mineralocorticoids, which essentially possess 21 C-atoms, and the androgens having 19 C-atoms. 

In general, the adrenocortical steroids (or adrenal corticosteroids) distinctly differ in their respective glucocorticoid activities i.e., carbohydrate-regulating), and mineralocorticoid activities (i.e., electrolyte-regulating). It has been observed that in human beings the following two compounds occur commonly  

Structure-Activity Relationship (SAR) Intensive and extensive clinical investigations have duly revealed that the anti-inflammatory activity emanated by the adrenal cortical steroids in humans invariably correlates intimately with their respective glucocorticoid activity. The advent of glaring and outstanding researches have evolved several synthetic steroids that exclusively possess distinctly higher glucocorticoid, and relatively lower mineralocorticosteroid activity in comparison to cortisone or cortisol that have been duly prepared, biologically screened, and marketed. 

Biological Activity Profile The biological activity profile of the glucocorticoids and the mineralocorticoids shall now be discussed briefly as under  

The adrenocortical steroids may be classified judiciously according to the categorization already shown as in Table 24.1. The various potent compounds belonging to different groups shall now be treated individually in the sections that follows  

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Schimmer, B.P. and Parker, K.L., Adrenocorticotropic hormone adrenocortical steroids and their synthetic analogs inhibitors of the synthesis and actions of adrenocortical hormones, in Goodman and Gilman s The Pharmacological Basis of Therapeutics, 9th ed., Hardman, J.G. and Limbird, L.E., Eds., McGraw-Hill, New York, 1996, chap. 59. 

Adrenocortical Steroids, Determination of Individual (Neher), 1, 127 Amino Aciduria (Bigwood, Crokaert, Schram, Soupart and Vis), 2, 201 Ammonia, Blood (Bessman), 2, 135 Ascorbic Acid in Man and Animals (Knox and Goswami), 4, 122 Automation (Marsh), 2, 201 Bile Pigments in Jaundice (Billing), 2, 268... 

Severe and prolonged hypothyroidism In severe and prolonged hypothyroidism, supplemental adrenocortical steroids may be necessary. 

Pharmacology These agents are synthetic adrenocortical steroids with basic glucocorticoid actions and effects. Glucocorticoids may decrease number and activity of inflammatory cells, enhance effect of beta-adrenergic drugs on cyclic AMP production, inhibit bronchoconstrictor mechanisms, or produce direct smooth muscle relaxation. Inhaler use provides effective local steroid activity with minimal systemic effect. 

Fluasterone is a stable adrenocortical steroid, a 16a-fluoro analogue of prasteron [dehydroepiandrosterone (DHEA)j. It is currently developed (phase II) for the treatment of metabolic syndrome (i.e. insulin resistance). Electrophilic... 

Mechanism of Action An adrenocortical steroid that controls the rate of protein synthesis, depresses the migration of polymorphonuclear leukocytes and fibroblasts, reduces capillary permeability, and prevents or controls inflammation. Therapeutic Effect Decreases tissue response to inflammatory process. 

Mechanism of Action An adrenocortical steroid that inhibits accumulation of inflammatory cells at inflammation sites, phagocytosis, lysosomal enzyme release and synthesis, and release of mediators of inflammation. Therapeutic Effect Prevents or suppresses cell-mediated immune reactions. Decreases or prevents tissue response to i nflammatory process. 

Mechanism of Action An adrenocortical steroid that suppresses migration of polymorphonuclear leukocytes and reverses increased capillary permeability Therapeutic Effect Decreases inflammation. 

As discussed in previous chapters, secretion of adrenocortical steroids is controlled by the pituitary release of corticotrophin (ACTH). The adrenal gland has two main parts, adrenal medulla, which is responsible for the release of catecholamines and adrenal cortex which secretes glucocorticoids. 

Secretion of adrenocortical steroids is controlled by the pituitary release of corticotropin (ACTH). Secretion of the salt-retaining hormone aldosterone is primarily under the influence of angiotensin. Corticotropin has some actions that do not depend on its effect on adrenocortical secretion. However, its pharmacologic value as an anti-inflammatory agent and its use in testing adrenal function depend on its secretory action. Its pharmacology is discussed in Chapter 37 and is reviewed only briefly here. 

Inhibitors of the synthesis or antagonists of the action of the adrenocortical steroids are important in the treatment of several conditions. These agents are described at the end of this chapter. 

Schimmer BP, Parker KL. Adrenocorticotropic hormone adrenocortical steroids and their synthetic analogs inhibitors of the synthesis and actions of adrenocortical hormones. In Brunton LL, et al, eds. 

Progesterone is the most important progestin in humans. In addition to having important hormonal effects, it serves as a precursor to the estrogens, androgens, and adrenocortical steroids. It is... 

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)... 

The relative levels of the enzymes expressed by the individual adrenocortical cell determine the series of hydroxylation steps that occurs and the ultimate steroid that is produced. Thus, the rate of production of a given adrenocortical steroid is determined by the product of... 

By contrast, deficiency of 17-hydroxylase results in impaired ability of the gonads (as well as the adrenals) to synthesize androgens (males) or estrogen (females) patients subsequently manifest with problems typically associated with primary hypogonadism. Deficiency of 17-hydroxylase is similar to that of 11 (3-hydroxylase in that there is adrenal overproduction of min-eralocorticoids, resulting in sodium retention and high blood pressure. Differential diagnosis is usually facilitated by examination of the complete profile of adrenocortical steroid hormones. 

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. 

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