Adrenocortical steroids glucocorticoids

THERap Cat Glucocorticoid anti-inflammatory. therap cat (vet) Adrenocortical steroid glucocorticoid topical anti -inflammatory. 

Proceeding further down the table, one encounters a cluster based on a triple of uses adrenocortical steroid, glucocorticoid, anti-inflammatory. The parasympathomimetia-miotia cluster occurs alone, followed by a cluster centered on sympathomimetia. 

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. 

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. 

Adrenocortical steroids are used for their action on specific cancers and also to treat some of the complications of cancer, e.g. hypercalcaemia, raised intracranial pressure. Their principal use is in cancer of the lymphoid tissues and blood. In leukaemias they may also reduce the incidence of complications such as haemolytic anaemia and thrombocytopenia. A glucocorticoid is preferred, e.g. prednisolone, as high doses are used and mineralocorticoid actions are not needed and cause fluid retention. 

The adrenocortical steroids permit the bexly to adjust to environmental changes, to. stress, and to changes in the diet. Aldosterone and. to a lesser extent, other mincralocortieoids maintain a constant electrolyte balance and blood volume, and the glucocorticoids have key roles in controlling carbohydrate. protein, and lipid metabolism. 

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... 

Adrenocortical steroid hormones have a vast array of biological functions. Cortisol, the primary human glucocorticoid, regulates the inflammatory response (Newton and Holden, 2007), carbohydrate and lipid metabolism, and stress response (Kassel and Herrlich, 2007). Aldosterone regulates blood pressure by modulating fluid and electrolyte balance (Brizuela et ah, 2006 Foster, 2004). In the adrenal cortex, dehydroepiandrosterone (DHEA), dehy-droepiandrosterone sulfate (DHEA-S), and androstenedione are the androgens produced (Havelock et ah, 2004 Rainey et ah, 2002). 

Agents that inhibit steps in the steroidogenic pathway and thus alter the biosynthesis of adrenocortical steroids are discussed, as are synthetic steroids that inhibit glucocorticoid action. The effects of corticosteroids are numerous and widespread, and include alterations in carbohydrate, protein, and lipid metabolism maintenance of fluid and electrolyte balance and preservation of normal function of the cardiovascular system, the immune system, the kidney, skeletal muscle, the endocrine system, and the nervous system. 

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 ... 

Rashef and Shapiro (1960) reported that pretreatment of adrenalecto-mizc d rats with either epinephrine or eortisone inereased the depressed rate of free fatty acid release by their mesenteric adipose tissue in vitro however, maximal effects were, obtained only when both were given. It was further pointed out that epinephrine alone was highly effective in restorii the depressed rate of free fatty acid release by tissue from adrenal demedul-lated rats. Reshef and Shapiro (1960) also observed that pretreatment of starved intact rats with cortisone had little effect on the release of free fatty acid by mesenteric adipose tissue. Such treatment, however, inereased and prolonged the response of tissue removed from rats injected with epinephrine (sec Section VI, A). These results may reflect in part the effects of glucocorticoid administration on the adipose tissue stores of the intact animal, but the interesting relation between the effects of epinephrine and adrenocortical steroids on the release of free fatty acids deserves further study. 

ADRENOCORTICAL HORMONES Adrenocortical steroids are secreted by the adrenal glands, small organs located near the upper end of each kidney. There are two types of adrenocortical steroids, called mineralocorticoids and glucocorticoids. Mineralocorticoids, such as aldosterone, control tis-... 

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. 

The steroidal nature of adrenocortical hormones was established in 1937, when Reichstein synthesized desoxycorticosterone. Eventually it was clearly established that the adrenal cortex elaborated a number of hormones and that these compounds differed in their amount of inherent metabolic (glucocorticoid) and electrolyte regulating (mineralocorticoid) activity. The actions of these hormones extend to almost every cell in the body. In humans, hydrocortisone (cortisol) is the main carbohydrate-regulating steroid, and aldosterone is the main electrolyte-regulating steroid. 

The remaining steroid lipids constitute two main classes of steroid hormones sex hormones and adrenocortical hormones. The sex hormones include androgens (testosterone, androsterone), estrogens (estrone, estradiol), and progestins (progesterone). The adrenocortical hormones include mineralocorticoids (aldosterone) and glucocorticoids (hydrocortisone). 

This compound, a potent steroid with both glucocorticoid and mineralocorticoid activity, is the most widely used mineralocorticoid. Oral doses of 0.1 mg two to seven times weekly have potent salt-retaining activity and are used in the treatment of adrenocortical insufficiency associated with mineralocorticoid deficiency. These dosages are too small to have important anti-inflammatory or antigrowth effects. 

The short-term action of ACTH on the adrenocortical cell is the stimulation of the conversion of cholesterol to glucocorticoid, mineralocorticoid or androgen-precursor steroids (Fig. 2). The conversion of cholesterol to the end-product steroids involves two mitochondrial cytochrome P-450 enzymes, cytochrome P-450scc (cho-... 

The adrenal cortex (AC) produces the glucocorticoid cortisol (hydrocortisone) in the zona fasciculata and the mineralocorticoid aldosterone in the zona glomerulosa. Both steroid hormones are vitally important in adaptation responses to stress situations, such as disease, trauma, or surgery. Cortisol secretion is stimulated by hypophyseal ACTH aldosterone secretion by angiotensin II in particular (p. 128). In AC failure (primary adrenocortical insuf ciency, Addison disease), both cortisol and aldosterone must be replaced when ACTH production is deficient (secondary adrenocortical insuf ciency), cortisol alone needs to be replaced. Cortisol is effective when given orally (30 mg/day, 2/3 a.m 1 /3 p.m.). In stress situations, the dose is raised 5- to 10-fold. Aldosterone is poorly effective via the oral route instead, the mineralocorticoid fludrocortisone (0.1 mg/day) is given. 

Adrenocortical hormone (Section 27.6) A steroid hormone secreted by the adj enal glands. Phere are two types of adrenocortical hormones mineralocorticoids and glucocorticoids. 

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