Corticosteroids Mineralocorticoid

Corticosteroids Glucocorticoids Mineralocorticoids Corticosteroid antagonists Receptor antagonists Synthetic inhibitors... 

Steroid hormones can be subdivided into sex hormones (androgens, estrogens, and progestins) and corticosteroids (glucocorticoids and mineralocorticoids). 

This section of the chapter discusses the hormones produced by the adrenal cortex or the adrenocortical hormones, which are the glucocorticoids and mineralocorticoids. These hormones are essential to life and influence many organs and structures of the body. The glucocorticoids and mineralocorticoids are collectively called corticosteroids. 

Decrease dose or change corticosteroid to one with less mineralocorticoid activity (e.g., dexamethasone)... 

FIGURE 26-5 Immunohistochemical localization of type I corticosteroid receptor (mineralocorticoid receptor) in the rat hippocampus. (A) Mineralocorticoid immunoreactivity is concentrated in pyramidal cell fields of the cornu ammonis (CA2). (B) High-power photomicrograph shows that steroid-bound mineralocorticoid receptors are primarily localized to neuronal cell nuclei. (Courtesy of Dr James P. Herman, Department of Anatomy and Neurobiology, University of Kentucky.)... 

Hydrocortisone given parenterally is the corticosteroid of choice because of its combined glucocorticoid and mineralocorticoid activity. The starting dose is 100 mg IV by rapid infusion, followed by a continuous infusion or intermittent bolus of 100 to 200 mg every 24 hours. IV administration is continued for 24 to 48 hours. If the patient is stable at that time, oral hydrocortisone can be started at a dose of 50 mg every 8 hours for another 48 hours. A hydrocortisone taper is then initiated until the dosage is 30 to 50 mg/day in divided doses. 

Corticosteroids synthesized by the adrenal gland are mineralocorticoids and GC. Min-eralocorticoids regulate fluid and electrolyte balance by affecting ion transport in the kidney. Cortisol, the primary circulating GC in most species (including humans), has many activities, including resistance to stress, regulation of intermediary metabolism, and immunosuppressive and anti-inflammatory effects. GC synthesis and secretion is... 

Triamcinolone is a corticosteroid that is more potent than hydrocortisone and has a longer duration of action. Triamcinolone has only slight mineralocorticoid activity, whereas hydrocortisone has high mineralocorticoid activity and therefore triamcinolone is unsuitable for disease suppression on a long-term basis. Triamcinolone is available as injection, dental paste, nasal spray and as cream or ointment preparations. Hydrocortisone is available as cream, tablets and injections. 

Corticosteroids are produced by the adrenal glands, and display two main types of biological activity. Glucocorticoids are concerned with the synthesis of carbohydrate from protein and the deposition of glycogen in the liver. They also play an important role in inflammatory processes. Mineralocorticoids are concerned with the control of electrolyte balance, promoting the retention of Na+ and CC, and the excretion of K+. Synthetic and semi-synthetic corticosteroid drugs are widely used in medicine. Glncocorticoids are primarily nsed for their antirhenmatic and anti-inflammatory activities, and mineralocorticoids are nsed to maintain electrolyte balance where there is adrenal insufficiency. 

However, the spectrum of biological properties of many corticosteroids, as a rule, is much broader than the spectrum of properties present in clean glucocorticoids, as well as clean mineralocorticoids by definition. 

Glucocorticoids and mineralocorticoids are uniquely produced by the adrenal cortex, and are collectively termed corticosteroids. Apart from aldosterone, glucocorticoid secretion is regulated by the pituitary hormone, corticotrophin. The principal corticosteroids synthesized in the body are illustrated in Figure 1.6. Glucocorticoids generally exhibit weak mineralocorticoid actions and vice versa. 

Various synthetic corticosteroids have also been developed. Some display greater potency than the native steroids, while others exhibit glucocorticoid activity with little associated mineralocorticoid effects, or vice versa. The major glucocorticoids used clinically are synthetic. They are usually employed as ... 

Betamethasone Synthetic corticosteroid, displays glucocorticoid activity, lacks mineralocorticoid activity Use mainly as anti-inflammatory and immunosuppressive effect... 

Deoxycortone acetate Modified form of natural corticosteroid (deoxycortone). Is a mineralocorticoid, displays no significant glucocorticoid action Used to treat Addison s disease and other adrenocortical deficiency states... 

Fludrocortisone acetate Synthetic corticosteroid with some glucocorticoid and potent mineralocorticoid activity Administered orally to treat primary adrenal insufficiency... 

GC exert their regulatory effects on the HPA system via two types of corticosteroid receptors the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) (Reul and De Kloet 1985). GRs occur everywhere in the brain but are most abundant in hypothalamic CRH neurons and pituitary corticotropes. MRs, in contrast, are highly expressed in the hippocampus and, at lower expression levels, in hypothalamic sites involved in the regulation of salt appetite and autonomic outflow. The MR binds GC with a tenfold higher affinity than does the GR (Reul and De Kloet 1985). These findings on corticosteroid receptor diversity led to the working hypothesis that the tonic influences of corticosterone... 

Fluorination of corticosteroids at C-9 or/and C-6 increases glucocorticoid activity, while mineralocorticoid activity, responsible for sodium retention (the main adverse effect of corticoids), is decreased (cf. Chapter 4). Fluorocorticoster-oids were the first fluorinated compounds to be used clinically. They are still major drugs against many inflammatory disorders rheumatoid polyarthritis, ORL (asthma, rhinitis), brain edema, dermatological, allergies, anaphylactic shock, Quincke s edema). 

Trapp T, Holsboer F Heterodimerization between mineralocorticoid and glucocorticoid receptor increases the functional diversity of corticosteroid action. Trends Pharmacol Sci 17 145-149, 1996... 

Mineralocorticoids are corticosteroids that help maintain blood volume and control renal excretion of electrolytes. Example aldosterone. 

Several biologic ligands are sufficiently lipid-soluble to cross the plasma membrane and act on intracellular receptors. One class of such ligands includes steroids (corticosteroids, mineralocorticoids, sex steroids, vitamin D), and thyroid hormone,... 

---