Glucocorticoids properties

Relative comparison, setting the mineralcorticoid and glucocorticoid properties of hydrocortisone as 1. 

The discovery in 1954 that fluorination of the glucocorticoid hormone cortisol could bring about remarkable changes in the biological properties of the hormone was entirely unexpected and violated the then prevalent belief that synthetic variants could not surpass a naturally occurring hormone in its biological activity. Because of the impact that fluorination of steroids has had on subsequent developments in this area the history of the discovery of fluorocortisol will be briefly recounted. 

Asthma is a chronic inflammatory disease. Therefore steroids represent the most important and most frequently used medication. Already after the fust treatment, steroids reduce cellular infiltration, inflammation, and the LAR, whereas changes in the EAR require prolonged treatment to lower the existent IgE levels. The mechanisms of steroid actions are complex and only incompletely understood. Besides their general antiinflammatory properties (see chapter glucocorticoids), the reduction of IL-4 and IL-5 production from T-lymphocytes is particularly important for asthma therapy. The introduction of inhaled steroids, which have dramatically limited side effects of steroids, is considered one of the most important advancements in asthma therapy. Inhaled steroids (beclomethasone, budesonide, fluticasone, triamcinolone, momethasone) are used in mild, moderate, and partially also in severe asthma oral steroids are used only in severe asthma and the treatment of status asthmaticus. Minor side effects of most inhaled steroids are hoarseness and candidasis, which are avoided by the prodrug steroid ciclesonide. 

In order to review these putative relationships it is first useful to define a subset of well-characterized hormones and neurotransmitters that have been implicated in behavior. The chemicals selected for discussion here are among those for which a robust relationship with behavior has been proposed, including steroids (estrogens, progestins, androgens and glucocorticoids), proteins (prolactin) and the neuropeptides (oxytocin and vasopressin). All of these chemicals may act as hormones, neurotransmitters and/or neuromodulators. In addition, to understand the action of these hormones, it is helpful to be familiar with some of the more common neurotransmitters (described below). Space does not permit a discussion of the behavioral effects of many additional compounds with endocrine or paracrine properties. 

Oakley RH, Sar M, Cidlowski JA. (1996) The human glucocorticoid receptor beta isoform. Expression, biochemical properties, and putative function. J Biol Chem. 271, 9550-9559. 

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. 

Unlike glucocorticoids, mineralocorticoids have an insignificant effect on carbohydrate volume. They do not exhibit any anti-inflammatory or anti-aUergy properties. They are used for chronic adrenal insufficiency, as well as for raising tonicity and work capacity of muscles. 

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 steroid-inhibiting properties of metyrapone have also been used in the treatment of Cushing s syndrome, and it remains one of the more effective drugs used to treat this syndrome. However, the compensatory rise in corticotrophin levels in response to falling cortisol levels tends to maintain adrenal activity. This requires that glucocorticoids be administered concomitantly to suppress hypothalamic-pituitary activity. Although metyrapone interferes with lip- and 18-hydroxylation reactions and thereby inhibits aldosterone synthesis, it may not cause mineralocorticoid deficiency because of the compensatory increased production of 11-desoxycorticosterone. 

Corticosterone. A natural corticoid with moderate glucocorticoid activity and some mineralocorticoid activity, possessing life-maintaining properties in adrenalectomized animals and several other activities peculiar to the adrenal cortex. Its actions closely resemble those of cortisol, except that it is not anti-inflammatory. 

The glucocorticoids also have powerful anti-inflammatory effects and when first introduced were considered to be the ultimate answer to the treatment of inflammatory arthritis. Although there are increasing data that low-dose corticosteroids have disease-modifying properties,... 

Glucocorticoids (corticosteroids) were the first hormonal agents recognized as having lympholytic properties. Administration of any glucocorticoid reduces the size and lymphoid content of the lymph nodes and spleen, although it has no toxic effect on proliferating myeloid or erythroid stem cells in the bone marrow. 

Glucocorticoids have potent anti-inflammatory and immunosuppressive properties. This is particularly evident when they are administered at pharmacological doses. A variety of synthetic glucocorticoids, some far more potent than cortisol, have been created for therapeutic use, such as hydrocortisone, prednisone, prednisolone, dexamethasone and betamethasone. 

The adrenal cortex produces steroidal hormones that are associated with carbohydrate, fat, and protein metabolism, electrolyte balance, and gonadal functions. One of these, cortisone. C2iH2805 (11), demonstrated a remarkable ability to relieve the symptoms of inflammatory conditions. Other glucocorticoid steroids, such as dexamethasone, Cj2H2gFO< (12, R = F, R = CIlj), and prednisolone, U21II28O5 (12, R — R — 11), also have antiinflammatory properties. 

However, corticosteroids and their metabolites (1) were early recognized as possessing powerful antiinflammatory and immunomodulatory properties. Even prior to 1950, reports of the antiarthritic properties of cortisone (1) by Hench and co-workers (2) indicated the potential for these compounds to reduce the suffering of patients with inflammatory diseases. This awareness, combined with the first synthesis of naturally occurring glucocorticoids (11-desoxycorticosterone), led not only to the massive increase in research in the area of steroid synthesis and physiology, but to a Nobel prize in 1950 for early steroid pioneers Hench, Reichstein, and Kendall. 

Since the glucocorticoids have immunosuppressive and anti-inflammatory properties, one would not expect allergic reactions to be a problem, except when excipients act as allergens. Nevertheless, allergic reactions to glucocorticoids themselves have been reported (SEDA-21, 419 291). Immunological reactions to glucocorticoids have... 

Pneumocystis jiroveci pneumonia has been precipitated or aggravated by glucocorticoids (SEDA-20, 377 SEDA-22, 450 272,350,351). There is some concern about the use of glucocorticoids as adjunctive therapy in patients with AIDS who develop Pneumocystis jiroveci pneumonia. The immunosuppressant properties of glucocorticoids have been reported to enhance the risk of tuberculosis and other AIDS-related diseases (for example Kaposi s sarcoma or cytomegalovirus infection). 

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