Glucocorticoid effect

Several cortisone derivatives with glucocorticoid effects are most active, if they contain fluorine in the 9or-position together with an Il(9-OH group. Both substituents are introduced by the cleavage of a 9,11 -epoxide with hydrogen fluoride. The regio- and stereoselective formation of the -epoxide is achieved by bromohydrination of a 9,11-double bond and subsequent alkali treatment (J. Fried, 1954). 

Steroids have mineralocorticoid and glucocorticoid effects. Betamethasone has little, if any, mineralocorticoid effect. However, it should be used with caution in patients predisposed to hypertension since mineralocorticoid effects may lead to sodium and water retention and an increase in blood pressure. When used systemically, especially at high doses, steroid therapy is associated with a risk of psychiatric reactions such as euphoria, irritability, mood lability and sleep disorders. Glucocorticoid side-effects include diabetes and osteoporosis. 

When given in larger than physiologic amounts, steroids such as cortisone and hydrocortisone, which have mineralocorticoid effects in addition to glucocorticoid effects, cause some sodium and fluid retention and loss of potassium. In patients with normal cardiovascular and renal function, this leads to a hypokalemic, hypochloremic alkalosis and eventually to a rise in blood pressure. In patients with hypoproteinemia, renal disease, or liver disease, edema may also occur. In patients with heart disease, even small degrees of sodium retention may lead to heart failure. These effects can be minimized by using synthetic non-salt-retaining steroids, sodium restriction, and judicious amounts of potassium supplements. 

A meta-analysis has shown that alfacalcidol and calci-triol prevent bone loss induced by glucocorticoid (effect size = 0.43) but not fractures (242). 

Bilateral subcapsular cataracts and glaucoma have been reported as possible risks (13), but they presumably reflect glucocorticoid effects. 

Bilateral macular degeneration has been described with tetracosactide (13), but presumably reflects glucocorticoid effects. 

Adcock IM, Ito K, Barnes PJ. Glucocorticoids effects on gene transcription. ProcAm Thorac Soc. 2004 1 247-254. 

As pointed out above, nt1 receptors have been discovered in lymphoma cells selected for resistance to the cytolytic glucocorticoid effect. Since receptors from which the M domain had been eliminated by cDNA manipulation still function to some extent in transfection studies it was important to find out whether nt1 receptors would also be able to mediate some hormonal response. This was in fact observed when nt lymphoma variants were transfected with a DNA construct consisting of the LTR region of the mouse mammary tumour virus coupled to the gene for chloramphenicol acetyltransferase (U. Gehring and H. Losert, unpublished experiments). Hormonal induction of enzyme activity was consistently observed but was low, as one might expect. 

The adrenocorticoids bind to specific intracellular cytoplasmic receptors in target tissues. The receptor-hormone complex then translocates into the nucleus where it acts as a transcription factor to turn genes on or off, depending on the tissue. This mechanism requires time to produce an effect. There are other glucocorticoid effects, such as their requirement for catecholamine-mediated dilation of vascular and bronchial musculature or lipolysis, whose effects are immediate. The bases for these actions are unknown. 

Some patients do well on hydrocortisone alone, with or without added salt, but most patients require a small amount of mineralocorticoid as well (fludrocortisone, 50-200 micrograms once a day, orally). If the dose of fludrocortisone should exceed 500 micrograms a day, an unlikely event, then its glucocorticoid effect must be taken into account. 

Elrugs with primarily glucocorticoid effects, e.g. prednisolone, are chosen, so that dosage is not limited by the mineralocorticoid effects that are inevitable with hydrocortisone. But it remains essential to use only the minimum dose that will achieve the desired effect. Sometimes therapeutic effect must be partly sacrificed to avoid adverse effects, for it has not yet proved possible to separate the glucocorticoid effects from each other indeed it is not known if it is possible to eliminate catabolic effects and at the same time retain anti-inflammatory action. In any case, in some conditions, e.g. nephrotic syndrome, the clinician cannot specify exactly what action they want the drug developer to provide. 

The release of natural corticotropin by the pituitary gland is controlled by the hypothalamus via corticotropin releasing hormone (CRH or cortico-liberin), production of which is influenced by environmental stresses as well as by the level of circulating hydrocortisone. High plasma concentration of any steroid with glucocorticoid effect... 

Horses appear to be more sensitive to the adrenosuppressive effects of aerosolized corticosteroids than human patients. Documentation of systemic absorption (adrenal suppression) of inhaled beclometasone and fluticasone raises concerns that other systemic glucocorticoid effects may occur following aerosol administration of corticosteroids. The administration of adrenosuppressive doses (>1600 p,g/day) of beclometasone dipropionate to asthmatic human patients does not produce the other systemic side-effects of glucocorticoid administration, including a roimd face (Cushingoid facies), polyuria, polydipsia, hyperglycemia, obesity, altered carbohydrate metabolism, osteoporosis, abortion, posterior subcapsular cataract and aseptic necrosis of the... 

Glucocorticoid effects involve interaction between the steroids and intracellular receptors that belong to the nuclear receptor superfamily. The effect is mediated via an interaction with DNA and modified gene transcription. Nuclear receptors for glucocorticoids are widely distributed and after activation undergo a conformational change which... 

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