Mineralocorticoids properties

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. 

Aldosterone and other steroids with mineralocorticoid properties promote the reabsorption of sodium from the distal part of the distal convoluted tubule and from the cortical collecting renal tubules, loosely coupled to the excretion of potassium and hydrogen ion. Sodium reabsorption in the sweat and salivary glands, gastrointestinal mucosa, and across cell membranes in general is also increased. Excessive levels of aldosterone produced by tumors or overdosage with synthetic mineralocorticoids lead to hypokalemia, metabolic alkalosis, increased plasma volume, and hypertension. 

Dexamethasone has been used either in the form of the free alcohol, or in one of the esterified forms in the treatment of conditions for which corticosteroid therapy is indicated. Its return to mineralocorticoid properties makes dexamethasone particularly suitable for treating conditions where water retention would be a disadvantage. 

The mineralocorticoid properties of carbenoxolone are probably exerted by displacement of aldosterone from non-specific receptor sites in cells, thus making it more available to affect mineral metabolism. What this means in practice is that in normal doses carbenoxolone can cause salt and water retention, with occasional hypokalemia. These effects are common but usually mUd they are detected more often during treatment if patients are weighed, their blood pressure measured, and serum potassium concentrations checked. Those who take prolonged courses, elderly patients, and those with hepatic, cardiac, or renal impairment are at special risk severe effects, with serious hypertension, heart failure, and hypokalemia of sufficient degree to induce myopathy and tubular necrosis, can usually be ascribed to ill-advised treatment of people in whom carbenoxolone is contraindicated, to its use in elderly patients, or to prolonged intake without supervision. 

Mineralocorticoid refers to those steroids that regulate salt homeostasis (sodium conservation and potassium loss) and extracellular fluid volume.Aldosterone is the most potent naturally occurring mineralocorticoid and is synthesized exclusively in the zona glomerulosa region of the adrenal cortex. This zone uniquely contains the enzyme aldosterone synthase, an obligatory enzyme in the synthetic pathway to aldosterone. Other adrenocortical steroids that have mineralocorticoid properties with varying degrees of potency include DOC, 18-hydroxy-DOC, corticosterone,... 

The zona glomerulosa also secretes 18-hydroxy-corticosterone, a precursor steroid in the aldosterone biosynthetic pathway. This steroid also has mineralocorticoid properties, but is usually present in the circulation in extremely low concentrations. Mineralocorticoids are also synthesized in the zona fasciculata DOC is the most potent, but corticosterone and cortisol also have weak mineralo-corticoid activity. All of these steroids are synthesized as products of the glucocorticoid pathway. 

Those steroids whose main function is the control of electrolyte balances are known as mineralocorticoids (MC). These compounds cause Na+ retention and promote renal excretion of K+. The purpose of MCs, then, is the maintenance of salt and water balance. The major mineralocorticoid hormone is aldosterone (Fig. 10-24, and relevant discussion). It should be pointed out that aldosterone has somewhat weak glucocorticoid effects and cortisol exhibits slight mineralocorticoid properties. 

Hydrocortisone is an adrenocorticoid with both glucocorticoid and mineralocorticoid properties. It is a weak antiinflammatory agent but a potent mineralocorticoid, having potency similar to that of cortisone and twice that of prednisone. Hydrocortisone (or cortisone) is usually the drug of choice for replacement therapy in patients with adrenal insufficiency. It is usually not used for immunosuppressant... 

Methylprednisolone is an intermediate-acting glucocorticoid with no mineralocorticoid properties (see also Tables 11 and 14). Glucocorticoids are used in ... 

Cortisone acetate or hydrocortisone usually is the corticosteroid of choice for replacement therapy in patients with adrenocortical insufficiency, because these drugs have both glucocorticoid and mineralocorticoid properties. Following oral administration, cortisone acetate and hydrocortisone acetate are completely and rapidly deacetylated by first-pass metabolism (37). Much of the oral cortisone, however, is inactivated by oxidative metabolism (Fig. 33.9) before it can be converted to hydrocortisone in the liver. The pharmacokinetics for hydrocortisone acetate is indistinguishable from that of orally administered hydrocortisone. Oral hydrocortisone is completely absorbed, with a bioavailability of greater than 95% and a half-life of 1 to 2 hours (23). The metabolism of hydrocortisone (Fig. 33.9) has been previously described. Cortisone acetate is slowly absorbed from IM injection sites over a period of 24 to 48 hours and is reserved for patients who are unable to take the drug orally. The acetate ester derivative demonstrates increased stability and has a longer duration of action when administered by IM injection. Thus, smaller doses can be used. Similarly, hydrocortisone may be dispensed as its 21-acetate (hydrocortisone acetate), which is superior to cortisone acetate when injected intra-articularly. Systemic absorption of hydrocortisone acetate from intra-articular injection sites usually is complete within 24 to 48 hours. When administered intrarectally, hydrocortisone is poorly absorbed (38,39). 

Adding a 6a-methyl group to prednisolone increases the glucocortiooid activity and effectively abolishes mineralooortiooid aotion. It has fivefold the gluoocorticoid activity of hydrocortisone (prednisolone has fourfold the gluoocorticoid activity) and none of its mineralocorticoid properties. It is used almost exolusively as a systemio product and is available as the free alcohol for oral administration and as various esters (Table 44.7). 

Note All adrenocorticoid drugs have both glucocorticoid and mineralocorticoid properties to some extent]... 

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. 

Carbenoxolone is a derivative of glycyrrhizic acid and both carbenoxolone and liquorice have ulcer healing properties. However, carbenoxolone has considerable mineralocorticoid activity, frequently producing Na+ and fluid retention, hypertension and hypokalemia. It is therefore not generally recommended for routine use. 

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. 

Because of its mineralocorticoid fluid-retaining properties, carbenoxolone opposes the therapeutic effects of diuretics and other drugs used to treat hypertension. 

While the progestogens have certain characteristic effects of their own, notably on the female menstrual cycle, the spectrum of adverse effects of any particular progestogen (particularly when given in high doses) is likely to depend heavily on the extent to which it also has glucocorticoid, mineralocorticoid, estrogenic, or androgenic properties. 

B Methylprednisolone. Given the patient s electrolyte abnormalities, all of the other corticosteroid options would be ruled out since they have mineralocorticoid effects that may make this patient s electrolyte abnormalities worse. Methylprednisolone has anti-inflammatory properties and no mineralocorticoid activity. 

For patients who are hospitalized and present with electrolyte abnormalities, corticosteroids with high anti-inflammatory properties and minimal mineralocorticoid activity are preferred. 

A -cortisol prednisolone, cortisone (ban. inn] (cortisone acetate [usan] Kendall s compound E Reichstein s Substance Fa Wintersteiner s compound F NSC 9703 Cortisyl ) is a natural adrenal cortical hormone, a CORTICOSTEROID, which is converted to hydrocortisone in the liver. It has both GLUCOCORTICOID and MINERALOCORTICOID activity. It can therefore be used orally to make up for hormonal deficiency (especially mineral balance), for instance, following surgical removal of the adrenal glands. It can also be used for its ANTIINFLAMMATORY and ANTIALLERGIC properties in treating rheumatoid arthritis and in rheumatic fever therapy, cortisone acetate cortisone. 

There are essential structural features that are necessary for glucocorticoid activity. The natural glucocorticoids also interact with the mineralocorticoid receptor and, therefore, will have salt-retaining properties. A large number of synthetic analogues have been prepared to decrease the mineralocorticoid effects in favor of increasing the glucocorticoid (anti-inflammatory) effect of the steroids. In addition, many derivatives are prepared to enhance pharmacokinetic parameters, most notably the synthesis of lipophilic and hydrophilic esters. 

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