Mineralocorticoid effect

Fludrocortisone is used for replacement therapy for primary and secondary adrenocortical deficiency. Even though this drug lias both mineralocorticoid and glucocorticoid activity, it is used only for its mineralocorticoid effects. 

Hypokalemic alkalosis (from mineralocorticoid effect of cortisol)... 

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. 

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 ... 

Most glucocorticoids have some mineralocorticoid effect, which is usually considered an undesirable activity. Through structural chemistry and structure-activity relationship (SAR) studies, molecular modifications can separate the two activities. 

Synthetic glucocorticoids are prednisolone, prednisone, methylprednisolone, dexamethasone, betamethasone and triamcinolone (Table 13.2). Hydrocortisone is available as either succinate or phosphate salts for oral and intravenous administration. It is the drug of choice when a rapid effect is required, e.g. acute adrenal insufficiency, or as peri-operative replacement therapy. Prednisolone can also be given intravenously. It has about 0.8 of the mineralocorticoid activity of hydrocortisone. Prednisone is a prodrug that is converted to prednisolone in the body. For chronic therapy, synthetic steroids without mineralocorticoid activity are preferred, such as dexamethasone, betamethasone or triamcinalone. Beclo-metasone passes membranes poorly and is more active topically than when given orally. It is used as an aerosol for chronic rhinitis and asthma, and topically in severe eczema. Fludrocortisone is a synthetic halogenated derivate of cortisol that is used for its mineralocorticoid effect. 

Some of the effects of glucocorticoids can be attributed to their binding to aldosterone receptors (ARs). Indeed, ARs bind aldosterone and cortisol with similar affinity. A mineralocorticoid effect of cortisol is avoided in some tissues by expression of llE>-hydroxysteroid dehydrogenase type 2, the enzyme responsible for biotransformation to its 11-keto derivative (cortisone), which has minimal affinity for aldosterone receptors. 

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. 

Glucocorticoid preparations differ with respect to relative anti-inflammatory and mineralocorticoid effect, duration of action, cost, and dosage forms available (Table 39-1), and these factors should be taken into account in selecting the drug to be used. 

When selecting a drug for use in large doses, a medium- or intermediate-acting synthetic steroid with little mineralocorticoid effect is advisable. If possible, it should be given as a single morning dose. 

Hypokalemia, secondary to mineralocorticoid effects, can cause cardiac dysrhythmias and cardiac arrest. 

Fluid retention due to mineralocorticoid effects can cause cardiac failure (1). 

On inorganic metabolism (mineralocorticoid effects) increased retention of sodium by the renal tubule, and increased potassium excretion in the urine. 

Spironolactone (see p. 534) is a competitive aldosterone antagonist which also blocks the mineralocorticoid effect of other steroids it is used in the treatment of primary hyperaldosteronism and as a diuretic, principally when severe oedema is due to secondary hyperaldosteronism, e.g. cirrhosis, congestive cardiac failure. 

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. 

Therapeutic use is seldom appropriate because the peptide hormone has to be injected selective glucocorticoid action (without mineralocorticoid effect) cannot be obtained, and clinical results are irregular. Corticotropin can not be relied on to restore adrenal cortisol output when a steroid is being withdrawn after prolonged therapy, as it does not restore function in the suppressed hypothalamic/pituitary part of the HPA axis. 

Licorice Antihypertensives Corticosteroids Digoxin Diuretics Antagonism of hypotensive effects Additive mineralocorticoid effects Risk of toxicity due to hypokalemia Additive hypokalemia... 

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. 

Excessive licorice ingestion may cause a form of chloride resistant alkalosis. Black licorice contains glycyrrhizic acid, which inhibits the enzyme ll-p hydroxysteroid dehydrogenase, which in turn catalyzes the conversion of cortisol to cortisone. The excess cortisol exerts a mineralocorticoid effect on the distal tubule aldosterone receptors. ... 

Mineralocorticoid excess also plays a significant role in the maintenance of metabolic alkalosis. In patients with volume-responsive metabolic alkalosis, intravascular volume depletion stimulates aldosterone secretion. As discussed earlier, excess mineralocorticoid activity may also underlie the generation of metabolic alkalosis. In either situation, the increased mineralocorticoid effect stimulates collecting duct H+ secretion. Metabolic alkalosis may also be maintained by persistent hypokalemia. Hypokalemia has a multitude of effects on renal acid-base homeostasis, enhancing proximal tubular bicarbonate reabsorption, stimulating ammoniagenesis and increasing distal tubular H secretion. ... 

A product, deglycyrrhizinised liquorice, in which the mineralocorticoidal effect is eliminated the exact mechanism of action is not known, but it provokes an increased production of mucin, increased number of new cells in the gastric mucosa and a spasmolytic effect. It is frequently formulated with some inorganic antacids. 

Licorice has a well-documented mineralocorticoid-like effect. This effect occurs not because licorice mimics mineralocorticoid action, but rather is due to the inhibition of 11-P-hydroxysteroid dehydrogenase (1 lP-OHSD), the enzyme that catalyzes the conversion ofcortisol to cortisone (Stewart et al., 1987). Deficiency or inhibition of this enzyme leads to an increase in renal cortisol, which can bind to mineralocorticoid receptors (Stewart et al., 1987). The inhibiting substance in licorice appears to be 3-monoglucuronylglycyrrhetinic acid, a metabolite of glycyrrhetinic acid (Kato et al., 1995). This resultant mineralocorticoid effect may cause sodium retention, hypertension, hypokalemia, and suppression of plasma renin activity (Epstein et al. 977). 

The cortisol molecule also has a small but significant salt-retaining (mineralocorticoid) effect. This is an importsuit cause of hypertension in patients with a cortisol-secreting adrenal tumor or a pituitary ACTH-secreting tumor (Cushing s syndrome). 

Hydrocortisone (e.g., Hydrocort) PO/IV/IM. Chemically identical to cortisol produced by adrenal glands. Preferred drug for replacement therapy. Has weak mineralocorticoid effects. Short acting. 

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