Corticosteroids excretion

Table 5.3.10 Corticosteroid excretion (fig/24 h) and diagnostic ratios in glucocorticoid remediable aldosteronism (GRA)...

V8. Visser, H. K. A, and Cost, W. S., C21-Corticosteroid excretion pattern in a familiar salt-losing syndrome. A new enzyme defect in the biosynthesis of aldosterone. Acta Endocrinol. Suppl. 89, 31-32 (1964). 

The saturated Cai compounds are then either conjugated with glucuronic acid and appear in urine as the glucuronides, or they are further broken down. The side chain is split off particularly easily from 17-hydroxy compounds. The products are 17-keto steroids, androsterone, etiocholanolone, and. others, which are also excreted as glucuronides (more rarely as sulfates). The amount of 17-keto steroids in urine can be estimated easily with Zimmermann s color reaction it is useful for the diagnosis of adrenal cortical activity. One should be aware, however, that only a part of the corticosteroid excretion is measured, together vith testosterone inactivation products. Normally, about 10-20 mg per day of 17-keto steroids are excreted. 

Factors that can predispose patients to developing metabolic bone disease include deficiencies of phosphorus, calcium, and vitamin D vitamin D and/or aluminum toxicity amino acids and hypertonic dextrose infusions chronic metabolic acidosis corticosteroid therapy and lack of mobility.35,39 Calcium deficiency (due to decreased intake or increased urinary excretion) is one of the major causes of metabolic bone disease in patients receiving PN. Provide adequate calcium and phosphate with PN to improve bone mineralization and help to prevent metabolic bone disease. Administration of amino acids and chronic metabolic acidosis also appear to play an important role. Provide adequate amounts of acetate in PN admixtures to maintain acid-base balance. 

N. Bodor, T. Loftsson, W. M. Wu, Metabolism, Distribution, and Transdermal Permeation of a Soft Corticosteroid, Loteprednol Etabonate , Pharm. Res. 1992, 9, 1275-1278 N. Bodor, W. M. Wu, T. Murakami, S. Engel, Soft Drugs 19. Pharmacokinetics, Metabolism and Excretion of a Novel Soft Corticosteroid, Loteprednol Etabonate, in Rats , Pharm. Res. 1995, 72, 875-879. 

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. 

A rhythmic variation has been observed in levels of plasma hydroxy-corticosteroids (A9, B13, D9) and in the excretion of 17-ketosteroids (P7). As shown in Table 5, urinary excretions of potassium, sodium, chloride, 17-hydroxycorticosteroids and water have been reported to be greatest between 10 am to noon and lowest between 4 am and 6 am (S21). In this study it was shown that within 5 weeks subjects could acclimate to similar patterns for a 21-hour, rather than a 24-hour, day. Heilman and his associates reported that about half of the day s cortisol production is achieved in the early morning hours during sleep and that production is minimal between noon and 10 pm (H7). In one study the plasma cortisol in normal men was 24.6 5.5 /xg/100 ml at 7 am 13.1 3.4 fig/100 ml at 9 am 11.8 fig/100 ml at noon 9.1 2.3 jag/100 ml at 7 PM and 6.3 /ig/100 ml at 10 pm (A9). 

Oral Treatment of hypokalemia in the following conditions With or without metabolic alkalosis digitalis intoxication familial periodic paralysis diabetic acidosis diarrhea and vomiting surgical conditions accompanied by nitrogen loss, vomiting, suction drainage, diarrhea, and increased urinary excretion of potassium certain cases of uremia hyperadrenalism starvation and debilitation corticosteroid or diuretic therapy. 

Lactation Glucocorticoids are excreted in breast milk. It is not known whether inhaled corticosteroids are excreted in breast milk, but it is likely. 

Corticosteroid metabolites are excreted in the urine by the kidneys mainly as glucuronides and sulfates, but also as non-conjugated products. Small amounts of non-metabolized drugs are also excreted in the urine, while negligible amounts of most of the drugs are excreted in the bile. 

Mechanism of Action Topical corticosteroids exhibit anti-inflammatory, antipruritic, and vasoconstrictive properties. Clinically, these actions correspond to decreased edema, erythema, pruritus, plaque formation, and scaling of the affected skin. Pharmacokinetics Approximately 3% is absorbed during an 8-hr period. Metabolized in the liver. Excreted in the urine. 

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

Praziquantel is a synthetic isoquinoline-pyrazine derivative. It is rapidly absorbed, with a bioavailability of about 80% after oral administration. Peak serum concentrations are reached 1-3 hours after a therapeutic dose. Cerebrospinal fluid concentrations of praziquantel reach 14-20% of the drug s plasma concentration. About 80% of the drug is bound to plasma proteins. Most of the drug is rapidly metabolized to inactive mono- and polyhydroxylated products after a first pass in the liver. The half-life is 0.8-1.5 hours. Excretion is mainly via the kidneys (60-80%) and bile (15-35%). Plasma concentrations of praziquantel increase when the drug is taken with a high-carbohydrate meal or with cimetidine bioavailability is markedly reduced with some antiepileptics (phenytoin, carbamazepine) or with corticosteroids. 

Rationally, 5/3-reduclase deficiency would not be a cause of MPH, but it seems appropriate to place this disorder adjacent to its 5a-counterpart. 5/3-Reductase (AKR1D1) is an essential bile-acid biosynthetic enzyme and patients with disabling mutations in this enzyme have a clinical phenotype associated with cholestasis and fiver failure. In addition to its importance in bile-acid synthesis, this aldoketo-reductase is responsible for reducing approximately two-thirds of the mass of synthesized androgens, corticosteroids, and aldosterone prior to their excretion, so has a vital role in steroid metabolism. 

We studied by GC-MS the urinary excretion of a single patient with a documented mutation [49] and have found that the 5/3-reduced androgen metabolite excretion relative to 5a is decreased by about 80%, and 5/ -corticosteroid metabolite excretion is essentially absent [63]. To date there has no report of an adverse endocrine phenotype related to corticosteroid, mineralocorticoid, or androgen metabolism. 

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