Corticosteroid secretion

Prostatic cancer In clinical trials involving 350 patients with metastatic prostatic cancer, 11 deaths were reported within 2 weeks of starting high-dose ketoconazole (1200 mg/day). It is not known whether death was related to therapy. High ketoconazole doses are known to suppress adrenal corticosteroid secretion. Hypersensitivity reactions Anaphylaxis occurs rarely after the first dose. Hypersensitivity reactions, including urticaria, have been reported. 

Cortisone is a natural corticosteroid secreted by the adrenal cortex along with many steroidal hormones. It has mainly glucocorticoidal activity and some degree of mineralo-corticoid activity. 

Warnings Hepatotoxicity, primarily of the hepatocellular type, has been reported Anaphylaxis may occur after the first dose Deaths within 2 weeks of treatment initiation have been reported in patients with prostate cancer the role of ketoconazole in these deaths has not been ascertained, but it is known that ketoconazole can suppress adrenal corticosteroid secretion... 

Varga I, Racz K, Kiss R, Futo L, Toth M, Sergev O, Glaz E. Direct inhibitory effect of etomidate on corticosteroid secretion in human pathologic adrenocortical cells. Steroids 1993 58(2) 64-8. 

Corticotropin (corticotrophin adrenocorticotrophin ACTH) is a straight-chain polypeptide with39 amino acid residues, and its function is to control the activity of the adrenal cortex, particularly the production of corticosteroids. Secretion of the hormone is controlled by corticotropin-releasing hormone (CRH) from the hypothalamus. ACTH was formerly used as an alternative to corticosteroid therapy in rheumatoid arthritis, but its value was limited by variable therapeutic response. ACTH may be used to test adrenocortical function. It has mainly been replaced for this purpose by the synthetic analoguetetracosactide (tetracosactrin) (Figure 7.10), which contains the first 24 amino acid residues of ACTH, and is preferred because of its shorter duration of action and lower allergenicity. 

Cortisone is a corticosteroid secreted by the adrenal cortex. It has glucocorticoid activity, as well as appreciable mineralocorticoid activity 25 mg cortisone acetate is equivalent in anti-inflammatory activity to about 5 mg prednisolone. 

All plant parts contain 13 capon glycosides. Two of these agents have a prolonged anti-inflammatory action similar to that of nonsteroidal anti-inflammatory medications. Another component is thought to affect corticosteroid secretion in the central nervous system. The fusiform roots are recognized for their vitamin and mineral content. 

Both type I and II pyrethroids cause marked adrenal activation in rats, probably by a direct activation of norepinephrine release. The type II pyrethroid deltamethrin causes increased corticosteroid secretion, and even moderate pyrethroid poisoning occurs against a background of profound adrenal activation - with corresponding behavioral and cardiovascular consequences. With only type II pyrethroids there is also a direct increase in cardiac contractility, although blood pressure remains well controlled. 

Time of Administration The presence or absence of food in the gastrointestinal tract, corticosteroid secretion rhythm, circadian cycle, urinary excretion pattern, fluid intake, and drug-metabolizing enzyme rhythms all can influence the effect of the medication. 

Exposure to both cold (K3) and heat (34°C) (K4, K5) will lead to stimulation of corticosteroid secretion within 24 hours, but we have shown that exposure to 30° C results in plasma corticosterone levels below those of controls at 20°C in the rat (T4). 

J3. James, V. H. T., Corticosteroid secretion by human placenta and foetus. European J. Steroids 1, 1-14 (1966). 

Glucocorticoids produce many adverse effects, especially with the high doses required for anti-inflammatory activity. (Similar effects arc produced by the excess corticosteroids secreted in Cushing s syndrome.)... 

HT has been found to stimulate corticosteroid secretion in various models. In addition, 5-HT is present in adrenochromaffin cells, but also in mast cells localized at the adrenocortical level [98, 99]. Therefore, 5-HT released within the adrenal gland may have a paracrine effect on corticoid secretion. In- frog and human, the receptor involved in 5-HT induced cortisol secretion displays the pharmacological profile of a typical 5-HT4-R [98, 99]. In human volunteers the aldosterone-stimulating effects were observed after administration of 5-HT4-agonists [137]. 

The greatest potassium loss occurs with the naturally occurring corticosteroids such as cortisone and hydrocortisone. Corticotropin (ACTH), which is a pituitary hormone, and tetracosactrin (a synthetic polypeptide) stimulate corticosteroid secretion by the adrenal cortex and can thereby indirectly cause potassium loss. Fludrocortisone also causes potassium loss. The synthetic corticosteroids (glucocorticoids) have a less marked potassium-depleting effect and are therefore less likely to cause problems. These include betamethasone, dexamethasone, prednisolone, prednisone and triamcinolone. 

There are many examples in mammalian cells in which the effectuation of hormone action is associated with variations in calcium concentration in the different cellular compartments. Such hormonal actions include stimulation of corticosteroid secretion in the adrenal, the effect of parathyroid hormone on renal tubules, reabsorption and release of calcium from the bone, the effect of melanocyte hormone on melano-phores, the stimulation of smooth muscle contraction by acetylcholine and its retraction by epinephrine, the effect of epinephrine on heart contraction, etc. The role of calcium in the sequence of steps following the hormonal stimulus is often difficult to interpret. 

Stress that leads to epinephrine secretion stimulates corticosteroid secretion, leading to reduced LH secretion. 

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