Glucocorticoids, effect metabolism

Inhaled glucocorticoid preparations, such as be-clomethasone dipropionate and betamethasone valerate, provide an effective alternative to systemic steroids in the treatment of chronic asthma, with lesser side effects than oral or parenteral glucocorticoids (see Chapter 39). In fact, inhaled glucocorticoids have become a mainstay of asthma therapy. Inhalation delivers the agent directly to the target site in relatively low doses, with the potential for more frequent administration. Moreover, inhaled glucocorticoids are metabolized in the lung before they are absorbed, which reduces their systemic effects. However, even modest doses of... 

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... 

Shimoyama M, Kitamura A, Tanigawa Y (1982) Glucocorticoid effects on poly (ADP-ribose) metabolism. In Hayaishi 0, Ueda K (eds) ADP-ribosylation reactions. Academic Press, London New York, pp 465-475... 

Besides the mineralcorticoid effect on the electrolyte metabolism, the adrenocortical hormones also influence the metabolism of glucose by promoting glycogen formation in the liver, especially from protein. This effect is termed the glucocorticoid effect and is manifested especially by the 11/3-hydroxy compounds. Emphasizing the breakdown of protein, this effect is also called the catabolic effect. The mechanism of this hormone action seems to involve the de novo formation of more enzymes of amino acid metabolism, e.g., tyrosine a-ketoglutarate transaminase, tr5rptophan pyrrolase, etc. (cf. Enzyme Induction, Chapt. VII-7). 

In the ebb phase, there is increased activity of the sympathetic nervous system and increased plasma levels of adrenaline and glucocorticoids but a decreased level of insulin. This results in mobilisation of glycogen in the liver and triacylglycerol in adipose tissue, so that the levels of two major fuels in the blood, glucose and long-chain fatty acids, are increased. This is, effectively, the stress response to trauma. These changes continue and are extended into the flow phase as the immune cells are activated and secrete the proinflammatory cytokines that further stimulate the mobilisation of fuel stores (Table 18.2). Thus the sequence is trauma increased endocrine hormone levels increased immune response increased levels of cytokines metabolic responses. 

A large amount of clinical data is available on some of the common anti-inflammatory drugs such as glucocorticoids and NSAIDs. Coupling of these drugs to drug carriers may favourably affect kinetics and metabolism, thereby improving effectiveness and safety. So,... 

Cortisol, the most important g/ucocorticoid, is synthesized by the adrenal cortex, it is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose. As a result, the blood glucose level rises (see p. 152). Synthetic glucocorticoids (e.g., dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects. 

Glucocorticoids are endogenous compounds that have an effect on carbohydrate, lipid, and protein metabolism, and which exhibit anti-inflammatory, desensitizing, and anti-aUergy action. They are immunodepressants, and they also possess anti-shock and anti-toxic action. 

The glucocorticoids induce a number of biological effects (Table 1.14), but their principal actions relate to modulation of glucose metabolism. The mineralocorticoids regulate water and... 

Such a medical adrenalectomy is an efficacious treatment for metastatic breast and prostate cancer, since it diminishes the levels of circulating sex hormones. Glucocorticoids are administered concomitantly to suppress enhanced corticotrophin release. Cortisol is preferable to dexamethasone in this situation because aminoglutethimide markedly enhances the hepatic microsomal metabolism of dexamethasone. Hepatic enzyme induction may be responsible for the development of tolerance to the side effects of aminoglutethimide, such as ataxia, lethargy, dizziness, and rashes. 

Mechanism of Action A long-acting glucocorticoid that inhibits accumulation of inflammatory cells at inflammation sites, phagocytosis, lysosomal enzyme release and synthesis, and releaseof mediators of inflammation. Therapeutic Effect Prevents and suppresses cell and tissue immune reactions and inflammatory process. Pharmacohinetics Rapidly, completely absorbed from the G1 tract after oral administration. Widely distributed. Protein binding High. Metabolized in the liver. Primarily excreted in urine. Minimally removed by hemodialysis. Half-life 3-4.5 hr. 

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