Development of glucocorticoid

These steioids aie capable of preventing or suppressing the development of the sweUing, redness, local heat, and tenderness which characterize inflammation. They inhibit not only the acute symptoms of the inflammatory process, such as edema, fibrin deposition, and capillary dilatation, but also the chronic manifestations. There is evidence that glucocorticoids induce the synthesis of a protein that inhibits phosphoHpase A 2 (60), diminishing the release of arachidonic acid from phosphoHpids (Fig. 2), thereby reducing chemotaxis and inflammation. 

Several steroidal and non-steroidal glucocorticoid receptor selective dissociated agonists are in development by many pharmaceutical companies and some are now in clinical development. This suggests that the development of dissociated glucocorticoids with a greater margin of safety is possible and may even lead to the development of oral compounds that do not have significant adverse effects. 

Immunotoxicity of organotin compounds is not mediated by stress-induced release of glucocorticoids, since adrenalectomy did not prevent development of thymus atrophy (Seinen Willems, 1976). Also, adrenal weights were unaffected in these studies. 

Recommend strategies to prevent the development of Cushing s syndrome associated with exogenous glucocorticoid administration. 

Monitor for adverse reactions from hydrocortisone administration. Glucocorticoid therapy at physiologic replacement doses should not lead to the development of Cushing s syndrome. However, careful monitoring should still be performed. Use the smallest effective dose. 

Cardiovascular Keep doses of NSAIDs and glucocorticoids low, consider initiation of folic acid to reduce homocysteine level elevations induced by methotrexate, consider initiation of low-dose aspirin and/or HMG-CoA reductase inhibitors (statins), and encourage smokers to discontinue tobacco use and assist with the development of a tobacco-cessation plan.11,12... 

Horai, R. et al., Production of mice deficient in genes for interleukin (IL)-la, IL-ip, and IL-1 receptor antagonist shows that IL-lp is crucial in turpentine-induced fever development and glucocorticoid secretion, J. Exp. Med., 187, 1463, 1998. 

Primary osteoporosis is the most common form of the condition. The secondary form of osteoporosis is diagnosed when an illness and/or medications are present with a negative impact on BMD. Examples of common chronic conditions in old people that can cause secondary osteoporosis are seen in Box 5.14. Examples of drugs that can cause secondary osteoporosis are glucocorticoids, too high doses of thyroid hormone, anticonvulsants, and heparin. Especially the use of glucocorticoids has been known to cause severe osteoporosis even within a short period of treatment. Depending on the doses the development of osteoporosis can occur within a few weeks or months. 

Several drugs are known to affect calcium metabolism and to Induce calcium loss (42). Amongst these are the use of glucocorticoids and thyroid extract. The use of both of these drugs can lead to the development of osteoporosis. It Is less well known that several other... 

Short-term use of glucocorticoids, even in massive dosages, is less likely to produce harmful reactions. They can, however, produce a variety of effects that are neither limited to high doses nor to long-term therapy. When a low dose of steroids (prednisone) was given for several months to a 38-year-old man to treat eczema of his hands and feet, he developed bilateral avascular necrosis (AVN) of the femur. He therefore had total bilateral hip replacement, and several experts have attributed his AVN to the steroid administration. The man sued his allergist, who settled the lawsuit shortly before trial for approximately 400,000. Most practitioners, however, are unaware of the risk of short-term or low-dose steroids. Yet many of these cases can be found in the courts, the literature, and the MedWatch databases. 

The exogenous administration of glucocorticoids can result in hypothalamic-pituitary-adrenal axis (HPA) suppression, which may subsequently lead to adrenal atrophy The degree of adrenal suppression is dependent on the dosage, duration, frequency, time, and route of administration of the specific glucocorticoids. At least one patient who received prednisone for neurological symptoms developed Cushing s syndrome. ... 

Recent in vitro hybridization studies in the rat have demonstrated that t)rpical antidepressants increase the density of glucocorticoid receptors. Such an effect could increase the negative feedback mechanism and thereby reduce the s)mthesis and release of cortisol. In support of this hypothesis, there is preliminary clinical evidence that metyrapone (and the steroid s)mthesis inhibitor ketoconazole) may have antidepressant effects. Recently several lipophilic antagonists of corticotrophin releasing factor (CRT) type 1 receptor, which appears to be hyperactive in the brain of depressed patients, have been shown to be active in animal models of depression. Clearly this is a potentially important area for antidepressant development. 

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. 

A. Glucocorticoid treatment of rheumatoid arthritis does not eradicate all symptoms, nor does it reverse the degenerative process. Suppression of the hypothalamic-pituitary-adrenal axis is an unwanted side effect of glucocorticoid therapy. While development of a sense of well-being may be attributed to the relief of symptoms, it is not the primary basis for employing the potent glucocorticoids. 

Interestingly, while peripheral neuroendocrine function appears normal in patients with panic disorder, decreased basal cortisol concentrations have been reported in most studies in PTSD patients. This relative hypocortisolism occurs in the context of increased feedback inhibition of the HPA axis (see Yehuda, 2000). However, a dissociation between central and adrenocortical (re)activity has been found in animal models of severe early-life stress as well as in abused children and women, suggesting that adrenal dysfunction may, at least in part, contribute to hypocortisolism in PTSD. In the face of hypocortisolism, it seems surprising that hippocampal atrophy is one of the most prominent findings in patients with PTSD, including adult survivors of childhood abuse with PTSD (see Newport and Nemeroff, 2000). While increased glucocorticoid sensitivity of hippocampal cells may play a role in the development of hippocampal atrophy, another potential mechanism may involve toxic effects of markedly increased cortisol responses to everyday stress in patients with PTSD. 

Effect on GIT Glucocorticoids stimulate production of acid and pepsin in the stomach and facilitate the development of peptic ulcer. 

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