Glucocorticoid adverse effects

Buffington GA, Dominguez JH, Piering WF, Hebert LA, Kauffinan HM, Lemann J. Interaction of rifampin and glucocorticoids. Adverse effect on renal allc aft function. JAMA (1976) 236, 1958-60,... 

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. 

Budesonide is a high-potency glucocorticoid used in CD that has low systemic bioavailability when administered orally.23 The formulation releases budesonide in the terminal ileum for treatment of disease involving the ileum or ascending colon. Due to its reduced bioavailability, budesonide may prevent some long-term adverse effects in patients who have steroid-dependent IBD.23,24... 

Intraarticular injections of depot forms may be useful when only a few joints are involved. If effective, injections may be repeated every 3 months. No one joint should be injected more than two or three times per year. Adverse effects of systemic glucocorticoids limit their long-term use. Dosage tapering and eventual discontinuation should be considered at some point in patients receiving chronic therapy. 

The well-appreciated adverse effects of glucocorticoids include hyperglycemia, hypertension, osteoporosis, fluid retention and electrolyte disturbances, myopathies, psychosis, and reduced resistance to infection. In addition, glucocorticoid use may cause adrenocortical suppression. Specific regimens for withdrawal of glucocorticoid therapy have been suggested. 

Orally administered glucocorticoids have substantial adverse effects, including immunosuppression, suppression of the synthesis of endogenous glucocorticoids themselves (that can be a problem when glucocorticoid therapy is stopped), resorption of bone, and retention of water. Nonetheless, they are important drugs for control of inflammation. They also augment resistance to stress. 

Pharmacotherapy. Acute relief of inflammatory symptoms can be achieved by prostaglandin synthase inhibitors nonsteroidal anti-inflammatory drugs, or NSAlDs, such as diclofenac, indomethacin, piroxicam, p. 200), and glucocorticoids (p. 248). The inevitably chronic use of NSAlDs is likely to cause adverse effects. Neither NSAlDs nor glucocorticoids can halt the progressive destruction of joints. 

The first point is that treatment with steroids is generally palliative rather than curative, and only in a very few diseases, such as leukemia and nephrotic syndrome, do corticosteroids alter prognosis. One must also consider which is worse, the disease to be treated or possible induced hypercortisolism. The patient s age can be an important factor, since such adverse effects as hypertension are more apt to occur in old and infirm individuals, especially in those with underlying cardiovascular disease. Glucocorticoids should be used with caution during pregnancy. If steroids are to be employed, prednisone or prednisolone should be used, since they cross the placenta poorly. 

D. Dexamethasone is a fluorinated glucocorticoid that is more potent and longer acting than cortisol. While devoid of salt-retaining activity in therapeutic doses, this glucocorticoid does possess most of the adverse effects observed with cortisol. Because it lacks mineralocorticoid activity, dexamethasone is not used in replacement therapy. 

Fluorination of corticosteroids at C-9 or/and C-6 increases glucocorticoid activity, while mineralocorticoid activity, responsible for sodium retention (the main adverse effect of corticoids), is decreased (cf. Chapter 4). Fluorocorticoster-oids were the first fluorinated compounds to be used clinically. They are still major drugs against many inflammatory disorders rheumatoid polyarthritis, ORL (asthma, rhinitis), brain edema, dermatological, allergies, anaphylactic shock, Quincke s edema). 

Long term use of glucocorticoids is associated with several adverse effects. High circulating... 

The glucocorticoids have important dose-related effects on carbohydrate, protein, and fat metabolism. The same effects are responsible for some of the serious adverse effects associated with their use in therapeutic doses. Glucocorticoids stimulate and are required for gluconeogenesis and glycogen synthesis in the fasting state. They stimulate phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and glycogen synthase and the release of amino acids in the course of muscle catabolism. 

When glucocorticoids are used for short periods (< 2 weeks), it is unusual to see serious adverse effects even with moderately large doses. However, insomnia, behavioral changes (primarily hypomania), and acute peptic ulcers are occasionally observed even after only a few days of treatment. Acute pancreatitis is a rare but serious acute adverse effect of high-dose glucocorticoids. 

Glucocorticoids are commonly used in the treatment of patients with moderate to severe active inflammatory bowel disease. Active disease is commonly treated with an initial oral dosage of 40-60 mg/d of prednisone or prednisolone. Higher doses have not been shown to be more efficacious but have significantly greater adverse effects. Once a patient responds to initial therapy (usually within 1-2 weeks), the dosage is tapered to minimize development of adverse effects. In severely ill patients, the drugs are usually administered intravenously. 

Substitution therapy is used in cases of primary and secondary adrenocortical insufficiency the aim is to provide glucocorticoids and mineralocorticoids in physiological amounts, and the better the dosage regimen is adapted to the individual s needs, the less the chance of adverse effects (1). 

The incidence and severity of adverse reactions to glucocorticoids depend on the dose and duration of treatment. Even the very high single doses of glucocorticoids, such as methylprednisolone, which are sometimes used, do not cause serious adverse effects, whereas an equivalent dose given over a long period of time can cause many long-term effects. 

This report highlights the risk of cardiovascular adverse effects with short courses of glucocorticoid therapy in elderly patients with inflammatory bowel disease, even with rather low-dosage regimens. Acute myocardial infarction occurred in an old man with coronary insufficiency and giant cell arteritis after treatment with prednisolone (SEDA-10, 343) but could well have been coincidental. 

Local adverse effects are common in patients with asthma who use inhaled glucocorticoids, as suggested by a survey of the prevalence of throat and voice symptoms in patients with asthma using glucocorticoids by metered-dose pressurized aerosol (SEDA-20, 369 35). 

Ocular hypertension and open-angle glaucoma are well-known adverse effects of ophthalmic administration of glucocorticoids (SEDA-17, 449). 

Glucocorticoids can cause neuropsychiatric adverse effects that dictate a reduction in dose and sometimes withdrawal of treatment. Of 32 patients with asthma (mean age 47 years) who took prednisone in a mean dosage of 42 mg/day for a mean duration of 5 days, those with past or current symptoms of depression had a significant reduction in depressive symptoms during... 

Tolerance to glucocorticoids in this, as in some other respects, varies from individual to individual some patients tolerate 30 mg of prednisone for a long time without developing Cushing s syndrome, while others develop symptoms at 7.5 mg the doses recommended today to avoid Cushing s syndrome in most patients are usually equivalent to hydrocortisone 20 mg. Cushing s syndrome and other systemic adverse effects can occur not only from oral and injected glucocorticoids, but also from topical and intranasal treatment (115) and intrapul-monary or epidural administration (SEDA-19, 376 SEDA-20, 370 116,117). 

The authors commented that fever associated with glucocorticoids occurs frequently, whereas leukopenia is rare. Fever and leukopenia are important signs of an exacerbation of systemic lupus erythematosus, and it would be difficult to distinguish between an exacerbation of the disease and an adverse effect of glucocorticoids. 

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