Adverse Effects of Glucocorticoids

The effectiveness and extensive clinical use of natural and synthetic glucocorticoids must be tempered by 

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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. 

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. 

There have been reviews of the mechanisms and adverse effects of glucocorticoids in rheumatoid arthritis (205) and the pathogenesis, diagnosis, and treatment of glucocorticoid-induced osteoporosis in patients with pulmonary diseases (206). Several mechanisms underlie the effect of glucocorticoids on bone, both biochemical and cellular. Effects on calcium are ... 

No adverse effects are to be expected after a single injection of a high dose of a glucocorticoid, but some serious complications have been observed with repeated use, including both infections and the known direct adverse effects of glucocorticoids. Cases of ventricular dysrhythmias and atrial fibrillation have been reported (SEDA-18, 391). With pulse therapy, the nature of the injected glucocorticoid seems to be important for example, hydrocortisone, which is more rapidly metabolized, seems to be better tolerated than dexamethasone (SEDA-6, 331). 

Most knowledge of the adverse effects of glucocorticoids has been acquired in connection with their use as oral products. However, various other routes of administration have been developed, sometimes specifically in the hope of securing a local therapeutic effect while avoiding systemic adverse reactions. Although experience has shown that the latter cannot be eliminated in this way, they can be diminished in some cases. In other cases, new problems arise. Administration by inhalation is covered in the monograph on inhaled glucocorticoids. 

Table 14-3. Potential Adverse Effects of Glucocorticoid Steroid Therapy...

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. 

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). 

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. 

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

Among the adverse effects of pulse glucocorticoid therapy, joint manifestations are rare. A woman with systemic lupus erythematosus and nephritis developed transient bilateral knee effusions during pulse therapy with high doses of glucocorticoids (279). 

The author proposed that raised arterial pressure, which is an adverse effect of high dose glucocorticoid treatment, and low oncotic pressure due to a low protein plasma concentration in a patient with nephrotic syndrome, could have increased trans-synovial fluid flow at a lower arterial pressure than normal. 

Primary esophageal histoplasmosis must be considered in patients who have a history of gastroesophageal reflux disease and are immunosuppressed by long-term glucocorticoids (SEDA-22,450 333). Oropharyngeal candidiasis is a well-described adverse effect of inhaled glucocorticoids. However, few cases of esophageal candidiasis have been reported (SEDA-22,179). 

Prenatal glucocorticoid therapy to enhance fetal lung maturation reduces neonatal morbidity and mortality. However, adverse effects of serial courses of betamethasone on mother and fetus can occur. 

Local and systemic adverse effects of ophthalmic glucocorticoids occur in children more often, more severely, and more rapidly than in adults, for unknown reasons. It could be that children have relatively immature chamber angles, giving rise to a rapidly increasing intraocular pressure (432). 

The local adverse effects of inhaled glucocorticoids have been studied in a prospective, cross-sectional, cohort study in 639 asthmatic children using beclomethasone (721 micrograms/day) or budesonide (835 micrograms/ day) for at least one month (28). The local adverse effects included cough (40%), thirst (22%), hoarseness (14%), dysphonia (11%), oral candidiasis (11%), perioral dermatitis (2.9%), and tongue hypertrophy (0.1%). A spacer doubled the incidence of coughing. 

Hypothalamic-pituitary-adrenal axis function provides one of the most sensitive markers of the systemic activity of inhaled glucocorticoids (35), and suppression can be used as a surrogate marker for adverse effects of inhaled glucocorticoids in other tissues. 

The local adverse effects of topical glucocorticoids (1,2) are listed in Table 1. They include transient local... 

Table 1 Local adverse effects of topical glucocorticoids...

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