General Medical Information

Glucocorticoids for Control of Severe or Chronic Symptoms

Richard L. Mabry

Glucocorticoids are clearly the most potent agents available to relieve the symptoms of many types of rhinosinusitis. They often are reserved for instances in which first-line measures fail, because they present a risk of serious side effects, even when topically administered. Discussion continues about whether glucocorticoids should replace antihistamines as a first-line measure in the management of allergy, and the final answer is yet to be determined.

Glucocorticoids ameliorate the effects of both acute and late-phase allergic reactions by decreasing capillary permeability, stabilizing lysosomal membranes, blocking migratory inhibitory factor, inhibiting arachidonic acid metabolism, and probably through the action of other mechanisms that are not fully understood. Systemic glucocorticoid administration can be associated with undesirable side effects and consequences. If such administration is necessary to relieve severe constitutional allergic symptoms, a single morning dose equivalent to 15 mg of prednisone or less presents the least risk of adrenal suppression. Treatment with larger doses or treatment for longer than 1 month must be terminated by means of gradual dosage tapering to allow endogenous cortisol production to resume. Glucocorticoid supplementation may be needed by these patients if they are exposed to stress, including surgery, before adrenal recovery occurs.

The rules for the use of glucocorticoids are as follows:

Establish an accurate diagnosis.
Use other, less hazardous measures first. Limit dosage to the smallest effective amount for the shortest time necessary to relieve symptoms or control the problem.
Use glucocorticoids locally, when possible, to concentrate the therapeutic effect and limit the likelihood of systemic complications.

Nasal glucocorticoid aerosols have replaced systemic therapy in the management of severe symptoms of allergic rhinosinusitis. All nasal glucocorticoid preparations can produce adverse local effects such as candidiasis, nasal irritation, dryness, bleeding, crusting, and in rare instances septal perforation. Local irritative effects occur most often after delivery by a propellant but also can follow administration through a pump spray. Nasal administration of glucocorticoids can have systemic effects, the risk varying with the preparation, dosage, and duration of therapy. Since 1998 the U.S. Food and Drug Administration has required labeling of all intranasal glucocorticoids that addresses the potential effects of these agents on growth velocity among children. Metaanalysis has shown that although use of an inhaled glucocorticoid can increase the risk of cataracts among older adults, the risk is not the same with the use of topical nasal glucocorticoids. A systemic effect is most likely in situations in which patients receive larger-than-recommended doses for prolonged periods or patients receive both intranasal and inhaled glucocorticoids for rhinitis and asthma.

Only a small fraction of an intranasally administered drug is absorbed at the target site, although the major fraction is swallowed and undergoes gastrointestinal absorption. The rapidity and extent of first-pass hepatic metabolism and the degree of direct absorption from the nose determine the systemic bioavailability of these drugs. This property is highly variable among available formulations. To further confuse the issue, conflicting data sometimes are available regarding the same drugs. The practitioner should thoughtfully assess the available data on systemic bioavailability of new nasal glucocorticoids and use those with the best safety profiles.

To ensure a patent airway necessary to gain proper benefit from nasal glucocorticoid sprays, concomitant use of a systemic decongestant may be needed. Large polyps and large septal deviations prevent proper mucosal contact and decrease the effectiveness of the medication. Patients must be taught to use glucocorticoid nasal sprays regularly during times of anticipated allergic symptoms (rather than on an as-needed, single-dose basis) and to stop therapy if side effects such as epistaxis, crusting, or pain occur. Long-term administration of nasal glucocorticoids requires regular intranasal examinations by the physician to avert serious consequences such as septal perforation; dosages and duration should be monitored to avoid systemic side effects.