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COPYRIGHT 2004 American Association of Neuroscience Nurses
Corticosteroids, a class of agents similar to natural corticosteroid hormones produced by the adrenal gland, are routinely prescribed for patients with brain tumors. These agents decrease tissue swelling and control signs and symptoms of brain tumors, including headaches, seizures, motor deficits, and altered mental status. Synthesized in the adrenal cortex, corticosteroids may be further divided into two classes, glucocorticoids and mineralocorticolds, based on their biologic activity.
Originally, the term glucocorticoid was given to agents such as hydrocortisone and prednisone to describe their effects on carbohydrate and protein metabolism, and the term mineral-ocorticoid was given to aldosterone and fludrocortisone and described their effects on regulating electrolyte and water homeostasis. However, carbohydrate metabolism is only one of a multitude of effects that glucocorticoids produce within the body, and the activity produced is a function of the specific receptor activated (i.e., glucocorticoid versus mineralocorticoid), as well as the agent and the prescribed dose (Gans & Smith, 1999).
This article provides an overview of the mechanism of action of corticosterioids and rationale for their use in patients with brain tumors. Practical implications on dosing, tapering, and side effects of dexamethasone are discussed as well.
Mechanism of Action
Glucocorticoid receptors are found intracellularly in almost all tissues. Glucocorticoids enter cells through passive diffusion and form a complex with a receptor protein. This complex then undergoes an irreversible activation and enters the cell nucleus, where it binds to DNA, leading to biological effects induced by these hormones, including increased hepatic gluconeogenesis, increased lipolysis, muscle catabolism, and inhibition of peripheral glucose uptake in muscle and adipose tissue (Gans & Smith, 1999; Greenspan & Stewler, 1997). The exact mechanism of action of corticosteroids remains unknown despite more than 40 years of research.
Rationale for Use
Corticosteroids decrease brain edema. In central nervous system tumors, corticosteroids have been found not only to reduce peritumoral and vasogenic brain edema, but also reduce increased intracranial pressure and frequency of plateau waves, decrease cerebral spinal fluid production, and decrease tumor cerebral blood flow (Behrens, Ostertag, & Wamke, 1998; Koehler, 1995; van Roost, Hart-mann, & Quade, 2001). The primary corticosteroid used to control cerebral edema is dexamethasone. More than 40 years ago, dexamethasone was used in patients with brain tumors, and it is still used today. Other steroids at equivalent doses probably also work, but given the clinical ease of use and comfort, dexamethasone is used.
Although corticosteroids decrease capillary permeability in the tumor itself, it has been found in animal models that dexamethasone may act differently and decrease edema by effects on bulk flow away from the tumor (Molnar, Lapin, & Goothuis, 1995). In addition, corticosteroids also improve patients' level of alertness and reduce or eliminate focal deficits (Anderson, Astmp, & Gyldensted, 1994; DeAngelis, 1994; Fishman, 2000).
Additional support for corticosteroid therapy in neurosurgical patients includes high concentrations of glucocorticoid receptors in certain types of brain tumors (Yu et al., 1981). Tumors that respond well to dexamethasone, such as cerebral metastases, are characterized by high levels of glucocorticoid receptors. Tumors known...
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