Glucocorticoids

Glucocorticoids

Most glucocorticoids are synthetic analogues of hormones secreted by the adrenal cortex. They exert anti-inflammatory, metabolic, and immunosuppressant effects. Drugs in this class include:

• beclomethasone
• betamethasone
• cortisone
• dexamethasone
• hydrocortisone
• methylprednisolone
• prednisolone
• prednisone
• triamcinolone.

Pharmacokinetics

Glucocorticoids are well absorbed when administered orally. After I.M. administration, they’re absorbed completely.

Distribution

Glucocorticoids are bound to plasma proteins and distributed through the blood.

Metabolism and excretion

Glucocorticoids are metabolized in the liver and excreted by the kidneys.

Pharmacodynamics

Glucocorticoids suppress hypersensitivity and immune responses through a process that isn’t entirely understood. Researchers believe that glucocorticoids inhibit immune responses by:

• suppressing or preventing cell-mediated immune reactions
• reducing levels of leukocytes, monocytes, and eosinophils
• decreasing the binding of immunoglobulins to cell surface receptors
• inhibiting interleukin synthesis.

Taking the red (and more) out

Glucocorticoids suppress the redness, edema, heat, and tenderness associated with the inflammatory response. They start on the cellular level by stabilizing the lysosomal membrane (a structure
within the cell that contains digestive enzymes) so that it doesn’t release its store of hydrolytic enzymes into the cells.

Now I get it!

How methylprednisolone works

Tissue trauma normally leads to tissue irritation, edema, inflammation, and production of scar tissue. Methylprednisolone counteracts the initial effects of tissue trauma, promoting healing.

No leaks, no drips

As corticosteroids, glucocorticoids prevent the leakage of plasma from capillaries, suppress the migration of polymorphonuclear leukocytes (cells that kill and digest microorganisms), and inhibit phagocytosis (ingestion and destruction).

To ensure a job well done, glucocorticoids decrease antibody formation in injured or infected tissues and disrupt histamine synthesis, fibroblast development, collagen deposition, capillary dilation, and capillary permeability.

Warning!

Adverse reactions to cortico-steroids

Corticosteroids affect almost all body systems. Their widespread adverse effects include:

• insomnia
• increased sodium and water retention
• increased potassium excretion
• suppressed immune and inflammatory responses
• osteoporosis
• intestinal perforation
• peptic ulcers
• impaired wound healing.

Diabetes and more

Endocrine system reactions may include:

• diabetes mellitus
• hyperlipidemia
• adrenal atrophy
• hypothalamic-pituitary axis suppression
• cushingoid signs and symptoms (such as buffalo hump, moon face, and elevated blood glucose levels).

Pharmacotherapeutics

Besides their use as replacement therapy for patients with adrenocortical insufficiency, glucocorticoids are prescribed for immunosuppression and reduction of inflammation and for their effects on the blood and lymphatic systems.

Drug interactions

Many drugs interact with corticosteroids:

• Aminoglutethimide, barbiturates, phenytoin, and rifampin may reduce the effects of corticosteroids.
• Their potassium-wasting effects may be enhanced by amphotericin B, chlorthalidone, ethacrynic acid, furosemide, and thiazide diuretics.
• Erythromycin and troleandomycin may increase their effects by reducing their metabolism.
• They reduce the serum concentration and effects of salicylates.
• The risk of peptic ulcers associated with nonsteroidal anti-inflammatory drugs and salicylates increases when these agents are taken with corticosteroids.
• The response to vaccines and toxoids may be reduced in a patient taking corticosteroids.
• Estrogen and hormonal contraceptives that contain estrogen increase the effects of corticosteroids.
• The effects of antidiabetic drugs may be reduced, resulting in increased blood glucose levels