67. Pathophysiological aspects of glucocorticoid therapy
Glucocorticoid drugs are drugs that are structurally similar to cortisol and have similar effects on the body. These drugs are mostly used for their anti-inflammatory effect. They’re among the strongest anti-inflammatory drugs available.
These drugs can be administered topically, by local injection, by inhalation, orally or parenterally.
Indications
Cortisol replacement therapy:
- Adrenocortical insufficiency
- Congenital adrenal hyperplasia
Acute systematic treatment:
- Asthma
- Allergies
- Anaphylactic shock
- Exacerbations of COPD
- Exacerbations of autoimmune diseases
Chronic systematic treatment:
- Chronic inflammatory diseases
- Asthma
- COPD
- IBD
- Rheumatic diseases
- Sarcoidosis
- Rheumatoid arthritis
- Sjögren syndrome
- SLE
- Organ transplant
Glucocorticoids are not used in infective inflammations. They may be effective in some forms of cerebral oedema.
Mechanism of action
The anti-inflammatory effect of glucocorticoids come mostly from changes in genetic expression. Activation of the glucocorticoid receptors has the following effects:
- Inhibition of neutrophil apoptosis
- Demargination of neutrophils
- Apoptosis of eosinophils, monocytes and lymphocytes
- Inhibition of phospholipase A2, which decreases the production of arachidonic acid, the precursor of thromboxanes and leukotrienes
- Inhibition of pro-inflammatory transcription factors like NF-κB
- Activation of anti-inflammatory transcription factors
The result is that the number of neutrophils increases, causing leukocytosis, even though the number of lymphocytes, monocytes and eosinophils decreases. The neutrophils’ function is inhibited however, and the immune system changes toward an anti-inflammatory state.
Glucocorticoid drugs do not have significant mineralocorticoid properties.
Complications
Even moderate doses of glucocorticoid therapy cause exogenous or iatrogenic Cushing syndrome or Cushingoid symptoms in the long-term. These complications are not seen in acute treatment.
Due to negative feedback on the pituitary, ACTH levels will decrease. In the long run this can lead to atrophy of the adrenal cortex. If the treatment is stopped abruptly secondary adrenal insufficiency can occur.