Prednisone, Methylprednisolone, Hydrocortisone and Dexamethasone

Mechanism

Mechanism of action

Their molecular mechanism mimics that of ICS, but when distributed systemically, they exert their effects in all tissues that express glucocorticoid receptors (GR-α and GR-β), as well as cross-mineralocorticoid effects depending on the affinity for the aldosterone receptor.

Comparative power and affinities

Indicators and dose

Select clinical indications

• Severe acute asthmatic crisis / Severe exacerbation of COPD: Short-term systemic rescue regimen (5 - 7 days) to accelerate the resolution of the inflammatory flare.
• Acute exacerbation of idiopathic pulmonary fibrosis or hypersensitivity pneumonitis.
• Severe Acute Respiratory Distress Syndrome (ARDS): Dexamethasone or methylprednisolone protocols (Meduri regimen) to attenuate alveolar cytokine storm.

Dosage and Clinical Adjustment

• Acute exacerbation of asthma or COPD: Prednisone 40 - 50 mg orally once a day for 5 to 7 days. Current international guidelines do not recommend tapering if treatment lasted less than 10 days, unless the patient has a history of chronic recurrent use.
• Life-threatening asthma attack (Emergency): Methylprednisolone 40 - 80 mg IV every 12 hours, or Hydrocortisone 100 - 200 mg IV every 6 hours.

Security

Critical Risk: Acute Adrenal Insufficiency due to Abrupt Withdrawal

The administration of systemic glucocorticoids at supraphysiological doses (7.5 mg per day of prednisone or its equivalent) for a period greater than 14 days induces persistent suppression of hypothalamic CRH and pituitary ACTH secretion by negative feedback. This causes bilateral atrophy of the adrenal cortex. Abrupt discontinuation of treatment may trigger a life-threatening acute Addisonian crisis, characterized by refractory hypotension, circulatory collapse, extreme hyponatremia, hyperkalemia, and severe hypoglycemia. The withdrawal of prolonged treatments should be carried out gradually and in a decreasing manner.

Systemic adverse effects (Chronic use)

• Metabolic and Endocrine: Iatrogenic Cushing syndrome, glucose intolerance and steroid diabetes, proximal limb girdle myopathy, body fat redistribution (moon face, buffalo hump).
• Bone: Osteoporosis induced by corticosteroids due to direct inhibition of osteoblasts, stimulation of osteoclasts and decreased intestinal absorption of calcium (monitoring with bone densitometry and prophylaxis with calcium, vitamin D and bisphosphonates is required).
• Cardiovascular and Renal: Water and sodium ion retention, refractory arterial hypertension, hypokalemia.
• Immune: Notable increase in the risk of bacterial, fungal or opportunistic infections (pneumonia due to *Pneumocystis jirovecii*, reactivated tuberculosis).