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 After Abrupt Withdrawal

The risk of glucocorticoid-induced adrenal insufficiency depends on dose, duration and individual susceptibility. The 2024 ESE/Endocrine Society guideline considers exposure at risk when it exceeds 3-4 weeks and approximately physiologic doses (4-6 mg/day prednisone or equivalent). Courses shorter than 3-4 weeks generally do not require tapering; for prolonged treatment, taper when the underlying disease is controlled and assess hypothalamic–pituitary–adrenal axis recovery. The abrupt discontinuation of therapy can precipitate a life-threatening acute addisonian crisis, characterized by refractory hypotension, circulatory collapse, severe hyponatremia, hyperkalemia and severe hypoglycemia. Long-term treatment should be withdrawn gradually.

Systemic adverse effects (Chronic use)

• Metabolic and Endocrine: Iatrogenic Cushing syndrome, glucose intolerance and steroid-induced diabetes, proximal girdle myopathy and redistribution of body fat (moon face, buffalo hump).
• Bone: Corticosteroid-induced osteoporosis through direct osteoblast inhibition, osteoclast stimulation and reduced intestinal calcium absorption (requiring bone density monitoring and preventive calcium, vitamin D and bisphosphonates).
• Cardiovascular and Renal: Retention of water and sodium ions, refractory hypertension, hypokalemia.
• Immune: Markedly increased risk of bacterial, fungal or opportunistic infections (Pneumocystis jirovecii pneumonia, reactivated tuberculosis).