How are steroids classified based on their duration of action?

Classification of Steroids Based on Duration of Action

Steroids are classified into three categories based on their duration of action: short-acting (8-12 hours), intermediate-acting (12-36 hours), and long-acting (36-72 hours), with this classification determining their clinical applications and dosing schedules. 1

Short-Acting Corticosteroids

Duration: 8-12 hours of biological activity with adrenocortical suppression lasting 1.25-1.5 days 2

• Hydrocortisone is the least potent short-acting corticosteroid and serves as the reference standard for potency comparisons 1
• Cortisone shares similar properties with hydrocortisone, including salt-retaining effects, making both suitable for replacement therapy in adrenocortical deficiency states 2
• Short-acting agents are preferred for alternate-day therapy because their brief suppressive effect on the hypothalamic-pituitary-adrenal (HPA) axis allows for recovery of normal adrenal function on off-steroid days 2

Intermediate-Acting Corticosteroids

Duration: 12-36 hours of biological activity with adrenocortical suppression lasting 1.25-1.5 days 2

• Prednisone and prednisolone are 4-5 times more potent than hydrocortisone and represent the most commonly used intermediate-acting agents 1
• Methylprednisolone has similar potency to prednisone (4-5 times hydrocortisone) and shares the same duration profile 1
• These agents are recommended for alternate-day therapy due to their relatively short suppressive effect on adrenal activity, allowing HPA axis recovery between doses 2
• When administered as a morning dose, intermediate-acting steroids like prednisolone cause peak hyperglycemia 6-9 hours after administration, with effects often normalizing overnight 3

Long-Acting Corticosteroids

Duration: 36-72 hours of biological activity with prolonged adrenocortical suppression lasting more than 1.5 days 2

• Dexamethasone is approximately 25 times more potent than hydrocortisone and represents the prototypical long-acting corticosteroid 1
• Betamethasone shares similar long-acting properties with dexamethasone and is used antenatally to reduce complications of preterm birth 4
• Long-acting corticosteroids are NOT recommended for alternate-day therapy because their prolonged suppressive effect on adrenal activity prevents adequate HPA axis recovery between doses 2
• Dexamethasone almost completely lacks sodium-retaining properties compared to hydrocortisone, making it unsuitable for adrenocortical replacement therapy 5

Clinical Implications of Duration Classification

Alternate-Day Therapy Considerations

• The rationale for alternate-day therapy is based on two principles: (1) the anti-inflammatory effect of corticosteroids persists longer than their physical presence, and (2) administration every other morning allows re-establishment of more normal HPA activity on the off-steroid day 2
• Only short- and intermediate-acting corticosteroids (hydrocortisone, cortisone, prednisone, prednisolone, methylprednisolone) should be used for alternate-day therapy 2
• The maximal activity of the adrenal cortex occurs between 2 AM and 8 AM, and exogenous corticosteroids suppress adrenocortical activity least when given at the time of maximal activity 2

Hyperglycemia Management Based on Duration

• Short-acting glucocorticoids (prednisone) administered once daily in the morning cause disproportionate hyperglycemia during the day, with blood glucose frequently normalizing overnight without treatment 6, 7
• For once-daily short-acting steroids, NPH insulin is the preferred treatment because its peak action (4-6 hours after administration) aligns with the steroid's peak hyperglycemic effect 7
• Long-acting glucocorticoids (dexamethasone) or multiple daily doses require long-acting basal insulin to control fasting blood glucose, as the hyperglycemic effect persists throughout the 24-hour period 6, 7

Common Pitfalls to Avoid

• Do not use dexamethasone or betamethasone for alternate-day therapy - their prolonged suppression of the HPA axis (>1.5 days) prevents adequate recovery between doses and increases the risk of adrenal insufficiency 2
• Do not assume all corticosteroids have the same duration profile - the choice between short-, intermediate-, and long-acting agents significantly impacts dosing frequency, HPA suppression risk, and suitability for alternate-day regimens 2, 1
• Do not rely on fasting glucose alone to monitor steroid-induced hyperglycemia - short- and intermediate-acting steroids cause peak hyperglycemia 6-9 hours after morning administration, which will be missed by fasting measurements 7, 3