Pharm 101: Corticosteroids

Classification

• Short-medium acting: hydrocortisone, prednisolone
• Intermediate-acting
• Long-acting: dexamethasone
• Mineralocorticoids: fludrocortisone

Pharmacodynamics

• Act on intracellular glucocorticoid receptors
• Anti-inflammatory and immunosuppressive effects:
  • Affects concentration, distribution and function of peripheral leukocytes
  • Suppression of inflammatory mediators (cytokines, chemokines)
  • Inhibit macrophages and APCs
  • Inhibit PLA2 –> decrease PG/LT/PAF
• Catabolic and antianabolic effects

Pharmacokinetics

• PO, IV, IM, topical administration
• Cortisol (naturally-occurring):
  • Bound to corticosteroid-binding globulin (CBG)
  • Half-life 60-90 minutes
  • Mostly hepatic metabolism
  • 20% converted to cortisone by kidneys

Relative potency

Drug name	Glucocorticoid activity	Mineralocorticoid activity
Cortisol	1	1
Aldosterone	0.3	3000
Cortisone	0.7	0.8
Prednisolone	4	0.5
Dexamethasone	25	0

Dexamethasone

• PO, IV, IM, topical administration
• Half-life 36-54 hours
• Compared with hydrocortisone, 30 times more potent, longer acting, and no salt retaining activity
• Clinical uses:
  • Croup: 0.15-0.60mg/kg PO, single dose
  • Anti-inflammatory effect
  • Anti-emetic
  • Diagnostic testing: dexamethasone suppression test

Hydrocortisone

• Clinical uses:
  • Acute airways disease
  • Anaphylaxis
  • Thyrotoxicosis
  • Sepsis

Corticosteroids in asthma

• Mechanism of action:
  • Anti-inflammatory, inhibit production of inflammatory cytokines
  • Contraction of engorged vessels in bronchial mucosa
  • Potentiate effects of beta-receptor agonists
• Do not directly cause bronchodilation, but reduce bronchial hyperactivity and reduce frequency of exacerbations if taken regularly

Adverse effects of chronic use

• Insomnia
• Peptic ulcer disease
• Acute psychosis
• Cushings syndrome (> 2 weeks):
  • Metabolic effects (moon face, truncal fat, weight gain, hyperglycaemia)
  • Osteoporosis
  • Hypertension
  • Impaired wound healing
• Adrenal suppression (> 2 weeks)

Further reading

• Nickson C. Corticosteroids Overview. LITFL
• Nickson C, Pearlman J. Steroid Conversion. LITFL

References

• Katzung BG. Basic and Clinical Pharmacology. 14e. 2018: 836-837, 840