Understanding Pharm: Approach to corticosteroids (blockers, synthetic systemic and topical)

In this article we will discuss synthetic steroids as well steroid “blockers” or antagonists. Let’s start with the steroid blockers.

Mineralocorticoid antagonists

• Spironolactone
  • Mechanism
    • Aldosterone receptor antagonist
    • K sparing diuretic
  • Indications
    • Heart failure
    • Hyperaldosteronism (e.g. Conn syndrome)
  • Adverse effects
    • Hyperkalemia
    • Non-specific action at sex hormone receptors
      • Gynecomastia
      • Antiandrogen effects
• Eplerenone
  • Quick note that this can be used instead of spironolactone if patients is experiencing anti-androgen effects due to spironolactone

Adrenocortical synthesis blockers

• Metyrapone
  • Mechanism
    • Inhibits enzymes in adrenal cortex to inhibit the synthesis of cortisol and corticosterone
  • Indications
    • Diagnostic test for HPA function
    • Cushing syndrome
  • Adverse effects
    • CNS depression
• Ketoconazole
  • Mechanism
    • Suppresses synthesis of glucocorticoids
  • Indications
    • Antifungal
    • Cushing syndrome
  • Adverse effects
    • Hepatotoxicity
    • QT prolongation
    • CYP3A4 inhibitor
    • Inhibits testosterone synthesis leading to gynecomastia

Systemic steroids

Next we have systemic steroids. Within systemic steroids we have mineralcorticoids and glucocorticoids; let’s start with mineralocorticoids.

• Fludrocortisone
  • Mechanism
  • Indications
  • Adverse effects

Now let’s dive into the synthetic systemic glucocorticoids, from weakest to strongest

• Hydrocortisone
  • Preferred for cortisol replacement therapy
  • Commonly used as topical anti-inflammatory
• Prednisone
  • Good choice for chronic anti-inflammatory therapy
  • Has good anti-inflammatory potency and low mineralocorticoid potency
• Betamethasone, dexamethasone
  • Anti-inflammatory effect only
  • Not good choice for chronic therapy due to high strength and adverse effects
  • Also used to support prematurely delivered infants

• Quick facts about potency comparisons
  • Prednisone or prednisolone is 4x as potent as cortisol
  • Methylprednisolone is 5x as potent as cortisol
  • Betamethasone or dexamethasone is 25x as potent as cortisol
  • Fludrocortisone is 10x as potent as cortisol (but is 125x as potent with respect to Na-retaining potency)

Topical steroids

• Topical percentages
  • Lower percentage means more potent when comparing between topical corticosteroids of different classes
    • Example
      • 0.1 % betamethasone vs 1 % hydrocortisone
      • 0.1 % betamethasone is more potent
  • Higher percentage means more potent when comparing between topical corticosteroids of the same class
    • Example
      • 1% hydrocortisone vs 2.5 % hydrocortisone
      • 2.5 % hydrocortisone is more potent

• Creams vs ointments
  • Creams
    • Cause less occlusion
    • Suitable for non-acute, wet lesions
    • Tend to be more cosmetically acceptable since residue is not visible after application
  • Ointments
    • Cause more occlusion
    • Greasy
    • More effective in dry, scaly or hyperkeratinized skin areas
    • They are more effective in treating chronic lesions (psoriasis)
    • They should not be used in areas such as the axilla, groin, or skin folds as their occlusive effect may cause maceration, folliculitis and potential systemic side
    • effects

• Guidelines regarding potency of topical steroids
  • Ultra-potent agents
    • Max 50 g/week (dispense 50 g tube to make it easy for the patient)
    • Limit duration <3 weeks
    • Only apply daily or BID
    • Occlusive dressings should be avoided
  • High potency agents
    • Use in areas of thicker skin
    • Maintenance therapy with a lower potency agent is advised
    • Higher potency agents are indicated in areas with
  • Low potency agents
    • Lower potency products are used on the face and other areas of thin skin
    • May be used in
      • Young children
      • Infants
      • Elderly
      • When application to large areas is required
  • Skin as a reservoir for corticosteroids
    • Steroids penetrate into blood and skin slowly, so the skin acts as revervoir
    • Frequency of application of cream should be reduced with repeated application
    • Maintenance OD and BID dosing is required for lower potency steroids

• Common topical corticosteroids
  • Creams
    • Ultra-high potency
      • Clobetasol propionate 0.05 %
    • High potency
      • Betamethasone dipropionate 0.05 %
    • Mid potency
      • Betamethasone valerate 0.1 or 0.05%
    • Low potency
      • Hydrocortisone
        • 2.5 %
        • 1 % (OTC)
        • 0.5 % (OTC)
  • Ointments
    • Ultra-high potency
      • Clobetasol propionate 0.05 %
    • High potency
      • Betamethasone dipropionate 0.05 %
    • Mid potency
      • Betamethasone valerate 0.1%
    • Low potency
      • Betamethasone valerate 0.05 %
      • Hydrocortisone
        • 1 % (OTC)
        • 0.5 % (OTC)

Side effects of steroids

• Skin atrophy
• Striae
• Telangiectasia
• Purpura
  • Bruising occurs with minimal trauma
• Fine hair growth
  • Reversible
• Acneform/Rosacea like eruptions
  • Common on the face with high potency agents
  • Reversible
• Hypopigmentation
  • More apparent in darker skinned people
  • Reversible
• Infections
  • Symptoms of bacterial, fungal, and viral infections may be masked
  • Conditions may worsen without being recognized
• Rebound dermatitis
  • With sudden discontinuation
• Systemic (CUSHINGOID):
  • Cataracts
  • Ulcers
  • Striae and skin bruising
  • Hirsutism, Hypertension, Hypercholesterolemia
  • Infections
  • Necrosis
  • Glycosuria
  • Osteoporosis/Obesity
  • Immunosuppression
  • Diabetes