Corticosteroids and Adrenal Insufficiency Quiz

Learning Objectives

• Familiarize with commonly prescribed corticosteroids and their therapeutic uses.
• Understand mechanisms through which corticosteroids suppress inflammation and immune responses.
• Manage toxicities related to chronic corticosteroid use.
• Distinguish between mineralocorticoids and corticosteroids.

Key Drugs to Know

• Hydrocortisone (Cortisol): Short-acting corticosteroid.
• Prednisone/Prednisolone: Intermediate-acting corticosteroid.
• Dexamethasone and Betamethasone: Long-acting corticosteroids.
• Fludrocortisone: Mineralocorticoid used for adrenal insufficiency.
• Fluticasone: Inhaled corticosteroid for respiratory conditions.

Corticosteroids Overview

• Produced by adrenal cortex: glucocorticoids (e.g., cortisol) and mineralocorticoids (e.g., aldosterone).
• Cortisol mediates stress response and regulates metabolism (glucose, lipids, proteins).
• Adrenal disorders: Addison's Disease (hyposecretion) and Cushing's Syndrome (hypersecretion).

Mechanism of Action

• Glucocorticoids bind to glucocorticoid receptors (GR) and influence gene transcription by interacting with DNA elements.
• Can also bind mineralocorticoid receptors (MR) in certain tissues, often mitigated by the enzyme 11β-hydroxysteroid dehydrogenase type 2.

Routes of Administration

• Administered via multiple routes: IV, oral, nasal sprays, topical applications, ophthalmic forms, and IM injections.

Equivalence of Corticosteroids

• Short-acting: Hydrocortisone (anti-inflammatory effect = 1), equivalent oral dose = 20 mg.
• Intermediate-acting: Prednisone (anti-inflammatory effect = 4), equivalent oral dose = 5 mg.
• Long-acting: Dexamethasone (anti-inflammatory effect = 30), equivalent oral dose = 0.8 mg.

Replacement Therapy

• Treat adrenal insufficiencies with hydrocortisone and fludrocortisone.
• Acute adrenal insufficiency requires immediate IV hydrocortisone.
• In congenital adrenal hyperplasia, treatment may include in utero dexamethasone to prevent female virilization.

Therapeutic Applications

• Nonendocrine diseases treated with glucocorticoids:
  • Allergic conditions, bronchial asthma, ocular diseases, inflammatory bowel diseases, cerebral edema, malignancies like leukemia and lymphomas.

Glucocorticoid Toxicity

• Two primary categories: Withdrawal toxicity and toxicity from prolonged supraphysiological doses.
• Common side effects include hyperglycemia, psychosis, osteoporosis, weight gain, and impaired wound healing.

Strategies to Reduce Toxicity

• Tapering Dose: Gradual reduction to prevent flares.
• Alternate Day Therapy: Minimizes side effects during long-term therapy.
• Localized Delivery: Focused treatment to reduce systemic exposure.

Inhibitors of Steroid Synthesis

• Drugs such as ketoconazole, metyrapone, and aminoglutethimide can inhibit steroidogenesis but have significant toxicity issues.

Mineralocorticoids

• Fludrocortisone used for adrenal insufficiency with mineralocorticoid deficiency, focused on retaining salt without anti-inflammatory effects.

Mineralocorticoid Antagonists

• Spironolactone: Treats hyperaldosteronism, restores potassium balance, and acts as a potassium-sparing diuretic.
• Eplerenone: Similar effects to spironolactone but lacking anti-androgenic properties.

Interesting Facts

• 90% of plasma cortisol is bound to corticosteroid-binding globulin (CBG); synthetic steroids predominantly bind to albumin.
• Glucocorticoids regulate approximately 10-20% of all genes.
• GR and MR have equal affinity for cortisol.