Glucocorticoids Lecture Notes

Glucocorticoids

Presented by Noha A. Fadel, Lecturer of Pharmacology, 2025.

Anatomy of the Adrenal Gland

The adrenal gland consists of two main parts:

• Adrenal Cortex:

  • Produces:

    • Glucocorticoids (e.g., Cortisol)

    • Mineralocorticoids (e.g., Aldosterone)

    • Androgens

  • Composed of three zones:

    • Zona glomerulosa

    • Zona fasciculata

    • Zona reticularis

• Adrenal Medulla:

  • Produces Catecholamines

Synthesis of Corticosteroids

The synthesis pathway involves several enzymes:

• Cholesterol is the precursor.

Corticosteroids Overview

• Corticosteroids are hormones synthesized from cholesterol in the adrenal cortex.

• Classes:

  • Glucocorticoids (e.g., Cortisol)

  • Mineralocorticoids (e.g., Aldosterone)

  • Sex steroids (Androgens)

Hypothalamo-Pituitary Axis

The Hypothalamo-Pituitary-Adrenal (HPA) axis regulates cortisol release:

1. Hypothalamus releases corticotropin-releasing hormone (CRH).

2. Pituitary gland is stimulated by CRH to secrete adrenocorticotropic hormone (ACTH).

3. Adrenal cortex is stimulated by ACTH to release cortisol.

Glucocorticoids: Cortisol

• Cortisol is the primary human glucocorticoid.

• Its production follows a diurnal pattern, with a peak in the early morning and a smaller peak in the late afternoon.

Cortisol as the Stress Hormone

• Cortisol is known as the body’s stress hormone.

• It regulates various processes in response to stress, including:

  • Energy regulation

  • Glucose metabolism

  • Immune function

• The main goal is to provide adequate ATP to the brain during stress.

Pharmacological Effects of Glucocorticoids

1. Metabolic Effects

• Carbohydrate metabolism: (anti-insulin effect)

  • ↑ gluconeogenesis and ↓ peripheral glucose utilization → hyperglycemia.

• Protein metabolism: (catabolic effect)

  • ↑ proteolysis → ↓ muscle mass.

• Fat metabolism:

  • ↑ lipolysis with redistribution of fats.

• Water and electrolyte balance:

  • Na/water retention and hypokalemia → Hypertensive effect.

  • Can be therapeutically used in septic shock due to hypertensive and anti-inflammatory effects.

2. Anti-inflammatory Effects

• ↓ phospholipase A2 (PLA2) enzyme → ↓ synthesis of PGs and LTs.

3. Immunosuppressant Effects

• Decreases the function of:

  • B cells (↓ Ag-Ab reaction)

  • T cells (↓ inflammatory mediators and cytokines release)

  • Histamine release from mast cells

4. Alter Blood Cells

• ↑ RBCs

• ↑ neutrophils

• ↓ lymphocytes

• ↓ eosinophils

5. Bone Effects

• ↓ bone matrix because decrease intestinal calcium absorption and inhibit osteoblast (bone formation).

Semisynthetic Derivatives of Corticosteroids

• Glucocorticoids are mainly used for their anti-inflammatory effect.

• Synthetic drugs were developed to:

  • Increase the anti-inflammatory effect

  • Decrease the salt-retaining effect

Therapeutic Uses of Glucocorticoids

• Replacement therapy in adrenocortical insufficiency (Hydrocortisone).

• Shock and hypotension (Hydrocortisone).

• Anti-inflammatory in inflammatory diseases (arthritis, neuritis,…itis) and allergic diseases (Urticaria, bronchial asthma).

• Immunosuppression in autoimmune disease (ulcerative colitis and myasthenia gravis) and organ transplantation.

• Stimulation of lung maturation in the fetus (Betamethasone).

• Cerebral edema (Dexamethasone) is used after brain surgery to minimize edema associated with tissue injury.

Adverse Effects of Glucocorticoids

1. Cushing-like syndrome:

   • Occurs with high doses and long-term use.

   • Characterized by moon face (round), buffalo hump (fat deposited on the back of the neck), truncal obesity, and muscle wasting.

2. Adrenal crisis (Addison’s disease):

   • Due to sudden withdrawal after prolonged use of exogenous steroids → steroid deficiency.

3. Hypertension:

   • Due to Na/water retention.

4. Hyperglycemia:

   • Due to increased gluconeogenesis.

5. Immune suppression:

   • Leads to flaring of infections.

6. Peptic ulcer:

   • Due to prolonged inhibition of gastroprotective PGs.

7. Glaucoma:

   • Increased intraocular pressure due to decreased drainage of aqueous humor.

8. Osteoporosis:

   • Due to decreased bone matrix.

9. Growth retardation:

   • Due to protein catabolism and decreased growth hormone release.

Glucocorticoids - Pharmacological vs. Adverse Effects

Administration of Glucocorticoids

• Dose of each type could be considered based on the anti-inflammatory effect of each type and its duration.

  • 20 mg of hydrocortisone = 5 mg of prednisolone

• When large doses of corticosteroids are required for more than 2 weeks, suppression of the hypothalamic-pituitary-adrenal axis occurs:

  • Alternate-day administration of corticosteroids may prevent this adverse effect by allowing the axis to function on days the hormone is not taken.

• Glucocorticoids should be stopped gradually after long-term administration (more than 21 days).

Dental Uses of Glucocorticoids

Glucocorticoids are administered topically, intra-articularly, or orally in several dental situations because of their anti-inflammatory actions.

1. Oral Lesions

   • Oral lichen planus

   • Erythema multiforme

   • Mucous membrane pemphigoid

   • Pemphigus vulgaris

   • Aphthous Stomatitis

2. Temporomandibular Joint arthritis

3. Oral Surgery

Specific Dental Uses Explained

• Oral lichen planus: inflammatory condition that affects mucous membranes and appears as white, lacy patches.

• Erythema multiforme: allergic reaction that occurs in response to medications or infections. It appears as pimple-like blisters on your mouth.

• Mucous membrane pemphigoid: autoimmune disorder affecting mucous membrane appeared as red inflamed blisters and sores lead to difficulty in eating.

• Aphthous Stomatitis: superficial ulcers creating severe pain commonly occurring in the oral cavity. Oral lichen planus