Corticosteroids

Question 1

Glucocorticoids:
What’s the main one?

Where’s it released from?

What’s its function?

What stimulates its release?

Mineralocorticoids:
What’s the main one?

Where’s it released from?

What’s its function?

Describe the RAAS

What’s its release inhibited by? When?

Answer 1

• CORTISOL
• Zona Fasciculata of Adrenal Cortex
• ‘Sugar’ hormone - Carbohydrate and protein metabolism with Anti-inflammatory and immunosuppressive effects
• Stress causes CRH release from Hypothalamus → ACTH from Anterior Pituitary → Cortisol

• ALDOSTERONE
• Zone Glomerulosa of Adrenal Cortex
• ‘Salt’ hormone - Water and electrolyte balance in the kidney
• ↓Na+/↑K+ → Renin release from kidney → Ang II production → Aldosterone
• ANP (Atrial Natriuretic Peptide) during ↑BV/BP

Question 2

GLUCOCORTICOIDS:
What are its Metabolic effects?

What are its Cardiovascular effects?

What are its Hormonal effects?

What are its Anti-inflammatory effects?

How does it affect the Eiocosanoid production pathway?

Answer 2

• Breakdown of Protein and Fats, ↓Glucose usage and ↑Gluconeogenesis, ↑Glycogen storage, Hyperglycaemia (Counters effects of Insulin)
• Vasoconstriction and ↓Vessel permeability = Hypertension
• Negative feedback on to HPA-axis
• • ↓Microvascular fluid exudation = ↓Cells getting to area of inflammation
  • ↓Inflammatory mediators - ↓COX2 = ↓Eicosanoid production
  • ↓Cytokines and Complement
  • ↓Function of Inflammatory effector cell - ↓T and B cell clonal expansion
  • ↓Chronic inflammatory events, so healing and repair are inhibited
• • ↓COX-2 expression
  • Inhibits PLA2 = ↓AA production

Question 3

Mechanism of Action:
What does the Glucocorticoids first do once inside a cell?

What then occurs after this? What are the effects?

What occurs last?

Why are these effects Slow?

Therapeutic Uses:
Give examples of Glucocorticoid drugs?

What are they used for?

Answer 3

• Binds to intracellular GC receptors (GCR) and dissociates it from the Heat Shock Protein (HSP) complex
• Glucocorticoid-GCR complex then goes into the nucleus to alter gene expression (↓/↑)
  o Induces IκBα (↓NFKB)
  o Prevents gene activation by other transcription factors that help express COX-2
• GCR then dissociates and is recycled by binding to the HSP complex again
• GCRs found throughout the body but only a small amount of the genome is steroid-sensitive

• Hydrocortisone, Prednisolone, Dexamethasone, Beclomethasone
• • Adrenal Insufficiency (Addison’s disease) - Combined with Mineralocorticoids
  • Inflammation e.g. Asthma
  • Immunosuppression to inhibit a reaction on tissue transplantation

Question 4

MINERALOCORTICOIDS:
What does it cause in the Kidneys?
→ How does it do this?

Where are its receptors found?

Therapeutic Uses:
Give examples of a Mineralocorticoid drug?

What’s it used for?

Answer 4

• ↑Na+ retention, Loss of K+ and H+
  → ↑ENaC channels, Na/H exchanger, Na/K pump
• Kidneys, Colon, Bladder
• Fludrocortisone
• • Adrenal Insufficiency (Addison’s disease) - Combined with Glucocorticoids
  • Postural Hypotension
  • Electrolyte disorders

Question 5

What are the Side-effects of Corticosteroid use?

Why is it important to slowly decrease the dosage?

Answer 5

- • Cushing’s syndrome
• Poor wound healing and Opportunistic infection
• Osteoporosis
• Gastric ulcers
• Growth suppression
• Behavioural and Reproductive problems

• Causes Prolonged HPA axis suppression even after cessation of use