corticosteroids Flashcards
Outline the hormonal regulation pathway of cortisol production.
CRH (from hypothalamus) → stimulates ACTH (from pituitary) → stimulates cortisol release (from adrenal cortex). Negative feedback inhibits CRH and ACTH.
physiological roles of aldosterone
Aldosterone binds the mineralocorticoid receptor (a nuclear receptor) → upregulates Na⁺/K⁺ ATPase in kidney → reabsorbs Na⁺, excretes K⁺ and H⁺
in excess: hypernatremia, hypokalemia, edema
metabolic effects of cortisol
↑ gluconeogenesis, ↓ peripheral glucose uptake, ↑ glycogen storage, ↑ lipolysis and lipogenesis (→ fat redistribution), ↑ protein catabolism in muscle, bone, and connective tissue.
how does cortisol exert its effect on gene exp
Cortisol binds intracellular glucocorticoid receptor → complex enters nucleus → binds GRE (Glucocorticoid Response Element) → alters gene expression via transactivation and transrepression
Describe the systemic immunological effects of corticosteroids
↓ lymphocytes, eosinophils, basophils (via apoptosis), ↓ lymph node size, ↑ neutrophils in blood (reduced extravasation), ↑ macrophage efferocytosis, ↓ type IV hypersensitivity.
What are the common endocrine/metabolic side effects of corticosteroids?
Hyperglycemia, moon face, truncal obesity, growth retardation, acne, hirsutism, menstrual changes, delayed wound healing, skin thinning, increased appetite, fluid retention.
Why must corticosteroids be tapered instead of stopped abruptly
Risk of adrenal insufficiency due to suppressed HPA axis. Withdrawal symptoms include fatigue, headache, fever, arthralgia.
Compare the anti-inflammatory and mineralocorticoid potency of common corticosteroids:
Hydrocortisone
Prednisone
Prednisolone
Methylprednisolone
Triamcinolone
Dexamethasone
Betamethasone
Cortisol: GC 1, MC 1
Prednisolone: GC 5, MC 0.3
Methylprednisolone: GC 5, MC 0
Dexamethasone: GC 30, MC 0
Betamethasone: GC 25–40, MC 0
List pro-inflammatory mediators downregulated by corticosteroids
Cytokines (TNF-α, IL-1β, IL-6, IFNs), chemokines (MCP-1, RANTES), enzymes (PLA2, 5-LOX, COX-2), adhesion molecules (ICAM-1, VCAM-1), IL-2 receptor, TCR.
List anti-inflammatory mediators upregulated by corticosteroids
Annexin-A1, β2-adrenoceptor, IL-1 receptor antagonist, IL-1RII (decoy), NEP, IκB-α, MKP-1, GILZ.
