Corticosteroids Flashcards
What does corticotrophin releasing factor do
Released from hypothalamus, stimulate anterior pituitary to release ACTH
What does aldosterone do
Unregulated basolateral Na+-K+ ATPase gene expression. This increases Na+ reabsorption at distal renal tubules, coupled to K+ and H+ excretion
What is fludrocortisone
Synthetic analogue of aldosterone
What are the effects of too much aldosterone
Hypernatriemia, hypokalemia, metabolic alkalosis, edema
What are the effects of hydrocortisone
Metabolic:
- increase gluconeogenesis
- decrease peripheral glucose uptake
- increase glycogen uptake
- increase lipolysis and lipogenesis resulting in net fat deposition
- aldosterone mineralcorticoid activity when there is too much corticosteroid
Catabolic:
- break down protein in lymph, muscle, skin, bone, connective tissue, releasing nitrogen which is excreted —> negative nitrogen and calcium balance
Feedback inhibition to decrease ACTH secretion
How does steroid regulate gene expression
Highly lipophilic steroid passes the plasma membrane, binds to glucocorticoid receptor. Steroid receptor forms homodimer and enters nucleus
What is the active form of steroid receptor
GR alphas. A-a homodimer necessary for active form
What gene targets do steroids decrease
Cytokines eg Tng-a, is-6, chemokines, inflammatory molecules eg cox-2, 5-lox, pla2, adhesion molecules
What gene targets are increased by steroids
Annexin a1 (PLA2) inhibitor
IL-1 receptor antagonist
IKB-a (inhibitor of NF-kB)
What do steroids do
Increases apoptosis of immune cells eg circulating T cells, monocytes —> immunosuppressive
Increase production and decrease extravasation of neutrophils, hence increased circulating neutrophils (adhesion molecules decreased so cannot travel outside of circulation)
Protein catabolism decrease size and lymphoid content of lymph nodes
Promote macrophage efferocytosis to promote reduction of inflammation
Decrease type 4 delayed hypersensitivity reaction
What drug is used as first line immunosuppressant in transplant
Steroids
Compare effect of steroid on cellular vs humoral immunity
More effect on cellular than humoral immunity
Cortisone vs cortisol/hydrocortisone
Cortisone is the prodrug form
Cortisone has ketone group while cortisol has hydroxy group
Compare prednisone, Prednisolone, cortisone, cortisol
Prednisone has double bound compared to cortisone.
Prednisone is prodrug form of Prednisolone
Prednisolone is more potent than hydrocortisol, works for increased duration (12-36h vs 8-12h)
Prednisolone less water retention effect than cortisol
Which steroids have no water retention effect
Methylprednisolone, triamcinolone, betamethasone, dexamethasone
(Also increasing potency and antiinflammatory effect)
What can steroids be used for
- Allergic reaction
- Collagen vascular disease eg rheumatoid arthritis, lupus erythematous
- GI disease eg Crohns
- Hematologic disorders eg leukemia, hemolytic anemia
- Organ transplant: prevent graft vs host disease and transplant rejection
- Dental conditions eg surgical swelling, gingivitis
Patient needs to stop taking steroid, what should be done
Do not immediately take patient off steroid. Must slowly taper dose as patient may not produce own cortisol
Patient needs to start steroids. What would be good choice to start with
Prednisolone as it is shorter acting (12-36 hours vs 24-72 hours for betamethasone and dexamethasone) and also no water retention effect
Give pulse therapy or on alternate days to minimise effect on cortisol production
What are the side effects of corticosteroids
Hyperglycemia (increase gluconeogenesis sand decrease peripheral glucose uptake)
Moon face, buffalo hump, truncal obesity due to lipid deposition
Muscle wasting due to protein catabolic effect
Growth retardation in pediatric patients
Acne, menstrual disturbances because steroid cross react with hormones
Skin thinning due to decreased collagen (catabolic)
Congestive heart failure, edema, hypertension due to Na+/fluid retention
Osteoporosis
Aseptic necrosis of femoral head as high dose of corticosteroid increase lipid level lead to lipid microemboli formation
Myopathy due to dexamethasone and triamcinolone breaking down muscle
Immunosuppression lead to opportunistic infections
Post subcapsular lens cataract
Peptic ulcer disease
Depression when corticosteroid suddenly withdrawn —> adrenal corticosteroid crisis
What happens when you abruptly withdraw corticosteroid
Lethargy, headache, fever, hypothalamic-pituitary-adrenal axis insufficiency
