Steroid Flashcards
Rx list
Aldosterone Hydrocortisone (cortisol) Prednisolone Dexamethasone Fludrocortisone
Adrenal steriods
- blood
- types
- own blood supply , from adrenal gland
- Glucocorticoids = anti-inflammatory, carb/protein metab
- Mineralocorticoids = water, elecrolyte balance
Steroid hormones synthesis
From cholesterol
Enzyme deficiency = everything downstream blocked
Which has high salt-retention?
Fludrocortisone
Mineralocorticoid replacement steroid of choice
Cortisol
Stimulated by
ACTH
Aldosterone
Stimulated by
Angiotensin 2 and K+
Hypothalamic-Pituitary-Adrenal (HPA) axis
How release cortisol
- Hypothal releases CRH
- Anterior pituitary releases ACTH
- stim cortisol
- cortisol - negative feedback regulation to posterior pituitary + hypothalamus
*Immune modulators can stim Hypothalamus/Ant. Pituitary
Glucocorticoid synth peaks in
Morning
Glucocorticoid during day
Peaks and troughs
Aldosterone less amount than ACTH
What does not effect ACTH secretion?
Aldosterone
Prob due to low level
Action of glucocorticoid in cell
Regulatory factors change (coactivator/corepressor)
Transrepression= alter other non steroid transcription factors
Glucocorticoid effects
- Blood glucose (UP liver synth, protein breakdown (muscle), free fatty acids (lipolytic signals NOT In face, back of neck)
- Calcium (down renal reabsorb, SLOW BONE GROWTH, Ca/Mg/PO4
- Cardio (HTN)
- Skeletal muscle wasting
- CNS - mood
- endocrine = DOWN growth hormone secretion, UP epinephrine, DOWN major hormone-binding proteins
Anti-inflammatory/immunosupressive
*STOP monocyte proliferation/antigen presentation
DOWN cytokine synthesis
- DOWN lymphocyte cytokine production
- DOWN prostaglandin/leukotriene products
DON’T FIX UNDERLYING DISEASE
GRE
Nucleotide sequence recognized by steroid receptor complex
How to inhibit inflammatory effects via Glucocorticoid receptor
- UP annexin A1 (lipocortin 1) = inhibit Phospholipase A2
- DOWN COX 2 synth (down macrophage, synoviocyte)
- DOWN TNF-a synth
TNF-a effect
Signal for many cell types in inflamation :
Macrophages, neutro, etc.
Corticosteroid Target Tissue Specificity
Cortisol binds to Mineralocorticoid receptor
Mineralocorticoid target tissue inactivates cortisol to cortisone with 11b-HSD2 = stop excessive stimulation to regulate aldosterone-receptor overactivity
What can do same stuff as aldosterone on mineralocorticoid receptor?
Cortisol
Licorice inactivates
Glycirrhizic acid inactivates enzyme (11B-HSD2)
Can’t convert cortisol to cortisone = too much cortisol, so high BP from adosterone receptor
Corticosteroids
Absorption
Metab
T1/2
Well absorbed
Liver metab to urine
Cortisol-VARY BY PATIENT (60-90mins)
Adrenocorticoid use
- Fetal lung maturity
- Hypercorticism
- Replacement Therapy (fludrocortisone)
Pituitary tumor
(Ectopic)
Dexamethasone suppression test
*will supress ACTH from pituitary but NOT from ectopic tumor)
Glucocorticoid toxicity
Not less than 2 weeks
can give cushing’s syndrome
Glucocorticoid
S.E.
- HTN
- Hyperglycemia
- Up Infxn
- Osteoporosis/necrosis