Pharmacology-Adrenal Steroids Flashcards
What would someone look like who has been on prednisone for an extended period of time?
Red cheeks, moon face, buffalo hump, ecchymoses, abdominal fat, stria, hypertension, thin skin, thin extremities and poor wound healing…same as Cushing’s syndrome.
What would someone look like who has been on mineralocorticoids for an extended period of time?
In combination with AT II, long-term elevations cause cardiovascular, renal adrenal and cerebrovascular damage.
What determines if pregnenolone will become aldosterone or cortisol?
Cells in the zona glomerulosa have the 21-hydroxylase to continue down the aldosterone pathway. Cells in the zona reticularis and zona fasciculata only have the 17-hydroxylase to continue down the cortisol pathway.
Where does the rate limiting step of steroid hormone synthesis start? Where does it go from there?
1) Cholesterol -> pregnenolone in mitochondria 2) StAR shuttles them to the smooth ER for the rest of the reactions.
A post-menopausal woman has estrogen-dependent breast cancer that continues to proliferate. What drugs would you give her?
Those that inhibit the aromatase that takes testosterone to estradiol.
How do corticosteroids cause high blood sugar?
They enter the cell and for a dimer with a glucocorticoid receptor. The dimer finds the binding domain on the DNA and causes release of repressor genes and initiates gene transcription of gluconeogenic and glycogenolytic proteins.
How do mineralocorticoids cause increased sodium retention?
Aldosterone enters the cell and forms a dimer with a mineralocorticoid receptor in the cytosol. This dimer finds the binding domain on DNA and releases the repressor causing activation of transcription of proteins that pump Na in from the urine and out to the blood and proteins that pump K in from the blood and out to the urine
Why do you inject joints with cortisone instead of cortisol?
Cortisone is the inactive form of cortisol. By putting that into the joint it sits there and is slowly converted to the active form cortisol by 11beta-HSD1.Then the active form binds the glucocorticoid receptor where inflammation is present and turns of NF-kB production of cytokines, chemokines, adhesion molecules and inflammatory enzymes as well as TNF-alpha, IL-6 and COX-2
How does the kidney prevent overactivation of the mineralocorticoid receptor by cortisol, which can bind the receptor in addition to aldosterone?
The kidney cells have the enzyme 11beta-HSD2, which converts cortisol to the inactive form of cortisone to prevent overactivation of mineralocorticoid receptors.
How do glucocorticoids feedback inhibit the pituitary and hypothalamus?
Some dimerize and kick off activators and DNA binding sites and cause repression, most glucocorticoids bind to protein machinery in the cell and deactivate them to stop production of CRH or ACTH.
When would you prescribe cortisol for replacement therapy?
Addison’s disease (not making cortisol so you replace it), Congenital Adrenal Hyperplasia (trick the pituitary and hypothalamus into thinking there is cortisol production to stop ACTH release and overproduction of androgens)
When would you prescribe cortisol for fetal lung syndrome?
Cortisol increases production of lung surfactant
A soldier is experiencing cerebral edema due to high altitudes. Why do you give hime glucocorticoids?
It can prevent cerebral edema
How do you know prednisone is a prodrug?
The C11 carbon has a carbonyl group instead of a hydroxyl group. This must be changed for activation, which is okay because it is activated in first-pass metabolism through the liver.
What happens when you take chronic steroid patient and take them off abruptly?
Their blood pressure will drop and they crash. This is because of pituitary-adrenal suppression (the adrenals get lazy when cortisol is given).
Drugs that inhibit steroid production enzymes
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