Adrenocorticosteroids & Adrenocortical Antagonists Flashcards
What do the adrenal glands produce?
steroid molecules
What controls secretion of the adrenal glands?
pituitary release of corticotropin (ACTH)
What controls the secretion of the salt retaining hormone aldosterone?
Angiotensin
What hypothalamic hormone stimulates the release of adrenocorticotropin from the adrenals?
Corticotropin-releasing hormone (CRH) (+)
The release of ACTH from the pituitary stimulates the ____ to release ____?
adrenal cortex
cortisol
What are the 3 pathways involved in adrenocortical hormone biosynthesis?
mineralocorticoid pathway
-aldosterone
glucocorticoid pathway
-cortisol
androgen & estrogen pathway
What are the physiologic effects of the adrenal hormones?
Regulation of intermediary metabolism
CV func
Growth
Immunity
Synthesis and secretion tightly regulated by CNS
The release of cortisol causes negative feedback on the ___ and ____.
anterior pituitary
hypothalamus
How much cortisol (hydrocortisone) do we release daily?
10-20mg
What controls circadian rhythm?
pulses of ACTH
peak in the early AM and after meals
What is corticosteroid binding globulin?
α2 globulin synthesized by the liver
Binds about 90% of the circulating cortisol under normal circumstances
What increases CBG? What decreases it?
pregnancy, estrogen administration, hyperthyroidism
hypothyroidism, genetic defects in synthesis, protein deficiency states
When are the actions of glucocorticoids most apparent?
in the fasting state when they contribute to maintenance of an adequate glucose supply to the brain
What is the half life? What can increase it?
60-90 mins
hydrocortisone when admin in large amounts, stress, hypothyroidism, liver disease
Where is cortisol metabolized? where is it excreted?
liver
urine
What are some adrenal cortex diseases?
Acute Adrenocortical Insufficiency
—Adrenal crisis
Chronic Adrenocortical Insufficiency
—-Addison’s Disease
Hypercortisolism
—Cushing’s Syndrome
Hyperaldosteronism
What is an adrenal crisis?
emergency state due to insufficient cortisol
Adrenal crisis is MCly seen in…
primary adrenal insufficiency, Addison’s Disease, than is disorders of the pituitary gland
Sxs of adrenal crisis?
Low blood pressure, dehydration, skin pigmentation may be increased
Weakness, abdominal pain, fever, confusion, N/V/D
How can you test for acute adrenocortical insufficiency?
Cosyntropin unable to stimulate an increase in serum cortisol to > 20mcg/ml
Tx for adrenal crisis?
Hydrocortisone 100-300mg IV, then 50-100mg Q6-8hrs
Fludrocortisone Acetate
-consider if pts not response to fluids/vasopressors
Examples of short-medium acting glucocorticoids…
Hydrocortisone*
Prednisone
Cortisone
Prednisolone
Methylprednisolone
Example of intermediate acting glucocorticoid?
Triamcinolone
What kind of steroid is fludrocortisone?
mineralocorticoid
Name two long acting glucocorticoids. Which one is super potent??
Betamethasone
Dexamethasone***
Cause of primary adrenal insufficiency?
dysfunction or absence of the adrenal cortices
s/s of chronic adrenal insufficiency (Addison’s disease)
Skin pigmentation
Hypotension, small heart
Low serum sodium
Elevated K+, Ca++, BUN
Tx for addison’s disease?
hydrocortisone +/- fludrocortisone
how is hydrocortisone dosed in Addison’s disease?
15–30 mg orally daily is drug of choice with 2/3 of dose given in the am and 1/3 given in the late afternoon
What kind of effect can be seen in pt taking Fludrocortisone acetate?
potent sodium retaining effect
When might you increase dose of Fludrocortisone acetate?
when might you decrease?
if patient is experiencing:
Postural hypotension
Hyponatremia
Or hyperkalemia
OR fatigue
Edema
Hypokalemia
OR hypertension
S/s of cushing’s syndrome
Central obesity, muscle wasting
Thin skin, hirsutism, purple striae
Psychological changes
Osteoporosis, hypertension, poor wound healing
elevated Sr cortisol
hyperglycemia
Tx for cushing’s syndrome caused by pituitary adenoma?
transsphenoidal surg
radiation
chemo
Supplement with 6-37 mos of corticosteroids until func. of pituitary normalizes
MOA of Ketoconazole in tx of cushing syndrome? contraindications?
blocks production of cortisol
hepatic disease
If surg is not an option in pt with cushing disease, what medications can you try?
Mitotane, Metyrapone, Mifepristone, Cabergoline, Pasireotide
What can cause hyperaldosteronism?
excess aldosterone secretion
low levels of angiotensin II
What are the 2 forms of hyperaldosteronism?
Primary: aldosterone producing adenoma (Conn’s syndrome)
Secondary: low (suppressed) levels of plasma renin activity and angiotensin II
Sxs of hyperaldosteronism?
Hypertension with hypokalemia or resistant HTN
Tetany/paralysis
Polydipsia/nocturnal polyuria
What drugs can be used in the tx of hyperaldosteronism?
Amiloride
Eplerenone
Spironolactone
ADEs of Amiloride? What should you monitor?
Electrolyte abnormalities (hyperkalemia), hypotension, N/V/D, HA
Monitor: Sr Cr, K, BP
ADEs of Eplerenone? What should you monitor?
Electrolyte abnormalities (hyperkalemia), hypotension, dizziness, headache; gynecomastia and menstrual irregularities are uncommon
Monitor: Sr Cr, K, BP
ADEs of Spironolactone? What should you monitor?
GI discomfort, impotence, gynecomastia, menstrual irregularities, electrolyte abnormalities (hyperkalemia), hypotension
Monitor: Sr Cr, K, BP
What’s the MC cause of cushing’s?
exogenous steroids
