Adrenal Pharmacology Flashcards
Causes of hyperaldosteronism
Primary, Secondary (cirrhosis, heart failure), Liddle’s, deoxycorticosterone mediated, Licorice
Liddle’s Syndrome
mutation in epithelial sodium channel leading to hyperaldosteronism
Tx for hyperaldosteronism
correct underlying cause, adrenalectomy, medications
Amiloride/midamore
K+ sparing diuretic that blocks ENaC and inhibits sodium reabsorptin into distal tubules
Spironolactone/adlactone
decrease action of mineralocorticoids –> prevent binding of aldosterone to mineralocorticoid receptor –> reduced upregulation of ENaC, K+ channel, and sodium/potassium pump
Eplerenone/Inspra
decrease action of mineralocorticoids –> prevent binding of aldosterone to mineralocorticoid receptor –> reduced upregulation of ENaC, K+ channel, and sodium/potassium pump
T/F spirinolactone can also bind androgen and progesterone receptors
T
Indications for spirinolactone
primary hyperaldosteronism, PCOS/hirsutism (b/c of non specific action), K+ sparing diuretic: essential hypertension, CHF, cirrhosis, hephrosis
Adverse effects of spirinolactone
hyperkalemia, volume depletion, gynecomastia, impaired libido, impotence, menstrual irregularities, teratogenic
Contraindications for spirinolactone
renal impairement, hyperkalemia, pregnancy
T/F Eplerenone can also bind androgen and progesterone receptors
F –> more specific than spirinolactone
Indications for Eplerenone
potassium sparing diuretic, primary hyperaldosteronism
Contraindications for Eplerenone
renal impairement, hyperkalemia, pregnancy
Contraindications for Amiloride
renal impairement, hyperkalemia
What do we monitor when tx hyperaldosteronism?
dehydration, bp, serum electrolytes, gynecomastia
Causes of mineralocorticoid deficiency
primary adrenal insufficiency, hyporeninemia (diabetic nephropathy),
Serum state of mineralocorticoid deficiency
high K, low Na, low volume
Tx of mineralocorticoid
replacement and fludrocortisone (Florinef)
Fludrocortisone
syntehtic mineralocorticoid –> maintain volume and control hyperkalemia
Side effects of Fludrocortisone
hypokalemia, volume overload
Hypercortisolemia causes
ACTH dependent: pituitary adenoma, ectopic
ACTH independent: adrenocortical adenoma, bilateral adrenal hyperplasia
Iatrogenic or surreptitious
Tx of Hypercortisolemia
correct underlying cause/surgery, medical tx is second line –> adrenal cytotoxic, decrease action of glucocorticoids, decrease glucorticoid production
Mifepristone tx of Hypercortisolemia
antagonist for glucocorticoid receptors –> hard to monitor effects
Mitotane tx of Hypercortisolemia
adrenal cytotoxic
Drugs that inhibit steroidogenesis for hypercortisolemia
metyrapone, ketoconazole, aminoglutethimide, etomidate
Drugs that inhibit ACTH secretion for hypercortisolemia
pasireotide (somatostatin analog), cabergolien
T/F pituitary adenomas express somatostatin and dopamine receptors
T –> can use pasireotide and cabergolinea s Tx
Pasireotide MOA
binds somatostatin receptor –> reduced cAMP –> decrease POMC –> decrease ACTH secretion + increased apoptosis/decreased cell growth via PTPase activation
Pasireotide side effects
hyperglycemia, cardiac conduction, gallstones
Enzyme blocked by metyrapone, ketoconazole, mitotane
11beta hydroxylase –> 11 deoxycortisol to cortisol
Enzymes blocked by ketoconazole
1 alpha, 3beta, 11beta –> nonspecific in steroidogenesis pathway
T/F somatostatin and dopamine analogs can be used to treat both acth dependent/independent hypercortisolemia
F –> work on pituitary so only ACTH dependent
T/F ketoconazole can increase liver function tests
T –> must monitor LFT
Why does secondary adrenal insufficiency only affect glucocorticoids but primary adrenal insufficiency affects both glucocorticoids and mineralocorticoids?
If adrenal is not working, cannot have cortisol or aldosterone; if pituitary ACTH is not available, cortisol will not be produced but angiotensin II and potassium can stimulate aldosterone production
Tx of glucocorticoid deficiency
hydrocortisone, prednisone, dexamethasone
Sick day replacement
outpt with fever/illness –> double or triple daily dose
Stress dose replacement
for inpatient illness/perioperative: IV or PO
Acute dose replacement for shock/adrenal crisis
IV –> taper down when appropriate
T/F at doses greater than 60-80mg daily, hydrocortisone has mineralocorticoid activity
T –> can overwhelm 11beta hsd2 shunt in aldosterone sensitive tissues like kidney –> excess hydrocortisone can bind and activate MCR –> dont need to supplement MC until HC <60-80
Metyrapone test for secondary adrenal insufficiency
to distinguish betwn primary/secondary insufficiency after cosyntropin –> metyrapone blocks cortisol production (11 beta hydroxylase)–> low cortisol should stimulate ACTH to restart cortisol production// if normal, ACTH will result in buildup of cortisol precursor: 11 deoxycortisol // if secondary insufficiency, ACTH will not start up –> no buildup of 11 deoxycortisol
