Adrenal Pharmacology Flashcards by Michal Trope

List 5 causes of hyperaldosteronism

Primary hyperaldosteronism
Secondary hyperaldosteronism (cirrhosis, heart failure)
Liddle’s Syndrome (mut in epithelial Na channel, reabsorb Na)
Deoxycorticosterone mediated (too many steroids, bind MCR receptor)
Licorice ingestion (pseudohyperaldosteronism

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What is Spironolactone?

Mineralocorticoid Receptor Antagonist (It also blocks androgen and progesterone receptors)

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What is a side effect of Spironolactone?

Hyperkalemia
Vol depletion
Gynecomastia, impaired libido (androgen binding)
Menstrual irreg in women
Teratogenic

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Why do we use Spironolactone?

Potassium sparing diuretic for essential hypertension, congestive heart failure, cirrhosis, nephrosis and for primary hyperaldosteronism

Off label: PCOS/hirsuitism because of antagonistic binding to androgen receptors

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What are the contraindications of Spironolactone?

Renal impairment
Hyperkalemia
Pregnancy

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What is Eplerenone?

More specific mineralocorticoid receptor antag (but more expensive)

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What do we use Eplerenone for?

K+ sparing diuretic

Primary hyperaldosteronism

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What are the contraindications for Eplerenone?

Renal impairment
Hyperkalemia
Pregnancy

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What is Amiloride?

Blocks the Na+ channel (ENaC)

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Why do we use Amiloride?

K+ sparing diuretic, but it is weak since you still have high aldosterone binding which makes many Na+ channels

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What are the contraindications of Amiloride?

Renal impariment, hyperkalemia

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How do we monitor K+ sparing diuretics?

Monitor for dehydration
Monitor BP
Monitor serum electrolytes (esp k+) and creatinine
In men, monitor for gynecomastia with spironolactone

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What are the 2 reasons to have a deficiency in mineralocorticoids?

Primary adrenal insufficiency (loss of glucocorticoids and mineralocorticoids_
Hyporeninemia (like someone wth diabetic nephropathy)

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How do we treat mineralocorticoid deficiencies?

Mineralocorticoid replacements

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What is fludrocortisone?

Is a synthetic mineralocorticoid replacement that acts like aldosterone used to control hyperkalemia and maintain intravascular volume

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Side effects of fludrocortisone?

Hypokalemia

Volume overload leading to edema, hyperT, congestive heart failure

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How do we monitor fludrocortisone replacement?

Ask pts about presyncope/lightheadedness, salt cravings (under replaced), swelling/edema (over replaced)

Check orthostatic BP/HR

Monitor blood work for Na and K levels and renin activity

What are 3 types of cushings?

ACTH Dependent

Pituitary adenoma
Ectopic ACTH production

ACTH Independent

Adrenocortical adenoma
Bilateral adrenal hyperplasia

Iatrogenic or surreptitious
-Exogenous glucocorticoid use

How do we treat cusings?

Correct underlying cause
Surgery (first line)
Medical (second line)

What is Metyrapone?

Drug that inhibits enzymes in steroidogenesis pathway to decrease production of glucocorticoids

What is Pasireotide?

A somatostatin analog that inhibits ACTH secretion that inhibits adenylyl cyclase pathway to decrase ACTH secretion and inhibits the tyrosine phos pathway to inc apoptosis and cell growth

What receptors do pit adenomas express that are significant for treatment?

Somatostatin and dopamine receptors (can use somatostatin analog or dopamine agonist on the pit to affect ACTH production)

What can you treat a pit adenoma with?

Somatostatin analog (like pasireotide) that selectively binds somatostatin receptor 5

What are side effects of Pasireotide?

Can cause inc of blood glucose levels, cardiac conduction defects or gallstones

How many people does Pasireotide work in?

50% of people, not that great of a drug

What drugs work at the level of 17-hydroxypregnenolone enzyme?

Aminoglutethimide, ketoconazole, mitotane

What drugs work at the level of 17-hydroxyprogesterone?

Ketoconazole

What drugs work at the level of 11-deoxycortisol?

Metyrapone, ketoconazole, mitotane

What do you do to monitor for drugs that dec cortisol?

- Screen for hyper or hypocortisolism - Monitor BP - Measure 24hr urine free cortisol - Check serum electrolytes/creatinine - Check LFTs (esp for ketoconazole and pasireotide) - Check HA1C - If hypercortisolemia from treatment, pts may require replacement hydrocortisone treatment at physiologic doses

What are 2 causes of glucocorticoid def?

- Primary adrenal insufficiecny (def in both gluco and mineralo) - Secondary adrenal insuf (def in glucocort only)

Why would a secondary def cause glucocorticoid def only?

Because 2ndary means that ACTH is low. ACTH is only a weak stim of aldosterone secretion with angiotensin II and K+ being more potent. Therefore you have adequate amounts of aldosterone . In primary, the actual adrenal gland is messed up, meaning that you can't make glucocorticoids or aldosterone

How do we treat glucocorticoid def?

Treat with cortisol replacement like hydrocortisone (shortest half life)

When is it impt to give more hydrocortisone?

When you're sick/have physical stress or in acute shock or adrenal crisis

What happens at hydrocortisone doses >60-80mg daily?

Hydrocortisone has mineralocorticoid activity because high dose can overwhelm cortisol cortisone shunt

When do you not use fludrocortisone replacement with primary adrenal insuff?

When hydrocortisone levels are >60-80mg because it works as the minderalocorticoid

How do we monitor hydrocortisone replacement?

- Clinical assessment - Ask about fatigue and appetite - Check BP, weight (lose weight with adrenal insuff, may gain if overdone) - Check for signs of over replacement (ie iatrogenic Cushing's)

How do we test for adrenal insufficiency?

- If baseline cortisol is low, perform ACTH stimulation test | - Test for adrenal insufficiency (primary and secondary)

What is cosyntropin?

A synthetic ACTH. Can use it to test for insufficiency. Give cosyntropin and then measure cortisol levels 20 and 60 min later. If cortisol levels are <20, have a primary insufficiency. If there is a secondary insufficiency, this test will be normal because you are lacking ACTH. Therefore when you replace ACTH with cosyntropin, the adrenal glands will be stimulated to produce cortisol unless you are in severe secondary where they have atrophied

How do we test for secondary adrenal insufficiency?

- Give metyrapone which blocks 11 beta hydroxylase to decrease cortisol production. - Under normal conditions, low cortisol stimulates ACTH which stimulates the pathway to increase cortisol - With Metyrapone, it can't inc cortisol because it is locking its conversion with Metyrapone. - Instead, get a buildup of cortisol pre-curser 11-deoxycortisol - If you are normal, ACTH levels will be high and cortisol levels will be low after this test - If you have a secondary insuff, cortisol and its precursor 11-deoxycortisol will be low (no ACTH to act as stimulus to increase it/stimulate the pathway) -Monitor pt closely when doing this test because you are essentially putting them in hypocortisol state

What are some side effects of chronic glucocorticoids?

iatrogenic cushings syndrome, associated with use of supraphysiologic dose (>5mg prednisone or equiv)

What is the equiv dose of hydrocortisone?

20mg

What is the equiv dose of dexamethasone?

0.75mg