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20 Cards in this Set
- Front
- Back
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Inhibitor's of early steps in adrenal hormone synthesis have a broad effect. Name 3 of these broad inhibitors.
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Mitotane
Aminoglutethimide Ketoconazole |
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What is Mitotane indicated for?
How does it work? What is an adverse effect? |
Severe Cushings Disease or Adrenocaortical carcinoma
Toxic to adrencortical mitochondria Hypercholesterolemia |
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What enzymes do Aminoglutethimide inhibit?
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They both inhibit the conversion of cholesterol to pregnenolone via
CYP11A1 Aminoglutethimide inhibits aromatase Ketoconazole inhibits 17 and 20 as well. |
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Name 2 drugs with more selective actions.
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Metyrapone
Trilostane |
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What is Metyrapone indicated for?
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Primary Cushings Syndrome
It is also a test of ACTH reserve because it inhibits cortisol which inhibits ACTH. |
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What is Trilostane indicated for?
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Treatment of secondary Cushing's Syndrome and Primary aldosteronism by reducing aldosterone and cortisol production.
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Describe the GC stimulation test.
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Dexamethasone is administered. A normal gland will produce a decreased amount of cortisol because ACTH is inhibited. An adrenal gland with cushings syndrome will continue to produce elevated cortisol levels.
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Describe the ACTH stimulation test.
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Administer Cosyntropin. A normal adrenal gland will produce cortisol
If the adrenal gland doesn't produce cortisol, then there is either a problem with the adrenal gland (primary insufficiency) or a long standing secondary deficiency that has caused adrenal atrophy. |
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Mitotane, Aminoglutethimide and Ketoconazole all have a broad effect on the inhibition of hormones.
What does Metyrapone inhibit? Trilostane? |
Metyrapone - Cortisol synthesis
Trilostane - Cortisol and aldosterone synthesis |
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What is used to treat life-threatening elevation in GC levels? How does this drug work?
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Mifepristone
GR antagonist |
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Summary of GC Excess Treatment: Correct Underlying Cause
Consider surgery or medical adrenalectomy: Decrease the production of GC's: Decrease the action of GC's: |
Mitotane
Aminoglutethimide, Metyrapone, Ketoconazole Mifepristone |
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Why is aldosterone not effective as replacement therapy?
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Short half life
Low affinity binding High first pass metabolism |
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Why is the collecting duct protected from the MC effects of cortisol?
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The kidney has the type II enzyme that converts cortisol to cortisone.
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What does hyperaldosteronism cause?
Hypoadolsteronism? |
Alkalosis
Acidosis |
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What is responsible for increased aldosterone secretion?
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Decreased blood pressure
Decrease sodium Increased potassium ACTH - minor |
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What is used in replacement therapy for hypoaldosteronism?
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Fludrocortisone - 100% MC at low doses
+ GC |
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What are fludrocortisones adverse effects
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Hypertension
Hypokalemia Heart failure |
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What 2 drugs are used in therapy for hyperaldosteronism?
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Eplerenone
Spirinolactone Hyperkalemia Volume depletion Gynecomastia in males |
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What causes Congenital Adrenal Hyperplasia? What are the consequences?
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A deficiency in the enzyme 21-hydroxylase. As a consequence, Aldosterone and Cortisol cannot be made and Testosterone is made in larger amounts. DHEA and Androstenedione are made and the liver converts them to Testosterone.
In males, this an acute salt wasting crisis. In females, this can cause a masculinizing effect and ambiguous genitalia. In more mild cases, it will cause hirsutism, acne and oligomenorrhea |
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How do you treat congenital adrenal hyperplasia?
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GC replacement to suppress ACTH
MC such as fludrocortisone |
