Adrenal Pharmacology (Exam 1) Flashcards
In order for corticosteroids to be released from the adrenal cortex, the hypothalamus releases _____, which stimulates the ant. pituitary to release _____, which stimulates the adrenal cortex.
CRF
ACTH
Corticosteroids refers to?
Steroids made by the adrenal cortex -> mineralocorticoids and glucocorticoids
Function of glucocorticoids?
metabolic, anti-inflammatory, and immunosuppressive
Function of mineralocorticoids?
Peripheral actions on salt and water metabolism
What are the zones of the adrenal cortex and what hormones does each produce?
Glomerulosa - Aldosterone
Fasiculata - Cortisol
Reticularis - DHEA
Where do glucocorticoids provide negative feedback?
At the ant pituitary on ACTH release
At the hypothalamus on CRF release
What hormone released by the zona fasiculata is a glucocorticoid?
Cortisol
Chronic use of GCs can cause?
Adrenal atrophy due to suppression of the HPA axis.
Insufficient adrenal response to environmental stressors known as adrenal crisis is treated with?
Supplemental GCs
Secretion or cortisol peaks when?
Early AM and evening
Cortisol in the blood is bound by _____.
Cortisol binding globulin (CBGs)
T/F? Only free cortisol is active?
True
T1/2 of cortisol?
60-90 minutes
Cortisol actions on muscle cells?
Decrease glucose uptake
Increase protein breakdown
Overall - Muscle wasting
Cortisol actions on fat cells?
Decrease glucose uptake
Increase fat breakdown peripherally.
Decrease fat breakdown centripetally.
Cortisol actions on liver cells?
Gluconeogenesis leading to hyperglycemia
Permissive effects of glucocorticoids?
Vasoconstrictor
Fat cell lipolytic response to epi, ACTH, GH
Normal cardiac output
What hormone released by the adrenal cortex is a mineralocorticoid?
Aldosterone
Effects of aldosterone?
Na+ reabsorption at kidney leading to increased blood volume and BP
Excess aldosterone would cause what symptoms?
Hypertension, hypokalemia, metabolic alkalosis
T/F? Anti-inflammatory effects of GCs can be separated from immunosuppressive effects.
False
Addison’s disease is ____ adrenal insufficiency.
Primary
Addison’s disease requires replacement of both GCs and MCs. What medications should be used to replace them?
Hydrocortisone or Prednisone Or Dexamethasone +/- fludrocortisone
What medication is used for it’s anti-inflammatory/immunosuppressive properties without MC activity?
Dexamethasone
Why must prednisone be given orally?
Gets metabolized to active form - prednisolone in the liver.
Rank the following drugs from most to least anti-inflammatory potency. Dexamethasone Cortisol Fludrocortisone Prednisone Triamcinolone Aldosterone
Dexamethasone Fludrocortisone Triamcinolone Prednisone Cortisol Aldosterone
Rank the following drugs from most to least salt-retaining potency.
Cortisol
Fludrocortisone
Prednisone
Aldosterone
Aldosterone
Fludrocortisone
Cortisol
Prednisone
What advantage do dexamethasone and prednisone have over hydrocortisone in the treatment of Addison’s disease?
They are longer acting than hydrocortisone
When would you add fludrocortisone to a patients treatment for Addison’s
If they are hypotensive.
T/F? DHEA can help with mood and well being in all patients with Addison’s.
False - only in some women
Treatment for adrenal crisis?
Volume replenishment
Large amounts of IV hydrocortisone if pervious diagnosis
Dexamethasone if no previous diagnosis
Why does the treatment differ for patients with a previous diagnosis of Addison’s?
Dexamethasone does not interfere with cortisol labs
Cushing’s disease is _____ hypercortisolism
Secondary
Treatment of choice for Cushing’s?
Surgery
What types of medications can be used for adjunctive therapy or pharmacotherapy in inoperable cases of Cushing’s?
Cortisol synthesis inhibitors
GC receptor antagonists
Somatostatin analogs
What cortisol synthesis inhibitors are used early? late?
Early - ketoconazole
late - Metyrapone, etomidate
What medication is a GC receptor antagonist?
Mifepristone (RU-486)
What medication is a somatostatin analog that is used in Cushing’s?
Pasireotide
Is the dose of ketoconazole higher or lower in Cushing’s when comparted to the antifungal dose?
Higher
Adverse reactions to ketaconazole?
headache, n/v, gynecomastia, impotence, reversible hepatotoxicity.
Adverse reactions to metyrapome?
Hirsutism in women, Na+ retention and HTN
Congenital adrenal hyperplasia is treated with?
Cortisol +/- fludrocortisone
Before surgery for a pheochromocytoma, what medications need to be given?
An alpha blocker - phenoxybenzamine (or terazosin/doxazosin)
A beta blocker - Metoprolol (or labetalol)
+/- nicardipine depending on BP
If a pheochromocytoma is inoperable, what medication would be added?
Metyrosine (catecholamine synthesis inhibitor
Treatment of choice for adrenomedullary hyperfunction?
Surgery
In Congenital adrenal hyperplasia is cortisol synthesis and secretion increased or decreased
It is decreased, which results in INCREASED ACTH and then ADRENAL HYPERPLASIA
What would you see with a 21-hydroxylase deficiency?
- No cortisol synthesis —– > increased ACTH—-> allowing excess androgen——> VIRILIZING
- No desoxycorticosterone OR aldosterone synthesis ——-> DECREASED MC activity ——-> Hypotension
What would you see with 17a-hydroxylase deficency?
- No cortisol synthesis —– > increased ACTH—–> INCREASED desoxycorticosterone——> INCREASED MC ACTIVITY———> Hypertension
- No adrenal androgen synthesis—-> NON-VIRILIZING
what would you see with 11-hydroxylase deficency?
- No cortisol synthesis —– > increased ACTH—-> allowing excess androgen——> VIRILIZING
- No cortisol synthesis —– > increased ACTH—–> INCREASED desoxycorticosterone——> INCREASED MC ACTIVITY———> Hypertension
is Phenoxybenzamine a reversible or irreversible α1-α2 receptor antagonist?
irreversible
________ is a competitive inhibitor of catecholamine synthesis
Metyrosine
What effect does physiologic levels of cortisol have on Carbohydrate?
increased gluconeogenesis—-> increased blood glucose (increased insulin)
What effect does physiologic levels of cortisol have on protein?
increased AA uptake into liver and kidney
DECREASED protein synthesis (except liver)
What effect does physiologic levels of cortisol have on lipids?
- increase lipolysis (peripherally)—-> increased fatty acids
What is the Net Physiologic Result of physiologic levels of glucocorticoids?
Maintenance of glucose supply to brain
