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31 Cards in this Set
- Front
- Back
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What is significant about the structures of adrenal steroids structurally and functionally.
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They are all derived from cholesterol and are similar structurally but they differ in minor oxidation points. However, these minor differences have major effects.
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How are adrenal steroids transported out of the adrenal medulla?
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They are bound the chaperone proteins so that they can be transported in the blood.
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What are the affects of glucocorticoids on metabolism?
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Stimulates hepatic glucose formation
Increases storage of glucose Decreases glucose utilization in the periphery Enhances protein and fat catabolism in the periphery Net result is increased plasma glucose, fat mobilization to the trunk, muscle wasting in the periphery. |
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What are the anti-inflammatory effects of glucocorticoids?
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Inhibit synthesis of leukotrienes and prostaglandins
Decrease histamine Decreased synthesis of interleukins and cytokines. Decreased reactive O2 species. |
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Dexamethasone
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Synthetic drug with highest anti-inflammatory effect and little-no mineralocorticoid effect
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Butamethasone
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High anti-inflammatory effect with little-no mineralocorticoid effect.
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Paramethasone
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High anti-inflammatory effect with little-no mineralocorticoid effect.
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9a-Flurocortisol
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High anti-inflammatory effects and high mineralocorticoid effects.
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Aldosterone
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Highest mineralocorticoid effects with very little anti-inflammatory effects.
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Cortisol
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Moderate anti-inflammatory and mineralocorticoid effects. Effects are equal.
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Addison's Disease
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Primary adrenal insufficiency. Usually caused by auto-immune reaction.
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How is addison's disease treated?
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Replacement 30-40mg cortisol (2/3 given am and 1/3 pm).
Cortisol alone has sufficient glucocorticoid and mineralocorticoid effects. |
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How does illness or stress affect treatment of addison's disease?
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Stress or illness will require a 2-3x increase in cortisol dose.
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What occurs in 21 hydroxylase defficiency?
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Decreased cortisol production causes and increase in ACTH (can lead to adrenal hyperplasia)
Decreased MCC production Increased androgen production (precocious puberty in males and virilization in females) |
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What occurs in 11 beta-hydroxylase deficiency.
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Decreased aldosterone and cortisol production. Increased levels of deoxycorticosterone can act as a MCC.
Increased androgen production (causes precocious puberty and males and virilization in females) |
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What occurs in 17a-hydroxylase defficiency?
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Decreased cortisol and adrenal androgens.
Normal aldosterone production Leads to high BP and feminization in males. |
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How do you treat adrenal enzyme deficiencies?
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Initial treatment - 100mg cortisol daily to reduce ACTH.
Reduce treatment to replacement levels. |
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What are the adverse effect of glucocorticoids on metabolism?
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Can cause increases in glucose production leading to "steroid diabetes"
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What are the adverse effects of GCCs on the skeleton?
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Can lead to osteoporosis.
Steroids decrease Ca absorption which leads to increased PTH. PTH casues bone resorption. |
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What are the effects of GCCs on wound healing?
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They cause delayed wound healing.
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What are the effects of giving GCCs on the adrenal gland?
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One week or more of treatment can lead to adrenal atrophy.
This may depress reactions to stress. |
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What form of GCC therapy is used to prevent adrenal atrophy?
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Alternate day therapy.
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What are some of the etiologies of Cushing's syndrome?
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Pituitary adenoma (Cushings disease)
Nonendocrine tumors secreting ACTH Abnormal adrenal gland responses Ectopic adrenal tissue |
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How is cushings disease diagnosed?
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High urinary free cotrisol >50-100mg/day.
Dexamethasone supression test. High dose of DXM supresses response = true cushings disease. |
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Mitotane
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Drug used to treat Cushings
Derived from DDT. Blocks cytochrome P450. Somewhat specific for reticularis and fasciculata. Major adverse effects. Destroy adrenal tissue. |
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Amphenone B
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Similar to mitotane
Blocks 21,17a,and 11b enzymes Does not destroy tissue Adverse effects have led to removal from US. |
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Metyrapone
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Specific inhibitor of 11B hydroxylase.
Rarely used. Used to pituitary reserve of ACTH. |
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Aminoglutethimide
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Inhibits conversion of cholesterol to pregnenolone.
Reduces MCC, GCC and androgens. Used to treat cushings syndrome secondary to adrenal cancer. |
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Ketoconazole
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Blocks steroid synthesis P450s
Causes compensatory increase in ACTH. Increases estrogen/testosterone ratio. Can cause gynecomastia and oligospermia in males and altered menstual cylce in females. |
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What is a GCC receptor antagonist?
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Mifepristone
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What is a MCC receptor antagonist?
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Spironolactone
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