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43 Cards in this Set
- Front
- Back
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Where are adrenocorticoids produced?
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Adrenal Cortex
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What are the two major types of adrenocorticoid and what are their functions?
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Glucocorticoid - metabolism, catabolims, inflammation, immune response
Mineralocorticoid - Na/K reabsorption in the collecting tubules of kidney. |
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What are steroids synthesized from?
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Cholesterol
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What are the main mineralocorticoid and glucocorticoid hormones?
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Aldosterone
Cortisol |
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What are the 2 main effects of aldosterone?
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-Promotes reabsorption of Na into the blood
-Acts on sweat glands to reduce loss of Na in perspiration |
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What are the 3 main effects of cortisol?
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-Gluconeogensis in liver
-Anti-inflammatory -Immune system depressant |
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T/F - Glucocorticoids and Mineralocorticoids are regulated by the same mechanisms
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False - Regulation is independent
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How are glucocorticoids signaled for synthesis and release?
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Hypothalamic-Pituitary-Adrenal Axis
a) Hypothalamus releases Cortiotropin Releasing Factor b) Anterior Pituitary releases AdrenoCorticoTropic Hormone c) Adrenal gland releases cortisol |
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How are mineralocorticoids signaled for release?
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Renin-Angiotensin system
Angiotensin II |
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What 3 disease states are associated with the adrenal cortex?
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Addisons Disease
Cushing's Disease Conn's Syndrome |
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What is the main cause of Addison's Disease?
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Hypo-adrenalism
Decreased secretion of adrenocorticoids |
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Name 4 things that present with Addison's Disease
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N/V
Anorexia Low Blood Pressure Weakness |
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What can cause this decrease in adrenocorticoids? (3)
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-Destruction of adrenal cortex by tuberculosis
-Decreased ACTH release due to diseased anterior pituitary |
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What is the main cause of Cushing's Disease?
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Hyperadrenalism
Increased secretion of adrenocorticoids |
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What 2 things can cause this increase in adrenocorticoids?
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-Tumor of the adrenal cortex
-Increased ACTH due to pituitary carcinoma |
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What is the cause of Conn's Syndrome?
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Inability of adrenal cortex to carry to 17-alpha hydroxylation during biosynthesis from cholesterol.
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What are the consequences of this?
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High secretion of aldosterone that lacks the 17-OH
Hypernatremia, polyuria, alkolosis, hypertension. |
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Draw the transition between cholesterol and aldosterone.
Name the intermetiates. |
Pregnalone
Progesterone 11-deoxycorticosterone Corticosterone Aldosterone |
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Describe the synthesis of cortisol.
What is the structural difference between aldosterone and cortisol? |
Cholesterol is converted to pregnalone, then 17alpha hydroxypregnalone, then 17alpha hydroxyprogesterone, then 11 deoxycortsol then cortisol.
The lone difference between aldosterone and cortisol is the position 17 hydroxyl group. |
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Draw Cholesterol
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Cholesterol
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What enzyme catalyzes the conversion between cholesterol and pregnalone?
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CYP-11A1
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What 3 things are caused by defects in this enzyme?
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Lack of corticosteroids
Feminization Hypertension |
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Where does the conversion from cholesterol to pregnalone take place?
Pregnalone to adrenocorticoids? |
Mitochondria
Endoplasmic Reticulum |
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A glucocorticoid binding its receptor can activate or repress associated genes. In what 3 ways does this action lead to anti-inflammatory/immune effects?
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-Inhibits genes encoding cytokines
-Inhibits production of prostaglandins, leukotrienes, and histamine -Inhibits production of collagenase, an enzyme involved in inflammation. |
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Natural aldosterone has an 11-OH and an 18-OCH3 that forms a hemiacetal and makes it very expensive to synthesize. What is the solution? What are these analogs used to treat?
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- Add a 9 alpha fluoro to cortisol increases the salt retaining and anti-inflammatory capacities. The product is called fludocortisone
- Addison's Disease |
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Why are first generation glucocorticoids undesirable?
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They have moderate salt retention activity.
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What are the 2 main clinical uses for glucocorticoids?
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Arthritis - rheumatoid
Pulmonary - Asthma |
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What drug is formed with the addition of a halogen to the 9 position of cholesterol?
What are the effects on GA's and MA's? |
Fludrocortisone
GA activity increases MA activity increases |
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What drug is formed by the addition of a methyl group to the 6 position of cholesterol?
What is the effect on GA/MA activity? |
Methylprednisolone
GA activity decreases MA activity decreases |
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What drug is created with a 1-isomerization?
What are the effects on GA/MA? |
Prednisone and Prednisolone
GA activity increases MA activity decreases |
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What drug is created with a halogen addition at position 9, isomerization at position 1 and a hydroxylation at position 16?
What is the GA/MA effect? |
Triamicolone
GA increases MA decreases |
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Replacement of the position 16 hydroxyl with an alpha methyl group forms this drug and these effects.
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Dextramethasone
GA increases MA decreases |
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Replacement of the position 16 hydroxyl with a beta methyl group forms this drug and these effects.
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Betamethasone
GA increases MA decreases |
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What are the 3 criteria for intranasal/inhaled glucocorticoids?
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Fast clearance after GI absorption
Short half life, lack of active metabolite High affinity for GR |
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Generally, compounds with a 9-F group are not used for rheumatoid arthritis. Why is this?
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The 9-F group tends to increases salt retention
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What does insertion of a hydroxyl group anywhere cause?
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Reduced salt retention.
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What are 3 more effects of the 9-F?
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Increases GA/MA and nearly prevents metabolic oxidation of the 11 hydroxyl group which is important to receptor binding.
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What is the effect of the position 1 isomerization of prednisolone and prednisone?
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It increases GA and decreases MA
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What 6 substituents greatly decrease salt retention?
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16 alpha OH
16 alpha, 17 alpha ketal 6 alpha methyl 16 alpha and beta methyls |
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What two drugs are mineralocorticoid receptor antagonists?
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Spironolactone
Eplerenone |
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What are the 3 inhibitors of adrenocorticoid synthesis?
How does each work? |
Ketoconazole - inhibits several CYP's
Aminoglutethimide - inhibits CYP 11a1 Metyrapone - inhibits cortisol biosynthesis by inhibiting 11 beta hydroxylase |
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What are the 3 primary routes of metabolism?
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4,5 reduction
3 - ketone reduction 20 - ketone reduction |
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What are the 2 primary metabolites?
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Tetrahydrocortisol
Tetrahydrocortisone |
