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Pharmacology > EXAM #5: ADRENAL AGENTS > Flashcards

EXAM #5: ADRENAL AGENTS Flashcards

1
Q

What hormone is released from the hypothalamus in the HPA axis?

A

Corticotropin-releasing hormone (CRH)

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2
Q

How does CRH act on in the Anterior Pituitary?

A

Receptors on the corticotropic cells of the Anterior Pituitary

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3
Q

What is the outcome of CRH activation of the Anterior Pituitary?

A

ACTH secretion

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4
Q

Where does ACTH exert its action?

A

ACTH activates receptors on the ADRENAL CORTEX

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5
Q

What happens when ACTH stimulates the adrenal cortex?

A

1) Increased steroidogenic enzyme expression

2) Stimulation of cortisol and adrenal androgens

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6
Q

What receptors does cortisol bind and activate?

A

Mineralcorticoid

Glucocorticoid

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7
Q

What happens with activation of the mineralcorticoid and glucocorticoid receptors?

A

1) Cortisol binds in cytosol

2) Receptors translocate to nucleus to DECREASE gene expression

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8
Q

What is the role of 11B-HSD2?

A
  • Enzyme in minerocorticoid sensitive tissues
  • Converts active Cortisol to INACTIVE Cortisone

Elevated levels of Cortisol can overwhelm this enzyme and cause adverse effects

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9
Q

What are the major adverse effects seen with elevated Cortisol levels?

A

1) Salt/water retention
2) Hypokalemia
3) HTN

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10
Q

What is the role of 11B-HSD1?

A

Activation of Cortisone to Cortisol

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11
Q

What is the benchmark corticosteroid drug? What is the anti-inflammatory to salt-retaining ratio?

A

Hydrocortisone

1:1

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12
Q

What is the relative duration of action of Prednisone? What is the anti-inflammatory to salt-retaining ratio?

A
  • Intermediate duration of action

- 4:0.8 ratio

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13
Q

What is the relative duration of action of Dexamethasone? What is the anti-inflammatory to salt-retaining ratio?

A
  • Long duration of action

- 30:0

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14
Q

What is the relative duration of action of Fludrocortisone? What is the anti-inflammatory to salt-retaining ratio?

A

Mineralcorticoid with 10:125 ratio

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15
Q

Which corticosteroids are prodrugs? How are they activated?

A

Cortisone and prednisone

*Activated by 11B-HSD1

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16
Q

What is Primary Adrenal Insufficiency or “Addison’s Disease?”

A

Autoimmune or tuberculoid induced destruction of the adrenal cortex leading to deficiency in cortisol, aldosterone, and androgens

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17
Q

What are the symptoms of Primary Adrenal Insufficiency?

A

Hypotension
Hyponatremia
Hyperkalemia
Hypoglycemia

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18
Q

How is Primary Adrenal Insufficiency treated?

A

1) Oral cortisol and liberal Na+ intake

2) Fludrocortisone (mineralcorticoid)

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19
Q

What is Secondary Adrenal Insufficiency?

A

1) Pituitary disease with a decrease in ACTH production and thus, cortisol
2) Hypothalamic disease with decrease in CRH
- Less ACTH
- Less Cortisol

*Note that because aldosterone is controlled by ACE II, people with secondary pituitary DO NOT have elevated aldosterone

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20
Q

How is Secondary Adrenal Insufficiency treated?

A

Cortisol

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21
Q

What is Cushing’s Disease?

A

Corticosteroid excess

22
Q

When is Cushing’s Syndrome commonly seen?

A

Iatrogenic chronic glucocorticoid therapy

Also seen with:

1) Pituitary tumor and increased ACTH
2) Ectopic ACTH tumor
3) Adrenal tumor

23
Q

What are the characteristic features of Cushing’s Syndrome?

A
  • Moon-face
  • Buffalo hump
  • Increased abdominal fat
  • Muscle wasting
  • Osteoporosis
  • Easy bruising
24
Q

What is the utility of high dose dexamethasone suppression test?

A

Determining the etiology of Cushing’s Syndrome

25
What happens with the high-dose dexamethasone test with pituitary hypersecretion of ACTH?
50% reduction in cortisol (b/c of some negative feedback)
26
What happens with the high-dose dexamethasone test with adrenal adenoma?
No reduction in cortisol - CRH and ACTH down
27
What happens with the high-dose dexamethasone test ectoptic ACTH production?
No reduction in cortisol - CRH down but ACTH up
28
What drugs are used to treat Cushing's Disease?
Ketoconazole Metyrapone Mifepristone
29
What is the MOA of Ketoconazole to treat Cushing's Disease?
Antifungal that inhibits 17a-hydroxylase
30
What toxicity is assocaited with Ketoconazole?
Liver toxicity
31
What is the MOA of Metyrapone to treat Cushing's Disease?
Inhibits 11B-hydroxylase
32
What is Metyrapone commonly used for aside from treating Cushing's Disease?
Diagnostic agent to evaluate ACTH production
33
What is the MOA of Mifepristone?
Glucocorticoid receptor antagonist
34
What is the indication for Mifepristone?
1) Inoperable ectopic ACTH production | 2) Adrenal carcinoma
35
What are low doses of Mifepristone used for?
Termination of pregnancy
36
What is the clinical utility for inhaled corticosteroids?
1) First-line in patients with persistent asthma | 2) B2 agonists more than twice a week= indication to start inhaled corticosteroid
37
What is the effect of corticosteroids in the treatment of asthma in patients using B2 agonist on a frequent basis?
1) Corticosteroids increase B2 receptor production | 2) Counter-acts receptor desensitization
38
What are the mechanisms of corticosteroids to treat asthma?
1) Reduced proliferation and hypertrophy of airway smooth muscle 2) Prevents leakage of vascular endothelium 3) Reduce adhesion of molecules in airway epithelial cells 4) Increased epithelial integrity
39
What are the beneficial effects of B2 agonists with corticosteroid use?
1) Increased nuclear translocation of GRs | 2) Increased binding of GR to GREs on genes
40
What is advair?
- Salmeterol= B2 agonist | - Fluticasone= glucocorticoid
41
What are the adverse systemic effects of inhaled glucocorticoids?
Impaired growth in children
42
What are the adverse local effects of inhaled glucocorticoids?
1) Dysphonia 2) Oropharyngeal candidiasis 3) Cough
43
What is the biggest long-term adverse effect of glucocorticoid administration and HPA axis suppression?
Inability to make cortisol in a time of stress-->hypotension
44
What secretes the steroid hormones?
Adrenal CORTEX
45
What are the steroid hormones secreted by the adrenal cortex referred to as?
Corticosteroids
46
What are the three classes of corticosteroids?
1) Glucocorticoids 2) Mineralcorticoids 3) Androgens
47
What is the primary glucocorticoid?
Cortisol
48
What is the primary mineralcorticoid?
Aldosterone
49
What is the effect of Aldosterone on Na+ and K+?
- Increases Na+ absorption | - Causes K+ EXCRETION
50
What are the two enzymes involved in the synthesis of the glucocorticoids that are drug targets
1) 17-a hydroxylase | 2) 11-B hydroxylase
51
Why is the rapid cessation of glucocorticoids dangerous?
1) Cortisol exerts a negative feedback on the hyothalamus and anterior pituitary 2) Synthesis of CRH and ACTH is inhibited with cortisol administration Thus, rapid cessation would lead to dangerous HYPOCORTISOLISM

Pharmacology (64 decks)

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