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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
Q

What happens with the high-dose dexamethasone test with pituitary hypersecretion of ACTH?

A

50% reduction in cortisol (b/c of some negative feedback)

26
Q

What happens with the high-dose dexamethasone test with adrenal adenoma?

A

No reduction in cortisol

  • CRH and ACTH down
27
Q

What happens with the high-dose dexamethasone test ectoptic ACTH production?

A

No reduction in cortisol

  • CRH down but ACTH up
28
Q

What drugs are used to treat Cushing’s Disease?

A

Ketoconazole
Metyrapone
Mifepristone

29
Q

What is the MOA of Ketoconazole to treat Cushing’s Disease?

A

Antifungal that inhibits 17a-hydroxylase

30
Q

What toxicity is assocaited with Ketoconazole?

A

Liver toxicity

31
Q

What is the MOA of Metyrapone to treat Cushing’s Disease?

A

Inhibits 11B-hydroxylase

32
Q

What is Metyrapone commonly used for aside from treating Cushing’s Disease?

A

Diagnostic agent to evaluate ACTH production

33
Q

What is the MOA of Mifepristone?

A

Glucocorticoid receptor antagonist

34
Q

What is the indication for Mifepristone?

A

1) Inoperable ectopic ACTH production

2) Adrenal carcinoma

35
Q

What are low doses of Mifepristone used for?

A

Termination of pregnancy

36
Q

What is the clinical utility for inhaled corticosteroids?

A

1) First-line in patients with persistent asthma

2) B2 agonists more than twice a week= indication to start inhaled corticosteroid

37
Q

What is the effect of corticosteroids in the treatment of asthma in patients using B2 agonist on a frequent basis?

A

1) Corticosteroids increase B2 receptor production

2) Counter-acts receptor desensitization

38
Q

What are the mechanisms of corticosteroids to treat asthma?

A

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
Q

What are the beneficial effects of B2 agonists with corticosteroid use?

A

1) Increased nuclear translocation of GRs

2) Increased binding of GR to GREs on genes

40
Q

What is advair?

A
  • Salmeterol= B2 agonist

- Fluticasone= glucocorticoid

41
Q

What are the adverse systemic effects of inhaled glucocorticoids?

A

Impaired growth in children

42
Q

What are the adverse local effects of inhaled glucocorticoids?

A

1) Dysphonia
2) Oropharyngeal candidiasis
3) Cough

43
Q

What is the biggest long-term adverse effect of glucocorticoid administration and HPA axis suppression?

A

Inability to make cortisol in a time of stress–>hypotension

44
Q

What secretes the steroid hormones?

A

Adrenal CORTEX

45
Q

What are the steroid hormones secreted by the adrenal cortex referred to as?

A

Corticosteroids

46
Q

What are the three classes of corticosteroids?

A

1) Glucocorticoids
2) Mineralcorticoids
3) Androgens

47
Q

What is the primary glucocorticoid?

A

Cortisol

48
Q

What is the primary mineralcorticoid?

A

Aldosterone

49
Q

What is the effect of Aldosterone on Na+ and K+?

A
  • Increases Na+ absorption

- Causes K+ EXCRETION

50
Q

What are the two enzymes involved in the synthesis of the glucocorticoids that are drug targets

A

1) 17-a hydroxylase

2) 11-B hydroxylase

51
Q

Why is the rapid cessation of glucocorticoids dangerous?

A

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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