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Endocrine Exam 1 > Pharmacology: Corticosteroids and Mineralocorticoids > Flashcards

Pharmacology: Corticosteroids and Mineralocorticoids Flashcards

1
Q

What are the 3 categories of steroid hormones secreted by the adrenal gland?

A
  1. Adrogenic/estrogenic steroids
  2. Glucocorticoids
  3. Mineralocorticoids
    (2 & 3 are considered corticosteroids)
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2
Q

What are important regulators of the reproductive system?

A

Androgenic/estrogenic steroids

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3
Q

What mediates intermediary metabolism and immune function?

A

Glucocorticoids

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4
Q

What is the most important glucocorticoid?

A

Cortisol

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5
Q

What has salt-retaining activities?

A

Mineralocorticoids

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6
Q

What is the most important mineralocorticoid?

A

Aldosterone

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7
Q

The classical model (free hormone hypothesis) that dominates endocrinology states that the MOA of steroids (including adrenal steroids) is what?

A
  1. Passively diffuse across plasma membrane
  2. Bind an intracellular receptor which links to a heat-shock protein
  3. Translocates into cell nucleus (where response elements on numerous DNA are located)
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8
Q

What 2 things can the response elements on numerous DNA do?

A

Stimulate or inhibit the transcription of various genes

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9
Q

What are 3 examples of endogenous glucocorticoids?

A
  1. Cortisol
  2. Corticosterone
  3. Cortisone
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10
Q

Cortisol accounts for what % of all glucocorticoid activity and is therefore the most important?

A

95%

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11
Q

What are 3 examples of synthetic glucocorticoids?

A
  1. Fludrocortisone
  2. Dexamethasone
  3. Betamethasone
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12
Q

What are clinical uses of glucocorticoids? (4)

A
  1. Adrenal insufficiencies (Addison’s)
  2. Anti-inflammatory effects (Rheumatoid arthritis, asthma)
  3. Depression of immune response (anti-cancer regimens and transplantation)
  4. Lipolysis
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13
Q

What does treatment for Chronic Addison’s Disease consist of?

A

20-30mg of hydrocortisone daily

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14
Q

What does therapy of 20-30mg of hydrocortisone daily for Chronic Addison’s disease require supplementation with?

A

Salt-retaining hormone like fludrocortisone

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15
Q

Why are long-acting synthetic glucocorticoids (like betamethasone) not suitable for treatment of Addison’s disease?

A

They are devoid of salt-retaining activity

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16
Q

True or False: Acute adrenoinsufficiency can be fatal?

A

TRUE

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17
Q

What is acute adrenoinsufficiency characterized by?

A

Abdominal pain, fatigue, darkening of skin, confusion, or coma

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18
Q

For adrenoinsufficiency, what does therapy include?

A

Large doses (100mg) of hydrocortisone intitially and then the dose is tapered down once patient is stabilized)

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19
Q

What else is an important part of therapy for adrenoinsufficiency?

A

Maintenance of fluid and electrolyte balance

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20
Q

When is a salt-retaining hormone added to the regimen for adrenoinsufficiency?

A

Once the dose of hydrocortisone has been lowered to 50mg/dL

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21
Q

What are 3 early events in the inflammation response?

A

Increased thromboxanes, prostaglandings, and leukotrienes

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22
Q

Increased thromboxanes, prostaglandings, and leukotrienes mediate the early steps of inflammation including what 3 things?

A
  1. Platelet aggregation
  2. Vascular permeability
  3. Vasoconstriction
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23
Q

What blocks inflammatory pathways?

A

Glucocorticoids

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24
Q

What regimens are glucocorticoids often used in?

A

Anti-cancer (ex. MOPP- Prednisone)

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25
Q

Due to the blocking of inflammatory pathways by glucocorticoids, it makes them useful for what?

A

Anti-asthma and anti-inflammatory

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26
Q

What are 3 treatment options for treatment of Cushing Syndrome?

A
  1. Surgical removal of ACTH-producing pituitary tumor
  2. Irradiation of pituitary tumor
  3. Removal of one or both adrenal glands
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27
Q

What is done pharmacologically for treatment of Cushing Syndrome after adrenalectomy (adrenocortical hypo/hyper function)?

A

Large doses of cortisol (300mg) are required initially, then the dose is tapered down

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28
Q

What is required if the adrenal glands are removed?

A

Long-term GC hormone replacement

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29
Q

Why are corticosteroids effecting in the setting of transplant rejection?

A

It is due to their ability to suppress antigens expression from transplant graft and interference with the sensitization of cytotoxic T lymphocytes

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30
Q

Glucocorticoids are useful for the treatment of what type of skin diseases?

A

Inflammatory (psoriasis)

-Synthetic topical non-absorbable glucocorticoids

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31
Q

Why is the use of glucocorticoids hampered in treating things like arthritis and asthma?

A

Adverse effects (osteoporosis)

32
Q

What do long-term glucocorticoids inhibit?

A

ACTH from the pituitary

33
Q

What type of effect does ACTH have on the adrenal cortex?

A

Trophic

34
Q

What will happen if exogenous GCs are withdrawn abruptly?

A

The patient will have chronic adrenal insufficiency

35
Q

How can you avoid chronic adrenal insufficiency due to the abrupt removal of GCs?

A

Taper GCs over months

36
Q

What are 5 toxicities associated with glucocorticoids?

A
  1. Iatrogenic Cushing’s Syndrome caused by prolonged use of synthetic glucocorticoids
  2. Osteoporosis
  3. Impaired wound healing
  4. Multiple disorders for energy storage and possible development of type II DM
  5. Redistribution of fat from periphery to trunk
37
Q

In cases of Cushing’s disease, production of GCs can be stopped by what 3 drugs?

A

Enzyme inhibitors: Mitotane, Metyrapone, or Ketoconazole

Trilostane is only for animals

38
Q

At higher doses, what drug blocks the GC intracellular receptor?

A

Mifepristone (RU-486)

39
Q

What are the 3 mineralocorticoids?

A

Aldosterone, Deoxycorticosterone, and Fludrocortisone

40
Q

What is a synthetic glucocorticoid and is the most commonly prescribed salt-retaining hormone?

A

Fludrocortison

41
Q

What has a similar pharmacology to aldosterone, but is less important pharmacologically?

A

Deoxycorticosterone

42
Q

What is the most important mineralocorticoid in humans?

A

Aldosterone

43
Q

What 2 pathways regulate Aldosterone?

A

ACTH and the renin-angiotensin pathways

44
Q

What is used both for diagnosis and treatment of aldosteronism that is a mineralocorticoid receptor antagonist?

A

Spironolactone

45
Q

What receptors does spironolactone inhibit and what a possible AE of this?

A

Androgen and progesterone receptors- It can cause gynecomastia in men

46
Q

What is a more selective mineralocorticoid receptor antagonist and it inidcated for patients with heart failure?

A

Eplerenone

47
Q

What needs to be monitored with eplerenone?

A

Potassium levels

48
Q

What is an endogenous precursor of aldosterone and is normally secreted in far lower amounts than aldosterone?

A

Deoxycorticosterone (DOC)

49
Q

What controls the release of DOC?

A

ACTH- This is unlike aldosterone

50
Q

What is fludrocortisone?

A

A potent synthetic steroid with both glucocorticoid and mineralocorticoid activity

51
Q

True or False: Fludrocortisone has a much lower first-pass effect than aldosterone?

A

TRUE

52
Q

What must be monitored with fludrocortisone?

A

Blood pressure and serum potassium

53
Q

What are 2 pathophysiologic functions of corticosteroids?

A
  1. Anti-inflammation

2. Immunosuppressant

54
Q

What are 3 general clinical uses of corticosteroids?

A
  1. Adrenoinsufficiency
  2. Adreno hypo and hyperfunction
  3. Diagnosis
55
Q

What are 3 general; toxicities and C/I of corticosteroids?

A
  1. Osteoporosis
  2. Na+ retention
  3. Type II DM
56
Q

What is a clinical term denoting a number of enzyme inherited deficiencies in the adrenal cortex?

A

Congenital adrenal hyperplasia

57
Q

What is the result of congential adrenal hyperplasia?

A

Increased androgen production by the fetal adrenal and ends with masculinizing the fetus

58
Q

For females what is the specific affects of congential adrenal hyperplasia?

A

Hirsuitism and virilization

59
Q

What is the most common deficiency with congential adrenal hyperplasia?

A

Steroid 21-hydroxylase

60
Q

What does a deficiency of steroid 21-hydroxylase cause?

A

The adrenal is unable to metabolize aldosterone or cortisol forcing steroid precursors of these into the androgen-producing pathway

61
Q

An infant with congential adrenal hyperplasia initially has symptoms to what?

A

Those of acute adrenal insufficiency

62
Q

How should infants with congential adrenal hyperplasia be treated?

A

Adminitraction of hydrocortisone accompanied by correct of fluid and electrolyte imbalance (similar to acute adrenal insufficiency)

63
Q

Once an infant with congential adrenal hyperplasia is stabilized, what kind of hydrocortisone is used?

A

ORAL

64
Q

Why must the dose of oral hydrocortisone be adjusted in congential adrenal hyperplasia?

A

To allow proper growth and bone maturation

65
Q

What can used to suppress ACTH without increasing growth inhibition in congenital adrenal hyperplasia?

A

Prednisone

66
Q

What should be administered orally with added salt to maintain normal BP, renin activity, and electrolytes for congential adrenal hyperplasia?

A

Fludrocortisone

67
Q

What is used to diagnose Cushing syndrome and in the differential diagnosis of depression (about 30%)?

A

Dexamethasone suppression test

68
Q

What is the general procedure of the dexamethasone suprression test?

A

1mg of dexamethasone is administered at night and cortisol levels are measured the next morning

69
Q

In a normal individual, what are the cortisol concentrations in the AM after administration of 1mg dexamethasone, in a Cushing’s Syndrome Patient?

A

Normal: Under 3mch/dL

Cushing Syndrome: Over 5mch/dL

70
Q

What can make the results of the dexamethasone suppression test inaccurate?

A

Depression, anxiety, alcoholism, and/or concurrent illness

71
Q

How do you distinguish between pseudo-Cushing’s syndrome and bonafide Cushing’s Syndrome?

A

Combine test of dexamathasone and CRH

-Small dose of dexamthasone is administered every 6 hours for 2 days, followed with a standard CRH test

72
Q

What is seen with distinguished Cushing’s syndrome after dexamethaosne suppression test and CRH?

A

Plasma cortisol concentration greater than 1.4mg/dL measured 15 minutes after cortisol administration

73
Q

What is done do distinguish between Cushing’s disease and steroid-producing tumors of the adrenal gland or in an ectopic ACTH sundrome?

A
  1. 5 mg oral dexamthasone is administered every 6 hours for 2 days, followed by oral 2mg every 6 hours for 2 days
    - 50% decrease in urine cortisol levels distinguishes Cushing’s disease
74
Q

Why do glucocorticoids cause osteoporosis?

A

GCs inhibit vitamin-D mediated calcium absorption (secondary hyperparathyroidism develops) and they also inhibit osteoblast function

75
Q

What is a potent synthetic steroid with both glucocorticoid and mineralocorticoid activity?

A

Fludrocortisone

76
Q

What is very effective in treating adrenocortical insufficiency associated with mineralocorticoid deficiency?

A

Fludrocortisone as low as 0.1mg dose 7 times per week

Anti-inflammatory and anti-growth adverse effects don’t occur at such low doses

Endocrine Exam 1 (11 decks)

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