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Pharm > Adrenal > Flashcards

Adrenal Flashcards

1
Q

What are the chemicals that are synthesized by the adrenal cortex?

A

Mineralocorticoids
Glucocorticoids
Androgens

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2
Q

What are the two chemicals that are secreted by the medulla of the adrenal glands?

A

Epi and norepi (catecholamines)

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3
Q

What is the function of the mineralocorticoids (aldosterone)? (3)

A

Increases Na reabsorption in the collecting tubule

Increases K excretion

Increase BP

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4
Q

What are the physiological effects of glucocorticoids?

A

Restoring homeostasis after exposure to stress:

Increases BG levels
Counterbalance immune system

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5
Q

What are the two glucocorticoids?

A

Cortisol, hydrocortisone

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6
Q

What are the two drug targets of corticosteroid biosynthesis?

A

17 alpha hydroxlaye

11 beta hydroxylase

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7
Q

What are the relative levels of aldosterone and cortisol in the blood normally?

A

High cortisol, low aldosterone

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8
Q

What is the effect of ACTH that is release from the anterior pituitary on the adrenal cortex?

A

Increased steroidogenic enzyme expression

Stimulates production of cortisol and adrenal androgens

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9
Q

What is the problem with long term use of corticosteroids?

A

Steroid rebound

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10
Q

What is the MOA of glucocorticoids and mineralocorticoids?

A

Freely cross the lipid membrane, and interact with receptors in the cytoplasm, and then enter the nucleus to alter expression

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11
Q

What is the intracellular messenger that is inhibited in glucocorticoid/mineralocorticoid use, to immune suppress pts?

A

NfKappaB

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12
Q

True or false: cortisol binds and activates mineralocorticoids and glucocorticoids

A

True

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13
Q

What enzyme activates cortisol into inactive cortisone?

A

11beta HSD1

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14
Q

What is the enzyme that converts cortisone into cortisol?

A

11beta-HSD2

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15
Q

What is the function of 11beta HSD1?

A

Activates cortisone to cortisol

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16
Q

What is the function of 11beta HSD2?

A

Inactivates cortisol into cortisone

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17
Q

What are the two short acting glucocorticoids? Which effect is predominant: anti inflammatory or salt retention?

A

Hydrocortisone
Cortisone

Both equally

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18
Q

What are the four intermediate acting corticosteroids? Which effect is predominant: anti inflammatory or salt retention?

A

Prednisone
Prednisolone
Methylprednisolone
Triamcinolone

Anti inflammatory

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19
Q

What are the two long acting corticosteroids? Which effect is predominant: anti inflammatory or salt retention?

A

Betamethasone
Dexamethasone

No salt retention

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20
Q

What is the use of fludrocortisone?

A

Increase salt retention (BP)

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21
Q

What makes the glucocorticoids prodrugs?

A

Adding a hydroxyl group to the ring

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22
Q

Is dexamethasone a prodrug? Prednisolone? cortisone? Prednisone?

A

Prednisone and cortisone are.

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23
Q

What are the causes the Addison’s disease?

A

Autoimmune or TB causes deficiency in cortisol, aldosterone, and androgens

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24
Q

What happens to ACTH and CRH levels in primary (Addison’s) adrenal insufficiency? Aldosterone? Why? What does this lead to?

A

Elevated– adrenal cortex is lacking a mechanism for feedback

Aldosterone decreases, leading to K retention and Na loss

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25
Q

What is the treatment for Addison’s? (2)

A

Fludrocortisone and oral cortisol

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26
Q

What are the effects of Addison’s?

A

Hypotension from unresponsiveness of vascular smooth muscle to catecholamines

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27
Q

What are the two causes of secondary adrenal insufficiency? What are CRH and ACTH levels in these?

A

Either decrease in ACTH from pituitary, causing an increase in CRH, and a decrease in cortisol

OR

No CRH from the hypothalamus, lowering ACTH, and lower cortisol

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28
Q

What is the treatment for secondary adrenal insufficiency? Why?

A

Cortisol

NOT fludrocortisone, since aldosterone function is still retained

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29
Q

When is Glucocorticoid levels highest physiologically? What is the effect on the dosing regimen with this?

A

In the morning

Higher doses then

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30
Q

What is the cause of Cushing’s syndrome?

A

Chronic glucocorticoid excess

  • Iatrogenic
  • Pituitary tumor that secretes ACTH
  • SCLC secretion of ACTH
  • Adrenal tumor that hypersecrete cortisol
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31
Q

What are the ssx of Cushing’s?

A
  • Buffalo hump
  • Increased abdominal fat
  • Muscle wasting
  • Moon facies
  • Poor wound healing
  • Thinning of the skin
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32
Q

What happens to bones in Cushing’s?

A

Osteoporosis

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33
Q

What happens to BP with Cushing’s? Why?

A

Increased d/t increased cortisol levels in the adrenal cortex (swamped 11bHSD2)

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34
Q

What happens with CRH and ACTH with: pituitary hypersecretion of ACTH

A

Increased ACTH

Decreased CRH

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35
Q

What happens with CRH and ACTH with: adrenal adenoma?

A

Decreased in both ACTH and CRh

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36
Q

What happens with CRH and ACTH with: ectopic ACTH production

A

Decreased CRH

Increased ACTH from ectopic production

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37
Q

What happens if dexamethasone is injected into a pt wit pituitary hypersecretion of ACTH? Why?

A

Usually around 50% reduction in cortisol

The pituitary is still somewhat responsive to dexamethasone.

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38
Q

What happens if dexamethasone is injected into a pt with ectopic production of ACTH? Why?

A

No reduction in cortisol

ACTH secreting adenoma has no regulatory function like the pituitary

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39
Q

What happens if dexamethasone is injected into a pt with adrenal adenoma? Why?

A

No reduction is cortisol

Tumors in the adrenal cortex would have no regulatory function with dexamethasone

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40
Q

What is the MOA of ketoconazole in treating Cushing’s?

A

Inhibits 17 alpha hydroxylase, which can lower cortisol production.

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41
Q

What is the major side effect of Ketoconazole?

A

Hepatotoxic

42
Q

What is the MOA of Metyrapone in treating Cushings?

A

Inhibits 11beta hydroxylase leading to decreased aldosterone and cortisol production

43
Q

Draw out aldosterone pathway

A
44
Q

What is the MOA of Mifepristone? What is it normally used for? What is its basis for the use in cushing’s?

A

Anti-progestin effects (abortion)

Glucocorticoid receptor antagonist at high doses

45
Q

What is the main use of glucocorticoids?

A

Anti-inflammatory effects
Reduce histamine release
Treats hypersensitivity

46
Q

What is the use of glucocorticoids in preterms?

A

Increased lung maturation

47
Q

What is the effect of glucocorticoids on: macrophages?

A

Decrease activation

Decrease cytokine release

48
Q

What is the effect of glucocorticoids on: PMNs?

A

Stabilize lysosomal membrane

Prevent release of catabolic enzymes

49
Q

What is the effect of glucocorticoids on: mast cells?

A

Inhibit release of histamine, prostaglandins

Increase annexin 1

50
Q

What is the effect of glucocorticoids on: eosinophils?

A

Inhibit release of histamine, prostaglandins

51
Q

What is the effect of glucocorticoids on: T cells?

A

Suppress activation

Decrease cytokine release

52
Q

What is the effect of inhibition of phospholipase A2 by glucocorticoids?

A

Decreased production of lipid mediators

53
Q

What is the effect of inhibition of COX by glucocorticoids?

A

Decreased prostaglandin release

54
Q

What is the effect of inhibition of Cytokine production by glucocorticoids?

A

Suppression of cell mediated inflammation

55
Q

What is the effects of corticosteroids on vessels?

A

Vasoconstriction

56
Q

What is the use of inhaled corticosteroids?

A

Asthma treatment

57
Q

What are the four inhaled corticosteroids?

A

Budesonide
Fluticasone
Mometasone
Triamcinolone

58
Q

Why should you treat asthma with glucocorticoids and not just beta2 receptor agonists?

A

Beta 2 use will downregulate the receptors, but glucocorticoids will increase it back

59
Q

What is the MOA of glucocorticoids in the asthma? (3)

A

Decreased cell leakiness
Decreased proliferation of airway smooth muscle
Decrease mucus secretion

60
Q

What is the effect of beta2 agonists on Glucocorticoid receptors?

A

Increase translocation of GRs, and increase binding of GR to GRE on genes

61
Q

What is Advair?

A

Fluticasone + salmeterol

62
Q

What percent of glucocorticoids are bound to albumin? Is this active?

A

greater than 90%

This is inactive

63
Q

What is the effect of glucocorticoid on liver disease?

A

Lower albumin means more available to work

64
Q

What is the relative affinity of dexamethasone for albumin? What is the significance of this?

A

Low

Those with liver disease need lower dosages

65
Q

What are the adverse effects of inhaled glucocorticoids?

A

Dysphonia
Oropharyngeal candidiasis
Cough

66
Q

True or false: inhaled glucocorticoids have a high first pass effect

A

True–most is swallowed

67
Q

What is the effect of glucocorticoids on: K levels

A

Decreased

68
Q

What is the effect of glucocorticoids on:BP

A

Increased

69
Q

What is the effect of glucocorticoids on: growth in children

A

Decreased

70
Q

What is the effect of glucocorticoids on: glaucoma

A

Increased risk

71
Q

What is the effect of glucocorticoids on: appetite?

A

Increased

72
Q

Why does high doses of glucocorticoids cause hypokalemia? Does this happen with dexamethasone?

A

Hits the glucocorticoid receptor in the kidneys

Does not occur with dexamethasone

73
Q

HPA axis suppression may not return for how long?

A

Over 12 months

74
Q

What are the measures to minimize the HPA axis suppression?

A

Use short acting compounds
Low dose
Short duration

75
Q

What is the effect of long term HPA suppression that may lead to death?

A

Times of stress will not increase BP, with vasodilation, causing death

76
Q

What are the drugs that induce p450s and thus increase degradation of glucocorticoids?

A

barbs
Carbamazepine
Rifampin

77
Q

What are the drugs that increase the effect of glucocorticoids? Why?

A

Estrogens/androgen d/t competition for p450s

78
Q

What is the interaction between cyclosporine and glucocorticoids?

A

Increase levels by inhibiting each other’s metabolism

79
Q

Why is coadministering glucocorticoid with NSAIDs bad?

A

Increases the risk of PUDs

80
Q

Which drugs can glucocorticoids reduce the effects of?

A

Hypoglycemic drugs
BP meds
Glaucoma meds

81
Q

What is the MOA of high dose glucocorticoid causing hypertension/hypokalemia? Would this be caused by dexamethasone?

A

Oversaturation of 11beta-HSD2, leading to inactivation of

82
Q

What is the therapeutic use and MOA of ketoconazole?

A

Inhibits 17 beta hydroxylase

83
Q

The adrenal cortex regulates what?

A

BP
Na
K
metabolism

84
Q

Steroid hormones are secreted by what organ? What are these?

A

Adrenal cortex
Glucocorticoids
Mineralocorticoids
Androgens

85
Q

Catecholamines are what? What organ secretes this?

A

Adrenal medulla

Epi and NE

86
Q

What is cholesterol converted into once inside the mitochondria? What enzyme converts this?

A

Pregnenolone via cholesterol desmolase

87
Q

After pregnenolone is converted from cholesterol by cholesterol desmolase, what is it next converted to? What enzyme does this?

A

17alpha-hydroxylase converts it to 17alpha-hydroxypregnenolone

88
Q

17-alpha-hydroxyPregnenolone is converted to what by what enzyme?

A

Converted into 17 hydroxyprogesterone via 3beta-HSD

89
Q

17 hydroxyproGesterone is converted to what by what?

A

11-beta-(OH)

21-hydroxylase

90
Q

What is the primary molecule that regulates aldosterone synthesis?

A

Angiotensin II

91
Q

Describe the HPA axis in terms of cortisol production?

A

Diurnal rhythms send signals to the hypothalamus to secrete CRH via the corticotroph cells. CRH causes ACTH release from the pituitary

92
Q

ACTH binds to what receptor? Where is this located? What does this cause?

A

MCR2 on the surface of the adrenal cortex, causing an increase in cholesterol import.

93
Q

Describe the events of the renin-angiotensin axis?

A

Renin released by kidneys Cleaves angiotensinogen to ang I. ACE converts ang I to II.

94
Q

How is the HPA axis inhibited with cortisol?

A

Cortisol will bind to glucocorticoid receptor on corticotrophs

95
Q

What is the effect of glucocorticoids on plasma glucose levels?

A

Increases

96
Q

What is the effect of glucocorticoids on liver gluconeogenesis?

A

Increases gluconeogenesis enzymes

97
Q

What is the effect of glucocorticoids on protein synthesis?

A

Reduces

98
Q

What is the effect of glucocorticoids on lipolysis?

A

increases

99
Q

What is the effect of glucocorticoids on insulin like action?

A

Inhibits insulin’s effects except in the brain and heart

100
Q

Both cortisol and aldosterone activate the same mineralocorticoid receptor in the adrenal cortex, but cortisol levels are always much higher? How does aldosterone exert its effects? What happens with high exogenous cortisol use?

A

11beta-HSD2 converts cortisol into inactive cortisone

High cortisol levels can saturate the 11beta-HSD2 enzyme, allowing cortisol to bind to the mineralocorticoid receptor, and allowing HTN and hypokalemia

101
Q

What happens to aldosterone levels in secondary adrenal insufficiency? What is the significance of this?

A

Stays normal.

Does not lead to K retention and Na loss like primary

102
Q

What is the effect of corticosteroids on the following: phospholipase, COX, NO synthase, cytokine production

A

All decreases

Pharm (73 decks)

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