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Pharm II > Adrenocorticosteroids and Adrenocortical Antagonists - DONE > Flashcards

Adrenocorticosteroids and Adrenocortical Antagonists - DONE Flashcards

1
Q

65 yo White Male presents with Strongyloides in the lungs. He is currently on mechanical ventilation, hypotensive and hyponatremic.
A cosyntropin stimulation test indicates a inadequate response.

A

IV Hydrocortisone/Oral Fludrocortisone

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2
Q

80 yo African American Female presents to clinic with history of CHF. She is currently receiving Furosemide 40 mg BID, Digoxin 0.125mg daily. Patient has 3 + pitting edema and DOE.

A

Spironolactone

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3
Q

Hypothalamus secretes __ to act on the Anterior PItuitary thus secreting __ to act on the Adrenal glands

A

CRF

ACTH

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4
Q

After ACTH acts on the Adrenal glands, ___ Is released and has a negative feedback on what?

A

Cortisol

Negative feedback on Ant Pit and Hypothalamus

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5
Q

What external stimulates the HPA AXIS to increase release of cortisol?

A

Stress

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6
Q

Regulation of the HPA axis is governed by ___

A

PVN

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7
Q

Parvocellular neurons contain both ___ and ____

A

CRF and Vasopressin

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8
Q

__ elicits ACTH release from Anterior pituitary

A

CRF

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9
Q

__ acts at the adrenal cortex to increase release and synthesis of glucocorticoids

A

ACTH

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10
Q

What are the 3 negative feedback effects of Stress on the HPA Axis?

A

Decrease hypothalamic CRF release
Decrease POMC transcription, ACTH secretion and CRF responsiveness
Decrease production in adrenal cortex

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11
Q

What is the negative feedback effect of ACTH on the HPA axis?

A

decrease hypothalamic CRF release

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12
Q

What is the 2 layers of the adrenal gland (including sublayers) and what is secreted from each??

A 
Cortex
  Zona Glomerulosa - Aldosterone
  Z. Fasciculta - Cortisol
  Z. Reticularis - Testosterone and Estradiol
Medula - Epi and Norepi
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13
Q

What is the name of the hormone steroid that secretes coritsol that effects metabolism and immune function?

A

Glucocorticoids

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14
Q

What is the name of the hormone steroid that secretes aldosterone and effects are salt retaining?

A

Mineralocorticoids

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15
Q

What are the 3 types of Hormone Steroids?

A

Glucocorticoids
Mineralocorticoids
Androgenic/Estrogenic

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16
Q

What hormone has the following effects: Metabolism, Stress response, CV function, Immunity, Fetal Lung Maturation, and Regulated by CNS-negative feedback?

A

Cortisol

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17
Q

The 3 necessary sites of the glucocorticoid activity on coritcosterone are: (Just read these, I doubt she will ask them but just incase!)

A
  1. Hydroxyl group at C17 with associated C20-C21 side chain
  2. Hydroxyl group at C11
  3. Keto C3 and double bond between C4 and C5
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18
Q

How many Glucocorticoid receptors are there and which one has the greater affinity for glucocorticoids? greater affinity for mineralocorticoids?

A

2
equal for glucocorticoids
Type 1 for mineralocorticoids

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19
Q

Glucocorticoid receptors have biological activity through ___

A

alternations in DNA gene transcription

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20
Q

How does Glucocorticoid enter the cell? and then bind to a receptor and cause what?

A

Passive diffusion

Dissociation from HSP-90 (activates it)

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21
Q

What occurs after Glucocorticoid binds to a receptor inside the cell?

A

Dimerizes and translocate into the nucleus

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22
Q

T/F GlucocorticoIds are absorbed rapidly from the GI because they are lipophilic.

A

TRUE!

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23
Q

T/F Glucocorticoids are absorbed slowly through the skin.

A

TRUE!!

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24
Q

T/F Majority of glucocorticoids (90-97%) are plasma protein bound. If true, to what proteins and which one has a higher affinity?

A

TRUE
Cortisol-binding globulin and Albumin
Higher affinity for Cortisol-binding globulin

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25
Q

Where are glucocorticoids metabolized?

A 
Liver
 - Reduction of C4-C5 bond
 - Reduction of Keto at C3
 - Hydroxylation at C6
Kidneys
 - 11 beta-hydroxysteroid dehydrogenase 
 - Cortisol -> Cortisone
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26
Q

What metabolic effects of cortisol are INCREASED?

A
  • increase in plasma glucose by glycogenolysis and gluconeogenesis
  • increase lipolysis
  • increase protein catabolism
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27
Q

What metabolic effects of cortisol are DECREASED?

A
  • decrease uptake of amino acids and protein synthesis
  • decrease Ca absorption from GI
  • decrease thyroid-stimulating hormone secretion
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28
Q

The anti-inflammatory actions of glucocorticoids that INHIBIT something include:

A

Inhibit PLA2, decreased prostaglandin, interleukin, and cytokine production
Inhibit cytokine production and secretion
Inhibit fibroblast proliferation

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29
Q

The anti-inflammatory actions of glucocorticoids that SUPPRESS something include:

A

Suppression of lymphocyte activity and responsiveness

Suppress antigen presentation by macrophages and immunoglobulin production

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30
Q

The anti-inflammatory actions of glucocorticoids that DECREASE something include:

A

Decrease tissue histamine levels
Decrease disposition of fibrogen and collagen
Decrease capillary proliferation

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31
Q

Who has the most risk for glucocorticoid-induced osteoporosis?

A

children and postmenopausal women

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32
Q

In glucocorticoid-induced osteoporosis, there is a ____ in intestinal absorption and renal calcium reabsorption.

A

decrease

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33
Q

In glucocorticoid-induced osteoporosis, there is a ___ in parathyroid hormone secretion catabolizes bone.

34
Q

What is the effect on osteoblast and osteoclast activity in glucocorticoid-induced osteoporosis?

A

Osteoblast are inhibited

Osteoclast have an increased activity

35
Q

What is known as excess glucocorticoids (either endogenous or exogenous)? and Whats a disease associated with it?

A

Hypercortisolemia

Cushing Syndrome

36
Q

What are the effects on plasma cortisol in Cushings? and what is a screening test you can do?

A

Decrease plasma cortisol

Dexamethasone suppression test

37
Q

When there is an adrenal adenoma such as a glucocorticoid producing tumor, this is known as?

38
Q

What is ACTH dependent from either a pituitary tumor, ecoptic ACTH production or ectopic CRF Production?

39
Q

Do you give a high or low dose of dexamethasone test?

40
Q

If the plasma cortisol level decreases by greater than 50%, this is a positive or negative test?

41
Q

If there is no cortisol suppression, decrease in plasma ACTH and increase in plasma ACTH, this is a positive or negative test?

42
Q

Why would the Plasma ACTH Level increase/decrease in a negative Dexamethosone suppression test?

A

If the cause it an adrenal tumor, it will decrease.

If the cause is a ACTH secreting tumor, it will increase.

43
Q

Other than a Dexamethasone test, what can be used to test for Hypercortisolemia?

A

Metyrapone test

44
Q

The Metyrapone test assess what area in the pathology of hypercortisolemia?

A

Assessment of HPA axis function

45
Q

The Dexamethasone suppression test assesses what area in the pathology of hypercortisolemia?

A

Site of dysfunction

46
Q

What is an inhibitor of 11-beta-hydroxylase?

A

Metyrapone

47
Q

If the plasma cortisol level decreases, increase in hypothalamic CRF, increase in plasma ACTH and 11-DOC, this is a positive or negative test?

A

Positive

This indicates the HPA axis is responsive to a decrease in cortisol.

48
Q

What does a negative metyrapone test indicate?

A

a lesion or alteration in the HPA axis

49
Q

What is called a decrease in plasma cortisol from an adrenal insufficiency?

A

Hypocortisolemia

50
Q

What is the most commonly the product of autoimmune polyendocrine deficiency syndrome?

51
Q

Secondary Hypocortisolemia is caused by: (could be 2 things)

A
  • Adrenal Suppression following exogenous glucocorticoids

- Following treatment for Cushings

52
Q

If you give a patient ACTH and there is an INCREASE RESPONSE to ACTH, this is a ___ dysfunction

53
Q

If you give a patient ACTH and there is an NO RESPONSE to ACTH, this is a ___ dysfunction

54
Q

If you give a patient CRH and there is an INCREASE RESPONSE to CRH, this is a ___ dysfunction

A

Hypothalamic

55
Q

If you give a patient CRH and there is an NO RESPONSE to CRH, this is a ___ dysfunction

56
Q

List the Glucocorticoid agonists in the short - medium half-life category which have high mineralocorticoid activity. (5)

A 
Cortisol
Cortisone
Predinsone
Prednisolone
Methylprednisolone
57
Q

List the Glucocorticoid agonist in the intermediate half-life category which have a minimal mineralocorticoid activity. (1)

A

Triamcinolone

58
Q

List the Glucocorticoid agonist in the long half-life category which have a minimal mineralocorticoid activity and maximal anti-inflammatory property. (2)

A

Dexamethasone

Betamethasone

59
Q

What is the MOST POTENT in anti-inflammatory activity when compared to cortisol?

A

Betamethasone

60
Q

What is the LEAST POTENT in anti-inflammatory activity when compared to cortisol?

61
Q

What drug has the GREATEST TOPICAL activity when compared to cortisol?

A

Betamethasone AND Dexamethasone

62
Q

What drug has the GREATEST SALT-RETAINING activity when compared to cortisol?

A

Fludrocortisone

63
Q

What drugs are in the form of injectable?

A 
Coritsol
Predinsolone
Methylprednisolone
Triamcinolone
Betamethasone
Dexamethasone
64
Q

What drugs are in the form of topical?

A

Cortisol
Triamcinolone
Betamethasone
Dexamethasone

65
Q

Side effects of glucocorticoid therapy for high concentrations and extended durations (Just read these!)

A 
Iatrogenic Cushing's syndrome
Immune system suppression
Osteoporosis
Peptic Ulcers
Growth suppression in children
Alterations in CNS Function
Reproductive problems
Prolonged suppression of HPA axis
66
Q

What are some strategies we can do to minimize the side effects of glucocorticoid therapy?

A 
Short or intermediate acting drugs
Pulse dosing
Alternate day dosing
Topical Administration
Adjunct therapy with other anti-inflammatory drugs
A combination of the above strategies
67
Q

What are some effects of the alternate day dosing strategy?

A

Less HPA Axis suppression
Less growth suppression
Anti-Inflammatory properties outlast HPA/Growth suppression
May not provide anti-inflammatory effects in some patients.

68
Q

What is the prototype hormone secreted from the zona glomerulosa of the adrenal cortex and it’s function?

A

Aldosterone (which is a mineralocorticoid)

Promotes sodium reabsorption and potassium excretion

69
Q

Where does Aldosterone bind in the nephron?

A

Distal and collecting tubules

70
Q

List the 3 Mineralocorticoid agonists

A

Aldosterone
Deoxycorticosterone
Fludrocortisone

71
Q

Name the endogenous mineralocorticoid agonist.

A

Aldosterone

72
Q

What is the precursor of aldosterone?

A

Deoxycorticosterone

73
Q

What mineralocorticoid agonist has glucocorticoid activity too?

A

Fludrocortisone

74
Q

The most widely used mineralocorticoid is…

A

Fludrocortisone

In adrenocortical insufficiency associated with mineralocorticoid deficiency

75
Q

Name the corticosteroid ANTAGONISTs that is a cytotoxic agent

76
Q

Name the enzyme inhibitors that are corticosteroid ANTAGONISTS

A

Metyrapone
Abiraterone
Aminoglutethimide
Ketoconazole

77
Q

Name the receptor antagonists of corticosteroid ANTAGONISTS

A

Mifepristone
Eplerenone
Spironolactone

78
Q

Which corticosteroid ANTAGONISTS decreases cortisol and sex steroid formation?

A

Abiraterone

79
Q

What corticosteroid ANTAGONISTS is a aldosterone antagonists AND Its more selective than Spironolactone?

A

Eplerenone

80
Q

T/F Spironolactone is an aldosterone antagonists?

Pharm II (13 decks)

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