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xD3 Pharm Exam 2 > Adrenal Corticosteroids (Welch) > Flashcards

Adrenal Corticosteroids (Welch) Flashcards

1
Q

Where are corticosteroids produced?

A

Adrenal Cortex

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2
Q

What are 3 classes of adrenocortical steroids?

A
  1. Glucocorticoids
  2. Mineralocorticoids
  3. Androgens
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3
Q

What are the adrenocortical steroids Glucocorticoids?

A
  1. Cortisol

2. Corticosterone

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4
Q

What are the adrenocortical steroids Mineralocorticoids?

A

Aldosterone

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5
Q

What are the adrenocortical steroids androgens?

A

Dehydroepiandrosterone

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6
Q

Are adrenocortical steroids synthesized and released by stimulation or are they stored, then released with stimulation?

A

Synthesized, not stored

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7
Q

What is the stimulus for Adrenocortical steroid synthesis and release?

A

fight or flight(severe infection, surgery, parturition, cold, exercise, stress)

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8
Q

Where do the stimuli for Adrenocortical steroid synthesis initially act?

A

hypothalamus to release CRH (corticotropic releasing hormone)

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9
Q

Where does Hypothalamic CRH act?

A

Anterior Pituitary to release ACTH (adrenocorticotropic hormone)

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10
Q

Where does Anterior Pituitary ACTH act?

A

Adrenal cortex

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11
Q

What inhibits the Hypothalamus from releasing CRH as well as the Anterior Pituitary from releasing ACTH?

A

Cortisol (glucocorticoid)

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12
Q

Synthesis and release of ACTH by anterior pituitary controlled by 3 main factors?

A
  1. Diurnal basal steroidogenesis
  2. Negative feedback from adrenal steroids (cortisol)
  3. Stress overrides inhibition of ACTH to increase release to aide fight or flight response
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13
Q

Is ACTH effective orally?

A

No must be administered IM or IV

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14
Q

Does straight ACTH have a long half-life?

A

No approximately 15 minutes

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15
Q

ACTH is a product of what?

A

Proopiomelanocortin (POMC)

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16
Q

What are 2 things that come from POMC?

A
  1. ACTH

2. B-endorphin

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17
Q

In fight-or-flight, what are the positive effects of the 2 POMC derivatives, ACTH and B-endorphin?

A
  1. ACTH will get Cortisol to feed body with sugar

2. B-Endorphin is endogenous opiod to decrease pain and keep body from going into shock during fight or flight

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18
Q

Coritcosterone, Cortisol, Testosterone, and Aldosterone all start from what first derivative of Cholesterol?

A

Pregnenolone

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19
Q

What is required for the conversion of cholesterol to Pregnenelone, the precursor to a bunch of adrenocoritical steroids?

A

ACTH and CRH to cause increase in cAMP leading to 20 alpha-hydroxylase to convert cholesterol to pregnenolone which is the rate-limiting step

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20
Q

Describe the cholesterol to aldosterone pathway.

A

CRH to ACTH to ↑cAMP to cholesterol + 20α- hydroxylase to Pregnenolone to Progesterone+21- hydroxylase to Corticosterone to 10-OH- Corticosterone to Aldosterone

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21
Q

Describe the Cholesterol to Cortisol pathway

A

CRH to ACTh to increased cAMP to cholesterol + 20 alpha-hydroxylase to pregnenolone to 17-OH pregnenolone to 17 OH_progesterone to 11-desoxycortisol to cortisol

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22
Q

The synthesis of cortisol does what to the release of CRH and ACTH?

A

Inhibits the release of CRH and ACTH

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23
Q

What are 2 functions of ACTH?

A
  1. Stimulates 20α-hydroxylase rate limiting step of conversion of cholesterol to pregnenolone
  2. Maintain the integrity of adrenal cortex
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24
Q

The synthetic peptide for ACTH, Cosyntropin (Cortrosyn) is used how?

A

Diagnostically, if given, cortisol levels should rise within 30 minutes

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25
Q

What is an inhibitor of 20-hydroxylase which will inhibit cholesterol to pregnenolone conversion, thereby inhibiting the production of Cortisol, Corticosterone, Aldosterone and Dehydroepiandrosterone?

A

Aminoglutethimide

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26
Q

What pt would indicate Aminogluthethemide treatment and what would be the side effects to that treatment?

A
  1. Cushing’s syndrome
  2. Profound Adrenal tumors
  3. Pt will have mineral imbalances, water retention preoblem, infertility
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27
Q

What are 2 things that Aminoglutethimide inhibits?

A
  1. 20 alpha-hydroxylase secretion

2. Aromatase that converts androgens to estrogens

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28
Q

What are 2 clinical uses for Aminoglutethimide?

A
  1. Hypersecretion of cortisol from adrenal tumors

2. Possible treatment for breast cancer

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29
Q

What are 3 adverse effects of Aminoglutethimide treatment?

A
  1. Hirsutism
  2. Hypothyroidism
  3. Leucopenia
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30
Q

What is a more directed chemotherapy to block cortisol, corticosterone, and aldosterone synthesis by blocking the 11 beta-hydroxylase from converting 11-deoxycortisol to cortisol?

A

Metyrapone

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31
Q

What steroid synthesis does Metyrapone NOT inhibit?

A

Dehydroepiandrosterone

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32
Q

What are 3 uses of Metyrapone?

A
  1. Diagnostic for PH / PIT / AC problems
  2. Treat adrenal neoplasms not under control of ACTH
  3. Treat Cushing’s syndrome
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33
Q

How is Metyrapone used diagnostically?

A

If you have confirmed that the adrenal cortex is normal w/ACTH, then metyrapone will cause 11-desoxycortisol to increase and a decrease in cortisol

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34
Q

If give Metyrapone diagnostically and 11- desoxycortisol excretion does not increase as desired, where does the problem lie?

A

In hypothalamus or anterior pituitary

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35
Q

What is a non-FDA approved treatment that is cytotoxic for adrenals and can attenuate Cushing’s disease that results from over-secretion of cortisol by a tumor or ectopic production of ACTH?

A

Mitotane (Lysodern) derivative of DDT

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36
Q

When a patient has inoperable adrenal tumor, they can be given the DDT derivative Mitotane, but what will be the follow on treatment?

A

Patient will be on steroid supplementation for life

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37
Q

What is an antifungal that inhibits glucocorticoid synthesis at higher doses, can be used to treat Cushing’s syndrome?

A

Ketoconazole

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38
Q

In general, what do steroids do when they act on the cell?

A

Cause release of HSP-90(heat shock protein-90), which keeps DNA folded, to open the DNA up allowing for DNA to be transcribed to mRNA and then translated to protein

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39
Q

What are 8 general effects of natural hormones?

A
  1. Carb and protein metabolism
  2. Electrolyte and water balance
  3. Lipid metabolism
  4. Cardiovascular
  5. Skeletal m.
  6. Growth and Cell division
  7. CNS
  8. Anti-inflammatory and immunosuppressive
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40
Q

Cortisol has a huge effect on what?

A

Carb and protein metabolism. Will increase glucose uptake in to eyes, brain, and large muscles (those things for fight or flight) and decrease glucose utilization in other cells

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41
Q

Adrenal insufficiency disease that has symptoms of decreased blood glucose (hypoglycemic), decreased mobilization of protein and fat, muscle weakness, and increased susceptibility to stress and infection?

A

Addison’s disease

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42
Q

What is an adrenal excess disease that has symptoms of increased blood glucose (hyperglycemic), diabetes mellitus, decreased tissue protein, increased plasma volume, and masculinization?

A

Cushing’s syndrome

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43
Q

What is the only difference between diabetes mellitus and Cushing’s syndrome?

A

Adrenal tumor in Cushing’s

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44
Q

Would an addison’s disease patient be alright taking insulin?

A

No. Will be hypersensitive because they are always hypoglycemic

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45
Q

What adrenocorticoid steroids are addison’s disease patients missing?

A
  1. Glucocorticoids (cortisol)

2. Mineralocorticoids (aldosterone)

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46
Q

Moon face, thin skin, obese with thin legs, poor wound healing, are all characteristics of what?

A

Cushing’s syndrome

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47
Q

What is decreased in Cushing’s syndrome?

A
  1. Glucose uptake by cells
  2. Glucose utilization by cells
  3. Protein synthesis by cells
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48
Q

What is increased in Cushing’s syndrome?

A
  1. Plasma glucose
  2. Urinary glucose
  3. Gluconeogenesis from proteins in cells
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49
Q

What adrenocorticosteroid is the major controller of Na retention?

A

Aldosterone

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50
Q

In Cushing’s disease, what does the increase in Aldosterone lead to?

A

More sodium retention so plasma has more volume causing edema and moonface

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51
Q

Because sodium is retained in the kidneys, what is excreted?

A

Hydrogen and potassium

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52
Q

What is caused by the excess loss of hydrogen and potassium in a Cushing’s syndrome patient who is retaining Na due to increased Aldosterone?

A
  1. Alkalotic

2. Hypokalemic

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53
Q

Hypokalemia leads to what symptoms?

A
  1. Cardiac arrhythmias

2. Muscle weakness

54
Q

Will an Addison’s disease patient have high or low plasma volume?

A

Low plasma volume

55
Q

What wil be the symptom of an Addison’s disease patient retaining Hydrogen?

A

They will be acidotic and will hyperventilate

56
Q

What will be a symptom of an Addison’s disease patient retaining postassium?

A

Hyperkalemia will cause cardiac problems

57
Q

Cortisol and corticosterone, when hypersecreted will redistribute body fat where?

A

Neck and face (away from extremities)

58
Q

Is aldosterone effective in lipid metabolism?

A

No

59
Q

The weakness and fatigue in Addison’s is due to what?

A

Reduced circulation (decreased plasma volume)

60
Q

Muscle weakness in Cushing’s syndrome is due to what?

A

Hypokalemia

61
Q

Muscle loss in Cushing’s sndrome is due to what?

A

Increased gluconeogenesis

62
Q

What 2 things glucocorticoids can inhibit with respect to the cell?

A
  1. Cell Division

2. DNA Synthesis

63
Q

How do steroids reduce manifestations of inflammation?

A
  1. Reduced number of peripheral leukocytes
  2. Interfere with leukocytes and macrophages
  3. Inhibit phospholipase A2
64
Q

What are 2 major players of inflammation that steroids inhibit to exert their ant-inflammatory effect?

A
  1. Phospholipase A2 to decrease production of prostaglandins in the body and leukotrienes in the lungs
  2. Inhibit NF-κβ to decrease the stimulation of pro- inflammatory proteins
65
Q

What patient would be more prone to apathy and depression: Addison’s, Cushing / Steroid patient?

A

Addison’s disease

66
Q

Which patient would have mood elevation, insomnia, and restlessness: Addison’s, Cushing / Steroid patient?

A

Cushing’s / Steroid patient

67
Q

Do steroids treat the underlying cause of inflammation?

A

No, strictly palliative to inhibit the early and late phenomena of inflammation

68
Q

Virtually every cytokine is stimulated by what and is therefore inhibited by high-dose steroids?

A

NF-kB

69
Q

What do glucocorticoids directly inhibit which inhibits the production of NF-kB that stops all the inflammatory protein signaling?

A

lkB-kinase

70
Q

Most adverse effects of steroid administration occur when?

A

Chronic administration

71
Q

What is the recovery for the pituitary and adrenals after long-term steroid treatment?

A

9 months

72
Q

What steroids do not contribute to hypokalemic alkalosis and edema?

A
  1. Triamcinolone

2. Dexamethasone

73
Q

What class of adrenocortical steroids alter mucosal defense mechanisms and contribute to ulcers. Can be found in Rheumatoid arthritis patients?

A

Glucocorticoids

74
Q

What is a risk with long-term steroid use that can be treated with bisphosphonates?

A

Osteoporosis

75
Q

What is a steroid therapy giving a single dose of intermediate acting Glucocorticoid on alternate mornings at 8am in an amount equivalent to the total dose ordinarily given over 48hrs to mimic the natural circadian rhythm of cortisol?

A

Alternate day therapy

76
Q

Why does the alternate day therapy give the glucocorticoid dose at 8 am?

A

Cortisol peaks at 8 am when hypothalamic- pituitary axis is lowest

77
Q

Why give an intermediate acting glucocorticoid for the alternate day therapy?

A

The shorter half life allows hypothalamic-pituitary axis to undergo its circadian rhythm but still have pharmacodynamic effect up to 36hrs

78
Q

What is the goal of alternate day therapy?

A
  1. Minimize metabolic effects and keep anti-inflammatory effects
  2. Stimulate normal cyclic steroid levels
79
Q

Can alternate day therapy be used to treat people with autoimmune disease like Rheumatoid Arthritis?

A

No

80
Q

Will a patient on alternate day therapy have a near-normal response to Metyrapone test (increase in 11-desoxycortisol excretion)?

A

Yes

81
Q

What is another reason to use alternate-day therapy?

A

To slowly stop steroid therapy

82
Q

Steroids used in acute cases after cessation of long-term steroid treatment, in chronic diseases where steroids are insufficient, or in hypopituitarism lacking ACTH, all have the goal of what?

A

Replacing needed steroids

83
Q

What are 2 steroids used along with aspirin in the treatment of Rheumatoid Arthritis?

A
  1. Prednisone

2. Triamcinolone

84
Q

When would the steroid Prednisone be indicated to treat Rheumatic Carditis?

A

For congestive heart failure, arrhythmias that do not respond to salicylates

85
Q

Why are steroids not treatment of choice for allergic diseases?

A

Slow to act

86
Q

What steroids are administered IV in life-threatening allergic situations?

A
  1. Dexamethasone

2. Methylprednisolone

87
Q

What is the treatment for bronchial asthma when all other means have failed?

A

Glucocorticoid by conventional route (inhalation) then methylprednisolone IV followed by prednisolone oral

88
Q

Can steroids be given daily for the prevention of bronchial asthma without the risk of adrenal suppression?

A

Yes, in low does (6-8 inhales 50μg/day) (Beclomethasone diprorionate, triamcinolone acetonide, flunisolide)

89
Q

Should steroid eyedrops be prescribed if the eye is infected

A

No

90
Q

What is the risk for treating eye inflammation with a steroid in a person with Glaucoma?

A

Risk of increasing intracellular pressure

91
Q

What steroid is best for Lymphoma treatment in children?

A

Prednisone

92
Q

Why is Prednisolone useful for treating breast cancer?

A

If decrease adrenal cortex, will decrease androgen production, which decreases estrogen

93
Q

What is the dosage for steroid Prednisone treatment in organ tansplants and what is it doing?

A

mg dosing (vs μg for asthma treatment) delays cell-mediated immunity

94
Q

Can Prednisone be used to treat ulcerative colitis or Crohn’s disease?

A

Yes, in mg doses

95
Q

What is ideal for the pharmacodynamics of steroids?

A

Desire low sodium retention to decrease the edema and increased blood pressure from water retention while still having anti-inflammatory effects

96
Q

What are 2 synthetic steroids that have good anti-inflammatory potency while having low sodium retention?

A
  1. Prednisolone

2. Traimcinolone

97
Q

What is the character of glucocorticoids in the plasma?

A

Highly protein-bound so has many drug interactions

98
Q

What is a huge drug interaction with steroids?

A

NSAIDS. Displace the glucocorticoid from the binding globulin and increase glucocorticoid effect on the body

99
Q

Are steroids classified by their therapeutic use?

A

No

100
Q

How are steroids classified?

A

By extent to which they suppress ACTH by negative feedback

101
Q

How long is short-acting ACTH suppression?

A

24-36 hrs

102
Q

How long is intermediate-acting ACTH suppression?

A

48 hrs

103
Q

How long is long-acting ACTH suppression?

A

Greater than 48 hours

104
Q

What are 4 oral short-acting steroids?

A
  1. Cortisol
  2. Cortisone
  3. Corticosterone
  4. Methylprednisolone
105
Q

What are 2 intermediate-acting steroids?

A
  1. Prednisolone

2. Triamcinolone

106
Q

What are 2 long-acting steroids?

A
  1. Dexamethasone

2. Betamethasone

107
Q

As steroids are altered to try and increase their anti-inflammatory effect and decrease their Na retention, a substitution at which Carbon will lead to loss of the mineralocorticoid (aldosterone) activity?

A

C16

108
Q

What is essential at C11 for a steroid to exert glucocorticoid action?

A

Hydroxyl or Ketone

109
Q

Glucose metabolism and what other steroid characteristic are linked because the same receptor mediates both on the cell?

A

Anti-inflammatory action

110
Q

What are 2 steroids that are prodrugs and what must they convert to in order to exert their action?

A
  1. Cortisone convert to active Cortisol

2. Prednisone convert to active Prednisolone

111
Q

What is the drug of choice for systemic anti-inflammatory effects?

A

Prednisolone

112
Q

Why is cortisone not used as a systemic anti-inflammatory?

A

Has higher mineralocorticoid action (Na retention)

113
Q

How is Predisone converted to its active form Prednisolone?

A

Liver type I 11B-hydroxysteroid dehydrogenase

114
Q

Can prednisone bind by itself to its receptor on the cell?

A

No. Must be converted to Prednisolone first.

115
Q

What is relatively more toxic than other glucocorticoids?

A

Triamcinolone

116
Q

Which has greater anti-inflammatory effect: Cortisone or Triamcinolone?

A

Triamcinolone

117
Q

What is the character of the C1-C2 bond of short acting versus intermediate and long acting steroids?

A

Short acting have single bond at C1-C2 Intermediate and long acting have double bond at C1- C2

118
Q

Of the short acting hydrocortisone (cortisol) and cortisone, the intermediate acting prednisone and prednisolone, and the long acting dexamethasone, which one has a methyl group on C16?

A

Dexamethasone

119
Q

Of the short acting hydrocortisone (cortisol) and cortisone, the intermediate acting prednisone and prednisolone, and the long acting dexamethasone, which one has the lowest sodium retention and the most anti-inflammatory potency

A

Dexamethasone

120
Q

Of the short acting hydrocortisone (cortisol) and cortisone, the intermediate acting prednisone and prednisolone, and the long acting dexamethasone, which one has the highest sodium retention and the most anti-inflammatory potency?

A

Hydrocortisone

121
Q

If a person has an adrenal insufficiency (e.g. Addison’s disease) when should their appointment be scheduled?

A

Mornings when cortisol is higher

122
Q

What should the dentist seek to alleviate and why on a patient with adrenal insufficiency?

A

Stress. It can increase cortisol demand.

123
Q

If pt has adrenal insufficiency and the surgery scheduled is major, or will last more than an hour, or will involve general anesthesia, will their normal steroid dose be adequate?

A

No, they will require steroid supplementation

124
Q

Will nitrous oxide or oral benzodiazepine sedation reduce plasma cortisol levels?

A

No

125
Q

What sedative drug class will increase cortisol metabolism and reduce plasma levels of cortisol and are therefore contraindicated in a patient with adrenal insufficiency?

A

Barbiturates

126
Q

If a patient is scheduled for surgery and they are taking an adrenocorticoal antagonist (aminoglutethimide, ketoconazole, Metyrapone,Trilostane, Mitotane) what should they be instructed to do with the consent of their prescribing physician?

A

Discontinue steroid antagonist 24 hrs prior to surgery

127
Q

What local anesthetic is indicated at the end of long procedures for pain control of pt with adrenal insufficiency?

A

Long-acting bupivicaine

128
Q

What are 2 things that can exacerbate hypotension and cause adrenal-insufficiency like symptoms?

A
  1. Blood/fluid loss

2. Anticoagulation therapy

129
Q

Patients whose blood pressure is at or below what mmHg should receive 5% dextrose fluid replacement, a vasopressor, or a glucocorticoid?

A

100 / 60

130
Q

What should a dentist be monitoring for to take quick corrective action on a patient with adrenal insufficiency?

A

Signs of hypotension, hypoglycemia, or hypovolemia

xD3 Pharm Exam 2 (5 decks)

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