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Adrenal Steroids: Glucocorticoids Flashcards

1
Q

What does the adrenal medulla secrete?

A

Epi

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2
Q

What does the adrenal cortex secrete?

A

Corticosteroids and Androgens

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3
Q

Corticosteroids include _______ and ______

A

Glucocorticoids, Mineralocorticoids

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4
Q

What are the functions of glucocorticoids?

A

Metabolic effects (mobilizes glucose), anti-inflammatory (SAIDs)

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5
Q

What is the function of mineralocorticoids?

A

Salt and water retention

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6
Q

Cortisol is a ______

A

Glucocorticoid
(and act at GC receptors)

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7
Q

Aldosterone is a _____

A

Mineralocorticoid
(and act at MC receptors)

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8
Q

What zone of the adrenal cortex secretes cortisol and androgens?

A

Zona fasciculata

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9
Q

The HPA axis is …

A

Hypothalamus (CRF) —> AP (ACTH) —> Adrenal Cortex (Cortisol)

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10
Q

Is cortisol stored?

A

No

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11
Q

Secretion of cortisol occurs in a diurnal rhythm, meaning ….

A

highest early in the AM
lowest in late afternoon

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12
Q

Cortisol is secreted in response to …

A

stress (physical, metabolic, mental)

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13
Q

mineralocorticoids (aldosterone) control ….

A

body fluid and electrolyte levels (sodium and water retention at the collecting duct of the renal nephron)

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14
Q

glucocorticoids have ______ and ______ effects

A

primary metabolic effects
CV effects

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15
Q

Glucocorticoids increase/decrease glucose?

A

increase

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16
Q

Glucocorticoids increase/decrease protein breakdown?

A

increase

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17
Q

Glucocorticoids increase/decrease CO?

A

increase
(also augments epi vasoconstriction)

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18
Q

cortisol is a __ _____ hormone

A

de novo

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19
Q

cortisol binds to ____ AND ____ receptors

A

GC and MC receptors

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20
Q

Aldosterone is regulated mainly by

A

RAAS

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21
Q

RAAS is activated by

A

Low BV, high K+

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22
Q

Aldosterone effects include:

A
  1. increase sodium and water retention
  2. increases K+ and H+ excretion
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23
Q

Cushing’s syndrome is

A

hypercortisolism
(moon face, buffalo hump, muscle wasting, bruise, easily, slow healing, osteoporosis, hypertension, diabetes, mental disturbances, infections)

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24
Q

Addison’s Diseases is

A

adrenal deficiency

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25
cortisol is anabolic/catabolic hormone?
catabolic
26
fat redistribution is Cushing syndrome leads to ...
buffalo hump
27
cortisol decreases body Ca2+ by
decreased GI absorption
28
cortisol alters ____ function
neuronal
29
cortisol ____ growth
inhibits
30
cortisol can induce fetal
lung surfactant
31
pharmacological doses of GC may cause sodium retention, CV issues, K+ and pH disturbances because
cortisol binds MC receptors
32
muscle wasting occurs in Cushing's syndrome because
high cortisol breaks down protein
33
Addison's Disease is adrenal deficiency and can cause
hyperpigmentation, weakness, weight loss, hypotension, depression, low glucose
34
GC withdrawal can cause
adrenal deficiency
35
adrenal hormones and many drug forms are/are not protein bound
are protein bound
36
adrenal steroids are lipid soluble/insoluble
lipid soluble (free hormones/drug can cross cell membranes easily)
37
adrenal steroid drugs activate ______ _____ _____ _____ receptors
intracellular nuclear transcription factors (turn transcription of specific genes on or off) (this takes time)
38
cortisol is slowly/rapidly degraded?
RAPDILY
39
adrenal steroid drugs impact metabolism by reduction of double bonds, conjugation and excreted by the
kidney
40
adrenal steroid drugs can be modified to alter receptor ____
specificity (anti-inflammatory drugs to eliminate MC-mediated adverse effects) (there are a few highly MC-selective for endocrine and related uses)
41
adrenal steroid drugs have structural modification that increase
potency, duration and receptor selectivity
42
Cortisone is a prodrug of
hydrocortisone
43
hydrocortisone has a shorter duration of action of about
8-12 hours (therefore it is good for most endocrine replacement)
44
hydrocortisone has activity and ____ and ____ receptors
GC and MC
45
Due to significant MC receptors effects, hydrocortisone
is used as SAIDs for low level inflammation
46
Prednisone (compared to hydrocortisone) has ____ metabolism, is _____ selective for GC vs. MC receptors and a _____ DOA
Slower metabolism (more potent) Partially selective for GC R Longer DOA (18-36 hours), 1/d admin, convenience/compliance)
47
Dexamethasone is ____ GC selective
HIGHLY (with minimum MC activity)
48
Dexamethasone DOA is
36-54 hours
49
Dexamethasone is very potent and therefore works at ____ doses
low
50
Dexamethasone is important for
very strong anti-inflammatory effects, powerful SAID reserved for severeinflammation
51
Hydrocortisone < prednisone < dexamethasone
increasing selectivity for GC receptors, slower metabolism/increase potency, increased DOA
52
Fludrocortisone use
Endocrine diseases when MC replacement/action is the goal Adrenal failure, 21-hydroxylase deficiency
53
Fludrocortisone has increased potency and selectivity for what kind of receptor?
MC
54
Fludrocortisone is orally effective with
1/d admin
55
In terms of DOA and selectivity, Hydrocortisone is
short-acting non-selective
56
In terms of DOA and selectivity, prednisone is
intermediate-acting partially GC selecting
57
In terms of DOA and selectivity, Dexamethasone is
long-acting highly GC selective
58
Spironolactone is a MC
antagonist
59
Spironolactone uses:
K+ sparing diuretic aldosterone-secreting tumors endocrine disorders with excess MCs
60
Glucocorticoid Preparations are:
1. orally effective, good for long-term replacement 2. water-soluble for parenteral use 3. poorly soluble suspension, sustained effect when given IM 4. local administration to avoid systemic toxicity (i.e. inhalers, nasal sprays, ointments, ophthalmic prep, enemas)
61
What are the most powerful anti-inflammatory drugs?
GCs
62
why are GCs not the first choice as an anti-inflammatory drug?
toxicities
63
GCs decrease redness and swelling via
vasoconstriction, decreased vascular permeability, decreased histamine release
64
GCs decrease fever and pain via
inhibit AA metabolism, decreases prostaglandin/leukotrienes from inflammatory cells and decrease COX2 expression
65
What are the WBC effects of GCs?
decrease all except increased circulating neutrophils
66
What are the cytokines and other mediators effects of GCs?
decrease cytokines, change in tissue degrading enzymes (collagenase)
67
What are the anti-inflammatory and immunosuppressive uses of GCs?
1. arthritis, bursitis 2. skin diseases (i.e. dermatitis) 3. collagen vascular disease (i.e. lupus) 4. hypersensitivity, allergic reaction 5. asthma
68
In terms of drug choice, hydrocortisone is used in:
many OTC preps
69
In terms of drug choice, prednisone
has a longer DOA
70
In terms of drug choice, dexamethasone is used
if very high doses are needed
71
Side effects/toxicities of GC drugs include ____ and ____ receptors toxicities
MC and GC
72
MC receptors toxicities include
high Na+, low K+, alkalosis, edema, HTN
73
GC receptor toxicities include:
1. poor wound healing (due to decreased fibrin, collagen) 2. increased risk of infection (due to immune suppression) 3. decreased response to stress (due to feedback suppression of HPA axis) Also: muscle wasting, weakness, skin thinning, easy brushing, fat redistribution, trunk obesity, osteoporosis, activation of peptic ulcer, diabetes/insulin resistance, weight gain, inhibition of growth in children, euphoria, insomnia, restlessness, psychosis, cataracts, glaucoma
74
contraindications of GC drug use include
CV disease, diabetes, ulcer, infections, osteoporosis, glaucoma ... etc.
75
short term high dose therapy of GC is
safe
76
long term low dose therapy of GC is
safe
77
long term high dose GC therapy can be
very toxic
78
GC steroid therapy is generally only palliative meaning ...
GCs do NOT treat underlying disease
79
Pros and Cons of GC use in terms of underlying disease
Pros: GCs may prevent irreversible tissue damage due to inflammation Cons: GCs may WORSEN underlying disease
80
Clinical strategies to limit toxicities of GC drugs include
use as last resort, lowest dose for shortest amount of time, reduce but maybe not eliminate symptoms, local administration, alternative day therapy, 2/3 dose AM and 1/3 dose PM to mimic normal diurnal rhythm and minimize HPA axis suppression
81
anti-inflammatory effect and toxic effects are mediated by the same/different GC receptor?
SAME

Pharm (6 decks)

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