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therapeutics 1 kappa epsilon version > Glucocorticoids > Flashcards

Glucocorticoids Flashcards

1
Q

Types of Adrenocorticoids

A

Glucocorticoids and Mineralocorticoids

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2
Q

Glucocorticoids:
_______ hormone
Increases ________ concentrations
Potent __________ effect

A

Stress; Glucose; Anti-inflammtory

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3
Q

Mineralocorticoids:
Regulates _________
Controls _________

A

Na/K+ level; Blood pressure

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4
Q

Adrenal Gland:

What comes from the Cortex?

A

Glucocorticoids; Mineralocorticoids; Androgens

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5
Q

Adrenal Gland:

what comes from the medulla?

A

Epinephrine and Norepinephrine

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6
Q

What is the HPA Axis

A

Hypothalamus Pituitary Adrenal Axis

1) Hypothal senses stress
2) Hypothal makes CRH
3) CRH goes to Ant. Pituitary
4) Ant. Pituitary makes ACTH
5) ACTH stimulates Adrenal gland
6) Adrenal gland makes cortisol

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7
Q

Stress Hormones: Epi vs. Cortisol

Epinephrine binds to what receptor?

A

Beta-adrenergic receptor (GPCR)

will stimulate GaS pathywat - more cAMP

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8
Q

Stress Hormones: Epi vs. Cortisol

Which one is immediate response and which one is long term response?

A

immediate: Epi
Cortisol: long term/has to regulate gene transcription

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9
Q

Stress Hormones: Epi vs. Cortisol

Cortisol binds to what receptor?

A

nuclear hormone receptor

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10
Q

Stress Hormones: Epi vs. Cortisol

Epi role in the body

A

breaks down glycogen/release insulin

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11
Q

Stress Hormones: Epi vs. Cortisol

Cortisol role in the body

A

induce gluconeogeneic enzymes

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12
Q

How does glucocorticoids affect the LIVER

A

increase gluconeogenesis and increase glycogen storage (because it becomes readily available glucose)

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13
Q

How does glucocorticoids affect the Muscle

A

promote protein degradation
decrease protein synthesis
decrease sensitivity to INSULIN

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14
Q

How does glucocorticoids affect the Adipose tissue

A 
promote lipolysis (break down for energy)
decrease sensitivity to insulin
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15
Q

Glucocorticoids reduce the sensitivity to insulin in what areas?

A

muscle and adipose tissues

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16
Q

How does glucocorticoids affect the immune system

A

blocks synthesis of cytokines and inhibits production of eicosanoids
leads to IMMUNOSUPRESSION AND ANTI-INFLAMMATION

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17
Q

Classic Model of Steroid Action:
Hormone binds to Hormone receptor and ______ is released; Then the hormone receptor will move to the _______ and work as a __________ factor

A

heat shock proteins; nucleus; transcription

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18
Q

Hormone receptors move to nucleus to affect transcription and do this by binding as a _______

A

dimer

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19
Q

what is the HRE

A

Hormone responsive elements - is where dimers bind on DNA

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20
Q

where is HRE found

A

upstream from steroid responsive genes

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21
Q

Glucocorticoids upregulate what kind of enzymes?

A

ones that cause gluconeogensis and anti-inflammatory proteins

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22
Q

what is lipocortin I?

A

it comes from glucocorticoids (somehow) and it will suppress phospholipase A2 –> will hault eicosanoid synthesis

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23
Q

what is NFkB?

A

it is Nuclear Factor kB - and it normally activates immune cells/causes cytokines to be made

24
Q

when NFkB is inactive - it is bound to ________ and forms a _________

A

IkB; heterodimer

25
Q

when the cell is under immune cell activation - what happens to NFkB?

A

IkB is removed from NFkB which allows NFkB to move to the nucleus and turn on transcription for cytokine genes

26
Q

Relationship b/w glucocorticoids and NFkB?

A

activated glucocorticoid receptor will bind to NFkB and prevent NFkB from making cytokines via altering gene transcription

27
Q

A __________ will sequester NFkB

A

GR-GR dimer

GR = glucocorticoid receptor

28
Q

Best Type of Glucocorticoid for therapy =

  • maximize _________ acitivity
  • minimize _________ activity
  • prevent _______ & ________
A

anti-inflammatory; mineralcorticoid; Cushing’s syndrome; Addisonian Crisis

29
Q

Glucocorticoids vs. Mineralcorticoids

what 2 things are NEEDED for GC activity?

A

11-B hydroxyl

C17 hydroxyl

30
Q

Glucocorticoids vs. Mineralcorticoids

What 2 things are required for BOTH (GC and MC)

A

4-5 double bond

C3 ketone

31
Q

Which Synthetic Glucocorticoid?

has a 9a-F

A

Fludrocortisone

32
Q

Which Synthetic Glucocorticoid?

used in mineralocorticoid replacement therapy

A

Fludrocortisone

33
Q

Which Synthetic Glucocorticoid?

has extra double bond b/w C1/C2

A

Prednisone/Prednisolone

34
Q

Which Synthetic Glucocorticoid?

Needs to be converted to its active form by the liver

A

Prednisone

35
Q

Which Synthetic Glucocorticoid?

Which two are enantiomers of each other?

A

Dexmethasone and Betamethasone

36
Q

Which Synthetic Glucocorticoid?

has a 6a-methyl group

A

methylprednisolone

37
Q

triamcinolone has increased ____-ilicity

A

hydro–

38
Q

dexamethasone has increased ____-ilicity

A

lipo–

39
Q

Since Dexamethasone does have increased lipophilicity - how does it affect binding and effect

A

it has INCREASED RECEPTOR BINDING and STRONGER EFFECT

40
Q

Glucocorticoids can be made into ProDrugs - they get activated ________ by _______

A

hydrolysis; esterases

41
Q

Glucocorticoids & ProDrugs:

What are the types of ProDrug “side chain”/”add-ons”

A

Acetate/butyrate; Phosphate; Succinate

42
Q

Glucocorticoids & ProDrugs:

How does Acetate/Butyrate affect the glucocorticoid

A
  • increases LIPOPHILLICITY
  • prolonged action/will stay at site LONGER
    (via injection)
43
Q

Glucocorticoids & ProDrugs:

How does Phosphate affect the glucocorticoid

A
  • increases SOLUBILITY
  • rapid hydrolysis
  • OPTIMAL for IV or IM
44
Q

Glucocorticoids & ProDrugs:

How does succinate affect the glucocorticoid

A
  • soluble

- SLOW hydrolysis

45
Q

Which adrenocorticoid(s) have the lowest MC activity (aka 0 on the chart he gave us..)

A
  • methylprednisolone
  • triamcinolone
  • dexamethasone
  • betamethasone
46
Q

Which adrenocorticoid(s) have the highest MC activity

A

fludrocortisone

47
Q

Adverse effects of Corticoids:

- if there is crossover mineralcorticoid activity…

A
  • EDEMA via Na/Water retention

- development of HTN

48
Q

Adverse effects of Corticoids:

what are the Cushing Like effects

A

Redistribution of fate aka
Moon face/Buffalo hump
-NON-REVERSIBLE

49
Q

Adverse effects of Corticoids:

What are some metabolic effects

A
  • steroid myopathy (lose muscle)
  • reduced long bone growth in children
  • osteoporosis
50
Q

How can corticoids lead to osteoporosis

A

glucocorticoids inhibit OSTEOBLASTS (they normally BUILD BONES)

51
Q

How to prevent osteoporosis from corticoids

A

bisphosphanates

52
Q

Adverse effects of Corticoids:

GI effect?

A

greater peptic ulcer risk

53
Q

Symptoms of Addisonian Crisis

A
  • inability to withstand stress
  • hypotension
  • weakness
54
Q

Why can Addisonian Crisis happen

A

its due to negative feedback on the hypothalamus and pituitary from prolonged doses of glucocorticoids

55
Q

Which Inhaled Glucocorticoid?

has rapid metabolism by the liver

A

Flunisolide/Aerobid

therapeutics 1 kappa epsilon version (17 decks)

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