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Flashcards in Corticosteroids DSA Deck (68):
1

aldosterone

mineralocorticoid

2

cortisol

glucocorticoid

3

CRH

corticotropin releasing hormone

4

ACTH

adrenicorticotropic hormone

5

dexamethasone

semisynthetic glucocorticoid

aka decadron

6

hydrocortisone

semisynthetic glucocorticoid

7

methylprednisolone

semisynthetic glucocorticoid


aka medrol

8

prednisolone

semisynthetic glucocorticoid

9

prednisone

semisynthetic glucocorticoid

10

fludrocortisone

mineralocorticoid

11

zona glomerulosa

ANG II receptor

synthesis of aldosterone

12

zona fasciculata and reticularis

17 alpha hydroxylase and 11-beta hydroxylase

regulated by ACTH

13

POMC

precursor protein

forms MSH, ACTH, LPH, and beta endorphin

14

ACTH MOA

GPCR activity

activates synthesis of corticosteroids

mobilization of cholesterol

also - trophic (growth) effect on adrenal cortical cells

15

diurnal ACTH

peak ACTH early in the morning

16

cortisol negative feedback

inhibit release of CRH from hypothalamus

inhibit release of ACTH from pituitary

17

therapeutic glucocorticoids

high doses for long time
-supress HPA axis

18

stress stimuli

injury, hemorrhage, infection, surgery, cold, pain, fear, etc.

can override normal negative feedback
-leading to elevated levels of adrenocortical steroids

19

cushings syndrome

hypercortisol

20

addisons disease

primary adrenocortical insufficiency

T cell mediated autoimmune destruction, infection, infiltration, cancer, b/l TB of adrenals, hemorrhage
-in adrenal cortex

decreased

21

secondary adrenocortical insufficiency

decreased circulating ACTH levels

adrenal atrophy and low levels of glucocorticoids

may be due to prolonged glucocorticoid tx**

22

ACTH plasma concentration measure

immunoradiometric assay

23

adrenal cortex steroids

corticosteroids - gluco and mineralo - 21 carbons

androgens - 19 carbons

24

type I GR

glucocorticoid receptor - GR

25

type II GR

mineralocorticoid receptor - MR

26

steroid hormone receptor mechanisms

in cytoplasm of cells

complexed with heat shock proteins
-dissociate when bind steroid

activated receptor - to nucleus and bind GREs**

GRE site binding - either activates or inhibits transcription of specific genes

27

cortisol and aldosterone

both bind MR with equal affinity

28

mineralocorticoid specificity

tissue specific localization of receptor

enzymatic protection against glucocorticoid excess
-11-beta hydroxysteroid DH inactivates cortisol to cortisone

differential binding of GR and MR to nuclear transcription factors

29

11-beta hydroxysteroid DH

inactivates cortisol to cortisone

30

effect of corticosteroids

decrease peripheral glucose uptake (anti-insulin)

stimulate protein breakdown and lipolysis

stimulate gluconeogenesis in liver

net effect - elevated blood glucose**

also - redistribution of body fat - moon facies and buffalo hump

31

aldosterone effect

enhance reabsorption of Na in kidney distal tubules and collecting ducts

increased K and H secretion in urine

32

excess aldosterone

elevated Na expansion of ECF volume, hyponatremia, hyperkalemia, acidosis

33

glucocorticoids and immunosuppression

can prevent or suppress inflammation

inhibit production and release of cytokines that normally stimulate proliferation and function of B and T cells

glucocorticoids - suppress IFN, GM-CSF, ILs, TNF, prostaglandins, and leukotrienes

34

IL-1

inflammatory cytokine
-stimulate release of CRH and ACTH
-increase glucocorticoids
-which in response inhibit immune/inflammatory response further

35

steroid absorption

lipophilic

diffuse across cell membranes

wide volume of distribution

36

steroid transport

90% cortisol bound to protein

albumin and corticosteroid binding globulin (CBG

37

transcortin

CBG
-corticosteroid binding globulin

38

higher steroid levels

binding capacity of CBG and albumin is overwhelmed - much more free state and is more active

39

biological half life

used for steroid

because plasma drug concentration does not correlate with time course of bio effects

40

anti-inflammatory effects

mediated by same receptor as metabolic effects
-none of glucocorticoid derivatives have selective anti-inflammatory activity without also affecting carb, protein, fat metabolism

41

compounds that are classified as glucocorticoids

also have modest but significant mineralocorticoid activity

42

long acting glucocorticoids

betamethasone
dexamethasone

43

short acting glucocorticoids

cortisol and cortisone

44

intermediate acting glucocorticoids

prednisone
prednisolone
methylprednisolone
triamcinolone

45

mineralocortoids

corticosterone

fludrocortisone

46

beclomethasone dipropionate

inhalation for asthma or COPD

47

toxicity of adrenocortical steroids

1 - withdrawal effects
2- continued use of high dose

48

withdrawal of adrenocorticosteroids

flare up of underlying disease

acute adrenal insufficiency**

consider this in any patient with high dose over 2 weeks

49

continued use of high dose corticosteroids

suppression of HPA axis
HTN and hypoerglycemia
increased infections
peptic ulcers
myopathy
behavioral changes
cataracts
osteoporosis
osteonecrosis
growth retardation

50

unharmful steroid therapy

single dose or short course (1 week)

51

steroid therapy for life-threatening disease

initial dose should be large - aimed at achieving rapid control of crisis

no benefit observed - dose doubled or tripled

52

steroid therapy regimens

alternate day - to diminish HPA suppression

pulse therapy - for high dose glucocorticoids

53

glucocorticoid therapy

palliative
because underlying cause of disease remains

54

glucocorticoids inhibit

both early inflammatory processes and later manifestations

55

lipocortins

induced by glucocorticoids
-inhibit phospholipase A2 activity and suppress release of lipid mediators from cells

56

rheumatoid arthritis

main cytokine - TNF-alpha

tx - glucocorticoids

57

osteoarthritis tx

intraarticular joint injections

58

ICS therapy

inhaled corticosteroids
-for tx of bronchial asthma

for prophylaxis

59

severe asthma attack tx

aggressive treatment with parenteral glucocorticoids

IV methylprednisolone
-followed by oral prednisone

dose tapered gradually

60

tx allergic disease

immediate epinephrine tx

glucocorticoids to suppress delayed inflammation

61

tx of ocular diseases

topical glucorticoids

may exacerbate glaucoma - increased intraocular eye pressure

may also mask ocular infection - CI in herpes simplex infections

62

CI for glucocorticoids in eye disease

herpes simplex infection

mechanical laceration/abrasion - impaired wound healing

63

skin disease tx

topical glucocorticoids
-hydrocortisone 1%

64

tx of ulcerative colitis and crohns

oral prednisone and enteric coated budesonide

65

cerebral edema tx

corticoisteroids useful with parasites and neoplasms

66

mitotane

o,p - DDD
-similar to insecticides

selective toxicity for adrenal cortex

used only to treat inoperable adrenal tumors

67

RU-486

progesterone receptor antagonist

aka mifepristone

use to terminate early pregnancy

inoperable patients with ectopic ACTH secretion or adrenal cracinoma failed to respond to other tx options

68

spironolactone

K-sparing diuretic
-competes for mineraolcorticoid receptor

aldosterone antagonist

effective tx for hyperaldosteronism