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Flashcards in Adrenocorticosteroids Deck (71):
1

where is the adrenal gland

top of kidneys

2

hypothalamic pituitary adrenal HPA axis mechanism

the hypothalamus releases peptide corticotropin-releasing factor (CRF) and travels to anterior pituitary to release ACTH

3

what does ACTH stimulate

In the adrenal cortex
z. glmerulose - water
z. gasciculata - cortisol
z. reticularis - androgens

4

addison disease

cortisol deficiency

5

primary cause of addison

adrenal dysfunction

6

secondary cause of addison

pituitary or hypothalalamic dysfunction

7

symptoms of addison

fatigue, muscle weakness, hypotension, hypoglycemia, fatal

8

cushing disease

cortisol excess

9

cause cushing

excess ACTH from pituitary secretion - often from tumor

10

symptoms of cushing

fatigue, muscle weakness, hypertension, weight gain, hyperglycemia, osteoporosis

11

where is adrenocorticotropic hormone ACTH formed

precursor from POMC (which also produces b-endorphins)

12

what is the chemistry of ACTH

- 39 polypeptide
- 1-19 amino acids have 30%
- 1-20 amino acids have 100%

13

what is cosyntropin

- diagnostic drug containing 1-24 ACTH toi test HPA axis

14

what is the ACTH MOA

- ACTH bound to G protein - protein kinase - mitochondria to turn on cholesterol synthesis

15

production of steroid mechanism

cholesterol to pregnenolone to cortisol, progesterone, androgens, aldosterone

16

what are thetherapeutic pharmacokinetics of ACTH

can't be taken orally, IV, intramuscular and is a peptide

17

how is addison disease treated

ACTH gel

18

how is primary adrenal insufficiency diagnosed

cosyntropin

19

what are mineralocorticoids

aldosterone and balances electrolytes

20

what are glucocorticoids

cortisol and metabolism of carbs, lipids, protein

21

how are corticosteroids beneficial/used for

- adrenal insufficiency
- collagen
- bronchial asthma
- inflammatory disease
- chemotherapy
- immunosuppression
- lupus

22

what are the glucocorticoid receptors

- N-terminal (site of transcription)
- central DNA binding protein: DBD
- C-terminal ligand: LBD

23

where are steroid receptors

inside the cell

24

role of glucocorticoid receptors

- decrease pro-inflammatory and increases anti-inflammatory

25

mechanism of anti-inflammatory gene expression

- cortisol binds cytosolic glucocorticoid receptor then GR binds to DNA (glucocorticoid response elements)

26

MOA corticosteroid inflammatory suppression

- steroid hormone binds to receptor
- translocation of steroid-receptor
- bind to DNA of regulaiton site
- transcription
- translocation

27

what are the genes that produce inflammatory cytokines

collagenase, elastase, plasminogen

28

what are the clinical effects of cortisol

- gluconeogenesis
- muscle weakness
- abnormal redistribution of fat
- atrophy of lymphoid tissue
- bone resorption
- ocular toxicity
- CNS
- mineralcorticoid activity

29

what are the gluconeogenic effects

- protein catabolism = gluconeogensis
- lipd catabolism = FA and TG syntehsis

30

how does hyperglycemia occur

decrease glucose utilization and increase glucose syn.

31

what are the site of gluconeogenic effects

liver, fat, muscle, bone

32

where does PEPCK expression occur

increases in the liver

33

where does PEPCK suppression occur

adipose tissue (releases FA for energy)

34

a lack of glycerol 3-P causes what

reduces lipogensis in adipose tissue

35

adverse effects on muscle

muscle weakness from: decrease glucose utilization, excretion potassium, decrease gene expression to repair

36

how does corticosteroids cause atrophy of lymph nodes, spleen, and thymus

reducing circulating monocytes, T cells, and plasma cells which leads to reduction of macrophages = anti-inflammatory and immunosuppressive

37

what are the effects of anti-inflammatory/immunosuppressive effects

long term treatment = infection from decrease levels of cytokines because corticosteroids cause inhbition

38

what are the key mediators of immune response regulated by glucocorticoids

- IL-1, 2, 6 and TNF alpha

39

redistribution of fat

changes in lipid metabolism - moon facies and buffalo hump

40

effects on bone

resorption by activation osteoclast and inhabiting osteoblasts and osteonecrosis from emboli in bone due to hyperlipidemia

41

effect on CNS

changes in glucose and electrolytes cause over expression in hippocampus and pre-frontal cortex

42

what are the components of the stress-brain loop

chronic stress cause increase glucocorticoids, cellular changes in hippocampus, and decreased regulation of cortisol

43

effects of mineralocorticoid

retention of sodium in distal and collecting duct

44

short term effect of mineralocorticoid

edema

45

long term effect of mineralocorticoid

- HTN and congestive heart failure
- alkalosis from loss of potassium and chloride at distal end

46

short term drugs

- Cortisol (smaller potency)
- Prednisone
- Prednisolone
- Meprednisone

47

medium term drugs

- Triamcinolone
- Paramethasone

48

long term drugs

- Betamethasone
- Dexamethasone

49

other drugs

- Fluorometholone
- Fludrocorticsone (higher potency)
- Medrysone

50

how are corticosteroids administered

- good absorption from GI tract and little from topically
- phosphate esters are water soluble and injected into synovial space
- acetate esters are lipid soluble

51

can phosphate esters penetrate corneal epithelium?

no

52

can acetate esters penetrate corneal epithelium?

yes

53

role of transocrotin

binding globulin and has high affinity but low capacity

54

role of albumin

plasma protein with low binding affinity but high binding capacity

55

metabolism corticosteroids location

in liver and kidney

56

how corticosteroids metabolised

glucuronide and sulfate conjugates
- excreted as 17-hydroxy and 17-keto-steroids

57

requirements of ocular corticosteroid therapy

cross blood-aqueous barrier (secreted from ciliary body) to diffuse from capillaries of iris, retina, ciliary body

58

why would we use ocular corticosteroid therapy

inflammation of optic nerve, retina, and uveal tract

59

corneal epithelium and endothelium are..

lipophili

60

stroma is..

hydrophilic

61

corticosteroid compounds must be..

bipolar with some affinity for water and lipid

62

what is the order from greatest to least of compounds that can penetrate the cornea

1. biphasic acid
2. alcohol
3. phosphate

63

what are the risks of long term corticosteroids

increase IOP and cataracts

64

prednisolone sodium phosphate

- mild superficial and does not penetrate cornea wall

65

prednisolone acetate

- bipolar solubility characteristics = treat many types of inflammation
- increase IOP because corneal permeability

66

medrysone

- mild surface inflammation
- IOP increased but less than prednisolone

67

loteprednol etabonate

- opthalmic 0.2 and 0.5%
- derived from prednisone
- chronic/long term

68

fluromoetholone alcohol (FML)

- liquidfilm, forte, ointment
- does not penetrate cornea (less likely to increase IOP)
- chronic/longterm

69

fluormotheolone acetate

- flarex
- chronic/longterm
- therapeutic = prednisolone acetate but less IOP effect

70

ocular toxicity of corticosteroids

- posterior subcapular cataracts
- glaucoma
- infection

71

corticosteroid reactions

- alkalosis
- edema
- HTN
- glaucoma
- infection and delayed would healing
- peptic ulcer
- muscle weakness
- mood changes
- osteoporosis
- hisutism
- growth suppresion
- hyperglycemia