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PHRM 825 Steroids Exam 2 > Corticosteroids > Flashcards

Corticosteroids Flashcards

1
Q

How does the hypothalamus and pituitary regulate the biosynthesis of cortisol?

A

the hypothalamus sends CRH to the pituitary gland then produces ACTH that then stimulates the adrenal gland to produce cortisol

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2
Q

What is the regulation of glucocorticoid synthesis?

A
  1. Stress
  2. hypothalamus
  3. produce CRH
  4. Pituitary gland
  5. ACTH made
  6. Adrenal gland makes cortisol
  7. can either go back in a feedback loop or produce physiological responses
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3
Q

what is the regulation of mineralocorticoid synthesis?

A
  1. liver
  2. angiotensinogen produced
  3. angiotensin 1
  4. angiotensin 2
  5. adrenal glands to produce aldosterone
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4
Q

what is a glucocorticoid and its structure?

A
  1. stress hormone
  2. inc. circulating glucose conc.
  3. potent anti-inflammatory effects
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5
Q

what is a mineralocorticoid and its structure?

A
  1. Na+ retention
  2. Inc. blood volume and BP
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6
Q

what are the two modes of actions of glucocorticoids?

A
  1. cortisol
  2. epinephrine
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7
Q

what is epinepherine’s mode of action?

A
  1. bind to GPCR
  2. initiate signal transduction pathway
  3. induce immediate response
  4. break down glycogen and release glucose
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8
Q

what is cortisol’s mode of action?

A
  1. bind to nuclear hormone receptor
  2. regulate gene transcription –> translation/production
  3. induce long term response
  4. induce gluconeogenic enzymes
  5. inhibit pro-inflammatory response
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9
Q

where do glucocorticoids have physiologic effects?

A
  1. liver
  2. muscle
  3. adipose tissues
  4. immune system
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10
Q

what are the effects of the liver?

A
  1. inc gluconeogenesis
  2. inc glycogen storage
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11
Q

what are the effects of the muscle?

A
  1. promote muscle degradation
  2. dec protein synthesis
  3. dec sensitivity to insulin
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12
Q

what are the effects of adipose tissue?

A
  1. promote lipolysis
  2. decrease sensitivity to insulin
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13
Q

what are the effects of the immune system?

A
  1. block the synthesis of cytokines –> immunosuppression
  2. inhibit production of eicosanoids –> anti-inflammation
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14
Q

what do the liver/muscle/adipose tissue have in common?

A

increase blood glucose levels

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15
Q

what is the cause of addison’s disease?

A
  1. hypoadrenalism
  2. destruction of the cortex by tuberculorsis or atrophy
  3. dec. secretion of ACTH
  4. cessation of long-term steroid use
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16
Q

How are each level of hormone affected by addison’s disease?

A
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17
Q

what is the cause of cushing’s disease?

A
  1. hyperaldreanlism
  2. tumors in adrenal cortex
  3. inc. production of ACTH due to pituitary carcinoma
  4. ectopic production of ACTH due to non-pituitary carcinoma
  5. long-term steroid use
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18
Q

how are each level of hormone affected by cushing’s disease?

A
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19
Q

what systemic corticosteroids are short-acting?

A
  1. hydrocortisone
  2. cortisone
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20
Q

what systemic corticosteroids are intermediate-acting?

A
  1. prednisone
  2. prednisolone
  3. methylprednisolone
  4. triamcinolone
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21
Q

what systemic corticosteroids are long-acting?

A
  1. dexmethasone
  2. betamethasone
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22
Q

what is fludrocortisone?

A
  1. F sub on carbon 9a
  2. greater glucocorticoid activity
  3. strong mineralocorticoid activity (Na+ retention –> edema)
  4. used in mineralocorticoid replacement therapy
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23
Q

what is prednisone/prednisolone?

A
  1. extra double bond on carbon 1 & 2
  2. more potent glucocorticoid activity
  3. reduced mineralocorticoid activity
  4. interconvertable @ C11 with hydroxysteroid dehydrogenase
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24
Q

what is methylprednisolone?

A
  1. methyl group on C6a
  2. more potent glucocorticoid activity
  3. reduced mineralocorticoid activity
25
what is triamcinolone?
1. F on C9a and OH on C16a 2. more potent glucocorticoid activity 3. reduced mineralocorticoid activity 4. inc. bioavailability 5. low oral bioavailability
26
what is dexmethasone?
1. methyl on C16a 2. inc. lipophilicity (receptor binding/ stronger) 3. inc. stability in human plasma 4. reduced MC activity
27
what is betamethasone?
1. enantiomer of demethasone 2. similar properties to dexmethasone
28
what do 21-esters do?
OH group can be modified to an ester to control the property of glucocorticoids - prodrugs activated through hydrolysis by esterases
29
what do acetates and butyrates do in terms of 21-ester position?
1. inc. lipophilicty 2. prolonged action upon IM or IA inj
30
what do succinates do in terms of 21-ester position?
1. soluble 2. slow hydrolysis
31
what do phosphates do in terms of 21-ester position?
1. inc. solubility 2. rapid hydrolysis by phosphatases 3. IV or IM inj for EC
32
what are the desired properties of inhaled glucocorticoids?
1. high potency 2. minimal systemic effects 3. prolonged action
33
what is triamcinolone acetonide?
1. acetonide is resistant to hydrolysis 2. 8x more potent than prednisolone
34
what is beclomethasone dipropionate?
1. 14x more potent than dexmethasone 2. converted rapidly to 17 monopropionate by hydrolysis
35
what is flunisolide?
1. rapid absorption from nasal or lung tissue 2. rapid metabolism by liver -- first path metabolism 3. minimal adverse effect from long term use
36
what is budesonide?
1. 1:1 mix of epimers 16,17 butylacetal 2. faster topical uptake 3. low oral bioavailability 4. first path metabolism
37
what is mometasone furoate?
1. highly potent 2. more rapid onset of action 3. negligible systemic availability -- rapid metabolism -- low oral bioavailability 4. poor solubility
38
what is fluticasone propionate?
1. inactivated by hydrolysis of thioester -- rapid first path metabolism 2. highly lipophilic and insoluble (poor) -- high potent -- poor absoprtion from GI -- rapid topical uptake
39
what is a potent topical glucocorticoid?
halogenated analogues
40
what forms have better potency for topical applications due to high lipophilicity?
acetonide or ester forms
41
what topical glucocorticoids have very high potency?
clobestasol propionate, halobetasol propionate
42
what topical glucocorticoids have high potency?
halcinonide, triamcinolone acetonide, fluocinonide
43
what topical glucocorticoids have medium potency?
betamethasone valerate, mometasone furoate, fluticasone propionate
44
what does a 21-chlorocorticoid do?
substitution here of a Cl instead of OH enhances TOPICAL anti-inflammatory activity
45
what are adverse effects of glucocorticoids?
1. crossover mineralocorticoid activity 2. metabolic effects 3. cushing's-like effects 4. impaired glucose tolerance 5. suppression of immune system 6. GI 7. CNS 8. cataracts 9. adrenal insufficiency upon withdrawal (addisonian crisis)
46
describe crossover mineralocorticoid activity better of adverse effects for glucocorticoids?
1. sodium and water retention 2. development of HTN 3. correctable with selective synthetic glucocorticoids
47
describe the metabolic effects better of adverse effects for glucocorticoids?
1. inc. glucose production 2. steroid myopathy 3. reduced long bone growth in children 4. osteoporosis
48
describe cushing's-like effects of adverse effects for glucocorticoids?
1. redistribution of fat 2. moon face 3. buffalo hump
49
describe impaired glucose tolerance of adverse effects for glucocorticoids?
1. hyperglycemia from gluconeogenesis 2. dec. insulin response -- may unmask diabetes
50
describe suppression of immune system of adverse effects for glucocorticoids?
1. inc. susceptibility to infections 2. impaired wound healing
51
describe GI of adverse effects for glucocorticoids?
1. greater peptic ulcer risk
52
describe CNS of adverse effects for glucocorticoids?
1. linked to glucose metabolism 2. euphoria 3. depression
53
describe adrenal insufficiency upon withdrawal of adverse effects for glucocorticoids?
1. delayed recovery of HT and PT 2. depressed ACTH release and adrenal response to ACTH 3. directly related to dose/duration of therapy 4. Symptoms -- hypotension, weakness, inability to handle stress 5. due to negative feedback
54
what drugs are systemic corticosteroids?
1. hydrocortisone 2. cortisone 3. prednisone 4. prednisolone 5. methylprednisolone 6. betamethasone 7. dexamethasone
55
what drugs are systemic meneralocorticoids?
1. fludrocortisone
56
what drugs are inhaled glucocrticoids?
1. traimcinolone acetonide 2. beclomethasone dipropionate 3. flunisolide 4. budesonide 5. mometasone furoate 6. fluticasone propionate
57
what drugs are topical glucocorticoids?
1. triamcinolone acetonide 2. fluocinonide 3. betamethasone valerate 4. clobestasol propionate 5. halobetasol propionate 6. halcinonide
58
what are some strategies to minimize the adverse effects of glucocorticoids?
1. no long term use 2. no smoking/ alcohol 3. maintain healthy lifestyle

PHRM 825 Steroids Exam 2 (8 decks)

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