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🄼💊MSY2 Pharm (Endocrine/Repro/Thyroid) > Adrenocorticosteroids and Blockers > Flashcards

Adrenocorticosteroids and Blockers Flashcards

1
Q

Physiological Effects of Glucocorticoids on immune system (5)

A
  1. DEC Leukocyte Mobilization (helps allergies)
  2. DEC Cytokines (helps allergies)
  3. DEC Prostaglandins (as COX2 inhibitor)
  4. INC iKB –> inhibits NFKB(repsonsible for inflammation)
  5. Prevents NFKB from entering nucleus
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2
Q

Physiological Effects of Glucocorticoids on CV system (3)

A
  1. INC Vasoactive factor response (Arterial tone)

when low –> hypOtension

when HIGH –> HTN

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3
Q

Physiological Effects of Glucocorticoids on Musculoskeletal system (3)

A
  • required for Muscle Function but also..
  • DEC Muscle Density
  • DEC Bone Density
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4
Q

Physiological Effects of Glucocorticoids on CNS system (2)

A
  • Emotion Modulator (Mood/Mania/Memory)
  • Wakefulness
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5
Q

Physiological Effects of Glucocorticoids on Liver Detox

A

INC enzyme expression and helps detoxify heavy metals/toxins

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6
Q

Physiological Effects of Glucocorticoids on Metabolism (4)

A
  1. Protein Catabolism–> Muscle Degradation
  2. Fat ReDistribution to Visceral
  3. Hepatic Gluconeogenesis
  4. DEC Peripheral glucose utilization
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7
Q

Physiological Effects of Glucocorticoids on GI Tract (3)

A
  1. INC Gastric Acid
  2. INC Digestive Enzymes
  3. DEC Ca+ uptake
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8
Q

How does ACTH affect Cholesterol?

A

INC Cholesterol uptake via GPCR

ACTH is Trophic Factor

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9
Q

Daily Secretion of Cortisol

A

10-20 mg / day

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10
Q

Daily Secretion of Aldosterone

A

0.125 mg / day

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11
Q

Cortisol Half life

A

60-90 min

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12
Q

Aldosterone Half life

A

15-20 min

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13
Q

List the Peak and Trough for Cortisol production

A

Peak = 8 AM (Circadian released)

Trough = 11 pm

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14
Q

Cortisol MOA

A
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15
Q

Compare how [Glucocorticoid Receptors] vs. [Mineralocorticoid Receptors] are affected by Cortisol?

A

Both with Equal Affinity

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16
Q

What enzyme deactivates Cortisol into Cortisone

A

11B HSD2

“time 2 go back to PCKS, Mr.Cortisol”

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17
Q

List the organs that are Aldosterone sensitive (3)

A

Colon

Kidney

Salivary Gland

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18
Q

Which tissues express [11B HSD1] (3)

A

LAB

Liver

Adipose

Brain

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19
Q

List the [short acting] synthetic corticosteroids (2)

A
  1. Hydrocortisone/cortisol
  2. Cortisone
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20
Q

List the [intermediate acting] synthetic corticosteroids (4)

A
  1. Fludrocortisone (High Mineralocorticoid potency)
  2. PrednisoLone (L for L**ive)
  3. Prednisone (inactive)
  4. Triamcinolone
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21
Q

List the [Long acting] synthetic corticosteroids (2)

A

Long Sex for Betty and Dex

  1. Dexamethasone
  2. Betamethasone
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22
Q

Which Corticosteroid has HIGH mineralocorticoid potency

A

Fludrocortisone-IA

IA= Intermediate Acting

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23
Q

Which Corticosteroid has No mineralocorticoid activity AND is not a [substrate of 11B HSD2]

A

Dexamethasone-LA

LA= Long Acting

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24
Q

Which Corticosteroids has the [HIGHEST Glucocorticoid potency] but [no mineralocorticoid acitivty] (2)

A
  1. Dexamethasone LA
  2. Betamethasone LA
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25
Q

Oral Corticosteroid metabolism

A

Can be active or inactive since inactive agents are converted –> active by [Liver 11BHSD1]

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26
Q

Topical Corticosteroid metabolism

A

[11BHSD1] is not in skin or joints so Topical Corticosteroids MUST be active already (i.e. hydrocortisone vs. PrednisoLone)

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27
Q

Which corticosteroid is given to mother for an effect on the fetus? Why?

A

Dexamethasone

[11BHSD2] in Placenta inactivates any corticosteroids that are substrates.

Dexamethasone is NOT a substrate of [11BHSD2]

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28
Q

Which Corticosteroids are used for HRT (2)

A

Hydrocortisone

Fludrocortisone

physiological doses

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29
Q

Indications for [Corticosteroid HRT] (2)

A

[Adrenal insufficiency]

CAH (Congenital Adrenal Hyperplasia)

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30
Q

NonEndocrine Corticosteroid indications (5)

A

CCAAR

  1. Autoimmune
  2. Anti-inflammatory/rejection
  3. Respiratory (Asthma vs. ARDS)
  4. CA (A.L.L.)
  5. Cerebral Edema
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31
Q

Corticosteroids used for NonEndocrine indications (2)

A

Prednisone

Dexamethasone

HIGHER physiological doses

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32
Q

How much time does it take for adrenal function to recover [post exogenous corticosteroid]

A

12 mo.

33
Q

Sx of Cortisol insufficiency (5)

A
  1. DEC blood glucose–>impaired brain/heart/kidney
  2. DEC response to vasoactive agents–> hypOtension
  3. DEC muscle function
  4. Hypercalcemia
  5. Hyperpigmentation from INC ACTH on MSU receptors
34
Q

Cortisol insufficiency is from primary or secondary adrenal insufficiency?

A

Secondary

Aldosterone insufficiency is from primary adrenal insufficiency

35
Q

Drug used to treat [nonacute Adrenal Insufficiency] (3)

A

Hydrocortisone

Dexamethasone

Fludrocortisone for Primary Adrenal insufficiency

36
Q

When would you see Acute Adrenal Insufficiency? (3)

A
  1. [Undiagnosed Adrenal Insufficiency] pt after serious illness
  2. pt with pre-existing adrenal insufficiency but who does NOT INC glucocorticoid usage during illness
  3. Abrupt withdrawal of Chronic Glucocorticoid therapy
37
Q

Sx of [Acute Adrenal Insufficiency] (5)

A

hypOvolemic shock

hypOnatremia

Hyperkalemia

NV

Weakness

38
Q

What’s the initial tx for [Acute Adrenal Insufficiency] (2)

A

[IV electrolytes] + [IV Hydrocortisone vs. Dex]

39
Q

What’s the ultimate tx for [Acute Adrenal Insufficiency] once it’s stable

A

[IV Hydrocortisone] tapered over 1-2 days to an [oral hydrocortisone + fludrocortisone]

40
Q

Pts with adrenal insufficiency should avoid what situations –> INC cortisol? (4)

A
  1. Stress
  2. Illness
  3. Surgery
  4. Pregnancy
41
Q

What affect does [CYP21 mutations] have on sex organ development (Male vs. Female)

A

Males = normal

Females = Hypervirilized + [ambiguous genitalia] from excess Testosterone

42
Q

Newborns with [CYP21 mutations] will suffer from [Acute Adrenal Crisis] within ____ weeks

A

1-3 Weeks

[Salt Wasters, Wt. Loss, hypOtension, dehydration, vomiting]

43
Q

Tx of CAH after birth (2)

A

Hydrocortisone + [Fludrocortisone PRN]

44
Q

Which [amniotic fluid substrate] is used as a prenatal screen for CAH

A

17-Hydroxypregnenolone (precursor of cortisol)

45
Q

CAH (Congenital Adrenal Hyperplasia) is mostly caused by

___ mutation

A

CYP21

46
Q

Tx of [CAH-CYP21 mutation] when discovered in utero (Female vs. Male)

A

Female baby= Give mother Dexamethasone 9th week gestation up until delivery

Male baby= tx can be delayed until after birth

47
Q

Which Corticosteroid treats RA

A

Prednisone

48
Q

How long should Prednisone be used to treat RA

A

< 3-4 weeks (used for flare ups only)

49
Q

Rhematoid joint pain tx regimen and which drug to use

A

Administered Directly into joint q3 mo. Because of joint, must use [active: PrednisoLone]

50
Q

Which Corticosteroid is used for Severe allergies

A

P for Pretty Bad Allergies

IV vs. [short term oral] Prednisone/PrednisoLone

51
Q

Which Corticosteroids are used for mild allergies (4)

A

Allergies Far Than Bad

Inhaled Glucocorticoids

  1. Triamcinolone
  2. Acetonide
  3. Beclumetasone
  4. Fluticasone
52
Q

Describe the Route of Delivery for Inhaled Glucocorticoids

A

High Drug concentration directly to Lung –>Avoids Significant 1st pass effect. <1% of swallowed glucocorticoid is bioavailale.

Low risk SE or HPA suppression

53
Q

How are Corticosteroids used to treat [NephrOtic syndrome]

A

DEC inflammation associated with [Minimal change Dz]

54
Q

How are Corticosteroids used to treat CA

A

DEC WBC # in the blood for ALL

55
Q

Which drug and How are Corticosteroids used to treat [NRDS]

A

Dexamethasone promotes Lung maturation when birth is < 31 week gestation

56
Q

When is it indicated to use Corticosteroids for Cerebral Edema? (4)

A

1st, Help Brian’s Brain…with Steroids!

  1. [1° AND metastatic brain tumors]
  2. Bacterial meningitis (prevents hearing loss)
  3. Brain Radiation exposure
  4. High Altitutde Cerebral Edema
57
Q

Contraindications for using Corticosteroids for Cerebral Edema (3)

A

Traumatic Brain injury

Stroke

Intracerebral Hemorrhage

58
Q

MOA for Corticosteroids in Cerebral Edema (3)

A
  • [INC CSF reabsorption] and [DEC CSF production]
  • DEC endothelial permeability and stabilizes BBB
  • DEC inflammation and cytokines
59
Q

Under what circumstances does HPA suppression occur following Corticosteroid tx

A

Chronic use of Corticosteroid (>20 mg prednisone for > 3 weeks)

60
Q

How should you withdrawal Corticosteroids to avoid adrenal crisis

A

Slow taper (10-20% DEC in dose every 1-2 weeks)

61
Q

Name the situations in which low dose Dex does not suppress cortisol levels (3)

A

[Pituitary Adenoma Cushing Dz]

[Pareneoplastic Cushing Syndrome (Ectopic)]

[Adrenal Cortisol Tumor]

62
Q

Name the situations in which HIGH dose Dex does not suppress cortisol levels (2)

A

[Pareneoplastic Cushing Syndrome (Ectopic)]

[Adrenal Cortisol Tumor]

63
Q

Name the [Adrenocorticoid synthesis] inhibitors (3)

A
  1. Ketoconazole = MOST EFFECTIVE
  2. Etomidate
  3. Metyrapone
64
Q

Ketoconazole MOA (3)

A
  1. Inhibits ACTH secretion
  2. High Doses inhibits [Human CYP11A1 and B1]
  3. inhibits [Fungal CYP450]
65
Q

Etomidate is an ____ that inhibits _____

A

Etomidate is an [IV Anesthetic/Sedative] that inhibits [CYP11A1 and B1]

66
Q

Etomidate Indication

A

Pts who are NPO

67
Q

Metyrapone MOA. How is Dehydration SE circumvented?

A

inhibits [CYP11B1 and B2] –> inhibits Cortisol and Aldosterone Synthesis.

DEC aldosterone levels is compensated by INC in 11-DOC

68
Q

Metyrapone SE

A

INC Androgen precursors –> Female Hirsuitism

It Blocks CYP11B1 and B2

69
Q

Which [Adrenocorticoid synthesis inhibitor] can be used in pregnancy

A

“Me Pregnant”

Metyrapone

70
Q

Mitotane Indication

A

Medical Adrenalectomy when Cushing Dz pts can’t tolerate surgery

71
Q

Mitotane MOA

A

Metabolized by CYP11B1 and A1 –> active compound that destroys mitochondria –> [Zona Fasciculata & Reticularis Necrosis]

72
Q

Mitotane Contraindication

A

Pregnancy (since it causes permanent fetal adrenal damage)

73
Q

Mitotane SE (4)

A

NOT well tolerated; 80% require dose reducations 2° to [NVD, Anorexia, Rash & Ataxia!]

74
Q

[Mifepristone Indication] in adrenal glands

A

Refractory Cushing’s Syndrome

75
Q

Mifepristone MOA (2)

A

[Progesterone R Blocker] and [Glucocorticoid R blocker at high dose]

76
Q

Mifepristone SE (2)

A
  1. Abortion! (DON’T USE IN PREGNANCY)
  2. Adrenal insufficiency
77
Q

Name the situations in which HIGH dose Dex DOES suppress cortisol levels and what this means

A

[Pituitary Adenoma Cushing Dz]

If after giving [low dose Dexamethasone] Cortisol levels don’t drop, but only drops with [HIGH dose Dexamethasone] = Dx is [Pituitary Adenoma Cushing Dz]

78
Q

In which organs do you find 11BHSD2 (4)

A

“time 2 go back to PCKS, Mr.Cortisol”

Placenta

Colon

Kidney

Salivary Glands

🄼💊MSY2 Pharm (Endocrine/Repro/Thyroid) (6 decks)

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