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Exam3Lec7Adrenocortocosteroids Flashcards

1
Q

Glucocorticords:
Mineralocorticoids:
Anti-glucocorticoids:

A
  • Glucocorticoids: Prednisone, Triamcinolone, Dexamethasone
  • Mineralocorticoid: Fludrocortisone
  • Anti-glucocorticoids: Ketoconazole
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2
Q

What was the effects of giving Dezamethasone to Covid 19 patients

A

effective: ventilator (severe covid)
not effective: no O2 is received (mild COVID)

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3
Q

What was the Conclusion about given corticosteroids with brain trauma patients?

A

DO NOT GIVE GLUCOCORTICOID

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4
Q

What are risk factors for cortiosteroid usage? 4

A
  • increase septsis
  • Increase chance in blood clots
  • Increase in fractures
  • new onset diabetes
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5
Q

how is the adrenal gland broken up? What do they secrete?

A

Adrenal gland: cortex & medulla
– Cortex: adrenocorticosteroids & androgens
– Medulla: epinephrine (catecholamines)

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6
Q

How is the cortex divided and what do they secrete?

A
  • Outer zona glomerulosa → aldosterone which regulates Na+ (H2O) kidney reabsorption
    * Aldosterone 1* regulated by Renin-Angiotensin System -> MINERALCORTICOIDS
  • Middle zona fasciculata → cortisol which involved w/ metabolism & resistance to stress -> GLUCOCORTIOCIDS
  • Inner zona reticularis → dehydroepiandrosterone (DHEA)-> ANDROGENS
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7
Q

With the top-down mechanism, what What is the highest level hormone?
Where is is released from?
What controls its secretion?

A

A
CRH (Corticotropin-releasing hormone)
CRH is released from the hypothalamus
CRH controls the secretion of ACTH

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8
Q

With the top-down mechanism, what is happening after CRH?

A

Adrenocorticotropic hormone (ACTH, corticotropin)
* ACTH is secreted from the pituirary
* enters the circulation and induces secretion of hormones from the adrenal cortex
* Stimulates the secretion from the two inner zones (not zona glom)
* DOES not exert significant control on horomone in the outer zone (Ang II)

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9
Q

Cortisol mediates feedback inhibition of what?

A

ACTH and CRH secretion

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10
Q

Synthetic glucocorticoids are used in the treatment of what?

A

many diseases
* Asthma, RA, allergies

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11
Q

Explain what is happening with CRH, ACTH and the adrenal cortex

A

CRH (hypothal)–> ACTH (ant pit)–> cortisol(F)–> androgens (R)

does not control outer layer so no aldosterone acitvated

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12
Q

Zona glomerulosa is under the control of what?

A

RAAS

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13
Q

What gives neg feedback on hypothalamus and ant pit and decreases CRH and ACTH?

A

Cortisol

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14
Q

Explain the mechanism of action of adrenocorticosteroids

A
  • Step 1: Hormones bind to specific intracellular cytoplasmic receptor
  • Step 2: Dimerization of ligand-bound receptor subunits
  • Step 3: Dimerized receptor-hormone complexes translocate to the nucleus
  • Step 4: Complexes attach to gene promoter elements
    – “transcription factor”
    – genes turned on or off (can be modified by co-adaptor proteins)

hormone binds to IC receptor–> dimerize–>translocaet–> DNA expression

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15
Q

Adrenocorticosteroid:
1. Fast or slow?
2. Glucocorticoids distribution?
3. Mineralocorticoid distribution?

A
  1. Takes time to produce an effect
  2. Glucocorticoid receptors are widely distributed
  3. Mineralocorticoid receptor distribution is more limited - kidney, colon, salivary & sweat glands (i.e., excretory organs)-> LESS SE

limited=less SE bc not going all over body

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16
Q

Principal human glucocorticoid =

A

Cortisol

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17
Q

How does cortisol levels work in our bodies

A

Diurnal production w/ early morning peak followed by decline & then smaller peak(s) in late afternoon

peak during meals, stress

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18
Q

What can influence cortisol secretions?

A

Meals, Stress, & Cortisol Plasma Concentration

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19
Q

What are the general effects of glucocorticoids? (5)

A
  1. Promote normal intermediary metabolism
  2. Glucocorticoids increase resistance to stress
  3. Alter blood cell concetrations in plasma
  4. Anti-inflammatory action
  5. Endocrine sytem effect
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20
Q

How does glucocorticoids promote intermediary metabolism?

A
  • ↑ AA uptake by liver & kidney
  • Promotes gluconeogenesis thru ↑ activity enzymes in the liver
  • Promotes enzymes that increase protein catabolism (except liver-> anabolism because increasing glucose)
  • Overall Objective: Provide (a) building blocks & (b) energy for glucose synthesis

breaking things down for energy

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21
Q

How does glucocorticoids affect Lipolysis?

A

Promote ↑ hormone-sensitive lipases (Lipolysis).
* Growth hormone (GH) and adrenaline induce lipolysis. Glucocorticoid augment these effect effects.
* Glucocorticoids primarily increase lipolysis in subcutaneous adipose tissue.
* Glucocorticoids can decrease lipolysis and increase lipogenesis in visceral adipose tissue (abdominal) (more on this later)

incr cubcutaneous
decr visceral

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22
Q

How might we get hypoglycemia with glucocorticoids?

A

During stress or fasting → if Glucocorticoid insufficiency → then hypoglycemia

no hormone to break it down

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23
Q

How does glucocortcoids increase resistance to stress?

A

↑ glucose concentrations. Provides the body w/ energy to combat stress
* trauma, fright, infection, bleeding, disease

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24
Q

How can glucocorticoids affect BP?
How?

A

Can cause a modest ↑ Blood Pressure (BP)
* Mechanism: Enhances vasoconstrictor actions of catecholamines/vasopressin

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25
What may cause low BP?
Adrenal insufficiency
26
What has been shown favorable for surivival after in hospital cardiac arrest?
Vasopressin, sterioids, and epinephrine -> work synergic and increase chance of ROSC
27
how can glucocorticoids alter blood cell concetrations in plasma? ⭐️
* **↑ plasma erythrocytes (increase O2 delivery), platelets (stop bleeding), & neutrophils (but shifts neutrophils away from sites of tissue inflammation)** * **↓ eosinophils, basophils=> decrease histamine, monocytes, lymphocytes**. Also, redistribution from circulation to lymphoid tissue-> TO SAVE ENGERY * But because they ↓ monocytes & lymphocytes, **↓ ability to fight infections, but useful in tx of leukemia** ## Footnote immune sytem decr, can't fight infec, anti-infam decr prostagandins
28
What is the anti-inflammatory action of glucocorticoids?
* Very important therapeutic property! * Dramatically ↓ inflammatory response & **suppress immunity** * ↓ plasma monocytes & lymphocytes * ↑ lipocortin, which **↓ phospholipase A2** (indirect inhibition). Blocks production/release of arachidonic acid. => ***↓ PG & LT.*** * **Inhibition of NFκB** → ↓ IL-6, IL-8, MCP-1, COX-2 (↓ PG) * **↓ mast cell degranulation**, ↓ histamine → ↓ capillary permeability ## Footnote decr prostaglandins
29
What is the endocrine system effects of glucocorticoids?
* ↑ exogenous glucocorticoid levels cause **feedback inhibition** * **↓ ACTH production w/ ↓ endogenous cortisol,** can ↓ TSH, and alter GH production (In Vivo Decrease GH and In Vitro Increase GH)
30
Glucocorticoids affect renal blood flow how?
Physiological cortisol concentration essential for normal glomerular filtration (**↑ renal blood flow)**
31
How does glucocorticoids affect gastric acid and pepsin? What is the effect?
* Glucocorticoid high doses, ↑ gastric acid & pepsin production (breaksdown proteins). * May exacerbate ulcers
32
How does glucocorticoids affect bone?
Glucocorticoid chronic therapy may **cause severe bone loss** * Decreased intestinal Ca2+ absorption * Increased renal Ca2+ excretion | LOTS OF Ca LOSS
33
How can glucocorticoids affect muscles
myopathy-> weaknesss | becasue breaking down amino acids from muscles
34
How does Glucocorticoids affect CNS?
* initially insomnia & euphoria → **depression** * High doses **↑ intracranial pressure** (worse after discontinuation – possible from decreased absorption of CSF) | After you stop taking them=> ICP
35
What is the function of mineralocorticoids
Control of plasma H2O volume & concentrations of Na+ & K+
36
What is the main mineralocorticoids?
aldosterone
37
What does aldosterone do/cause?
* ↑ reabsorption of Na+, HCO3- & H2O in kidney collecting tubules & ducts * ↓ reabsorption of K+ and H+ in urine (i.e., ↑ excretion) * Effects mediated by activation of mineralocorticoid receptors
38
What are the consequences and SE of glucocorticoids ?
* Hypertension: Retention of Na+ & H2O, ↑ blood volume → ↑ BP * Hypokalemia & Alkalosis-> can alter heart rhythm and pH
39
What is identical to endogenous cortisone?
hydrocortisone
40
What gets metabolized by liver enzymes to inactivate ?
- C3 Ketone Group - C4-5 Double Bond
41
What is important for glucocorticoid activity? ⭐️
C11 hydroxyl group
42
Fill in
43
What drugs are selective for anti-inflammatory?
* Triamcinolone * betamethasone * Dexamethasone * Paramethasone
44
What mineralocorticoids that affects both anti inflammatory and salt retaining effect?
Fludrocortisone
45
Semisynthetic glucocorticoids?
– Vary in anti-inflammatory potency – Vary in Na+ retention – Vary in duration of action
46
What is the duration of action: * Short acting * intermediate acting * long acting
– Short Acting, 8-12 hrs (Cortisol, Cortisone) – Intermediate Acting, 12-36 hrs (Prednisone, Triamcinolone) – Long Acting, 36-72 hrs (Betamethasone, Dexamethasone)
47
What is affected in 1,2,3 adrenal insuffiency?
1: adrenal galnd 2: pit 3: hypothalam
48
What disease is 1* adrenal insufficiency?
Addision disease: inadequate secretion of cortisol by **adrenal glands**
49
Addision disease 1. Symptoms? 2. Cause? 3. Dianostic test? 4. Treatment? 5. Divide dosage?
1. **Symptoms**: weakness, no energy, low BP 2. **Possible Cause**: Autoimmune damage to the adrenal cortex resulting in dysfunction 3. **Diagnostic Test**: ***Negative response to the administration of ACTH (ACTH NEGATIVE)***-> if adrenal glands dont make cortisol then the gland is not working- 4. **Treatment**: Hydrocortisone (identical to natural cortisol) 5. **Divide Dosage**: 2/3 in morning & 1/3 in afternoon. Approximates daily cortisol conc.
50
Besides Hydrocortisone for addison disease, what else you might adminster and why?
Administration of Fludrocortisone may also be necessary to ↑ mineralcorticoid activity to normal
51
What conditions can be for 2* or 3* adrenal insufficiency?
* Deficit in ACTH production from pituitary (2*) * Deficit in CRH production from hypothalamus (3*)
52
What are the possible causes of 2* or 3* Adrenal Insufficiency
* Adenoma of the Pituitary (2°) * Brain Tumor (3°) * Acute Brain Injury (2° or 3°) * Withdrawal of Synthetic Glucocorticoids (2°or3°)-> because you shut down natural hormones
53
2* or 3* Adrenal Insufficiency: 1. Diagnostic test 2. Treatment 3. Additional characterisitcs
1. Diagnostic Test: **Adrenal cortex responds to ACTH bolus injection by syn & releasing adrenal corticosteroids (ATCH POSITIVE** 2. Treatment: Hydrocortisone 3. Additional Characteristics: Aldosterone synthesis less impaired than cortisol
54
Cushing syndrome: 1. Condition? 2. Cause? 3. Presentation?
1. Condition: Pathologically increased cortisol 2. Possible Cause: Pituitary tumor causing excess ACTH (Cushing’s Disease) 3. Presentation: ↑ cortisol → ↑ weight, ↑ hair, ↑ BP, osteoporosis
55
What is the diagnostic test for cushing syndrome?
* Dexamethasone suppression test * **If High Dose Dex causes ↓ cortisol release, suggestive of pituitary tumor (Cushing’s Disease)** * If High Dose Dex has no effect, suggestive of adrenal tumor or ectopic ACTH secreting tumor
56
Chronic high dose glucocorticoids can also cause what?
a Cushing-like syndrome
57
What is congenital adrenal hyperplasia
Group of diseases that produce a deficiency in the enzymes that synthesize cortisol
58
congenital adrenal hyperplasia: 1. Findings? 2. Symptoms? 3. Treatment?
1. Diagnostic Findings: **↑ ACTH** 2. Virilization of ♀, overproduction of adrenal androgens 3. Treat with **corticosteroids** * Normalizes androgen concentrations (i.e., ↓ androgen production) by ↓ the release of CRH & ACTH though feedback inhibition
59
How does glucocorticoids relief inflammatory? SE?
* Glucocorticoids ↓ inflammation (redness, swelling, heat, tenderness), e.g., RA, OA, skin * **Mechanism of Action: ↓ plasma conc. of leukocytes by redistribution, ↓ lymphocytes, ↓ basophils, ↓ eosinophils, ↓ monocytes** * ↓ ability to respond to mitogens & antigens * **↓ PG & LT**, important inflammatory effect * ↓ histamine release from mast cells & basophils
60
how does glucocorticoids alleviate severe allergies? What drugs? ⭐️
* Glucocorticoids alleviate symptoms of asthma, allergic rhinitis, drug allergies, transfusion allergies * **Beclomethasone, Triamcinolone** * Inhalation therapy for Asthma, ↓ systemic side effects
61
* What is common in premature infants? * What is the regulator of lung maturation?
* Premature infants → respiratory distress syndrome * Fetal cortisol → regulator of lung maturation
62
What is used to help respiratory distress syndrome? ⭐️
Intramuscular injection (IM) of **Betamethasone or Dexamethasone** to the mother 24 hrs before birth (prenatal period)
63
How does sterioids affect immunosuppression?
Organ transplants: Prevent/treat rejection
64
What is the metabolism of adrenocortcosteroid
**Corticosteroids metabolized 1* by liver enzymes** * Glucuronosyltransferase (UGT) * Sulfotransferase (SULT) * Hepatic dysfunction with ↑ t1/2
65
What is an issue with gluco.
**Suppression of hypothalamic-pituitary-adrenal axis (HPA)** * Large doses of glucocorticoids, e.g., > 2 weeks * Limit suppression by QOD dosing (every other day). Allows HPA to recover * Do not abruptly stop administration of corticosteroids; may cause severe withdrawal symptoms & exacerbate disease processes * Slowly taper off the use of synthetics to alleviate HPA suppression & prevent acute adrenal insufficiency syndrome → otherwise can cause death
66
What are the SE of gluco?
* **osteoporosis** * **increase appetite** * **cushing like syndrome** * cataracts * **Hyperglycemia** => new onset diabetes * **hypokalemia** * Peptic ulcers * Glaucoma * Hypertension * Edema * Euphoria/Depression/Psychosis * Impaired wound healing: ↑ infection risk
67
How do you get osteoporsis? treatment?
* ↓ intestinal Ca2+ absorption, ↓ bone formation, ↓ sex hormone syn. * Treat these side effects with Ca2+ & Vit D (helps absorption) | side affect of steroids
68
What effect is on appetite of steriods?
increase * predinisone-> chemotherapy
69
What are symptoms of cushing like syndrome?
* Redistribution of fat (buffalo hump), Puffy face (moon face), ↑ hair, Acne, Insomnia
70
What is the antiglucocorticoids?
Ketoconazole
71
Ketoconazole 1. Therapeutic use? 2. MOA? 3. SE?
* **Therapeutic use**: Cushing Syndrome (increase cortisol) and Antifungal * **Mechanism of action**: Inhibits cortisol biosynthesis by Inhibiting **CYP17A1 & CYP11A1** (at higher doses) * **Side effects**: Hepatoxicity and Heart Function by ↑ QTc prolongation (delayed ventricular repolarization), Tachycardia and Caused by drug inhibition of cytochrome P450 enzymes (CYP)
72
Where does ketoconazole block

Pharmacology (26 decks)

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