Pharmacology of Adrenal Steroids Flashcards Preview

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Flashcards in Pharmacology of Adrenal Steroids Deck (38)
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1


What are the layers of the adrenal gland (superficial to deep)?

 

  1. Zona Glomerulosa (Cortex)
  2. Zona Fasciculata (Cortex)
  3. Zona Reticularis (Cortex)
  4. Medulla

2

In what portion of the adrenal are the following steroids made?

  1. Aldosterone
  2. Androgens
  3. Cortisol

  1. Aldo - Zona Glomerulosa
  2. Andro - Zona Reticularis
  3. Cortisol - Zona Fasiculata and Reticularis

3

What are the naturally occuring glucocorticoids, mineralocorticoids, and sex hormones made w/i the adrenal?

 

  1. Gluc - Cortisol
  2. Mineral - Aldosterone and Deoxycorticosterone
  3. Sex Hormones - Testosterone, Estradiol, Estrone

4


Describe the general mechanism of glucocorticoid action

5

Describe the hypothalamic-pituitary-adrenal axis

6

Describe glucocorticoid metabolic effects. What is the overarching goal of these metabolic effects?

 

  1. Increase gluconeogenesis
  2. Release amino acids through muscle catabolism
  3. Inhibit peripheral glucose uptake
  4. Stimulate lipolysis

GOAL: Maintain adequate glucose for the brain

7

What are the glucocorticoid effects on inflammation?


Overall anti-inflammatory effects

  1. Upreg. of anti-inflamm proteins
  2. Downreg. of pro-inflamm proteins
  3. Decreased WBC presence and function at sites of inflamm

8

Four major effects of excess cortisol?

 

  1. Inhibition of bone formation (osteoporosis)
  2. Suppression of calcium absorption
  3. Delayed wound healing
  4. Catabolic effects on skin, connective tissue, msucle, peripheral fat, lymphoid tissue

9


What two proteins (mentioned in lecture) are upregulated by aldosterone?

 

  1. Na+/K+ATPase
  2. Epithelial Na+ channel expression

10


Blood concentrations of cortisol are 2000x higher than aldosterone. How then does aldo exhibit any tissue specific effect whatsoever?

In aldo-specific cells, 11Beta-Hydroxysteroid Dehydrogenase Type 2 converts active cortisol into inactive cortisone.

11


What are the two most significant regulators of aldosterone secretion?

 

  1. Extracellular K+ concentration
  2. Angiotensin II

12


What are the general goals of modifying molecular structure of corticosteroids?

MODIFY:

  1. Affinity of steroid for mineralocorticoid vs. glucocorticoid receptors
  2. Extent of protein binding
  3. Stability/t1/2

13

What is the most commonly used synthetic mineralocorticoid? What is its mineralocortioid activity compared to cortisol?


Fludrocortisone; 125x > cortisol

14


A patient has decreased levels of cortisol and aldosterone. ACTH is elevated. Dx?


Primary adrenocortical insufficiency

15


A patient has low cortisol and low ACTH. Dx?


Secondary adrenocortical insufficiency

16


What are two major causes of secondary adrenal insufficiency?

 

  1. Suppression from exogenous glucocorticoid Tx
  2. Hypopituitarism

17


A patient presents with symptoms that make you suspect adrenal insufficiency. Since you're a clever med student, what do you look for to differentiate betwixt the two?

Secondary Adrenal Insufficiency has:

  1. NO hyperpigmentation
  2. Near-normal aldosterone levels

18


What are precipitating causes of acute adrenal crises?

 

  • Events such as trauma, sepsis, surgery (ie stress) in chronic adrenal insufficiency
  • Hemorrhagic destruction of gland
  • Rapid withdrawal of steroids

19


Describe the method used in order to diagnose adrenal insufficiency

 

  1. Administer Cosyntropin
  2. Normal: cortisol > 18 ug/dL, Abnormal: cortisol < 18 ug/dL

20

Describe the strategy for primary adrenal insufficiency treatment

  1. Glucocorticoid: Highest dose Hydrocortisone in the morning and lower dose in the afternoon (mimic diurnal variation)
  2. Mineralocorticoid: Fludrocortisone once a day. Liberal salt intake

21


How should primary adrenal insufficiency Tx be changed in a patient with minor febrile illness? Severe stress/trauma?

 

  • Minor febrile: Increase glucocorticoid dose 2x-3x for a few days of illness. Do NOT increase mineralcorticoid
  • Stress/trauma: Inject prefilled Dexamethasone IM

22


Describe the steroid coverage for those with primary AI going into surgery with moderate illness, major illness, those going into moderately stressful surgery and major surgery.

  1. Moderate illness: Hydrocortisone (HC) 50 mg PO BID/IV
  2. Severe Illness: HC 100 mg IV Q 8hr
  3. Moderate Surgery: HC 100 mg IV just before procedure
  4. Major Surgery: HC 100 mg IV before anesthesia and then Q8 hr for first 24hr

23


Describe the process of treating a patient with an acute adrenal crisis

  1. Obtain blood for serum cortisol, renin, ACTH but do not delay Tx while waiting for definitive proof of Dx
  2. Large amounts of IV fluid
  3. High-dose IV glucocorticoids: Dexamethasone 4 mg IV every 12-24 hr if no previous Dx of adrenal insufficiency, Hydrocortisone 100 mg IV every 6 hrs until stable
  4. Gradual tapering

24


Why should hypotonic solution not be used in acute renal crises?


It will worsen hyponatremia

25

 

  1. Two examples of ACTH-dependent glucocorticoid excess?
  2. Two examples of ACTH-independent glucocorticoid excess?

 

  1. Pituitary Adenoma (Cushing's disease), Ectopic ACTH production (SCLC)
  2. Adrenal adenoma or carcinoma

26


Describe the procedure used to diagnose Cushing's syndrome.

 

  • Measure ACTH
  • 24 hr cortisol excretion
  • Low-dose overnight dexamethasone suppression test
  • Midnight salivary cortisol level

Dx requires at least TWO of these tests to be positive

27


Describe the findings of a dexamethasone suppression test on a patient with Cushing's Syndrome


Normally, a patient would have suppressed ACTH and cortisol, but in a patient with CS, cortisol remains high

28


What will be the general lab findings of ACTH and Cortisol in a patient with:

  1. ACTH independent process?
  2. ACTH dependent process?

 

  1. Low ACTH, High Cortisol
  2. High ACTH, High Cortisol

29


What is a risk of surgical treatment of Cushing's Syndrome?


Patients are at risk for adrenal insufficiency due to abrupt drop in cortisol levels

30


What are the 5 medications to treat Cushing's Syndrome? Mechanisms?

  • Aminoglutethimide - Blocks cholesterol conversion to pregnenolone
  • Ketoconazole - Nonselective inhibitor of adrenal and gonadal steroid synthesis
  • Mitotane - Nonselective cytotoxic action on adrenal cortex
  • Metyrapone - 11Beta-Hydroxylase inhibitor (Blocks conversion of 11-Deoxycortisol to cortisol)
  • Mifepristone - glucocorticoid receptor antagonist