Pharmacology of Adrenal Steroids Flashcards Preview

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Flashcards in Pharmacology of Adrenal Steroids Deck (38)
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1
Q


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

A

 

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

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

  1. Aldosterone
  2. Androgens
  3. Cortisol
A
  1. Aldo - Zona Glomerulosa
  2. Andro - Zona Reticularis
  3. Cortisol - Zona Fasiculata and Reticularis
3
Q

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

A

 

  1. Gluc - Cortisol
  2. Mineral - Aldosterone and Deoxycorticosterone
  3. Sex Hormones - Testosterone, Estradiol, Estrone
4
Q


Describe the general mechanism of glucocorticoid action

A
5
Q

Describe the hypothalamic-pituitary-adrenal axis

A
6
Q

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

A

 

  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
Q

What are the glucocorticoid effects on inflammation?

A


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
Q

Four major effects of excess cortisol?

A

 

  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
Q


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

A

 

  1. Na+/K+ATPase
  2. Epithelial Na+ channel expression
10
Q


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

A

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

11
Q


What are the two most significant regulators of aldosterone secretion?

A

 

  1. Extracellular K+ concentration
  2. Angiotensin II
12
Q


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

A

MODIFY:

  1. Affinity of steroid for mineralocorticoid vs. glucocorticoid receptors
  2. Extent of protein binding
  3. Stability/t1/2
13
Q

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

A


Fludrocortisone; 125x > cortisol

14
Q


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

A


Primary adrenocortical insufficiency

15
Q


A patient has low cortisol and low ACTH. Dx?

A


Secondary adrenocortical insufficiency

16
Q


What are two major causes of secondary adrenal insufficiency?

A

 

  1. Suppression from exogenous glucocorticoid Tx
  2. Hypopituitarism
17
Q


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?

A

Secondary Adrenal Insufficiency has:

  1. NO hyperpigmentation
  2. Near-normal aldosterone levels
18
Q


What are precipitating causes of acute adrenal crises?

A

 

  • Events such as trauma, sepsis, surgery (ie stress) in chronic adrenal insufficiency
  • Hemorrhagic destruction of gland
  • Rapid withdrawal of steroids
19
Q


Describe the method used in order to diagnose adrenal insufficiency

A

 

  1. Administer Cosyntropin
  2. Normal: cortisol > 18 ug/dL, Abnormal: cortisol < 18 ug/dL
20
Q

Describe the strategy for primary adrenal insufficiency treatment

A
  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
Q


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

A

 

  • Minor febrile: Increase glucocorticoid dose 2x-3x for a few days of illness. Do NOT increase mineralcorticoid
  • Stress/trauma: Inject prefilled Dexamethasone IM
22
Q


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.

A
  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
Q


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

A
  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
Q


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

A


It will worsen hyponatremia

25
Q

 

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

 

  1. Pituitary Adenoma (Cushing's disease), Ectopic ACTH production (SCLC)
  2. Adrenal adenoma or carcinoma
26
Q


Describe the procedure used to diagnose Cushing's syndrome.

A

 

  • 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
Q


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

A


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

28
Q


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

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

 

  1. Low ACTH, High Cortisol
  2. High ACTH, High Cortisol
29
Q


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

A


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

30
Q


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

A
  • 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
31
Q


What is the utility of the Metyrapone test? What would be the findings of a healthy patient?

A

The metyrapone test is used to test the anterior pituitary. A patient is given a dose of metyrapone which blocks the conversion of 11-deoxycortisol (DOC) to cortisol. Therefore, in a normal patient, ACTH and DOC should increase.

32
Q


What are clinical indicators to test for aldosteronism?

A

 

  • HTN w/ hypokalemia
  • Tx-resistant HTN
  • Adrenal incidentaloma
  • Early-onset HTN
  • Severe HTN
  • Whenever considering secondary HTN
33
Q


What are screening tests that should be performed if primary aldosteronism is suspected? Findings in a patient with primary aldo.?

A

 

  1. Plasma aldo concentration (Increased)
  2. Plasma renin activity (Decreased)
  3. PAC/PRA ratio (>20 ng/dL)
  4. Urine collection (Elevated aldo and decreased Na+)
34
Q


What are the surgical and medical treatments for primary aldosteronism?

A

 

  • Surgery - remove unilateral adenoma
  • Medical - spironolactone (AR antag.) or Eplerenone
35
Q


What is the most common enzyme deficiency in congenital adrenal hyperplasia? How does this lack of enzyme perturb steroid levels and what are clinical manifestations of these perturbations?

A

 

  • 21-Hydroxylase Deficiency resulting in defective conversion of 17-hydroxyprogesterone to 11-deoxycortisol (and progesterone to DOC)
  • Reduced cortisol causes reduced negative feedback and increased ACTH. Adrenal androgen production is increased causing hirsutism, other forms of virilization, and salt wasting
36
Q


How is late-onset 21Beta-Hydroxylase deficiency diagnosed?

A


Cosyntropin stimulation test: with a 21Beta-hydroxylase deficiency, there will be increased levels of plasma 17-hydroxyprogesterone

37
Q

What is a serious sequela of chronic supraphysiologic steroid use? What is the risk of rapid steroid withdrawal?

A

 

  1. Iatrogenic Cushing's Syndrome (osteoporosis, diabetes, infection, etc.)
  2. Acute Adrenal Crisis
38
Q


What is the purpose of alternate day steroid Tx? What is a contraindication for this strategy? Medications used for this strategy?

A


To minimize side effects of:

  • Hypothalamic-Pituitary-Adrenal suppression
  • Iatrogenic Cushing's syndrome

Contraindicated for Tx of adrenal insufficiency

Prednisone, Prednisolone, Methylprednisolone