Pharm - Steroids Flashcards by Dr. Acula

3 Zona of Adrenal Cortex from Outside In:

Glomerulosa — Fasciculata — Reticularis

15% — 75% — 10%

How well did you know this?

Not at all

Perfectly

Main hormone(s) of each adrenal cortex

Glomerulosa = aldosterone (mineralcorticoid)
Fasciculata = cortisol (glucocorticoid)
Reticularis = cortisol and Androgens

remember: salty dinner, sweet desert, sex

How well did you know this?

Not at all

Perfectly

Where and on what hormones does cortisol have negative feedback effects?

Hypothalamus – CRH (corticotropin releasing hormone)

Anterior Pituitary – ACTH

How well did you know this?

Not at all

Perfectly

How and through what receptor do glucocorticoids affect BP?

Increases BP – a1 adrenergic receptors on arterioles –> increased sensitivity to NE and Epi

How well did you know this?

Not at all

Perfectly

Glucocorticoids (increase/decrease) gluconeogenesis

Increase gluconeogensis – MORE GLUCOSE FOR BRAIN

How well did you know this?

Not at all

Perfectly

Glucocorticoids (increase/decrease) amino acid release through muscle catabolism

Increase

How well did you know this?

Not at all

Perfectly

Glucocorticoids (increase/decrease) peripheral glucose uptake

Decrease – MORE FOR BRAIN

How well did you know this?

Not at all

Perfectly

Glucocorticoids (increase/decrease) lipolysis

Increase – less fat, more SUGAR for brain

How well did you know this?

Not at all

Perfectly

Glucocorticoids (increase/decrease) bone Formation

Decrease

How well did you know this?

Not at all

Perfectly

Glucocorticoids (increase/decrease) anti-inflammatory proteins

Increase – up-regulation

How well did you know this?

Not at all

Perfectly

Glucocorticoids (increase/decrease) pro-inflammatory proteins

Decrease – downregulation

How well did you know this?

Not at all

Perfectly

2 Naturally occurring mineralcorticoids:

-Aldosterone

- -Deoxycorticosterone

How well did you know this?

Not at all

Perfectly

(High/Low) potassium upregulates aldosterone

High

How well did you know this?

Not at all

Perfectly

Blood concentration of [cortisol/aldosterone] is higher

Cortisol – 2000fold higher than Aldosterone

How well did you know this?

Not at all

Perfectly

What prevents cortisol from binding to aldosterone receptors?

11B-hydroxysteroid dehydrogenase TYPE 2 – converts intracellular cortisol to cortisone

–Type 1 reverses

How well did you know this?

Not at all

Perfectly

What commonly used corticosteroid has 0 mineralcorticoid activity (relative to cortisol)?

Dexamethasone – 30 anti-inflammatory, 0 mineralcorticoid, 36-72hr

How well did you know this?

Not at all

Perfectly

What commonly used corticosteroid has the highest mineralcorticoid activity (relative to cortisol)

Fludrocortisone – 10 anti-inflammatory, 125 mineralcorticoid

How well did you know this?

Not at all

Perfectly

Cause of primary vs. secondary adrenocortical insufficiency:

Primary – anatomic destruction of adrenal gland

Secondary – decreased pituitary production of ACTH

How well did you know this?

Not at all

Perfectly

[Primary/Secondary] Adrenal insufficiency causes hyperpigmentation

Primary – hyperpigmented skin, hand creases, and nails

Cortisol and ACTH levels in Primary adrenal insufficiency

-Low cortisol – can’t make

- -High ACTH – can’t use

Cortisol and ACTH levels in Secondary adrenal insufficiency

-Low cortisol – doesn’t make

- -low ACTH – doesn’t make

What is Cosyntrpin test and how does it work?

ACTH stimulation test to determine primary vs 2ndary adrenal insufficiency

-Primary = No increase in Cortisol
-2ndary = Increase in Cortisol

Na and K changes in acute Adrenal Insufficiency “Adrenal Crisis”

-Hyperkalemia

- -Hyponatremia – b/c high ADH from cortisol deficiency, low mineralcorticoid

CAH inheritence is [autosomal/x-linked] [dominant/recessive]

Autosomal recessive

Most common form of CAH involves what enzyme?

21-hydroxylase deficiency

What is increased in most common form of CAH?

17-hydroxy-progesterone and androgens (DHEA, androstenedione, testosterone, estradiol)

In Cushing's Syndrome, glucocorticoids are [increased/decreased]

Increased -- too much adrenal cortex activity

ACTH dependent Cushing's Syndrome causes:

- -Pituitary adenoma (Cushing's Disease) | - -Ectopic ACTH production (small cell lung Cx, bronchial carcinoid)

ACTH independeing Chushing's Syndrome causes:

- -Adrenal adenoma | - -Adrenal carcinoma

Characteristics of abdominal striae in Cushing's Syndrome

- -Greater than 1cm in width | - -Violaceous color

4 Diagnostic tests for Cushing's Syndrome

1--ACTH 2--24hr urine free cortisol excretion 3--Low dose overnight dexamethasone suppression test 4--Midnight salivary cortisol level test **Need 2+ tests for diagnosis

ACTH dependent Cushing's Syndrome has what ACTH and Cortisol levels?

- -High ACTH | - -High Cortisol

ACTH independent Cushing's Syndrome has what ACTH and Cortisol levels?

- -Low ACTH | - -High Cortisol

What is the mechanism of Metyrapone?

- -Selective inhibitor of 11-hydroxylase - -Results in increased 11-deoxycortisol - -Increased ACTH due to lower feedback inhibition

This drug for Cushing's Syndrome was developed as a progesterone receptor antagonist, but has glucocorticoid receptor antagonist activity at higher concentrations

Mifepristone (RU-486)

This drug for Cushing's Syndrome blocks conversion of cholesterol to pregnenolone

Aminoglutethimide

This drug for Cushing's Syndrome is a potent, nonselective inhibitor of adrenal and gonadal steroid synthesis; imidazole derivative

Ketoconazole -- antifungal

This drug for Cushing's Syndrome is a DDT insecticide relative w/ bad side effect profile

Mitotane -- nonselective cytotoxic action on adrenal cortex

This drug for Cushing's Syndrome binds to somatostatin receptors to block release of ACTH

Pasireotide -- high affinity for somatostatin receptor subtype 5

Classic presentation of Primary aldosteronism:

Hypertension w/ hypokalemia

2 Drugs used for medical management of Primary Aldosteronism:

- -Spirinolactone -- aldosterone receptor blocker | - -Eplerenone -- less anti-androgen effect

What Cushing Syndrome cause leads to bilateral adrenal atrophy?

Exogenous corticosteroids ( low ACTH) No atrophy causes: - -Primary adrenal adenoma/hyperplasia/carcinoma - -Cushing Disease (ACTH secreting pituitary adenoma) - -Paraneoplastic ACTH secretion

[FA] | Cortisol mnemnoic: BIG FIB

Blood pressure = increased Insulin resistance Gluconeogenesis + lipolysis, proteolysis --> hyperglycemia Fibroblast activity --> striae Inflammatory and Immune = ---inhibit leukotriene, prostaglandin synthesis ---inhibit WBC adhesion --> neutrophilia ---block histamine release from mast cells ---reduce eosinophils ---block IL-2 producction Bone formation = decreased ( low osteoblast activity)

Scenario: Already know high 24hr urine cortisol, high midnight salivary cortisol and no suppression w/ overnight low-dose dexamethasone test. - -What if ACTH is low? - -What if ACTH is high?

Low ACTH = think adrenal tumor or exogenous glucoccorticoid cause High ACTH = high dose dexamethasone suppression to differentiate Cushing disease (suppressed) vs. ectopic secretion (no suppression)

How is metyrapone stimulation test used?

Metyrapone given to block 11-hydroxylase (11-deoxycortisol-->cortisol) Normal: low cortisol, compensatory high ACTH, 11-deoxycortisol Primary adrenal insufficiency: high ACTH, low 11-deoxycortisol 2ndary adrenal insufficiency: low ACTH, low 11-deoxycortisol