"Pharmacology Steroid Pharmacology Rachel L. Hopkins"

Question 1

How do glucocorticoids increase blood pressure?

Answer 1

Glucocorticoids such as cortisol (stress hormone) upregulate alpha 1 receptors in arterioles that result in increased sensitivity to norepi and epi.

At high concentrations, they can bind to aldosterone receptors as well.

Question 2

Do glucocorticoids increase or decrease bone formation?

Answer 2

Decrease

Question 3

What is the result of glucocorticoids’ causing decreased leukocyte presence and leukocyte functioning at sites of inflammation?

Answer 3

Glucocorticoids are potent anti-inflammatories with immunosuppressive properties.

They upregulate anti-inflammatory proteins, and downregulate pro-inflammatory ones.

Question 4

What are the naturally occurring mineralocorticoids in the body?

Answer 4

Aldosterone
Deoxycorticosterone
(Cortisol - weak)

Question 5

What are the functions of mineralocorticoids in the body?

Answer 5

Active in the DCT and collecting ducts of the kidney;

Maintain electrolyte balance and intravascular volume

Question 6

K+ and Angiotensin II have strong effects on what steroid?

Answer 6

Aldosterone

Weaker influences on aldosterone include adrenocortocitropic hormone (ACTH) and sodium deficiency

Question 7

Cortisol and aldosterone bind to aldosterone receptors with the same affinity. Cortisol is also present in the blood about 2000x higher than aldosterone. How does the body prevent overwhelming cortisol binding?

Answer 7

11-beta-hydroxysteroid dehydrogenase type 2 converts cortisol to cortisone

Question 8

Treatment of Adrenal insufficiency, congential adrenal insufficiency, and dianosing Cushing’s syndrome, all involve what drug class?

Answer 8

Corticosteroids

Question 9

Class: Fludrocortisone

Answer 9

(Synthetic) Mineralcorticoid

Question 10

MOA: Fludrocortisone

Answer 10

Binds aldosterone receptor (AR) which increases Na+K+ATPase expression and increase epithelial sodium channel experession

Question 11

Use: Fludrocortisone

Answer 11

Chronic primary adrenal insufficiency (maintenance); CAH

Question 12

Fludrocortisone is structurally similar to:

Answer 12

aldosterone

Question 13

What causes primary adrenocortical insufficiency?

Answer 13

Anatomic destruction of the adrenal gland

Question 14

What causes secondary adrenocortical insufficiency?

Answer 14

Decreased pituitary production of ACTH;

Can be iatrogenic (suppression from exogenous glucocorticoid therapy)

Question 15

Side effects: Fludrocortisone

Answer 15

Primary aldosteronism

Question 16

Hyponatremia, hyperkalemia, anemia, eosinophilia, azotemia, all characterize lab findings of what disorder?

Answer 16

Primary adrenal insufficiency
Signs and symptoms: weakness, fatigue, nausea, vomiting, diarrhea, salt craving, postural dizziness, anorexia, weight loss, skin pigmentation, pigmentation of mucous membranes, hypotention, vitiligo

Question 17

How are the findings of secondary adrenal infficiency different from primary?

Answer 17

No hyperpigmentation (ACTH is low);
Near-normal aldosterone levels

Question 18

How is adrenal insufficiency diagnosed?

Answer 18

Test cortisol levels at baseline and 30-60 minutes after a dose of cosyntropin

Question 19

Low cortisol, high ACTH characterizes what dx?

Answer 19

Primary adrenal insufficiency

Question 20

Low cortisol, low ACTH characterizes what dx?

Answer 20

Secondary adrenal insufficiency

Question 21

What is adrenal crisis?

Answer 21

Volume depletion;
hypotension;
lassitude, nausea, vomiting;
Hyperkalemia;
Hyponatremia (mineralocorticoid deficiency, increased ADH caused by cortisol deficiency)

Question 22

How is adrenal crisis treated?

Answer 22

High dose IV glucocorticoid (ie dexamethasone, hydrocortisone)

Do not delay treatment, as adrenal crisis is life-threatening.

Question 23

Class: Hydrocortisone

Answer 23

Glucocorticoid

Question 24

MOA: Hydrocortisone

Answer 24

Binds GR, which regulates expression of genes with many effects on carbohydrate metabolism and immune function

Question 25

Uses: Hydrocortisone

Answer 25

Chronic primary adrenal insufficiency (maintenance); | CAH

Question 26

What is the goal of treatment of chronic adrenal insufficiency?

Answer 26

To replace physiologic glucocorticoids and mineralocorticoids

Question 27

Side effects: Hydrocortisone

Answer 27

Cushing's; glucocorticoid-induced osteoporosis; iatrogenic adrenal insufficiency

Question 28

Class: Dexamethasone

Answer 28

Glucocorticoid

Question 29

MOA: Dexamethasone

Answer 29

Binds GR, which regulates expression of genes with many effects on carbohydrate metabolism and immune function

Question 30

Uses: Dexamethasone

Answer 30

``` Emergency treatment (severe adrenal crisis, PAI); suppression test (Cushing's dx); CAH ```

Question 31

Side effects: Dexamethasone

Answer 31

Cushing's; | glucocorticoid-induced osteoporosis; iatrogenic adrenal insufficiency

Question 32

What is "stress dosing?"

Answer 32

The adjustment of dosing of glucocorticoids when a person with chronic adrenal insuffiency is ill.

Question 33

What is the most common congenital adrenal hyperplasia?

Answer 33

21-hydroxylase deficiency, which results in the overproduction of androgens (converts progesterone to DOC...--> aldosterone AND converts 17-OH-progesterone to 11-deoxycortisol...--> cortisol)

Question 34

How is 21-hydroxylase defiency treated?

Answer 34

Dexamethasone, prednisone or hydrocortisone. Sometimes fludrocortisone is used if salt-wasting is occurring Giving steroids suppresses ACTH and reduces overproduction of androgens

Question 35

Cushing's disease is caused by:

Answer 35

pituitary adenoma | ACTH-dependent glucocorticoid excess

Question 36

Cushing's syndrome, when paraneoplastic, is caused by:

Answer 36

Small cell lung carcinoma, bronchial carcinoid | These involve ectopic ACTH production

Question 37

Adrenal adenoma and adrenal carcinoma both product what kind of Cushing's syndrome?

Answer 37

ACTH-independent

Question 38

Weight gain, menstrual irregularity, hirsutism, psychiatric dysfunction, backache, muscle weakness, fractures and loss of scalp hair all charactterize what diagnosis?

Answer 38

Cushing's syndrome Also... truncal obesity, plethora, moon face, HTN, bruising, thinning sking, red-purple striae (like stretch marks), proximal myopathy, ankle edema, hump on back, impaired glucose tolerance, diabetes, infections, osteoporisis, renal calculi, cataracts and glaucoma

Question 39

How is Cushing's syndrome diagnosed?

Answer 39

Administer ACTH and monitor 24-hour cortisol excretion in urine; or overnight dexamethasone test; or midnight salivary cortisol test 2 of these tests must be +

Question 40

Uses: Aminoglutethimide

Answer 40

Cushing's syndrome

Question 41

MOA: Aminoglutethimide

Answer 41

Blocks conversion of cholesterol to pregnenolone

Question 42

Uses: Ketoconazole

Answer 42

Cushing's syndrome

Question 43

MOA: Ketoconazole

Answer 43

Potent, nonselective inhibitor of adrenal and gonadal steroid synthesis

Question 44

Class: Ketoconazole

Answer 44

Anti-fungal imidazole derivitive

Question 45

Class: Mitotane

Answer 45

DDT insecticide relative

Question 46

MOA: Mitotane

Answer 46

Nonselective cytotoxic action on adrenal cortex

Question 47

Uses: Mitotane

Answer 47

Cushing's syndrome

Question 48

Which treatment for Cushing's syndrome is known to have a bad side effect profile?

Answer 48

Mitotane

Question 49

MOA: Metyrapone

Answer 49

Relatively selective inhibitor of 11-hydroxylation (interferes with cortisol and corticosterone synthesis)

Question 50

Uses: Metyrapone

Answer 50

Cushing's syndrome

Question 51

T/F: Metyrapone can be used diagnostically to test anterior pituitary function.

Answer 51

True

Question 52

MOA: Mifepristone

Answer 52

Progesterone receptor antagonist; GR antagonist at high concentrations --created generalized glucocorticoid resistance

Question 53

Uses: Mifepristone

Answer 53

Cushing's (controls hyperglycemia secondary to hypercortisolism)

Question 54

When is Mifepristone indicated?

Answer 54

To control hyperglycemia secondary to hypercortisolism in adults with endogenous Cushing's syndrome who have failed or are not candidates for surgery; Cortisol-induced psychosis

Question 55

Side effects: Mifepristone

Answer 55

Fatigue, nausea, headache, hypokalemia (moderate to severe), arthralgias, edema, endometrial thickening in women; adrenal insufficiency

Question 56

Class: Pasireotide

Answer 56

Somatostatin analog

Question 57

MOA: Pasireotide

Answer 57

Binds to somatostatin receptor (subtype 5) and blocks release of ACTH from corticotropes

Question 58

Uses: Pasireotide

Answer 58

Cushing's syndrome

Question 59

Side effects: Pasireotide

Answer 59

hyperglycemia; | GI symptoms

Question 60

Primary aldosteronism is characterized by:

Answer 60

High aldosterone and low renin; HTN; hypokalemia

Question 61

When should primary aldosteronism be in the differential?

Answer 61

HTN with hypokalemia Tx resistant HTN HTN

Question 62

Surgery may be indicated in the treatment of primary aldosteronism if:

Answer 62

the source is a unilateral adenoma

Question 63

Medical treatment is indicated for primary aldosteronism if:

Answer 63

the source is bilateral adrenal hyperplasia

Question 64

MOA: Spironolactone

Answer 64

Aldosterone receptor antagonist

Question 65

Use: Spironolactone

Answer 65

Primary aldosteronism

Question 66

Side effects: Spironolactone

Answer 66

Anti-androgenic

Question 67

MOA: Eplerenone

Answer 67

Aldosterone receptor antagonist

Question 68

Uses: Eplerenone

Answer 68

Primary aldosteronism Less anti-androgen effects

Question 69

Toxicity from glucocorticoids can result in:

Answer 69

Insomnia; Behavior changes (is hypomania, psychosis); Peptic ulcers; Pancreatitis

Question 70

Patients who are withdrawn from long-term and/or high steroid therapy are at risk for:

Answer 70

Adrenal crisis