Exam 3: L24-25 ACTH And Adrenal Steroids

Question 1

Hydrocortisone

Answer 1

Preferred replacement therapy for Adrenocortical
Insufficiency
Equal mineralocorticoid and glucocorticoid

Question 2

Cortisone

Answer 2

Inactive and must convert to hydrocortisone in the liver

80% potency of hydrocortisone d/t metabolic loss

Question 3

What is Fludrocortisone?

Answer 3

An oral synthetic adrenocortical steroid with mineralocorticoid and glucocorticoid activity

Fludrocortisone has high glucocorticoid effects but more significant mineralocorticoid properties.

Question 4

What are the pharmacologic actions of Fludrocortisone similar to?

Answer 4

Aldosterone

Fludrocortisone mimics the actions of aldosterone in the body.

Question 5

When is Fludrocortisone used in combination with glucocorticoids?

Answer 5

For replacement therapy in primary adrenocortical insufficiency

This is especially important in conditions where both cortisol and aldosterone are absent.

Question 6

What is the most severe form of 21-hydroxylase deficiency that Fludrocortisone is indicated for?

Answer 6

Salt-losing adrenogenital syndrome

In this condition, both cortisol and aldosterone are virtually absent.

Question 7

In what situation is Fludrocortisone given independently of glucocorticoids?

Answer 7

When only aldosterone replacement is necessary

This includes conditions like corticosterone methyloxidase deficiency (18-hydroxylase deficiency).

Question 8

Fill in the blank: Fludrocortisone has high _______ effects but much more significant _______ properties.

Answer 8

glucocorticoid, mineralocorticoid

This highlights the dual activity of Fludrocortisone.

Question 9

What type of effects do Prednisone and Prednisolone have?

Answer 9

More glucocorticoid effects than mineralocorticoid

Question 10

What must happen for Prednisone to be active?

Answer 10

It must be converted to prednisolone in the liver

Question 11

What is the most commonly prescribed oral glucocorticoid?

Answer 11

Prednisone

Question 12

For what purposes is Prednisone typically used?

Answer 12

Anti-inflammatory purposes

Question 13

How should Prednisone be administered for it to be effective?

Answer 13

Orally, not topically or injected locally

Question 14

What are the anti-inflammatory effects of Triamcinolone, Methylprednisolone, and Betamethasone?

Answer 14

Highest anti-inflammatory effects with no salt-retaining effects

Question 15

What type of activity do Triamcinolone, Methylprednisolone, and Betamethasone have?

Answer 15

Virtually no mineralocorticoid activity

Question 16

What is the primary use of Triamcinolone, Methylprednisolone, and Betamethasone?

Answer 16

Typically only used for anti-inflammatory purposes

Question 17

What is a key difference among newer glucocorticoid drugs compared to older ones?

Answer 17

Differences exist in duration of action and potency

Question 18

Fill in the blank: Prednisone is similar to _______ and hydrocortisone.

Answer 18

cortisone

Question 19

Does Dexamethasone have mineralocorticoid activity?

Answer 19

No

Question 20

What type of activity does Dexamethasone have?

Answer 20

Very high glucocorticoid activity

Question 21

For what purpose is Dexamethasone typically used?

Answer 21

Anti-inflammatory purposes

Question 22

Why is Dexamethasone the preferred glucocorticoid for cerebral edema?

Answer 22

Because of its ability to enter the CNS

Question 23

When is Dexamethasone used in relation to endogenous cortisol levels?

Answer 23

When endogenous cortisol levels have to be measured

Question 24

What is a specific test that uses Dexamethasone?

Answer 24

Dexamethasone suppression tests

Question 25

Fill in the blank: Dexamethasone is preferred for cerebral edema due to its ability to enter the _______.

Answer 25

CNS

Question 26

What is Fluticasone commonly prescribed for?

Answer 26

Asthma: Inhaled and intranasal Rhinitis: intranasal May use oral if inhaled not working ## Footnote Fluticasone is marketed under the brand names Flovent® and Flonase®.

Question 27

Fluticasone is categorized as what type of medication?

Answer 27

Glucocorticoid

Question 28

What is Ketoconazole (Nizoral®)?

Answer 28

Orally active antifungal agent that also inhibits steroidogenesis at higher doses ## Footnote Ketoconazole is primarily known for its antifungal properties but has significant effects on hormone synthesis.

Question 29

What is the mechanism of action of Ketoconazole?

Answer 29

Inhibits 17a-hydroxylase → decreased androgens first then cortisol ## Footnote At even higher doses, it also inhibits the conversion of cholesterol to pregnenolone, thereby inhibiting all steroid synthesis.

Question 30

What are the primary therapeutic effects of Ketoconazole?

Answer 30

Typically first line inhibitor of steroid biosynthesis used in patients with Cushing's ## Footnote It is used off label for other conditions not approved by the FDA.

Question 31

What is a significant pharmacokinetic property of Ketoconazole?

Answer 31

Metabolized by and is a strong inhibitor of CYP3A4 ## Footnote This can lead to interactions with other medications that are metabolized by the same enzyme.

Question 32

What are some common adverse effects of Ketoconazole?

Answer 32

Reversible hepatotoxicity, gynecomastia, libido decrease, and impotence ## Footnote These side effects are important to consider when prescribing the drug.

Question 33

What are the contraindications/precautions associated with Ketoconazole?

Answer 33

Potentially teratogenic, not first line drug in pregnancy ## Footnote It is crucial to avoid its use in pregnant women due to potential risks to the fetus.

Question 34

What is the mechanism of action of Metyrapone?

Answer 34

Relatively selective inhibitor of 11ß1-hydroxylase, the terminal enzyme in cortisol synthesis ## Footnote It also reduces deoxycorticosterone levels, and thus aldosterone.

Question 35

What cortisol precursor is increased by Metyrapone?

Answer 35

11-deoxycortisol

Question 36

What are the therapeutic indications for Metyrapone?

Answer 36

* Tests of adrenal function * Short-term management of symptoms while cause of Cushing's is being determined * Long-term treatment of Cushing's disease (off-label)

Question 37

Which patient group can Metyrapone be given to that other drugs in its class cannot?

Answer 37

Pregnant women

Question 38

What are some adverse effects of Metyrapone?

Answer 38

* GI disturbances * Sedation * Dizziness * Rash * Hirsutism (androgen shunt)

Question 39

True or False: Metyrapone is considered a first-line drug for long-term management in non-pregnant women.

Answer 39

False

Question 40

How does Metyrapone affect aldosterone function?

Answer 40

Increases 11-deoxycortisol, which sustains aldosterone functions

Question 41

What is a notable advantage of Metyrapone compared to mitotane?

Answer 41

Less toxicity

Question 42

What is Osilodrostat also known as?

Answer 42

Isturisa®

Question 43

When was Osilodrostat FDA approved?

Answer 43

March 2020

Question 44

What is the mechanism of action of Osilodrostat?

Answer 44

Inhibitor of 11ß1-hydroxylase and aldosterone synthesis

Question 45

What condition is Osilodrostat indicated for?

Answer 45

Cushing's syndrome

Question 46

What is a key indication for using Osilodrostat?

Answer 46

When pituitary surgery is not an option or has not been curative

Question 47

What is significant about Osilodrostat in the context of Cushing's disease?

Answer 47

First cortisol synthesis inhibitor to be FDA-approved for treatment

Question 48

How is Osilodrostat metabolized?

Answer 48

By multiple hepatic enzymes, including CYP3A4

Question 49

What dosage adjustment is necessary when combining Osilodrostat with ketoconazole?

Answer 49

Decreased dose

Question 50

What is a common adverse effect of Osilodrostat that affects 43% of patients?

Answer 50

Hypocortisolism leading to adrenal insufficiency

Question 51

List three adverse effects of Osilodrostat that occurred in more than 20% of patients.

Answer 51

* Fatigue * Nausea * Headache * Edema

Question 52

What percentage of patients taking Osilodrostat experienced hypertension?

Answer 52

10%

Question 53

What are two adverse effects associated with women taking Osilodrostat?

Answer 53

* Hirsutism * Acne

Question 54

What are two potential serious adverse effects of Osilodrostat?

Answer 54

* Hypokalemia * Prolonged QT interval

Question 55

Has Osilodrostat been tested in pregnant women?

Answer 55

No, but no problems in pregnant animals at normal doses

Question 56

What was the effect of high doses of Osilodrostat in pregnant animals?

Answer 56

Decreased fetal viability

Question 57

What is Mifepristone also known as?

Answer 57

RU 486, Mifeprix®

Question 58

What is the primary mechanism of action of Mifepristone?

Answer 58

Powerful antagonist of progesterone receptors, and at higher doses, glucocorticoid receptors

Question 59

What is Mifepristone approved for?

Answer 59

Inducing abortions

Question 60

What condition can Mifepristone help manage in inoperable patients?

Answer 60

Ectopic ACTH secretion or adrenal carcinoma who have failed to respond to other therapies

Question 61

What symptoms can Mifepristone provide rapid relief from?

Answer 61

Some hypercortisolemia symptoms like psychosis

Question 62

What are some contraindications or precautions for Mifepristone?

Answer 62

Abdominal pain, amenorrhea, fatigue, gastrointestinal upset, pregnancy

Question 63

What is Spironolactone also known as?

Answer 63

Aldactone®

Question 64

What is the mechanism of action of Spironolactone?

Answer 64

Competitive mineralocorticoid receptor antagonist

Question 65

What additional receptor antagonism properties does Spironolactone have?

Answer 65

Androgen and progesterone receptor antagonist properties

Question 66

What are the therapeutic uses of Spironolactone?

Answer 66

* Potassium-sparing diuretic * Primary hyperaldosteronism (also for diagnosis) * Hypertension * Heart Failure * Treat ascites associated with cirrhosis * Decrease hirsutism in women

Question 67

What adverse effects can Spironolactone cause?

Answer 67

* Hyperkalemia * Cardiac arrhythmias * Gynecomastia and impotence in men * Menstrual irregularities in women * Gastrointestinal upset * Sedation * Headache * Skin rashes