PTN - Glucocorticoids (Eblen)

Question 1

What is the major symptom of hyperaldosteronism?

Answer 1

Hypertension

Aldosterone acts on cells of the renal tubule, causing an increased reabsorption of sodium. Sodium that enters the blood draws water in through an osmotic gradient, leading to increased blood volume.

Question 2

A patient with redistribution of fat, muscle wasting, hyperglycemia, and hyperlipidemia likely has what condition?

Answer 2

Cushing’s Syndrome

Cushing Syndrome is characterized as an excess production and release of ACTH. ACTH excess causes an increase in cortisol production, which induces breakdown of muscle and fat, but fat gets redistributed into the face (moon face) and back of neck (buffalo hump).

Excess cortisol can also act on mineralocorticoid receptors, causing increased production of aldosterone, which would increase sodium and water reabsorption in the blood –> hypervolemia and hypertension

Question 3

What drug can be given to a patient to inhibit all steroidogenisis? What enzyme is blocked by this drug? This drug is the most effective treatment for what condition?

Answer 3

Ketoconazole (high dose)

Ketoconazole blocks desmolase, an enzyme that converts cholesterol into pregnenalone, a precursor for all steroid hormones.

Most effective against Cushing Syndrome

Question 4

What is the role of glucocorticoids on the immune system?

Answer 4

Immunosuppression and anti-inflammatory effect

Question 5

What is the function of prednisone?

Answer 5

Functions as a glucocorticoid to decrease inflammation and cause immunosuppression

Question 6

A patient with Addison’s disease has an imbalance of what hormones? This is treated with what medication?

Answer 6

Addison’s Disease causes primary adrenal failure, which prevents production of glucocorticoids and aldosterone.

Treat glucocorticoid deficiency with glucocorticoids (prednisone, dexamethasone, beclomethasone)

Treat aldosterone deficiency with fludrocortisone

Question 7

True or False: Glucocorticoids, when given in correct doses, can cure conditions such as Addison’s disease.

Answer 7

False

Glucocorticoids will treat the disease by supplying these molecules, but it will not cure it

Question 8

What drug inhibits desmolase?

Answer 8

Ketoconazole

Question 9

What drug inhibits 11-beta-hydroxylase?

Answer 9

Metyrapone

11-beta-hydroxylase is involved in the conversion of 11-deoxycortisol into cortisol (the last step in cortisol production)

Inhibition of this enzyme also blocks formation of aldosterone

Question 10

Which receptor does fludrocortisone preferentially bind to?

Answer 10

Mineralocorticoid receptor

Binding induces function of aldosterone, leading to increased sodium and water reabsorption by kidney

Question 11

What is the name of the condition that results from a sudden cessation of glucocorticoids from a patient, instead of gradually weaning them off?

Answer 11

Acute adrenal insufficiency

Question 12

What class of adrenal steroids affects metabolism?

Answer 12

Glucocorticoids

Question 13

In what layer of the adrenal cortex is cortisol synthesized? Aldosterone? Sex hormones?

Answer 13

• Cortisol - zona fasciculata
• Aldosterone - zona glomerulosa
• Sex hormones - zona reticularis

Question 14

On which receptor(s) will dexamethasone bind and act on?

Answer 14

Dexamethasone only binds to glucocorticoid receptors, regardless of concentration of the drug.

Question 15

In the production of adrenal steroids, what are two enzymes that are common targets of drugs in prevention of steroid formation?

Answer 15

Desmolase - inhibits conversion of cholesterol to pregnenalone (inhibits all steroid hormone synthesis)

11-beta-hydroxylase - inhibits production of cortisol and aldosterone

Question 16

How does the body compensate for the potential of cortisol to bind to both, glucocorticoid and mineralocorticoid receptors, in order to prevent unwanted activation of the mineralocorticoid receptors?

Answer 16

Excess cortisol is converted into cortisone (an inactive form) via 11-beta-hydroxysteroid dehydrogenase type 2

Question 17

Moon face and the buffalo hump is associated with what condition? What drug can be given to mitigate this condition?

Answer 17

Cushing Syndrome (ACTH excess)

Treat with ketoconazole and metyrapone

Question 18

What is the most potent synthetic glucocorticoid?

Answer 18

Dexamethasone

Question 19

Name the 4 glucocorticoid receptor agonist drugs.

Answer 19

1. Cortisol
2. Prednisone
3. Beclomethasone
4. Dexamethasone

Question 20

What makes beclomethasone different than the other 3 glucocorticoid agonists?

Answer 20

It has to be inhaled

Question 21

What are the 2 mineralocorticoid receptor antagonists? What do they treat?

Answer 21

Spironolactone and Eplerenone

Both treat primary hyperaldosteronism –> decreased blood pressure