Endocrine 05

Front 1

What 6 major groups of steroid compounds are synthesized by the normal adrenal gland?

Back 1

1. Glucocorticoids
2. Mineralocorticoids
3. Progestins
4. Androgens
5. Estrogens
6. Vitamin D-related steroids

Front 2

Describe the structure of glucocorticoids and mineralocorticoids

Back 2

All glucocorticoids and mineralocorticoids appear to require the 3-keto group, 4-5 double bond, and C17 side chain for biologic activity

Front 3

What is the primary secretory product of the human adrenal gland?

Back 3

Cortisol, the quintessential glucocorticoid

Front 4

What structural component is necessary for a steroid compound to bind to the glucocorticoid receptor?

Back 4

11-beta-hydroxyl group

Front 5

What structural component greatly enhanced glucocorticoid activity?

Back 5

The 17-alpha-hydroxyl and 21-hydroxyl groups

Front 6

What structural changes are usually added to synthetic glucocorticoids?

Back 6

1. C-1-2 double bond
2. C16 alpha methylation or hydroxylation
3. C-9 fluorination

Front 7

Describe the significance of a C-1-2 double bond on a synthetic glucocorticoid

Back 7

-Substantially delays hepatic metabolism of the A ring
-Gives a 5-fold increase in potency over cortisol (eg, prednisolone, prednisone)

Front 8

Describe the significance of C-16 alpha methylation or hydroxylation on a synthetic glucocorticoid

Back 8

-Delays metabolism of the D ring
-Greatly enhances the ratio of glucocorticoid to mineralocorticoid activity

Front 9

Describe the significance of C-9 fluorination on a synthetic glucocorticoid

Back 9

-Increases electronegativity of the C-11 hydroxyl group
-Enhances the ability of the molecule to interact with its receptor
-This substitution appears as well to reduce oxidation of the C-11 hydroxyl group by 11-hydroxysteroid dehydrogenase
-Both glucocorticoid and mineralocorticoid activities are increased

Front 10

Describe 11-hydroxysteroid dehydrogenase

Back 10

-An enzyme that reduces oxidation of the C-11 hydroxyl group of glucocorticoids
-Important in mineralocorticoid-responsive tissues in limiting access of glucocorticoids to the mineralocorticoid receptor

Front 11

Describe dexamethasone

Back 11

-Has a C-1-2 double bond, a C-16 alpha methylation, and C-9 fluorination
-30x the glucocorticoid potency of cortisol

Front 12

Describe the significance of C-21 hydroxyl group substitutions on glucocorticoids

Back 12

Alters absorption of parenterally administered compounds

Front 13

Describe the absorption of C-21 hydrophilic (eg, phosphate) steroids

Back 13

Absorbed rapidly into aqueous media and are used in IM preparations in which rapid systemic distribution is desired (eg, dexamethasone phosphate)

Front 14

Describe the absorption of C-21 hydrophobc (eg, acetate, propionate or succinate) steroids

Back 14

Delays aqueous absorption and are used in parenteral preparations in which a delayed systemic distribution is desired (eg, dexamethasone acetate)

Front 15

Contrast C-11 keto steroids and their C-11-hydroxyl counterparts

Back 15

-C-11-keto steroids are less expensive to manufacture
-C-11 keto steroids are not active glucocorticoids
-These compounds can not be used in topical steroid preparations

Front 16

Describe activation of C-11 keto steroids

Back 16

-Undergo C-11 hydrogenation in the liver to gain biologic activity
-eg. cortisone -> cortisol [hydrocortisone]
-eg. prednisone-> prednisolone

Front 17

Describe the serum half-life, and relative potency of Cortisol

Back 17

Serum Half Life: 80-90 min
Rel. Pot.
Glucocorticoid: 1.0
Mineralocorticoid: 1.0

Front 18

Describe the serum half-life, and relative potency of Cortisone

Back 18

Serum Half Life: 30 min
Rel. Pot.
Glucocorticoid: 0.8
Mineralocorticoid: 0.8

Front 19

Describe the serum half-life, and relative potency of Prednisone

Back 19

Serum Half Life: 60
Rel. Pot.
Glucocorticoid: 3.5-4.0
Mineralocorticoid: 0.8

Front 20

Describe the serum half-life, and relative potency of Prednisolone

Back 20

Serum Half Life: 210-250
Rel. Pot.
Glucocorticoid: 4.0
Mineralocorticoid: 0.8

Front 21

Describe the serum half-life, and relative potency of Dexamethasone

Back 21

Serum Half Life: 280
Rel. Pot.
Glucocorticoid: 30
Mineralocorticoid: 0

Front 22

Describe the absorption of synthetic glucocorticoids

Back 22

Absorbed rapidly from the GI tract

Front 23

Describe the transport of glucocorticoids in the blood

Back 23

-Some (eg, cortisol) are transported largely bound to the specific steroid binding protein transcortin
-Others (eg, dexamethasone) are only weakly associated with the serum proteins

Front 24

Describe metabolism and excretion of glucocorticoids and mineralocorticoids

Back 24

-For most, occurs primarily in the liver through reduction of the 3-keto and 4-5 double bonds of the A ring

-Subsequent attachment of a glucuronide or sulfate group at the 3-hydroxyl position facilitates renal excretion

Front 25

What is the primary natural occuring mineralocorticoid?

Back 25

Aldosterone

Front 26

Describe the clinical use of aldosterone

Back 26

Not used therapeutically

Front 27

Describe desoxycorticosterone (DOC)

Back 27

-A naturally occuring mineralocorticoid
-The first synthetic corticosteroid available for clinical use
-Rarely used today

Front 28

Describe 9-alpha-fluorocortisol

Back 28

-The only widely used synthetic mineralocorticoid
-In clinical doses no important glucocorticoid effects are observed