Corticosteroids

Question 1

Binds to Beta-adrenergic receptor (GPCR)
Initiates signal transduction cascade
Induces immediate response
Breaks down glycogen and release glucose

Answer 1

Epinephrine

Question 2

Binds to glucocorticoid receptor
Regulates gene transcription and thus translation and protein production
Induces long term, persistent biological response
Induces gluconeogenic enzymes
Inhibit pro-inflammatory processes

Answer 2

Cortisol (hydrocortison)

Question 3

Which part of the kidneys make glucocorticoids, mineralocorticoids, and androgens?

Answer 3

Cortex of the adrenal gland

Question 4

Which part of the kidneys make epinephrine and norepinephrine?

Answer 4

Medulla of adrenal gland

Question 5

Stress hormones
Increase circulating glucose concentration
Potent anti-inflammatory effects

Answer 5

Glucocorticoids

Question 6

Adrenocorticoid that leads to Na+ retention and increased blood volume and pressure

Answer 6

Mineralocorticoids

Question 7

Regulation of glucocorticoid synthesis

Answer 7

Stress -> Hypothalamus -> CRH -> ACTH -> Cortisol -> physiological responses

Question 8

DNA-binding domains of activated dimers that bind to specific DNA sequences, upstream of steroid responsive genes

Answer 8

Glucocorticoid Responsive Elements (GRE)

Question 9

Catalyzes the rate-limiting step in gluconeogenesis

Answer 9

PEP carboxykinase

Question 10

Suppresses phospholipase A2, which has a critical role in eicosanoid synthesis

Answer 10

lipocortin I

Question 11

Destruction of the cortex by tuberculosis or atrophy

Answer 11

Addison’s disease (primary)

Question 12

What happens to CRH, ACTH, Cortisol and Aldosterone in Primary adrenal insufficiency?

Answer 12

Adrenal defect: Increased CRH and ACTH, decreased Cortisol and Aldosterone

Question 13

What happens to CRH, ACTH, Cortisol and Aldosterone in Secondary adrenal insufficiency?

Answer 13

Pituitary defect: increased CRH and decreased ACTH, Cortisol, and not affected aldosterone

Question 14

What happens to CRH, ACTH, Cortisol and Aldosterone in Tertiary adrenal insufficiency?

Answer 14

Hypothalamic defect: decreased CRH, ACTH, and Cortisol. Aldosterone not affected.

Question 15

This condition has a few causes:
Tumors in the adrenal cortex
Increased production of ACTH due to pituitary carcinoma
Ectopic production of ACTH due to non-pituitary carcinoma

Answer 15

Cushing disease

Question 16

What happens to CRH, ACTH and Cortisol in Adrenal affected Cushing disease?

Answer 16

Decreased CRH and ACTH, increased Cortisol

Question 17

What happens to CRH, ACTH and Cortisol in Pituitary affected Cushing disease?

Answer 17

Decreased CRH and increased ACTH and Cortisol

Question 18

What happens to CRH, ACTH and Cortisol in Ectopic affected Cushing disease?

Answer 18

Decreased CRH, ACTH and increased Cortisol and Ectopic ACTH

Question 19

What is this glucocorticoid?

Answer 19

Cortisone

Question 20

How is cortisol inactivated?

Answer 20

Oxidation of 11 hydroxyl to ketone

Question 21

How is Cortisone activated?

Answer 21

Catalyzed by 11Beta-hydroxysteroid dehydrogenase in the liver

Question 22

What are the short-acting systemic corticosteroids (2)

Answer 22

(-sone): Hydrocortisone and cortisone

Question 23

What are the intermediate-acting corticosteroids? (4)

Answer 23

(-olone) Prednisone, Prednisolone, Methylprednisolone, and Triamcinolone

Question 24

What are the long-acting corticosteroids? (2)

Answer 24

(-methasone) Dexamethasone and Betamethasone

Question 25

Where is the Florine positioned at? Greater glucocorticoid activity, strong mineralocorticoid activity (intense Na retention leading to edema) Used in mineralocorticoid replacement therapy

Answer 25

Fludrocortisone: 9alpha-F

Question 26

Where is the altered ring structure? More potent glucocorticoid activity, stronger binding to the glucocorticoid receptor Reduced mineralocorticoid activity Interconvertible by 11Beta-hydroxysteroid dehydrogenase

Answer 26

Prednisone/prednisolone Double bond between C1 and C2

Question 27

Where is the methyl group located? Potency similar to that for prednisolone Reduced mineralocorticoid activity

Answer 27

Methylprednisolone: 6alpha-methyl group

Question 28

Where is the F and OH located at? Glucocorticoid activity similar to prednisone Reduced mineralocorticoid activity Increased hydrophilicity Low oral bioavailability

Answer 28

Triamcinolone: 9alpha-F and 16alpha-OH

Question 29

Where is the methyl group located? Increased lipophilicity (increased receptor binding, significantly stronger effect) Increased stability in human plasma Reduced mineralocorticoid activity

Answer 29

Dexamethasone: 16alpha-methyl group

Question 30

Enantiomer of dexamethasone at what location? Has similar properties as dexamethasone

Answer 30

Betamethasone: 16Beta instead of 16alpha (Dexamethasone)

Question 31

Which modifications of 21-esters increase lipophilicity and prolonged action upon IM or intra-articular injection

Answer 31

Acetate and butyrate

Question 32

Which modification of 21-esters is soluble and has slow hydrolysis (peak 30-40min)?

Answer 32

Succinate

Question 33

Which modification of 21-esters increases solubility, has rapid hydrolysis by phosphatases, and IV or IM injection for emergency use?

Answer 33

phosphate

Question 34

T/F: Glucocorticoids are are method of stopping an asthma attack while its happening?

Answer 34

FALSE

Question 35

Which type of glucocorticoid? where acetonide is resistant to hydrolysis 8x more potent than prednisolone

Answer 35

Triamcinolone acetonide (Azmacort) Inhaled

Question 36

Which type of glucocorticoid? Converted rapidly to 17-monopropionate by hydrolysis 14x more potent than dexamethasone

Answer 36

Beclomethasone dipropionate Inhaled

Question 37

Which type of glucocorticoid? Rapid absorption from nasal or lung tissue Rapid metabolism by the liver: extensive first-path metabolism, minimal systemic adverse effect with long-term therapy

Answer 37

Flunisolide (Aerobid)

Question 38

Which type of glucocorticoid? 1:1 mixture of epimers at 16, 17-butylacetal Faster topical uptake Low oral bioavailability Extensive first-path metabolism

Answer 38

Budesonide (Pulmicort) Inhaled

Question 39

Which type of glucocorticoid? Highly potent, more rapid onset of action, negligible systemic availability (Rapid metabolism, low oral bioavailability)

Answer 39

Mometasone furoate (Asmanex) Inhaled

Question 40

Which type of glucocorticoid? Inactivate by hydrolysis of thioester (Rapid first-path metabolism) Highly lipophilic and insoluble (highly potent, poor absorption from GI, rapid topical uptake)

Answer 40

Fluticasone propionate Inhaled

Question 41

What are the three high potency topical glucocorticoids?

Answer 41

Triamcinolone acetonide, Fluocinonide, and Halcinonide

Question 42

What are two very high potency topical chlorocorticoids?

Answer 42

Clobetasol propionate and halobetasol propionate

Question 43

What are three medium potency topical glucocorticoids?

Answer 43

Betamethasone valerate, fluticasone propionate and mometasone furoate

Question 44

High lipophilicity Minimal systemic effect Prolonged action Are desired properties of what?

Answer 44

Topical glucocorticoids

Question 45

High potency Minimal systemic effects Prolonged action Are desired properties of what?

Answer 45

Inhaled glucocorticoids