Glucocorticoids

Question 1

What kind of activity does Fludrocortisone have?

Answer 1

good glucocorticoid activity

Strong mineralcorticoid activity

Question 2

What kind of ADE does fludrocortisone have?

Answer 2

Strong mineralcortocoid activity causes strong Na+ retention leading to edema

Question 3

What structural differences does fludrocortisone have compared to hydrocortisone?

Answer 3

It has a 9alpha-Fluorine

Question 4

what kind of activity does prednisone have?

Answer 4

Strong glucocorticoid activity

reduced mineralcorticoid activity

Question 5

What kind of activity does prednisolone have?

Answer 5

Strong glucocorticoid activity

reduced mineralcorticoid activity

Question 6

What is the structural difference between prednisone and hydrocortisone?

Answer 6

Prednisone has a C1=C2 double bond

Prednisone has C11 double bond oxygen

Question 7

What is the structural difference between prednisolone and hydrocortisone?

Answer 7

prednisolone has a C1=C2 double bond

Question 8

Which is more selective for the glucocorticoid receptor, prednisone or prednisolone?

Answer 8

Prednisone

Question 9

Which has a rapid onset between prednisone and prednisolone?

Answer 9

Prednisolone

Question 10

What is the activity of methylprednisolone?

Answer 10

very reduced mineralcorticoid activity

Strong glucocorticoid activity

Question 11

how does methylprednisolone differ from hydrocortisone?

Answer 11

It has a C1=C2 and a 6alpha-CH3 group

Question 12

What effect does the -CH3 in methylprednisolone have on the mineralcorticoid receptor?

Answer 12

The -CH3 sterically clashes with the mineralcorticoid receptor

Question 13

What kind of activity does triamcinolone have?

Answer 13

Strong glucocorticoid activity

reduced mineralcorticoid activity

Question 14

What structure modifications does triamcinolone have?

Answer 14

9alpha-fluorine

16alpha-OH

Question 15

How does the 16a-OH affect activity?

Answer 15

Reduces mineralcorticoid activity

Increases solubility –> decreases bioavailability

Question 16

How does the 9a-F affect activity?

Answer 16

Enhances glucocorticoid activity

Question 17

What structural alteration does dexamethasone have?

Answer 17

It has a 16a-methyl group

C1=C2

Question 18

What affect does the 16a-methyl group have on activity?

Answer 18

Increases lipophilicity –> increases receptor binding –> increases effects

Question 19

What is the activity of dexamethasone?

Answer 19

Reduced mineralcorticoid activity

Strongest glucocorticoid activity

Question 20

What is the structural modification of betamethasone?

Answer 20

16beta-methyl group

C1=C2

Question 21

What are 3 21-ester modifications?

Answer 21

Acetate/butyrate
phosphate
succinate

Question 22

How does a 21-ester modification affect the drug?

Answer 22

Makes it a prodrug that is activated by esterases

Question 23

How does a 21-ester acetate modification affect drug properties?

Answer 23

Increases lipophilicity

Increases duration of action upon IM injection

Question 24

How does a 21-ester phosphate modification affect the drug?

Answer 24

increases solubility
Rapidly hydrolized–> decreases time to onset
optimal for IM/IV injection

Question 25

How does a 21-ester succinate affect the drug?

Answer 25

Soluble | Slows hydrolysis

Question 26

What are ADE of corticoids?

Answer 26

``` Crossover mineralcorticoid activity metabolic effects osteoporosis Cushings-like Impaired glucose tolerance immunosupression GI effects CNS effects Cataracts ```

Question 27

Triamcinolone Acetonide

Answer 27

Inhaled glucocorticoid | Azamacort, Nasocort

Question 28

What are some unique properties of triamcinolone acetonide?

Answer 28

8x more potent than prednisolone Acetonide is resistant to hydrolysis Highly soluable

Question 29

Beclomethasone dipropionate

Answer 29

Vanceril, Qvar

Question 30

What are some unique properties of Qvar?

Answer 30

- rapidly converted hydrolyzed - 14x more potent than dexamethasone - Lipophillic

Question 31

What are some unique structural properties of Qvar?

Answer 31

9-Cl, 2 Ester-CH2CH3 groups

Question 32

Flunisolide

Answer 32

Aerobid

Question 33

What are some unique properties of flunisolide?

Answer 33

- rapid absorption from nasal/lung tissue | - rapid liver metabolism

Question 34

What is a unique structural property of flunisolide?

Answer 34

-6Fluorine

Question 35

Budesonide

Answer 35

Pulmicort

Question 36

What is a unique structural property of budesonide?

Answer 36

1:1 mix of 16,17 butylacetal

Question 37

What are some unique properties of budesonide?

Answer 37

Faster topical uptake low oral bioavailability extensive first pass metabolism

Question 38

Mometasone furoate

Answer 38

Asmanex

Question 39

What are some unique structural features of mometasone furoate?

Answer 39

Aromatic group on carboxylic acid | Cl on right side

Question 40

fluticasone propionate

Answer 40

flovent, flonase

Question 41

What is a unique structural feature of fluticosone propionate?

Answer 41

S- - F group | thioester

Question 42

What are some properties of fluticasone?

Answer 42

``` Inactivated by hydrolysis of thioester very lipophilic and insoluble very potent poor GI absorption Rapid topical uptake ```

Question 43

What are 2 types of adenocorticoids?

Answer 43

Glucocorticoids | mineralocorticoids

Question 44

What is an example of glucocorticoids?

Answer 44

cortisone (hydrocortisone)

Question 45

What is an example of mineralocorticoids?

Answer 45

aldosterone

Question 46

What is the function of glucocorticoids?

Answer 46

- stress hormones - increase glucose concentrations - potent anti- inflammatory effects

Question 47

What is the function of mineralocorticoids?

Answer 47

- Na reuptake in the kidney | - controls BP

Question 48

What part of the adrenal gland releases adrenal hormones--glucocorticoids, mineralocorticoids and androgens?

Answer 48

The adrenal cortex

Question 49

What is the HPA axis?

Answer 49

Stress--> brain-->hypothalamus--> Corticotropin releasing hormone--> pituitary gland-->releases adrenocorticotropic hormone--> stimulates the adrenal gland to release cortisol