Adrenocoricoids

Question 1

Most important propery of glucocorticoids?

Question 2

2 parts of the cortex and their functions

Question 3

Synthesis of aldosterone, cortisol and 11-Deoxycorticosterone.

Question 4

4 Important roids and their function 2 mineral 2 gluco

Answer 4

Question 5

2 mineralcorticoids name them

Answer 5

11-deoxycorticosterone, aldosterone

Question 6

Mineral and Antimineralocorticoids

Endogenous agonists? 2

Synthetic Antagonists?

Flowchart

Answer 6

Question 7

Mineral and Antimineralocorticoids

Synthetic Antagonists 2 types

Question 8

Spironolactone

What is it?

What is essential for activity?

An intact what is also important?

What at the 7 position improves antagonist activity and oral bioavailability?

Eplerenone has the same activity but what is it lacking?

Answer 8

Question 9

All synthetic glucocorticoids are preduced from?

Question 10

What is the active and inactive form of glucocorticoids?

Question 11

4 routes of glucocorticoid metabolism

Question 12

What do glucocorticoid esters do?

All of these are inactive? What do they need?

Answer 12

Block glucuronidation at the 21 position and prolong the duration of activity

Need to be activated they are inactive prodrugs

Question 13

What 3 zones is the adrenal cortex broen up into?

What do each of these secrete or produce?

Answer 13

Question 14

Biosynthetic pathway of 3 products

Answer 14

Question 15

Adrenal Cortex Steroids Key Fx

Mineralcorticoids what do they do?

Glucocorticoids Favors? Important in function of? Reduce what response?

Answer 15

Question 16

Aldosterone

Where is it produced?

What is the active form and what does it look like?

Answer 16

Question 17

Aldosterone has high ____ activity?

Why are semi-synthetics made?

Answer 17

Question 18

What is absent in 11-deoxycorticosterone? 2 things

Answer 18

Question 19

Since 11-deoxy lacks an OH at C11 and an Aldehyde at C18 what changes with its acitivity?

But it still has significant activity?

What activtiy does it lack?

Answer 19

Question 20

Spironolactone

What type of inhibitor is it? At what receptors?

What is it called and why?

Answer 20

Question 21

Eplerenone (Inspra)

Similar to Spironolactone

what receptor does it act on?

Initially used to treat what? Then used for?

Answer 21

Question 22

Glucocorticoids

In the synthetic pathway?

Answer 22

Question 23

Glucocorticoid flow chart

Chart starts with endogenous agonists

Answer 23

Question 24

Hydrocortisone (Cortisol) and Cortisone

Where is it produced?

What about it in tissues?

Answer 24

Question 25

Cortisol and Cortisone What is the active form? Both of these compounds contain too much of what type of activity?

Answer 25

Question 26

Metabolism of Glucocorticoids Undergo extensive metabolism in four main routes

Answer 26

Question 27

What are the products of 3-keto-4-ene reduction for Hydrocortisone and Cortisone?

Answer 27

Question 28

Glucocorticoids What does 3-keto-4-ene reduction do for activity? What happens to the product of this metabolism once done? What rxn and what does this mean for PK?

Answer 28

Question 29

Glucocorticoids What activity does the 11b-OH give the molecule?

Answer 29

Question 30

Metabolism of Glucocorticoids 11b-hydroxyl What type of process is it and what enzyme is responsible for it? What type of metabolite is it?

Answer 30

Question 31

Metabolism of Glucocorticoids 21 hydroxyl This is a common site for what 2 rxns?

Answer 31

Question 32

Metabolism of Glucocorticoids 21-hydroxyl MEtabolism at this point leads to increased?

Answer 32

Question 33

Metabolism of Glucocorticoids 6b-hydroxylation Metabolism via what enzyme? What happends to activity?

Answer 33

Question 34

Synthetic Analogs 5 examples of Esters of GLucs Where is the modification at for these esters?

Answer 34

Question 35

3 specific gluco esters What route are each of these and their names What do these esters block? So then these have a? What are these types of drugs called?

Answer 35

Question 36

Synthetic Analogs Structurally modified gluc nucleus 7ish examples

Answer 36

Question 37

This drug has a modification at the 1 to form a double bond between 1 and 2 in the A ring

Answer 37

Question 38

Prednisolone and Prednisone both have a d1 Alkene What does this do for activity? \_\_\_\_ ____ at the C21 position is easily esterified to form what?

Answer 38

Question 39

This compound has a methyl group at the C6 position what is it? What purpose does this serve? What does it do for activity?

Answer 39

Question 40

As well as a 6a methyl group methylprednisolone also has what? It is similar to prednisolone What is its anti-inflammatory activity compared to hydrocortisone?

Answer 40

Question 41

This drug contains a 6a-Fluoro group What does it do for activity? What does it decrease?

Answer 41

Question 42

6a-fluroprednisolone Activity compared to hydrocortisone? The A ring still has?

Answer 42

Question 43

This drug has a 9a-Fluorogroup This one is lacking what in one of the rings? What does this do for activity? How is binding improved?

Answer 43

Question 44

What does a 9a-Fluoro prevent? What does this compound lack? This drug is only useful for the treatment of?

Answer 44

Question 45

This drug has a 16a-Hydroxy What does this do for activity? This drug also has a combinations of two other structural features what does this mean for activity?

Answer 45

Question 46

Triamcinolone Has a modification at the 16 position how can it be modified further to produce a more lipophilic variant? Why would this be useful?

Answer 46

Question 47

Triamcinolone activity compared to hydrocortisone?

Answer 47

Question 48

These compounds have a 16a or 16b modification What is the addition? What does this prevent and suppress? What activity is reduced?

Answer 48

Question 49

What combination in 16a/b Methylprednisolone give potent anti-inflam activity?

Answer 49

Question 50

21-chloro What does it do? There is also something on the C17 position that increases potency and gives a more lipophilic compound making it good for?

Answer 50

Question 51

Momestasone has a combination of 5 things that give it strong anti-inflammatory action What is the onset of action compared to Triamcinolone?

Answer 51

Question 52

What modifications does beclomethasone have? What gives it its potent gluco action?

Answer 52

Question 53

This one is widely used in inhalers?

Answer 53