Adrenocoricoids Flashcards
Most important propery of glucocorticoids?
2 parts of the cortex and their functions
Synthesis of aldosterone, cortisol and 11-Deoxycorticosterone.
4 Important roids and their function 2 mineral 2 gluco
2 mineralcorticoids name them
11-deoxycorticosterone, aldosterone
Mineral and Antimineralocorticoids
Endogenous agonists? 2
Synthetic Antagonists?
Flowchart
Mineral and Antimineralocorticoids
Synthetic Antagonists 2 types
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?
All synthetic glucocorticoids are preduced from?
What is the active and inactive form of glucocorticoids?
4 routes of glucocorticoid metabolism
What do glucocorticoid esters do?
All of these are inactive? What do they need?
Block glucuronidation at the 21 position and prolong the duration of activity
Need to be activated they are inactive prodrugs
What 3 zones is the adrenal cortex broen up into?
What do each of these secrete or produce?
Biosynthetic pathway of 3 products
Adrenal Cortex Steroids Key Fx
Mineralcorticoids what do they do?
Glucocorticoids Favors? Important in function of? Reduce what response?
Aldosterone
Where is it produced?
What is the active form and what does it look like?
Aldosterone has high ____ activity?
Why are semi-synthetics made?
What is absent in 11-deoxycorticosterone? 2 things
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?
Spironolactone
What type of inhibitor is it? At what receptors?
What is it called and why?
Eplerenone (Inspra)
Similar to Spironolactone
what receptor does it act on?
Initially used to treat what? Then used for?
Glucocorticoids
In the synthetic pathway?
Glucocorticoid flow chart
Chart starts with endogenous agonists
Hydrocortisone (Cortisol) and Cortisone
Where is it produced?
What about it in tissues?
Cortisol and Cortisone
What is the active form?
Both of these compounds contain too much of what type of activity?
Metabolism of Glucocorticoids
Undergo extensive metabolism in four main routes
What are the products of 3-keto-4-ene reduction for Hydrocortisone and Cortisone?
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?
Glucocorticoids
What activity does the 11b-OH give the molecule?
Metabolism of Glucocorticoids
11b-hydroxyl
What type of process is it and what enzyme is responsible for it?
What type of metabolite is it?
Metabolism of Glucocorticoids
21 hydroxyl
This is a common site for what 2 rxns?
Metabolism of Glucocorticoids
21-hydroxyl
MEtabolism at this point leads to increased?
Metabolism of Glucocorticoids
6b-hydroxylation
Metabolism via what enzyme?
What happends to activity?
Synthetic Analogs
5 examples of Esters of GLucs
Where is the modification at for these esters?
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?
Synthetic Analogs
Structurally modified gluc nucleus
7ish examples
This drug has a modification at the 1 to form a double bond between 1 and 2 in the A ring
Prednisolone and Prednisone both have a d1 Alkene
What does this do for activity?
____ ____ at the C21 position is easily esterified to form what?
This compound has a methyl group at the C6 position what is it?
What purpose does this serve?
What does it do for activity?
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?
This drug contains a 6a-Fluoro group
What does it do for activity?
What does it decrease?
6a-fluroprednisolone
Activity compared to hydrocortisone?
The A ring still has?
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?
What does a 9a-Fluoro prevent?
What does this compound lack?
This drug is only useful for the treatment of?
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?
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?
Triamcinolone activity compared to hydrocortisone?
These compounds have a 16a or 16b modification
What is the addition?
What does this prevent and suppress?
What activity is reduced?
What combination in 16a/b Methylprednisolone give potent anti-inflam activity?
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?
Momestasone has a combination of 5 things that give it strong anti-inflammatory action
What is the onset of action compared to Triamcinolone?
What modifications does beclomethasone have?
What gives it its potent gluco action?
This one is widely used in inhalers?
