Adrenal Steroids - Pharmacodynamics Flashcards
What is the MOA of adrenal steroids?
1 - Glucocorticoids enter cells and bind with specific receptors in the cytosol
2 - The receptor steroid complex is transported into the nucleus where it modulates gene expression in some way
3 - Altered enzyme syntesis (increases rate or turns a process on or off)
4 - Altered membrane permeability and transport processes
5 - Altered synthesis of structural proteins
6 - The function of this class of drugs is really to alter physiologic processes (direct effects on cells, indirect effects via homeostatic responses (increase insulin/decrease glucagon)
Overall glucocorticoids put more glucose into the blood, then you release insulin and you get a redistribution of fat (with too much cortisol)
What do the heat shock proteins (SHP90) do?
Hold the receptor in the right confirmation for binding of cortisol (the steroid). Once they bind you get rid of the heat shock proteins and you dimerize. Then you recruit co-activators or co-repressors (to repress a gene).
What is the Glucocorticoid Response Element(GRE)?
The complex that binds the steroid-receptor complex once it enters the DNA
How do glucocorticoids decrease the synthesis of serotonin?
Parachlorophenylalanine represses Tryptophan hydroxylase, the rate limiting step in the synthesis of serotonin.
What is CRH used for?
In diagnosis to distinguish between hypothalamic and pituitary dysfunction in ACTH deficiency and excess
What is ACTH used for?
1 - To distinguish between pituitary and adrenal pathology
2 - Stimulates the adrenal cortex to secrete glucocorticoids, mineralcorticoids, and androgens
What are the sources of ACTH?
1 - Synthetic
2 - Animal (antibody production - anaphylactic reactions, diminished effect)
ACTH use carries the same concerns as does direct use of glucocorticoids
Which are the adrenal steroids?
1 - Glucocorticoids: have important effects on intermediary metabolism
2 - Mineralocorticosteroids: steroids with important salt retains effects at the level of the kidney (Aldosterone)
3 - Androgenic and/or estrogenic steroids: Mainly produced by the gonadal tissue
What is the drug of choice for infantile spasms in epilepsy?
ACTH
What is the glucocorticoid permissive effect?
2 types of response to glucocorticoids: Dose related and permissive effects (there is a threshold where a process will only proceed when the corticosteroid is present but increased dose above threshold does not increase the effect)
