Glucocorticoids Flashcards
Glucocorticoid anti-inflammatory drugs
Drugs targe the same receptor as endogenous ___________ glucocorticoid.
Mechanism of glucocorticoid action
Cortisol is present in plasma bound to cortisol- binding globulin (CBG), enters cell as free molecule [S].
-Binding of cortisol to cytosolic receptor releases stabilizing proteins (Hsp90), allowing S-R complex to dimerize and enter the nucleus and bind the glucocorticoid response element on DNA – regulates transcription by RNA polymerase II, activating or inhibiting transcription of target genes
Resulting effects on protein synthesis bring about the final hormone response – delayed onset, occurring in hours or longer.
NOTE: Some actions of GCs occur within minutes (e.g., suppression of ACTH release) and can’t be explained by above pathway. Proposed mechanisms include interactions with membrane receptors.
Regulation of cortisol release:
What control the synthesis/secretion of cortisol from the adrenal cortex (zona fasciculata)?
What can chronic use of synthetic GCs do to adrenal gland?
HPA Axis
In which zone of the adrenal cortex is cortisol produced?
Pharmacology HPA axis
Glucocorticoid metabolic effects
What are its effects on protein? Carbohydrate? Lipids?
Mineralocorticoid effects:
Pharmacology of glucocorticoids:
On cellular events, at what points do clucocorticoids block immunity responses?
T cell activatin
Cytokine production by T cells
Eosinophil release of histamine, citokines
Mast cell mediator release
Effects on inflammatory mediators:
At what points do GCs supress inflammatory reactions?
They block COX pathway and the production of arachidonic acid from phospholipids via phospholipase A2
GC- Structure and relation to their activity:
Which drug allows separation of mineralocorticoid vs glucocorticoid actions?
Can you separata anti-inflammatory from immunosupressive actions?
Dexamethasone
Metabolism of glucocorticoids:
In the liver the enzyme_________ activates cortisone back to cortisol.
In the kidneys the enzyme_______ deactivates cortisol by coverting it back to cortisone.
11B-HSD1; 11B-HSD2
Metabolism of Glucocorticoids
In the fetus, what enzyme is not present?
Can you treat mother without effect on fetus?
What would be the best option for treating fetus with GCs?
Sample question:
Why? See table
Use of individual agents:
1- Which one is administered orally and parenterally, and has a ratio od GC:MC of 1:1?
2- Which one is the most commonly used GC for steroid burst therapy and has a ratio of GC:MC of 15:1, and has no topical activity?
3- Which one has minimal MC actions and can be given oraly or IV?
Use of differenct glucocorticoids:
Which one is the most potent GC and shows the greatest suppression of ACTH from pituitary?
Which one is a potent systemic agent with excelent topical activity and has no mineralocorticoid action?
Rheumatoid Arthritis
In early disease what is used to control inflammation?
What is DMARD?
Disease Modifying Antirheumatic Drugs
