How/when are glucocorticoids released?
Diurnal rhythm in response to sleep/wake cycles
How is glucocorticoid release regulated?
negative feedback
______ use of ______ can suppress the HPA axis and result in adrenal atrophy and insufficient adrenal response to environmental stressors (adrenal crisis).
Chronic; pharmacologic doses of glucocorticoids
Chronic use of pharmacologic doses of glucocorticoids can suppress the _____ and result in adrenal atrophy and insufficient adrenal response to environmental stressors (adrenal crisis).
HPA axis
Chronic use of pharmacologic doses of glucocorticoids can suppress the HPA axis and result in _____ and insufficient adrenal response to environmental stressors (_____).
adrenal atrophy; adrenal crisis
_____ is present in plasma bound to cortisol-binding globulin (CBG).
Cortisol
Cortisol is present in plasma bound to _____.
cortisol-binding globulin (CBG)
What is the normal half life of cortisol?
60-90 mins
What organ eliminates cortisol?
the liver via reduction, then the kidney via conjugation
How can mineralcorticoid activity be separated from glucocorticoid activity?
by synthesizing structural changes
What is the overall metabolic goal of glucocorticoids?
maintain glucose supply to the brain
Why can excessive glucocorticoid use lead to a diabetes-like state?
bc it stimulates gluconeogenesis
Why can excessive glucocorticoid use lead to muscle wasting and atrophy?
bc protein synthesis is decreased- can lead to catabolism
Why can excessive glucocorticoid use lead to centripetal obesity?
bc it stimulates lipogenesis in the central tissues
What are the permissive effects of glucocorticoids?
vasoconstriction, bronchodilation with catecholamines; lipolysis
What are the mineralocorticoid effects?
aldosterone-like actions
Why can excessive glucocorticoid use lead to increased sodium and fluid retention?
bc it induces Na+ reabsorption from renal distal tubules and increased secretion of H+ and K+
What are the major glucocorticoid effects?
anti-inflammatory, suppress the immune system, reduced vasodilation, decrease cell activation
How do glucocorticoids reduce inflammation?
reduce leukotrienes by inhibiting phospholipase A2; decrease prostaglandins by blocking COX-2
When using these agents in _____ replacement regimens (e.g., Addison’s disease), it is necessary to use an agent with both glucocorticoid and mineralocorticoid activity such as cortisol.
physiologic
When using these agents in physiologic replacement regimens (e.g., _____), it is necessary to use an agent with both glucocorticoid and mineralocorticoid activity such as _____.
Addison’s disease; cortisol
When using these agents in physiologic replacement regimens (e.g., Addison’s disease), it is necessary to use an agent with both _____ and ______ activity such as cortisol.
glucocorticoid; mineralocorticoid
When using these agents in _____ doses for their anti-inflammatory or immunosuppressive actions, it is desirable to select an agent with minimal or no mineralocorticoid activity (e.g., dexamethasone).
pharmacologic
When using these agents in pharmacologic doses for their _____ or _____ actions, it is desirable to select an agent with minimal or no mineralocorticoid activity (e.g., dexamethasone).
anti-inflammatory; immunosuppressive
When using these agents in pharmacologic doses for their anti-inflammatory or immunosuppressive actions, it is desirable to select an agent with _____ (e.g., _____).
minimal or no mineralocorticoid activity; dexamethasone
Mineralocorticoid activity refers to _____ at the kidney.
salt (Na+)-retaining actions
______ activity refers to salt (Na+)-retaining actions at the kidney.
Mineralocorticoid
Glucocorticoid activity refers to _____ effects as well as _____ actions.
metabolic; anti-inflammatory
______ activity refers to metabolic effects as well as anti-inflammatory actions.
Glucocorticoid
What is the natural glucocorticoid molecule?
cortisol
What is the natural mineralocorticoid molecule?
aldosterone
11-hydroxy glucocorticoids are _____.
physiologically active
_____ are physiologically active.
11-hydroxy glucocorticoids
11-keto glucocorticoids are prodrugs that must be ____.
activated
What does 11β hydroxysteroid dehydrogenase I do?
activates 11-keto glucocorticoids
_____ are prodrugs that must be activated.
11-keto glucocorticoids
