corticosteroids Flashcards
Corticosteroids Drug Names
10 of them
- ) Hydrocortisone
- ) Prednisone
- ) Methylprednisolone
- ) Triamcinolone
- ) Dexamethasone
- ) Metyrapone
- ) Ketoconazole
- ) Fludrocortisone
- ) Spironolactone
- ) Cosyntropin
Short-to-medium- acting Glucocorticoids Drug Names
3 of them
- ) Hydrocortisone
- ) Prednisone
- ) Methylprednisolone
Intermediate-acting Glucocorticoids Drug Names
1 of them
1.) Triamcinolone
Long-acting Glucocorticoids Drug Names
1 of them
1.) Dexamethasone
Glucocorticoid synthesis inhibitor and antagonists Drug Names
(2 of them)
- ) Metyrapone
- ) Ketoconazole
Note that these are anti-fungal
Mineralocorticoids agonists Drug Names
1 of them
1.) Fludrocortisone
Glucocorticoid and Mineralocorticoid antagonists Drug Names
2 of them
- ) Metyrapone
2. ) Spironolactone
Glucocorticoid, mineralocorticoid, androgen, progesterone and estrogen agonist Drug Names
(1 of them)
1.) Cosyntropin
Regulation of Adrenocortical Hormone Secretion
The secretion of adrenocortical steroids is controlled by the pituitary release of corticotropin(ACTH). In the pituitary: ACTH synthesized from proopiomelanocortin (POMC). ACTH production is stimulated by corticotropin-releasing hormone (CRH), a peptide synthesized in the hypothalamus. Blood CRH and ACTH concentrations peak between 4 AM and 8 AM, and are lowest in the late evening or early sleep period. ACTH’s actions are mediated by the melanocortin receptor 2 (MC2R), a G protein-coupled
receptor found in the adrenal cortex, and results in adrenal cortex secretion of glucocorticoids, mineralocorticoids and androgen precursors.
Aldosterone biosynthesis
A 3-beta-hydroxysteroid dehydrogenase, associated with the smooth endoplasmic reticulum catalyzes the conversion of pregnenolone to progesterone. CYP21A2 (21-hydroxylase, P450c21) then catalyze hydroxylations on C21 on progesterone to 11-deoxycorticosterone, which is then metabolized by CYP11B1 (11-beta-hydroxylase, p450c11) to corticosterone, a precursor of aldosterone. (See Figure 6)
Cortisol biosynthesis
involves CYP17 (17-alpha-hydroxylase, P450c17) that catalyzes hydroxylation at C17 on pregnenolone to 17-hydroxy-pregnenolone. A 3 betahydroxysteroid dehydrogenase (associated with the smooth endoplasmic reticulum) catalyzes the conversion of 17-hydroxy-pregnenolone to 17-hydroxy-progesterone. Then CYP21A2 (21-hydroxylase, P450c21) catalyzes hydroxylations on C21 on 17-hydroxy- L25-L26-4 progesterone to 11-β-deoxycortisol, which is finally metabolized by CYP11B1 (11-betahydroxylase, p450c11) to cortisol or hydrocortisone. (See Figure 6)
Most endogenous cortisol is metabolized in the______ which is responsible for converting_____ to ______ as well as _____ to ______
Most endogenous cortisol is metabolized in the liver which is responsible for converting
inactive steroids to active metabolites as well as deactivating active steroids to inactive metabolites.
Most endogenous cortisol is metabolized in the______ which is responsible for converting_____ to ______ as well as _____ to ______
- liver
- inactive steroids to active metabolites as well as deactivating active steroids to less active or inactive metabolites.
Cortisol’s (10-20 mg synthesized daily in a normal adult in the absence of
stress) rate of production follows _________ governed by ACTH, peaking early morning and after meals. (See Figure 7)
circadian rhythm
Cortisol’s (10-20 mg synthesized daily in a normal adult in the absence of
stress) rate of production follows _________ governed by _______, peaking ______ and _______
(See Figure 7)
- circadian rhythm
- ACTH
- early morning
- after meals.
More than 90 % of cortisol circulates bound to ____________, a α2-globulin synthesized by liver. (See Figure 8)
-corticosteroid-binding globulin
CBG
CBG levels may rise with_______, ______, and _______
-pregnancy, estrogen administration, and hyperthyroidism.
_______ has low affinity for cortisol, so _____-bound cortisol is considered free
cortisol.
Albumin
The half-life of cortisol is_____
70-120 min in circulation
Glucocorticoids exert two types of negative feedback control on ACTH secretion, which
differ in the time required for their inhibitory effects. The _________ acts almost immediately and is responsible for normal minute-to-minute physiologic control. The_________ suppresses basal CRH and ACTH secretion when pharmacologic doses of glucocorticoids are administered. The amount of ACTH secreted at any time is
influenced by the _______ and ________ from circulating
glucocorticoids. (See Figure 1)
- fast feedback system
- delayed feedback system
- integration of CRH stimulation
- negative feedback
Mineralocorticoid secretion regulation appears more complex. The ________ responds to electrolyte and volume changes by increasing or decreasing __________. ACTH also stimulates aldosterone secretion, but the effect is attenuated within 24 hours and there is ___________________. Aldosterone exhibits a slight_________ and serum concentrations tend to peak in the morning.
-renin-angiotensin system -aldosterone secretion -no significant feedback effect on ACTH production -circadian rhythmicity
Steroids are very ____ soluble
lipid
Molecular mechanism of action of adrenocortical hormones (just read over)
1.) Mechanism of action is mediated by either the glucocorticoid receptors or
mineralocorticoid receptors.
2.) Two genes for the corticoid receptor have been identified (a) the glucocorticoid receptor,
and (b) the mineralocorticoid receptor.
- ) When not bound to a glucocorticoid, the receptor remains in the cytoplasm, in complexes with heat shock proteins (Hsp). (See Figure 9 & 10)
- ) 2 molecules of Hsp90 dissociate from the receptor in the presence of the glucocorticoid.
5.) Ligand-bound receptor complex is transported into the nucleus, where it interacts with
glucocorticoid receptor elements (GREs) in the promoters of responsive genes.
L25-L26-5
6.) Receptor interaction with promoter of target genes regulates their transcription: either promoting or inhibiting specific mRNAs.
7.) Besides GREs, the corticosteroid-bound complex influences function of other
transcriptions factors which regulate growth factors, proinflammatory cytokines, and
mediate anti-growth, anti-inflammatory, immunosuppressive effects of glucocorticoids.
The glucocorticoids influence_____ cells in the body, and thus have _______ effects
- most
- widespread
Glucocorticoids affect _______, ______, and _______ metabolism. In contrast, mineralocorticoids have ______ on intermediary metabolism. These responses are critical survival responses to _________.
(See Figure 11)
- carbohydrate, protein, and fat
- little effect
- starvation and severe stress.
In general, glucocorticoids enhance ______ and _________
glucose production and insulin release.
_______ stimulate hepatic gluconeogenesis
Glucocorticoids
Glucocorticoids increase_______ and release of amino acids from peripheral and______
- proteolysis
- intestinal tissues.
Glucocorticoids enhance______ and_____ , with increased release of
fatty acids and glycerol into the circulation and______.
- fatty acid mobilization and lipolysis
- hepatic cholesterol synthesis
Net result of intermediary metabolism of glucocorticoids: maintain an adequate_____
glucose supply to the brain.
