Glucocorticoids Flashcards
CORTICOSTEROIDS
- Glucocorticoids and mineralocorticoids (21C)
- Androgens (19C)
Outer cortex of the adrenal gland secretes…
Corticosteroids
Inner medulla of the adrenal gland secretes…
Catecholamines
Catecholamines
Epinephrine, norepinephrine
Adrenaline, noradrenaline
Fight or flight hormones
Prepare the body for extra effort in danger, stress, difficult tasks
Exogenous intake of glucocorticoids (as drugs) can lead to…
- Suppression of endogenous function of the adrenal gland
- Atrophy of zona glomerulosa, fasciculata, reticularis
ZG - mineralocorticoids (aldosterone)
ZF - glucocorticoids (cortisol)
ZR - androgens (androstenedione)
Precursor of steoid synthesis
Cholesterol
Receptors involved in steroid synthesos do dot exhibit much specificity because…
Receptors involved in steroid synthesis do not exhibit much specificity because…
Many enzymatic steps with similar pathways and final structures are involved in hormone synthesis
Drugs with a similar molecular structure to a parent cmpd, apart from some functional groups
Analogues are drugs with a similar molecular structure to a parent cmpd, apart from some functional groups
Major mineralocorticoid produced by adrenal cortex
Aldosterone is the major mineralocorticoid produced by adrenal cortex
- FLUDROCORTISONE - main pharmacologic equivalent (fluorinated aldosterone)
Aldosterone acts at the distal convoluted tubule to promote… ___ reabsorption and __ excretion
Aldosterone acts at the distal convoluted tubule to promote… Na+ reabsorption and K+ excretion
Retention of more Na+ –> Water retention –> BP increases
Hyperaldosteronism
- Retention of more Na+ –> Water retention –> BP increases
- Manifests as hypertension and hypokalemia
Aldosterone secretion is controlled by…
RAAS
(Mineralocorticoids effects)
Sodium retention manifests as…
(Mineralocorticoids effects)
Sodium retention manifests as…
Hypertension
Edema
Cardiac failure (chronic)
(Mineralocorticoids effects)
Potassium excretion results to __________ and manifests as _______ and _______
(Mineralocorticoids effects)
Potassium excretion results to HYPOKALEMIA and manifests as MUSCLE WEAKNESS and METABOLIC ALKALOSIS
Fludrocortisone has both glucocorticoid (at high/low conc) and mineralocorticoid activity (at high/low conc)
Fludrocortisone has both glucocorticoid (at HIGH conc) and mineralocorticoid activity (at LOW conc)
At very low levels, glucocorticoid activity (will/will not) manifest
At very low levels, glucocorticoid activity WILL NOT manifest
At high levels, glucocorticoid activity will manifest
Anti-inflammatory
Glucose elevating effect
At high levels, glucocorticoid activity will manifest
Main endogenous glucocorticoid
Cortisol is the main endogenous glucocorticoid
Hydrocortisone - main pharmacologic equivalent
Cortisol has metabolic (glucose, protein, lipid metab), anti-inflammatory, and immunosuppressive effects
Anti-inflammatory and immunosuppressive effects - clinically relevant
One of the most impt effects of glucocorticoids
Maintains normal BP
Permissive effect
In the presence of glucocorticoids, the vasoconstriction effects of catecholamines can reverse hypotension (ie synergism of cortisol and catecholamines)
Cortisol production is controlled by __________ mainly via _____
Cortisol production is controlled by HPA AXIS mainly via ACTH
*hypothalamic-pituitary-adrenal axis
Average secretion of cortisol
25-30 umol/m2 per day
9-11 mg/day
Cortical secretion follows a 24-hr biological rhythm
Highest plasm conc: ?
Lowest plasma conc: ?
Cortical secretion follows a 24-hr biological rhythm
Highest plasm conc: AM
Dips in the afternoon
Lowest plasma conc: PM
(long/short acting) potent agents are NOT prefered because they make cortisol levels high all day
LONG ACTING potent agents are NOT prefered because they make cortisol levels high all day
Normal ACTH secretion will be suppressed –> adrenal hypertrophy
