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27 Cards in this Set

  • Front
  • Back
corticosteroids are produced where
adrenal cortex
two major physiologic and pharmacologic groups of corticosteroids
glucocorticoids- effects on intermediary metabolism, immune responses, inflammation
mineralocorticoids- regulate sodium and potassium reabsorption in collecting tubules of the kidney
MOA of glucocorticoids
enter cell, bind to cytosolic receptors that transport the steroid into the nucleus
-steroid-receptor complex alters gene expression by binding to glucocorticoid response elements (GREs)
-tissue specific responses to steroids due to presence in each tissue of different protein regulators that control interaction between hormone-receptor complex and particular response elements
metabolic effects of glucocorticoids
-stimulate gluconeogenesis
- blood glucose rises
- muscle protein is catabolized
- insulin secretion is stimulated
- lipolysis and lipogenesis are stimulated- net increase of fat deposition in certain areas (face, shoulders, back)
catabolic effects of glucocorticoids
- muscle protein catabolism
- lymphoid and connective tissue, fat, skin undergo wasting under influence of high concentration of steroids
- catabolic effects on bone= osteoporosis
- growth inhibition in children
immunosuppressive effects of glucocorticoids
-inhibit cell mediated immunologic functions-esp those dependent on lymphocytes
- actively lymphotoxic and are important in treatment of hematologic cancers
-do not interfere with development of normal acquired immunity
- delay rejection reactions in pt with organ transplants
anti-inflammatory effects of glucocorticoids
- dramatic effect on distribution and function of leukocytes
- increase neutrophils and decrease lymphocytes, eosinophils, basophils, and monocytes
- migration of leukocytes inhibited
biomechanical explanation of anti-inflammatory effects of glucocorticoids
-induced synthesis of an inhibitor of phospholipase A2, decreased mRNA for cyclooxygenase-2 (COX-2), decreases in IL-2 and IL-3, decreases in platelet activating factor (PAF)
Other effects of glucocorticoids
-required for normal renal excretion of water
- effects on CNS-behavioral changes
- large doses stimulate gastric acid secretion and decrease resistance to ulcer formation
major natural glucocorticoid and its regulation
cortisol
- regulated by ACTH and varies during the day
circadian rhythm of cortisol
peak levels in the morning and trough occurs around midnight
form of cortisol in plasma
95% bound to corticosteroid-binding globulin
route of cortisol absorption/excretion
given orally, absorbed well from the GI tract
- cleared by the liver
-short duration of action
-diffuses poorly across normal skin but is readily absorbed across inflamed skin/mucous membranes
secondary effect of cortisol
small salt-retaining mineralocorticoid effect
- important cause of HTN in patients with a cortisol-secreting adrenal tumor or a pituitary ACTH-secreting tumor (Cushings)
synthetic glucocorticoids
prednisone and active metabolite (prednisolone), dexamethasone, triamcinolone
properties of synthetic vs, cortisol
longer half-life and duration of action, reduced salt-retaining effect, better penetration of lipid barriers for topical activity
glucocorticoids that penetrate the airway mucosa but have very short half-lives after they enter, reducing systemic effects and toxicity
beclomethasone and budesonide
Clinical Uses of glucocorticoids
adrenal disorders- preserve life in patients with chronic adrenal cortical insufficiency (Addison's disease)
- necessary in acute adrenal insufficiency associated with life-threatening shock, infection, trauma
- used in CAH, where synthesis of abnormal forms of corticosteroids are stimulated by ACTH
- giving potent synthetic suppresses ACTH secretion enough to reduce synthesis of abnormal
Clinical use of nonadrenal disorders
inflammatory or immunological (asthma, organ transplant rejection, collagen diseases, rheumatic disorders)
- treatment of hematopoietic cancers, neuro disorders, chemo-induced vomiting, hypercalcemia, mountain sickness
blucocorticoid with low degree of protein binding
pregnant women in premature labor to hasten maturation of fetal lungs
toxicity of glucocorticoids
-some life threatening- growth inhibition, diabetes, muscle wasting, osteoporosis, salt retention, psychosis
- minimize these by alternate-day therapy
- doses need to be tapered over several months to allow recovery of normal adrenal function
Major mineralocorticoid
-aldosterone--> regulates blood pressure and blood volume
secretion of aldosterone regulated by
ACTH and renin-angiotensin system
other mineralocorticoids
deoxycorticosterone, naturally occurring precursor of aldosterone
- fludrocortisone- glucocorticoid activity- long duration of action so favored for replacement therapy after adrenalectomy
Receptor Antagonists of corticosteroids
spironolactone and eplerenone- antagonists of aldosterone at its receptor- diuretics
Mifepristone (RU-486)
competitive inhibitor of glucocorticoid receptors as well as progesterone receptors and used in Cushing's
synthesis inhibitors
-ketoconazole- antifungal that inhibits the cytochrome P450 enzymes needed for synthesis of all steroids- used when steroids are bad- adrenal carcinoma, hirsutism, breast and prostate cancer)
-aminoglutethimide- blocks conersion of cholesterol to pregnenolone- inhibits synthesis of all hormonally active steroids- in conjunction w/ other drugs for treatment of steroid-producing adrenocortical cancer
- metyrapone- inhibits normal synthesis of cortisol but not precursors- diagnostic tests of adrenal function