25. Corticosteroids Flashcards
What are the 5 layers of the adrenal gland?
What does each layer produce?
Capsule
Zona glomerulosa- mineralcorticoid (aldosterone)
Zona fasciculata- glucocorticoid (cortisol)
Zona reticularis- androgens (DHEA and androstenodione
Medulla- catecholamines (adrenaline)
Slide 3
What controls secretion of cortisol, adrenal androgens, and aldosterone?
Secretion of cortisol and adrenal androgens is controlled by ACTH
Secretion of aldosterone is controlled by ACTH and mainly by the renin-Ang II system (RAS)
What is aldosterone?
What is dehydroepiandrosterone (DHEA)?
Aldosterone- major natural mineralocorticoid, synthesis of sodium channels and Na/K ATPase for sodium reabsorption, important for Na K balance, blood volume, and blood pressure
DHEA- weak androgen, declines after age 20, seems to have protection against diabetes mellitus, immune disorders & cancer
Slide 5
What are glucocorticoids effects(
Metabolic effects on carbs, lipids, and proteins Anti inflammatory effects Increased bone catabolism Osteoporosis Behavioural changes Peptic ulcer
Slides 6-7
How does prednisone and other glucocorticoids inhibit COX2?
Repressing COX-2 gene and enzyme expression
Repressing the expression of cytokines that activate COX-2
Blocking the function of phospholipase A2 therefore limiting the availability of arachidonic acids
Slides 9-11
What is cortisol?
Major natural glucocorticoid
Circadian rhythm peak in am and trough around midnight
In plasma 95% of cortisol is bound to corticosteroid-binding globulin (CBG)
Has a small but significant salt retaining (mineralcorticoid) effect
Reason why hypertension is seen in orients with cortisol secreting adrenal tumor or a pituitary ACTH secreting tumor
Slide 12
What is the administration and therapeutics of corticosteroids?
Cortisol is reserved for replacement therapy in primary adrenocortical failure- Addison’s disease or in adrenal biosynthesize defects that lead to adrenal hyperplasia as ACTH secretion is high with no endogenous cortisol production and release
Rest of potent long acting synthetic corticosteroids are reserved for the management of severe forms of inflammation, autoimmune diseases & for immunosuppresion
Chronic glucocorticoid treatment should be tapered slowly with gradually decreasing doses so endogenous cortisol can be elaborated
Slide 15-17
What is adrenal insufficiency and secondary adrenal insufficiency(
AI- associated with life threatening shock, infection, or trauma. Primary adrenal cortical insufficient (addisons disease). All regions of the adrenal cortex are destroyed, deficiencies in cortisol, aldosterone & reduced androgen levels
SAI- lack of pituitary ACTH or following prolonged steroid therapy and rapid withdrawal of such long term corticosteroid treatment
Slide 18
How is Addison’s disease treated?
Oral: hydrocortisone, prednisone, or fludrocortisone
In Addisonian crisis (acute adrenal insufficiency, adrenal crisis), give hydrocortisone for rapid onset of action
For non endocrine diseases, potent corticosteroids are used
Slide 19
What is Cushing’s syndrome?
Caused by a hypersecretion of glucocorticoids due to either increased ACTH or adrenal adenomas
Symptoms: moon face, Buffalo hump, weight gain, muscle wasting, steroid acne, bruising, thin skin
Treatment: surgical excision; adrenal steroid biosynthesis inhibtors or mifepristone
Slide 20
What are the adverse effects of chronic corticosteroid therapy?
Skin- easy bruising, thin, striae, facial erythema, acne, atrophy…
Ophthalmologic- posterior subcapsular cataracts, glaucoma, increases intra ocular pressure
Cardiovascular- hypertension, congestive heart failure
Metabolic- diabetes, truncal obesity
GI- peptic ulcer, fatty liver, pancreatitis
Neurologic- intracranial hyper tensions
Slide 22-24
What are corticosteroid antagonists?
Aldosterone receptor antagonist spironolactone- k sparing diuretic
Inhibits Na reabsorption and K secretion
Uses- hypertension, edema, hypokalemia hirsutism
Steroid competitive antagonist mifepristone- acts as antagonist at both glucocorticoid & progesterone receptors
Slide 25
What are corticosteroid synthesis inhibitors?
Used in treatment of adrenal cancer when surgical therapy is impractical or unsuccessful because of metastases
Antifungal agent ketoconazole- inhibits cytochrome P450 enzymes, therefore inhibiting they synthesis of all steroids both gluco and minerals
Aminoglutethimide- blocks conversion of cholesterol to pregnenolone, rate limiting step, inhibits synthesis of all steroids
Metryrapone- inhibitor of 11β-hydroxylase
Slides 26-28
