adrenal steroids Flashcards
biochemistry of adrenal steroids
not stored, synthesized when needed rate of secretion= rate of synthesis
Zona glomerulosa: cholesterol -> pregnenolone ->desoxycorticosterone -> aldosterone
zona fasciculata and reticularis: cholesterol -> pregnenolone -> desoxycortisol ->cortisol
zona fasciculata and reticularis: cholesterol -> pregnenolone -> androstenedione
synthesis of cortisol is controlled by adrenocorticotropic hormone (ACTH). synthesis of aldosterone controlled by angiotensin 2 and plasma potassium
90% bound in plasma to corticosteroid binding globulin (CBG) and albumin
inactived in liver by: reduction of A ring, sulfate conjugation, glucuronide conjugation
MOA of adrenal steroids
binds to cytosolic steroid receptor, translocated to nucleus, stimulates transcription of mRNA, stimulates mRNA directed protein synthesis, proteins mediate glucocorticoid effect
steroid actions on carbohydrate and protein metabolism
mediated by glucocorticoid receptor, enhances liver gluconeogenesis from protein, stimulates amino acid mobilization (sk muscle, skin) increases plasma glucose, increases liver glycogen, increases urinary nitrogen excretion, reduces peripheral glucose utilization
steroid actions on lipid metabolism
redistribution of body fat- moonface, buffalo hump
stimulates release of fatty acids from adipose tissue
steroids on mineral and electrolyte metabolism
mediated by mineralcorticoid receptor in kidney
cortisol= aldosterone» cortisone
increases sodium REAB, increases potassium and hydrogen ion excretion, responsible for CV effects HTN
steroids on CNS
sleepiness and lability of mood
steroids on immune system
cell trafic or accumulation- reduce access of cells to target tissue, lymphocytopenia and monocytopenia redistribution of cells out of vascular space
prevent neutrophil adherence to endothelium, inhibit action of chemotactic factors
cell function:
MCROPHAGE: inhibits Ag processing, binding to Fc receptors, synthesis and release of IL1
B-cells
Tcells: interferes with macrophage Ag processing, interferes with actions of lymphokines (IL2, M@ migration inhibitory factor, M@ aggregating factor, monocyte chemotactic factor and lymphotoxin)
Absence of IL1 prevents activation of IS
reduces IL2 synthesis
steroids on anti-inflammatory activity
inhibits signs an symptoms of inflammation by inhibiting immune system
inhibits arachidonic acid release so synthesis of PGs and leukotrienes is reduced
inhibits induction of COX2 by cytokines
decrease capillary permeability
therapeutics of steroids
therapeutic dose is variable and may change with therapy, reevaluate frequently. a single dose is usually without harmful effects but prolonged therapy has lethal potential. use is not etiological or curative in most cases. Palliative or symptomatic therapy. abrupt discontinuation may be life-threatening due to adrenal insufficiency
therapeutic use of steroids
adrenal insufficiency- steroid therapy
rheumatoid arthritis- use only in progressive disease in combination with salicylates, gold salts and PT
osteoarthritis- given into joint for acture inflammation
allergic disease- hay fever serum sickness, drug reaction, anaphylaxis, bronchial asthma
inflammatory disease of eye, ear skin used locally
cerebral edema
organ transplantation, thrombocytopenia, liver disease, collagen diseases, renal diseases
toxicity of steroids
rapid withdrawal- acute adrenal insufficiency occurs, salt wasting and CV collapse
Prolonged therapy: suppression of pituitary- adrenal function, reduce dosage slowly’
Cushings- moonface with buffalo hump, poor wound healing, thin skin, HTN, thin extremities, striae
synthesis inhibitors of steroids
metyrapone
blocks 11 B- hydroxylation so synthesis is stopped at 11 desoxycortisol
11-desoxycortisol doesnt inhibit ACTH release so plasma ACTH levels continue to increase
ACTH stimulates synthesis and excretion of 17-hydroxycorticoids as 11 desoxycortisol (used as a diagnostic test)
mifepristone
competitive antagonist at progesterone and glucocorticoid receptor, termination of pregnancy, treat cushing disease
spironolactone eplerenone
competitve antagonist at mineralocorticoid receptor, diuretics, treats HTN, cardiac hypertrophy and Hrt failure
Drospirenone
progesterone receptor agonist (used with E to supress ovulation, hormone replacement therapy in post menopausal women)
mineralocorticoid receptor antagonist: diuretic, antagonizes the salt retaining effects of estrogen
androgen receptor antagonist
