Steroids Flashcards
Are steroids stored or synthesized as needed?
They are synthesized as needed. The rate of secretion equals the rate of synthesis
Where is aldosterone synthesized?
Zona glomerulosa
What are the steps in aldosterone synthesis
Cholesterol –> Pregnenolone –> Deoxycorticosterone –> Aldosterone
Where is cortisol synthesized?
Zona fasciculata and reticularis
What are the steps in cortisol synthesis?
Cholesterol –> Pregnenolone –> Deoxycortisol –> Cortisol
Where is androstenedione synthesized?
Zona fasciculata and reticularis
What are the steps in androstenedione synthesis?
Cholesterol –> Pregnenolone –> Androstenedione
What hormone regulates the synthesis of cortisol?
ACTH
What controls the synthesis of aldosterone? (2 items)
Angiotensin II and plasma potassium
How are steroids inactivated in the liver? (3 items)
- Reduction of A ring
- Sulfate conjugation
- Glucuronide conjugation
What is the mechanism of adrenocorticosteroid hormones? (5 steps)
- Binds to cytosolic steroid receptor
- Translocated to nucleus
- Stimulates transcription of mRNA
- Stimulates mRNA directed protein synthesis
- Proteins mediate glucocorticoid effects
What effect do glucocorticoids have on gluconeogenesis from liver?
Increases
What effect do glucocorticoids have on amino acids in the body?
Increased mobilization from skeletal muscle, skin etc.
What effect do glucocorticoids have on plasma glucose levels?
Increase
What effect do glucocorticoids have on urinary nitrogen excretion?
Increase
What effect do glucocorticoids have on peripheral glucose utilization?
Reduces
What are the 6 major effects of glucocorticoids on carbohydrate and protein metabolism?
- Enhanced liver gluconeogenesis
- Stimulation of amino acid mobilization
- Increased plasma glucose levels
- Increased liver glycogen
- Increased urinary nitrogen excretion
- Reduced peripheral glucose utilization
What are the 2 major effects of glucocorticoids on lipid metabolism?
- Redistribution of body fat (moon face, buffalo hump)
2. Stimulation of release of fatty acids from adipose tissue
What enzyme is responsible for the specificity of the glucocorticoid receptor?
11B hydroxysteroid dehydrogenase
What substance inhibits 11B hydroxysteroid dehydrogenase?
Licorice – glycyrrhizic acid
How are the relative affinities of Cortisol and Aldosterone for the mineralocorticoid receptor?
The are about the same
What kind of affinity does Cortisone have for the mineralocorticoid receptor?
none
What effects does activation of the mineralocorticoid receptor have on electrolyte and mineral levels? (3 items)
- Increase in Na reabsorption
- Increase in K+ and H+ excretion
- Increase in blood pressure
What effects do glucocorticoids have on CNS? (2 items)
- Sleepiness
2. Lability of mood
How do glucocorticoids suppress the immune system? (3 items)
- They affect cell traffic or accumulation. They reduce access of cells to target tissue. They cause redistribution of cells out of the vascular space.
- They prevent neutrophil adherence to endothelium
- They inhibit action of chemotactic factors.
How do glucocorticoids affect macrophage function? (3 items)
- Inhibit antigen processing
- Inhibit binding to Fc receptors
- Inhibit synthesis and release of IL-1
How do glucocorticoids affect T-lymphocyte function? (4 items)
- They interfere with macrophage antigen processing
- Interfere with action of lymphokines
- Absence of IL-1 prevents activation
- Reduces IL-2 synthesis
How do glucocorticoids exert their anti-inflammatory effects? (4 items)
- Inhibits signs and symptoms of inflammation by inhibiting immune system
- Inhibits arachidonic acid release so synthesis of PGs and Leukotrienes is reduced
- Inhibits induction of cyclooxygenase-2 by cytokines
- Decreases capillary permeability
Why are glucocorticoids used in adrenal insufficiency?
steroid replacement therapy
When are glucocorticoids used in rheumatoid arthritis?
Only in progressive disease and in combination with salicylates, gold salts, and physical therapy.
How are steroids administered in osteoarthritis?
intra-articular injection
What types of allergic diseases are steroids effective for? (5 items)
- Hay fever
- Serum sickness
- Drug reaction
- Anaphylaxis
- Bronchial asthma
What are 6 examples of steroid drugs?
- Cortisol
- Dexamethasone (Decadron)
- Prednisolone
- Fludrocortisone (Florinef)
- Aldosterone
What is the most potently anti-inflammatory steroid?
Dexamethasone
What are the first and second most potent steroids for sodium retention?
- Aldosterone
2. Fludrocortisone
What is the major contraindication for steroid use?
existing infection - particularly TB
What toxic effects are experienced with rapid withdrawal of steroids?
- Adrenal insufficiency
2. Salt wasting and cardiovascular collapse
What adverse effects occur with prolonged steroid therapy?
- Suppression of pituitary and adrenal function
2. Cushings syndrome
What are the symptoms of Cushing’s syndrom? (6 effects)
- Moon face and buffalo hump
- Poor wound healing
- Thin skin
- Hypertension
- Thin extremities
- Striae
What is Metyrapone?
It is a steroid synthesis inhibitor
How does Metyrapone work?
It blocks 11-beta hydroxylation so synthesis is stopped at 11-desoxycortisol
This causes ACTH levels to rise and stimulate excretion of 17-hydroxycorticoids and 11-desoxycortisol
What is the name of a competitive antagonist of the progesterone and glucocorticoid receptor?
Mifepristone
What is the clinical use of Mifepristone? (2 uses)
- Termination of pregnancy
2. Treatment of Cushing disease
How do Spironolactone and Eplerenone work?
They are competitive antagonists of the mineralocorticoid receptor.
What are Spironolactone and Eplerenone used for?
Diuresis
- Treatment of hypertension
- Cardiac hypertophy and heart failure
What drug is a progesterone receptor agonist, mineralocorticoid antagonist, and androgen receptor antagonist?
Drospirenone
What is the progesterone receptor antagonism of Drospirenone used for?
- Used with estrogen to suppress ovulation
2. Used with estrogen as hormone replacement therapy in post-menopausal women
What is the advantage of the mineralocorticoid antagonism of Drospirenone used for?
- Diuresis
2. Antagonizes the salt retaining effects of estrogen
