Adrenocorticoids Flashcards
What are examples of glucocorticoids?
-cortisol (natural)
-cortisone
-corticosterone
-prednisone (synthetic)
-prednisolone
-triamcinolone
-betamethasone
-dexamethasone
-fluticasone
-flunisolide
What are examples of Mineralcocorticoids?
-aldosterone (natural)
-deoxycorticosterone
-fludrocortisone (synthetic)
What are examples of androgens?
DHEA
What is transcortin (CBG)?
corticosteroid-binding globulin, protein that binds cortisol in the blood to keep it inactive and as a supply
note that synthetic glucocorticoids do not do this
What are the metabolic effects of corticosteroid binding?
-increase blood glucose
-increase amino acids
-increase triglycerides
to maintain energy supplies to critical organs during stress
What effect does cortisol have on the HPA axis?
inhibits further release corticotropin releasing hormone (CRH), from the hypothalamus, and adrenocorticotropic hormone (ACTH), from the anterior pituitary gland
What can override the feedback inhibition of cortisol?
severe or chronic stress
What are the immune system effects of cortisol?
cortisol has anti-inflammatory effects by blocking mediators of inflammation and inflammatory cytokines
Describe Cushing’s syndrome/disease
hyper-secretion of glucocorticoids
What are the treatment options for Cushings?
-surgery, radiation, chemotherapy (bc typically tumor related)
-cortisol inhibiting drugs
What is the main cause of endogenous Cushings?
pituitary ACTH- producing adenoma (responsible for 70% of cases)
Describe Addison’s Disease
hypocortisolism, adrenal insufficiency
What is the cause of PRIMARY adrenal insufficiency?
lack of glucocorticoids and mineralocorticoids due to autoimmune reactions that destroy the adrenal cortex, infection, or surgical removal of adrenal glands
What is the cause of SECONDARY adrenal insufficiency?
lack of ACTH due to hypothalamic or pituitary disorders or abrupt ceasing of long-term glucocorticoid treatment
What is the treatment for Addisons?
replacing/substituting glucocorticoids and mineralocorticoids
What is the function of 11beta-HSD 1 in the liver?
11-keto is converted to 11-OH on glucocorticoids, 11-OH is necessary for action, drugs such as prednisone and cortisone require this activity to be active because they are prodrugs
What is the function of 11beta-HSD 2 in the liver?
11-OH is converted to 11-keto on glucocorticoids (except dexamethasone) to inactivate the drug
What is the indication for oral hydrocortisone?
adrenal insufficiency
What are common uses of glucocorticoids?
-asthma and COPD
-rheumatoid arthritis
-skin diseases
-allergies
-organ rejection
What glucocorticoids are inhaled to treat asthma?
-fluticasone
-beclomethasone
-budesonide
-flunisolide
-triamcinolone
What are the precautions of glucocorticoids?
-adjusting doses= high doses may lead to iatrogenic Cushings
-hyperglycemia
-muscle wasting
-fat deposition
-hidden infection
What are the contraindications for glucocorticoid treatment?
-hypertension, heart disease
-infection
-diabetes
-osteoporosis
-glaucoma
-peptic ulcer
What is the function of glucocorticoids?
-facilitate stress response, both physical and emotional
-promote metabolism (glucose utilization, lipid metabolism, protein utilization)
-inhibit immune function and inflammation
What is the function of mineralocorticoids?
control electrolyte balance (sodium retention, potassium excretion, fluid volume)
Describe the function of aldosterone (mineralocorticoid)
receptors located in the kidney, regulates Na+ reabsorption and K+ and H+ excretion
What factors can impact aldosterone regulation/levels?
-renin-angiotensin system = increase aldosterone
-potassium ion loading= increase aldosterone
-ACTH= increase aldosterone
How does renin effect aldosterone?
renin secretion by juxtaglomerular cells is regulated by baroreceptors specifically senses of decreased extracellular fluid volume (low BP) -> renin converts angiotensin to angiotensin I which is then converted to angiotensin II by ACEs, angiotensin II stimulates aldosterone synthesis
What is the indication of Fludrocortisone?
mineralocorticoid agonist, treats hypoaldosterone (Addisons Disease)
What are the adverse effects of mineralocorticoid agonists?
hypokalemia and hypertension
What drugs are mineralocorticoid antagonist?
spironolactone and eplerenone
Describe Spironolactone
-mineralocorticoid receptor blocker
-treat symptoms of hyperaldosteronism, hypertension
-also androgen receptor blocker so can treat hirsutism in women or acne
What are the adverse effects of mineralocorticoid antagonists?
hyperkalemia, cardiac arrhythmia, menstrual abnormalities
Describe Metyrapone
-inhibit 11beta-hydroxylase
-decreased synthesis of both cortisol and aldosterone
-only drug available for pregnant women with Cushings
-may also be used for diagnostic test for adrenal function
Describe Mifepristone
-high affinity glucocorticoid and progesterone antagonist
-used in inoperable ACTH- secreting tumor
What drugs are adrenocortical inhibitors?
-mitotane
-metyrapone
-osilodrostat
-aminoglutethimide
-ketoconazole
-mifepristone
What is the main use of adrenocortical inhibitors?
Cushings
