Adrenocorticosteroids Flashcards
Glucocorticoid agonist?
Prednisone Hydrocortisone Dexamethasone Beclomethasone Triamcinolone Methylprednisolone
Mineralocorticoid analog?
Aldosterone
Fludrocortisone
Glucocorticoid antagonist?
Mifepristone
Mineralocorticoid antagonist?
Spirnolactone
Cortisol (hydrocortisone)?
Natural occuring glucocorticoid that is synthesized and secreted by the CNS.
Metabolic effect…
- stimulates and required for gluconeogenesis and glycogen synthesis esp in fasting state (or times or stress) leading to an increase in serum glucose levels - it inhibits glucose uptake by muscle cells
- stimulates lipolysis
- stimulates protein catabolism and AA release
- **net result is to maintain adequate glucose supply to the brain (esp during fasting)
Catabolism…
- lymphoid and CT, muscle, peripheral fat and skin (high concentration leads to wasting)
- catabolic effect on bone = osteoporosis
- growth retardation = children
* *these are limitations and AE of long-term tx with glucocorticoids
Immunosuppressive effect…
- increased neutrophils in the blood and decreased migration from blood vessels
- decreased lymphocytes, monocytes, eosinophils and basophils from vascular bed to lymphoid tissue
- vasoconstriction due possibly to suppression of mast cell degranulation [decreased histamine release and capillary permeability]
- *****Anti-inflammatory effect…
1. inhibition of PLA2 blocking arachidonic acid release
2. COX-2 synthesis reduction through NF-kB inhibition
3. induction of MAPK phosphatase I (pro-inflammatory signal pathway inhibited)
Other effects…
- CNS - behavioral changes associated with insomnia, euphoria, depression
- Increased intracranial pressure in large doses
- Peptic ulcer formation due to stimulation of gastric acid or suppression of immune system so you cannot respond to H. pylori
- Suppression of ACH release, GH, TSH and LH release with chronic use
- increased platelets and RBCs
- Impaired renal function
- encourage development of fetal lungs as ENaC protein is moved tot he cell membrane [encourages fluid filled to air filled environmental development of lungs]
Synthetic glucocorticoids?
Prednisone Dexamethasone (IV, IM, topical) Beclomethasone (aerosol, topical_ Triamcinolone (IM, aerosol, topical) Methylprednisolone (IV, IM) *all can be given orally
**given orally and rapidly absorbed, longer t1/2 compared to hydrocortisone, reduced salt-retaining effects
Prednisone = prodrug rapidly converted to active prenisolone
Beclomethasone - short half life with little systemic toxicity, penetrates airway mucosa
Mineralocorticoides?
MOA - bind to mineralocorticoid receptor that leads to increased expression of Na+/K+ ATPase and increased expression of ENaC to promtoe Na+ reabsorption from renal tubules and promote K+ and H_ excretion
Natural mineralocorticoid = aldosterone
Synthetic mineralocorticoid = fludrocortisone
**salt-retaining hormone due to under control and regulation fo CRH, ACTH, RAA
Addison’s disease?
Chronic adrenocortical insufficiency characterized by weakness, fatigue, weight loss, hypotension, hyperpigmentation, inability to maintain blood glucose levels during fasting.
Tx - daily hydrocortisone (increase dose during stress) + mineralocorticoid (fludrocortisone)
**Need mineralocorticoid WITH glucocorticoid effect
Acute adrenocortical insufficiency?
Assocaited with life-threatining shock, infection or trauma.
Tx - start immediately with Large amounts of parenteral hydrocortisone +
correction of fluid & electrolyte abnormalities - Can administer salt-retaining hormone once hydrocortisone levels are reduced (~ 5 days)
Congenital adrenal hyperplasia?
Decreased steroid levels lead to an increase in ACTH production and hyperplasia of adrenal gland b/c you lack the negative feedback mechanism. There are increased amts of cortisol precursors that are diverted to the androgen pathway.
**21-hydroxylase def is most common
Tx - glucocorticoid admin lead to suppression of ACTH, Treat initially as an acute adrenal crisis
Once stabilized: oral hydrocortisone or prednisone + fludrocortisone
Cushing’s syndrome?
Due to bilateral adrenal hyperplasia secondary to ACTH-secreting pituitary adenoma - manifestations are due to chronic presence of excessive glucocorticoides
Tx - remove tumor, irradiation of pituitary tumor, resection or one or both adrenals, pts MUST receive high doses of cortisol before and after surgery but dose has to be slowly decreased to prevent withdrawal
Primary aldosteronism?
Excessive production by adrenal adenoma most commonly from malignant tumor. Symptoms lead to a renal loss of K+ = hypokalemia, alkalosis, elevated serum Na+
Dx and Tx - spirnolactone
Dexamethasone suppression test?
Cushing syndrome = dexamethasone suppresses cortisol release in individuals with pituitarydependent Cushing’s syndrome (not released from adrenal tumors)
Depressive psychiatric states
How do you stimulate lung maturation in fetus?
Dexamethasone via IM steroid - if premature delivery is expected, tx mother with large doses of glucocorticoids reducing incidence of RDS
Synthetic corticoids used to treat cerebral edema and hodgkins lymphoma?
Cerebral edema = dexamethasone
Hodgkin’s lymphoma = prednisone
**can also be used to chemo-induced vomiting, allergic reactions, inflammatory conditions, hematologic disorders, organ transplants, renal disorders, hypercalcemia, mountain sickness, IBD, idiopathic orthostatic hypotension (fludrocortisone)
