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Flashcards in Adrenocorticosteroids Deck (22):
1

Glucocorticoid agonist?

Prednisone
Hydrocortisone
Dexamethasone
Beclomethasone
Triamcinolone
Methylprednisolone

2

Mineralocorticoid analog?

Aldosterone
Fludrocortisone

3

Glucocorticoid antagonist?

Mifepristone

4

Mineralocorticoid antagonist?

Spirnolactone

5

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...
1. lymphoid and CT, muscle, peripheral fat and skin (high concentration leads to wasting)
2. catabolic effect on bone = osteoporosis
3. growth retardation = children
**these are limitations and AE of long-term tx with glucocorticoids

Immunosuppressive effect...
1. increased neutrophils in the blood and decreased migration from blood vessels
2. decreased lymphocytes, monocytes, eosinophils and basophils from vascular bed to lymphoid tissue
3. 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]




6

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

7

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

8

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

9

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)

10

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

11

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

12

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

13

Dexamethasone suppression test?

Cushing syndrome = dexamethasone suppresses cortisol release in individuals with pituitarydependent Cushing’s syndrome (not released from adrenal tumors)

Depressive psychiatric states

14

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

15

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)

16

AE of synthetic corticosteroids?

1. metabolic effects - Cushing's syndrome
2. peptic ulcers
3. certain disorders (esp bacterial and mycotic infections) may be masked by the use of steroids
4. myopathy
5. nausea, dizziness, weight loss
6. CNS - euphoria, psychosis, depression
7. increased intraocular pressure (glaucoma)
8. post subcapsular cataracts
9. sodium and fluid retention, loss of potassium
10. growth retardation
11. adrenal suppression

17

What are the contraindications for synthetic corticosteroids?

• Peptic ulcers
• Heart disease or hypertension with heart failure
• TB, varicella zoster infections
• Psychoses
• Diabetes
• Osteoporosis
• Glaucoma

18

Spirnolactone?

Mineralocorticoid antagonist that acts by competing with aldosterone for its receptor.

Used for..
1. aldosteronism (dx and tx)
2. hirsutism in women (as it acts as androgen antagonists)
3. diuretic

AE... HYPERKALEMIA (leading to cardiac arrhythmia), menstrual abnormalities, gynecomastia, sedation, headache, GI disturbances, skin rashes

19

Mifepristone?

Antagonist at glucocorticoid and progesterone receptors.

Used for.. inoperable patients with ectopic ACTH syndrome or adrenal carcinoma

20

Aminoglutethimide?

corticosteroid synthesis inhibitor that blocks conversion of cholesterol to pregnenolone by reducing synthesis of all hormonally active steroids.

Used for.. adrenal cancer (with hydrocortisone or dexamethasone)

21

Ketoconazole?

Corticosteroid synthesis inhibitor that acts as a potent and non-selective inhibitor of adrenal and gonadal steroid synthesis

used for.. cushing's syndromea nd prostate cancer

22

Metyrapone?

corticosteroid synthesis inhibitor that is relatively selective inhibitor of steroid 11-hydroxylation where it interferes with cortisol and coritcosterone synthesis.

Used to test for adrenal function and treat pregnant women with cushing's

AE... salt and water retention, hirsutism, transient dizziness, GI disturbances