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Why are inhaled glucocorticoids safer than oral glucocorticoids for asthma?

Precursor for aldosterone, cortisol, androgens:

Difference between gluco and mineralocorticoids:
deliver local steroid, not systemic

cholesterol

gluco - metabolic
mineralo - salt, H2O, electrolytes
Major function of glucocorticoids:

Most important endogenous glucocorticoid:

How does cortisol affect mRNA expression?

What % of human genes have GRE's?
suppress inflammation, tx for inflammatory/autoimmune dz

cortisol

cortisol binds to receptor in cytosol, complex moves to nucleus, binds to GRE-gene promoter elements

10%
Glucocorticoids have what effect at low and high doses?

Explain feedback for cortisol regulation:
Low - physiologic - usually adrenocortical insufficiency
High - pharmacoogic - anti-inflammatory, autoimmune

cortisol negative feedbacks to anterior pituitary (ACTH), and hypothal (CRH)
Normal adult secretes how much cortisol/day:

When does CBG get saturated?

When does CBG increase?

When does CBG decrease?
10-20 mg/day

~20-30 mg - increased free cortisol after that

pregnancy, estrogen, administration, hyperthyroid

hypothyroid, genetic defect, protein deficiency
Pharmaceutical preparation of cortisol:

Effect on carbs, fat, muscle:

Cortisol effect on bone:
hydrocortisone

stimulates lipolysis (increased free fatty acids), muscle catabolism, increased serum glucose

increases bone resorption, causes osteoporosis in Cushing's syndrome
High-dose, long term therapy has what effect on immunity?

CNS effects?

Gastric effects?
suppresses function, so increased susceptibility to infections

behavioral changes, insomnia, euphoria, depression

increased gastric acid, pepsin - higher risk for PUD
Which short-medium acting corticosteroid has the highest Na+ retaining potency?

Dexamethasone Suppression test is used for what?

Can stimulate what in the fetus?
cortisol

dx for Cushing's syndrome

lung maturation
Which bones are commonly affected by osteoporosis in long-term steroid use?

How to prevent it?

Effect on glucose?

Major AE's of iatrogenic Cushing's:

How should you D/C any corticoids?
ribs, vertebrae

supplement with Ca++, Vitamin D, bisphosphonates

hyperglycemia, glycosuria

moon face, fat redistribution, insomnia, weight gain

taper the dose
Mineralocorticoids primarily act where?

AE's?

Main synthetic compound for aldosteorne:

aldosterone antagonists:
nephron - DCT, CD - promote Na+ absorption, K+ secretion

high Na+, low K+, alkalosis, HTN, water retention

fludrocortisone - widely used in aldosterone insufficiency

spironolactone, eplerenone
4 major drugs that inhibit steroid synthesis;

Drug that blocks conversion of cholesterol to pregnenolone:

Used for inoperable patients with ectopic ACTH secretion and adrenal carcinoma unresponsive to other treatments:
aminoglutethimide, ketoconazole, metyrapone, mitotane, (also RU486, mifepristone)

aminoglutethimide

RU486 (mifepristone)
Which aldosterone antagonist is more selective for kidney, less systemic effects?
eplerenone
Which drug is an intermediate acting corticosteroid?

Class with most potent anti-inflammatory action;

Which short-medium acting has almost no mineralocorticoid action?
triamcinolone

long-acting (dex, betamethasone)

methylprednisilone