Download Adrenocorticosteroids

Adrenocorticosteroids
Hypothalamic-pituitary-adrenal axis
‫בקרת משק המים והמלח‬
CRF
‫מטבוליזם נורמלי ותגובה לסטרס‬
Adrenaline
Noradrenaline
Adrenocorticosteroids
Glucocorticoids (Cortisol)
CORTISOL = [hydrocortisone]
Regulated by ACTH (from the pituitary) – affected by stress and cortisol
blood levels
Secretion varies during the day (circadian rhythm),
Peak in the morning:
Glucocorticoids (Cortisol)
Metabolic effects
Stimulate gluconeogenesis ⇒ ⇑Blood sugar, ⇑insulin secretion
Lipolysis + Lipogenesis ⇒ Fat deposition [“moon face”, “buffalo hump”]
Catabolic effects
catabolism of muscle protein, connective tissue, fat, skin
Bone (osteoporosis)- vit. D and Ca2+ antagonism
Growth inhibition in children
Immune system
Leukocytes↓
↓ → Immune suppression (especially in lymphocytic disorders)
Inhibition of inflammation
Gastrointestinal system
Stimulation of gastric acid secretion →Peptic ulcers
Glucocorticoids (Cortisol): Uses
Long acting
Prednisone, predinsolone, dexamethasone
Inflammation (also skin)
Intermediate
acting
Short acting
Immune disorders (autoimmune diseases – lupus.., allergies)
Supression of graft rejection
Lymphocytic Leukemias
beclomethasone, budesonide
For inhalation and intranasal- asthma and allergic rhinitis
bethamethasone
Fetal lung maturation
Glucocorticoids (Cortisol): Uses
Treatment and Diagnostics
Cortisol defficiency – exogenous cortisol treatment:
Adrenal insufficiency- primary (Addison’s syndrome) or secondary, acute
or chronic.
Congenital adrenal hyperplasia (“bad enzymes”)- less cortisol and
aldosterone and more androgens produced → masculinity, hair
Cortisol overproduction- dexamethasone as diagnostics
Cushing’s : ACTH↑ (tumor) → adrenal hyperplasia → cortisol is
overproduced
Diagnosis- low dose dexamethasone suppression test
Treatment- surgical ( with addition of exogenous cortisol),
Metyrapone- inhibition of cortisol synthesis
Cushing’s symptoms (or Glucocorticoid side effects)
Lipodystrophy
Buffalo hump
Moon face
Hirsutism, weight gain, muscle degradation, akne, thinning of the skin
Cushing’s symptoms ( or Glucocorticoid side effects)
Infections
Osteoporosis
Hyperglycemia (diabetes)
Muscle weakness
Growth retardation in children
Long term effects: glaucoma, cataracts, peptic ulcers
Life threatening adrenal suppression
•To avoid: local application, alternate-day therapy. Slow withdrawal to allow
recovery of normal adrenal function.
Synthetic Glucocorticoids
Drug
Duration [hours]
Anti-inflammatory
Salt retaining
Topical
(mainly glucocorticoids)
Cortisol
8-12
1
1
-
Prednisone
12-24
4
0.3
+
Triamcinolone
15-24
5
0
+++
Dexamethasone
24-36
30
0
+++++
(mainly mineralocorticoids)
Aldosterone
1-2
0.3
3000
-
Fludrocortisone
8-12
10
125-250
-