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Adrenocorticosteroids พญ. มาลียา มโนรถ
Adrenocorticosteroids Emotional stress Hypothalamus CRF Anterior pituitary gland ACTH Adrenal cortex Adrenal steroids Diurnal rhythms Trauma negative inhibition
Adrenocorticosteroids Glucocorticoids – important effects on intermediary metabolism Mineralocorticoids – salt-retaining activity Sex hormones – androgenic or estrogenic activity
Glucocorticoids Natural steroids –cortisol (hydrocortisone) –cortisone –corticosterone Synthetic steroids –prednisolone –triamcinolone
Corticosteroid secretion : diurnal rhythm Stress : tenfold CortisolAldosterone Rate of secretion under optimal condition10 mg/d0.125 mg/d Concentration in peripheral plasma 8 a.m.16 g/100 ml0.01 g/100 ml 4 p.m. 4 g/ml0.01 g/ml
Pharmacokinetics Natural : adrenal glands Synthetic : cholic acid, plants PO : rapidly & completely absorbed Bound to plasma protein (CBG) Metabolized : liver T 1/2 of cortisol min
Mechanism of action H + R (cytosolic receptor) HRC GREs (glucorticorticoid response element : nucleus) Expression hsp 90
Glucocorticoid effects Influence the function of most cells ญ Liver glycogen deposition ญ Gluconeogenesis ญ Protein catabolism ญ Bone catabolism ฏ Inflammatory responses ฏ Immunological responses
Relative potencies of corticosteroids Na + Anti-inflammatory retention effect Natural steroids Cortisol11 Aldosterone3,000? Synthetic steroids Prednisolone0.254 Triamcinolone< Betamethasone< Dexamethasone<
Beclomethasone Budesonide readily penetrate the airway mucosa but have very short half-life after enter the blood
Topical activity Glucocorticoids Cortisol0 Prednisolone+/- Triamcinolone+++ Dexamethasone+++++ Mineralocorticoids Aldosterone0 Fludrocortisone0
Adverse Reactions Hyperglycemia (DM occasionally) Protein loss muscle wasting Bone catabolism : osteoporosis Fluid retention Adrenal suppression Infections
Clinical Uses Substitution therapy acute adrenal insufficiency Nonendocrine disease –collagen disease –allergic disease –bronchial asthma –skin disease
Mineralocorticoids Aldosterone, Fludrocortisone, Deoxycortone Effects : ญ Na + reabsorption ญ K + excretion
Aldosterone Synthesized : zona glomerulosa Reduction in blood volume Aldosterone secretion Several influences Metabolism : similar cortisol
Fludrocortisone Potent steroid : glucocorticoid & mineralocorticoid activity
Adverse Reactions Na + & H 2 O retention Hypokalemia Hypertension Muscle weakness
Clinical Uses Adrenal insufficiency (Addison’s disease or following adrenalectomy)
Antagonists of Adrenocortical Agents Glucocorticoid antagonists –Mitotane : adrenal carcinoma –Ketoconazole : Cushing’s disease due to several causes –Mifepristone (RU 486)
Antagonists of Adrenocortical Agents Mineralocorticoid antagonists –Spironolactone : 1 o aldosteronism
1 ADRENOCORTICOSTEROIDS Major categories of action: Glucocorticoids: affecting intermediary metabolism & resistance to stress Mineralocorticoids: regulation.
Lísek, 2003 Corticosteroids Slíva, M.D.. Lísek, 2003 ADRENOCORTICOSTEROIDS GLUCOCORTICOIDS MINERALOCORTICOIDS SEXUAL HORMONS Lísek, 2003.
OST 529 Systems Biology: Endocrinology Keith Lookingland Associate Professor Dept. Pharmacology & Toxicology.
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The cortex consists of 3 layers 1 st is zona granulosa - mineralocorticoids, for example aldosterone. The inner 2 layers are zona fasiculata and zona reticularis.
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By: Dylan K.. What is Mineralocorticoid? This chemical derives from early observations that these hormones were involved in the retention of sodium,
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Lecture 1 Dr. Zahoor Ali Shaikh 1. There are two Adrenal glands, one above each kidney. Adrenal gland has outer cortex and inner medulla. - Outer.
Adrenocortical hormones. The adrenal cortex secretes 3 types of hormones: Mineralocorticoids (mainly aldosterone) Glucocorticoids (mainly cortisol = hydrocortisol)
The Adrenal Cortex. Basic principles of steroid endocrinology Steroid effects fall into 3 categories: –Mineralocorticoid –Glucocorticoid –Androgen/Estrogen.
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Adrenal gland. ? What is the adrenal gland The adrenal glands (also known as suprarenal glands) are the triangle-shaped and orange- colored endocrine.
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Adrenal Gland Dr Sandeep Associate professor. In human adrenal glands weigh ~4g, are located above upper pole of each kidney in the retroperitoneal space.
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