Adrenocorticoids Steroidal hormones synthesized by the adrenal glands
Adrenocorticoids Steroidal hormones synthesized by the adrenal glands An inner medulla, which is a source of the catecholamines epinephrine and norepinephrine. An outer cortex, which secretes several classes of steroid hormones (glucocorticoids and mineralocorticoids, plus a few others). 11/23/2020 MEDC 603 Steroids 1
Adrenocorticoids Hydrocortisone (11 b, 17 a, 21 -trihydroxypregn-4 -ene-3, 20 -dione) 11/23/2020 Aldosterone (11 b, 21 -dihydroxypregn-4 -ene-3, 18, 20 -trione) MEDC 603 Steroids 2
Overall Equilibrium in Aldosterone Opened form hemi-acetal form Aldosterone 11/23/2020 MEDC 603 Steroids 3
Adrenocorticoids Biological Activities 1. Glucocorticoid Activity 1. 1 Effects on Metabolism 1. 1. 1 Stimulation of gluconeogenesis, particularly in the liver 1. 1. 2 Mobilization of amino acids from extrahepatic tissues 1. 1. 3 Inhibition of glucose uptake in muscle and adipose tissue 1. 1. 4 Stimulation of fat breakdown in adipose tissue 1. 2 Effects on Inflammation and Immune Function 1. 2. 1 Anti-inflammatory properties 1. 2. 2 Immunosuppressive properties 1. 3 Other Effects of Glucocorticoids 1. 3. 1 Multiple effects on fetal development (promote maturation of the lung) 1. 3. 2 Miscellaneous effects (Excessive glucocorticoid levels affect many systems, e. g. , inhibition of bone formation, suppression of calcium absorption and delayed wound healing. ) 2. Mineralocorticoid Activity 2. 1 Effect on Electrolytes 2. 1. 1 Increased re-absorption of sodium 2. 1. 2 Increased renal excretion of potassium 2. 2 Effect on Water 2. 2. 1 Increased re-absorption of water 11/23/2020 MEDC 603 Steroids 4
Adrenocorticoids Disease States Addison's disease: Affects about 1 in 100, 000 people; caused by adrenal insufficiency (90%); typical by auto-immune disorders; both cortisol and aldostertone hormones are lacking. Cushing's disease: Affects about 10 to 15 million people / yr; caused by adrenal hyper-activity (cortisol); typical because of tumor growth exposure to prednisone for asthma, rheumatoid arthritis, lupus or other inflammatory diseases 11/23/2020 Conn's syndrome: May affect 15% of patients with high blood pressure; caused by hyper production of aldosterone; inability of adrenal cortex to carry out 17 a-hydroxylation; hypertension, loss of potassium in the urine, muscle weakness and passing of large volumes of urine (polyuria) MEDC 603 Steroids 5
Glucocorticoids Selected Indications • • • 11/23/2020 Allergic Rhinitis Asthma Rheumatoid Arthritis Multiple Sclerosis Carpal Tunnel Syndrome COPD Cystic Fibrosis Gout Herniated Disc Inflammatory Bowel Disease Sinusitis Dermatitis Osteoarthritis Temporal Arteritis Psoriasis Shingles Tennis Elbow Lupus Erythematosus MEDC 603 Steroids 6
Biochemical Mechanism of Action Cortisol Anti-inflammatory Action Receptor Lipocortin e s a p i ol h sp o Ph A 2 Aldosterone Mineralocorticoid Action Receptor Aldosteroneinduced protein Prostaglandins leucotrienes Cell membrane phospholipids 11/23/2020 Regulates Na+-K+-ATPase Pump Na+ Influx MEDC 603 Steroids 7
Biosynthesis of Adrenocorticoids Corticosterone 11/23/2020 MEDC 603 Steroids 8
Metabolism of Adrenocorticoids 11/23/2020 MEDC 603 Steroids 9
Structure-Activity Relationships Antiinflammatory activity 11/23/2020 Saltretaining activity Plasma half life Hydrocortisone 1 1 120 m Cortisone 0. 8 30 m MEDC 603 Steroids 10
Structure-Activity Relationships Antiinflammatory activity 11/23/2020 Saltretaining activity Prednisone 4 1 Prednisolone 4 0. 6 MEDC 603 Steroids Plasma half life 60 m 115 -212 m 11
Structure-Activity Relationships Antiinflammatory activity 6 a-methyl prednisolone Triamcinolone 11/23/2020 4 Saltretaining activity 0 5 MEDC 603 Steroids Plasma half life 78 -188 m 0 200+ m 12
Structure-Activity Relationships Antiinflammatory activity Dexamethasone Betamethasone 11/23/2020 30 35 MEDC 603 Steroids Saltretaining activity 0 Plasma half life 110 -210 m 0 300+ m 13
Structure-Activity Relationships Antiinflammatory activity Saltretaining activity Plasma half life 0. 2 800 30 m 11 -deoxy corticosterone 0 40 60 m Fludrocortisone 10 Aldosterone 11/23/2020 MEDC 603 Steroids 800 300+ m 14
- Slides: 14