Adrenocorticoids.ppt

MEDC 603 Steroids * Adrenocorticoids Hydrocortisol (11b,17a,21-trihydroxy- pregn-4-ene-3,20-dione) Aldosterone (11b,21-dihydroxy- pregn-4-ene-3,18,20-trione) Adrenocorticoids Adrenocorticoids Addison’s Disease Cushing’s Disease Conn’s Syndrome ? Disease States Adrenocorticoids Allergic Rhinitis Rheumatoid Arthritis Asthma Multiple Sclerosis Carpal Tunnel Syndrome Dermatitis COPD Osteoarthritis Cystic Fibrosis Temporal Arteritis Gout Psoriasis Herniated Disc Shingles Inflammatory Bowel Disease Tennis Elbow Sinusitis Lupus Erythematosus ? Selected Indications Opened form hemi-acetal form Aldosterone Overall Equilibrium in Aldosterone Overall Structure of Adrenocorticoids ~ planar A ring Differences in the substitution pattern 3D structure of hydrocortisol Biochemical Mechanism of Action Cortisol Aldosterone Receptor Receptor Lipocortin Aldosterone- induced protein Phospholipase A2 Cell membrane phospholipids Prostaglandins leucotrienes Regulates Na+-K+-ATPase Pump Na+ Influx Anti-inflammatory Action Mineralocorticoid Action Metabolism of Adrenocorticoids Reduction C-20 Reduction C-4 Reduction C-3 Metabolism of Adrenocorticoids Oxidation C-11 Reduction at C-3, C-4 and C-20 positions Structure-Activity Relationships Hydrocortisone 1 1 120 m Anti- Salt- Plasma inflammatory retaining half activity activity life Cortisone 0.8 0.8 30 m * * *